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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): 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
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): 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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
Front Immunol ; 12: 726283, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721388

RESUMO

Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.


Assuntos
COVID-19/imunologia , Citocinas/sangue , SARS-CoV-2/fisiologia , Sistema ABO de Grupos Sanguíneos , Idoso , Biomarcadores , COVID-19/diagnóstico , COVID-19/mortalidade , Progressão da Doença , Feminino , Fator de Crescimento de Hepatócito/sangue , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Respiração Artificial , Índice de Gravidade de Doença , Análise de Sobrevida
12.
Sci Rep ; 11(1): 21522, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728658

RESUMO

There is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Receptores de Interleucina-6/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/imunologia , COVID-19/mortalidade , COVID-19/virologia , Humanos , Razão de Chances , Respiração Artificial , SARS-CoV-2/isolamento & purificação , Taxa de Sobrevida
13.
Sci Rep ; 11(1): 21472, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728661

RESUMO

Acute healthcare services are extremely important, particularly during the COVID-19 pandemic, as healthcare demand has rapidly intensified, and resources have become insufficient. Studies on specific prepandemic hospitalization and emergency department visit (EDV) trends in proximity to death are limited. We examined time-trend specificities based on sex, age, and cause of death in the last 2 years of life. Datasets containing all hospitalizations and EDVs of elderly residents in Friuli-Venezia Giulia, Italy (N = 411,812), who died between 2002 and 2014 at ≥ 65 years, have been collected. We performed subgroup change-point analysis of monthly trends in the 2 years preceding death according to sex, age at death (65-74, 75-84, 85-94, and ≥ 95 years), and main cause of death (cancer, cardiovascular, or respiratory disease). The proportion of decedents (N = 142,834) accessing acute healthcare services increased exponentially in proximity to death (hospitalizations = 4.7, EDVs = 3.9 months before death). This was inversely related to age, with changes among the youngest and eldest decedents at 6.6 and 3.5 months for hospitalizations and at 4.6 and 3.3 months for EDVs, respectively. Healthcare use among cancer patients intensified earlier in life (hospitalizations = 6.8, EDVs = 5.8 months before death). Decedents from respiratory diseases were most likely to access hospital-based services during the last month of life. No sex-based differences were found. The greater use of acute healthcare services among younger decedents and cancer patients suggests that policies potentiating primary care support targeting these at-risk groups may reduce pressure on hospital-based services.


Assuntos
Serviço Hospitalar de Emergência/tendências , Hospitalização/tendências , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/virologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/patologia , Causas de Morte , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Itália , Neoplasias/mortalidade , Neoplasias/patologia , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Assistência Terminal
14.
Medicine (Baltimore) ; 100(41): e27345, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731106

RESUMO

ABSTRACT: The impact of preoperative radiotherapy (PRT) on survival in patients with stage II and III esophageal squamous cell carcinoma (ESCC) remains controversial. The aim of this study was to explore the effect of PRT on survival of these patients.Patients with stage II and III ESCC who underwent chemotherapy ± PRT were identified and retrieved from the SEER database from 2010 to 2015. Cox regression analysis was used to identify independent prognostic factors in patients. Subgroup analysis stratified by T stage and N stage was performed. Kaplan-Meier survival analysis was performed to assess disease specific survival (DSS).A total of 1160 patients were retrieved, of whom 289 (24.9%) underwent PRT plus chemotherapy, and 871 (75.1%) did not receive PRT. In multivariate analysis, PRT plus chemotherapy was a favorable prognostic factor for patients with stage T2 (hazard ratio [HR], 0.364, 95% CI, 0.202-0.658; P < .001), T3 (HR, 0.536, 95% CI, 0.413-0.695; P < .001) and T4 (HR, 0.318, 95% CI, 0.125-0.805; P = .016), but PRT plus chemotherapy was not statistically significant on DSS in patients with T1 disease (HR, 0.556, 95% CI, 0.262-1.179; P = .126). All 3 different N stages (N0, N1, and N2 + N3) were statistically significant (P < .05) in chemotherapy with or without PRT.In conclusion, patients with stage II and III ESCC at the T2-T4 stage gained significant survival benefit from PRT plus chemotherapy.


