Controversy on the CONVINCE study findings: the PRO take / Controvérsia sobre os achados do estudo CONVINCE: a perspectiva PRO

ABSTRACT The CONVINCE study, recently published in the New England Journal of Medicine, reveals a groundbreaking 23% reduction in the relative risk of all-cause mortality among end-stage kidney patients undergoing high convective volume hemodiafiltration. This significant finding challenges the conventional use of high-flux hemodialysis and offers hope for improving outcomes in chronic kidney disease patients. While some controversies surround the study's findings, including concerns about generalizability and the causes of death, it is essential to acknowledge the study's design and its main outcomes. The CONVINCE study, part of the HORIZON 2020 project, enrolled 1360 patients and demonstrated the superiority of hemodiafiltration in reducing all-cause mortality overall, as well as in specific patient subgroups (elderly, short vintage, non-diabetic, and those without cardiac issues). Interestingly, it was shown that hemodiafiltration had a protective effect against infection, including COVID-19. Future research will address sustainability, dose scaling effects, identification of subgroups especially likely to benefit and cost-effectiveness. However, for now, the findings strongly support a broader adoption of hemodiafiltration in renal replacement therapy, marking a significant advancement in the field.

RESUMO O estudo CONVINCE, publicado recentemente no New England Journal of Medicine, revela uma redução inovadora de 23% no risco relativo de mortalidade por todas as causas entre pacientes renais em estágio terminal submetidos à hemodiafiltração de alto volume de convecção. Esse achado significativo desafia o uso convencional da hemodiálise de alto fluxo e oferece esperança de melhoria dos desfechos em pacientes com doença renal crônica. Embora algumas controvérsias cerquem os achados do estudo, incluindo preocupações sobre a generalização e as causas de óbito, é essencial reconhecer o desenho do estudo e seus principais desfechos. O estudo CONVINCE, parte do projeto HORIZON 2020, inscreveu 1.360 pacientes e demonstrou a superioridade da hemodiafiltração na redução da mortalidade por todas as causas em geral, bem como em subgrupos específicos de pacientes (idosos, HD de curta duração, não diabéticos e aqueles sem problemas cardíacos). Curiosamente, demonstrou-se que a hemodiafiltração teve um efeito protetor contra infecções, incluindo a COVID-19. Pesquisas futuras abordarão sustentabilidade, efeitos de escalonamento da dose, identificação de subgrupos especialmente propensos a se beneficiar e a relação custo-benefício. No entanto, por ora, os achados apoiam fortemente uma adoção mais ampla da hemodiafiltração na terapia renal substitutiva, marcando um avanço significativo na área.

Risk factors for acute kidney injury in patients hospitalized with COVID-19 / Fatores de risco para lesão renal aguda em pacientes hospitalizados com COVID-19

Abstract Introduction: Acute kidney injury (AKI) occurs frequently in COVID-19 patients and is associated with greater morbidity and mortality. Knowing the risks of AKI allows for identification, prevention, and timely treatment. This study aimed to identify the risk factors associated with AKI in hospitalized patients. Methods: A descriptive, retrospective, cross-sectional, and analytical component study of adult patients hospitalized with COVID-19 from March 1 to December 31, 2020 was carried out. AKI was defined by the creatinine criteria of the KDIGO-AKI guidelines. Information, regarding risk factors, was obtained from electronic medical records. Results: Out of the 934 patients, 42.93% developed AKI, 60.59% KDIGO-1, and 9.9% required renal replacement therapy. Patients with AKI had longer hospital stay, higher mortality, and required more intensive care unit (ICU) admission, mechanical ventilation, and vasopressor support. Multivariate analysis showed that age (OR 1.03; 95% CI 1.02-1.04), male sex (OR 2.13; 95% CI 1.49-3.04), diabetes mellitus (DM) (OR 1.55; 95% CI 1.04-2.32), chronic kidney disease (CKD) (OR 2.07; 95% CI 1.06-4.04), C-reactive protein (CRP) (OR 1.02; 95% CI 1.00-1.03), ICU admission (OR 1.81; 95% CI 1.04-3.16), and vasopressor support (OR 7.46; 95% CI 3.34-16.64) were risk factors for AKI, and that bicarbonate (OR 0.89; 95% CI 0.84-0.94) and partial pressure arterial oxygen/inspired oxygen fraction index (OR 0.99; 95% CI 0.98-0.99) could be protective factors. Conclusions: A high frequency of AKI was documented in COVID-19 patients, with several predictors: age, male sex, DM, CKD, CRP, ICU admission, and vasopressor support. AKI occurred more frequently in patients with higher disease severity and was associated with higher mortality and worse outcomes.

