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.

The genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

Comprehensive analysis of immunogenic cell death-related gene and construction of prediction model based on WGCNA and multiple machine learning in severe COVID-19.

The death of coronavirus disease 2019 (COVID-19) is primarily due to from critically ill patients, especially from ARDS complications caused by SARS-CoV-2. Therefore, it is essential to contribute an in-depth understanding of the pathogenesis of the disease and to identify biomarkers for predicting critically ill patients at the molecular level. Immunogenic cell death (ICD), as a specific variant of regulatory cell death driven by stress, can induce adaptive immune responses against cell death antigens in the host. Studies have confirmed that both innate and adaptive immune pathways are involved in the pathogenesis of SARS-CoV-2 infection. However, the role of ICD in the pathogenesis of severe COVID-19 has rarely been explored. In this study, we systematically evaluated the role of ICD-related genes in COVID-19. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis based on ICD differentially expressed genes. The results showed that immune infiltration characteristics were altered in severe and non-severe COVID-19. In addition, we used multiple machine learning methods to screen for five risk genes (KLF5, NSUN7, APH1B, GRB10 and CD4), which are used to predict COVID-19 severity. Finally, we constructed a nomogram to predict the risk of severe COVID-19 based on the classification and recognition model, and validated the model with external data sets. This study provides a valuable direction for the exploration of the pathogenesis and progress of COVID-19, and helps in the early identification of severe cases of COVID-19 to reduce mortality.

Oral administration of PEDV-dissolved Alg-CS gel induces high and sustained mucosal immunity in mice.

Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.

Smoking cessation among tuberculosis patients during the coronavirus disease-2019 pandemic.

Smoking has been recognized as a significant risk factor for COVID-19 and mortality. The World Health Organization (WHO) has recommended smoking cessation to reduce the impact of COVID-19. This study aimed to evaluate the smoking cessation rate of patients starting tuberculosis (TB) treatment at six months using motivational interviewing based on the WHO "five steps to quit" model. In addition, we assessed the knowledge about smoking and the barriers to smoking cessation. We conducted a retrospective cohort study. Outpatients aged >18 years, smokers, and those who are starting TB treatment in two outpatient TB clinics were invited to participate. Patients received information about the importance of smoking cessation, especially in TB patients, and standardized advice based on guidelines. This information was repeated during phone calls during the second and fourth months of treatment. During the study period, 111 patients were included. The primary outcome was the smoking cessation rate at the end of the sixth month of treatment, which was 26.8% (19/71). The barriers to smoking cessation described by the patients were anxiety/depression (47.4%), seeing someone smoking (38.5%), drug use (19.2%), and alcohol abuse (2.6%). The assessment of knowledge about smoking showed that patients had some information gaps. In conclusion, TB smokers who tried to quit smoking during the COVID-19 pandemic faced many challenges. Despite this, we demonstrated a reasonable smoking cessation rate with a nurse-conducted motivational interview.

Neuropsychiatric complications of coronavirus disease 2019: Mount Sinai Health System cohort study.

OBJECTIVE: To describe the frequency of neuropsychiatric complications among hospitalized patients with coronavirus disease 2019 (COVID-19) and their association with pre-existing comorbidities and clinical outcomes. METHODS: We retrospectively identified all patients hospitalized with COVID-19 within a large multicenter New York City health system between March 15, 2020 and May 17, 2021 and randomly selected a representative cohort for detailed chart review. Clinical data, including the occurrence of neuropsychiatric complications (categorized as either altered mental status [AMS] or other neuropsychiatric complications) and in-hospital mortality, were extracted using an electronic medical record database and individual chart review. Associations between neuropsychiatric complications, comorbidities, laboratory findings, and in-hospital mortality were assessed using multivariate logistic regression. RESULTS: Our study cohort consisted of 974 patients, the majority were admitted during the first wave of the pandemic. Patients were treated with anticoagulation (88.4%), glucocorticoids (24.8%), and remdesivir (10.5%); 18.6% experienced severe COVID-19 pneumonia (evidenced by ventilator requirement). Neuropsychiatric complications occurred in 58.8% of patients; 39.8% experienced AMS; and 19.0% experienced at least one other complication (seizures in 1.4%, ischemic stroke in 1.6%, hemorrhagic stroke in 1.0%) or symptom (headache in 11.4%, anxiety in 6.8%, ataxia in 6.3%). Higher odds of mortality, which occurred in 22.0%, were associated with AMS, ventilator support, increasing age, and higher serum inflammatory marker levels. Anticoagulant therapy was associated with lower odds of mortality and AMS. CONCLUSION: Neuropsychiatric complications of COVID-19, especially AMS, were common, varied, and associated with in-hospital mortality in a diverse multicenter cohort at an epicenter of the COVID-19 pandemic.

