StemCell Therapy

Introduction

Pancreatic cancer (PC) with high aggressiveness and malignancy has become an enormously common cancer of the digestive system during 10 years. Globally, the 5year overall survival (OS) rate of patients with PC is less than 9%, and the mortality rate is predicted to peak by 2030.1 Due to insidious symptoms, only less than 10% of PC is initially diagnosed with a local stage, and the prognosis of PC is extremely poor.2 Therefore, further investigation into novel cancer-related genes is required and meaningful for the improvement of prognosis.

SWI/SNF complexes are evolutionarily conserved multi-subunit molecular machines that mediate transcriptional regulation3 and are linked to a poor prognosis across several cancer types.46 Among them, Actin-like 6A (ACTL6A), encoded by Actl6a, acts as a chromatin-remodeling factor and regulates the function of progenitor and stem cell transcriptionally.7,8 In addition, ACTL6A expression is associated with prognosis in many types of cancer, such as hepatocellular carcinoma,9 colon cancer,10 and esophageal squamous cell carcinoma.11 Recently, research revealed that epithelial-to-mesenchymal transition (EMT) was also regulated by ACTL6A.9,12 In addition, the study showed that ACTL6A overexpression could lead to increased repair of cisplatin-DNA adducts and cisplatin resistance.13 However, the role of ACTL6A in tumorigenicity and clinical prognosis of PC remains unclear so far.

In this connection, we analyzed the differences of ACTL6A expression in PC tissues and normal tissues, and we investigated the prognostic effect of ACTL6A on PC based on cases in public databases and confirmed it in our center.

Differential expression of Actl6a mRNA between pancreatic tumor and normal tissues was analyzed using the Gene Expression Profiling Interactive Analysis website (GEPIA; http://gepia.cancerpku.cn/). Data for 179 patients with PC and 171 normal tissue samples analyzed on the GEPIA website were obtained from TCGA and normal tissue samples from Genotype-Tissue Expression (GTEx).1416 The gene expression, determined as transcripts per million (TPM), was calculated by log2 (TPM + 1) for comparison. Based on the expression levels of Actl6a mRNA, the overall survival (OS) of patients was also analyzed.

A total of 60 patients with PC confirmed by histopathology from January 2013 to June 2020 at Zhongda Hospital, Medical School of Southeast University were selected for the study. Sixty paired pancreatic tumor and normal tissues from patients who did not receive chemotherapy or radiotherapy were obtained to detect ACTL6A expression. Any patients with incomplete epidemiological and clinical information or lack of follow-up information were excluded. The results of serum tumor markers were collected from 60 healthy individuals who were admitted to the hospital for physical examination at the same time. All patients provided informed consent. Patients were followed up by telephone or at office visits every 3 months from the end date of surgery. The latest follow-up ended in July 2021. According to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, pathological stages were validated. The study was conducted with approval from the ethics committee of Zhongda Hospital, Southeast University. The study protocol protected the private information of enrolled patients in accordance with the provisions of the Helsinki Declaration.

The paraffin-embedded pathological specimens were cut into 4-m-thick sections. After being dewaxed in xylene and rehydrated in grade alcohol, the paraffin sections were submerged in a pH 6.0 citric acid solution and heated at 95C for approximately 15 minutes for antigen retrieval. Next, the sections were incubated with rabbit ACTL6A antibody (Abcam Corp, USA, diluted 1:200) overnight at 4C and washed 3 times with phosphate buffer saline (PBS). The sections were then incubated with horseradish peroxidase-conjugated secondary antibody for 30 minutes at room temperature in the dark. After stained with freshly prepared 3,3-diaminobenzidine (DAB), they were counterstained with hematoxylin and differentiated with 1% hydrochloric acid. PBS was used to substitute the primary antibody as negative control. Finally, the sections were dehydrated with alcohol and sealed with neutral gum, and pictures were taken by microscope for positive cell calculation. Immunohistochemical staining analysis was performed independently by two pathologists according to the staining intensity and the percentage of positive cells. The staining intensities were 0 (negative), 1 (positive 1+), 2 (positive 2+), and 3 (positive 3+), respectively. The percentages of cells were 0 (negative), 1 (125%), 2 (2650%), 3 (5175%), and 4 (76100%), respectively.17,18 Total scores were calculated by multiplying the scores of staining intensity and percentage.

Statistical analyses and mapping were performed using SPSS software (version 18.0, IBM Corporation, Armonk, NY, USA), GraphPad Prism (Version 8.4.3, GraphPad Software, La Jolla, CA, USA), and R (version 3.4.1, http://www.r-project.org/) in the present study. Wilcoxon test was used to evaluate significant differences between pancreatic cancer and normal tissues, and the 2 test and continuity correction were used to explore the relationship between ACTL6A expression and clinicopathological features. The diagnostic efficiency of ACTL6A expression was analyzed through receiver operating characteristic (ROC) curves for PC. The sensitivity and specificity were evaluated at an optimal cutoff. The expression of ACTL6A was classified as high expression and low expression according to the cutoff. Survival analysis was analyzed using KaplanMeier curve, and difference among groups was assessed using Log rank test. Both univariable and multivariable analyses were used in survival analysis, respectively. The clinicopathological factors with significant associations (p < 0.1) in the aforementioned univariable analysis were subjected to multivariate analysis. p < 0.05 was considered to be statistically significant.

To explore the potential role of ACTL6A in PC, the expression of Actl6a mRNA was analyzed with the publicly available GEPIA database. In clinical PC specimens (n = 178) and normal tissues (n = 171), Actl6a mRNA had significant differential expression between the two groups. What is more, Actl6a mRNA was upregulated in PC than normal tissues (p < 0.05, Figure 1A). Then, the protein expression of ACTL6A was validated and compared in PC samples (n = 60) and normal tissues (n = 60) with immunohistochemistry staining in our center. The typical immunohistochemical results of normal tissues and PC tissues are shown in Figure 1B, which demonstrated that ACTL6A was mainly observed in the nucleus of cells. By multiplying the staining intensity and percentage, the protein expression of ACTL6A was also overexpressed in pancreatic cancer (p < 0.001, Figure 1C). Table 1 shows the number of patients with different scores based on immunohistochemistry staining. The results above indicated that ACTL6A was upregulated in PC.

Table 1 The Number of Patients in Different Scores Based on Immunohistochemistry Staining

Figure 1 Expression of ACTL6A in PC and normal tissues. (A) Differential expression of Actl6a mRNA between pancreatic tumor and normal tissues. (B) Immunohistochemical results of typical normal tissues and PC tissues with different staining intensities. (C) Differential expression of ACTL6A between pancreatic tumor and normal tissues. (D) ACTL6A represented a moderate diagnostic value. The ROC of pancreatic cancer samples and normal tissues. (E) ROC for the diagnostic efficiency of ACTL6A, serum CEA, and serum CA199. *p<0.05.

Abbreviations: ACTL6A, actin like 6A; PC, pancreatic cancer; ROC, receiver operating characteristic curves; CA199, carbohydrate antigen 199; CEA, carcinoembryonic antigen.

