Cilta-Cel Efficacy and Safety in Patients with Progressive Multiple Myeloma after Exposure to Non-Cellular Anti-BCMA Immunotherapy

Introduction: CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating cilta-cel, an anti-BCMA CAR-T therapy, in several multiple myeloma (MM) patient (pt) populations. Objective(s): To report updated results with longer follow-up on cohort C pts with previous exposure to a non-cellular anti- BCMA immunotherapy. Method(s): Cohort C pts had progressive MM after treatment (tx) with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and non-cellular BCMA-targeting agent. A single cilta-cel infusion (target dose 0.75x106 CAR+ viable T cells/kg) was administered 5-7 days post lymphodepletion. Primary endpoint was minimal residual disease (MRD) negativity at 10-5. Secondary endpoints included overall response rate (ORR), duration of response (DOR), and adverse events (AEs). Result(s): As of June 1, 2022, 20 pts (13 ADC exposed;7 BsAb exposed) were treated with cilta-cel;4 pts did not receive cilta-cel due to either low cellular yield (n=2, 1 in each group) or death due to progressive disease (PD) prior to dosing (n=2, 1 in each group) and 6 pts received anti-BCMA tx as their last line of therapy (n=4 ADC, n=2 BsAb). During prior anti-BCMA tx, best responses included VGPR (ADC: 2 pts;BsAb: 1 pt), sCR (ADC: 1 pt), and CR (BsAb: 1 pt);the rest had best response of stable disease or PD (1 pt not evaluable). Baseline characteristics are presented in Figure 1A. Median time from last anti- BCMA agent to cilta-cel infusion was 195 d;median administered dose of cilta-cel was 0.65x106 CAR+ viable T cells/kg. At a median follow-up of 18.0 mo, 7/10 evaluable pts (70%) were MRD negative at 10-5 (ADC: 5/7 [71.4%], BsAb: 2/3 [66.7%]). ORR: full cohort, 60%;ADC, 61.5%;BsAb, 57.1% (Figure 1B). Median DOR: full cohort, 12.8 mo;ADC, 12.8 mo;BsAb, 8.2 mo. Median PFS: full cohort, 9.1 mo;ADC, 9.5 mo;BsAb, 5.3 mo. Cilta-cel responders had a shorter median duration of last anti- BCMA agent exposure (29.5 d) compared with non-responders (63.5 d). Responders also had a longer median time from last anti-BCMA tx exposure to apheresis (161.0 d) than non-responders (56.5 d). Most common AEs were hematologic. CRS: n=12 (60%;all Gr1/2), median time to onset 7.5 d, median duration 6.0 d. ICANS: n=4 (20%, 2 Gr3/4), median time to onset 9.0 d, median duration 7.0 d. No patient had movement or neurocognitive tx emergent AE/parkinsonism. There were 12 deaths (PD: 8;COVID-19 pneumonia: 2 [not tx related];subarachnoid hemorrhage: 1 [not tx related];C. difficile colitis: 1 [tx related]). (Figure Presented)(Figure Presented)Conclusions: Pts with heavily pretreated MM and previous exposure to a non-cellular anti-BCMA therapy had favorable responses to cilta-cel. However, depth and DOR appear lower than that seen in anti-BCMA-naive pts treated with cilta-cel (at 27.7 mo, median DOR was not reached in heavily pre-treated but anti-BCMA naive CARTITUDE-1 pts). These data may inform tx plans, including sequencing and washout period between BCMA-targeting agentsCopyright © 2023 American Society for Transplantation and Cellular Therapy

A qualitative assessment of entrepreneurship amidst COVID-19 pandemic in Pakistan

This study aims to explore the support and impede factors of entrepreneurial activities amidst the COVID-19 pandemic. By using the qualitative method, 18 in-depth interviews were conducted with entrepreneurs operating micro-, small- and medium-scale enterprises. Interviews were transcribed for content analysis to generate themes using NVivo 12. COVID-19 has adversely affected the entrepreneurial activity in Pakistan was a key theme found after analysis. Three main categories were found as situations provoking business decline and their manifestation, entrepreneurial actions and reactions to COVID-19 crisis, and their futuristic plans amidst COVID-19. This research highlights issues entrepreneurs face to follow protocols of lockdown, social distancing, and operational hours. The findings of this study contribute to the scholarship of entrepreneurship and areas for the empirical investigation to develop efficient ecosystems to support entrepreneurs. This study suggests government and non-government stakeholders devise strategies for entrepreneurial revival post-COVID-19. This is probably one of the first qualitative assessment of the likely effects of the COVID-19 pandemic on entrepreneurship. It also recommends interesting related research areas and suggestions on how to empower entrepreneurs to overcome it. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of College of Management, National Cheng Kung University.

In Silico Insight into the Inhibitory Effects of Active Antidiabetic Compounds from Medicinal Plants Against SARS-CoV-2 Replication and Post-translational Modification

Background: The recent reemergence of the coronavirus (COVID-19) caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted the search for effective treatments in the forms of drugs and vaccines. Aim(s): In this regard, we performed an in silico study on 39 active antidiabetic compounds of medicinal plants to provide insight into their possible inhibitory potentials against SARS-CoV-2 replications and post-translational modifications. Top 12 active antidiabetic compounds with potential for dual inhibition of the replications and post-translational modifications of SARS-CoV-2 were ana-lyzed. Result(s): Boswellic acids, celastrol, rutin, sanguinarine, silymarin, and withanolides expressed binding energy for 3-chymotrypsin-like protease (3CLpro) (-8.0 to-8.9 Kcal/mol), papain-like protease (PLpro) (-9.1 to-10.2 Kcal/mol), and RNA-dependent RNA polymerase (RdRp) (-8.5 to-9.1 Kcal/-mol) which were higher than the reference drugs (Lopinavir and Remdesivir) used in this study. Sanguinarine, silymarin, and withanolides are the most druggable phytochemicals among other phy-tochemicals as they follow Lipinski's rule of five analyses. Sanguinarine, silymarin, and withano-lides expressed moderate solubility with no hepatotoxicity, while silymarin and withanolides could not permeate the blood-brain barrier and showed no Salmonella typhimurium reverse mutation as-say (AMES) toxicity, unlike sanguinarine from the predictive absorption, distribution, metabolism, elimination, and toxicity (ADMET) studies. Conclusion(s): Sanguinarine, silymarin, and withanolides could be proposed for further experimental studies for their development as possible phytotherapy for the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.

Face Masks Use and Face Perception: Social Judgments and Emotion Recognition

An outbreak of the severe acute respiratory syndrome corona virus (SARS-CoV-2) made face masks use a norm in individuals' daily lives. The information individuals obtained with face perception is potentially affected by regular face mask use. This study investigated the effects of face masks, ethnicities, and sex on the social judgments including sex, age, trustworthiness, facial attractiveness, and approachability. Later, the effects of face masks, ethnicities, and sex, and facial expressions of happy, neutral, and sad faces on valence and arousal were studied. Likert-type scales and Self-Assessment Manikin were used in an online experiment by Psychopy to capture face perception. Only sex influences sex score in an apparent manner, and unmasked faces appear as more attractive. Face masks and ethnicities do not seem to have effects on sex, age, attractiveness, trustworthiness, and approachability. Faces with different expressions influence the scoring in valence and arousal scale. The results of the present study may be informative for the current pandemic for people to have fruitful social engagements. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Ecological Footprint Assessment of E-Learning in India