Identification of Age-Related Characteristic Genes Involved in Severe COVID-19 Infection Among Elderly Patients Using Machine Learning and Immune Cell Infiltration Analysis.

Elderly patients infected with severe acute respiratory syndrome coronavirus 2 are at higher risk of severe clinical manifestation, extended hospitalization, and increased mortality. Those patients are more likely to experience persistent symptoms and exacerbate the condition of basic diseases with long COVID-19 syndrome. However, the molecular mechanisms underlying severe COVID-19 in the elderly patients remain unclear. Our study aims to investigate the function of the interaction between disease-characteristic genes and immune cell infiltration in patients with severe COVID-19 infection. COVID-19 datasets (GSE164805 and GSE180594) and aging dataset (GSE69832) were obtained from the Gene Expression Omnibus database. The combined different expression genes (DEGs) were subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Diseases Ontology functional enrichment analysis, Gene Set Enrichment Analysis, machine learning, and immune cell infiltration analysis. GO and KEGG enrichment analyses revealed that the eight DEGs (IL23A, PTGER4, PLCB1, IL1B, CXCR1, C1QB, MX2, ALOX12) were mainly involved in inflammatory mediator regulation of TRP channels, coronavirus disease-COVID-19, and cytokine activity signaling pathways. Three-degree algorithm (LASSO, SVM-RFE, KNN) and correlation analysis showed that the five DEGs up-regulated the immune cells of macrophages M0/M1, memory B cells, gamma delta T cell, dendritic cell resting, and master cell resisting. Our study identified five hallmark genes that can serve as disease-characteristic genes and target immune cells infiltrated in severe COVID-19 patients among the elderly population, which may contribute to the study of pathogenesis and the evaluation of diagnosis and prognosis in aging patients infected with severe COVID-19.

Clinical characteristics and prognosis of patients with COVID-19 on mechanical ventilation undergoing continuous renal replacement therapy.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients. METHODS: This multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation. RESULTS: Of the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group. CONCLUSION: This study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients.

Early Outcomes From a Multicenter Transcatheter Self-Expanding Pulmonary Valve Replacement Registry.

BACKGROUND: Transcatheter pulmonary valve replacement (TPVR) with the self-expanding Harmony valve (Medtronic) is an emerging treatment for patients with native or surgically repaired right ventricular outflow tract (RVOT) pulmonary regurgitation (PR). Limited data are available since U.S. Food and Drug Administration approval in 2021. OBJECTIVES: In this study, the authors sought to evaluate the safety and short-term effectiveness of self-expanding TPVR in a real-world experience. METHODS: This was a multicenter registry study of consecutive patients with native RVOT PR who underwent TPVR through April 30, 2022, at 11 U.S. CENTERS: The primary outcome was a composite of hemodynamic dysfunction (PR greater than mild and RVOT mean gradient >30 mm Hg) and RVOT reintervention. RESULTS: A total of 243 patients underwent TPVR at a median age of 31 years (Q1-Q3: 19-45 years). Cardiac diagnoses were tetralogy of Fallot (71%), valvular pulmonary stenosis (21%), and other (8%). Acute technical success was achieved in all but 1 case. Procedural serious adverse events occurred in 4% of cases, with no device embolization or death. Hospital length of stay was 1 day in 86% of patients. Ventricular arrhythmia prompting treatment occurred in 19% of cases. At a median follow-up of 13 months (Q1-Q3: 8-19 months), 98% of patients had acceptable hemodynamic function. Estimated freedom from the composite clinical outcome was 99% at 1 year and 96% at 2 years. Freedom from TPVR-related endocarditis was 98% at 1 year. Five patients died from COVID-19 (n = 1), unknown causes (n = 2), and bloodstream infection (n = 2). CONCLUSIONS: In this large multicenter real-world experience, short-term clinical and hemodynamic outcomes of self-expanding TPVR therapy were excellent. Ongoing follow-up of this cohort will provide important insights into long-term outcomes.

