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1.
Gene ; 806: 145922, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454032

RESUMO

Gastric cancer (GC)-derived cell lines were generally used in basic cancer research and drug screening. However, it is always concerned about the difference between cultured cells and primary tumor by oncologists. To address this question, we compared differentially expressed genes (DEGs) in primary cancers, healthy tissues, and cell lines both in vitro and in silico. Seven reported genes with decreased expression in GCs by DNA methylation were analyzed in our cohort studies and experimentally validation. Selected datasets from TCGA (The Cancer Genome Atlas), CCLE (The Broad Institute Cancer Cell Line Encyclopedia), and GTEx (The Genotype-Tissue Expression project) were used to represent GCs, GC-derived cell lines, and healthy tissues respectively in the in silico analysis. Thirty gastric tissues together with six cell lines were used for validations. Unexpectedly, we experimentally found that reported cancer-related downregulated genes were only found in cancer cell lines but not in biopsies. The unchanged gene expressions in primary GCs were generally consistent with our cohort study, using information from cancerous (TCGA) and healthy tissues (GETx). Substantial differences were also found between DEGs of cancer tissues (TGCA)/ healthy tissues (GTEx) pair and cell lines (CCLE)/ healthy tissues (GTEx) pair, which confirmed the significant differences between primary cancer and cancer cell lines. Moreover, elevated expression of YWHAQ (14-3-3 δ) and THBS1 were observed in the GC biopsies, which might be potential biomarkers for GC diagnosis, considering the increased YWHAQ and THBS1 associated with poor survival rates in gastric cancer patients. In sum, it is suggested that cautions should be taken when using GC cell lines to study genes that show great differences between cell lines and tissues.


Assuntos
Proteínas 14-3-3/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Trombospondinas/genética , Proteínas 14-3-3/metabolismo , Idoso , Atlas como Assunto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Metilação de DNA , Conjuntos de Dados como Assunto , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Cultura Primária de Células , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Trombospondinas/metabolismo , Células Tumorais Cultivadas
2.
J Med Virol ; 94(1): 407-412, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34491572

RESUMO

The ChAdOx1 nCoV-19 vaccine (Oxford University-Astra Zeneca) has demonstrated nearly 70% efficacy against symptomatic COVID-19 in trials and some real-world studies. The vaccine was the first to be approved in India in early January 2021 and is manufactured by the Serum Institute of India. Favorable short-term safety data of the vaccine in India in a real-world setting has been recently demonstrated. Here, we report secondary objective (COVID-19 occurrence) measures of the same ongoing prospective observational study in prioritized recipients of the vaccine. The findings are based on participants who could complete at least 2 months of follow-up (n = 1500; female/male: 472/1028; mean age: 38.8 years). Laboratory confirmed SARS-CoV-2 infection was observed in 27/65 participants (41%) who received a single dose and 271/1435 (19%) who received both doses. Specifically, among doctors, 18/27 (66.7%) one dose recipients and 131/377 (34.7%) fully vaccinated developed SARS-CoV-2 infection. The majority of the cases were mild in all groups, and most were breakthrough infections. The occurrence of "severe" COVID-19 was 7.7 times lower (0.4%) in fully vaccinated participants compared to partially vaccinated (3.1%). Four deaths were observed in the study. One of the four deaths was due to sepsis, two due to unspecified cardiac events, and one due to unspecified post-COVID-19 complications. The results of this preliminary analysis necessitate vigorous research on the performance of vaccines against variants, optimal timing of vaccination, and also optimal timings of effectiveness studies to guide future vaccination policy.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina/imunologia , SARS-CoV-2/imunologia , Adulto , COVID-19/epidemiologia , COVID-19/mortalidade , Comorbidade , Feminino , Humanos , Imunização Secundária/estatística & dados numéricos , Índia/epidemiologia , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Vacinação
3.
J Med Virol ; 94(1): 318-326, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34516010

RESUMO

When hospitals first encountered coronavirus disease 2019 (COVID-19), there was a dearth of therapeutic options and nearly 1 in 3 patients died from the disease. By the summer of 2020, as deaths from the disease declined nationally, multiple single-center studies began to report declining mortality of patients with COVID-19. To evaluate the effect of COVID-19 on hospital-based mortality, we searched the Vizient Clinical Data Base for outcomes data from approximately 600 participating hospitals, including 130 academic medical centers, from January 2017 through December 2020. More than 32 million hospital admissions were included in the analysis. After an initial spike, mortality from COVID-19 declined in all regions of the country to under 10% by June 2020 and remained constant for the remainder of the year. Despite this, inpatient, all-cause mortality has increased since the beginning of the pandemic, even those without respiratory failure. Inpatient mortality has particularly increased in elderly patients and in those requiring intubation for respiratory failure. Since June 2020, COVID-19 kills one in every 10 patients admitted to the hospital with this diagnosis. The addition of this new disease has raised overall hospital mortality especially those who require intubation for respiratory failure.