RESUMO Introdução: Lesão renal aguda (LRA) ocorre frequentemente em pacientes com COVID-19 e associa-se a maior morbidade e mortalidade. Conhecer riscos da LRA permite a identificação, prevenção e tratamento oportuno. Este estudo teve como objetivo identificar fatores de risco associados à LRA em pacientes hospitalizados. Métodos: Realizou-se estudo descritivo, retrospectivo, transversal e de componente analítico de pacientes adultos hospitalizados com COVID-19 de 1º de março a 31 de dezembro, 2020. Definiu-se a LRA pelos critérios de creatinina das diretrizes KDIGO-LRA. Informações sobre fatores de risco foram obtidas de prontuários eletrônicos. Resultados: Dos 934 pacientes, 42,93% desenvolveram LRA, 60,59% KDIGO-1 e 9,9% necessitaram de terapia renal substitutiva. Pacientes com LRA apresentaram maior tempo de internação, maior mortalidade e necessitaram de mais internações em UTIs, ventilação mecânica e suporte vasopressor. A análise multivariada mostrou que idade (OR 1,03; IC 95% 1,02-1,04), sexo masculino (OR 2,13; IC 95% 1,49-3,04), diabetes mellitus (DM) (OR 1,55; IC 95% 1,04-2,32), doença renal crônica (DRC) (OR 2,07; IC 95% 1,06-4,04), proteína C reativa (PCR) (OR 1,02; IC 95% 1,00-1,03), admissão em UTI (OR 1,81; IC 95% 1,04-3,16) e suporte vasopressor (OR 7,46; IC 95% 3,34-16,64) foram fatores de risco para LRA, e que bicarbonato (OR 0,89; IC 95% 0,84-0,94) e índice de pressão parcial de oxigênio arterial/fração inspirada de oxigênio (OR 0,99; IC 95% 0,98-0,99) poderiam ser fatores de proteção. Conclusões: Documentou-se alta frequência de LRA em pacientes com COVID-19, com diversos preditores: idade, sexo masculino, DM, DRC, PCR, admissão em UTI e suporte vasopressor. LRA ocorreu mais frequentemente em pacientes com maior gravidade da doença e associou-se a maior mortalidade e piores desfechos.

Brazilian Dialysis Survey 2022 / Censo Brasileiro de Diálise 2022

Abstract Introduction: The Brazilian Dialysis Survey (BDS) is an annual national survey about patients on chronic dialysis that contributes to health policies. Objective: To report the 2022 epidemiological data from the BDS of the Brazilian Society of Nephrology (BSN). Methods: A survey was carried out in Brazilian chronic dialysis centers using an online questionnaire that included clinical and epidemiological aspects of patients on chronic dialysis, dialysis therapy data, and dialysis center characteristics. Results: Overall, 28% (n = 243) of the centers answered the questionnaire. In July 2022, the estimated total number of patients on dialysis was 153,831. The estimated prevalence and incidence rates of patients per million population (pmp) were 758 and 214, respectively. Of the prevalent patients, 95.3% were on hemodialysis (HD, 4.6% of these on hemodiafiltration) and 4.7% on peritoneal dialysis (PD). Only 1.3% of patients were not vaccinated against COVID-19. The prevalence of anemia (Hb < 10g/dL) was 27% and hyperphosphatemia (P > 5.5mg/dL) reached 30%. The estimated overall crude annual mortality rate was 17.1%. Conclusions: The absolute number and prevalence rate of patients on chronic dialysis continue to increase. A growing number of patients were receiving hemodiafiltration. The mortality rate decreased, probably due to the end of COVID-19 pandemic. The conclusions were drawn in the context of relatively low voluntary participation, which imposed methodological limitations on our estimates.