Vaccine Attitudes and Uptake Among Latino Residents of a Former COVID-19 Hotspot.

Early in the COVID-19 pandemic, the Centers for Disease Control and Prevention identified Prince William County (PWC), Va. as a hotspot with a high disease rate among Latinos. This study uses spatial, survey, and qualitative data to understand attitudes towards vaccine uptake among PWC Latinos. A quantitative analysis (n=266) estimates the association for vaccine acceptance among Latinos. Next, qualitative interviews with Latinos (n=37) examine vaccine attitudes. Finally, a spatial analysis identifies clusters of social vulnerability and low vaccine uptake in PWC and adjacent counties. Our findings show that a substantial proportion of PWC Latinos had low vaccination rates as of December 2022, two years after the vaccine's release. Side effects and safety and approval concerns were cited in both the quantitative and qualitative studies. Persistent vaccine disparities are concerning given the high hospitalization and mortality rates that prevailed among Latinos early in the pandemic.

[A Case of Interstitial Pneumonia Induced by Immune Checkpoint Inhibitors for Gastric Cancer During the COVID- 19 Pandemic].

BACKGROUND: The novel coronavirus disease(corona virus disease 2019: COVID-19)has calmed down worldwide, and the severity of the disease is decreasing. On the other hand, due to the emergence of strain mutations, the number of infected people shows a wavy course. I have experienced a case of gastric cancer that underwent chemotherapy including an immune checkpoint inhibitors(ICI) early after COVID-19, so I will report it including a discussion. CASE: A 71-year-old man. The patient visited our hospital with a chief complaint of stomach discomfort, and gastrointestinal endoscopy revealed advanced gastric cancer accompanied by narrowing of the gastric lumen. The histopathological examination showed a poorly differentiated adenocarcinoma. A CT scan of the chest and abdomen showed thickening of the entire gastric wall, indicating the presence of enlarged adjacent lymph nodes and infiltration into adjacent organs. No other obvious distant metastases were observed. Staging laparoscopy was performed, it revealed infiltration of the posterior wall of the stomach into the celiac artery and anterior surface of the pancreas. We determined that curative resection would be difficult. As a result of planning chemotherapy for locally advanced gastric cancer, the patient contracted COVID-19 due to a hospital- acquired infection. The patient's COVID-19 infection was managed with supportive care alone without severe complications, and they recovered within the course of treatment. Two weeks after the onset of the infection, chemotherapy(FOLFOX+ Nivo)was initiated. The patient completed up to 9 courses of chemotherapy, and the treatment response was determined to be stable disease(SD). Due to a tendency of stenosis in the gastric lumen, the possibility of future dilation procedures was considered. As a result, the patient underwent second-line chemotherapy with a combination of wPTX+RAM. After completing 1 course of treatment, the patient developed drug-induced interstitial pneumonia, which was managed with intensive care and steroid pulse therapy, resulting in improvement. There was progression of gastric lumen stenosis, and an endoscopic dilation procedure/stent placement was performed. Subsequently, there was a rapid increase in malignant ascites and a decline in activities of daily living(ADL), leading to palliative care. Unfortunately, the patient succumbed to cancer-related complications 10 months after the diagnosis. DISCUSSION: In this case, the serial antibody titers of COVID-19 also indicated the sustained effectiveness of the multi-drug combination chemotherapy. The treatment course suggests a suspicion of drug-induced interstitial pneumonia due to PTX/RAM, but the long-term imaging follow-up implies that ICI may be the cause. When using ICI, COVID-19 infection alone may pose a potential risk factor.

Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Department.

BACKGROUND COVID-19 increases the risk of acute cardiovascular diseases (CVDs), including acute coronary syndrome (ACS), acute pulmonary embolism (APE), and acute myocarditis (AMyo). The actual impact of CVDs on mortality of patients with COVID-19 remains unknown. This study aimed to determine whether CVDs influence the course of COVID-19 pneumonia and if they can be easily detected by using common tests and examinations. MATERIAL AND METHODS Data of 249 consecutive patients with COVID-19 hospitalized in a dedicated cardiology department were analyzed. On admission, clinical status, biomarkers, computed tomography, and bedside echocardiography were performed. RESULTS D-dimer level predicted APE (AUC=0.850 95% CI [0.765; 0.935], P<0.001) with sensitivity of 69.4% and specificity of 96.2% for a level of 4968.0 ng/mL, and NT-proBNP predicted AMyo (AUC=0.692 95% CI [0.502; 0.883], P=0.004) and showed sensitivity of 54.5%, with specificity of 86.5% for the cut-off point of 8970 pg/mL. Troponin T levels were not useful for diagnostic differentiation between CVDs. An extent of lung involvement predicted mortality (OR=1.03 95% CI [1.01;1.04] for 1% increase, P<0.001). After adjusting for lung involvement, ACS increased mortality, compared with COVID-19 pneumonia only (OR=5.27 95% CI [1.76; 16.38] P=0.003), while APE and AMyo did not affect risk for death. CONCLUSIONS D-dimer and NT-proBNP, but not troponin T, are useful in differentiating CVDs in patients with COVID-19. ACS with COVID-19 increased in-hospital mortality independently from extent of lung involvement, while coexisting APE or AMyo did not.

Loneliness and Mortality Risk Among Cancer Survivors in the United States: A Retrospective, Longitudinal Study.

BACKGROUND: Loneliness, a subjective feeling of being isolated, is a prevalent concern for elderly people and more so among cancer survivors because a cancer diagnosis and its subsequent treatment may result in long-term adverse health effects. This study aimed to examine the association of loneliness and mortality risk among cancer survivors in the United States. METHODS: We identified a longitudinal cohort of cancer survivors aged ≥50 years from the nationally representative panel surveys of the 2008-2018 Health and Retirement Study. Follow-up for vital status was through 2020. Loneliness was measured using an 11-item abbreviated version of the UCLA Loneliness Scale (Version 3), including questions about lacking companionship and feeling isolated from others. A score was assigned according to the responses to each question, with 1 for least lonely, 2 for moderately lonely, and 3 for the loneliest option. Items were summed to create total loneliness scores for each individual, which were categorized into 4 levels: 11-12 (low/no loneliness), 13-15 (mild loneliness), 16-19 (moderate loneliness), and 20-33 (severe loneliness) based on the sample distribution. Time-varying Cox proportional hazard models with age as a time scale were used to examine the association of loneliness and survival among cancer survivors. RESULTS: A total of 3,447 cancer survivors with 5,808 person-years of observation were included, with 1,402 (24.3%), 1,445 (24.5%), 1,418 (23.6%), and 1,543 (27.6%) reporting low/no, mild, moderate, and severe loneliness, respectively. Compared with survivors reporting low/no loneliness, survivors reporting greater loneliness had a higher mortality risk, with the highest adjusted hazard ratios (aHRs) among the loneliest group (aHR, 1.67 [95% CI, 1.25-2.23]; P=.004) following a dose-response association. CONCLUSIONS: Elevated loneliness was associated with a higher mortality risk among cancer survivors. Programs to screen for loneliness among cancer survivors and to provide resources and support are warranted, especially considering the widespread social distancing that occurred during the COVID-19 pandemic.