Assuntos
COVID-19/mortalidade , Mortalidade Hospitalar/tendências , Insuficiência Respiratória/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Pacientes Internados/estatística & dados numéricos , Intubação/estatística & dados numéricos , Respiração Artificial/mortalidade , SARS-CoV-2
4.
J Med Virol ; 94(1): 147-153, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34411312

RESUMO

This study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty-six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/µl; interquartile range [IQR]: 4.2-6.3) than in moderate-severe cases (2.6 log10 copies/µl; [IQR: 1.1-4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/µl [IQR: 6.0-6.5]) than in survivors (3.9 log10 copies/µl [IQR: 1.6-4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19, with higher quality than each separate test.


Assuntos
COVID-19/virologia , Nasofaringe/virologia , RNA Viral/sangue , SARS-CoV-2/isolamento & purificação , Carga Viral , Viremia , Adolescente , Adulto , Idoso , COVID-19/mortalidade , COVID-19/fisiopatologia , Criança , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
5.
J Med Virol ; 94(1): 197-204, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427922

RESUMO

Coronavirus disease 2019 (COVID-19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID-19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID-19 cases and death cases. Real-data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID-19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, USA, UAE, Poland, Colombia, Turkey, and Switzerland). The total number of confirmed cases and death cases in different waves of COVID-19 were compared to that of the previous one for equivalent periods. The total number of death cases in each wave was presented as a percentage of the total number of confirmed cases for the same periods. In all the selected 12 countries, Wave 2 had a much higher number of confirmed cases than that in Wave 1. However, the death cases increase was not comparable with that of the confirmed cases to the extent that some countries had lower death cases than in Wave 1, UAE, and Spain. The death cases as a percentage of the total number of confirmed cases in Wave 1 were much higher than that in Wave 2. Some countries have had Waves 3 and 4. Waves 3 and 4 have had lower confirmed cases than Wave 2, however, the death cases were variable in different countries. The death cases in Waves 3 and 4 were similar to or higher than Wave 2 in most countries. Wave 2 of COVID-19 had a much higher spread rate but much lower severity resulting in a lower death rate in Wave 2 compared with that of the first wave. Waves 3 and 4 have had lower confirmed cases than Wave 2; that could be due to the presence of appropriate treatment and vaccination. However, that was not reflected in the death cases, which were similar to or higher than Wave 2 in most countries. Further studies are needed to explain these findings.


Assuntos
Vacinas contra COVID-19 , COVID-19/epidemiologia , SARS-CoV-2/genética , Ásia/epidemiologia , COVID-19/mortalidade , COVID-19/transmissão , COVID-19/virologia , Europa (Continente)/epidemiologia , Saúde Global , Humanos , Mutação , Índice de Gravidade de Doença , América do Sul/epidemiologia , Estados Unidos/epidemiologia
6.
J Med Virol ; 94(1): 211-221, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34436785

RESUMO

Prognostic predictors are of paramount interest for prompt intervention and optimal utilization of the healthcare system in the ongoing context of the COVID-19 pandemic. The platelet-to-lymphocyte count ratio (PLR), has emerged as a potential tool for risk stratification of critically ill patients with sepsis. The current systematic review explores the utility of PLR as a prognostic predictor of COVID-19 patients. We screened the electronic databases until May 15, 2021 after enrolling in PROSPERO (CRD42021220269). Studies evaluating the association between PLR on admission and outcomes in terms of mortality and severity among COVID-19 patients were included. We retrieved 32 studies, with a total of 2768 and 3262 COVID-19 patients for mortality and disease severity outcomes. Deceased and critically ill patients had higher PLR levels on admission in comparison to survivors and non-severe patients (mean differences [MD] = 66.10; 95% confidence interval [CI]: 47.75-84.44; p < 0.00001 and MD = 86.74; 95% CI: 67.7-105.7; p < 0.00001, respectively). A higher level of PLR on admission in COVID-19 patients is associated with increased morbidity and mortality. However, the evidence is of low quality and further studies regarding the cut-off value of PLR are the need of the hour.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico , Contagem de Linfócitos , Contagem de Plaquetas , COVID-19/mortalidade , COVID-19/fisiopatologia , Humanos , Prognóstico , Índice de Gravidade de Doença
7.
J Med Virol ; 94(1): 222-228, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34449894

