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1.
Nat Commun ; 11(1): 4912, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999275

RESUMO

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues.


Assuntos
Glicemia/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Ilhotas Pancreáticas/metabolismo , Locos de Características Quantitativas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Glicemia/metabolismo , Linhagem Celular Tumoral , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diacilglicerol Quinase/genética , Diacilglicerol Quinase/metabolismo , Elementos Facilitadores Genéticos , Feminino , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RNA-Seq , Análise de Sequência de DNA , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Adulto Jovem
2.
Radiographics ; 40(6): 1574-1599, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33001783

RESUMO

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in coronavirus disease 2019 (COVID-19), which was declared an official pandemic by the World Health Organization on March 11, 2020. The infection has been reported in most countries around the world. As of August 2020, there have been over 21 million cases of COVID-19 reported worldwide, with over 800 000 COVID-19-associated deaths. It has become apparent that although COVID-19 predominantly affects the respiratory system, many other organ systems can also be involved. Imaging plays an essential role in the diagnosis of all manifestations of the disease, as well as its related complications, and proper utilization and interpretation of imaging examinations is crucial. With the growing global COVID-19 outbreak, a comprehensive understanding of the diagnostic imaging hallmarks, imaging features, multisystemic involvement, and evolution of imaging findings is essential for effective patient management and treatment. To date, only a few articles have been published that comprehensively describe the multisystemic imaging manifestations of COVID-19. The authors provide an inclusive system-by-system image-based review of this life-threatening and rapidly spreading infection. In part 1 of this article, the authors discuss general aspects of the disease, with an emphasis on virology, the pathophysiology of the virus, and clinical presentation of the disease. The key imaging features of the varied pathologic manifestations of this infection that involve the pulmonary and peripheral and central vascular systems are also described. Part 2 will focus on key imaging features of COVID-19 that involve the cardiac, neurologic, abdominal, dermatologic and ocular, and musculoskeletal systems, as well as pediatric and pregnancy-related manifestations of the virus. Vascular complications pertinent to each system will be also be discussed in part 2. Online supplemental material is available for this article. ©RSNA, 2020.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pandemias , Pneumonia Viral/diagnóstico por imagem , Tromboembolia/diagnóstico por imagem , Trombose/diagnóstico por imagem , Angiografia/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Progressão da Doença , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Inflamação , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Artéria Pulmonar/diagnóstico por imagem , Receptores Virais/fisiologia , Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/etiologia , Avaliação de Sintomas , Tromboembolia/sangue , Tromboembolia/etiologia , Trombose/sangue , Trombose/etiologia , Microangiopatias Trombóticas/diagnóstico por imagem , Microangiopatias Trombóticas/etiologia , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodos
4.
Int J Med Sci ; 17(16): 2468-2476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029089

RESUMO

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/mortalidade , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Pró-Calcitonina/sangue , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , China/epidemiologia , Comorbidade , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Progressão da Doença , Feminino , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
6.
PLoS Med ; 17(10): e1003358, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33001967