Assuntos
Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Terapia Neoadjuvante/métodos , Radioterapia/estatística & dados numéricos , Adulto , Idoso , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER
15.
J Neurosurg Pediatr ; 28(5): 544-552, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34724647

RESUMO

OBJECTIVE: The aim of this cohort study was to describe and analyze the surgical treatment and outcome of posterior fossa arachnoid cysts (PFACs) in infants. METHODS: Patients presenting with a PFAC at infancy or prenatally, between the years 2000 and 2019, and who were surgically treated before the age of 2 years, were included in this study. Patient data were retrospectively collected including baseline characteristics and surgical variables. Factors related to revision surgery were analyzed through uni- and multivariate analysis. RESULTS: Thirty-five patients, of whom 54.3% were male, were included. The cyst was diagnosed prenatally in 23 patients (65.7%). Surgery was typically recommended after a mean cyst follow-up of 3.4 ± 3.9 months, with a mean age at surgery of 6.1 ± 5.1 months. In 54.3% of patients (n = 19), surgery was performed before the age of 6 months. The PFAC was treated purely neuroendoscopically in 57.1% of patients (n = 20), while 28.6% of patients underwent open cyst procedures (n = 10), 5.7% (n = 2) were treated with a shunt, and 8.6% (n = 3) underwent a combined procedure. Additional surgery was required in 31.4% of patients (n = 11; mean 2.36 ± 2.11 surgeries per patient). At the last follow-up (61.40 ± 55.33 months), no mortality or permanent morbidity was seen; radiological improvement was apparent in 83.9% of the patients. Those patients treated before the age of 6 months (p = 0.09) and who presented before surgery with a stable cyst size that was maintained throughout preoperative monitoring (p = 0.08) showed a trend toward higher revision rates after surgical treatment. CONCLUSIONS: PFACs in infancy may require surgical treatment before the age of 6 months. Navigated endoscopy was a valid surgical option. Overall mortality or permanent morbidity was rare. Additional surgery was required in up to 30% of the patients; younger age and a preoperatively stable cyst might be risk factors for revision surgery.


Assuntos
Cistos Aracnóideos/cirurgia , Fossa Craniana Posterior/cirurgia , Procedimentos Neurocirúrgicos/métodos , Cistos Aracnóideos/diagnóstico por imagem , Cistos Aracnóideos/mortalidade , Derivações do Líquido Cefalorraquidiano , Fossa Craniana Posterior/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Hidrocefalia/cirurgia , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Neuroendoscopia/métodos , Neuronavegação , Procedimentos Neurocirúrgicos/mortalidade , Diagnóstico Pré-Natal , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
16.
Medicine (Baltimore) ; 100(41): e27483, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731127

RESUMO

BACKGROUND: The benefit of loco-regional treatments such as hepatic arterial infusion (HAI) in terms of survival and response rate is unclear. The aim of this work is to quantitatively summarize the results of both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing fluoropyrimidine-HAI (F-HAI) to systemic chemotherapy (SCT) for the treatment of colorectal liver metastases (CRLMs). METHODS: We searched the Cochrane Library, PubMed, EMBASE, and Web of Science up to July 1, 2021. The outcome measures were tumor response rate and overall survival (OS). Both RCTs and NRSIs comparing HAI to SCT for patients with unresectable CRLMs were included. The outcome measures were tumor response rate and OS. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 16 studies including 11 RCTs and 5 NRSIs were identified for the present meta-analysis. Nine RCTs compared F-HAI to SCT for patients with unresectable CRLMs and the pooled result indicated that patients who received F-HAI experienced more than twofold response rate than SCT, with a pooled risk ratio of 2.10 (95%CI 1.59-2.79; P < .00001). In addition, the pooled result based on RCTs showed that F-HAI had a significant benefit regarding OS, with a pooled HR of 0.83 (95% CI 0.70-0.99; P = .04). Similarly, the benefit of F-HAI in terms of OS was also observed in the results of NRSIs. CONCLUSIONS: Our results indicated that the F-HAI regimen had a greater tumor response rate and survival advantage than SCT for patients with unresectable CRLMs. Future propensity score-matched analyses with a large sample size should be conducted to support the evidence of our results based on RCTs and NRSIs.