To investigate the diagnostic value of ACTL6A expression for PC, we performed ROC analysis on total scores of pancreatic cancer and normal pancreatic tissue, as shown in Figure 1D and E, and the AUC value was 0.724, which was higher than that of carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA). These results represented a moderate diagnostic value for PC. The specificity and sensitivity of ACTL6A expression for PC diagnosis were 0.867 and 0.567, respectively. The cut-off value established for ACTL6A expression for the diagnosis of PC was 5.

To further understand the role of ACTL6A in PC, we analyzed the relationship between ACTL6A expression and the clinicopathological characteristics. Patients with PC were divided into ACTL6A low-expression group (score 05; n = 34) and ACTL6A high-expression group (score 612; n = 26) with the cut-off value of score 5. The relationship between ACTL6A expression and clinicopathological factors of pancreatic cancer is summarized in Table 2. Lymphovascular space invasion (LVSI) of PC was significantly associated with ACTL6A expression, which was more likely to occur in the ACTL6A high group. LVSI was present in 55.9% (19/34) of patients in the ACTL6A high group and 26.9% (7/26) in ACTL6A low group.

Table 2 Relationships Between the Expression Level of ACTL6A and the Clinicopathological Characteristics of PC Patients

The survival data of 178 PC patients was obtained from TCGA dataset. Patients are split into two groups according to the median value of Actl6a mRNA expression. One-half (89 patients) was defined as high Actl6a mRNA expression, and the other was defined as low Actl6a mRNA expression. Obviously, high Actl6a mRNA was associated with poor overall survival in patients with PC (p < 0.001, Figure 2A). Furthermore, based on data from our center, the KaplanMeier method was used to investigate the relationship between the expression of ACTL6A protein and OS of patients. The median OS in PC patients for the high and low expression of ACTL6A was 8.0 0.4 months and 13.0 1.6 months, respectively. Obviously, patients with low ACTL6A expression had significantly longer survival time than those with high ACTL6A expression (p < 0.001, Figure 2B).

Figure 2 (A) KaplanMeier curves of overall survival in PC patients with high and low Actl6a mRNA expression. (B) KaplanMeier curves of overall survival in PC patients with high and low ACTL6A expression.

Abbreviations: ACTL6A, actin like 6A; PC, pancreatic cancer.

Univariate and multivariate Cox analyses were performed to identify the prognostic factors on OS of patients with PC. The results demonstrated that ACTL6A overexpression (p = 0.032) and grade (p = 0.008) were risk factors for survival in patients with PC through univariate Cox analysis. Further multivariate Cox analysis showed that ACTL6A expression (p = 0.046) was an independent risk factor for poor prognosis of PC (Table 3). As shown in Figure 3A and B, the forest plot visualizes the specific HR of risk factors.

Table 3 Univariate and Multivariate Analysis of Clinicopathological Characteristics Affecting Prognosis of Patients with PC

Figure 3 Forest plot of univariate (A) and multivariate (B) cox regression.

Abbreviations: ACTL6A, actin like 6A; PC, pancreatic cancer; LVSI, lymphovascular space invasion.

Worldwide, PC has become a malignancy with a dismal prognosis and high mortality, which has a 5-year survival rate of less than 10%.19 There are two clinical features that are involved with the poor prognosis of PC. First, initial symptoms of PC are insidious, which leads to many challenges for early diagnosis. Second, PC has a significant potential for invasion and metastasis.20 In detail, the distant spread may occur in the early stages of PC, and more than 50% of patients with PC have no possibility to be treated with surgical resection.21 Scientific problems covering early diagnosis, the mechanisms of metastasis, and the risk factors of prognosis are necessary to be solved to improve survival of PC. In this study, we clarified that ACTL6A is highly expressed in PC, and it is a reliable marker for predicting the prognosis of PC patients.

ACTL6A is involved in a variety of cellular processes, including vesicle transport, spindle orientation, nuclear migration, and chromatin remodeling.7,22 Increasing evidence has suggested its involvement with tumorigenesis and development of cancer.7 ACTL6A has been reported to be overexpressed in a variety of malignancies, including hepatocellular carcinoma,9 ovarian cancer,18 cervical cancer,23 and esophageal squamous cell carcinoma,11 which is correlated with the prognosis of patients with malignancies. This evidence suggests that ACTL6A is a potential oncogene, and it is observed that ACTL6A expression is also upregulated in PC in our study, which is consistent with previous studies. Researchers have been constantly exploring diagnostic markers for PC. Jelski et al reported that the activity of alcohol dehydrogenase (ADH) class III isoenzyme in pancreatic cancer was significantly higher than that in normal tissues.24 And the total activity of ADH and class III isoenzyme was increased in the serum of patients with PC, which can be due to the release of this isoenzyme from PC cells.25 Nevertheless, it was not observed that other types of ADH isoenzymes (I, II, IV) had a significant change in either pancreatic tissue or serum. Further exploration revealed that ADH III had the diagnostic value for PC.26 Also, our evidence demonstrated a potential role for ACTL6A as a marker of PC.

ACTL6A plays a vital role in the invasion and metastasis of tumors by promoting EMT, leading to poor prognosis. ACTL6A expression is higher in fibroblasts and progenitor cells and inhibits the epithelial properties of epidermal tissues.27,28 Moreover, the functions of ACTL6A are similar to features of stem cells, including the inhibition of cell differentiation and the ability of self-renewal, which is closely related to the biological functions of EMT.28 In hepatocellular carcinoma, ACTL6A activated Notch1 signaling via SOX2, which regulated EMT to affect the biological function and clinical prognosis of hepatocellular carcinoma. Other studies also revealed ACTL6A as an EMT activator to promote metastasis in osteosarcoma29 and colon cancer,10 respectively. Some studies mentioned the potential role of ACTL6A involvement with tumors. Zhang et al found that ACTL6A was a glycolytic regulator by phosphoglycerate kinase 1(PGK1) in ovarian cancer and participated in FSH-induced tumorigenesis of ovarian cancer.18 And in triple negative breast cancer, ACTL6A promoted tumor cell proliferation by enhancing the stability of MYC oncogene.30 Additional evidence suggested that ACTL6A promoted the progression of cervical cancer and laryngeal squamous cell carcinoma through activation of yes-associated protein (YAP) signaling.23,31 Besides, ACTL6A could stabilize transcriptional regulators YAP and transcriptional coactivator with PDZ-binding motif (TAZ) to regulate the proliferation, migration, and invasion of glioma.32 Further studies revealed that the knockdown of ACTL6A gene resulted in the inhibition of protein kinase B (AKT) signaling pathway to suppress cell migration and increased sensitivity of glioma cells to temozolomide.33 Moreover, in vivo and in vitro, Shrestha et al revealed that p21Cip1, a tumor suppressor, was suppressed by ACTL6A in epidermal squamous cell carcinoma, leading to epidermal squamous cell carcinoma progression.34 More importantly, overexpressed ACTL6A was related to cisplatin-induced DNA damage and led to resistance to cisplatin.13 These studies have further confirmed the contribution of ACTL6A in the invasion, metastasis, and clinical prognosis of tumors.