Maintaining essential health services during a pandemic: lessons from Costa Rica's COVID-19 response.

Studies on COVID-19 usually focus on health system responses to decrease the rate of COVID-19 infection and death, but patients with other diseases also require access to health services during the pandemic. This paper describes the structures and processes by which the Costa Rican Social Security Fund (CCSS) changed in response to the COVID-19 pandemic, which helped to sustain essential health services (EHSs). We conducted a desk review of the local literature and semistructured qualitative interviews with key informants from the CCSS. We found that the CCSS implemented changes in structure, such as creating a specialised COVID-19 centre and hiring additional interim health workers. The CCSS also implemented changes in processes, including leveraging its integrated network to optimise its resources and support alternative care modalities. These changes generated changes in outputs and outcomes that helped sustain EHSs for non-COVID-19 patients. These interventions were possible primarily due to Costa Rica's underlying health system, particularly its integrated nature with a single institution in charge of healthcare provision financed through mandatory health insurance, a unique digital medical record system and a contingency fund.

Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination.

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.

SARS-CoV-2 and its ORF3a, E and M viroporins activate inflammasome in human macrophages and induce of IL-1α in pulmonary epithelial and endothelial cells.

Inflammasome assembly is a potent mechanism responsible for the host protection against pathogens, including viruses. When compromised, it can allow viral replication, while when disrupted, it can perpetuate pathological responses by IL-1 signaling and pyroptotic cell death. SARS-CoV-2 infection was shown to activate inflammasome in the lungs of COVID-19 patients, however, potential mechanisms responsible for this response are not fully elucidated. In this study, we investigated the effects of ORF3a, E and M SARS-CoV-2 viroporins in the inflammasome activation in major populations of alveolar sentinel cells: macrophages, epithelial and endothelial cells. We demonstrated that each viroporin is capable of activation of the inflammasome in macrophages to trigger pyroptosis-like cell death and IL-1α release from epithelial and endothelial cells. Small molecule NLRP3 inflammasome inhibitors reduced IL-1 release but weakly affected the pyroptosis. Importantly, we discovered that while SARS-CoV-2 could not infect the pulmonary microvascular endothelial cells it induced IL-1α and IL-33 release. Together, these findings highlight the essential role of macrophages as the major inflammasome-activating cell population in the lungs and point to endothelial cell expressed IL-1α as a potential novel component driving the pulmonary immunothromobosis in COVID-19.

Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice.

Viral myocarditis, an inflammatory disease of the myocardium, is a significant cause of sudden death in children and young adults. The current coronavirus disease 19 pandemic emphasizes the need to understand the pathogenesis mechanisms and potential treatment strategies for viral myocarditis. Here, we found that TRIM29 was highly induced by cardiotropic viruses and promoted protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated endoplasmic reticulum (ER) stress, apoptosis, and reactive oxygen species (ROS) responses that promote viral replication in cardiomyocytes in vitro. TRIM29 deficiency protected mice from viral myocarditis by promoting cardiac antiviral functions and reducing PERK-mediated inflammation and immunosuppressive monocytic myeloid-derived suppressor cells (mMDSC) in vivo. Mechanistically, TRIM29 interacted with PERK to promote SUMOylation of PERK to maintain its stability, thereby promoting PERK-mediated signaling pathways. Finally, we demonstrated that the PERK inhibitor GSK2656157 mitigated viral myocarditis by disrupting the TRIM29-PERK connection, thereby bolstering cardiac function, enhancing cardiac antiviral responses, and curbing inflammation and immunosuppressive mMDSC in vivo. Our findings offer insight into how cardiotropic viruses exploit TRIM29-regulated PERK signaling pathways to instigate viral myocarditis, suggesting that targeting the TRIM29-PERK axis could mitigate disease severity.

Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital.

It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688-0.571; 0.696, 0.439-1.103; 1.056, 0.941-1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613-2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745-1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities.