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Archive for the ‘Stem Cell Complications’ Category

First Man Cured of AIDS Dies From Cancer – The Keystone Newspaper

Wednesday, October 7th, 2020

By Dylan Adams News Editor

Timothy Ray Brown, the first known person to be cured of HIV, died on Sept. 29 at age 54 after battling cancer.

Timothy Ray Brown, a figurehead in the AIDS and HIV community, passed away surrounded by friends after a five-month battle with leukemia, stated Tim Hoeffgen, Browns partner.

Brown received a positive HIV diagnosis in 1995 while studying in Berlin.

In 2006, Brown was diagnosed with acute myeloid leukemia, which is a cancer that builds in the bone marrow and blood interfering with blood cell production. After bouts of infections from several rough rounds of chemotherapy, Browns leukemia came out of remission.

Due to leukemia in his bones, Brown required a stem cell transplant, a process that allows healthy stem cells to be introduced into a host to stimulate the immune system and healthy bone marrow growth. At the time, the survival rates for stem cell transplant were around fifty percent.

Doctors found a match to Browns genetic type, a donor with the CCR5 Delta 32 mutation, a protein that acts as a doorway to stop the HIV from infecting new cells. Three months after Brown stopped taking his HIV medication, doctors found he no longer had HIV in his blood.

After another round of stem cell treatment in February of 2008, Brown went through several near-death complications, almost going blind and becoming paralyzed but slowly recovering. His body was still successfully fighting off HIV.

In July 2012, the Timothy Ray Brown Foundation was created during the World AIDS Conference in Washington, DC. This foundation was built for Brown to show his support and work with medical institutions and scientists to develop a unifying cure and vaccination against HIV.

Brown would often donate large amounts of blood and tissue samples to researchers in the hope of progressing closer towards an HIV cure. According to his partner, Hoeffgen, Tims lifework was to tell his story about his HIV cure and become an ambassador of hope to those in need.

Doctors have since used Brown as a blueprint to work on a potential cure and vaccine for HIV. Most notably for the second person to ever be cured of HIV the London Patient, Adam Castillejo who went through similar stem cell transplants in 2019 before coming forward to the public.

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No on Prop 14: Not the best way to support stem-cell research – Los Angeles Times

Wednesday, October 7th, 2020

In 2004, after President George W. Bush cut off all federal funding for embryonic stem-cell research on religious grounds, Californians strongly backed Proposition 71, a $3-billion bond measure to fund this kind of research, even though such funding is usually not the purview of states.

Supporters of the proposition including this editorial board believed it would allow California to stand out as a leader in this field, advance a budding avenue of research that might save lives and alleviate suffering, bolster its biotech sector and fund possible blockbuster treatments that might earn the state royalties as well. Embryonic stem cells are particularly valuable to research because they are undifferentiated, meaning they do not have a particular function, and researchers could conceivably turn them into specialized cells in order to regenerate human cells and tissue.

In the years since, Proposition 71 gave rise to a burst of scientific discovery. Two cancer treatments it helped fund, for blood and bone-marrow cancers, have been approved by the FDA, though neither of those employed embryonic stem cells and could have been funded even under Bush administration rules. It has also supported promising advances in the treatment of diabetes, bubble boy immune deficiency and vision-robbing retinitis pigmentosa, but other efforts have fallen short in clinical trials.

Moreover, the money helped build laboratories and other infrastructure that give California a head start on research and development, making the state the it place for stem-cell research. Researchers in the state moved to the head of the pack for private grants, because projects are less likely to need the time and money to create facilities before work can begin.

Now that Proposition 71 funding has practically run out, the issue is back on the November ballot with Proposition 14, which seeks nearly double the amount worth of bonds $5.5 billion to continue the juggernaut.

This time, voters should reject the measure, with the caveat that the issue could be reconsidered in a couple of years, if its proponents bring it back in better-designed and more modest form and if there are more successes in human trials and financial payback.

We have long had reservations about how the California Institute for Regenerative Medicine, established as a result of Proposition 71, was set up. Though funded publicly, it is not overseen by the governor and Legislature like other state agencies, and its governing board is too large, at 29 members. Those members generally have ties to the advocacy organizations and research institutions that have received most of the money.

The driving force behind the initiative has been Robert N. Klein II, a Bay Area lawyer and real estate investor. There is no doubting Kleins sincerity in his cause. He knows too well the suffering inflicted by intractable diseases; his son Jordan died of complications of Type I diabetes in 2016. His accomplishment in persuading the state to invest billions in a specific avenue of biomedical research has been exceptional.

However, Klein developed these initiatives largely behind closed doors with little to no public input; he has strong ideas about how things should be run on the stem-cell front and has steadfastly resisted more government oversight. Thats fine when hes investing his own money; its a fatal flaw when he is asking voters for nearly $8 billion, the estimated cost of paying off the bonds over time, according to the Legislative Analysts Office.

Kleins role and the bloated structure of CIRMs super-sized governing board have given rise to some serious ethical mishaps, including a board member who improperly intervened to try to get funding for his organization. (He is no longer on the board.) After this and several other examples of impropriety, rules were tightened. Board members must recuse themselves from votes when there is a conflict of interest, but with 29 members who all want certain projects to receive funding, there is too much potential for mutual back-scratching. Instead of repairing this problem, the new proposition would expand CIRMs board to 35 members and retain its troubling independence from oversight by the governor and Legislature, leaving it open to further conflicts of interest.

Proposition 71 hasnt yet yielded a significant financial return on investment for the state or the cures that were ballyhooed at the time. Though no one ever promised quick medical miracles, campaign ads strongly implied they were around the corner if only the funding came through. Proponents oversold the initiatives and voters cant be blamed if they view this new proposal with skepticism.

In the years since Proposition 71 passed, more resources have become available. President Obama reversed Bushs order and restored federal funding, which meant that between CIRM and the National Institutes of Health, along with private grant and investment funding, stem-cell research has been healthy, if not downright flush. That funding has stayed and even grown under President Trump, to more than $2 billion a year, with about $321 million of that in human embryonic stem-cell research. (There have, though, been recent threats to embryonic research from a group of conservative senators.)

The idea was never for California to become the long-term replacement for federal funding. It was to kick-start an industry that would then operate on its own. If that has failed to happen under Proposition 71 as promised, it shouldnt be the responsibility of California taxpayers to fix it. Thats especially true right now, at a time of yawning needs to address the cost of twin health and economic crises and the worsening effects of climate change. Private money for stem cell-work will continue to be available; its not as though research will collapse.

No doubt, the pace of responsible science is incremental and the outcomes uncertain even with the best research efforts. Yet the backers still couch the possibilities in grandiose terms. In a recent interview with the Times editorial board, Klein talked about the money that would be saved by wiping out Alzheimers disease which has so far has frustrated attempts to treat it effectively, despite many billions of dollars in research.

Embryonic stem cell research remains important, and there might be ways in which the state can contribute less grandiose funding while maximizing its investment. For example, scientific research has a well-known valley of death, where many projects cant get funding to make the transition from laboratory to human clinical trials.

Offering some matching help to get projects through that phase might attract businesses and scientists to California, while spending far less than the billions proposed in Proposition 14. Its worth noting that stem-cell work isnt the only kind of research that faces the valley of death problem; its an issue for most basic research that seeks to make the leap to human trials and that might be equally in need of state help.

Now is not the time for a huge new investment in specialized medical research. First, it makes sense to wait until after the election; if Democrats do well, there should be growing support for embryonic stem-cell research at the federal level, which is where such funding should take place. The future of Californias pandemic-battered economy and budget remains to be seen. Waiting also would give voters a chance to find out how well the states stem-cell research projects continue without state dollars, and whether some of the promising advances lead to breakthrough therapies and a return on Californias investment.

There would be an opportunity to rethink and rewrite any future proposals, which should include a far more modest ask of taxpayers as well as fixes to the structure and inflated size of the CIRM board. The institute should also be placed under the same state oversight as other agencies reporting to the governor.

If CIRM needs money for a basic operating budget over the next couple of years, that could be covered by the states general fund. The agency still needs to administer already-funded projects and could use that time to discuss a more affordable path forward. Right now, the state has other, more urgent spending priorities.

Editors note: This newspapers owner, the physician and scientist Dr. Patrick Soon-Shiong, played no role in the editorial boards deliberations on this measure.

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PA Health Secretary: Sickle Cell Disease Treatment Hinges On Getting Testing – LevittownNow.com

Thursday, September 24th, 2020

Provided by the Pennsylvania Department of Health:

Secretary of Health Dr. Rachel Levine today reminded Pennsylvanians of the seriousness of sickle cell disease and the importance of getting tested for it. Sickle cell disease is the most common inherited blood disease.

We want people to get tested for sickle cell disease if they believe they could be a carrier of it, Levine said. We inherit traits from our parents like eye and hair color, but they also pass along internal traits like blood type and sickle cell conditions. It is important to be tested to confirm if you have sickle cell disease, so that treatment for the disease can be started right away to further protect yourself and your family.

Sickle cell disease is an inherited blood disease where an individuals red blood cells take a crescent or sickle shape. This change in shape can create blockages that prevent blood from reaching parts of the body. As a result, people with sickle cell complications can experience anemia, gallstones, stroke, chronic pain, organ damage and even premature death.

According to the Centers for Disease Control and Prevention (CDC), sickle cell disease affects approximately 100,000 Americans. This disease has a greater influence on African American and Hispanic populations but is also found among many other races and ethnicities.

Sickle cell disease is one of the 10 mandatory diseasesscreened for newborns. These screenings are conducted with the goal of eliminating or reducing death, disease and disability in newborn children. In addition, sickle cell disease can be diagnosed before birth to provide an early diagnosis and find treatment.

Treatment can help those with sickle cell disease live well and be healthy, but there is ultimately no cure for sickle cell disease. Treatment requires:

Finding good medical care and getting regular checkups;

Staying up to date on vaccinations and washing hands frequently to prevent infections;

Learning healthy habits;

Looking into clinical studies; and

Finding support and assistance.

Studies have shown that donated bone marrow or stem cell transplants have helped cure sickle cell disease in children with severe cases of the disease. This means that the healthy donated bone marrow or stem cell transplant replaces an individuals bone marrow that is not working properly. Bone marrow or stem cell transplants can be risky and for the donation to work the individual would need to be a close match like a brother or sister.

The Wolf administration has developed aprescribing guideline for the treatment of acute and chronic pain in patients with sickle cell diseaseto assist physicians treating patients with the disease. The guideline provides best practices to treat acute painful crises that occur with sickle cell disease patients as well as best practices for chronic pain care. The sickle cell disease guideline addresses the specific needs of that patient population. This can help prevent the misapplication of recommendations to populations that are outside the scope of other prescribing guidelines, including patients experiencing acute sickle cell crises. It is especially important to have resources specifically for the treatment of sickle cell disease patients as this patient population often experiences racial disparities and stigma.

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Regenerative Therapy by Dr. Roshni Patel on Better CT – Farmington, CT – Patch.com

Thursday, September 24th, 2020

When youre in pain, its important to find effective, long-lasting solutions that can provide short recovery periods. This is what regenerative medicine offers. Over the past decade, there has been a growing field of medicine that utilizes the bodys own healing capabilities using platelet-rich plasma and mesenchymal stem cells (MSCs). This growing field is labeled as regenerative medicine. Regenerative therapies focus on healing and help regrow damaged tissue naturally. Regenerative injection therapy is used to provide relief to musculoskeletal injuries that involve damage to ligaments, tendons, cartilage, joints, and discs.

Watch video of PRP:

PRP therapy on Better CT

PRP is safeas we are using what your body naturally produces, concentrating the desired critical components and transplanting them into the affected area for effective tissue regeneration and healing. There is no risk of rejection and very minimal overall procedural risk.

FDA regulations do not allow for the cloning of stem cells or growing them in a lab. Also, stem cells derived from fat cells are not approved by the FDA as it does not allow for manipulation. This leaves us to another rich stem cell source in our body which is bone marrow. Stem cells exist in our bodies and are rudimentary cells that can differentiate into other cells.

Think of bone marrow stem cells as the mother cell that is responsible for producing new blood cells. Bone marrow contains hundreds of growth factors and is often used for severe degenerative conditions or where PRP therapy may not be sufficient to provide the growth factors needed to provide relief.

Lastly, there are many offshoot therapies that use biologics derived from placental tissue or blood cord. These biologics are sometimes marketed as Stem cells but are not stem cells and contain zero viable cells. What they contain are growth factors that can also aid when combined with PRP or Stem Cells derived from your own body.

MSCs and PRPmay be used to target a number of conditions that could benefit from their healing and regenerative qualities. Especially when considering chronic pain, alternative solutions may be necessary if it has been difficult to find relief. Along with generalized joint pain, MSCs and PRPmay be used to target:

With so many options for joint pain out there, you may be wondering what benefits choosing stem cell therapy provides. Overall, because mesenchymal stem cell therapy utilizes biologic material harvested directly from the patients body, the general benefits include minimal risk, minimal recovery time, and minimal worry:

Avoid surgery and its many complications and risks: Stem cell therapy is a minimally invasive, non-surgical procedure.