In this research, we reveal a correlation between the expression of ACTL6A and the invasion and prognosis of PC. It was found that LVSI was more likely to occur in PC patients with high ACTL6A expression, which might be related to the high aggressiveness caused by ACTL6A. Univariate and multivariate Cox analysis suggested that ACTL6A expression and grade were independent risk factors for poor prognosis of PC. This study also confirmed ACTL6A as a valid prognostic biomarker and potential therapeutic target in PC. Given a follow-up and survival analysis of survival data of PC patients, patients with high ACTL6A expression had significantly poorer prognosis. It was suggested that ACTL6A expression in PC was a risk factor, which was consistent with the existing studies. And ACTL6A overexpression was associated with tumor progression. However, whether ACTL6A could induce PC cell proliferation, invasion, and metastasis in vitro, as well as the specific regulatory mechanisms, deserved further investigation.

In conclusion, it was found that levels of ACTL6A expression were elevated in PC tissues, which was associated with LVSI. Moreover, it was demonstrated that ACTL6A was an independent risk prognostic indicator for PC. ACTL6A could be used as a valuable biomarker to predict the prognosis of PC, assisting clinicians to develop preventative measures and better treatment strategies to improve mortality in patients with PC.

The authors are grateful to all the patients, researchers and institutions that participated in the TCGA and GTEx database.

The authors report no conflicts of interest in this work.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209249.

2. Zhang L, Sanagapalli S, Stoita A. Challenges in diagnosis of pancreatic cancer. World J Gastroenterol. 2018;24(19):20472060.

3. Mittal P, Roberts CWM. The SWI/SNF complex in cancer - biology, biomarkers and therapy. Nat Rev Clin Oncol. 2020;17(7):435448.

4. Naito T, Udagawa H, Umemura S, et al. Non-small cell lung cancer with loss of expression of the SWI/SNF complex is associated with aggressive clinicopathological features, PD-L1-positive status, and high tumor mutation burden. Lung Cancer. 2019;138:3542.

5. Cyrta J, Augspach A, De Filippo MR, et al. Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity. Nat Commun. 2020;11(1):5549.

6. Fukumoto T, Magno E, Zhang R. SWI/SNF complexes in ovarian cancer: mechanistic insights and therapeutic implications. Mol Cancer Res. 2018;16(12):18191825.

7. Krasteva V, Buscarlet M, Diaz-Tellez A, Bernard MA, Crabtree GR, Lessard JA. The BAF53a subunit of SWI/SNF-like BAF complexes is essential for hemopoietic stem cell function. Blood. 2012;120(24):47204732.

8. Panwalkar P, Pratt D, Chung C, et al. SWI/SNF complex heterogeneity is related to polyphenotypic differentiation, prognosis, and immune response in rhabdoid tumors. Neuro Oncol. 2020;22(6):785796.

9. Xiao S, Chang RM, Yang MY, et al. Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition. Hepatology. 2016;63(4):12561271.

10. Zeng Z, Yang H, Xiao S. ACTL6A expression promotes invasion, metastasis and epithelial mesenchymal transition of colon cancer. BMC Cancer. 2018;18(1):1020.

11. Li RZ, Li YY, Qin H, Li SS. ACTL6A promotes the proliferation of esophageal squamous cell carcinoma cells and correlates with poor clinical outcomes. Onco Targets Ther. 2021;14:199211.

12. Nieto MA, Huang RY, Jackson RA, Thiery JP. Emt: 2016. Cell. 2016;166(1):2145.

13. Xiao Y, Lin FT, Lin WC. ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer. Proc Natl Acad Sci U S A. 2021;118(3):e2015808118.

14. Cancer Genome Atlas Research N; Weinstein JN, Collisson EA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013;45(10):11131120.

15. Consortium GT. Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science. 2015;348(6235):648660.

16. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98W102.

17. Rao X, Wang J, Song HM, Deng B, Li JG. KRT15 overexpression predicts poor prognosis in colorectal cancer. Neoplasma. 2020;67(2):410414.

18. Zhang J, Zhang J, Wei Y, Li Q, Wang Q. ACTL6A regulates follicle-stimulating hormone-driven glycolysis in ovarian cancer cells via PGK1. Cell Death Dis. 2019;10(11):811.

19. Zhu H, Li T, Du Y, Li M. Pancreatic cancer: challenges and opportunities. BMC Med. 2018;16(1):214.

20. Ansari D, Tingstedt B, Andersson B, et al. Pancreatic cancer: yesterday, today and tomorrow. Future Oncol. 2016;12(16):19291946.

21. Lamb YN, Scott LJ. Liposomal irinotecan: a review in metastatic pancreatic adenocarcinoma. Drugs. 2017;77(7):785792.

22. Zhao K, Wang W, Rando OJ, et al. Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling. Cell. 1998;95(5):625636.

23. Zhao J, Li L, Yang T. MiR-216a-3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A-mediated YAP signaling. J Cell Physiol. 2020;235(12):97189728.

24. Jelski W, Chrostek L, Szmitkowski M. The activity of class I, II, III, and IV of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in pancreatic cancer. Pancreas. 2007;35(2):142146.

25. Jelski W, Zalewski B, Szmitkowski M. Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with pancreatic cancer. Dig Dis Sci. 2008;53(8):22762280.

26. Jelski W, Kutylowska E, Laniewska-Dunaj M, Szmitkowski M. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) as candidates for tumor markers in patients with pancreatic cancer. J Gastrointestin Liver Dis. 2011;20(3):255259.

27. Bao X, Tang J, Lopez-Pajares V, et al. ACTL6a enforces the epidermal progenitor state by suppressing SWI/SNF-dependent induction of KLF4. Cell Stem Cell. 2013;12(2):193203.

28. Lu W, Fang L, Ouyang B, et al. Actl6a protects embryonic stem cells from differentiating into primitive endoderm. Stem Cells. 2015;33(6):17821793.

29. Sun W, Wang W, Lei J, Li H, Wu Y. Actin-like protein 6A is a novel prognostic indicator promoting invasion and metastasis in osteosarcoma. Oncol Rep. 2017;37(4):24052417.

30. Jian Y, Huang X, Fang L, et al. Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer. J Exp Clin Cancer Res. 2021;40(1):56.

31. Dang Y, Zhang L, Wang X. Actin-like 6A enhances the proliferative and invasive capacities of laryngeal squamous cell carcinoma by potentiating the activation of YAP signaling. J Bioenerg Biomembr. 2020;52(6):453463.

32. Ji J, Xu R, Zhang X, et al. Actin like-6A promotes glioma progression through stabilization of transcriptional regulators YAP/TAZ. Cell Death Dis. 2018;9(5):517.

33. Chen X, Xiang Z, Li D, Zhu X, Peng X. ACTL6A knockdown inhibits cell migration by suppressing the AKT signaling pathway and enhances the sensitivity of glioma cells to temozolomide. Exp Ther Med. 2021;21(2):175.

34. Shrestha S, Adhikary G, Xu W, Kandasamy S, Eckert RL. ACTL6A suppresses p21(Cip1) expression to enhance the epidermal squamous cell carcinoma phenotype. Oncogene. 2020;39(36):58555866.