RESUMO

The current study aimed at characterizing the dynamics of SARS-CoV-2 nucleocapsid (N) antigenemia in a cohort of critically ill adult COVID-19 patients and assessing its potential association with plasma levels of biomarkers of clinical severity and mortality. Seventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial plasma (n = 340) specimens were collected. A lateral flow immunochromatography assay and reverse-transcription polymerase chain reaction (RT-PCR) were used for SARS-CoV-2 N protein detection and RNA quantitation and in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were measured. SARS-CoV-RNA N-antigenemia and viral RNAemia were documented in 40.1% and 35.6% of patients, respectively at a median of 9 days since symptoms onset. The level of agreement between the qualitative results returned by the N-antigenemia assay and plasma RT-PCR was moderate (k = 0.57; p < 0.0001). A trend towards higher SARS-CoV-2 RNA loads was seen in plasma specimens testing positive for N-antigenemia assay than in those yielding negative results (p = 0.083). SARS-CoV-2 RNA load in tracheal aspirates was significantly higher (p < 0.001) in the presence of concomitant N-antigenemia than in its absence. Significantly higher serum levels of ferritin, lactose dehydrogenase, C-reactive protein, and D-dimer were quantified in paired plasma SARS-CoV-2 N-positive specimens than in those testing negative. Occurrence of SARS-CoV-2 N-antigenemia was not associated with increased mortality in univariate logistic regression analysis (odds ratio, 1.29; 95% confidence interval, 0.49-3.34; p = 0.59). In conclusion, SARS-CoV-2 N-antigenemia detection is relatively common in ICU patients and appears to associate with increased serum levels of inflammation and tissue-damage markers. Whether this virological parameter may behave as a biomarker of poor clinical outcome awaits further investigations.


Assuntos
COVID-19/virologia , Proteínas do Nucleocapsídeo de Coronavírus/sangue , Estado Terminal , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/sangue , Biomarcadores/análise , Biomarcadores/sangue , COVID-19/mortalidade , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/sangue , Fosfoproteínas/imunologia , Estudos Prospectivos , RNA Viral/análise , RNA Viral/sangue , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Traqueia/virologia , Adulto Jovem
8.
J Med Virol ; 94(1): 229-239, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34449896

RESUMO

Observational studies indicate that pleural effusion has an association with risk and the clinical prognosis of COVID-19 disease; however, the available literature on this area is inconsistent. The objective of this systematic review and meta-analysis is to evaluate the correlation between COVID-19 disease and pleural effusion. A rigorous literature search was conducted using multiple databases. All eligible observational studies were included from around the globe. The pooled prevalence and associated 95% confidence interval (CI) were calculated using the random effect model. Mantel-Haenszel odds ratios were produced to report overall effect size using random effect models for severity and mortality outcomes. Funnel plots, Egger regression tests, and Begg-Mazumdar's rank correlation test were used to appraise publication bias. Data from 23 studies including 6234 COVID-19 patients was obtained. The overall prevalence of pleural effusion in COVID-19 patients was 9.55% (95% CI, I2 = 92%). Our findings also indicated that the presence of pleural effusions associated with increased risk of severity of disease(OR = 5.08, 95% CI 3.14-8.22, I2 = 77.4%) and mortality due to illness(OR = 4.53, 95% CI 2.16-9.49, I2 = 66%) compared with patients without pleural effusion. Sensitivity analyses illustrated a similar effect size while decreasing the heterogeneity. No significant publication bias was evident in the meta-analysis. The presence of pleural effusion can assist as a prognostic factor to evaluate the risk of worse outcomes in COVID-19 patients hence, it is recommended that hospitalized COVID-19 patients with pleural effusion should be managed on an early basis.


