Risk Factors of In-hospital Death in COVID-19 Patients：a Meta-analysis

Background The worldwide COVID-19 pandemic has turned into a global catastrophic public health crisis，and the conclusion about the risk factors of hospital death in COVID-19 patients is not uniform. Objective To explore risk factors of in-hospital death in patients with COVID-19 by a meta-analysis. Methods Case-control studies about risk factors of in-hospital death in COVID-19 patients were searched from databases of the Cochrane Library，ScienceDirect，PubMed，Medline，Wanfang Data，CNKI and CQVIP from inception to October 1，2021. Literature screening，data extraction and methodological quality assessment were conducted. Meta-analysis was performed using Stata 15.1. Meta-regression was used to explore the potential sources of heterogeneity. Results Eighty studies were included which involving 405 157 cases〔349 923 were survivors（86.37%），and 55 234 deaths（13.63%）〕，that were rated as being of high quality by the Newcastle-Ottawa Scale. Meta-analysis showed that being male〔OR=1.49，95%CI（1.41，1.57），P<0.001），older age〔WMD=10.44，95%CI（9.79，11.09），P<0.001〕，dyspnoea〔OR=2.09，95%CI（1.80，2.43），P<0.001〕，fatigue〔OR=1.49，95%CI（1.31，1.69），P<0.001〕，obesity〔OR=1.46，95%CI（1.43，1.50），P<0.001〕，smoking〔OR=1.18，95%CI （1.14，1.23），P<0.001〕，stroke〔OR=2.26，95%CI（1.41，3.62），P<0.001〕，kidney disease〔OR=3.62，95%CI （3.26，4.03），P<0.001〕，cardiovascular disease〔OR=2.34，95%CI（2.21，2.47），P<0.001〕，hypertension〔OR=2.23，95%CI（2.10，2.37），P<0.001〕，diabetes〔OR=1.84，95%CI（1.74，1.94），P<0.001〕，cancer〔OR=1.86，95%CI （1.69，2.05），P<0.001〕，pulmonary disease〔OR=2.38，95%CI（2.19，2.58），P<0.001〕，liver disease〔OR=1.65，95%CI（1.36，2.01），P<0.001〕，elevated levels of white blood cell count〔WMD=2.03，95%CI（1.74，2.32），P<0.001〕，neutrophil count〔WMD=1.77，95%CI（1.49，2.05），P<0.001〕，total bilirubin〔WMD=3.19，95%CI（1.96，4.42），P<0.001〕，aspartate transaminase〔WMD=13.02，95%CI（11.70，14.34），P<0.001〕，alanine transaminase 〔WMD=2.76，95%CI（1.68，3.85），P<0.001〕，lactate dehydrogenase〔WMD=166.91，95%CI（150.17，183.64），P<0.001〕，blood urea nitrogen〔WMD=3.11，95%CI（2.61，3.60），P<0.001〕，serum creatinine〔WMD=22.06，95%CI （19.41，24.72），P<0.001〕，C-reactive protein〔WMD=76.45，95%CI （71.33，81.56），P<0.001〕，interleukin-6 〔WMD=28.21，95%CI（14.98，41.44），P<0.001〕，and erythrocyte sedimentation rate〔WMD=8.48，95%CI（5.79，11.17），P<0.001〕were associated with increased risk of in-hospital death for patients with COVID-19，while myalgia〔OR=0.73，95%CI（0.62，0.85），P<0.001〕，cough〔OR=0.87，95%CI（0.78，0.97），P=0.013〕，vomiting〔OR=0.73，95%CI （0.54，0.98），P=0.030〕，diarrhoea〔OR=0.79，95%CI（0.69，0.92），P=0.001〕，headache〔OR=0.55，95%CI（0.45，0.68），P<0.001〕，asthma〔OR=0.73，95%CI（0.69，0.78），P<0.001〕，low body mass index〔WMD=-0.58，95%CI （-1.10，-0.06），P=0.029〕，decreased lymphocyte count〔WMD=-0.36，95%CI（-0.39，-0.32），P<0.001〕，decreased platelet count 〔WMD=-38.26，95%CI（-44.37，-32.15），P<0.001〕，increased D-dimer〔WMD=0.79，95%CI（0.63，0.95），P<0.001〕，longer prothrombin time〔WMD=0.78，95%CI（0.61，0.94），P<0.001〕，lower albumin〔WMD =-1.88，95%CI（-2.35，-1.40），P<0.001〕，increased procalcitonin〔WMD=0.27，95%CI（0.24，0.31），P<0.001〕，and increased cardiac troponin〔WMD=0.04，95%CI（0.03，0.04），P<0.001〕were associated with decreased risk of in-hospital death due to COVID-19. According to the meta-regression result，the heterogeneity in gender，renal disease，cardiovascular diseases，asthma，white blood cell count，neutrophil count，platelet count，hemoglobin，and urea nitrogen differed siangificnatly by country（P<0.05）. Conclusion The risk of in-hospital death due to COVID-19 may be increased by 25 factors（including being male，older age，dyspnoea，fatigue，obesity，smoking，stroke，kidney disease，cardiovascular disease，hypertension，diabetes，cancer，pulmonary disease，liver disease，elevated levels of white blood cells，neutrophil count，total bilirubin，aspartate transaminase，alanine transaminase，lactate dehydrogenase，blood urea nitrogen，serum creatinine，C-reactive protein，interleukin-6，and erythrocyte sedimentation rate），and may be decreased by 13 factors（including myalgia，cough，vomiting，diarrhoea，headache，asthma，low body mass index，decreased lymphocyte count and platelet count，increased D-dimer，longer prothrombin time，lower albumin，increased procalcitonin and cardiac troponin）. The conclusion drawn from this study needs to be further confirmed by high-quality，multicenter，large-sample，real-world studies. © 2023 Chinese General Practice. All rights reserved.