View post:
Upregulated expression of actin-like 6A is a risk factor | CMAR - Dove Medical Press

As the COVID-19 pandemic continues to evolve, five studies presented during the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition shed light on the persisting burden that COVID-19 has had on people with underlying blood disorders.

We take care of the patients at the highest risk for COVID-19 illness and those who are among the least likely to respond to the vaccine; these and other studies underscore the dual vulnerability facing many of our patients, said press briefing moderator,Laura Michaelis, MD, of the Medical College of Wisconsin. Hematologists have continued to play a unique role in contributing to the emerging science of COVID-19, especially given our expertise in clotting, and ASH has continued to provide leadership in an uncertain time with vetted resources and timely guidance for how best to manage our patients amid the pandemic.

Two studies analyze data from theASH Research Collaborative (ASH RC) COVID-19 Registry for Hematology, which started in the early days of the pandemic to provide real-time observational data summaries to clinicians on the front lines of the fight against COVID-19, as well as researchers and providers around the world.

In September 2021, the Centers for Disease Control and Prevention (CDC) awarded the ASH RC funding to identify the overall burden of COVID-19, the effects of health disparities and outcomes, and the areas where future resources should be focused for treatment for people living with hematologic malignancies. Specifically, CDC funding, in part, supports additional data submissions to the ASH RC COVID-19 Registry, real-time public data summaries, and research activities. As the Registry dataset has grown, researchers have identified potential drivers of severe illness, hospitalization, and mortality. The data also suggest that aggressive supportive treatment of COVID-19 can improve outcomes for many patients and should be offered.

A third study conducted among individuals living with sickle cell disease suggests COVID-19 infection can cause occlusive events, resulting in pain episodes, but these patients seem to respond to COVID-19 treatments and also were quick to adopt precautions and shift to virtual appointments as needed.

The final two studies look at antibody response following vaccination among people with various hematologic malignancies, helping give clues into which groups of patients may still be at high risk of COVID-19 after getting the vaccines.

A number of studies have shown that people with blood cancers have less than optimal responses to vaccination, and there is a need to continue to push for mitigation strategies, said Dr. Michaelis.

Abstract 3040: Risks for Hospitalization and Death Among Patients with Blood Disorders from the ASH RC COVID-19 Registry for Hematology

Patients with blood cancers, particularly those with more advanced disease, are especially vulnerable to serious COVID-19 outcomes, including an elevated chance of severe illness and death from COVID-19, according to an analysis of more than 1,000 patients in the ASH RC COVID-19 Registry for Hematology. Based on the report, 17% of patients with blood cancers who developed COVID-19 died from COVID-related illness, a strikingly higher mortality rate than what was seen in the general population, according to researchers. Older age, male sex, poor cancer prognosis, and electing to defer intensive care when it was recommended were all independently associated with a heightened chance of dying.

In our analysis, having a poor prognosis for underlying disease prior to COVID-19 and deciding to forgo ICU-level care for that disease were the most powerful predictors of mortality among patients with blood cancer and COVID-19and the two may very well be related, saidLisa K. Hicks, MD, MSc, of St. Michaels Hospital in Toronto, Canada. If someone is sick enough to require ICU-level care and their preference is not to receive this type of care, we would expect that decision to have a major impact on their survival.

According to the data, patients whose physician had estimated that they had less than six months to live due to their cancer before getting COVID-19 had six-fold higher odds of dying and these odds nearly doubled among people who decided to forgo more intensive care due to COVID-19. However, these groups represented a small proportion of the overall sample with only 7% estimated to have a pre-COVID-19 prognosis of under six months, and 9% deferring ICU care.

Of particular interest to the field was whether blood cancer treatment would affect COVID-19 mortality. Most patients included in the dataset (71%) received cancer treatment during the previous year; others were either in remission or had not yet needed treatment. In addition, receiving cancer treatment in the year prior to COVID-19 infection did not significantly increase the risk of death as some had feared; however, it was linked to an increased risk of hospitalization if infected by COVID-19. Older age, being male, having active cancer, and having other health conditions were also associated with an increased risk of hospitalization from COVID-19 among patients with blood cancers.

In the early days of the pandemic, there was a lot of uncertainty about whether we should withhold or modify blood cancer treatments in regions with high levels of COVID-19, said Dr. Hicks. The data are somewhat reassuring in that, while recent cancer treatment was linked to a higher risk of hospitalization among those with blood cancer and COVID-19, it wasnt independently associated with a statistically greater likelihood of dying. The type of blood cancer was also not associated with a higher risk of COVID-19 mortality. These findings suggest that patients who need treatment for their hematologic malignancy should likely proceed with that treatment.

Data were collected between April 1, 2020, and July 2, 2021, as part of the ASH RCs COVID-19 Registry for Hematology, which is a public-facing, volunteer registry reporting outcomes of COVID-19 infection in patients with underlying blood disorders. A total of 1,029 patients from around the globe were included in this analysis. Of these, 41% were female. The median age was 50 to 59 years of age, and patients ranged from five to more than 90 years of age; 27% had at least one co-existing condition such as heart disease, hypertension, respiratory disease, or diabetes. Researchers sought to identify factors associated with a higher likelihood of hospitalization and death from COVID-19.

Of people included in the analysis, 354 (34%) had acute leukemia or myelodysplastic syndromes (MDS), 255 (25%) had lymphoma, 206 (20%) had plasma cell dyscrasia (myeloma/amyloid/POEMS), 116 (11%) had chronic lymphocytic leukemia (CLL), and 98 (10%) had myeloproliferative neoplasm (MPN).

Patients with MPN and plasma cell dyscrasia had less severe COVID-19 illness overall compared to patients with CLL, leukemia, MDS, or lymphoma, which Dr. Hicks said is not surprising as patients with MPN typically live with their disease for many years, are generally in better health, and may not require immunosuppressive treatment.

The data from the ASH RC COVID-19 Registry has limitations and findings should generally be regarded as hypothesis generating, Dr. Hicks said. Nonetheless, the data do suggest that patients with blood cancers are at substantial risk from COVID-19; this finding has implications for our patients, how we manage our clinics amid COVID-19 and the changing variants, and how vaccines, boosters, and antibody treatments are distributed.

In this analysis, 17% of those with blood cancers died of COVID-19; the mortality rate among those infected with SARS-CoV-2 in the general U.S. population has been reported to be between 1.6% and 6.2% at various times during the pandemic, Dr. Hicks added.

The ASH RC Registry is a public voluntary registry that continues to accrue cases and provide the information on a public dashboard to help keep the hematology community apprised on changing trends. Dr. Hicks said the team will also be looking at how the risks of hospitalization and death changed as vaccines and COVID-19 treatments became more widely available.

Abstract 2800: Clinical Predictors of Outcome in Adult Patients with Acute Leukemias and Myelodysplastic Syndrome and COVID-19 Infection: Report from the American Society of Hematology Research Collaborative (ASH RC) Data Hub

In separate analyses of 257 patients with acute leukemia or MDS who developed COVID-19 and are part of the ASH RC COVID-19 Registry for Hematology, both neutropenia (a type of low white blood cell count) and having active MDS or leukemia (versus being in remission) were found to strongly and independently predict severe COVID-19 illness.Once hospitalized, active disease by itself whether someone was newly diagnosed or had relapsed was not tied to a greater odds of dying from COVID-19, nor was receiving ongoing cancer treatment.