Assuntos
COVID-19/complicações , Derrame Pleural/complicações , COVID-19/diagnóstico , COVID-19/mortalidade , Feminino , Humanos , Masculino , Derrame Pleural/diagnóstico , Derrame Pleural/epidemiologia , Prevalência , Prognóstico , Índice de Gravidade de Doença
9.
J Med Virol ; 94(1): 272-278, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468994

RESUMO

Data pertaining to risk factor analysis in coronavirus disease 2019 (COVID-19) is confounded by the lack of data from an ethnically diverse population. In addition, there is a lack of data for young adults. This study was conducted to assess risk factors predicting COVID-19 severity and mortality in hospitalized young adults. A retrospective observational study was conducted at two centers from China and India on COVID-19 patients aged 20-50 years. Regression analysis to predict adverse outcomes was performed using parameters including age, sex, country of origin, hospitalization duration, comorbidities, lymphocyte count, and National Early Warning Score 2 (NEWS2) score at admission. A total of 420 patients (172 East Asians and 248 South Asians) were included. The predictive model for intensive care unit (ICU) admission with variables NEWS2 Category II and higher, diabetes mellitus, liver dysfunction, and low lymphocyte counts had an area under the curve (AUC) value of 0.930 with a sensitivity of 0.931 and a specificity of 0.784. The predictive model for mortality with NEWS2 Category III, cancer, and decreasing lymphocyte count had an AUC value of 0.883 with a sensitivity of 0.903 and a specificity of 0.701. A combined predictive model with bronchial asthma and low lymphocyte count, in contrast, had an AUC value of 0.768 with a sensitivity of 0.828 and a specificity of 0.719 for NEWS2 score (5 or above) at presentation. NEWS2 supplemented with comorbidity profile and lymphocyte count could help identify hospitalized young adults at risk of adverse COVID-19 outcomes.


Assuntos
COVID-19/diagnóstico , COVID-19/etnologia , Adulto , Grupo com Ancestrais do Continente Asiático , COVID-19/mortalidade , COVID-19/fisiopatologia , China , Comorbidade , Progressão da Doença , Escore de Alerta Precoce , Feminino , Hospitalização , Humanos , Índia , Unidades de Terapia Intensiva , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
10.
Gene ; 807: 145964, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34530087

RESUMO

AIMS: We aimed to investigate the role of G protein subunit alpha Z(GNAZ) in the progression and prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Oncomine, GEO, TCGA, GEPIA2, Kaplan-Meier Plotter, TIMER2, Metascape, CCLE, LinkedOmics, and UALCAN databases were used to analyze the differential expression of GNAZ in HCC and normal liver tissues, relationship between GNAZ expression and prognosis of patients with HCC, and expression of GNAZ in common human HCC cell lines. Western blotting was performed to analyze GNAZ expression, while the Cell Counting Kit 8 assay was used to determine cell proliferation, and flow cytometry was used to evaluate the cell cycle and apoptosis. Wound healing and transwell invasion assays were used to investigate cell metastasis and invasion. RESULTS: Using Oncomine, Gene Expression Omnibus (GEO), and GEPIA2 databases, GNAZ was found to be overexpressed in HCC tissues compared with that in adjacent normal liver tissues, and western blotting analysis showed GNAZ overexpression in seven patients with HCC who underwent surgical resection of HCC and para-cancerous tissues (p < 0.01). Survival analysis revealed that high GNAZ expression was negatively associated with overall survival (OS), recurrence-free survival, progression-free survival, and disease-specific survival in patients with HCC (p < 0.05). GNAZ overexpression was associated with worse 4- month, 6- month, 12- month, 24- month, 36- month, 48- month, and 60-month OS, as well as with different clinicopathological characteristics of patients with HCC, including hepatitis virus infection state; alcohol consumption state; male; female; Asian; microvascular invasion, Stage I-II, Stage II-III, and Stage III-IV; and grade II (Cox regression, p < 0.05). KEGG/GO biological process enrichment indicated that the genes similar to GNAZ in HCC were mainly enriched in the cell cycle, cell cycle phase transition, DNA replication checkpoint, and regulation of G0 to G1 transition. siRNA-GNAZ significantly reduced the viability of JHH-2 and SNU-761 cells from 12 to 96 h; increased the percentage of cells in the G0/G1 phase and decreased that of cells in the S and G2/M phases (p < 0.05); and markedly downregulated the expression of cyclin D, cyclin E, and CDK2 protein. siRNA-GNAZ also significantly increased the percentage of JHH-2 and SNU-761 cell apoptosis at late stages, while the number of surviving cells decreased (p < 0.05), and upregulated the expression of apoptosis-related proteins Bax and caspase 3 protein. Furthermore, siRNA-GNAZ remarkably reduced the healing of scratch wounds in JHH-2 and SNU-761 cells and the number of invasive cells compared with that in the control group (p < 0.001). CONCLUSION: Our study demonstrated that GNAZ plays a pivotal role as a potential oncogene and predicts poor prognosis in patients with HCC. It promotes tumor proliferation via cell cycle arrest, apoptosis, migration, and invasion. Thus, GNAZ may be a potential candidate biomarker providing useful insight into hepatocarcinogenesis and aggressiveness.


Assuntos
Carcinoma Hepatocelular/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Idoso , Apoptose/genética , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , China , Feminino , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transcriptoma/genética
11.
West J Emerg Med ; 22(6): 1262-1269, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34787549

RESUMO

INTRODUCTION: Coinfection with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and another virus may influence the clinical trajectory of emergency department (ED) patients. However, little empirical data exists on the clinical outcomes of coinfection with SARS-CoV-2 METHODS: In this retrospective cohort analysis, we included adults presenting to the ED with confirmed, symptomatic coronavirus 2019 who also underwent testing for additional viral pathogens within 24 hours. To investigate the association between coinfection status with each of the outcomes, we performed logistic regression. RESULTS: Of 6,913 ED patients, 5.7% had coinfection. Coinfected individuals were less likely to experience index visit or 30-day hospitalization (odds ratio [OR] 0.57; 95% confidence interval [CI], 0.36-0.90 and OR 0.39; 95% CI, 0.25-0.62, respectively). CONCLUSION: Coinfection is relatively uncommon in symptomatic ED patients with SARS-CoV-2 and the clinical short- and long-term outcomes are more favorable in coinfected individuals.


Assuntos
COVID-19/terapia , Coinfecção/virologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/mortalidade , Coinfecção/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença
13.
JAMA Netw Open ; 4(11): e2134241, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34757409

RESUMO

Importance: The influence of sleep-disordered breathing (SDB) and sleep-related hypoxemia in SARS-CoV-2 viral infection and COVID-19 outcomes remains unknown. Controversy exists regarding whether to continue treatment for SDB with positive airway pressure given concern for aerosolization with limited data to inform professional society recommendations. Objective: To investigate the association of SDB (identified via polysomnogram) and sleep-related hypoxia with (1) SARS-CoV-2 positivity and (2) World Health Organization (WHO)-designated COVID-19 clinical outcomes while accounting for confounding including obesity, underlying cardiopulmonary disease, cancer, and smoking history. Design, Setting, and Participants: This case-control study was conducted within the Cleveland Clinic Health System (Ohio and Florida) and included all patients who were tested for COVID-19 between March 8 and November 30, 2020, and who had an available sleep study record. Sleep indices and SARS-CoV-2 positivity were assessed with overlap propensity score weighting, and COVID-19 clinical outcomes were assessed using the institutional registry. Exposures: Sleep study-identified SDB (defined by frequency of apneas and hypopneas using the Apnea-Hypopnea Index [AHI]) and sleep-related hypoxemia (percentage of total sleep time at <90% oxygen saturation [TST <90]). Main Outcomes and Measures: Outcomes were SARS-CoV-2 infection and WHO-designated COVID-19 clinical outcomes (hospitalization, use of supplemental oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and death). Results: Of 350 710 individuals tested for SARS-CoV-2, 5402 (mean [SD] age, 56.4 [14.5] years; 3005 women [55.6%]) had a prior sleep study, of whom 1935 (35.8%) tested positive for SARS-CoV-2. Of the 5402 participants, 1696 were Black (31.4%), 3259 were White (60.3%), and 822 were of other race or ethnicity (15.2%). Patients who were positive vs negative for SARS-CoV-2 had a higher AHI score (median, 16.2 events/h [IQR, 6.1-39.5 events/h] vs 13.6 events/h [IQR, 5.5-33.6 events/h]; P < .001) and increased TST <90 (median, 1.8% sleep time [IQR, 0.10%-12.8% sleep time] vs 1.4% sleep time [IQR, 0.10%-10.8% sleep time]; P = .02). After overlap propensity score-weighted logistic regression, no SDB measures were associated with SARS-CoV-2 positivity. Median TST <90 was associated with the WHO-designated COVID-19 ordinal clinical outcome scale (adjusted odds ratio, 1.39; 95% CI, 1.10-1.74; P = .005). Time-to-event analyses showed sleep-related hypoxia associated with a 31% higher rate of hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005). Conclusions and Relevance: In this case-control study, SDB and sleep-related hypoxia were not associated with increased SARS-CoV-2 positivity; however, once patients were infected with SARS-CoV-2, sleep-related hypoxia was an associated risk factor for detrimental COVID-19 outcomes.


Assuntos
COVID-19 , Causas de Morte , Hospitalização , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/complicações , Idoso , COVID-19/complicações , COVID-19/mortalidade , COVID-19/terapia , Estudos de Casos e Controles , Pressão Positiva Contínua nas Vias Aéreas , Prestação Integrada de Cuidados de Saúde , Oxigenação por Membrana Extracorpórea , Feminino , Florida , Mortalidade Hospitalar , Humanos , Hipóxia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Ohio , Respiração Artificial , Fatores de Risco , SARS-CoV-2 , Sono , Síndromes da Apneia do Sono/patologia , Síndromes da Apneia do Sono/terapia
14.
BMJ ; 375: e066534, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759038

RESUMO

OBJECTIVE: To determine the use of epinephrine (adrenaline) before defibrillation for treatment of in-hospital cardiac arrest due to a ventricular arrhythmia and examine its association with patient survival. DESIGN: Propensity matched analysis. SETTING: 2000-18 data from 497 hospitals participating in the American Heart Association's Get With The Guidelines-Resuscitation registry. PARTICIPANTS: Adults aged 18 and older with an index in-hospital cardiac arrest due to an initial shockable rhythm treated with defibrillation. INTERVENTIONS: Administration of epinephrine before first defibrillation. MAIN OUTCOME MEASURES: Survival to discharge; favorable neurological survival, defined as survival to discharge with none, mild, or moderate neurological disability measured using cerebral performance category scores; and survival after acute resuscitation (that is, return of spontaneous circulation for >20 minutes). A time dependent, propensity matched analysis was performed to adjust for confounding due to indication and evaluate the independent association of epinephrine before defibrillation with study outcomes. RESULTS: Among 34 820 patients with an initial shockable rhythm, 9630 (27.6%) were treated with epinephrine before defibrillation, contrary to current guidelines. In comparison with participants treated with defibrillation first, participants receiving epinephrine first were less likely to have a history of myocardial infarction or heart failure, but more likely to have renal failure, sepsis, pneumonia, and receive mechanical ventilation before in-hospital cardiac arrest (P<0.0001 for all). Treatment with epinephrine before defibrillation was strongly associated with delayed defibrillation (median 3 minutes v 0 minutes). In propensity matched analysis (9011 matched pairs), epinephrine before defibrillation was associated with lower odds of survival to discharge (25.2% v 29.9%; adjusted odds ratio 0.81, 95% confidence interval 0.74 to 0.88; P<0.001), favorable neurological survival (18.6% v 21.4%; 0.85, 0.76 to 0.92; P<0.001), and survival after acute resuscitation (64.4% v 69.4%; 0.76, 0.70 to 0.83; P<0.001). The above findings were consistent in a range of sensitivity analyses, including matching according to defibrillation time. CONCLUSIONS: Contrary to current guidelines that prioritize immediate defibrillation for in-hospital cardiac arrest due to a shockable rhythm, more than one in four patients are treated with epinephrine before defibrillation, which is associated with worse survival.


Assuntos
Cardioversão Elétrica/mortalidade , Epinefrina/administração & dosagem , Parada Cardíaca/terapia , Adulto , Arritmias Cardíacas/complicações , Arritmias Cardíacas/mortalidade , Cardioversão Elétrica/métodos , Feminino , Parada Cardíaca/etiologia , Parada Cardíaca/mortalidade , Humanos , Masculino , Alta do Paciente/estatística & dados numéricos , Pontuação de Propensão , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento
15.
JAMA Netw Open ; 4(11): e2134330, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34767021

RESUMO

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.


Assuntos
Antagonistas de Androgênios/efeitos adversos , COVID-19/complicações , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , COVID-19/epidemiologia , COVID-19/mortalidade , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Fatores de Risco , Tennessee/epidemiologia
16.
BMJ ; 375: e068302, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789505

RESUMO

OBJECTIVE: To review the evidence on the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, CINAHL, Biosis, Joanna Briggs, Global Health, and World Health Organization COVID-19 database (preprints). ELIGIBILITY CRITERIA FOR STUDY SELECTION: Observational and interventional studies that assessed the effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality. MAIN OUTCOME MEASURES: The main outcome measure was incidence of covid-19. Secondary outcomes included SARS-CoV-2 transmission and covid-19 mortality. DATA SYNTHESIS: DerSimonian Laird random effects meta-analysis was performed to investigate the effect of mask wearing, handwashing, and physical distancing measures on incidence of covid-19. Pooled effect estimates with corresponding 95% confidence intervals were computed, and heterogeneity among studies was assessed using Cochran's Q test and the I2 metrics, with two tailed P values. RESULTS: 72 studies met the inclusion criteria, of which 35 evaluated individual public health measures and 37 assessed multiple public health measures as a "package of interventions." Eight of 35 studies were included in the meta-analysis, which indicated a reduction in incidence of covid-19 associated with handwashing (relative risk 0.47, 95% confidence interval 0.19 to 1.12, I2=12%), mask wearing (0.47, 0.29 to 0.75, I2=84%), and physical distancing (0.75, 0.59 to 0.95, I2=87%). Owing to heterogeneity of the studies, meta-analysis was not possible for the outcomes of quarantine and isolation, universal lockdowns, and closures of borders, schools, and workplaces. The effects of these interventions were synthesised descriptively. CONCLUSIONS: This systematic review and meta-analysis suggests that several personal protective and social measures, including handwashing, mask wearing, and physical distancing are associated with reductions in the incidence covid-19. Public health efforts to implement public health measures should consider community health and sociocultural needs, and future research is needed to better understand the effectiveness of public health measures in the context of covid-19 vaccination. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178692.


Assuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/métodos , Saúde Pública , COVID-19/mortalidade , COVID-19/transmissão , Vacinas contra COVID-19/uso terapêutico , Saúde Global , Desinfecção das Mãos/métodos , Humanos , Incidência , Máscaras , Distanciamento Físico , Quarentena/métodos , SARS-CoV-2 , Instituições Acadêmicas , Viagem , Organização Mundial da Saúde
17.
Taiwan J Obstet Gynecol ; 60(6): 1043-1046, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34794735

RESUMO

OBJECTIVES: Aim of this study is to evaluate the prognosis of pregnant women having SARS-CoV-2 infection and investigate whether there was a difference in perinatal outcomes between pregnant women who had SARS-CoV-2 infection and those who did not. MATERIALS AND METHODS: This prospective observational study was conducted with 116 singleton pregnancies. Cases enrolling in the study were divided into two groups. While those in the first group had a history of SARS-CoV-2 infection (n = 46) the second group consisted of healthy pregnant women (n = 70). RESULTS: Emergency Cesarean section was performed on three SARS-CoV-2 infected pregnancies (30, 33 and 34 gestational weeks). Intensive care unit admission was required for all three cases after delivery and two of them died. Among the pregnancies that had an infection in the third trimester, 71.4% (n = 20) of them had delivery in 14 days after diagnosis and 17.4% (n = 8) of their newborns were followed up at newborn intensive care unit. Overall, only one newborn had a positive swab test result for SARS-CoV-2. There was no statistically significant difference between groups regarding their delivery week (37.02 ± 5.85 vs 38.5 ± 2.33). Similarly, there was no significant difference between groups, concerning mean age, parity, and birth weight (P = 0.707, P = 0.092, P = 0.334; P < 0.05). Furthermore, the difference between SARS-CoV-2 infected pregnancies that were followed up as inpatient or outpatient with respect to the delivery week and birth weight was not significant (p > 0.05). Also, APGAR 5 scores of hospitalized women (9.3 ± 1.1) were found to be lower than the outpatient group (9.8 ± 0.8) (P = 0.043; p < 0.05). CONCLUSION: No significant difference was detected between groups in terms of the delivery week, birth weight, and APGAR scores. The inpatient group was found to have lower APGAR 5 scores.


Assuntos
COVID-19/diagnóstico , Cesárea/estatística & dados numéricos , Parto Obstétrico , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez/mortalidade , Gestantes/psicologia , Aborto Espontâneo/epidemiologia , Peso ao Nascer , COVID-19/mortalidade , COVID-19/terapia , COVID-19/virologia , Feminino , Humanos , Recém-Nascido , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/terapia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , SARS-CoV-2
18.
BMC Nephrol ; 22(1): 359, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34719384

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common among patients hospitalised with COVID-19 and associated with worse prognosis. The aim of this study was to investigate the epidemiology, risk factors and outcomes of AKI in patients with COVID-19 in a large UK tertiary centre. METHODS: We analysed data of consecutive adults admitted with a laboratory-confirmed diagnosis of COVID-19 across two sites of a hospital in London, UK, from 1st January to 13th May 2020. RESULTS: Of the 1248 inpatients included, 487 (39%) experienced AKI (51% stage 1, 13% stage 2, and 36% stage 3). The weekly AKI incidence rate gradually increased to peak at week 5 (3.12 cases/100 patient-days), before reducing to its nadir (0.83 cases/100 patient-days) at the end the study period (week 10). Among AKI survivors, 84.0% had recovered renal function to pre-admission levels before discharge and none required on-going renal replacement therapy (RRT). Pre-existing renal impairment [odds ratio (OR) 3.05, 95%CI 2.24-4,18; p <  0.0001], and inpatient diuretic use (OR 1.79, 95%CI 1.27-2.53; p <  0.005) were independently associated with a higher risk for AKI. AKI was a strong predictor of 30-day mortality with an increasing risk across AKI stages [adjusted hazard ratio (HR) 1.59 (95%CI 1.19-2.13) for stage 1; p < 0.005, 2.71(95%CI 1.82-4.05); p < 0.001for stage 2 and 2.99 (95%CI 2.17-4.11); p < 0.001for stage 3]. One third of AKI3 survivors (30.7%), had newly established renal impairment at 3 to 6 months. CONCLUSIONS: This large UK cohort demonstrated a high AKI incidence and was associated with increased mortality even at stage 1. Inpatient diuretic use was linked to a higher AKI risk. One third of survivors with AKI3 exhibited newly established renal impairment already at 3-6 months.


Assuntos
Injúria Renal Aguda , COVID-19 , Terapia de Substituição Renal , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos de Coortes , Mortalidade Hospitalar , Humanos , Incidência , Unidades de Terapia Intensiva/estatística & dados numéricos , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Gravidade do Paciente , Terapia de Substituição Renal/métodos , Terapia de Substituição Renal/estatística & dados numéricos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Reino Unido/epidemiologia
20.
Front Immunol ; 12: 765330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777382

RESUMO

Aims: Although the exact factors promoting disease progression in COVID-19 are not fully elucidated, unregulated activation of the complement system (CS) seems to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by SARS-CoV-2. In particular, the lectin pathway (LP) has been implicated in previous autopsy studies. The primary purpose of our study is to investigate the role of the CS in hospitalized COVID-19 patients with varying degrees of disease severity. Methods: In a single-center prospective observational study, 154 hospitalized patients with PCR-confirmed SARS-CoV-2 infection were included. Serum samples on admission to the COVID-19 ward were collected for analysis of CS pathway activities and concentrations of LP proteins [mannose-binding lectin (MBL) and ficolin-3 (FCN-3)] & C1 esterase inhibitor (C1IHN). The primary outcome was mechanical ventilation or in-hospital death. Results: The patients were predominately male and had multiple comorbidities. ICU admission was required in 16% of the patients and death (3%) or mechanical ventilation occurred in 23 patients (15%). There was no significant difference in LP activity, MBL and FCN-3 concentrations according to different peak disease severities. The median alternative pathway (AP) activity was significantly lower (65%, IQR 50-94) in patients with death/invasive ventilation compared to patients without (87%, IQR 68-102, p=0.026). An optimal threshold of <65.5% for AP activity was derived from a ROC curve resulting in increased odds for death or mechanical ventilation (OR 4,93; 95% CI 1.70-14.33, p=0.003) even after adjustment for confounding factors. Classical pathway (CP) activity was slightly lower in patients with more severe disease (median 101% for death/mechanical ventilation vs 109%, p=0.014). C1INH concentration correlated positively with length of stay, inflammatory markers and disease severity on admission but not during follow-up. Conclusion: Our results point to an overactivated AP in critically ill COVID-19 patients in vivo leading to complement consumption and consequently to a significantly reduced AP activity in vitro. The LP does not seem to play a role in the progression to severe COVID-19. Apart from its acute phase reaction the significance of C1INH in COVID-19 requires further studies.


Assuntos
COVID-19/imunologia , Proteínas do Sistema Complemento/imunologia , SARS-CoV-2 , Adulto , Idoso , COVID-19/sangue , COVID-19/mortalidade , COVID-19/terapia , Proteína Inibidora do Complemento C1/imunologia , Estado Terminal , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Lectinas/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial , Índice de Gravidade de Doença
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