Resumo Introdução: O Censo Brasileiro de Diálise (CBD) é uma pesquisa nacional anual sobre pacientes em diálise crônica que contribui para as políticas de saúde. Objetivo: Informar os dados epidemiológicos de 2022 do CBD da Sociedade Brasileira de Nefrologia (SBN). Métodos: Foi realizada uma pesquisa em centros brasileiros de diálise por meio de um questionário online que incluiu aspectos clínicos e epidemiológicos de pacientes em diálise crônica, dados da terapia dialítica e características do centro de diálise. Resultados: No total, 28% (n = 243) dos centros de diálise ativos cadastrados na SBN responderam ao questionário. Em julho de 2022, o número total estimado de pacientes em diálise era de 153.831. As taxas estimadas de prevalência e incidência de pacientes por milhão (ppm) de habitantes foram 758 e 214, respectivamente. Dos pacientes prevalentes, 95,3% estavam em hemodiálise (HD; 4,6% desses em hemodiafiltração) e 4,7% em diálise peritoneal (DP). Apenas 1,3% dos pacientes não foram vacinados contra a COVID-19. A prevalência de anemia (Hb < 10g/dL) foi de 27% e de hiperfosfatemia (P > 5,5mg/dL) alcançou 30%. A taxa bruta total anual de mortalidade estimada foi de 17,1%. Conclusões: O número absoluto e a taxa de prevalência de pacientes em diálise crônica continuam a aumentar. Um número crescente de pacientes estava em hemodiafiltração. A taxa de mortalidade diminuiu, provavelmente devido ao fim da pandemia da COVID-19. As conclusões foram de um contexto de participação voluntária relativamente baixa, o que impõe limitações metodológicas às nossas estimativas.

Enteric coronavirus nsp2 is a virulence determinant that recruits NBR1 for autophagic targeting of TBK1 to diminish the innate immune response.

Non-structural protein 2 (nsp2) exists in all coronaviruses (CoVs), while its primary function in viral pathogenicity, is largely unclear. One such enteric CoV, porcine epidemic diarrhea virus (PEDV), causes high mortality in neonatal piglets worldwide. To determine the biological role of nsp2, we generated a PEDV mutant containing a complete nsp2 deletion (rPEDV-Δnsp2) from a highly pathogenic strain by reverse genetics, showing that nsp2 was dispensable for PEDV infection, while its deficiency reduced viral replication in vitro. Intriguingly, rPEDV-Δnsp2 was entirely avirulent in vivo, with significantly increased productions of IFNB (interferon beta) and IFN-stimulated genes (ISGs) in various intestinal tissues of challenged newborn piglets. Notably, nsp2 targets and degrades TBK1 (TANK binding kinase 1), the critical kinase in the innate immune response. Mechanistically, nsp2 induced the macroautophagy/autophagy process and recruited a selective autophagic receptor, NBR1 (NBR1 autophagy cargo receptor). NBR1 subsequently facilitated the K48-linked ubiquitination of TBK1 and delivered it for autophagosome-mediated degradation. Accordingly, the replication of rPEDV-Δnsp2 CoV was restrained by reduced autophagy and excess productions of type I IFNs and ISGs. Our data collectively define enteric CoV nsp2 as a novel virulence determinant, propose a crucial role of nsp2 in diminishing innate antiviral immunity by targeting TBK1 for NBR1-mediated selective autophagy, and pave the way to develop a new type of nsp2-based attenuated PEDV vaccine. The study also provides new insights into the prevention and treatment of other pathogenic CoVs.Abbreviations: 3-MA: 3-methyladenine; Baf A1: bafilomycin A1; CoV: coronavirus; CQ: chloroquine; dpi: days post-inoculation; DMVs: double-membrane vesicles; GABARAP: GABA type A receptor-associated protein; GFP: green fluorescent protein; GIGYF2: GRB10 interacting GYF protein 2; hpi: hours post-infection; IFA: immunofluorescence assay; IFIH1: interferon induced with helicase C domain 1; IFIT2: interferon induced protein with tetratricopeptide repeats 2; IFITM1: interferon induced transmembrane protein 1; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISGs: interferon-stimulated genes; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; NBR1: NBR1 autophagy cargo receptor; nsp2: non-structural protein 2; OAS1: 2'-5'-oligoadenylate synthetase 1; PEDV: porcine epidemic diarrhea virus; PRRs: pattern recognition receptors; RIGI: RNA sensor RIG-I; RT-qPCR: reverse transcription quantitative polymerase chain reaction; SQSTM1: sequestosome 1; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; VSV: vesicular stomatitis virus.

Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression.

Background: Coronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses. Methods: Sequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes. Results: The analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L, IFI44, RSAD2, ISG15, IFIT3, OAS1, EIF2AK2, IFI27, OASL, and EPSTI1. Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified. Conclusion: This research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.

Computational identification and experimental verification of a novel signature based on SARS-CoV-2-related genes for predicting prognosis, immune microenvironment and therapeutic strategies in lung adenocarcinoma patients.