Minimal post-procedural recovery time: One of the most time-consuming factors of any injury is not always the treatment itself, but actually the recovery time. With stem cell therapy, recovery time is minimal.

No risk of rejection: Due to using biologics extracted from the patient, there is no risk of rejection.

No communicable disease transmission: As the cells originate within your own body, there is no risk of spreading disease from or to another person.

If you are suffering from joint pain, back pain, or a debilitating condition like osteoarthritis, it is important to consider all of your available options. Our elite team of professionals can determine if you are the right candidate for MSCs. If youre interested in learning more, contact us today.

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Seattle Genetics and Merck Announce Two Strategic Oncology Collaborations – The Baytown Sun

Tuesday, September 15th, 2020

BOTHELL, Wash. & KENILWORTH, N.J.--(BUSINESS WIRE)--Sep 14, 2020--

Seattle Genetics, Inc. (Nasdaq: SGEN) and Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced two new strategic oncology collaborations.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200914005237/en/

The companies will globally develop and commercialize Seattle Genetics ladiratuzumab vedotin, an investigational antibody-drug conjugate (ADC) targeting LIV-1, which is currently in phase 2 clinical trials for breast cancer and other solid tumors. The collaboration will pursue a broad joint development program evaluating ladiratuzumab vedotin as monotherapy and in combination with Mercks anti-PD-1 therapy KEYTRUDA (pembrolizumab) in triple-negative breast cancer, hormone receptor-positive breast cancer and other LIV-1-expressing solid tumors. Under the terms of the agreement, Seattle Genetics will receive a $600 million upfront payment and Merck will make a $1.0 billion equity investment in 5.0 million shares of Seattle Genetics common stock at a price of $200 per share. In addition, Seattle Genetics is eligible for progress-dependent milestone payments of up to $2.6 billion.

Separately, Seattle Genetics has granted Merck an exclusive license to commercialize TUKYSA (tucatinib), a small molecule tyrosine kinase inhibitor, for the treatment of HER2-positive cancers, in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe. Seattle Genetics will receive $125 million from Merck as an upfront payment and is eligible for progress-dependent milestones of up to $65 million.

Collaborating with Merck on ladiratuzumab vedotin will allow us to accelerate and broaden its development program in breast cancer and other solid tumors, including in combination with Mercks KEYTRUDA, while also positioning us to leverage our U.S. and European commercial operations, said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. The strategic collaboration for TUKYSA will help us reach more patients globally and benefit from the established commercial strength of one of the worlds premier pharmaceutical companies.

These two strategic collaborations will enable us to further diversify Mercks broad oncology portfolio and pipeline, and to continue our efforts to extend and improve the lives of as many patients with cancer as possible, said Dr. Roger M. Perlmutter, President, Merck Research Laboratories. We look forward to working with the team at Seattle Genetics to advance the clinical program for ladiratuzumab vedotin, which has shown compelling signals of efficacy in early studies, and to bring TUKYSA to even more patients with cancer around the world.

Ladiratuzumab Vedotin CollaborationDetails

Under the terms of the agreement, Seattle Genetics and Merck will collaborate and equally share costs on the global development of ladiratuzumab vedotin and other LIV-1-targeting ADCs. The companies have agreed to jointly develop and share future costs and profits for ladiratuzumab vedotin on a 50:50 basis worldwide. Merck will pay Seattle Genetics $600 million upfront and make a $1.0 billion equity investment in 5.0 million shares of Seattle Genetics common stock at a price of $200 per share. In addition, Seattle Genetics will be eligible to receive up to $2.6 billion in milestone payments, including $850 million in development milestones and $1.75 billion in sales milestones.

The companies will jointly develop and commercialize ladiratuzumab vedotin and equally share profits worldwide. The companies will co-commercialize in the U.S. and Europe. Seattle Genetics will be responsible for marketing applications for approval in the U.S. and Canada, and will record sales in the U.S., Canada and Europe. Merck will be responsible for marketing applications for approval in Europe and in countries outside the U.S. and Canada, and will record sales in countries outside the U.S., Europe and Canada. Including the upfront payment, equity investment proceeds and potential milestone payments, Seattle Genetics is eligible to receive up to $4.2 billion.

The closing of the equity investment is contingent on completion of review under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (HSR Act).

TUKYSA Collaboration Details

Under the terms of the agreement, Merck has been granted exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe. Seattle Genetics retains commercial rights and will record sales in the U.S., Canada and Europe. Merck will be responsible for marketing applications for approval in its territory, supported by the positive results from the HER2CLIMB clinical trial.

Merck will also co-fund a portion of the TUKYSA global development plan, which encompasses several ongoing and planned trials across HER2-positive cancers, including breast, colorectal, gastric and other cancers set forth in a global product development plan. Seattle Genetics will continue to lead ongoing TUKYSA global development planning and operational execution. Merck will solely fund and conduct country-specific clinical trials necessary to support anticipated regulatory applications in its territory.

Seattle Genetics will receive from Merck $125 million as an upfront payment and is eligible to receive progress-dependent milestones of up to $65 million. Seattle Genetics will also receive $85 million in prepaid research and development payments to be applied to Mercks global development funding obligations. In addition, Seattle Genetics would receive tiered royalties on sales of TUKYSA in Mercks territory.

The financial impact of these collaborations is not included in Seattle Genetics 2020 guidance.

Seattle Genetics Conference Call Details

Seattle Genetics management will host a conference call to discuss these collaborations today at 6:00 a.m. Pacific Time (PT); 9:00 a.m. Eastern Time (ET). The event will be simultaneously webcast and available for replay from the Seattle Genetics website at http://www.seattlegenetics.com, under the Investors section. Investors may also participate in the conference call by calling 844-763-8274 (domestic) or +1 412-717-9224 (international). The conference ID is 10147850.

About Ladiratuzumab Vedotin

Ladiratuzumab vedotin is a novel investigational ADC targeted to LIV-1. Most metastatic breast cancers express LIV-1, which also has been detected in several other cancers, including lung, head and neck, esophageal and gastric. Ladiratuzumab vedotin utilizes Seattle Genetics proprietary ADC technology and consists of a LIV-1-targeted monoclonal antibody linked to a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE) by a protease-cleavable linker. This novel ADC is designed to bind to LIV-1 on cancer cells and release the cell-killing agent into target cells upon internalization. Ladiratuzumab vedotin may also cause antitumor activity through other mechanisms, including activation of an immune response by induction of immunogenic cell death.

About TUKYSA (tucatinib)

TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth. TUKYSA in combination with trastuzumab and capecitabine was approved by the U.S. Food and Drug Administration (FDA) in April 2020 for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. In addition, TUKYSA received approval in Canada, Singapore, Australia and Switzerland under the Project Orbis initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology products among international partners. A marketing application is under review in the European Union.

TUKYSA is being evaluated in several ongoing clinical trials and additional studies are planned. Current trials include the following:

For additional information, visit http://www.clinicaltrials.gov.

TUKYSA Important Safety Information

Warnings and Precautions

If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

Adverse Reactions

Serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in 2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.

Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; those occurring in 1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; those occurring in 2% of patients were hepatotoxicity (8%) and diarrhea (6%).

The most common adverse reactions in patients who received TUKYSA (20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Lab Abnormalities

In HER2CLIMB, Grade 3 laboratory abnormalities reported in 5% of patients who received TUKYSA were: decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

Drug Interactions

Use in Specific Populations

For more information, please see the full Prescribing Information for TUKYSA here.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

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Seattle Genetics and Merck Announce Two Strategic Oncology Collaborations - The Baytown Sun

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Three-year-old bone marrow donor, Bengaluru doctors give Iraqi boy a new lease of life – The Indian Express

Tuesday, September 15th, 2020

Written by Ralph Alex Arakal | Bengaluru | Updated: September 14, 2020 8:12:24 amAhmed and his family after the successful bone marrow transplant (Express photo)

A three-year-old girl from Iraq became a lifesaver for her 18-year-old brother after she donated her bone marrow for a successful transplantation that took place in Bengaluru.

Ahmed had undergone splenectomy in his native country and was referred to Manipal Hospitals in Bengaluru since only optimal treatment is available in Iraq. According to doctors at the hospital, the teenager was also suffering from symptomatic anemia (needing frequent blood transfusions) and jaundice.

Dr Mallikarjun Kalashetty, consultant Haematology, Haemato-Oncology & Bone Marrow Transplantation at Manipal Hospitals, said Ahmed required an allogeneic bone marrow transplantation.

The best donors for such patients are the human leukocyte antigen (HLA)-matched siblings who are normal or with a minor form of haemoglobinopathy (a hereditary condition involving an abnormality in the structure of haemoglobin) or thalassaemia (a blood disorder involving lower-than-normal amounts of an oxygen-carrying protein), Dr Kalashetty explained.

However, things were not easy for the medical team at the hospital considering the age of the donor the patients three-year-old younger sister and the obvious language barrier. Transfusion experts at the hospital soon realised the process was challenging as they required the processing of 8-10 litres of blood from the donor aged three, weighing 18 kilograms, who had only a blood volume of about 1.3 litres.

Considering her age, the donor had to be sedated to elicit co-operation during apheresis (extracting blood and separating components) in multiple sittings and preserve the stem cells through cryopreservation. To counter the low volume of blood going into the apheresis machine, we filled the dead spaces with compatible RBC, and to reduce the fluid overload, we determined and monitored the volume of the fluid going into the body of the child, Dr C Shivaram, consultant transfusion medicine said.

However, the allogeneic bone marrow transplantation was successful and Ahmed has now recovered from the sickle-cell disease. He did have few complications after transplantation like mucositis, febrile neutropenia, and viral reactivation, which were successfully managed, Dr Kalashetty said.

Ahmeds quality of life has improved significantly and his parents are overjoyed to see their son doing so well after suffering from the illness for several years. The satisfaction of seeing the joy on the faces of the patient and his family is unmatched, he said.

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‘Mini organs’ offer treatment hope for children with intestinal failure study – The Northern Farmer

Friday, September 11th, 2020

Mini organs grown using stem cells from a patients tissue could offer hope for children with intestinal failure, a study suggests.

Scientists at the Francis Crick Institute, Great Ormond Street Hospital (GOSH) and UCL Great Ormond Street Institute of Child Health (ICH) have grown human intestinal grafts using stem cells from patient tissue.

The team hope the findings could one day lead to personalised transplants for children with intestinal failure.

Dr Vivian Li, senior author and group leader of the Stem Cell and Cancer Biology Laboratory at the Crick, said: Its urgent that we find new ways to care for children without a working intestine because, as they grow older, complications from parental nutrition can arise.

Weve set out a process to grow one layer of intestine in the laboratory, moving us a step closer to being able to offer these patients a form of regenerative medicine, which uses materials created from their own tissue.

This would reduce some of the risks that transplant patients face, such as their immune system attacking the transplant.

Children with intestinal failure cannot absorb the nutrients essential for their overall health and development, researchers said.

While they can be fed intravenously, via a process called parenteral nutrition, this is associated with severe complications such as line infections and liver failure, they added.

If complications arise, or in severe cases the children need a transplant, researchers said there is a shortage of suitable donor organs and problems can arise after surgery such as the body rejecting the transplant.

The proof-of-concept study, published in Nature Medicine on Monday, showed how intestinal stem cells and small intestinal or colonic tissue taken from patients can be used to grow the inner layer of small intestine in the laboratory with the capacity to digest and absorb peptides and digest sucrose in food.

The researchers took small biopsies of intestine from 12 children who either had intestinal failure or were at risk of developing the condition.

In the lab they then stimulated the biopsy cells to grow into mini-guts, also known as intestinal organoids, generating over 10 million intestinal stem cells from each patient over the course of four weeks.

The researchers also collected small intestine and colon tissue that would have been discarded from other children undergoing essential surgery to remove parts of their gut.

Using laboratory techniques cells were removed from these tissues leaving behind a skeleton structure which formed scaffolds.

The researchers placed the mini-guts onto these scaffolds where they grew on this structure to form a living graft.

Due to specific culture conditions, the stem cells changed into many of the different types of cells that exist in the small intestine and the grafts were able to digest and absorb peptides, the building blocks of proteins, as well as digest sucrose into glucose sugars.

The authors said research was the first step in efforts to engineer all the layers of the intestine for transplantation in the hope that laboratory-grown organs could offer a safe and longer-lasting alternative to traditional donor transplants.

Senior author Professor Paolo De Coppi, consultant paediatric surgeon at GOSH, said the research was an important step forward in regenerative medicine.

He added: Although this research is in the lab right now, were concentrating on making this a realistic and safe treatment option.