For this retrospective analysis, which included data from 135 patients with acute myeloid leukemia (AML), 82 with acute lymphocytic leukemia (ALL) and 40 with MDS who were diagnosed with COVID-19 from 2019 to present, researchers sought to identify characteristics that put patients at higher risk of severe illness or death from COVID-19. At the time of COVID-19 diagnosis, 46% were in remission and 44% had active disease.

COVID-19 severity was defined as mild (no hospitalization required), moderate (hospitalization required), or severe (ICU admission required). After adjusting for several risk factors, active disease and neutropenia at the time of COVID-19 diagnosis were also associated with severe COVID-19 illness that necessitated ICU-level care.

Overall, one out of five (21%) patients died from COVID-19, which was higher than the mortality rate reported for the registry as a whole (17%) or what was seen in the general public during the same period of time, researchers reported. Mortality among hospitalized patients with COVID-related illness was 34%, and mortality among patients once admitted in the ICU was 68%. The two factors most strongly associated with a higher likelihood of dying among these patients were: 1) how long someone was perceived to live from the underlying MDS or leukemia before getting COVID-19, as defined as a physicians estimated prognosis of less than six months survival, and 2) whether or not they decided to go to the ICU if it was recommended. Older age, male sex, and neutropenia at diagnosis were also associated with COVID-19 mortality though less strongly.

This is a particularly vulnerable population and we suspected they may do worse because they are immunocompromised and, as it is, the average survival for acute blood cancers if untreated is three to six months, so if COVID-19 comes together with that diagnosis, its very concerning, saidPinkal Desai, MD, MPH, of Weill Cornell Medical College, New York. Our data suggest these patients can survive COVID-19 and their underlying disease itself was not associated with worse mortality, which means that if these patients are given appropriate and aggressive treatment, we can help them recover. But if there are decisions that are made after they get to the hospital (for example, whether to go to the ICU) that clearly plays a role.

In fact, patients for whom ICU-level care was recommended and declined had five times higher odds of dying compared with patients who opted to go to the ICU.

Patients who went to the ICU did better regardless of disease status, said Dr. Desai. Just having acute leukemia or MDS puts these patients at high risk of severe COVID-19, and they need to be hospitalized and receive treatments, but decisions about the ICU should be individualized, a patients prognosis should be discussed, and if a patient wants aggressive care for COVID-19 that should be offered.

Patients were more likely to forgo ICU care if they were older, male, smokers, or if they had active disease or an estimated pre-COVID-19 survival of less than six months. Forgoing ICU care was associated with a higher COVID-19 mortality in all patients.

Our data show that these patients do survive COVID-19 after receiving care in the ICU and underscore that cancer treatments should not be withheld as inferior treatment would quickly put many of these patients into the category of a prognosis of less than six months, said Dr. Desai. COVID-19 vaccination is also critically important.

The data are limited in that they were collected before COVID-19 vaccines were widely available; future data should inform about mortality rates among vaccinated patients.

Patient Vigilance and Virtual Visits Credited for Reducing Exposure, Illness, and Death Due to COVID-19 in Cohort With Sickle Cell Disease

Abstract 3105: COVID-19 Infection and Outcomes at a Comprehensive Sickle Cell Center

The Georgia Comprehensive Sickle Cell Center at Grady Hospital in Atlanta the nations largest treatment center for adults living with sickle cell disease (SCD) quickly switched to offering virtual visits for routine follow-up care of its more than 1,300 patients as the COVID-19 pandemic emerged. People living with SCD, an inherited disorder characterized by crescent- or sickle-shaped red blood cells, are immunocompromised and thus at high risk for COVID-19. The center established a database to track all COVID-19 cases among its patients.

The first report from that database the largest single-center study to date on COVID-19 in people with SCD now shows that between March 2020 and March 2021, just 55 (4%) of the centers 1,343 patients contracted COVID-19, of whom 16 (29%) were hospitalized and two ultimately died from complications of infection with the virus. Eleven patients (20%) required neither hospitalization nor emergency-room treatment for complications of either COVID-19 or SCD during the one-year follow-up period.

Our findings show that when supported by virtual visits, most of our patients successfully reduced their exposure to and complications from COVID-19, said study authorFuad El Rassi, MD, of Emory University and director of research at the Grady Comprehensive Sickle Cell Center. They understood the risks and followed recommendations to stay at home and avoid interacting with other people.

The 55 patients who contracted COVID-19 were aged 28 on average and 51% were female. Of those who visited an emergency room or were hospitalized during the year of follow-up, 27 (49%) sought care for a painful episode of SCD and 15 (27%) for complications of COVID-19. Among those who sought care for COVID-19 symptoms, 32 (58%) had pain as their primary symptom, followed by cough and fever (40%) and shortness of breath (31%); 25% had chest X-ray evidence of pneumonia. Sixteen patients received treatment, with nine receiving the antibody treatment remdesivir, eight receiving the steroid drug dexamethasone, and seven receiving red-blood-cell products to treat pain.

Twenty cases of COVID-19 were diagnosed between March and September of 2020. The two patient deaths from COVID-19 occurred in June and July of 2020. Among the 35 cases diagnosed between October 2020 and March 2021, no patients died and the number of hospitalizations decreased as better treatments for COVID-19 became available.

One of the patient deaths was due to a blood clot in the lungs, Dr. El Rassi said. This unfortunately occurred before it became the standard of care to treat hospitalized COVID-19 patients with blood thinners, he said.

Despite the second peak in COVID-19 cases in the winter of 2021, there were no reported deaths among our patients who developed the disease, Dr. El Rassi added. This suggests that the patients vigilance in staying home may have been crucial to reducing illness and death, and having the option for virtual visits was also key. Patients who needed blood tests or to obtain medication refills were sent to satellite centers.

Patient adherence to COVID-19 precautions was measured based on their responses to physician questions at intake and during virtual follow-up visits.

Dr. El Rassi and his colleagues plan to conduct further studies to evaluate the impact of the delta variant on diagnosis, illness, and death from COVID-19 among the sickle cell centers patients.

Some People With Blood Disorders May Continue to Face High Risk of COVID-19 After Vaccination

Abstract 218: Antibody Response to Vaccination with BNT162b2, mRNA-1273, and ChADOx1 in Patients with Myeloid and Lymphoid Neoplasms

According to a new study, about 15% of people with blood cancers and other blood disorders had no vaccination-related antibodies after receiving a COVID-19 vaccine. While researchers say it is encouraging that 85% of study participants did show an antibody response, the findings suggest that additional precautions may be warranted to prevent COVID-19 infection among people with blood disorders.

The study examined antibody levels after COVID-19 vaccination in people with blood cancers such as lymphoid and myeloid neoplasms, autoimmune disorders, and non-cancerous disorders of blood or immune cells. The results suggest that patients with lymphoma and those currently receiving treatment are the least likely to build antibodies in response to a COVID-19 vaccine.