Background: Early research indicates that cancer patients are more vulnerable to adverse outcomes and mortality when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, the specific attributes of SARS-CoV-2 in lung Adenocarcinoma (LUAD) have not been extensively and methodically examined. Methods: We acquired 322 SARS-CoV-2 infection-related genes (CRGs) from the Human Protein Atlas database. Using an integrative machine learning approach with 10 algorithms, we developed a SARS-CoV-2 score (Cov-2S) signature across The Cancer Genome Atlas and datasets GSE72094, GSE68465, and GSE31210. Comprehensive multi-omics analysis, including assessments of genetic mutations and copy number variations, was conducted to deepen our understanding of the prognosis signature. We also analyzed the response of different Cov-2S subgroups to immunotherapy and identified targeted drugs for these subgroups, advancing personalized medicine strategies. The expression of Cov-2S genes was confirmed through qRT-PCR, with GGH emerging as a critical gene for further functional studies to elucidate its role in LUAD. Results: Out of 34 differentially expressed CRGs identified, 16 correlated with overall survival. We utilized 10 machine learning algorithms, creating 101 combinations, and selected the RFS as the optimal algorithm for constructing a Cov-2S based on the average C-index across four cohorts. This was achieved after integrating several essential clinicopathological features and 58 established signatures. We observed significant differences in biological functions and immune cell statuses within the tumor microenvironments of high and low Cov-2S groups. Notably, patients with a lower Cov-2S showed enhanced sensitivity to immunotherapy. We also identified five potential drugs targeting Cov-2S. In vitro experiments revealed a significant upregulation of GGH in LUAD, and its knockdown markedly inhibited tumor cell proliferation, migration, and invasion. Conclusion: Our research has pioneered the development of a consensus Cov-2S signature by employing an innovative approach with 10 machine learning algorithms for LUAD. Cov-2S reliably forecasts the prognosis, mirrors the tumor's local immune condition, and supports clinical decision-making in tumor therapies.

Analysis of the expression of the Serpina1 gene in SARS-CoV-2 infection: Study of a new biomarker.

INTRODUCTION: The SERPINA1 gene encodes the protein Alpha-1 Antitrypsin (AAT1). Possible imbalances between the concentrations of proteases and antiproteases (AAT1) can lead to the development of serious pulmonary and extrapulmonary pathologies. In this work we study the importance of this possible imbalance in patients with COVID-19. OBJECTIVES: To correlate the severity of the symptoms of SARS-COV-2 infection with the AAT1 concentrations at diagnosis of the disease. METHODS: An observational, prospective, cross-sectional, non-interventional, analytical study was carried out where 181 cases with COVID-19 admitted to the "Lozano Blesa" University Clinical Hospital of Zaragoza were selected. The concentration of AAT1 was studied in all of them and this was correlated with the clinical aspects and biochemical parameters at hospital admission. RESULTS: 141 cases corresponded to patients with severe COVID and 40 patients with mild COVID. AAT1 levels were positively correlated with the days of hospitalization, severity, C-Reactive Protein, ferritin, admission to Intensive Care, and death, and presented a negative correlation with the number of lymphocytes/mm3. AAT1 concentrations higher than 237.5 mg/dL allowed the patient to be classified as "severe" (S72%; E78%) and 311.5 mg/dL were associated with the risk of admission to Intensive Care or Exitus (S67%; E79%). CONCLUSIONS: Levels of the SERPINA1 gene expression product, AAT1, correlate with the severity of COVID-19 patients at diagnosis of the disease, being useful as a prognostic biomarker.

Impact of metabolic dysfunction-associated steatotic liver disease on COVID-19 hospitalizations: A propensity-matched analysis of the United States.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), formally known as nonalcoholic fatty liver disease, is the most common chronic liver disease in the United States. Patients with MASLD have been reported to be at a higher risk of developing severe coronavirus disease 2019 (COVID-19) and death. However, most studies are single-center studies, and nationwide data in the United States is lacking. AIM: To study the influence of MASLD on COVID-19 hospitalizations during the initial phase of the pandemic. METHODS: We retrospectively analyzed the 2020 National Inpatient Sample (NIS) database to identify primary COVID-19 hospitalizations based on an underlying diagnosis of MASLD. A matched comparison cohort of COVID-19 hospitalizations without MASLD was identified from NIS after 1: N propensity score matching based on gender, race, and comorbidities, including hypertension, heart failure, diabetes, and cirrhosis. The primary outcomes included inpatient mortality, length of stay, and hospitalization costs. Secondary outcomes included the prevalence of systemic complications. RESULTS: A total of 2210 hospitalizations with MASLD were matched to 2210 hospitalizations without MASLD, with a good comorbidity balance. Overall, there was a higher prevalence of severe disease with more intensive care unit admissions (9.5% vs 7.2%, P = 0.007), mechanical ventilation (7.2% vs 5.7%, P = 0.03), and septic shock (5.2% vs 2.7%, P <0.001) in the MASLD cohort than in the non-MASLD cohort. However, there was no difference in mortality (8.6% vs 10%, P = 0.49), length of stay (5 d vs 5 d, P = 0.25), and hospitalization costs (42081.5 $ vs 38614$, P = 0.15) between the MASLD and non-MASLD cohorts. CONCLUSION: The presence of MAFLD with or without liver cirrhosis was not associated with increased mortality in COVID-19 hospitalizations; however, there was an increased incidence of severe COVID-19 infection. This data (2020) predates the availability of COVID-19 vaccines, and many MASLD patients have since been vaccinated. It will be interesting to see if these trends are present in the subsequent years of the pandemic.

Efficacy and safety of bamlanivimab in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Monoclonal antibodies (mAbs) have shown clinical benefits against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have reported the use of bamlanivimab as a promising treatment option for COVID-19. AIM: To synthesize the latest evidence for the efficacy and safety of bamlanivimab alone in the treatment of adult patients with COVID-19. METHODS: A literature search was conducted in PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar using "SARS-CoV-2", "COVID-19", "LY-CoV555", and "Bamlanivimab" keywords up to January 25, 2023. The quality of included studies was assessed using the Cochrane bias tools. The Comprehensive Meta-Analysis software version 3.0 was used to analyze the data. RESULTS: A total of 30 studies involving 47368 patients were included. A significant difference was observed between the bamlanivimab and standard of care/placebo groups in terms of mortality rate [risk ratio (RR) = 50, 95% confidence interval (CI): 0.36-0.70], hospitalization rate (RR = 0.51; 95%CI: 0.39-0.68), and emergency department (ED) visits (RR = 0.69; 95%CI: 0.47-0.99); while the two groups exhibited no significant difference in terms of intensive care unit (ICU) admission (P > 0.05). Compared to other mAbs, bamlanivimab was associated with a higher rate of hospitalization (RR = 1.44; 95%CI: 1.07-1.94). However, no significant difference was detected between the bamlanivimab and other mAbs groups in terms of mortality rate, ICU admission, and ED (P > 0.05). The incidence of any adverse events was similar between the bamlanivimab and control groups (P > 0.05). CONCLUSION: Although the results suggest the efficacy and safety of bamlanivimab in COVID-19 patients, further research is required to confirm the efficacy of this drug for the current circulating SARS-CoV-2 variants.

Country-based modelling of COVID-19 case fatality rate: A multiple regression analysis.

BACKGROUND: The spread of the severe acute respiratory syndrome coronavirus 2 outbreak worldwide has caused concern regarding the mortality rate caused by the infection. The determinants of mortality on a global scale cannot be fully understood due to lack of information. AIM: To identify key factors that may explain the variability in case lethality across countries. METHODS: We identified 21 Potential risk factors for coronavirus disease 2019 (COVID-19) case fatality rate for all the countries with available data. We examined univariate relationships of each variable with case fatality rate (CFR), and all independent variables to identify candidate variables for our final multiple model. Multiple regression analysis technique was used to assess the strength of relationship. RESULTS: The mean of COVID-19 mortality was 1.52 ± 1.72%. There was a statistically significant inverse correlation between health expenditure, and number of computed tomography scanners per 1 million with CFR, and significant direct correlation was found between literacy, and air pollution with CFR. This final model can predict approximately 97% of the changes in CFR. CONCLUSION: The current study recommends some new predictors explaining affect mortality rate. Thus, it could help decision-makers develop health policies to fight COVID-19.

Respiratory pathogenic microbial infections: a narrative review.

Respiratory infectious diseases have long been recognised as a substantial global healthcare burden and are one of the leading causes of death worldwide, particularly in vulnerable individuals. In the post COVID-19 era, there has been a surge in the prevalence of influenza virus A and other multiple known viruses causing cold compared with during the same period in the previous three years, which coincided with countries easing COVID-19 restrictions worldwide. This article aims to review community-acquired respiratory illnesses covering a broad spectrum of viruses, bacteria, and atypical microorganisms and focuses on the cluster prevalence of multiple known respiratory pathogens in China, thereby providing effective prevention and control measures.

Deaths in Immigration and Customs Enforcement (ICE) detention: A Fiscal Year (FY) 2021-2023 update.

Background: This study describes the deaths of individuals in Immigration and Customs Enforcement (ICE) detention between FY2021-2023, updating a report from FY2018-2020, which identified an increased death rate amidst the COVID-19 pandemic. Methods: Data was extracted from death reports published online by ICE. Causes of deaths were recorded, and death rates per 100,000 admissions were calculated using population statistics reported by ICE. Reports of individuals released from ICE custody just prior to death were also identified and described. Results: There were 12 deaths reported from FY2021-2023, compared to 38 deaths from FY2018-2020. The death rate per 100,000 admissions in ICE detention was 3.251 in FY2021, 0.939 in FY2022, and 1.457 in FY2023, compared with a pandemic-era high of 10.833 in FY2020. Suicide caused 1 of 12 (8.3%) deaths in FY2021-2023 compared with 9 of 38 (23.7%) deaths in FY2018-2020. COVID-19 was contributory in 3 of 11 (25%) medical deaths in FY2021-2023, compared with 8 of 11 (72.7%) in the COVID-era months of FY2020 (p = 0.030). Overall, 4 of 11 (36.3%) medical deaths in FY2021-2023 resulted from cardiac arrest in detention facilities, compared with 6 of 29 (20.3%) in FY2018-2020. Three deaths of hospitalized individuals released from ICE custody with grave prognoses were identified. Conclusions: The death rate among individuals in ICE custody decreased in FY2021-2023, which may be explained in part by the release of vulnerable individuals following recent federal legal determinations (e.g., Fraihat v. ICE). Identification of medically complex individuals released from ICE custody just prior to death and not reported by ICE indicates that reported deaths underestimate total deaths associated with ICE detention. Attentive monitoring of mortality outcomes following release from ICE custody is warranted.

Current remarks and future directions on the interactions between metabolic dysfunction-associated fatty liver disease and COVID-19.

During the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, particular interest rose regarding the interaction between metabolic dysfunction-associated fatty liver disease (MAFLD) and the COVID-19 infection. Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes. One of the proposed mechanisms is the inflammatory response pathway, especially the one involving cytokines, such as interleukin 6, which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver. This should increase our vigilance in terms of early detection, close follow up and early treatment for individuals with MAFLD and COVID-19 infection. In the direction of early diagnosis, biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed. COVID-19 is a newly described entity, expected to be of concern for the years to come, and MAFLD is a condition with an ever-increasing impact. Delineating the interaction between these two entities should be brought into the focus of research. Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective, and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.

Physical activity decreases in patients on the liver transplant waiting list and influences postoperative outcome-a prospective cohort study.

Background: Physical deconditioning affects patients suffering from end-stage liver disease (ESLD). Liver transplantation (LT) is the only curative option for ESLD. Growing evidence suggests that pre-habilitation is beneficial in reducing post-surgical morbidity and mortality. We investigated physical activity (PA) in patients awaiting LT in a country with long waiting times. Methods: Prospective, single center, longitudinal study in Bern, Switzerland between June 2019 and February 2020 (halted due to SARS-CoV-2 pandemic), with follow-up data up to six months post-transplant. Patients were instructed to use a wrist tracker (FitBit) to monitor PA, which was assessed using mixed-effects generalized linear models. The study was approved by the local ethics committee (BASEC ID 2019-00606). Results: Thirty-five patients were included [71% male, median 59 years, body mass index (BMI) 28 kg/m2, lab Model End-Stage Liver Disease (MELD) 11], 17 (49%) pre-frail and 5 (14%) frail according to the Liver Frailty Index (LFI). Twenty-eight patients underwent transplantation with 0 ninety-day mortality and 15 (53.6%) composite adverse clinical outcome. Median daily steps were 4,661 [interquartile range (IQR), 1,685-8,609] and weekly moderate PA (MPA) was 41 min (IQR, 0-127 min). Longitudinal analysis showed that female patients and patients on nutritional support had an increase in MPA between weeks 20 and 40. A significant decrease was seen in MPA after week 40, whilst no significant association was seen with age, Child-Pugh Score, LFI or quality of life at time of inclusion. MPA was significantly associated with the occurrence of the composite clinical endpoint after week 30 of waiting time (odds ratio 0.882, P=0.026). World Health Organization (WHO)-recommended MPA was significantly associated with less adverse composite clinical outcomes (P<0.001). Conclusions: In patients listed for LT, MPA decreased over time, showing a significant association with adverse outcome, specifically after week 30 on the waiting list. Our data support the implementation of routine pre-habilitation in patients awaiting LT.

Predictors of mortality in hospitalized African American COVID-19 patients with cancer.

Background: Coronavirus disease 2019 (COVID-19) manifest differently depending on patients' background and pre-existing conditions. It remains unclear how African Americans with cancer have been affected in comparison to those without. In this study, we aim to identify demographic, clinical, and laboratory markers associated with mortality in COVID-19 patients with cancer. Methods: We reviewed all COVID-19 hospitalized patients' records from Dec. 2019 to Oct. 2021 at Howard University Hospital. Patients having a history of, or active, cancer were reviewed. Clinical, treatment, lab test values, and pathological data were extracted. Univariable and multivariable analyses were conducted on the entire cohort as well as on cases and controls separately, using SPSS software. Results: Out of 512 COVID-19 infected patients, 49 had cancer, either active or history of cancer (cases) and 463 COVID-19 were cancer-free (controls), allowing for comparison. African American race was predominant in both cases and controls, 83.7% and 66.7% respectively. Cancer patients were older than non-cancer patients (mean age: 70.6 vs. 56.3 years) and had an increased length of hospital stay (mean 13.9 vs. 9.4 days). Mortality is significantly higher among cancer patients (n=10, 20.4%, P=0.03) compared to non-cancer COVID-19 patients (n=41, 8.9%). Among cancer patients, breast cancer was more prevalent in females and prostate cancer in males (54% and 52%, respectively). A comparison of patients with active vs. previous cancer showed no significant difference in the clinical outcome, death vs. discharge (P=0.34). A higher reduction in albumin level in cancer cases, from the time of admission to day 5, was significantly associated with death during the hospital stay compared to those discharged (n=24, 49.0%, P<0.001). In controls, lymphopenia (n=436, 94.2%, P=0.05), aspartate aminotransferase (AST) (n=59, 12.7%, P=0.008) and albumin (n=40, 8.6%, P=0.02) have shown an association with increased mortality. Conclusions: Albumin level has an inverse relationship with clinical outcomes among all COVID-19 infected cancer patients. Reduction in albumin level during the hospital stay, particularly in COVID-19 cancer patients should be considered as a predictor of mortality. Further research with a large cohort size is needed to verify and identify other predictors of outcomes in COVID-19 patients with cancer.

Comparison of ELISA with automated ECLIA for IL-6 determination in COVID-19 patients: An Italian real-life experience.

Objectives: Coronavirus disease 2019 (COVID-19) has a wide spectrum of clinical severity. A cytokine storm is associated with COVID-19 severity. Of these, IL-6 is significantly associated with higher mortality and is also a marker for predicting disease prognosis. IL-6 may act as a target for therapeutics and, a blockade of IL-6 function by Tocilizumab has been described as a treatment of the inflammatory process COVID-19-related. This study aims to describe our experience comparing two different methods, in detail Human IL-6 Instant ELISA and the Elecsys IL-6 based on ECLIA, for the IL-6 assessment. Design and methods: IL-6 levels from serum samples of 104 COVID-19 patients, admitted to the AOU Careggi (Hospital in Florence -Italy), were assessed by using the two above-mentioned methods, and the results were analysed through Passing-Bablok regression fit and Bland-Altman plot. Results: The regression exhibited a linear relation between the methods with a regression equation (y = - 0.13 + 0.63 x; 95 % C.I. intercept = - 0.13 to 4.55; 95 % C.I. slope = 1.03 to 1.26 with R2 = 0.89, p > 0.05), showing a positive slope. The agreement of the two methods reported a bias of -25.0 pg/mL. Thus, the two methods correlate but do not agree in terms of numeric results. Conclusions: The two assays showed good comparability. However, because of the extremely wide linear range of the ECLIA, its throughput and its capacity for immune profiling, it represents an interesting emerging technology in the immunology field.

Mortality risk factors in the dependent population of Castilla-La Mancha (Spain) before and during the first COVID-19 wave.

The coronavirus disease pandemic has had an important impact worldwide. The population aged over 65 years and aged dependent persons are the population groups which have suffered in a highest level the consequences of the pandemic in terms of cases and death. In Spain, the situation is similar to other countries, but regional studies are needed because competencies on long-term care depend on regional public administration. Thus, the aim of this work is to analyse social and individual factors associated with the risk of mortality of legally recognised dependent people during the pandemic compared to a non-pandemic period. The data were extracted from the administrative database on individuals included in Castilla-La Mancha's long-term care system and it was merged with the information from the Spanish National Death Index administered by the Ministry of Health, Consumption and Social Welfare. The results show that the risk of mortality between March and June 2020 was positively associated with being male; being older than 65, with an especially high impact in the group aged over 90; having a higher level of dependency; living in a nursing home; and living in a place with more population density. Intraregional differences related to health areas also exists in both pandemic and non-pandemic periods. These findings are critical with a view to enhancing protocols for the care of the most vulnerable population groups.

Therapeutic development targeting host heparan sulfate proteoglycan in SARS-CoV-2 infection.

The global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an urgent need for effective therapeutic options. SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic that has resulted in significant morbidity and mortality worldwide. The virus is known to enter host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, and emerging evidence suggests that heparan sulfate proteoglycans (HSPGs) play a crucial role in facilitating this process. HSPGs are abundant cell surface proteoglycan present in many tissues, including the lung, and have been shown to interact directly with the spike protein of SARS-CoV-2. This review aims to summarize the current understanding of the role of HSPGs in SARS-CoV-2 infection and the potential of developing new therapies targeting HSPGs.

Does Western or Chinese Zodiac Sign Predict COVID Infections and Death?

INTRODUCTION: Humans have been fascinated by and studying the sky since the beginning of time. Beliefs in Chinese and Western astrology persist in modern society and have gained increasing interest in light of the COVID-19 pandemic. Zodiac signs are typified by certain qualities, for example, obsessive-compulsive traits in Libras and Virgos or the highly social traits in Leos and Geminis. We investigate whether the various characteristics or personalities purported of assigned birth signs may alter the predisposition to COVID-19 infections or mortality. METHODS: This is a retrospective, single-center cohort study of 2545 adult patients with confirmed COVID-19 infection presenting to the emergency room over a 14-month period (September 2020 to November 2021). COVID-19 infectivity was determined based on polymerase chain reaction (PCR) testing. Western and Chinese Zodiac signs were designated using date of birth. Both Zodiac signs were evaluated for risk of infection and death. RESULTS: Mortality rates across the zodiac and astrology signs showed no statistical difference using the 12-sample test for equality of proportions. Coincidentally, the mean age for the deceased was 74.5 years, and it was 53.9 years for those alive, resulting in a difference of 20.6 years. A two-sample t-test confirms that the observed difference of 20.6 years of age between the two groups is statistically significant with a p-value <0.05. The coefficient of the predictor age is statistically significant. The odds ratio estimate of age is 1.06, with the corresponding 95% confidence interval (CI) being (1.048, 1.073). This means that the odds of dying increase by 6% for every additional year. DISCUSSION: Astrology once held a significant impact on beliefs in medicine and continues in Chinese and Ayurvedic medicine. Our study utilized local data to determine if COVID-19 infection rates and mortality might have a relationship to astrological designations of Chinese and Western zodiac signs. Data analysis demonstrated that there was no statistical significance found between Western and Chinese Zodiac signs and mortality or infections. Similar to many previous studies, age can be a risk factor for mortality.

Effect of Surfactant Therapy on Clinical Outcomes of COVID-19 Patients With ARDS: A Systematic Review and Meta-Analysis.

INTRODUCTION: The COVID-19 pandemic has brought unprecedented challenges, not only in terms of public health but also in the realm of innovative therapeutic approaches to combat the severe respiratory complications associated with the virus. The effect of surfactant therapy on reducing mortality in COVID-19 patients with acute respiratory distress syndrome (ARDS) hasn't been explored before. METHODS: We conducted a search on PubMed, Scopus, Science Direct, and Clinicaltrials.gov to identify relevant studies, incorporating subject headings and keywords related to "Surfactant Therapy," "COVID-19," and "ARDS." Binary random effects were used to estimate the odds ratio (OR) for 28-day mortality, and continuous random effects were used to estimate the mean difference (MD) for length of hospitalization with their respective 95% confidence interval (CI). Analysis was performed with RevMan Version 5.4.1 (The Cochrane Collaboration, London, GBR). RESULTS: We included four studies with 126 patients. Patients who received surfactant had lower odds of mortality (OR 0.53, 95% CI (0.23, 1.20), p=0.13) and a shorter duration of hospital stay (MD -5.69, 95% CI [-7.06, -4.30], p <0.00001) compared to patients who did not receive surfactant therapy. However, the findings regarding mortality were not statistically significant. CONCLUSIONS: The COVID-19 patients with ARDS who received surfactant therapy had lower hospitalization stays and mortality rates, indicating that surfactant therapy may improve clinical outcomes in COVID-19 patients with ARDS. However, the results were not significant, and further research with more prospective studies and randomized clinical trials (RCTs) with larger sample sizes is needed to confirm these findings and assess their practical significance and generalizability.