The global pandemic has provided a chance to compare the ecological assessment of online and offline teaching-learning processes. This is attributed to the worldwide lockdown that has enforced academic institutions to shut their campuses and transform all teaching-learning activities to online mode. In this case study, a methodology has been developed to assess the ecological footprint (EF) of the online and offline teaching-learning processes. This case study represents an effort to assess the environmental impact of the online and offline teaching- learning processes for an Indian academic institute during the COVID-19 lockdown period. Online/offline teaching-learning is characterized into two different modes (i.e., Mode I and Mode II). The EF of online teaching-learning for Mode I and Mode II is 2.82 × 10–3 gha/hr and 4.62 × 10–3 gha/hr, respectively. The EF of offline teaching-learning for Mode I and Mode II is 3.86 × 10–2 gha/hr and 3.88 × 10–2 gha/hr, respectively. The results indicate that online teaching-learning has a comparatively lower environmental impact than offline teaching-learning (i.e., 7.2% to 11.9% of the offline teaching-learning). The study recommends that policymakers take decisions on switching from offline education to online education considering the EF of this transformation. © 2023 selection and editorial matter, Zdzislaw Polkowski, Samarjeet Borah, Sambit Kumar Mishra, and Darshana Desai;individual chapters, the contributors.

Cerebrovascular Complications of COVID-19 on Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: Evidence of cerebrovascular complications in COVID-19 requiring venovenous extracorporeal membrane oxygenation (ECMO) is limited. Our study aims to characterize the prevalence and risk factors of stroke secondary to COVID-19 in patients on venovenous ECMO. DESIGN: We analyzed prospectively collected observational data, using univariable and multivariable survival modeling to identify risk factors for stroke. Cox proportional hazards and Fine-Gray models were used, with death and discharge treated as competing risks. SETTING: Three hundred eighty institutions in 53 countries in the COVID-19 Critical Care Consortium (COVID Critical) registry. PATIENTS: Adult COVID-19 patients who were supported by venovenous ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five hundred ninety-five patients (median age [interquartile range], 51 yr [42-59 yr]; male: 70.8%) had venovenous ECMO support. Forty-three patients (7.2%) suffered strokes, 83.7% of which were hemorrhagic. In multivariable survival analysis, obesity (adjusted hazard ratio [aHR], 2.19; 95% CI, 1.05-4.59) and use of vasopressors before ECMO (aHR, 2.37; 95% CI, 1.08-5.22) were associated with an increased risk of stroke. Forty-eight-hour post-ECMO Pa co2 -pre-ECMO Pa co2 /pre-ECMO Pa co2 (relative ΔPa co2 ) of negative 26% and 48-hour post-ECMO Pa o2 -pre-ECMO Pa o2 /pre-ECMO Pa o2 (relative ΔPa o2 ) of positive 24% at 48 hours of ECMO initiation were observed in stroke patients in comparison to relative ΔPa co2 of negative 17% and relative ΔPa o2 of positive 7% in the nonstroke group. Patients with acute stroke had a 79% in-hospital mortality compared with 45% mortality for stroke-free patients. CONCLUSIONS: Our study highlights the association of obesity and pre-ECMO vasopressor use with the development of stroke in COVID-19 patients on venovenous ECMO. Also, the importance of relative decrease in Pa co2 and moderate hyperoxia within 48 hours after ECMO initiation were additional risk factors.

Effect of convalescent plasma transfusion on outcomes of coronavirus disease 2019: a meta-analysis with trial sequential analysis.

The aim of this review was to update evidence for benefit of convalescent plasma transfusion (CPT) in patients with coronavirus disease 2019 (COVID-19). Databases were searched for randomized controlled trials (RCT) comparing CPT plus standard treatment versus standard treatment only in adults with COVID-19. Primary outcome measures were mortality and need for invasive mechanical ventilation (IMV). Twenty-Six RCT involving 19,816 patients were included in meta-analysis for mortality. Quantitative synthesis showed no statistically significant benefit of adding CPT to standard treatment (RR = 0.97, 95% CI = 0.92 to 1.02) with unimportant heterogeneity (Q(25) = 26.48, p = .38, I2 = 0.00%). Trim-and-fill-adjusted effect size was unimportantly changed and level of evidence was graded as high. Trial sequential analysis (TSA) indicated information size was adequate and CPT was futile. Seventeen trials involving 16,083 patients were included in meta-analysis for need of IMV. There was no statistically significant effect of CPT (RR = 1.02, 95% CI = 0.95 to 1.10) with unimportant heterogeneity (Q(16) = 9.43, p = .89, I2 = 3.30%). Trim-and-fill-adjusted effect size was trivially changed and level of evidence was graded as high. TSA showed information size was adequate and indicated futility of CPT. It is concluded with high level of certainty that CPT added to standard treatment of COVID-19 is not associated with reduced mortality or need of IMV compared with standard treatment alone. In view of these findings, further trials on efficacy of CPT in COVID-19 patients are probably not needed.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

A novel group decision-making framework under Pythagorean fuzzy N-soft expert knowledge

Many scholars have been challenged by multi-attribute group decision-making problems that have stimulated the appearance of increasingly general models. Pythagorean fuzzy sets were a reaction by Yager who in 2013, suggested this model to improve the performance of intuitionistic fuzzy sets. Another hybrid model –soft expert sets– deals with uncertain parameterized information. It considers opinions of different experts, improving the single-agent experience of soft sets. N-soft expert sets and their fuzzy version, namely, fuzzy N-soft expert sets, consider the ratings given to objects by more than one expert with respect to relevant parameters. The arguments supporting the need for independent allocation of membership and non-membership degrees apply to the fuzzy expressions imposed on top of the benefits of the N-soft expert environment. These challenges converge on the formulation of a new hybrid model called Pythagorean fuzzy N-soft expert sets that improves upon Pythagorean fuzzy sets with the benefits of N-soft expert sets. We study their scope of application with practical examples. Afterwards we discuss certain basic operators (subsethood, complement, union and intersection), prove some of their remarkable properties, and provide the concepts of equal, agree, and disagree-Pythagorean fuzzy N-soft expert sets. We present an algorithm for group decision-making problems in this framework and we explore three applications of this methodology, namely, to the analysis of wheat varieties, employee selection, and recovery order of patients suffering COVID-19. In the end, we provide a sensitivity analysis comparing the proposed model with some existing models to guarantee its cogency and feasibility. © 2023 The Author(s)

Blockchain based integrity assurance framework for COVID-19 information management & decision making at National Command Operation Center, Pakistan

The uncontrollable spread of contagious disease COVID-19 is a perennial threat to mankind and has resulted in an unprecedented lockdowns in several countries including Pakistan which in turn has caused an adverse socio-economic impact to all industries. The strategic leadership and concerned state authorities are trying hard to combat and control the spread of COVID-19 pandemic. The effective use of Information Management & Decision Support (IMDS) System can play significant role in combating pandemic and its spread, managing relief actions effectively, accessing vulnerable communities to roll out targeted subsidies by ensuring the coordinated effort and subsequent implementation. Reliable information is significantly critical to assist government and public health agencies in determining the best way forward to control this global health emergency. Therefore, this paper aims to strengthen capacity of IMDS System used by government institutions and authorities for decision making and information dissemination. In this research work, we addressed the integrity-based issues that include completeness, correctness, and freshness of data by proposing a block chain-based integrity protection mechanism. The proposed novel framework is a cascaded formulation of Integrity Assurance (IA) Protocol, Cryptographic Merkle Hash Tree, Digital Signature, and Blockchain. Beside cascaded formulation, two (2) schemes for MHT Generation are also presented in the framework. The proposed framework ensures fairness, completeness, and correctness of data that will be very helpful for secure data management, integration, and utilization in analysis for decision-making. The proposed framework achieved an accuracy of more than 98.09% with better quantitative performance in standard evaluation parameters. © 2023 John Wiley & Sons, Ltd.

Morbid obesity's impact on COVID-19 patients requiring venovenous extracorporeal membrane oxygenation: The covid-19 critical care consortium database review.

Introduction: Obesity is associated with a worse prognosis in COVID-19 patients with acute respiratory distress syndrome (ARDS). Veno-venous (V-V) Extracorporeal Membrane Oxygenation (ECMO) can be a rescue option, however, the direct impact of morbid obesity in this select group of patients remains unclear.Methods: This is an observational study of critically ill adults with COVID-19 and ARDS supported by V-V ECMO. Data are from 82 institutions participating in the COVID-19 Critical Care Consortium international registry. Patients were admitted between 12 January 2020 to 27 April 2021. They were stratified based on Body Mass Index (BMI) at 40 kg/m2. The endpoint was survival to hospital discharge.Results: Complete data available on 354 of 401 patients supported on V-V ECMO. The characteristics of the high BMI (>40 kg/m2) and lower BMI (≤40 kg/m2) groups were statistically similar. However, the 'high BMI' group were comparatively younger and had a lower APACHE II score. Using survival analysis, older age (Hazard Ratio, HR 1.49 per-10-years, CI 1.25-1.79) and higher BMI (HR 1.15 per-5 kg/m2 increase, CI 1.03-1.28) were associated with a decreased patient survival. A safe BMI threshold above which V-V ECMO would be prohibitive was not apparent and instead, the risk of an adverse outcome increased linearly with BMI.Conclusion: In COVID-19 patients with severe ARDS who require V-V ECMO, there is an increased risk of death associated with age and BMI. The risk is linear and there is no BMI threshold beyond which the risk for death greatly increases.

Impact of COVID-19 and Online Streaming Services on the Movie Theater

Movie Theaters in India face a big crisis amid COVID-19, which leads to the shutdown of Theaters for more than five months. In the meantime, Online Streaming Services are expanding their business and revenue like never before. This scenario raises the very prominent questions (1) whether the movie theater business will survive this hard time and get back to normal growth and business once COVID-19 cases will reduce. The situation gets back to `old normal'. (2) Will Online Streaming services and Movie Theater business co-exist in the future, as Satellite TV and Movie Theater exist for many decades. Based on data from an empirical survey conducted among regular moviegoers, this paper questions the claims of the industry that the Movie Theater business is in danger due to the emergence of online streaming services. It has been observed that the increase in traffic on these online streaming services is mainly because of the lockdown situation, and once theater reopens and the COVID-19 health crisis went, people will get back to Theaters in a large number. Data from the reopening of Theaters in other countries are also showing the same result.

Association Between Patient Race and Ethnicity and Outcomes With COVID-19: A Retrospective Analysis From a Large Mid-Atlantic Health System.

BACKGROUND: Members of racial and ethnic minority groups have been disproportionately impacted by coronavirus-2019 (COVID-19). The objective of the study is to describe associations between race and ethnicity on clinical outcomes such as need for mechanical ventilation and mortality. METHODS: Retrospective cohort study of patients with severe COVID-19 infection admitted within a large, not-for-profit healthcare system in the mid-Atlantic region between March and July, 2020. Patient demographic data and clinical outcomes were abstracted from the electronic health record. Logistic regressions were performed to estimate associations between race and ethnicity and the clinical outcomes. RESULTS: The study population (N = 2931) was stratified into 1 of 3 subgroups: non-Hispanic White (n = 466), non-Hispanic Black (n = 1611), and Hispanic (n = 654). The average age of White, Black, and Hispanic patients was 69 ± 17.06, 64 ± 15.9, and 50 ± 15.53 years old, respectively (P < .001). Compared to White patients, Black and Hispanic patients were at increased odds of needing mechanical ventilation due to COVID-19 pneumonia (odds ratio [OR] Black = 1.35, 95% confidence interval [CI] = 1.04 to 1.75, P < .05; OR Hispanic = 1.43, 95% CI = 1.06 to 1.93, P < .05). When compared to White patients, Hispanic patients were at decreased odds of death (OR = 0.45, 95% CI = 0.32 to 0.63, P < .001). However, when adjusting for age, there were no statistically significant differences in the odds of death between these groups (adjusted OR [aOR] Black = 1.05, 95% CI = 0.80 to 1.38, P = .71; aOR Hispanic = 1.10, 95% CI = 0.76 to 1.60, P = .62). CONCLUSION: Our analysis demonstrated that Hispanic patients were more likely require mechanical ventilation but had lower mortality when compared to White patients, with lower average age likely mediating this association. These findings emphasize the importance of outreach efforts to communities of color to increase prevention measures and vaccination uptake to reduce infection with COVID-19.

Modern Diagnostics Processes among New Strains of Coronaviruses: A Review

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the COVID-19 disease, which is a considerable outbreak that appeared in late 2019, and within a short period, this disease rapidly extended globally. Its prompt airborne transmission and highly infectious pneumonia-like symptoms in patients caused turmoil worldwide. This virus has a relatively high mortality rate compared to previous outbreaks such as Middle East respiratory syndrome coronavirus and SARS-CoV. Therefore, the World Health Organization declared COVID-19 a global health pandemic on January 30, 2020. However, the recent COVID-19 outbreak and newly emerged variants such as Delta and Omicron are having a huge spike in the human population. This rise has been a kind of challenging situation worldwide as perception is still limited in terms of modes of transmission, severity, diagnostics clinical oversight. Therefore, this review highlights the importance of these issues via a Medline search using the terms novel, coronavirus, sources, genetic nature, contagious routes, clinical characteristics, and diagnostic procedures for COVID-19. The authors extensively reviewed the analysis of behavior and impacts of this virus’s activities worldwide. The study reveals that patients’ epidemiology and clinical characteristics in different frames are sensitive toward commanding this virus and its associated diseases. Finally, the parametric data gathered for this study are also presented for use in forecasting models. Along with these searches, the authors have comprehensively discussed the current modern diagnostic processes. © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

In silico investigation and identification of bioactive compounds from medicinal plants as potential inhibitors against SARS-CoV-2 cellular entry

The present study conducted an in silico investigation and identifications of bioactive compounds from medicinal plants against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cellular entry. Thirty nine (39) bioactive compounds with evidence of in vitro or in vivo antidiabetic activities from medicinal plants were utilized in order to provide insight about their possible inhibitory potentials against SARS-CoV-2 cellular entry. Results from this study showed that silymarin, sanguinarine, withanolides, boswellic acids, fisetin, celastrol, neferine, ursolic acid, rutin, gambogic acid, quercetin, and luteolin expressed multiple binding capacity against nucleocapsid dimerization domain (−10.7 to −8.4kcal/mol), spike's protein binding domain (−10.0 to −8.1kcal/mol), and spike receptor-binding domain (−10.8 to −9.0kcal/mol) compared to lopinavir and remdesivir which were used as reference compounds in the study. However, withanolides, fisetin, luteolin, sanguinarine, and silymarin are most druggable phytochemicals as they obey the Lipinski's rule of five analyses with no signs of in silico predictory toxicity. Thus, they are recommended for further studies for the development of phytotherapy formulation to combat SARS-CoV-2 disease. © 2022 Elsevier Inc. All rights reserved.

CARTITUDE-2 Cohort A: Updated Clinical Data and Biological Correlative Analyses of Ciltacabtagene Autoleucel (cilta-cel) in Lenalidomide-Refractory Patients With Progressive Multiple Myeloma (MM) After 1-3 Prior Lines of Therapy (LOT)

Context: CARTITUDE-2 (NCT04133636) Cohort A is assessing cilta-cel in lenalidomide-refractory patients with progressive MM after 1-3 prior LOT. Objective(s): To present updated results from CARTITUDE-2 Cohort A. Design(s): Phase 2, multicohort study. Patient(s): Lenalidomide-refractory patients with progressive MM after 1-3 prior LOT (PI and IMiD included) and no previous exposure to BCMA-targeting agents. Intervention(s): Single cilta-cel infusion (target dose 0.75x106 CAR+ viable T-cells/kg) after lymphodepletion Main Outcome Measure(s): Primary endpoint was minimal residual disease (MRD) negativity at 10-5. Management strategies were used to reduce risk of movement/neurocognitive adverse events (MNTs). Pharmacokinetics (PK) (Cmax/Tmax of CAR+T-cell transgene levels), cytokine release syndrome (CRS)-related cytokines over time, peak cytokine levels by response/CRS, association of cytokine levels with immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR+T-cell CD4/CD8 ratio by response/CRS/ICANS are being evaluated. Result(s): As of January 2022 (median follow-up [MFU] 17.1 months), 20 patients (65% male;median age 60 years;median 2 prior LOT;95% refractory to last LOT) received cilta-cel. Overall response rate was 95% (90% >=complete response;95% >=very good partial response). Median times to first and best response were 1.0 month and 2.6 months, respectively. All 16 MRD-evaluable patients achieved MRD negativity at 10-5. Median duration of response was not reached. At 12 months, event-free rate was 79% and progression-free survival rate was 75%. 95% of patients had CRS (gr3/4 10%);median time to onset was 7 days and median duration was 3 days. Neurotoxicity was reported in 30% of patients (5 gr1/2;1 gr3/4) and ICANS in 15% (all 3 gr1/2);1 patient had gr2 facial paralysis. No MNTs were observed. 1 death occurred due to COVID-19 (treatment-related), 2 due to progressive disease, and 1 due to sepsis (not treatment-related). Preliminary PK analyses showed peak CAR-T cell expansion at day 10.5;median persistence was 153.5 days. Conclusion(s): At MFU of 17.1 months, a single cilta-cel infusion resulted in deep and durable responses in lenalidomide-refractory MM patients with 1-3 prior LOT. We will present updated PK/cytokine/CAR-T subset analyses and clinical correlation to provide novel insights into biological correlates of efficacy/safety in this population. Copyright © 2022 Elsevier Inc.

Coronavirus disease 2019 in Africa: why the recent spike in cases?

This chapter assesses the recent cases of COVID-19 pandemic in Africa. COVID-19, a global pandemic, is spreading so fast across all continents with African region not left out of its ravaging and devastating effects. Nigeria, on May 31, 2020, became the first country in West Africa to hit the 10,000 mark of confirmed COVID-19 cases. This recent spike in COVID-19 cases with accompanying increase in the number of fatalities calls for concern. As of July 21, 2020, Nigeria ranked third in Africa, just behind South Africa and Egypt, while the total number of confirmed cases in Africa has increased to 736,288. What would have led to the increasing cases in Africa? We found that poverty, hunger, people's violation of health guidelines, and increase in the number of laboratory tests for suspected COVID-19 cases are responsible for the sudden and sustained rise in cases in the continent. © 2022 Elsevier Inc. All rights reserved.

Dexamethasone

The corticosteroid drug “dexamethasone” has been in use since 1960s for reducing inflammation in a variety of conditions such as certain cancers and other inflammatory disorders. It is an affordable agent and currently off-patent in most countries and listed in multiple formulations since 1977 in the World Health Organization model list of essential medicines. The cytokines production and damaging effect has been limited through the use of dexamethasone and this will also block B cells from antibodies production and inhibit the T cell's protective function potential leading to elevated viral load in the plasma that persists for longer time after a patient survives SARS. In addition, dexamethasone would chunk the macrophages from clearing the resultant nosocomial infections. Thus, dexamethasone may be valuable for the immediate relief in severe cases of COVID-19, but could be dangerous on the long run as the body will be barred from producing protective antibodies in addition to the persistence of the virus. © 2022 Elsevier Inc. All rights reserved.