Assuntos
Antimetabólitos/administração & dosagem , Antineoplásicos/administração & dosagem , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Fígado/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Humanos , Fígado/irrigação sanguínea , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos Observacionais como Assunto , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
17.
Medicine (Baltimore) ; 100(41): e27507, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731135

RESUMO

BACKGROUND: The study was conducted to investigate the value of Positron emission tomography computed tomography (PET/CT) in predicting invasiveness of ground glass nodule (GGN) by the method of meta-analysis. METHODS: Two researchers independently searched for published literature on PET/CT diagnosis of GGN as of November 30, 2020. After extracting the data, RevMan5.3 was used to evaluate the quality of the included literature. The Stata14 software was used to test the heterogeneity of the original study that met the inclusion criteria, to calculate the combined sensitivity, specificity, positive likelihood ratio and negative likelihood ratio, the prior probability and posttest probability. The summary receiver operator characteristic curve was drawn and the area under the curve was calculated. Using Deeks funnel plot to evaluate publication bias. RESULTS: Five studies were finally included, including 298 GGN cases. The included studies had no obvious heterogeneity and publication bias. The combined sensitivity and specificity of PET/CT for predicting invasive adenocarcinoma presenting as GGN were 0.74 (95% confidence interval [CI]: 0.68-0.79), 0.82 (95% CI: 0.71-0.90), positive likelihood ratio and negative likelihood ratio were 4.1 (95% CI: 2.5-6.9), 0.32 (95% CI: 0.25-0.40), and the diagnostic odds ratio was 13 (95% CI: 7-26). The prior probability is 20%, the probability of GGN being invasive adenocarcinoma when PET/CT was negative was reduced to 7%, and the probability of GGN being invasive adenocarcinoma when PET/CT was positive was increased to 51%. The area under the curve of the summary receiver operator characteristic curve was 0.85. CONCLUSION: PET/CT has high diagnostic accuracy for invasive adenocarcinoma presenting as GGN.


Assuntos
Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Área Sob a Curva , Humanos , Nódulos Pulmonares Múltiplos/mortalidade , Nódulos Pulmonares Múltiplos/patologia , Invasividade Neoplásica/patologia , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade , Taxa de Sobrevida
18.
Medicine (Baltimore) ; 100(41): e27535, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731149

RESUMO

ABSTRACT: Enhancer RNAs (eRNAs), a subclass of lncRNAs, are derived from enhancer regions. The function of eRNAs has been reported by many previous studies. However, the role of eRNAs in gastric cancer, especially the prognosis-associated eRNAs, has not been studied yet.In this study, we have used a novel approach to screened key eRNAs in gastric cancer. Kaplan-Meier correlation analysis and Co-expression analysis were used to find the most significant survival-associated eRNAs. Enrichment analysis is applied to explore the key functions and pathways of screened eRNAs. The correlation and survival analysis are used to evaluate targeted genes in the pan-cancer analysisA total of 63 prognostic-associated eRNAs in gastric cancer were identified, the top 6 eRNAs were LINC01714, ZNF192P1, AC079760.2, LINC01645, EMX2OS, and AC114489.2. The correlation analysis demonstrated the top 10 screened eRNAs and their targeted genes. The results demonstrated that EMX2OS was ranked as the top eRNA according to the results of the Kaplan-Meier analysis. The correlation analysis demonstrated that eRNA EMX2OS is correlated with age, grade, stage, and cancer status. The pan-cancer analysis demonstrated that EMX2OS was associated with poor survival outcomes in adrenocortical carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, kidney renal clear cell carcinoma, stomach adenocarcinoma, and uveal melanoma.In this study, survival-related eRNAs were screened and the correlation between survival-related eRNAs and their targeted genes was demonstrated. EMX2OS plays a prognosis-associated eRNA role in gastric cancer, which might be a novel therapeutic target in clinical practice.


Assuntos
Adenocarcinoma/genética , Proteínas de Homeodomínio/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Adenocarcinoma/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Elementos Facilitadores Genéticos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , RNA Antissenso/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida
19.
Medicine (Baltimore) ; 100(41): e27538, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731152

RESUMO

ABSTRACT: This study was performed to verify whether lactate dehydrogenase to albumin (LDH/ALB) ratio could be used as an independent prognostic factor in patients with severe infection requiring intensive care.We reviewed electronic medical records of patients hospitalized to the intensive care unit via the emergency department with a diagnosis of infection between January 2014 and December 2019. From the collected data, ALB-based ratios (LDH/ALB, blood urea nitrogen to albumin, C-reactive protein to albumin, and lactate to albumin ratios) and some severity scores (modified early warning score, mortality in emergency department sepsis score [MEDS], and Acute Physiology And Chronic Health Evaluation II [APACHE II] score) were calculated. LDH/ALB ratio for predicting the in-hospital mortality was compared with other ALB-based ratios and severity scales by univariable and receiver-operating characteristics curve analysis. Modified severity scores by LDH/ALB ratio and multivariable logistic regression were used to verify the independence and usefulness of the LDH/ALB ratio.The median LDH/ALB ratio was higher in non-survivors than survivors (166.9 [interquartile range: 127.2-233.1] vs 214.7 [interquartile range: 160.2-309.7], P < .001). The area under the receiver-operating characteristics curve of the LDH/ALB ratio (0.642, 95% confidence interval: 0.602-0.681, P < .001) was not lower than that of other ALB-based ratios and severity scores. From multivariable logistic regression, LDH/ALB ratio was independently associated with in-hospital mortality (odds ratio = 1.001, 95% confidence interval: 1.000-1.002, P = .047). Area under the receiver-operating characteristics curves of MEDS and APACHE II scores were improved by modification with LDH/ALB ratio (MEDS: 0.643 vs 0.680, P < .001; APACHE II score: 0.675 vs 0.700, P = .003).LDH/ALB ratio may be useful as the prognostic factor in patients with severe infection requiring intensive care.


Assuntos
Albuminas/análise , Doenças Transmissíveis/sangue , Cuidados Críticos/métodos , Unidades de Terapia Intensiva/estatística & dados numéricos , L-Lactato Desidrogenase/sangue , APACHE , Idoso , Idoso de 80 Anos ou mais , Nitrogênio da Ureia Sanguínea , Proteína C-Reativa/análise , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/mortalidade , Comorbidade , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Mortalidade Hospitalar/tendências , Humanos , Ácido Láctico/análise , Masculino , Prognóstico , Estudos Retrospectivos , Sepse/mortalidade , Índice de Gravidade de Doença
20.
Medicine (Baltimore) ; 100(41): e27560, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731158

RESUMO

ABSTRACT: The aim of this study is to report the differences in clinicopathological features of oral tongue squamous cell carcinoma (OTSCC) and survival between adolescent and young adult (AYA) patients and elderly patients and to find the prognosticators. The medical records of 101 AYA patients and 175 control patients with OTSCC who underwent surgery were reviewed. Variables related to prognosis and their clinicopathological associations were analyzed. The 5-year overall survival (5y-OS) rates of AYA and control patients with stage I and II OTSCC were 94.4% and 89.6% (P = .353), respectively, and their 5-year disease-free survival (5y-DFS) rates were 82.0% and 76.6%, respectively (P = .476). The 5y-OS rates of patients with stages III and IV OTSCC were 83.3% and 66.7% (P = .333), respectively, and their 5y-DFS rates were 75.0% and 57.1% (P = .335), respectively. Logistic regression analysis revealed that there was no significant clinicopathological difference in AYA and control group. Furthermore, there was no significant difference in 5y-OS rates between patients who underwent elective neck dissection (END) and those who underwent therapeutic neck dissection (TND) in both group (P = 0.717 and 0.688). Overall, the present study revealed the clinicopathological features and prognosis of OTSCC were similar in AYA patients and elderly patients. Moreover, as there was no significant difference in OS between patients who underwent END and those who underwent TND in AYA and control groups, our results suggest that the indication for END in AYA patients with clinical N0 OTSCC is similar to that for elderly patients.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Esvaziamento Cervical/métodos , Neoplasias da Língua/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Estudos de Casos e Controles , Intervalo Livre de Doença , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Masculino , Esvaziamento Cervical/tendências , Estadiamento de Neoplasias/métodos , Estudos Retrospectivos , Terapêutica/métodos , Adulto Jovem
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