Some patients with hematologic diseases do not have an adequate antibody response and might, therefore, not have sufficient protection from vaccination, saidSusanne Saussele, MD, of III. Medizinische Klinik, Medizinische Fakultt Mannheim, Universitt Heidelberg, Germany. This study can help guide vaccination strategies for these patients. In addition, our study suggests that when it is possible to delay beginning treatment for their underlying disorder, it may be best to wait so that a patient can receive a vaccine or booster first.

People with blood disorders face a high risk of hospitalization and death if they become infected with COVID-19, especially if they are older or have received therapies that reduce B-cells, a type of immune cell. Since the majority of participants in the study did respond to COVID-19 vaccines, the results underscore the role of vaccination as an important strategy for preventing severe disease, researchers said. However, the findings also suggest vaccination should be complemented with other precautions. We should recommend ongoing protective measures such as masks, social distancing, and screenings, as well as prioritizing vaccination for family members and caregivers to protect the patients, Dr. Saussele said.

For the study, the researchers recruited 373 patients treated for blood disorders at University hospital Mannheim in Germany and measured vaccine-related antibodies in their blood a median of 12 weeks after final vaccination. More than 90% of participants had blood cancer, while 9% had either autoimmune disease or a non-malignant blood disorder. Most patients had received the Pfizer-BioNTech [BNT162b2]vaccine; 10% received the Moderna vaccine [mRNA-1273], 7% received the AstraZeneca vaccine [ChADOx1], and 6% received one dose from each of the two vaccine types.

Overall, 85% of participants tested positive for vaccine-related antibodies and 15% tested negative. The rate of negative antibody results was highest among those with lymphoid neoplasms, a group of diseases that include lymphoma, myeloma, and lymphoid leukemia. Among these patients, 36% tested negative for vaccine-related antibodies. Patients with indolent non-Hodgkin lymphoma, a slow-growing type of lymphoma, had the weakest response to vaccination overall.

Being on active therapy was associated with a reduced antibody response. Overall, 61% of study participants were on active therapy. Of those who tested negative for vaccine-related antibodies, most (71%) were on active therapy. Therapies correlated with a negative response were rituximab, ibrutinib/acalabrutinib, and ruxolitinib.

Our study suggests that most people with blood malignancies not only those who are currently under treatment should monitor their antibody levels and work closely with their care team to determine how to continue to protect themselves from COVID-19, Dr. Saussele said. Antibody measurements offer a hint of who has responded to the vaccine and can perhaps ease up on precautions a bit.

Dr. Saussele noted that the results are limited in that the study did not examine participants T-cell response to vaccination, meaning that some patients level of protection may have been underestimated. The researchers plan to continue to measure antibody levels for at least a year and to assess participants rates of breakthrough infections and response to vaccine boosters.

Strong Antibody Response Seen in Patients With AML and MDS After Second Dose of mRNA COVID-19 Vaccine

Abstract 217: Responses to SARS-Cov-2 Vaccines in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia

In one of the largest studies to date of the antibody response to vaccination against COVID-19 in people who had been treated for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), patients responded well to two doses of the Moderna mRNA vaccine and saw a particularly dramatic increase in levels of antibodies against the virus after receiving their second vaccine dose.

We observed a strong antibody response to the vaccine in a group of patients at high risk for severe COVID-19, including among patients who were on active treatment for AML or MDS, said Jeffrey Lancet, MD, of the H. Lee Moffitt Cancer Center and Research Institute in Florida. The fact that antibody levels increased so dramatically after the second vaccine dose suggests potential utility in additional dosing, even for patients who initially respond poorly to the vaccine.

Previous studies had shown that patients with other types of blood cancer specifically, B-cell lymphomas or chronic lymphocytic leukemia often have a poor antibody response to vaccination with one of the COVID-19 mRNA vaccines. Treatment of these cancers suppresses the ability of the immune system to produce white blood cells such as B cells and T cells to fight off infection.

The treatment of myeloid cancers such as AML and MDS, including allogeneic transplantation, also suppresses white blood cells and leaves patients vulnerable to infection, said Dr. Lancet. We conducted this study to find out whether patients with these cancers would also have a suppressed or absent immune response to COVID-19 vaccination.

The study involved 46 patients who either had previously or were currently undergoing treatment for AML or MDS. The patients median age was 68 years; 59% were male and 96% were white. On average, they were about two years out from the diagnosis of their cancer. Fifteen patients (33%) were receiving treatment for their cancer at the time they were vaccinated. Thirty-two patients (70%) had undergone a transplant of blood-forming stem cells from a healthy donor as part of their cancer treatment. Forty patients (87%) were in remission when they were vaccinated. (Note that some patients are counted twice e.g., if they had undergone a stem cell transplant and were in remission, they would be counted in both categories. For this reason, the percentages add up to more than 100%.)

All patients received a first dose of the Moderna mRNA vaccine (this vaccine type was being given at the clinic) in late January 2021 and a second dose four weeks later. The investigators collected blood specimens from each patient before each vaccine dose was administered and again at four weeks after the second dose. The primary aims of the study were to describe the immune response and assess the safety profile of the vaccine in a cohort of patients with AML or MDS.

Blood test results at 29 days after the first vaccine dose showed that 70% of patients had an antibody response; at 57 days following the second dose 97% had an antibody response. Antibody levels were significantly higher after the second dose compared with after the first dose. Patients antibody response was not significantly affected by age, gender, race, disease status (i.e., active or in remission), time from disease diagnosis to vaccination, number of treatments patients had undergone for their cancer, whether patients had received a stem cell transplant, or whether they were on active treatment at the time of vaccination.

The most common adverse events following vaccination were the typical ones reported after vaccination with a COVID-19 mRNA vaccine, such as fatigue, headache, arm swelling, and mild pain at the injection site.

The study results should be confirmed in a larger group of patients, Dr. Lancet said. However, based on these data, we feel comfortable advising patients with AML or MDS that they should get vaccinated against COVID-19. Due to their vulnerability to COVID-19, they stand to benefit from the vaccine more than most.

This is an observational study without an identified control, or comparator, group, Dr. Lancet cautioned. Another limitation is that because the participants were overwhelmingly white, it is not known whether patients of other races or ethnicities would show a similar antibody response. In addition, the actual protective effect of the vaccine and the T-cell responses to it in this patient population are not yet known; the researchers are currently gathering these data.

The investigators are now following the same cohort of patients to determine whether a third dose of the vaccine can achieve even higher antibody levels than were seen after the second dose.

This press release was published by the American Society of Hematology on December 11, 2022.

Go here to read the rest:
COVID-19 Takes a Toll on People with Blood Cancers and Disorders - Cancer Health Treatment News

Posted on Jan 01, 2022 | Author Dr. Tasaduk Hussain Itoo

Mental health forms a crucial part of one's overall health, comprising emotional, psychological, and social well-being of a person. Broadly, it involves how we think, feel and act. Any negative alteration in such aspects can interfere with one's ability of thinking, behaviour, mood, emotions and feelings, thereby amounting to mental health disorders.

Mental health disorders pose a strong risk to development of heart disease, the effects can arise both, directly through biological pathways, and indirectly through risky health behaviours including substance abuse.

