Management of lung cancer in the COVID-19 pandemic: A review

Since its inception, the COVID-19 pandemic has affected health care as a whole. Cancer patients in general and those suffering from lung cancer in particular are a vulnerable group because of their many intrinsic characteristics and care needs. How SARS-CoV-2 (COVID-19) infection affects these patients regarding their risk of infection and outcome in this patient cohort is still to be determined. In this review, we tried to summarize our main concerns regarding COVID-19 in the context of cancer patients from a clinical and multidisciplinary approach. Different types of lung cancer treatments (chemotherapy, radiation therapy and immunotherapy) may also influence the risk of infection and condition the patient's risk of having a worse outcome. Lung cancer patients require frequent radiologic study follow-ups, which may be affected by COVID-19 pandemic. COVID-19 related incidental radiologic findings can appear in routinely scheduled radiology tests, which may be difficult to interpret. Also cancer treatment induced pneumonitis may have similar radiologic features similar to those in acute SARS-CoV-2 pneumonia and lead to a wrong diagnosis. The different health care needs, the requirement for continuous health care access and follow-ups, and the clinical traials in which this patient population might be enrrolled are all being affected by the current COVID-19 health crisis. The COVID-19 pandemic has put health care providers and institutions in difficult situations and obliged them to face challenging ethical scenarios. These issues, in turn, have also affected the psychological well-being of health care workers.Copyright © The Author(s) 2021.

Viruses and the risk of lung cancer: prevention and treatment

Lung cancer is the most common cancer in males and the second most common among females both in Europe and worldwide. Moreover, lung cancer is the leading cause of death due to cancer in males. The European region accounts for 23% of total cancer cases and 20% of cancer-related deaths. Relationships have been described between a number of infectious agents and cancers, but our knowledge of the role of viruses, both respiratory and systemic, in the pathogenesis of lung cancer is still rudimentary and has been poorly disseminated. In this chapter, we review the available evidence on the involvement of HPV, Epstein-Barr virus, HIV, cytomegalovirus and measles virus in the epidemiology and pathogenesis of lung cancer.Copyright © ERS 2021.

Expansion of human T cells using xenogeneic free and gamma irradiated human platelet lysate

Commercially available human platelet lysate (hPL) is produced using expired human platelets obtained from accredited blood banks in the United States. These platelets were originally intended for use in patient transfusion. The safety of platelets used in transfusion is managed by the U.S. Food Drug Administration (FDA), as well as the American Association of Blood Banks (AABB). These organizations set standards, including testing for transmissible diseases. The United States record for blood safety is well established, with extremely low rates of disease transmission, making the platelet units used for hPL manufacture low risk. The Covid-19 pandemic has increased awareness of emerging infectious diseases, even though transmission of Covid-19 via blood transfusion has not been documented. For that reason, gamma irradiated hPL offers an additional safety measure in the clinic. Chimeric Antigen Receptor (CAR) expressing T-cells have demonstrated potent clinical efficacy in patients with hematological malignancies. In addition, there are several phase I clinical trials evaluating the use of CAR-T-cells for targeting of solid tumorassociated antigens. Some of the challenging issues found during production of CAR-T cells are the efficiency of T cell transduction to generate CAR-T cells, the expansion of T cells to clinically relevant numbers and the long-term survival in vivo of the therapeutic cells. The use of human platelet lysate has been demonstrated to improve these issues. Our data from experiments performed using human CD3+ from donors demonstrates that human platelet lysates offer an improved performance on T cell expansion versus serum derived products. hPL efficiently promotes T cell expansion, with higher cell yields and lower cell exhaustion rate. Additionally, we efficiently developed a protocol for suspension culture of T cells, which could facilitate the large-scale expansion of allogeneic CAR-T cells.