A study of sustained androgen signaling dependence in metastatic castrate resistant prostate cancer (mCRPC)

Background: Advanced androgen signaling inhibition, a prevailing therapy approach in advanced prostate cancer, incurs variable response. Therapy selection guided by predictors is an unmet need. Methods: We reviewed MDACC GU department and Hellenic Sister Institute records for Abiraterone Acetate (AA) treated mCRPC patients (pts) with extraordinary response (absence of radiographic/clinical progression for ≥3 years). We compared to reported findings for COU-AA-302 and real world experience to identify candidate predictors of outcome. We applied a previously proposed COU-AA-302 response prognostic model. Archived diagnostic and subsequent tumor specimens were retrieved for molecular characterization. Results: Forty four of 430 reviewed mCRPC pts had extraordinary response. Table depicts features. Median time to AA discontinuation was 5.8 yr (range 3-12.5+) and 20 pts are on treatment. Safety profile is acceptable with no overt increase in fractures or cardiovascular, metabolic morbidity. All pts experienced >50% PSA decline with nadir ≤0.1 in 80%, occurring within 5mo (median) (range <1-57). Median time to PSA progression 5.9 yr (95% CI 4.4-7.5), median rPFS 11.5 yr. Median OS 9.4 yr (95% CI 8.1-10.7). Pretreatment features differed significantly from other datasets for: Longer time from cancer diagnosis (median 8.5 yr), longer time to CRPC (median 3.1 yr), bone metastatic burden (63% ≤3 lesions), and PSA (median 5.5 yr). We applied the model to the cohort and it predicted only 7/44 (16%). Tissue analyses to be reported at meeting due to COVID19 research shutdown. [Formula presented] Conclusions: Extraordinary response to enhanced androgen signaling inhibition in mCRPC appears linked to androgen signaling ‘addiction’ and limited disease volume. Available prognostic models are not sensitive enough to guide selection. Routine biopsy derived predictors will help guide therapeutic strategies and improve curative fraction in advanced prostate cancer. Ref: https://doi.org/10.1016/j.clgc.2017.07.014. Clinical trial identification: MDACC: PA16-0736. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: S.K. Subudhi: Advisory/Consultancy: Valeant;Honoraria (self), Advisory/Consultancy: Dendreon;Honoraria (self), Advisory/Consultancy, and Ownership interest: Apricity Health;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen;Honoraria (self), Advisory/Consultancy: Polaris;Advisory/Consultancy: Amgen;Advisory/Consultancy: Bayer;Advisory/Consultancy: Exelixis;Research grant/Funding (institution): Bristol-Myers-Squibb;Research grant/Funding (institution): AstraZeneca;Honoraria (self): Compugen;Honoraria (self): Parker Institute of Cancer Immunotherapy;Honoraria (self): Society for Immunotherapy od Cancer. C. Logothetis: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Janssen;Research grant/Funding (institution): Bristol-Myers-Squibb;Advisory/Consultancy, Research grant/Funding (institution): Pfizer. E. Efstathiou: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tolmar;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Honoraria (self), Advisory/Consultancy, Research g ant/Fun ing (institution), Travel/Accommodation/Expenses: Oric. All other authors have declared no conflicts of interest.