Scientific research has revealed that people experiencing mental health issues like depression, anxiety, stress and even PTSD over a long period of time may experience certain physiologic effects on their body, such as increased cardiac reactivity (e.g., increased heart rate and blood pressure), reduced blood flow to the heart, and heightened levels of cortisol. Over the course of time, these physiologic effects can lead to calcium build-up in the arteries, metabolic disease and heart disease.

Conversely, it has been evidenced that mental health disorders like depression, anxiety, and PTSD can develop after major cardiac events like heart failure, stroke, and heart attack more so after an acute heart disease event from factors like pain, fear of death or disability including financial problems associated with the event.

Furthermore,it has been revealed thatthe impact of medicines used to treat mental health disorders pose a strong risk towards development of cardio-metabolic disease risk use of some antipsychotic medications has been associated with obesity, insulin resistance, diabetes, heart attacks, atrial fibrillation, stroke including death.

Moreover, mental health disorders such as anxiety and depression may increase the chance of adopting unhealthy behaviours such as smoking, alcoholism, sedentary lifestyle or development of resistance to taking prescribed medications. This is because people experiencing a mental health disorder may have fewer healthy coping strategies for stressful situations thus making it difficult for them to make healthy lifestyle choices to reduce their risk of heart disease.

Defining the preventive interventions

The first framework focuses on when in the course of a disease the preventive intervention is required. Primary prevention occurs before any evidence of disease and aims to reduce or eliminate causal risk factors, prevent onset and thus reduce incidence of the disease. Examples include vaccinations to prevent infectious diseases and encouraging healthy eating habits and physical activity to prevent obesity, diabetes, hypertension, and other chronic diseases and conditions.

Secondary prevention occurs at a latent stage of disease: after a disease has begun but before the person has become symptomatic. The goals that ultimately reduce the prevalence of the disease are early identification through screening as well as providing interventions to prevent the disease from becoming manifest. Screening tools and tests are examples of secondary prevention.

Finally, tertiary prevention is an intervention implemented after a disease is established, with the goal of preventing disability, further morbidity, and mortality. Medical treatments delivered during the course of diseases can be considered tertiary prevention. Relapse prevention is another form of tertiary prevention. For example, while talking about mental health disorders, primary, secondary, and tertiary prevention are exemplified respectively by eliminating certain forms of dementia that stem from vitamin deficiencies, screening for problematic drinking that precedes alcohol use disorder, and providing psychosocial treatments to reduce disability among individuals with serious mental illnesses.

The second approach of prevention, largely focuses on who receives an intervention, also has three levels of prevention: universal, selective, and indicated. Universal preventive interventions are given to the entire group (e.g., a school, an entire community, or the whole population), regardless of individuals' level of risk for the disease. Examples include fortification or enrichment of foods, school-based curricula about substance abuse, and informational campaigns, such as public announcements about wearing seat belts or not texting while driving.

Selective preventive interventions are those delivered to a subgroup at increased risk for a disease outcome. Examples include use of hypolipidaemic drugs among those with hyperlipidaemia (to prevent later cardiovascular disease) and pneumococcal vaccination in older adults.

Indicated preventive interventions are those given to an even more select group that is at particularly high risk or is already exhibiting subclinical symptoms. Examples include lifestyle modifications for pre-diabetes or pre-hypertension. While talking about mental health disorders universal, selective, and indicated preventive interventions are exemplified respectively by social and emotional development curricula provided in elementary schools, group-based psychotherapy for children of parents with depressive disorders, and efforts to identify and treat adolescents and young adults who appear to be at clinical high risk.

Prevention of heart diseases

Controlling high blood pressure: This is one of the most important things one can do to reduce their heart disease risk. Exercising, managing stress, maintaining a healthy weight and limiting the amount of sodium in your diet and avoiding alcohol can all help to keep high blood pressure in check. In addition to recommending lifestyle changes, one may need to take medications to treat high blood pressure.

Controlling diabetes: One can manage diabetes with diet, exercise, weight control and medications.

Lowering the amount of cholesterol and saturated fat in one's diet: Eating less cholesterol and fat, especially saturated fat and trans fats may reduce plaque formation in arteries. Besides dietary changes, one may need to take cholesterol-lowering medications.

Exercising regularly: Exercise reduces risk of heart disease in many ways. It can lower blood pressure, increase the level of high-density lipoprotein cholesterol, and improve the overall health of blood vessels and heart. It also helps in losing weight, controlling diabetes and reducing stress.

Eating a diet rich in fruits and vegetables: A diet containing five or more daily servings of fruits or vegetables may reduce risk of heart disease. Following a diet which emphasizes olive oil, fruit, nuts, vegetables and whole grains may be helpful.

Quitting tobacco use: Smoking raises the risk of heart disease for smokers and non-smokers exposed to second-hand smoke. So, quitting tobacco use reduces risk of heart disease.

Avoiding alcohol: It can be a risk factor for heart disease. Heavy alcohol consumption increases risk of high blood pressure, ischemic heart disease and heart attack.

Avoiding drug abuse: Certain drugs, such as cocaine and methamphetamines, are established risk factors for ischemic heart disease.

Anti-platelet drugs are commonly used as preventive medications. Platelets are cells in one's blood that form clots. Anti-platelet drugs make these cells less sticky and less likely to clot. The most commonly used anti-platelet medication is aspirin.

Anticoagulants: The drugs, which include heparin and warfarin reduce blood clotting. Heparin is fast acting and may be used over a short period of time in the hospital. Slower acting warfarin may be used over a longer term.

Link:
Mental health disorders and heart diseases - Rising Kashmir

LEIDEN, Netherlands & CAMBRIDGE, Mass., Dec. 30, 2021 (GLOBE NEWSWIRE) -- ProQR Therapeutics N.V. (Nasdaq:PRQR) (“ProQR”), a company dedicated to changing lives through the creation of transformative RNA therapies for genetic eye diseases, today announced that it has amended its convertible debt financing agreement entered into in 2020 with Kreos Capital (“Kreos”) and Pontifax Medison Debt Financing (“Pontifax”).

Continue reading here:
ProQR Announces Amendment to Convertible Debt Financing Agreement with Pontifax Ventures and Kreos Capital

NEW YORK, Dec. 30, 2021 (GLOBE NEWSWIRE) -- Immunovant, Inc. (Nasdaq: IMVT), a clinical-stage biopharmaceutical company focused on enabling normal lives for people with autoimmune diseases, announced that the Company achieved alignment with the FDA Division of Neurology 1 (“FDA”) to move forward in myasthenia gravis (“MG”). Immunovant plans to start its Phase 3 study for batoclimab in MG in the first half of calendar year 2022.

Original post:
Immunovant Provides Regulatory Update Regarding Initiation of Phase 3 Trial for Batoclimab in Myasthenia Gravis in the First Half of 2022

EMERYVILLE, Calif., Dec. 30, 2021 (GLOBE NEWSWIRE) -- Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing the next generation of cancer and infectious disease immunotherapies, today announced that Gritstone management will participate in the following upcoming investor conferences in January.