Whats significant here is weve shown that scaffolds can be created using tissue from the colon, not only tissue from the small intestine.

Its an important step forward in regenerative medicine and were optimistic about what this means for patients, but more research lies ahead before we can safely and effectively translate this approach to treatment.

As well as proving that biopsies taken from children could be used to grow functioning intestinal grafts, the researchers said that the grafts can survive and mature when transplanted into mice.

Researchers said the next step was to start growing the other layers of the intestine such as muscle and blood vessels.

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What Is Covid-19 Doing to Our Hearts? – The New Republic

Friday, September 11th, 2020

Brady Feeney hadnt even taken any classes at Indiana University when he fell ill with Covid-19. Three weeks after he moved to Bloomington, the incoming freshman was in the emergency room, struggling to breathe. Before his illness, Feeney had been a perfectly healthy teenager, with no preexisting conditions. In high school, he was a three-time all-state football player and won two state titles in Missouri. But after two weeks of hell fighting the virus, his mother said, his bloodwork indicated possible heart problems.

When SARS-CoV-2 first struck the United States, the medical community had two working assumptions: First, this was primarily a respiratory disease, and second, it seemed to hit older people much harder than younger people, with eight out of 10 confirmed Covid-19 deaths in the U.S. happening in adults 65 or older. But now, new research is challenging both of these assumptions.

Growing evidence suggests that SARS-CoV-2 doesnt only infect the lungs. It also affects the brain, kidneys, and heart. At first, doctors and researchers wondered if these issues beyond the lungs came just from the stress of having Covid-19 and being on a ventilator or life support. But increasingly, research indicates that the virus may be attacking other organs in the body directlyand this may be more common than previously thought, even among those who arent sick enough to be hospitalized. Some have suggested that Covid-19 is actually a blood vessel disease; the lungs are merely the way the virus enters the body, but from there it gets into the bloodstream and takes up residence in major organs, leaving patients with complex, long-lasting symptoms. Moreover, experts now believe, healthy young people can get mild cases of the coronaviruseven not knowing they were sickthat could leave them with lasting cardiovascular damage. Even those who seem to have recovered from the deadly respiratory illness are not free of its complications.

Heart failure could be the next chapter of the coronavirus illness, Dr. Gregg C. Fonarow, interim chief of UCLAs Division of Cardiology, recently argued in a co-authored editorial in the journal JAMA Cardiology. Even if in younger adults Covid-19 may not be fatal, there still may be important health consequences, he told me.

Myocarditis, or inflammation of the heart, is usually a rare condition that can occur with viral infections, including the flu. But from the start of the pandemic, doctors were seeing heart inflammation among patients hospitalized with serious cases of Covid-19, Fonarow said: Early research showed that 20 to 30 percent of those hospitalized had heart issues. Left untreated, myocarditis can damage the heart and lead to heart attacks and arrhythmias, among other complications.

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What Is Covid-19 Doing to Our Hearts? - The New Republic

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Tweet Chat Recap: Evaluating Treatment Approaches for Relapsed/Refractory DLBCL – Targeted Oncology

Friday, September 11th, 2020

Targeted Oncology was joined by Kami J. Maddocks, MD, associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer CenterJames, for the discussion of a 76-year-old man with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in a recent tweet chat. In this case scenario, the patient presented with stage IV high-risk disease and received R-CHOP (Rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, prednisone), and radiotherapy.

Although the treatment appeared well-tolerated, the patient presented with similar symptoms as at diagnosis after completing 6 cycles with complete response to the therapy. According to the work-up, the patient is ineligible for transplant.

The patient was ineligible for stem cell transplantation (SCT), which Maddocks speculates may be due to the patients age, although other considerations could include comorbidities or intolerance to R-CHOP. Eligibility is the first thing she considers for her patients as it is currently the standard of care and the only curative approach for patients to receive salvage chemotherapy followed by consolidation with autologous SCT.

Maddocks told Targeted Oncology, In some patient cases, [the reason for ineligibility] is age even though there's no specific age cutoff, but we know that it's harder on the marrow as patients get older to collect stem cells and get that aggressive salvage chemotherapy. Patient comorbidities [can also impact eligibility], so heart conditions, lung conditions, renal insufficiency can be a problem. Performance status and then lastly, just if the patient had trouble getting to their initial chemotherapy with R-CHOP or had a lot of complications, then it's probably going to be harder for them to tolerate even more aggressive or intensive therapy.

In a twitter poll ahead of the chat, Targeted Oncology asked what the next best line of therapy for this patient might be, with 4 potential different treatment options. The option that drew the most attention, however, was the recently approved regimen of tafasitamab (Monjuvi) and lenalidomide (Revlimid).

Maddocks tweeted, All these options are potential therapeutic choices for this patient, but the combination of tafasitamab/lenalidomide is the only option approved in this setting. The treatment has a promising ORR [overall response rate], and CR [complete response], and the remissions for patients who respond are durable!

During the tweet chat, Maddocks reviewed each of the different treatment options in the poll, and why she selected this combination regimen as the next best line of therapy for this particular patient. Following the chat, she spoke with Targeted Oncology to share further insights on each of these therapeutic approaches and the importance of the FDAs approval of tafasitamab plus lenalidomide in this setting.

The combination of tafasitamab plus lenalidomide held the majority vote, which Maddocks agreed would be the next best line of therapy for this patient.

For patients who are not candidates or considered eligible for a salvage chemotherapy followed by autologous SCT, the tafasitamab/lenalidomide combination was recently approved in the setting of first relapse, and it's the only approved therapy in this setting, Maddocks said. Historically, we would give some sort of palliative chemotherapy approach if patients were candidates and interested in pursuing therapy, or consideration of clinical trial, but this is the only therapy approved in this setting.

The approval of tafasitamab in combination with lenalidomide includes an indication for patients who are not eligible for autologous SCT, as describes the patient in our case. This regimen was approved on the basis of the phase 2 L-MIND (NCT02399085) clinical trial, which explored this use of this regimen in 81 patients with relapsed/refractory DLBCL. Two-year follow-up demonstrated an ORR of 58.5%, which included CRs in 41.3% of patients and partial responses (PRs) in 17.5% of patients. In addition, 15.0% achieved stable disease, and the median duration of response was 34.6 months (95% CI, 26.1-34.6).1

I think this patient case is the perfect example of where this can fit into the treatment landscape, Maddocks explained. For patients who first relapse from the standard R-CHOP therapy, the toxicities were generally manageable, and with the response rate, this is a great option for patients at first relapse who are not going to be candidates for a transplant. I think maybe patients who go on to get palliative chemotherapy or maybe patients who get treatment with plans to go to transplant but just don't tolerate it and dont look like they're going to [undergo] aggressive therapy, this may be an option for those patients too, understanding that there is some role for CAR T in a set of those patients.

This study, which was presented during the 25th Congress of the European Hematology Association (EHA), demonstrated that the majority of toxicities were hematologic, and most were reversible. The most common grade 3 hematologic treatment-emergent adverse events (TEAEs) were neutropenia in 49.4% of patients, thrombocytopenia in 17.3%, and febrile neutropenia in 13.2%.1

These were able to be managed by holding the dose growth factor, and there was a population of patients who had to be dose-reduced on the lenalidomide. The starting dose was 25 mg, so the majority were able to maintain 20 mg if they were dose-reduced, although a few had to be reduced more than once, Maddocks said. The most common grade 3/4 or serious AEs were infection, probably not surprisingly, and overall, that's probably similar to what you see with other options in this setting. There was a small number of infusion reactions, but these were all grade 1 in the trial and were easily managed.

Non-hematologic TEAEs of grade 3 included pneumonia in 8.6% of patients and hypokalemia in 6.2%. Serious AEs reported included pneumonia in 8.6%, febrile neutropenia in 6.2%, and pulmonary embolism in 3.7%, as well as bronchitis, lower respiratory tract infection, atrial fibrillation, and congestive cardiac failure in 2.5% each.1

Given the safety profile of this combination of tafasitamab plus lenalidomide, this regimen is particularly suitable for a large proportion of patients with DLBCL, Gilles Salles, MD, PhD, lead author of L-MIND, toldTargeted Oncology. We do know that the median age of occurrence of DLBCL is in the late 60s, and there are many, many patients that are over 70 and that are not usually transplant eligible. Clearly this is a great opportunity for patients to receive this non-cytotoxic regimen.

Although this regimen is an exciting opportunity for patients with DLBCL and relapsed/refractory disease, 1 challenge that needs to be addressed is the potential use of tafasitamab plus lenalidomide in sequence with CAR T-cell therapy. There is very little experience, if any, of patients receiving the combination regimen after receiving CAR T-cell therapy. The combination and CAR T cells both target the same antigen, CD19, which can be problematic. As its known that some patients will lose CD19 expression on CAR T-cell therapy, the regimen may no longer be an effective treatment option.

For those patients that had failed CAR T-cell therapy, substantial proportions, about 30% of them, may have lost CD19 expression and then may not be eligible anymore for this regimen. There is, however, a substantial proportion of patients that retains CD19 and in whom tafasitamab/lenalidomide can be used as a treatment option, Salles commented.

A large proportion of patients will maintain CD19 expression following CAR T-cell therapy, so tafasitamab plus lenalidomide may still be effective in a percentage of patients.

Its hard to say because we dont have a lot of data, but we do know there are other CD19-directed therapies outside of CAR T cell development, Maddocks told Targeted Oncology. I think in the next few years, were going to see patients treated both pre- and post-CAR T with other CD19-directed therapies, and well have more information on this.

The combination of polatuzumab vedotin (Polivy) plus bendamustine (Bendeka) and rituximab (BR) was approved by the FDA as treatment of patients with relapsed/refractory DLBCL after 2 prior lines of therapy in June 2019 based on the findings from the phase 1b/2 GO29365 (NCT02257567) clinical trial. Although this option is also not FDA-approved for the treatment of patients after first relapse, Maddocks noted that this was the only treatment evaluated in a randomized trial. The study had included patients who were ineligible for transplant.

Significant improvements were observed with polatuzumab vedotin plus BR compared with BR alone in an international, multicenter, open-label study, particularly in regard to the ORR, CRs, progression-free survival (PFS), and overall survival (OS). CRs were observed in 40.0% of the patients with the combination versus 17.5% with BR alone. Survival rates favored the combination as well, with a median PFS of 9.5 months with the combination versus 3.7 months with BR alone (HR, 0.36; 95% CI, 0.21-0.63; P <.001) and a median OS of 12.4 months versus 4.7 months (HR, 0.42; 95% CI, 0.24-0.75; P =.002), respectively.2

The addition of polatuzumab did increase toxicity from the standpoint of cytopenias, but that didn't really translate to increased serious infections. It did add neuropathy as a side effect, but most of that was reversible, so I think this was a regimen that, by the addition of polatuzumab, was something that you could offer patients that did give them somewhat of a better overall response and was more durable than just giving them a palliative chemotherapy alone, Maddocks added. This is also a regimen that's been used in patients who were not able to achieve a remission to bridge them to CAR T or in some patients after CAR T, and so I can understand why this was definitely one of the more favorable choices.

In the study, grade 3/4 neutropenia was observed more frequently in the combination arm (42.6%) compared with the BR alone arm (33.3%), but the occurrence of grade 3/4 infections was comparable between the 2 groups (23.1% vs. 20.5%, respectively). In addition, the study authors noted that although many of the fatal AEs occurred after disease progression, 11 patients in the BR arm experienced fatal AEs compared with 9 in the combination arm, infection being the most common, which was the cause in 4 patients in each arm.2

Although the regimen appeared tolerable in this setting, Maddocks tweeted, it is more attractive than chemotherapy alone and understandable why it was chosen [as the second-best option in the Twitter poll].

Among the treatment options considered in our twitter poll ahead of the tweet chat, selinexor (Xpovio) only caught the attention of 16.7% of voters, similar to CAR T-cell therapy. However, both of these options are currently only approved in patients who have received at least 2 prior lines of therapy, which this case did not.

In regard to selinexor in particular, Maddocks tweeted, Looking at the single arm phase 2 data, it also has the lowest overall response rates of all the options listed with an ORR of 28%.

Selinexor received its approval from the FDA in June 2020, which is indicated for the treatment of adult patients with relapsed/refractory DLBCL, not otherwise specified, who have received at least 2 prior systemic therapies. This is the only oral single-agent therapy approved in this setting, and it is also the only nuclear export inhibitor approved by the FDA for use in hematologic malignancies.

The agent was approved on the basis of the phase 2b SADAL clinical trial, which demonstrated an ORR of 29% with 13% CRs and 16% PRs. The responses achieved in the study were durable, which led to a median duration of response of 9.2 months in the overall population (95% CI, 4.8-23.0) and 13.5 months in those who had achieved a CR (95% CI, 9.3-23.0).3

The most common treatment-related AEs were cytopenias and gastrointestinal/constitutional symptoms, which were generally reversible and manageable with dose modifications and/or standard supportive care approaches. The most common on-hematologic AEs, which were mostly grade 1/2, were nausea (52.8%), fatigue (37.8%), and anorexia (34.6%). The most common grade 3/4 AEs included thrombocytopenia (39.4%), neutropenia (20.5%), and anemia (13.4%). No treatment-related grade 5 AEs were observed.

CAR T-cell therapy, on the other hand, offers a unique option to this patient case even though it is still only approved in patients who have progressed or relapsed after 2 prior therapies or SCT. The TRANSCEND-PILOT-017006 (NCT03483103) study is evaluating the potential for CAR T-cell therapy lisocabtagene maraleucel (liso-cel) as treatment of patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who have received at least 1 prior therapy and are ineligible for SCT. While this does appear promising for introducing CAR T-cell therapy earlier on for patients with DLBCL, the treatment is not available off trial and is not a standard approach.

Maddocks told Targeted Oncology, It's very clear who's eligible for autologous transplant by age and comorbidities, but with CAR T, it's not so clear all the time who is going to be a candidate. There's not as great of data or information on who is going to be a candidate for that or not. Probably more patients are going to be a candidate for transplant, but there is still going to be patients that are comorbidities that they're not going to be a candidate for CAR T cells, and while they're approved in this setting and they can be very effective, there's also logistical issues, including that right now there's only certain centers, most often transplant centers, that are able to administer CAR T cells, so the patient has to have access to a center, they have to be able to get through the time that their leukapheresis cells are sent out and then sent back, and there's still barriers to cost and insurance in some patients, too.

This particular patient case does represent a challenge, Maddocks said. Historically, this is not a patient that's going to be a candidate for an autologous SCT, and that's going to be the only curative approach. CAR T is not approved in this setting, which is the other curative approach we know outside of patients who are unable to get to autologous STC, or at least appears to be likely curative for a percentage of patients.

Overall, CAR T-cell therapy is not a viable treatment option for the patient depicted in our tweet chat discussion, although it can still offer curative opportunities to a select group of patients with DLBCL who are ineligible for transplant.

In conclusion, tafasitamab plus lenalidomide helps fulfill the unmet need of patients who are in first relapse but are ineligible for transplant, which is the only curative option for patients with relapsed/refractory DLBCL. Although CAR T cells appear hopeful in this space, more research needs to be done to further determine their role in the treatment paradigm.

When you look at relapsed DLBCL, in general, and have these options, it's exciting for our patients to be able to have these. All of these have come up in the last 1 to 2 years, CAR T being a little bit longer than the other 3 regimens, but they all have offered patients tolerable therapy in the setting of previously not having these options.

Reference

1. Salles G, Duell J, Gonzlez-Barca E, et al. Long-term outcomes from the phase II L-MIND study of Tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Presented at: Presented at: EHA25 Virtual; June 11-21, 2020. Abstract EP1201.

2. Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma.J Clin Oncol. 2019;38(2):155-165. doi: 10.1200/JCO.19.00172

3. Kalakonda N, Cavallo F, Follows G, et al. A phase 2b study of selinexor in patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL).Hematol Oncol. 2019;37(S2). doi: 10.1002/hon.31_2629

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Tweet Chat Recap: Evaluating Treatment Approaches for Relapsed/Refractory DLBCL - Targeted Oncology

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Roche receives FDA clearance for BK virus quantitative test on cobas 6800/8800 Systems to support better care for transplant patients – Yahoo Finance

Friday, September 11th, 2020

Basel, 8 September 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced U.S. Food and Drug Administration (FDA) 510k clearance for the cobas BKV Test on the cobas 6800 and 8800 Systems. The test was previously granted FDA Breakthrough Device designation demonstrating the improved treatment or diagnosis of life-threatening diseases or conditions for transplant patients. The test provides standardised, high-quality results that can help healthcare professionals better assess the risk of complications caused by the BK virus in transplant patients and identify effective treatment options.

BK virus (BKV) is a member of the polyomavirus family that can cause severe transplant-associated complications. Infection can occur without symptoms and happen early in life. After primary infection, the virus can remain inactive, only to possibly reactivate in immunocompromised individuals such as transplant recipients.

Our diagnostic tests can help clinicians greatly improve patient treatment plans and make quick adjustments for personalised healthcare, said Thomas Schinecker, CEO Roche Diagnostics. This FDA clearance allows Roche to offer healthcare professionals a transplant testing portfolio that includes Cytomegalovirus, Epstein-Barr virus and BK virus so they can simultaneously monitor and improve care for transplant patients who are at risk for these common infections or viral reactivations which can cause further illness or death.

The cobas BKV Test is a polymerase chain reaction (PCR) viral load test that runs on the fully automated and widely available cobas 6800 and cobas 8800 Systems. Along with the previously approved cobas EBV and CMV Tests, the cobas BKV Test has been calibrated to the World Health Organization (WHO) International Standard. This means that test results are reported in international units, making it possible for laboratories anywhere in the U.S. to obtain comparable results when measuring levels of BKV DNA.

About the cobas BKV TestThe cobas BKV Test was previously granted Breakthrough Device Designation by the FDA, together with the cobas EBV Test.

The cobas BKV Test is a real-time polymerase chain reaction (PCR) test with dual-target technology that provides quantitative accuracy and guards against the risk of sequence variations that may be present in the BK virus. The cobas BKV Test has robust coverage with a limit of detection of 21.5 IU/mL and an expanded linear range from 21.5 IU/mL to 1E+08 IU/mL in EDTA plasma.

The test offers an alternative to lab-developed tests (LDTs) or Analyte Specific Reagent (ASR) combinations, potentially minimising variability and complexity in testing, reducing workload and alleviating risk for laboratories. The test supports the goal of result standardisation across institutions by providing reproducible, high-quality results for clinical decision-making.

The fully automated cobas BKV Test and the cobas CMV and cobas EBV Tests can run on the cobas 6800/8800 Systems simultaneously, providing absolute automation with proven performance and flexibility, leading to time savings and increased efficiency.

About BK polyomavirus BK polyomavirus (BKV) is a member of the polyomavirus family that can cause transplant-associated complications including nephropathy in kidney transplantation and hemorrhagic cystitis in hematopoietic stem cell transplantation. Infection can occur early in life, often with no symptoms. After primary infection, the virus can remain inactive throughout life, only to possibly reactivate in immunocompromised individuals, such as patients who receive solid-organ transplants. For kidney transplant patients, BKV infection is considered the most common viral complication, causing polyomavirus nephropathy (PVN) in up to 10 percent of kidney transplant recipients, and about 50 percent of PVN-affected patients will experience transplant graft failure.1 BKV is also associated with hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.2

About the cobas 6800/8800 SystemsWhen every moment matters, the fully automated cobas 6800/8800 Systems offer the fastest time to results with the highest throughput and the longest walk-away time available among automated molecular platforms. The systems provide up to 96 results in about three hours and 384 results for the cobas 6800 System and 1,056 results for the cobas 8800 System in an eight hour shift.*

Both systems make it possible for labs to perform up to three tests in the same run with no pre-sorting required. The systems also enable up to eight hours (cobas 6800 System) and four hours (cobas 8800 System) of walk-away time with minimal user interaction.*

These real-time PCR systems serve the areas of infectious disease, donor screening, sexual health, transplant, respiratory and antimicrobial stewardship.

Through an ever-increasing worldwide install base of cobas 6800/8800 Systems, labs are quickly and easily processing millions of tests per month to meet the changing demands of their communities, their customers, and the patients relying on the results of each assay. Globally, labs know and trust that a Roche assay guarantees high precision, accuracy, and traceability to World Health Organization standards.

Today, rapid advancements in healthcare technology, a shortage of skilled workers, industry-wide consolidation, and the proven need to be ready for the next outbreak have health systems looking to lay a reliable foundation for the future. With proven performance, absolute automation, and unmatched flexibility delivering unparalleled throughput 24/7cobas 6800/8800 Systems are designed to ensure a labs long-term sustainability and success now, more than ever.

Learn more now: http://www.cobas68008800.com or http://diagnostics.roche.com.*May vary based on workflow demands

About RocheRoche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve peoples lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the worlds largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2019 employed about 98,000 people worldwide. In 2019, Roche invested CHF 11.7 billion in R&D and posted sales of CHF 61.5 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit http://www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References[1] Jamboti, J. S. (2016) BK virus nephropathy in renal transplant recipients. Nephrology, 21: 647 654. doi: 10.1111/nep.12728. [2] Hirsch HH, Randhawa PS; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13528. doi:10.1111/ctr.13528

Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com

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Coronavirus, Charity, and the Trolley Problem – Crooked

Friday, September 11th, 2020

I signed up to be a bone marrow donor in 2016, after an anonymous strangers marrow saved my father. It started out easy enough: The registry mailed me a kit to swab my cheeks, I mailed it back, and then I heard nothing for years. This wasnt unusual. Marrow transplantation requires finding complex and rare genetic matches; according to Be The Match, only about one out of every 430 people who sign up will ever go on to donate. I expected it would be a while before I got to pay my dads transplant forward. It did not occur to me that my opportunity might arise at the height of a global coronavirus pandemic.

The coronavirus created a tangle of moral dilemmas that most Americans never expected to face. At the extremes, weve resolved these dilemmas easily. Weve designated whole categories of labormostly underpaid, perennially underappreciatedessential because we accept that even with a plague lurking, people must eat and medicate and have working showers in which to cry. On the opposite end of the spectrum, weve trained our online shaming apparatus on the most reckless and selfish offendersthe wealthy New Yorkers who fled to the Hamptons, the house parties posted to Instagram with weak defensive captions (we only took our masks off for the body shots).

The longer we live in the shadow of an uncontained virus, the more agonizing the in-between dilemmas become. How long should people be expected to remain isolated from their loved ones? Is there a point at which the negative effects of physical distancing begin to outweigh the toll of the disease itself? On the one hand, we should do everything in our power to protect the most vulnerable in our communities. On the other hand, what should we tell the vulnerable seniors who feel they dont have endless spare months to let pass without embracing their grandchildren? Are our individual mitigation responsibilities lessened by the fact that we all made sacrifices to buy an incompetent president time to get this under control, and he squandered it? Are we that much more obligated to pick up the slack?

In some sort of sick philosophical joke, the moral waters get even murkier when you throw altruism into the mix. For all of the guidance reminding us of the impact of our selfish choices on strangersyou might not kill your own grandmother by going to that dive bar, but think of the bartenders roommates grandmothermoral experts have had far less to say about the boundaries around charitable acts. How should we think about helping strangers when doing so requires a dangerous level of social interaction? How should we measure the suffering of the people we want to help against the harm we risk causing to unseen others in the process? That quandary leads to another awful question that most people should never have to confront: When does human life become too risky to save?

Be The Match first notified me that it had identified me as a potential match in June, when coronavirus cases in Los Angeles, where I live, had just begun to spike. By the time I was confirmed as the patients best match and asked to proceed with a donation several weeks later, the city had become a full-blown hotspot. The idea of navigating the whole process in plague conditions made me nervous, but underneath the anxiety was a distinct whiff of relief. Like a lot of people, Id spent the last few months in a horrified daze, helpless to do anything but stay home, donate money, and cyberbully the mayor. Here, finally, was a task that felt equal to the urgency of the moment. Here was somethingsomeonereal. I just wasnt allowed to know who.

Be The Match will put donor and recipient in contact one year after the transplant, if both have consented; until then, everything is completely anonymous. I was told that my recipient was a man in the United States, along with his age (surprisingly young), and diagnosis (a type of blood cancer). Because matches are typically found within shared ancestries, I assume that he is, like me, an Ashkenazi Jew, and because he needed a bone marrow transplant, his situation must have been dire.

Fortunately, helping people like him has become simpler. When most people think of donating for a bone marrow transplant, they imagine general anesthesia; a very big needle; a painful recovery. This is one of the two ways to donate, but its grown much less common. Ninety percent of donors (including me) are instead asked to donate peripheral blood stem cells (PBSC), through a process called apheresis. While a donor is awake and watching Party Down, their blood flows through a tube attached to one arm, gets spun around in a centrifuge that separates out the extra blood-forming stem cells, and is returned through a tube into the other arm. This can take several hours, but its painless, and neednt even happen at a hospital. Usually.

(Sarah Lazarus)

On August 13, two nurses met me at the San Bernardino blood bank where I was scheduled to donate later that month. We were all there for an assessment, to make sure my arm veins could handle the apheresis needles. It was a weird little ritual. The two women bent on either side of me, intently tapping along my upturned arms in total silence as if waiting for something to tap back. They then switched sides, tapped the opposite arm, and issued their verdict: Too small. I would need to donate through a central line placed in one of my larger veins, and that could only happen at a hospital. I would probably be sent to a medical center two hours south in La Jolla, they told me.

This was a complication, but not necessarily a big deal. Be The Match footed the bill for all of my donation-related expenses, including the fancy car service that seemed safer, COVID-wise, than using Lyft. (I am a genius who moved to Los Angeles without a drivers license. A worse essay for another time.) Donating at the La Jolla hospital would mean a longer commute, maybe even one night in a hotel, but that was about it.

Later that morning I was waiting for my next appointment at an urgent care center when Heather, my donor coordinator, called to tell me that La Jolla didnt have an opening on the right day. Neither did the next-closest option, she told me as I paced around the parking lot, and the patients team couldnt shift his treatment schedule.

So my question for you is, would you feel comfortable flying to Boise, Idaho?

I went back inside to the busy waiting room and reclaimed my seat. Across the room, a man in a UPS uniform freed his nose to rest obscenely on top of his mask. I hunched over my phone and googled, Boise coronavirus. My phone informed me that it was dying. The UPS man coughed. On a TV in the corner, the president admitted he was sabotaging the post office to steal the election. I googled, airports coronavirus. At last, a nurse called me back and started checking my vitals.

Your heart rate is really elevated, she said, frowning at the reading. Any idea why?

As of this writing, Be The Matchs COVID-19 FAQ page was last updated on April 6. Heres part of the section on air travel:

Q: Are there alternatives to donors traveling for donation?A: Possibly. If you feel uncomfortable traveling, we respect your decision. However, it is extremely important that you tell us right away so we can look for alternatives. Donation is time-sensitive, and any delay can have a negative impact on the recipients wellbeing. It may be possible to arrange for donation to occur somewhere within driving distance.

There was an alternative to Boise, it turned out, if I felt uncomfortable. I could donate at the La Jolla hospital a day later than originally planned. My cells would be cryogenically frozen and given to the patient a week or two later, instead of immediately. Heather told me that the patients team preferred me to stick with the original date, that a delayed transplant would be riskier for him, but, for confidentiality reasons, they couldnt tell me how much riskier.

We dont want you to feel pressured, Heather emphasized. You should only agree to travel if you feel comfortable.

Did I feel comfortable? It depended on the circumstances, which I wasnt allowed to know. The window of risks were willing to take expands as the stakes get higher; anyone who showed up to a Black Lives Matter protest this summer or signed up to be a poll worker this fall can attest to that. I wouldnt feel at all comfortable flying for the heck of it, but I would certainly do it to save a life. This fell somewhere on the vast spectrum in between, but I had no idea where.

How do you make a call about your personal risk tolerance when its also a choice about the course of a strangers cancer treatment? If the pandemic had taught us all a valuable lesson about the interconnectedness of our fates, I was now being beaten over the head with it. Stuck without enough facts to make an informed decision, I thought about my dads old hospital room in Baltimore, the airlock separating his ward from the rest of the building because any mundane microbe could kill the patients on the other side. I imagined a somber-looking doctor walking through those doors to give my vulnerable recipient the news.

Im afraid theres been a change of plans, he would say, removing his glasses. It seems your donor is a pussy-ass bitch.

I called Heather back and told her to arrange my donation in Boise.

In most respects, my pre-donation medical screening was extremely, almost ludicrously thorough. I submitted vials and vials of blood to check for a host of diseases and disorders. I peed in a cup to make sure I wasnt pregnant. I had more blood drawn, to make sure I really wasnt pregnant. After the second pregnancy test confirmed the results of the first pregnancy test, I got the following email from Heather:

The result of your repeat pregnancy test on 8/13 was negative, but we are still required to complete our pregnancy assessment with you today. The assessment consists of a single question Is there any chance you could be pregnant? Please respond via email when convenient.

I have not touched another person in five months, I wrote back.

Thank you for completing the pregnancy assessment, Heather replied.

In one respect, my pre-donation medical screening seemed oddly lax. I wasnt tested for coronavirus until the day before my flight, and only then because I panicked.

(Sarah Lazarus)

The PBSC donation process begins in earnest a few days before the stem cells are actually collected, with five rounds of filgrastim injections. Its a drug normally given to cancer patients to bring up low white-blood cell counts after chemo or radiation. In my case, it would send my healthy bone marrow into overdrive, to produce enough cells for the donation. The injections have a few side effects: bone pain, fatigue, headaches, nausea. Essentially, filgrastim makes you feel like you have the flua particularly special feeling in the year of our lord 2020. My side effects were mild and I knew to expect them, and I was managing them fine until an extra one showed up.

The night after receiving my second round of shots, I went for a walk around my neighborhood. It was a hot night, and I was tired and achy from the medication; this was not a fast walk. And yet within a few blocks I noticed that my breathing was quick and shallow, and my heart was pounding as if Id just run a sprint. When I tried to take a deep breath, it felt like there was an elastic band cinched around my chest.

Shortness of breath was not on my list of filgrastim side effects. Neither were the heart palpitations, which continued long after I went home and collapsed on my bed.

I put an empty Gatorade bottle on my stomach and watched it pulse up and down as I considered how fucked I was. I had assumed my fatigue and body aches were side effects; what if those were symptoms, too? I mentally tallied up my appointments from over the past week. I had been to five different medical facilities, been a passenger in three different cars. Of course I had caught it. How stupid to think I wouldnt catch it.

The timing was a nightmare. At some point while I was receiving the filgrastim injections, the patient began a course of high-dose chemo to kill off his own blood-forming stem cells in preparation for the transplant. If I had to back out of donating after that treatment began, the patient would die quickly.

For a few desperate minutes, I thought about keeping these symptoms to myself. I didnt have a fever. As long as I didnt develop one, maybe I could get to Boise and finish the donation leaving no one the wiser. What was the moral math, I wondered, of proceeding with travel plans that might seed multiple new outbreaks (but also might not) and lead to numerous deaths (but maybe none), knowing that if I didnt, one person would certainly die? Had anyone solved that particular trolley problem? My heart palpitations got worse. This was insane. I texted Heather everything and asked if she could arrange for a rapid coronavirus test the next day.

It was nearly 11 p.m. by this point, later in Heathers time zone. She made sure my shortness of breath wasnt an emergency, then said shed see how I was feeling in the morning to assess whether a test was necessary.

I went to bed and thought about what they would tell the patient. Would his doctors be allowed to explain why I couldnt donate? Would he think I had just bailed? Would he and his family hate me? What did it say about my motivations that I was fixated on this? Probably nothing good. I drifted off into a stress dream, and then it was dawn.

My breathing was still labored in the morning, and now, compounding my dread, I had a definite tickle in my throat that verged on a cough. Heather and the medical team decided this did indeed warrant a coronavirus test, and went about setting one up. In the meantime, Heather told me, I should proceed with my third day of filgrastim.

When my home nurse Maria arrived at 8 a.m. to do the honors, I stopped her outside to inform her that I might be a vector of death. She was unimpressed. (Ok, sweetie. Can I come in and wash my hands?) Soon afterwards, Heather called to let me know she had found a doctors office that would send someone to test me at my apartment, and deliver results within 24 hoursjust fast enough that I could still make my flight if I tested negative. Be The Match picked up the tab for this, too, but the receipt came to my email. The cost of a rapid PCR test, antibody test, and home visit came out to a cool $900.

The unaffordable testing nurse arrived an hour later cloaked in full PPE. She coached me on how to swab my own mouth and throat for the diagnostic test, then we made small talk while waiting for the little white antibody tray, which looked for all the world like yet another pregnancy test, to reveal either one or two lines. She had been doing these home visits for two weeks, she told me, and none of her patients had yet tested positive for an infection. For no good reason at all, this made me feel better. The antibody test came up negative. The nurse wished me luck with my other results and headed off to her next appointment, leaving me alone with my wonderful thoughts.

I had nothing to do for the rest of the day but wait. By late afternoon my throat felt better, and my breathing had become less conspicuous. At one point I started to pack a bag, wondered if I was jinxing it, and unpacked the bag. At 10 p.m., less than 12 hours after my throat swab, the results arrived in my inbox. NOT DETECTED. I texted Heather a screenshot and lay down on the floor, awash with relief.

(Sarah Lazarus)

The travel and donation themselves were mercifully uneventful. My parents, who were very pleased that I was donating and terrified that I was flying, had shipped me a steady stream of hand sanitizer, KN95 masks, surgical masks, disinfectant wipes, face shields, safety glasses, and gloves. I wore only some of this to the airport, unless you are my parents, in which case I wore all of it. In any event, I felt protected. My terminal at LAX was deserted, and Heather had booked me a first class seat on Delta, which limits capacity to 50 percent. After barely leaving my immediate neighborhood for half a year, the feeling of takeoff, even for a two-day trip to Boise, was sensational.

The next day I arrived at the hospital at 7:15 a.m. By 8:30 Id had a central line inserted above my collarbone, in a painless 15-minute procedure under local anesthesia. The song We Are Young was playing, and the doctors threading a tube into my neck were chatting quietly about a patient whod given them trouble over the weekend. (Im just saying, if youre cussing people out and trying to beat me up, you probably didnt have too bad of a stroke.) Ive had much less pleasant mornings.

By 9:30 I was in bed and hooked up to the apheresis machine, where I would remain for the next seven hours. At one point my calcium levels dropped too low and I threw up; this was the excitement peak of the day. I spent the rest of the time comfortably reading or watching Netflix, keeping an eye on the stem cells slowly collecting in the bag above my head, and carefully avoiding any RNC coverage that might cause the nausea to recur. At around 4:30 I was loosed from the machine, and after waiting a couple more hours while the lab made sure I had forked over enough cells, the nurse removed my central line and I was officially done.

I was exhausted that evening, but the next day felt well enough to go for a walk along the Boise River, where I took 50 terrible photos of a great blue heron. My shortness of breath, whatever it had been, was gone. The day after that I was just a little more fatigued than usual, and by day three I was back to my 2020-adjusted tiredness baseline.

Coronavirus complications aside, the actual donation process was remarkably easy; shockingly easy, when you consider the scale of what it means for the recipient. It was a time commitment for a few weeksIm lucky to have employers who were happy to give me the necessary leaveand involved some mild discomfort, but as a baby about both pain and scheduling, I would not hesitate to do this again.

I also came away with a clearer sense of how to approach the kind of altruistic acts that standard social-distancing guidelines say we shouldnt engage in. The people and organizations that facilitate charity, particularly sensitive medical charity, have existing support systems that theyve retrofitted to help mitigate the extra risks. Those systems may be imperfect and require some self-advocacy, but when combined with ones own diligence and added layers of protection (and, if one is lucky, a concerned Jewish mother), its possible to get help to the people who need it with risk levels not much higher than we tolerate in normal times. There is a way to be selfless without being self-sacrificing, or worse, becoming an inadvertent menace.

Even so, pandemic experiences like this one wont be universally feasible. One might live with immunosuppressed family members or roommates, or have care-taking responsibilities, or lack the spare emotional bandwidth, or have any number of circumstances more complex than my own. And thats finethere will still be people in need of a lifeline on the other side of this crisis, and that lifeline will be no less appreciated.

I asked my dad, Mitchell Lazarus, what he thought potential donors should know about the recipient experience. He sent me this:

The diagnosis is, literally, a death sentence: you will soon die. Word of a matching donor who has agreed to participate is a reprieve the only possible reprieve. I have felt relief many times in my life, but except possibly for the safe birth of my children, nothing like that. I was in a chemo chair when they came by and told me. I called my wife and said, I have a donor, and I started to cry.

Patients in the transplant ward talk a lot about our donors, despite not knowing who they are. Everybody everybody! tears up when talking about their donors.

True story: I was in the hallway on the transplant floor, talking with the woman in the room next to mine. A nurse walking by stopped and said, Mr. Lazarus, are you having trouble with allergies? (which would require attention). I said no, I was talking about my donor. No other explanation needed. She patted my arm and walked on.

I am a chimera. The rest of me has my own DNA, but my blood cells carry my donors DNA, not mine. Somebody elses blood pumps through my body, keeping me alive, not just through treatment, but every second of every day for the rest of my life. How can you not be grateful to someone who literally gave you the rest of your life?

At some point during the 24 hours after I was unhooked from the machine, a volunteer courier arrived at the hospital in Boise. He or she or they retrieved the bag of my donated cells, flew with it to wherever the recipient is located, and hand-delivered it to his hospital. The patient almost certainly received the transplant before I made it back to Los Angeles. If all goes well, my stem cells will navigate their way into his bone marrow, where theyll settle in, multiply, and start producing healthy blood cells. If all goes well, this perfect stranger will eventually have my blood type, and potentially even my childhood immunitieshe might soon, in other words, have my immune system. If all goes well, may that sucker protect us both.

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Coronavirus, Charity, and the Trolley Problem - Crooked

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Global Induced Pluripotent Market By 2026 Emerging Technology, Opportunities, Analysis And Future Threats With Key Players Like Thermo Fisher…

Friday, September 11th, 2020

Induced Pluripotent MarketIs Expected To Rise To An Estimated Value Of Usd 2.33 Billion By 2026, Registering A Substantial Cagr In The Forecast Period Of 2019-2026. This Rise In Market Value Can Be Attributed To The Increasing Prevalence Of Chronic Diseases And Ailments Requiring The Development Of Modern Technologically Advanced Therapeutic Options.

The strategies encompassed in the Induced Pluripotent report mainly include new product launches, expansions, agreements, joint ventures, partnerships, acquisitions, and others that boost their footprints in this market. This gives more accurate understanding of the market landscape, issues that may affect the industry in the future, and how to best position specific brands. The base year for calculation in the report is taken as 2017 whereas the historic year is 2016 which will tell you how the Induced Pluripotent market is going to perform in the forecast years by informing you what the market definition, classifications, applications, and engagements are.

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Few of the major competitors currently working in the induced pluripotent market are Bristol-Myers Squibb Company; CELGENE CORPORATION; Astellas Pharma Inc.; Thermo Fisher Scientific; Cell Applications, Inc.; Axol Bioscience Ltd.; Organogenesis Holdings; Merck KGaA; FUJIFILM Holdings Corporation; Fate Therapeutics; KCI Licensing, Inc.; Japan Tissue Engineering Co., Ltd.; Vericel; ViaCyte, Inc.; STEMCELL Technologies Inc.; Horizon Discovery Group plc; Lonza; Takara Bio Inc.; Promega Corporation and QIAGEN.

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Market Restraints

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Headaches, confusion and delirium with COVID-19: How SARS-CoV-2 attacks the brain – Firstpost

Friday, September 11th, 2020

The ACE2 receptor that the virus targets is rare in the brain. But new research shows that the virus could enter brain cells via this method too.

The coronavirus targets the lungs foremost, but also the kidneys, liver and blood vessels. Still, about half of patients report neurological symptoms, including headaches, confusion and delirium, suggesting the virus may also attack the brain.

A new study offers the first clear evidence that in some people, the coronavirus invades brain cells, hijacking them to make copies of itself. The virus also seems to suck up all of the oxygen nearby, starving neighboring cells to death.

Its unclear how the virus gets to the brain or how often it sets off this trail of destruction. Infection of the brain is likely to be rare, but some people may be susceptible because of their genetic backgrounds, a high viral load or for other reasons.

If the brain does become infected, it could have a lethal consequence, said Akiko Iwasaki, an immunologist at Yale University who led the work.

The study was posted online Wednesday and has not yet been vetted by experts for publication. But several researchers said it was careful and elegant, showing in multiple ways that the virus can infect brain cells.

Scientists have had to rely on brain imaging and patient symptoms to infer effects on the brain, but we hadnt really seen much evidence that the virus can infect the brain, even though we knew it was a potential possibility, said Dr. Michael Zandi, consultant neurologist at the National Hospital for Neurology and Neurosurgery in Britain. This data just provides a little bit more evidence that it certainly can.

Zandi and his colleagues published research in July showing that some patients with COVID-19, the illness caused by the coronavirus, develop serious neurological complications, including nerve damage.

In the new study, Iwasaki and her colleagues documented brain infection in three ways: in brain tissue from a person who died of COVID-19, in a mouse model, and in organoids clusters of brain cells in a lab dish meant to mimic the brains three-dimensional structure.

Brain scans of coronavirus patients from a study published in July. The new study offers the first clear evidence that in some people, the coronavirus invades brain cells, hijacking them to make copies of itself, and the virus also seems to suck up all of the oxygen nearby, starving neighbouring cells to death. By [Apoorva Mandavilli/Ross W. Paterson, Rachel L. Brown, et al./Brain, Oxford University Press] 2020 The New York Times

The coronavirus is much stealthier: It exploits the brain cells machinery to multiply, but doesnt destroy them. Instead, it chokes off oxygen to adjacent cells, causing them to wither and die.

The researchers didnt find any evidence of an immune response to remedy this problem. Its kind of a silent infection, Iwasaki said. This virus has a lot of evasion mechanisms.

These findings are consistent with other observations in organoids infected with the coronavirus, said Alysson Muotri, a neuroscientist at the University of California, San Diego, who has also studied the Zika virus.

The coronavirus seems to rapidly decrease the number of synapses, the connections between neurons.

Days after infection, and we already see a dramatic reduction in the amount of synapses, Muotri said. We dont know yet if that is reversible or not.

The virus infects a cell via a protein on its surface called ACE2. That protein appears throughout the body and especially in the lungs, explaining why they are favoured targets of the virus.

Previous studies have suggested, based on a proxy for protein levels, that the brain has very little ACE2 and is likely to be spared. But Iwasaki and her colleagues looked more closely and found that the virus could indeed enter brain cells using this doorway.

Its pretty clear that it is expressed in the neurons and its required for entry, Iwasaki said.

Her team then looked at two sets of mice one with the ACE2 receptor expressed only in the brain, and the other with the receptor only in the lungs. When they introduced the virus into these mice, the brain-infected mice rapidly lost weight and died within six days. The lung-infected mice did neither.

The structure and cross-sectional view of the novel coronavirus SARS-CoV-2. Image: Wikimedia

Despite the caveats attached to mouse studies, the results still suggest that virus infection in the brain may be more lethal than respiratory infection, Iwasaki said.

The virus may get to the brain through the olfactory bulb which regulates smell through the eyes or even from the bloodstream. Its unclear which route the pathogen is taking, and whether it does so often enough to explain the symptoms seen in people.

I think this is a case where the scientific data is ahead of the clinical evidence, Muotri said.

Researchers will need to analyse many autopsy samples to estimate how common brain infection is and whether it is present in people with milder disease or in so-called long-haulers, many of whom have a host of neurological symptoms.

Forty percent to 60% of COVID-19 patients experience neurological and psychiatric symptoms, said Dr. Robert Stevens, a neurologist at Johns Hopkins University. But the symptoms may not all stem from the virus invading brain cells. They may be the result of pervasive inflammation throughout the body.

For example, inflammation in the lungs can release molecules that make the blood sticky and clog up blood vessels, leading to strokes. Theres no need for the brain cells themselves to be infected for that to occur, Zandi said.

But in some people, he added, it may be low blood oxygen from infected brain cells that triggers strokes: Different groups of patients may be affected in different ways, he said. Its quite possible that youll see a combination of both.

Some cognitive symptoms, like brain fog and delirium, might be harder to pick up in patients who are sedated and on ventilators. Doctors should plan to dial down sedatives once a day, if possible, in order to assess COVID-19 patients, Stevens said.

Apoorva Mandavilli. c.2020 The New York Times Company

Link:
Headaches, confusion and delirium with COVID-19: How SARS-CoV-2 attacks the brain - Firstpost

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Post-COVID heart damage alarms researchers: ‘There was a black hole’ in infected cells – Yahoo Movies UK

Friday, September 11th, 2020

Shelby Hedgecock contracted the coronavirus in April and thought she had fought through the worst of it the intense headaches, severe gastrointestinal distress and debilitating fatigue but early last month she started experiencing chest pain and a pounding heartbeat. Her doctor put her on a cardiac monitor and ordered blood tests, which indicated that the previously healthy 29-year-old had sustained heart damage, likely from her bout with COVID-19.

I never thought I would have to worry about a heart attack at 29 years old, Hedgecock told Yahoo News in an interview. I didnt have any complications before COVID-19 no preexisting conditions, no heart issues. I can deal with my taste and smell being dull, I can fight through the debilitating fatigue, but your heart has to last you a really long time.

Hedgecocks primary-care physician has referred her to a cardiologist she will see this week; the heart monitor revealed that Hedgecocks pulse rate is wildly irregular, ranging from 49 to 189 beats per minute, and she has elevated inflammatory markers and platelet counts. She was told to go to the emergency room if her chest pain intensifies before she can see the specialist. A former personal trainer who is now out of breath just from walking around the room, Hedgecock is worried about what the future holds.

She is far from alone in her struggle. Dr. Ossama Samuel is a cardiologist at New Yorks Mount Sinai Hospital, where he routinely sees coronavirus survivors who are contending with cardiac complications. Samuel said his team has treated three young and otherwise healthy coronavirus patients who have developed myocarditis an inflammation of the heart muscle weeks to months after recovering from the virus.

Shelby Hedgecock in a hospital bed. (Shelby Hedgecock)

Myocarditis can affect how the heart pumps blood and trigger rapid or abnormal heart rhythms. It is particularly dangerous for athletes, doctors say, because it can go undetected and can result in a heart attack during strenuous exercise. In recent weeks, some collegiate athletes have reported cardiac complications from the coronavirus, underscoring the seriousness of the condition.

Last month, former Florida State basketball center Michael Ojo died from a heart attack in Serbia; Ojo had recovered from the coronavirus before he collapsed on the basketball court. An Ohio State University cardiologist found that between 10 and 13 percent of university athletes who had recovered from COVID-19 had myocarditis.When the Big Ten athletic conference announced the cancellation of its season last month, Commissioner Kevin Warren cited the risk of heart failure in athletes. Researchers have estimated that up to 20 percent of people who get the coronavirus sustain heart damage.

Samuel said he feels an obligation to warn people, particularly since some of the patients he and Mount Sinai colleagues have seen with myocarditis had only mild cases of the coronavirus months ago.

We are now seeing people three months after COVID who have pericarditis [inflammation of the sac around the heart] or myocarditis, Samuel said. He said he believes a small fraction of coronavirus survivors are sustaining heart damage, but when a disease is so widespread it is concerning that a tiny fraction is still sizable.

Samuel said he worries particularly about athletes participating in team sports, since many live together and spend time in close quarters. Teammates may all get the coronavirus and recover together, Samuel said, but the one who really gets that crazy myocarditis could be at risk of dying through exercise or training.

Story continues

Its a concern about what do you do: Should we do sports in general, should we do it in schools, should we do it in college, should we just do it for professionals who understand the risk and they're getting paid? Samuel asked. I hope we dont scare the public, but we should make people aware.

Samuel is recommending that patients recovering from COVID-19 with myocarditis avoid workouts for three to six months.

Todd McDevitt, who runs a stem-cell lab at Gladstone Institutes, which is affiliated with the University of California at San Francisco, recently published images that show how the coronavirus can directly invade the heart muscle. McDevitt said he was so alarmed when he saw a sample of heart muscle cells in a petri dish get diced by the coronavirus that he had trouble sleeping for nights afterward.

Todd McDevitt. (Facebook)

McDevitt said his teams research was spurred by their desire to understand if the coronavirus is entering heart cells and how it is affecting them. He was surprised to see the heart muscle samples he was studying react to a very small amount of the coronavirus, usually within 24 to 48 hours. He said the virus decimated the heart cells in his petri dishes.

Cell nuclei the hubs of all the genetic information, all of the nuclear DNA in many of the cells were gone, McDevitt said. There was a black hole literally where we would normally see the nuclear DNA. Thats also pretty bizarre.

While McDevitts study has not yet been peer-reviewed it is still in pre-print he said he felt compelled to share the findings as soon as possible. He said his team also sampled tissues from three COVID-19 patient autopsies and found similar damage in the heart muscles of those patients, none of whom had been flagged for myocarditis or heart problems while they were alive.

This is probably not the whole story yet, but we think we have insights into the beginning of when the virus would get into some of these people and what it might be doing that is concerning enough that we should probably let people know, because clinicians need to be thinking about this, McDevitt said in an interview. We dont have any means of bringing heart muscle back. ... This virus is [causing] a very different type of injury, and one we haven't seen before.

McDevitt said the chopped-up heart muscles he and his colleagues saw are so concerning because when the microfibers in the muscle are damaged, the heart cant properly contract.

If heart muscle cells are damaged and they cant regenerate themselves, then what youre looking at is someone who could prematurely have heart failure or heart disease due to the virus, McDevitt said. This could be a warning sign for a potential wave of heart disease that we could see in the future, and its in the survivors thats the concern.

McDevitt said he believes the risk of heart disease is serious and one people should consider as they assess their own risk of getting the coronavirus.

I am more scared today of contracting the virus, by far, than I was four months ago, he said.

In lab experiments, infection of heart muscle cells with SARS-CoV-2 caused long fibers to break apart into small pieces, shown above. (Gladstone)

The medical journal the Lancet recently reported that an 11-year-old child had died of myocarditis and heart failure after a bout of COVID-induced multisystem inflammatory syndrome (MIS-C). An autopsy showed coronavirus embedded in the childs cardiac tissue.

A recent study from Germany found that 78 percent of patients who had recovered from the coronavirus and who had only mild to moderate symptoms while ill with the disease had indications of cardiac involvement on MRIs conducted more than two months after their initial infection.Lead investigator Eike Nagel said it is concerning to see such widespread cardiac impact; six in 10 of the patients Nagels team studied experienced ongoing myocardial inflammation.

We found an astonishingly high level of cardiac involvement approximately two months after COVID infection, Nagel said in an email. These changes are much milder than observed in patients with severe acute myocarditis.

The scale of the cardiac impact on relatively healthy, young patients surprised many doctors. Nagel said the findings are significant on a population basis, and that the impact of COVID-19 on the heart must be studied more.

Dr. Gregg Fonarow. (UCLA)

Dr. Gregg Fonarow, chief of UCLAs Division of Cardiology and director of the Ahmanson-UCLA Cardiomyopathy Center, said the picture is evolving, but the new studies showing cardiac impact in even young people with mild cases of COVID-19 have raised troubling new questions.

We really do need to take seriously individuals that have had the infection and are having continued symptoms, [and] not just dismiss those symptoms, Fonarow said. There could be, in those who had milder or even asymptomatic cases, the potential for cardiac risk.

Fonarow said it is important to understand whether a more proactive screening and treatment approach is needed to better address the needs of patients who have recovered from the coronavirus and who may still have weakened heart function. Fonarow said he found McDevitts research to be potentially significant because it proves from a mechanistic standpoint that there can be direct cardiac injury from the virus itself.

Even if it were going to impact, say, 2 percent of the people that had COVID-19, when you think of the millions that have been infected, that ends up in absolute terms being a very large number of individuals, Fonarow said in an interview. You dont want people to be unduly alarmed, but on the other hand you dont want individuals to be complacent about, Oh, the mortality rate is so low with COVID-19, I dont really care if Im infected because the chances that it will immediately or in the next few weeks kill me is small enough, I dont need to be concerned. There are other consequences.

_____

Read more from Yahoo News:

See the original post here:
Post-COVID heart damage alarms researchers: 'There was a black hole' in infected cells - Yahoo Movies UK

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‘There was a black hole’ in infected cells – Sports Grind Entertainment

Friday, September 11th, 2020

Shelby Hedgecock contracted the coronavirus in April and thought she had fought through the worst of it the intense headaches, severe gastrointestinal distress, and debilitating fatigue but early last month she started experiencing intense chest pain and a pounding heartbeat. Her doctor put her on a cardiac monitor and ordered blood tests, which indicate the previously healthy 29-year-old had sustained heart damage, likely from her bout with COVID-19.

I never thought I would have to worry about a heart attack at 29 years old, Hedgecock told Yahoo News in an interview. I didnt have any complications before COVID-19 no pre-existing conditions, no heart issues. I can deal with my taste and smell being dull; I can fight through the debilitating fatigue, but your heart has to last you a really long time.

Hedgecocks primary care physician has referred her to a cardiologist she will see this week; the heart monitor revealed Hedgecocks pulse rate is wildly irregular, ranging from 49 to 189 beats per minute, and she has elevated inflammatory markers and platelet counts. Hedgecock was told to go to the emergency room if her chest pain intensifies before she can see the specialist. A former personal trainer who is now out of breath just from walking around the room, Hedgecock is worried about what the future holds.

Hedgecock is far from alone in her struggle. Dr. Ossama Samuel is a cardiologist at New Yorks Mount Sinai Hospital, where he routinely sees coronavirus survivors who are contending with cardiac complications. Samuel said his team has treated three young and otherwise healthy coronavirus patients who have developed myocarditis an inflammation of the heart muscle weeks to months after recovering from the virus.

Myocarditis can affect how the heart pumps blood and trigger rapid or abnormal heart rhythms. It is particularly dangerous for athletes, doctors say, because it can go undetected and can result in a heart attack during strenuous exercise. In recent weeks, some collegiate athletes have reported cardiac complications from coronavirus, underscoring the seriousness of the condition.

Story continues

Last month, former Florida State basketball center Michael Ojo died from a heart attack in Serbia; Ojo had recovered from coronavirus before he collapsed on the basketball court. An Ohio State University cardiologist found that between 10 and 13 percent of university athletes who had recovered from COVID-19 had myocarditis. When the Big Ten athletic conference announced the cancellation of its season last month, Commissioner Kevin Warren cited the risk of heart failure in athletes. Researchers have estimated that up to 20 percent of people who get coronavirus sustain heart damage.

Samuel said he feels an obligation to warn people, particularly since some of the patients he and other Mount Sinai colleagues have seen with myocarditis had only mild cases of coronavirus months ago.

We are now seeing people three months after COVID who have pericarditis [inflammation of the sac around the heart] or myocarditis, Samuel said. He said he believes a small fraction of coronavirus survivors are sustaining heart damage, but when a disease is so widespread it is concerning that a tiny fraction is still sizable.

Samuel said he worries particularly about athletes participating in team sports since many live together and spend time in close quarters. Teammates may all get coronavirus and recover together, Samuel said, but the one who really gets that crazy myocarditis could be at risk of dying through exercise or training.

Its a concern about what do you do: Should we do sports in general, should we do it in schools, should we do it in college, should we just do it for professionals who understand the risk and theyre getting paid? Samuel asked. I hope we dont scare the public, but we should make people aware.

Samuel is recommending patients recovering from COVID-19 with myocarditis avoid workouts for three to six months.

Todd McDevitt, who runs a stem-cell lab at the University of California at San Francisco-affiliated Gladstone Institutes, recently published images that show how coronavirus can directly invade the heart muscle. McDevitt said he was so alarmed when he saw a sample of heart muscle cells in a petri dish get diced by the coronavirus that he had trouble sleeping for nights afterward.

McDevitt said his teams research was spurred by their desire to understand if the coronavirus is entering heart cells and how it is affecting them. McDevitt was surprised to see the heart muscle samples he was studying react to a very small amount of coronavirus, usually within 24-48 hours. He said the virus decimated the heart cells in his petri dishes.

Cell nuclei the hubs of all the genetic information, all of the nuclear DNA in many of the cells were gone, McDevitt said. There was a black hole literally where we would normally see the nuclear DNA. Thats also pretty bizarre.

While McDevitts study has not yet been peer-reviewed it is still in pre-print he said he felt compelled to share the findings as soon as possible. He said his team also sampled tissues from three COVID-19 patient autopsies and found similar damage in the heart muscles of those patients, none of whom had been flagged for myocarditis or heart problems while they were alive.

This is probably not the whole story yet, but we think we have insights into the beginning of when the virus would get into some of these people and what it might be doing that is concerning enough that we should probably let people know because clinicians need to be thinking about this, McDevitt said in an interview. We dont have any means of bringing heart muscle back. This virus is [causing] a very different type of injury and one we havent seen before.

McDevitt said that the chopped up heart muscles he and his colleagues saw is so concerning because when the microfibers in the muscle are damaged, the heart cant properly contract.

If heart muscle cells are damaged and they cant regenerate themselves, then what youre looking at is someone who could prematurely have heart failure or heart disease due to the virus, McDevitt said. This could be a warning sign for a potential wave of heart disease that we could see in the future, and its in the survivors thats the concern.

McDevitt said that he believes the risk of heart disease is serious and one people should consider as they assess their own risk of getting the coronavirus.

I am more scared today of contracting the virus, by far, than I was four months ago, McDevitt said.

The Lancet recently reported an 11-year-old child had died of myocarditis and heart failure after a bout of COVID-induced multi-system inflammatory syndrome (MIS-C). An autopsy showed coronavirus embedded in the childs cardiac tissue.

A recent study from Germany found that 78 percent of patients who had recovered from coronavirus and who had only mild to moderate symptoms while ill with the disease had indications of cardiac involvement on MRIs conducted more than two months after their initial infection.Lead investigator Eike Nagel said it is concerning to see such widespread cardiac impact; six in 10 of the patients Nagels team studied experienced ongoing myocardial inflammation.

We found an astonishingly high level of cardiac involvement approximately two months after COVID infection, Nagel said in an email. These changes are much milder than observed in patients with severe acute myocarditis.

The scale of the cardiac impact on relatively healthy, young patients surprised many doctors. Nagel said the findings are significant on a population basis, and that the impact of COVID-19 on the heart must be studied more.

Gregg Fonarow, chief of UCLAs Division of Cardiology and director of the Ahmanson-UCLA Cardiomyopathy Center, said the picture is evolving, but the new studies showing cardiac impact in even young people with mild cases of COVID have raised troubling new questions.

We really do need to take seriously individuals that have had the infection and are having continued symptoms [and] not just dismiss those symptoms, Fonarow said. There could be, in those who had milder or even asymptomatic cases, the potential for cardiac risk.

Fonarow said it is important to understand whether a more proactive screening and treatment approach is needed to better address the needs of patients who have recovered from coronavirus and who may still have weakened heart function. Fonarow said he found McDevitts research to be potentially significant because it proves from a mechanistic standpoint that there can be direct cardiac injury from the virus itself.

Even if it were going to impact, say, 2 percent of the people that had COVID 19, when you think of the millions that have been infected that ends up in absolute terms being a very large number of individuals, Fonarow said in an interview. You dont want people to be unduly alarmed, but on the other hand you dont want individuals to be complacent about, Oh, the mortality rate is so low with COVID-19, I dont really care if Im infected because the chances that it will immediately or in the next few weeks kill me is small enough, I dont need to be concerned. There are other consequences.

_____

Read more from Yahoo News:

Read more:
'There was a black hole' in infected cells - Sports Grind Entertainment

Read More...

New Report: Regenerative Medicine & Advanced Therapies Sector Thriving Despite COVID-19 – PharmiWeb.com

Tuesday, August 11th, 2020

Cell, Gene & Tissue-Based Therapy Developers Poised to Break Year-Over-Year Global Financing Records

WASHINGTON, D.C. August 6, 2020 The Alliance for Regenerative Medicine (ARM), the leading international advocacy organization dedicated to realizing the promise of regenerative medicines and advanced therapies, today announces the publication of its H1 2020 Global Sector Report, Innovation in the Time of COVID-19. The report provides an in-depth look at trends and metrics in the gene, cell, and tissue-based therapeutic sector in the midst of the pandemic.

As the voice of the sector globally, ARM regularly publishes sector data reports to showcase clinical and scientific progress, as well as advancements and remaining challenges in the policy environment surrounding cell, gene and tissue-based therapies. The report also includes updated metrics on fundraising and clinical trials from more than 1,000 therapeutic developers worldwide.

Highlights from the H1 2020 Global Sector Report include:

Janet Lambert, CEO of ARM, commented: The regenerative medicine and advanced therapy sector has shown remarkable resilience in the face of many new challenges posed by COVID-19. Most importantly, were continuing to see patients benefit from the profound therapeutic effects of both approved products and those currently in clinical development. ARM will continue to work with our membership and with policymakers in the second half of 2020 to further advance these transformative technologies. We are committed to bringing these life-changing therapies to patients in need.

This report is the latest in ARMs series of global regenerative medicine sector reports, providing up-to-date metrics on financings and the clinical landscape, as well as expert commentary on key trends and progress in the field. The full report is available online here, with key sector metrics and infographics available here. For more information, please visit http://www.alliancerm.org or contact Kaitlyn (Donaldson) Dupont at kdonaldson@alliancerm.org.

About the Alliance for Regenerative Medicine

The Alliance for Regenerative Medicine (ARM) is the leading international advocacy organization dedicated to realizing the promise of regenerative medicines and advanced therapies. ARM promotes legislative, regulatory and reimbursement initiatives to advance this innovative and transformative sector, which includes cell therapies, gene therapies and tissue-based therapies. Early products to market have demonstrated profound, durable and potentially curative benefits that are already helping thousands of patients worldwide, many of whom have no other viable treatment options. Hundreds of additional product candidates contribute to a robust pipeline of potentially life-changing regenerative medicines and advanced therapies. In its 11-year history, ARM has become the voice of the sector, representing the interests of 360+ members worldwide, including small and large companies, academic research institutions, major medical centers and patient groups. To learn more about ARM or to become a member, visit http://www.alliancerm.org.

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New Report: Regenerative Medicine & Advanced Therapies Sector Thriving Despite COVID-19 - PharmiWeb.com

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Embryos could be vulnerable to covid-19 in second week of pregnancy: Study – Livemint

Tuesday, August 11th, 2020

LONDON :Human embryos could be susceptible to COVID-19 as early as the second week of pregnancy, if the mother gets sick, potentially affecting the chances of a successful pregnancy, according to a study.

Scientists at the UK's University of Cambridge and California Institute of Technology in the US found that genes thought to play a role in how the SARS-CoV-2 virus infects our cells have been found to be active in embryos as early as during the second week of pregnancy.

While initially recognised as causing respiratory disease, the SARS-CoV-2 virus, which causes COVID-19 disease, also affects many other organs, they said.

Advanced age and obesity are risk factors for complications but questions concerning the potential effects on foetal health and successful pregnancy for those infected with SARS-CoV-2 remain largely unanswered, according to the researchers.