Systematic Review of the Clinical Effectiveness of Tixagevimab/Cilgavimab for Prophylaxis of Covid-19 in Immunocompromised Patients

Background/Aims Immunocompromised patients have a reduced ability to generate antibodies after COVID-19 vaccination, and are at a high risk of SARSPOSTERS CoV-2 infection, complications and mortality. Tixagevimab/Cilgavimab (Evusheld) is a combination of two monoclonal antibodies which bind to the SARS-CoV-2 spike protein, preventing the virus entering human cells. Tixagevimab/Cilgavimab has been approved as COVID-19 prophylaxis for immunocompromised individuals, and is being used in over 32 different countries. The phase III PROVENT clinical trial found that high-risk participants prophylactically administered Tixagevimab/Cilgavimab had a significantly reduced risk of COVID- 19 infection after three and six months compared to controls. However, the PROVENT trial was conducted prior to the SARS-CoV- 2 Omicron wave, and did not include participants who had been previously vaccinated or infected. This systematic review provides an updated summary of the real-world clinical evidence of the efficacy of Tixagevimab/Cilgavimab for immunocompromised patients. The review reports breakthrough COVID-19 infections as its primary outcome. COVID-19-related hospitalisations, ITU admissions and mortality were included as secondary outcomes. Methods Two independent reviewers conducted electronic searches of PubMed and Medxriv, on 03/08/22 and 01/10/22. Clinical studies which reported the primary outcome of breakthrough COVID-19 infections after Tixagevimab/Cilgavimab administration were included. Clinical effectiveness was determined using the case-control clinical effectiveness methodology. Odds ratios and 95% confidence intervals (CI) between intervention and control groups were also calculated. The GRADE tool was used to assess the level of certainty for the primary outcome. Results 17 clinical studies were included in the review, with a total of 24,773 immunocompromised participants from across the world, of whom 10,775 received Tixagevimab/Cilgavimab. One randomised controlled trial, ten retrospective cohort studies (two of which were preprints) and six prospective cohort studies (one preprint) were included. The majority of studies reported clinical outcomes during the SARS-CoV-2 Omicron wave. Six studies compared a Tixagevimab/Cilgavimab intervention group to a control group. Reasons for participant immunocompromise included rheumatology patients treated with immunosuppressant drugs, transplant recipients and those with malignancies. Overall, the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab against COVID- 19 breakthrough infection was 40.47% (CI 29.82-49.67;p<0.0001), COVID-19 hospitalisation- 69.23% (CI: 50.78-81.64;p<0.00001), ITU admission- 87.89% (CI: 47.12-98.66;p=0.0008), all-cause mortality- 81.29% (66.93-90.28;p<0.0001 and COVID-19-specifc mortality- 86.36% (CI:-6.21-99.70;p=0.0351). Conclusion There is a growing body of real-world evidence validating the original PROVENT phase III study regarding the clinical effectiveness of Tixagevimab/Cilgavimab as prophylaxis for immunocompromised groups, notably demonstrating effectiveness during the Omicron wave. This systematic review demonstrates the significant clinical effectiveness of prophylactic Tixagevimb/Cilgavimab at reducing COVID-19 infection, hospitalisation, ITU admission and mortality for immunosuppressed individuals. It is critically important that largerscale and better-controlled studies are performed to highlight the significant clinical benefit of prophylactic antibody treatment in immunocompromised groups.

Convalescent Plasma Treatment of Severe Covid-19 Cases in the Bronx, Ny

Junior Physician Investigator Award Recipient Purpose of study Severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) is the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic. Convalescent plasma obtained from recovered persons was used for previous respiratory pandemics. Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) was proposed as an option that may hold promise as treatment for COVID-19. Our aim was to retrospectively evaluate the efficacy of CCP treatment of patients with severe to life-threatening COVID-19 hospitalized at Montefiore Medical Center (MMC) in the Bronx, NY between April 13 to May 4, 2020. Methods used We administered CCP as part of the Mayo Clinic expanded access investigational new drug (IND) program for hospitalized patients. We compared the mortality and clinical outcome of 73 patients with COVID-19 who received 200 mL of CCP with a Spike protein IgG titer >=1:2,430 (median 1:47,385) within 72 hours of admission to 1:1 propensity score-matched controls. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroids, and anticoagulation use (figure 1). We additionally measured Spike protein IgG and neutralizing antibody titer in CCP and pre- and post-transfusion Spike protein IgG, IgM and IgA titer in CCP recipients. The primary outcome was all-cause mortality at day 28 post-CCP. The secondary outcomes were improvement in oxygenation status or mortality at day 28 post-CCP. Exploratory outcomes were associations between pre-CCP SARS-CoV-2 antibody titers and mortality at day 28. Summary of results There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared to matched controls, CCP recipients < 65 years had 4-fold lower mortality and 4-fold lower deterioration in oxygenation or mortality at day 28 (figure 2, 3). There was no association between CCP IgG or neutralizing antibody titer and clinical outcome. For CCP recipients, pre-transfusion Spike protein IgG, IgM and IgA titers were associated with mortality at day 28 in univariate analyses but not in multivariable analyses. Pre-transfusion Spike protein IgG titer was significantly correlated with Ddimer and detected viral load measured by cycle threshold (Ct) value of nasopharyngeal SARS-CoV-2 reverse-transcriptase- polymerase-chain-reaction (figure 4). No adverse effects of CCP were observed. Conclusions We report that CCP administration within 72 hours of hospitalization demonstrated a possible signal of reduced mortality in patients < 65 years. Pre-transfusion IgG titer may be a proxy for disease severity that may be useful in identifying those who are more likely to respond to CCP. Data from controlled trials is needed to validate this finding and establish the effect of ageing on CCP efficacy. (Figure Presented).

The First Reported Case of Lorlatinib-Associated Diabetic Ketoacidosis

Introduction: Lorlatinib is a third-generation tyrosine kinase inhibitor that inhibits anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1). Although 2-10% of patients with non-small cell lung cancer developed hyperglycemia in phase 2 and 3 studies of lorlatinib, only one case has subsequently reported hyperglycemia >500 mg/dL, and no cases of diabetic ketoacidosis (DKA) have been previously reported. Phase 1 trials in neuroblastoma are ongoing. Case Description: A 34-year-old woman with ALK-mutated paraspinal neuroblastoma presented with DKA 14 months after initiation of lorlatinib. Prior to starting lorlatinib, her hemoglobin A1c had been 5.0% (n: < 5.7%). After 12 months of therapy, her A1c increased to 7.8%, prompting the initiation of metformin 500 mg daily. However, two months later she was admitted for DKA with a blood glucose of 591 mg/dL (n: 65-99 mg/dL), CO2 17 mmol/L (n: 20-30 mmol/L), anion gap 18 (n: 8-12), moderate serum ketones, and 3+ ketonuria. Her A1c was 14.8%, C-peptide was 1.2 ng/mL (n: 1.1-4.3 ng/mL), and her glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies were negative. She was also found to be incidentally positive for COVID-19 but was asymptomatic without any oxygen requirement. The patient's DKA was successfully treated with IV insulin infusion, and she was discharged after 3 days with insulin glargine 27 units twice daily and insulin aspart 16 units with meals. One month later, her hemoglobin A1c had improved to 9.4%, and the patient's oncologist discontinued lorlatinib due to sustained remission of her neuroblastoma and her complication of DKA. After stopping lorlatinib, her blood glucose rapidly improved, and she self-discontinued all her insulin in the following 3 weeks. One month later, she was seen in endocrine clinic only taking metformin 500 mg twice daily with fasting and post-prandial blood glucose ranging 86-107 mg/dL. Discussion(s): This is the first reported case of DKA associated with lorlatinib. This case highlights the importance of close glucose monitoring and the risk of severe hyperglycemia and DKA while on lorlatinib therapy. Discontinuation of lorlatinib results in rapid improvement of glycemic control, and glucose-lowering treatments should be promptly deescalated to avoid hypoglycemia.Copyright © 2023