Read this article:
Gritstone Announces Presentations during Three Upcoming Investor Conferences

Meet with InMed’s CEO Eric A. Adams, Shane Johnson, SVP and General Manager of BayMedica and Chris Meiering, VP of Commercial Operations Meet with InMed’s CEO Eric A. Adams, Shane Johnson, SVP and General Manager of BayMedica and Chris Meiering, VP of Commercial Operations

Originally posted here:
Registration Now Open For Tribe Public’s Webinar Event "Addressing The Increasing Demand For Rare Cannabinoids" Featuring InMed’s...

WALTHAM, Mass., Dec. 30, 2021 (GLOBE NEWSWIRE) -- Repligen Corporation (NASDAQ:RGEN), a life sciences company focused on bioprocessing technology leadership, today announced that it will present virtually at the 40th Annual J.P. Morgan Healthcare conference being held January 10-13.  Tony J. Hunt, President and Chief Executive Officer, will present on Wednesday, January 12, 2022, at 9:45 a.m. EST.

Read the original post:
Repligen Corporation to Present at 40th Annual J.P. Morgan Healthcare Conference

VANCOUVER, British Columbia, Dec. 30, 2021 (GLOBE NEWSWIRE) -- Lotus Ventures Inc. (CSE: J) (OTC: LTTSF) (“Lotus” or the “Company”), a trusted cannabis producer in Canada is pleased to report its Fiscal 2021 full year results and a second consecutive year reporting a profit for the year ended August 31, 2021.

View post:
Lotus Ventures Inc. Reports Fiscal 2021 Results

- Positive Phase 3 data in 2nd/3rd line NSCLC (Dublin-3): Superior efficacy benefit in plinabulin and docetaxel combination in overall survival, 2-year and 3-year OS rate, PFS, ORR, and significant reduction of grade 4 neutropenia vs. docetaxel alone

Read the original post:
BeyondSpring Announces Third Quarter 2021 Financial Results and Provides a Corporate Update

Company now expects to release topline 52-week results from MAESTRO-NAFLD-1 in January 2022 Company now expects to release topline 52-week results from MAESTRO-NAFLD-1 in January 2022

View post:
Madrigal Provides Update on Timeline for Topline Results from the Phase 3 MAESTRO-NAFLD-1 Clinical Trial of Resmetirom

WOBURN, Mass., Dec. 30, 2021 (GLOBE NEWSWIRE) -- Biofrontera Inc. (Nasdaq: BFRI), a biopharmaceutical company specializing in the commercialization of dermatological products, announced that through the exercise of outstanding warrants the majority ownership of Biofrontera AG was diluted below 50%. Biofrontera AG’s shareholding in Biofrontera Inc. of 8,000,000 shares is unchanged, but now represents approximately 47% of the currently outstanding shares. As a result, Biofrontera Inc. is no longer considered a subsidiary of Biofrontera AG. Biofrontera Inc.’s common stock and warrants are traded on the Nasdaq Capital Market under the ticker symbols “BFRI” and “BFRIW,” respectively.

Continue reading here:
Biofrontera Inc. announces reduction of Biofrontera AG shareholding to less than 50% through warrant exercises

MALVERN, Pa., Dec. 30, 2021 (GLOBE NEWSWIRE) -- Ocugen, Inc. (Nasdaq: OCGN), a biopharmaceutical company focused on discovering, developing, and commercializing novel therapeutics and vaccines, announced today that its partner, Bharat Biotech, posted results from a Phase 2/3 trial conducted in India of candidate vaccine, COVAXIN™ (BBV152), in children, aged 2 – 18 years, demonstrating a robust neutralizing antibody response and favorable safety profile on the pre-print server, medRXiv. Using a two-dose regimen administered 28-days apart, antibody responses in subjects were comparable to adult data from a previous phase 3 study. Those results demonstrated a greater than 93% reduction in severe disease. These pediatric data were the basis of Ocugen’s pediatric Emergency Use Authorization (EUA) submission in the United States for children 2-18 on November 5, 2021.

See the article here:
Ocugen Partner, Bharat Biotech, Announces Positive Immunogenicity and Safety Data From COVAXIN™ (BBV152), COVID-19 Candidate Vaccine, in Children 2...

Company announcement – No. 78 / 2021

Read more:
Total number of shares and voting rights in Zealand Pharma at December 30, 2021

NEW YORK and LONDON, Dec. 30, 2021 (GLOBE NEWSWIRE) -- Akari Therapeutics, Plc (Nasdaq: AKTX) (“Akari” or the “Company”), a biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where the complement and/or leukotriene systems are implicated, today announced that it has entered into definitive agreements with institutional investors and accredited investors, led by existing investors of the Company, including Dr. Ray Prudo, the Company’s Chairman, to receive gross proceeds of approximately $6.0 million.

Here is the original post:
Akari Therapeutics, Plc Announces $6.0 Million Registered Direct Offering

THE WOODLANDS, Texas, Dec. 30, 2021 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that it has submitted a New Drug Application to the U.S. Food and Drug Administration seeking approval for the marketing and sale of sotagliflozin to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure irrespective of left ventricular ejection fraction. The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing.

Read the original here:
Lexicon Submits New Drug Application for Sotagliflozin for the Treatment of Heart Failure in Adults With Type 2 Diabetes

Key Points:

Continue reading here:
Mesoblast Provides Update Following Meeting With FDA’s OTAT on Remestemcel-L for Children With Acute Graft Versus Host Disease

HALIFAX, Nova Scotia, Dec. 30, 2021 (GLOBE NEWSWIRE) -- MedMira Inc. (MedMira) (TSXV: MIR), reported today on its financial results for the quarter ended October 31, 2021.

More here:
MedMira Reports First Quarter Results FY2022

DURHAM, N.C., Dec. 31, 2021 (GLOBE NEWSWIRE) -- Humacyte, Inc. (Nasdaq: HUMA), a clinical-stage biotechnology platform company developing universally implantable bioengineered human tissue at commercial scale, today announced the appointment of Surgical Key Opinion Leaders (KOLs) Alan P. Kypson, M.D., FACS; Luigi Pascarella, M.D., FACS; and Todd E. Rasmussen, M.D., FACS, (Col, ret. USAF MC), to new advisory positions. In these roles, the KOLs will lend their expertise and support to guide the education and clinical advancement efforts of the Human Acellular VesselTM (HAV) and help identify opportunities to advance the Company's early stage complex tissue constructs pipeline and platform.

View post:
Humacyte Announces the Appointments of Three Surgical and Cardiovascular Opinion Leaders to Advisory Roles

The Phase 1 Study Will be Comprised of Two Parts: Phase 1a Dose-escalation that will Evaluate the Safety and Tolerability of NXP800 in Patients with Advanced Solid Tumors, Followed by a Phase 1b to Evaluate Preliminary Efficacy in Specific Populations The Phase 1 Study Will be Comprised of Two Parts: Phase 1a Dose-escalation that will Evaluate the Safety and Tolerability of NXP800 in Patients with Advanced Solid Tumors, Followed by a Phase 1b to Evaluate Preliminary Efficacy in Specific Populations

Continue reading here:
Nuvectis Pharma Initiates Phase 1 Clinical Trial of NXP800