In the journal Open Biology, the researchers described how they used technology to culture human embryos through the stage they normally implant in the body of the mother to look at the activity - or 'expression' - of key genes in the embryo. On the surface of the SARS-CoV-2 virus are large 'spike' proteins. Spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body, the researchers explained. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell.

The virus manipulates the host cell's machinery to allow the virus to replicate and spread, they said.

The researchers found patterns of expression of the genes ACE2, which provide the genetic code for the SARS-CoV-2 receptor, and TMPRSS2, which provides the code for a molecule that cleaves both the viral spike protein and the ACE2 receptor, allowing infection to occur.

These genes were expressed during key stages of the embryo's development, and in parts of the embryo that go on to develop into tissues that interact with the maternal blood supply for nutrient exchange.

Gene expression requires that the DNA code is first copied into an RNA message, which then directs the synthesis of the encoded protein.

"Our work suggests that the human embryo could be susceptible to COVID-19 as early as the second week of pregnancy if the mother gets sick," said Professor Magdalena Zernicka-Goetz, who holds positions at both the University of Cambridge and Caltech.

"To know whether this really could happen, it now becomes very important to know whether the ACE2 and TMPRSS2 proteins are made and become correctly positioned at cell surfaces.

If these next steps are also taking place, it is possible that the virus could be transmitted from the mother and infect the embryo's cells," Zernicka-Goetz said.

Professor David Glover, also from Cambridge and Caltech, noted that genes encoding proteins that make cells susceptible to infection by the novel coronavirus become expressed very early on in the embryo's development.

"This is an important stage when the embryo attaches to the mother's womb and undertakes a major remodelling of all of its tissues and for the first time starts to grow," Glover said.

He added that COVID-19 could affect the ability of the embryo to properly implant into the womb or could have implications for future foetal health.

The team said that further research is required using stem cell models and in non-human primates to better understand the risk.

However, they said their findings emphasise the importance for women planning for a family to try to reduce their risk of infection.

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Embryos could be vulnerable to covid-19 in second week of pregnancy: Study - Livemint

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New Study Presents Cell-based Therapy for MN Diseases or Spinal Cord Disorders – Mirage News

Tuesday, August 11th, 2020

The spinal cord is a bundle of nerves inside the spine that gives your body structure and support. Spinal cord injuries (SCIs) tend to be devastating and most are permanent. Recent research has shown that motor neuron obtained from skin cells could serve as potential treatments for spinal cord injuries, and thus has received considerable research attention. With this, a new door has been opened for treating not only spinal cord injuries, caused by workplace accidents and car crashes, but also Lou Gehrigs disease, known as amyotrophic lateral sclerosis or ALS.

A research team, led by Professor Jeong Beom Kim and his research team in the School of Life Sciences at UNIST has demonstrated that human fibroblasts can be converted into induced motor neurons (iMNs) by sequentially inducing two transcription factors, POU5F1(OCT4) and LHX3. The research team further investigated the therapeutic effects of iMNs for treating traumatic spinal cord injury using rodent spinal cord injury model. Their findings indicate that the sequential induction of two transcription factors is essential for generating self-renewing iMNICs more efficiently. This method not only ensures large-scale production of pure iMNs, but also facilitates the feasibility of iMNs for SCI treatment.

The spinal cord is responsible for transmitting signals from the brain to the rest of the body, and vice versa. Along with motor and sensory deficits, damage to the spinal cord can cause long-term complications, including limited mobility. Although there are many treatment options available for people with SCI, most of them have adverse side effects that impact therapy. And this is why stem cell (SC) therapies to restore functions of damaged tissues are attracting attention, recently. Among those cells constituting the spinal cord, motor neurons that involved in the regulation of muscle function have emerged as a promising candidate for the stem cell-based therapy for SCIs. Despite these encouraging advances, ethical issue of embryonic stem cells (ESCs) and tumorigenic potential of induced pluripotent stem cells (iPSCs) have impeded their translations into clinical trials.

Figure 1. The experimental scheme for the generation of induced motor neurons (iMNs) from human fibroblasts via sequential transduction of two transcription factors.

To overcome these limitations, Professor Kim and his research team established an advanced direct conversion strategy to generate iMNs from human fibroblasts in large-scale with high purity, thereby providing a cell source for the treatment of SCI. These iMNs possessed spinal cord motor neuronal identity and exhibit hallmarks of spinal MNs, such as neuromuscular junction formation capacity and electrophysiological properties in vitro. Importantly, their findings also show that transplantation of iMNs improved locomotor function in rodent SCI model without tumor formation. According to the research team, This proof-of-concept study shows that our functional iMNs can be employed to cell-based therapy as an autologous cell source. Through this, they resolved the problem of immune rejection, and thus reduce the risk of cancer.

In the study, we succeeded in generating iMNs from human fibroblasts by overexpressing POU5F1(OCT4) and LHX3, says Hyunah Lee (Combined MS/Ph.D program of Life Sciences, UNIST), the first author of the study.

Figure 2. Therapeutic effects of iMNs in rat spinal cord injury model in vivo. (A) The position of hindlimbs in control rat and iMN-transplanted rat after 8 weeks of transplantation. (B) C staining analysis of spinal cords after 8 weeks of transplantation (I; Control, J; iMN-transplanted).

The developed motor nerve cell manufacturing method has the advantage of being capable of mass production. A sufficient amount of cells is required for patient clinical treatment, but the existing direct differentiation technique has limited the number of cells that can be obtained. On the other hand, the method developed by the research team is capable of mass production because it undergoes an intermediate cell stage capable of self-renewal. After injecting the produced cells into the spinal cord injury mice, it was confirmed that the lost motor function is restored and the nerves are regenerated in the damaged spinal cord tissue.

Although further investigation on mechanism responsible for cell fate conversion may be needed, our strategy is a safer and simpler methodology that may provide new insights to develop personalized stem cell therapy and drug screening for MN diseases or spinal cord disorders, says Professor Kim. If combined with SuPine Patch, an adhesive hydrogel patches with the purpose of regenerating the damaged spinal cords, its therapeutic effects will be maximized. He adds, As the incidence of spinal cord injury is high due to industrial accidents, synergistic effects with public hospitals specializing in industrial accidents scheduled to be built in Ulsan should be expected.

This study has been jointly carried out with Professor Kims startup company, SuPine Therapeutics Inc. with the support of the Ministry of SMEs and Startups (MSS). The findings of this research have been published in the 2020 June issue of the online edition of eLife, a renowned academic journal of the European Molecular Biology Organizationl (EMBO).

Journal Reference

Hyunah Lee, Hye Yeong Lee, Byeong Eun Lee, et al., Sequentially induced motor neurons from human fibroblasts facilitate locomotor recovery in a rodent spinal cord injury model, eLife, (2020).

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New Study Presents Cell-based Therapy for MN Diseases or Spinal Cord Disorders - Mirage News

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Stromal Vascular Fraction Market 2019 to 2029 Size by Product Analysis, Application, End-Users, Regional Outlook, Competitive Strategies and Forecast…

Tuesday, August 11th, 2020

Stromal vascular fraction is gaining significant importance in various fields, including internal medicine, orthopaedics, plastic and general surgery,and wound healing.

Ease of harvest, abundant availability, and stable phenotype are some factors increasing the demand for stromal vascular fraction. Also, stromal vascular fraction secretes several soluble factors with anti-inflammatory, immunomodulatory, and analgesic effects, which leads to an alternative treatment option for various diseases, significantly benefitting the growth of thestromal vascular fraction marketduring the forecast period.

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Company Profiles

Delivery of stromal vascular fraction by intra-articular injection has advantages over surgical implantation, such as less invasiveness, better patient compliance, and lower cost.

The global stromal vascular fraction market was valued atUS$ 76 Mnin 2018, and is expected to witness a CAGR of around4%over the forecast period (2019-2029).

Key Takeaways of Stromal Vascular Fraction Market Study

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Stromal vascular fraction has emerged as an efficient alternative in the field of regenerative medication. However, better-structured and significant clinical investigations need to be carried out to demonstrate and define the therapeutic potential of stromal vascular fraction,says a PMR analyst.

Stromal Vascular Fraction Manufacturers Focusing on Innovative Methods to Optimize Tissue Recovery

Consistent up-gradation and innovation in methods to recover adipose tissue-derived mesenchymal stem cells (ATD-MSCs) for autologous use in regenerative medication applications are expected to offer significant opportunities for the stromal vascular fraction market.

For instance, LipoCell from Tissyou, is furnished with a semipermeable film that separates fat tissues from squander components with the assistance of continuous irrigation. The dialysis of the tissue limits the pressure and trauma to the cell and extracellular matrix, evacuating the blood and oil deposits, which are pro-inflammatory.

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More Valuable Insights on Stromal vascular fraction Market

Persistence Market Research brings a comprehensive research report on the forecasted revenue growth at global, regional, and country levels, and provides an analysis of the latest industry trends in each of the segments from 2014 to 2029.

The global stromal vascular fraction market is segmented in detail to cover every aspect of the market and present a complete market intelligence approach to the reader.

The study provide compelling insights on the stromal vascular fraction market on basis of product (SVF isolation products, SVF aspirate purification products, and SVF transfer products), application (cosmetic applications, orthopedic applications, soft tissue applications, and others), and end user (hospitals, ambulatory surgical centers, stem cell laboratories, and others), across six major regions.

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Stromal Vascular Fraction Market 2019 to 2029 Size by Product Analysis, Application, End-Users, Regional Outlook, Competitive Strategies and Forecast...

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Stem Cells Used to Treat Severe Complications from COVID …

Sunday, July 12th, 2020

Patients with COVID-19 have been observed to experience a wide variety of symptoms, ranging from a mild cough to acute respiratory failure.So,what causes the most severe cases of coronavirus infection? In some instances,COVID-19 fatalities occur when a patients own immune system inflicts too much damage on the individuals infected organs.

In a general sense, the immune system protects the body from pathogens througha seriesofchemical signaling networks.These signals are received by specificreceptor cells which in turn respond by enhancingimmune responses like inflammation, fever, and cell death.One type of chemical signal that is prevalent in the immune systems response to coronavirus is a cytokine. These tiny proteinscancarry outmany differentfunctions, but the most prevalenttype ofcytokine in coronavirus research is one that promotes inflammation.

In a healthyimmune system, the body must be able to recognize and control the intensity ofimmuneresponses bysignaling for the suppression of a response after its activation. This cycle of enhancing and suppressing immune functions keeps fevers from running too highandinflammation from damaging tissue.As people age, the immune cells that produce cytokines often become less efficient. In some of these patients, there is a lack of balance between signals that promote immune responses and signals that suppress them.When these individuals contract coronavirus, the immune systemmay beactivated in what is called a cytokine storm. During this process, cytokines are sent out in a surge that causes severe amounts ofinflammationin the lungs, leading to tissue damage. At this point,the virus may haveinfected other organs where increasing inflammationwilllead toevenmore damage. If there is a lack of signalingto stop this immune response, organ damage may besufficient to cause death. In patients at risk of experiencing this cytokine storm, professionals are considering using mesenchymal stem cells to prevent and repair tissue damage.

A stem cellis a specific kind of cell thatdoesnot have a specialized function in thebody.Instead,theyhave the potential to differentiate intomanyspecific types of cells, such as red blood cells or neurons. There are three main types of stem cells: embryonic, induced pluripotent, and adult. Adult stem cells, which are found in small quantities in all types of tissue in the human body, are most of interest to researchers seeking to treat COVID-19.Thesetypes ofcells are only capable of developing into limited types of tissue, likely the type that they already reside in. Mesenchymal stem cells(or MSCs)are a type of adult stem cell that may be derived fromseveraldifferent organs, including the bone marrow, fat, and umbilical cords. Theyhave the potential to become the cells that are responsible for creating bone, cartilage, or fat. Aside from their ability to differentiate into other cell types, MSCs have severalother properties that make them of interest in treating COVID-19. First, these stem cellscansuppress the activity of certain immune cells. Evidence suggests that through these functions, MSCs may be able to regulate inflammatory responses.Second, MSCscan secrete growth factors that stimulate the development ofsurrounding cells.

Trials are now taking place totest the efficacy ofMSCs to treat severecomplications from COVID-19. In these studies, MSCs are injected intoapatient experiencingrespiratory infection.The MSCs then accumulate in the lungs, where their regulatory properties counteract or prevent thecytokine storm. The stem cells regenerative properties also serve a purpose to repair and regrow damaged tissue.A recent study conducted in Beijing, China treated seven coronavirus patients who had either critically severe, severe, or normal reactions to the virus. All seven patients exhibited symptoms including shortness of breath, fever, and weakness. Within two days of their MSC transplant, these symptoms had disappeared in all the patients.Manysimilartrials are now being conducted in multiple different countries.

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Stem Cells Used to Treat Severe Complications from COVID ...

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