IDWeek 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

High-Cited Papers in Global COVID-19 Vaccine Research

Aim and Background: The coronavirus disease 2019 (Covid-19) virus pandemic is still ravaging the world with its ongoing resurgence and the continuous mutation, suggesting the need for continuous research on safe and effective novel vaccines. Presently several types of vaccines have been developed and emerged in the global market to control COVID-19 virus. Consequently, the knowledge and information on COVID-19 have been expanding at a high level. Researchers need to gain relevant knowledge regarding the different vaccines;however scattered information makes this process time-consuming and laborious. The present study aimed to evaluate the characteristics and trends in global COVID-19 vaccine high-cited literature using bibliometric and visualizations methods and offer some directions and suggestions for future research. Methodology: Studies published between December 2019 and 22 Nov 2022 on COVID-19 vaccines were retrieved from the Scopus database. From the 16026 studies retrieved, 406 were identified as high-cited papers (HCPs) having received 100 or more citations. From the 406 HCPs, information about publications outputs, countries, institutions, journals, keywords, and citation counts was identified. Data analysis and visualization were conducted using Microsoft Excel, VOSviewer and Bibliometrix R software. Result(s): The 406 global HCPs on COVID-19 vaccines research were identified in Scopus database since Dec 2019 till 30 Nov 2022 using a search strategy, which received 123614 citations, averaging 304.17 citations per publication (CPP). An external funding was received by 53.20% (216 publications), which were cited 76107 times (with an average of 352.35 CPP). The 7086 authors from 694 organizations affiliated to 76 countries and publishing in 121 journals were involved in global COVID-19 vaccine research. The most productive countries were USA (n=213), U.K (n=91), China (n=36) and Germany (n=35). The most impactful countries in terms of citations per paper (CPP) and relative citation index (RCI) were South Africa (794.68 and 2.61), Germany (507.11 and 1.67), U.K. (396.59 and 1.30) and Spain (367.5 and 1.121). The most productive organizations were University of Oxford, U.K., Imperial College London, U.K. (n=25 each), Center for Disease Control and Prevention (CDC), USA and Tel Aviv University (n=19 each) and the most impactful organizations were University of Cambridge, U.K (783.4 and 2.57), Emory University, USA (780.1 and 2.56), John Hopkins Bloomberg School of Public Health, USA (702.67 and 2.31) and National Institute of Allergy and Infectious Diseases. USA (676.41 and 2.22). The most productive authors were A.J. Pollard (n=16) and T. Lambe (n=14) (of University of Oxford), O. Tureci and P.R. Dormitzer (n=12 each) (of BioNTechSE, Germany) and the most impactful were D. Cooper (1239.22 and 4.07), K.J. Janseu (1228.11 and 4.03) (BioNTechSE, Germany, K.A. Swanson (987.0 and 3.24) (University of Oxford, U.K.) and P.R. Dormitzer (983 and 3.23) (BioNTechSE, Germany). The most productive journals were New England Journal of Medicine (n=53), The Lancet (n=28), Nature (n=22) and JAMA (N=17). The most impactful journals (as per citations per paper) were New England Journal of Medicine (613.15), Lancet (496.39), Human Vaccines and Immunotherapeutics (369.67) and Nature (360.64). Among population age groups, the major focus was on adults (51.48%) and Middle Aged (39.16%). Among publication types, the major focus was Clinical Studies (26.85%), Epidemiology (22.66%) and Genetics (21.92%). The most significant keywords by frequency of appearances were "Covid-19" (n=388), "Covid-19 Vaccines" (n=357), "Vaccination" (n=221), "Prevention and Control" (n=181) and "Vaccine Immunogenicity" (n=133), Conclusion(s): The HCPs in COVID-19 vaccine research was done mainly by the authors and institutions of high-income Countries (HIC) and was published in high-impact medical journals. Our research has identified the leading countries, institutions, journals, hotspots and development trend in the field that could provide the foundati n for further investigations. The bibliometric analysis will help the clinicians to rapidly identify the potential collaborative partners, identify significant studies, and research topics within their domains of COVID-19 vaccines.Copyright Author (s) 2023.

Bimekizumab safety in patients with moderate-to-severe plaque psoriasis: Analysis of pooled data from up to three years of treatment in Phase 2 and 3 clinical trials

Background: Bimekizumab (BKZ) is a monoclonal IgG1 antibody used in the treatment of psoriasis which selectively inhibits interleukin (IL)-17F in addition to IL-17A.1,2 Data pooled over two years have indicated that BKZ is generally well-tolerated.3 We report three-year BKZ pooled safety data in patients with moderate-to-severe plaque psoriasis. Method(s): Safety data were evaluated for all patients who received one or more dose BKZ in four Phase 3 trials (BE SURE [NCT03412747], BE VIVID [NCT03370133], BE READY [NCT03410992], and their ongoing open-label extension BE BRIGHT open-label extension [NCT03598790;data cut-off : 10/23/2021]) and four Phase 2 trials (BE ABLE 1 [NCT02905006], BE ABLE 2 [NCT03010527], PS0016 [NCT03025542], PS0018 [NCT03230292]). Safety data were evaluated separately for patients receiving BKZ dosed 320mg every four weeks (Q4W) or every eight weeks (Q8W). Exposureadjusted incidence rates (EAIRs) for treatmentemergent adverse events (TEAEs) are the incidence of new cases per 100 patient-years (PY). Result(s): Total BKZ exposure was 4,245.3 PY (N=1,789) across Phase 2/3 trials, and 3,876.4 PY (N=1,495) in Phase 3 trials. TEAEs occurred at a rate of 186.1 across Phase 2/3 trials, serious TEAEs at 5.6, and TEAEs leading to discontinuation at 3.5. Eighteen deaths occurred (0.4/100 PY), all unrelated to study treatment except one (relationship unknown). TEAEs occurred less frequently in Q8W- than Q4W-treated patients in Phase 3 trials. Consistent with previous reports, most common TEAEs (EAIR) in Phase 2/3 trials were nasopharyngitis (15.3), oral candidiasis (10.2), and upper respiratory tract infection (7.1).3 EAIR of serious infections was 1.2. Most frequently reported were serious coronavirus infections (0.2). There were no cases of active tuberculosis. EAIR of oral candidiasis was 10.2, decreased vs two-year data (12.6),3 and was less common with BKZ Q8W vs Q4W. The vast majority of oral candidiasis events were mild or moderate (99.4%);none were serious. EAIRs of hepatic events (4.0) and elevated liver enzymes (3.4) were decreased vs. two-year data (4.3 and 3.6, respectively).3 EAIRs for inflammatory bowel disease (0.1), adjudicated major adverse cardiac events (0.6), and adjudicated suicidal ideation and behavior (0.1) were low. EAIRs for other safety topics of interest were also low and were similar to or lower than two-year EAIRs.3 Conclusion(s): BKZ was well-tolerated over three years. No safety signals were identified;EAIRs of TEAEs did not increase compared with data from two years.3.

Immune-Viral Dynamics Modeling of the Basis for Individual Variation in Covid-19

Background: Viral dynamics models provide mechanistic insights into viral disease and therapeutic interventions. A detailed, mechanistic model of COVID-19 was developed and fit to data from molnupiravir (MOV) trials to characterize the SARS-CoV-2 viral dynamics in MOV-treated and untreated participants and describe the basis for variation across individuals. Method(s): An Immune-Viral Dynamics Model (IVDM) incorporating mechanisms of viral infection, viral replication, and induced innate and adaptive immune response described the dynamics of viral load (VL) from pooled data from MOV Phase 2 and 3 trials (N=1958). Population approaches were incorporated to estimate variation across individuals and to conduct an extensive covariate analysis. Nineteen parameters in a system of five differential equations described SARS-CoV-2 viral dynamics in humans. Six population parameters were successfully informed through fitting to observed trial data while the remaining parameters were fixed based on literature values or calibrated via sensitivity analysis. Result(s): Final viral dynamics and immune response parameters were all estimated with high certainty and reasonable inter-individual variabilities. The model captured the viral load profiles across a wide range of subpopulations and predicted lymphocyte dynamics without using this data to inform the parameters, suggesting inferred immune response curves from this model were accurate. This mechanistic representation of COVID-19 disease indicated that the processes of cellular infection, viral production, and immune response are in a time-varying, non-equilibrium state throughout the course of infection. MOV mechanism of action was best described as an inhibitory process on the infectivity term with estimated AUC50 of 10.5 muM*hr. Covariates identified included baseline viral load on infectivity and age, baseline disease severity, viral clade, baseline viral load, and diabetes on immune response parameters. Greater variation was identified for immune parameters than viral kinetic parameters. Conclusion(s): These findings show that the variation in the human response (e.g., immune response) is more influential in COVID-19 disease than variations in the virus kinetics. The model indicates that immunocompromised patients (due to HIV, organ transplant, active cancer, immunosuppressive therapies) develop an immune response to SARS-CoV-2, albeit more slowly than in immunocompetent, and MOV is effective in further reducing viral loads in the immunocompromised.

Safety application of novel coronavirus pneumonia antiviral drugs.

Three antiviral drugs, including interferon alpha (aerosol inhalation), lopinavir/ritonavir (oral medication), and ribavirin (intravenous infusion), are recommended by Diagnosis and Treatment of Novel Coronavirus Pneumonia (revised version, the 5th ed), which was issued by the National Health Commission of People's Republic of China and National Administration of traditional Chinese Medicine. In addition, clinical trials on a new antiviral drug-remdesivir which is not yet on the market has also been launched in China. Medication safety related data on treatment for infections of severe acute respiratory syndrome coronavirus, middle respiratory syndrome coronavirus, human immunodeficiency virus, lopinavir/ritonavir, and ribavirin, safety data of remdesivir in animal experiment, phase I clinical trials and clinical trials of treating Ebola virus infection, and preliminary reports of treatment in novel coronavirus pneumonia were briefly reviewed, aiming to provide evidence for clinical safety medication.Copyright © 2020 by the Chinese Medical Association.

Benefit from BCON? The unmet need of bladder cancer patients unsuitable for chemoradiation treated with radical radiotherapy alone: A single institution retrospective case note review

Introduction & Objectives: Bladder preservation is routinely used as an alternative to radical cystectomy in the UK and is becoming more accepted elsewhere globally. The gold standard is for patients to receive radiotherapy with a radiosensitiser most commonly concurrent chemotherapy e.g. 5FU/mitomycin C, gemcitabine or cisplatin. Patients with poor performance status or comorbidities may be unable to be offered concurrent treatment with chemotherapy but alternative treatment with concurrent carbogen +/- nicotinamide as a hypoxic modifier may be of benefit. Our aim therefore was to retrospectively review patients with bladder TCC treated with radical radiotherapy alone in the last 5 years who may have benefited from carbogen +/- nicotinamide radiosensitisation at a large cancer centre in the north of England. Material(s) and Method(s): In this single institution retrospective case note review, electronic records were reviewed for 175 patients who had received radiotherapy to the bladder for TCC between 2017-2022. Patients who had radical radiotherapy (RT) alone without radiosensitisation were scrutinised to ascertain whether they would have been candidates for carbogen and nicotinamide using the inclusion/exclusion criteria previously defined in the Bladder Carbogen Nicotinamide (BCON) Randomised Phase 3 trial. Result(s): We analysed 175 patients. Of these, 133 received had radical RT without radiosensitisation. The most common reason for not offering radiosensitisation was the presence of co-morbidities (27.8%). Of interest, the proportion of patients having chemotherapy radiosensitisation did not change after COVID19 in March 2020 (21.5% pre- vs 27.5% post;p=0.32 chi2). Conversely, the proportion of patients receiving neo-adjuvant chemotherapy reduced though failed to reach significance (12.6% pre- vs 5% post;p=0.08 chi2). After review of the notes and criteria from the original BCON trial, 106 patients (79.6%) could have benefited from carbogen +/- nicotinamide. Of these, 14 patients (13.2%) could have been offered carbogen alone due to poor renal function. The most common reason for not being eligible for BCON was respiratory disease with reduced respiratory drive (44%). Conclusion(s): The National Institute for Health and Care Excellence (NICE) state that all radical RT for bladder TCC should be with a radiosensitiser. Due to logistical and departmental issues, the BCON regimen is not currently offered as a standard alternative to radiosensitisation with chemotherapy. BCON has been demonstrated to be tolerable and, whilst updated follow-up data failed to demonstrate statistical significance for overall survival (OS), meta-analysis of hypoxia modification has shown significant improvement in OS compared to RT alone. Hypoxia modification with carbogen +/- nicotinamide should be considered for all patients unsuitable for chemotherapy radiosensitisation.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Updated efficacy and safety of taletrectinib in patients (pts) with ROS1+ non-small cell lung cancer (NSCLC)

Background Taletrectinib is a potent, next-generation, CNS-active, ROS1 tyrosine kinase inhibitor (TKI) with selectivity over TRKB. In previous reports from TRUST-I, taletrectinib showed meaningful clinical efficacy and was well tolerated in pts with ROS1+ NSCLC (n = 109) regardless of crizotinib (CRZ) pretreatment status. We report updated efficacy and safety data with ~1.5 yr follow-up. Methods TRUST-I is a multicenter, open-label, single-arm study with two cohorts: ROS1 TKI-naive and CRZ-pretreated. Pts in both cohorts received taletrectinib 600 mg QD. Key study endpoints included IRC-confirmed ORR (cORR), DoR, disease control rate (DCR), PFS, and safety. A pooled analysis of ORR, PFS, and safety including pts from additional clinical trials was also conducted. Results In the 109 pts from TRUST-I (enrolled prior to Feb 2022) the median follow-up was 18.0 mo in TKI-naive (n = 67) and 16.9 mo in CRZ-pretreated pts (n = 42). cORR was 92.5% in TKI-naive and 52.6% in CRZ-pretreated pts (table). Median DoR (mDoR) and mPFS were not reached. Intracranial-ORR was 91.6%;ORR in pts with G2032R was 80.0%. In a pooled analysis with phase I studies, ORR was 89.5% and 50.0% for TKI-naive and CRZ-pretreated pts, respectively;mPFS was 33.2 mo and 9.8 mo. In 178 pts treated at 600 mg QD, treatment-emergent adverse events (TEAEs) were 92.7%;most (64.0%) were grade 1-2. The most common TEAEs were increased AST (60.7%), increased ALT (55.6%), and diarrhea (55.6%). Neurological TEAEs (dizziness, 18.5%;dysgeusia, 12.4%) and discontinuations due to TEAEs (3.4%) were low. Further updated results will be presented. [Formula presented] Conclusions With additional follow-up, taletrectinib continued to demonstrate meaningful efficacy outcomes including high response rates, prolonged PFS, robust intracranial activity, activity against G2032R, and tolerable safety with low incidence of neurological AEs. Clinical trial identification NCT04395677. Editorial acknowledgement Medical writing and editorial assistance were provided by Arpita Kulshrestha of Peloton Advantage, LLC, an OPEN Health company, and funded by AnHeart Therapeutics, Inc Legal entity responsible for the study AnHeart Therapeutics, Inc. Funding AnHeart Therapeutics, Inc. Disclosure S. He: Financial Interests, Personal, Other, Employment: AnHeart Therapeutics. T. Seto: Financial Interests, Institutional, Research Grant: AbbVie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical;Financial Interests, Personal, Other, Employment: Precision Medicine Asia;Financial Interests, Personal, Speaker's Bureau, Honoraria for lectures: AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Towa Pharmaceutical. C. Zhou: Financial Interests, Personal, Other, Consulting fees: Innovent Biologics Qilu, Hengrui, TopAlliance Biosciences Inc;Financial Interests, Personal, Speaker's Bureau, Payment or honoraria: Eli Lilly China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnositics, AnHeart. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Efficacy of low dose whole-lung irradiation for the treatment of moderate to severe COVID-19 pneumonia: Meta-analysis.

Objective To systematically evaluate the efficacy of low dose whole-lung irradiation in COVID-19 pneumonia based on the present evidence. Methods All literature related to the application of low dose whole-lung irradiation in COVID-19 pneumonia were retrieved from Pubmed, Embase, the Cochrane Library, Web of Science, Google scholar, Scoupus, CNKI, Wanfang database, VIP database until May 2022. Two researchers independently screened the literature. For the literature that met the inclusion criteria, both data extraction and literature quality evaluation were blinded. Revman 5.3 software was used for statistical analysis. Results A total of 5 controlled clinical trials involving 194 patients met the inclusion criteria. No statistically significant differences were detected in the low dose whole-lung irradiation group compared with the best supportive care group for clinical recovery rates, intubation rates, radiographic improvement rates and 28 d-overall survival. Conclusions In patients of COVID-19 pneumonia, low dose whole-lung irradiation conferred no significant benefit to clinical outcomes. Currently, the routine use of low dose whole-lung irradiation for the treatment of moderate to severe COVID-19 pneumonia is not recommended.Copyright © Chinese Medical Journals Publishing House Co.Ltd. All Rights Reserved.

The post-COVID-19 cardiologic pandemic.

Since the beginning of the COVID-19 pandemic, the implications for cardiology have been clear significantly greater than those caused by other respiratory viral epidemics in the past. Among several cardiovascular consequences of COVID-19 the most significant are: 1) higher risk of COVID-19 in patients with pre-existing cardiovascular disease;2) multiple cardiovascular complications in COVID-19;3) association between COVID-19 and coagulopathy;4) consequences of COVID-19 on cardiovascular pathologies of non-COVID-19 patients;and 5) impact of COVID-19 on clinical trials in cardiology.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Current Advances in Novel SARS-CoV-2 Disease (COVID-19) Treatment and Intervention Strategies

Background: During the eleven months of the novel SARS-CoV-2 disease (COVID-19) outbreak in China and its global spread, there is a remarkable understanding of its epidemiology, pathobiol-ogy, and clinical management strategies. While countering a heavy toll on health and the economy, world's regional authorities are enforcing safety guidelines and providing patient care. Currently, there is no globally approved treatment or intervention for COVID-19. Method(s): A structured online literature search for peer-reviewed articles was conducted on PubMed, Europe PMC, Google, WHO, CDC, FDA, and ClinicalTrials portals, using phrases such as COVID-19 treatment and intervention, COVID-19 drugs and COVID-19 vaccines. Result(s): Analysis of the retrieved data showed that as a part of 'Solidarity Clinical Trials', hundreds of treatment and intervention strategies, including antiviral drugs, cytokine antagonists, convalescent plasma therapy, and vaccine candidates, have been registered worldwide. While remdesivir, the anti-Ebola virus drug, has been approved as an 'emergency use' drug in the USA, favipiravir, the anti-flu drug, has been recently approved in Russia. Tocilizumab and sarilumab, the cytokine (IL-6) antagonists, have entered Phase-II/III clinical trials in hospitalized COVID-19 patients. Among the leading vaccine candidates, Phase-III clinical trial results of Moderna, Pfizer and Oxford vaccines seem to be game changers for COVID19. Conclusion(s): The world health authorities have strongly and quickly responded to the COVID-19 pan-demic. Nonetheless, world bodies must unite in combating this health crisis by developing cost-effective drugs and vaccines and making them accessible to resource-poor countries.Copyright © 2021 Bentham Science Publishers.