RESUMO

BACKGROUND: Loss of smell and taste are commonly reported symptoms associated with coronavirus disease 2019 (COVID-19); however, the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in people with acute loss of smell and/or taste is unknown. The study aimed to determine the seroprevalence of SARS-CoV-2 antibodies in a community-based population with acute loss of smell and/or taste and to compare the frequency of COVID-19 associated symptoms in participants with and without SARS-CoV-2 antibodies. It also evaluated whether smell or taste loss are indicative of COVID-19 infection. METHODS AND FINDINGS: Text messages, sent via primary care centers in London, United Kingdom, invited people with loss of smell and/or taste in the preceding month, to participate. Recruitment took place between 23 April 2020 and 14 May 2020. A total of 590 participants enrolled via a web-based platform and responded to questions about loss of smell and taste and other COVID-19-related symptoms. Mean age was 39.4 years (SD ± 12.0) and 69.1% (n = 392) of participants were female. A total of 567 (96.1%) had a telemedicine consultation during which their COVID-19-related symptoms were verified and a lateral flow immunoassay test that detected SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies was undertaken under medical supervision. A total of 77.6% of 567 participants with acute smell and/or taste loss had SARS-CoV-2 antibodies; of these, 39.8% (n = 175) had neither cough nor fever. New loss of smell was more prevalent in participants with SARS-CoV-2 antibodies, compared with those without antibodies (93.4% versus 78.7%, p < 0.001), whereas taste loss was equally prevalent (90.2% versus 89.0%, p = 0.738). Seropositivity for SARS-CoV-2 was 3 times more likely in participants with smell loss (OR 2.86; 95% CI 1.27-6.36; p < 0.001) compared with those with taste loss. The limitations of this study are the lack of a general population control group, the self-reported nature of the smell and taste changes, and the fact our methodology does not take into account the possibility that a population subset may not seroconvert to develop SARS-CoV-2 antibodies post-COVID-19. CONCLUSIONS: Our findings suggest that recent loss of smell is a highly specific COVID-19 symptom and should be considered more generally in guiding case isolation, testing, and treatment of COVID-19. TRIALS REGISTRATION: ClinicalTrials.gov NCT04377815.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/complicações , Transtornos do Olfato/virologia , Pneumonia Viral/complicações , Distúrbios do Paladar/virologia , Adulto , Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Londres , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Testes Imediatos , Soroconversão , Estudos Soroepidemiológicos , Envio de Mensagens de Texto
7.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(8. Vyp. 2): 17-23, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33016672

RESUMO

OBJECTIVE: To evaluate the hemostasis of plasma aminothiols in different subtypes of ischemic stroke (IS). MATERIAL AND METHODS: The study included 177 patients, aged 62 (55-68) years, admitted in the first 8-24 hours since IS onset. The pathogenetic subtype of IS was clarified according to the results of clinical and instrumental examination by the Trial of ORG 10172 in Acute Stroke Treatment criteria. Determination of the total plasma aminothiols levels, their reduced forms and redox status was performed using the ultra-efficient Acquity H-Class UPLC liquid chromatograph (Waters, CSHA). RESULTS: Large-artery atherosclerosis was diagnosed in 24.3% patients, cardioembolic stroke in 20.3%, lacunar stroke in 55.4%. Significant differences in total levels of cysteine (Cys), glutathione (Gsh) and homocysteine (Hcy) were identified in patients with different IS subtypes. Patients with large-artery atherosclerosis and lacunar stroke showed the highest level of Hcy, patients with cardioembolic stroke had the lowest levels of Cys and Gsh. CONCLUSION: Total levels of plasma aminothiols are associated with different subtypes of IS.


Assuntos
Aterosclerose , Isquemia Encefálica/complicações , Cisteína , Glutationa , Homocisteína , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/sangue , Cisteína/sangue , Glutationa/sangue , Homocisteína/sangue , Humanos , Pessoa de Meia-Idade , Oxirredução
8.
Drugs Today (Barc) ; 56(9): 573-582, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33025951

RESUMO

Bempedoic acid is a new, first-in-class oral ATP-citrate lyase (ACLY) inhibitor that has to be converted to its CoA thioester before it inhibits ACLY. This conversion only occurs in the liver and not in skeletal muscle. This may explain why, unlike the statins, bempedoic acid does not cause myalgia. Bempedoic acid given at a dosage of 180 mg orally once daily produces a highly significant reduction in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B and importantly also in high-sensitivity C-reactive protein. It has recently been approved by both the Food and Drug Administration (FDA) and the European Commission for use in adult patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease who require additional lowering of LDL-C, and for the treatment of adults with primary hypercholesterolemia (heterozygous familial and nonfamilial) or mixed dyslipidemia, respectively.


Assuntos
ATP Citrato (pro-S)-Liase/antagonistas & inibidores , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Lipídeos/sangue , Humanos
9.
Discov Med ; 29(157): 129-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002409

RESUMO

Sepsis is a life-threatening clinical condition demanding accurate and rapid diagnosis of the culprit pathogen, thereby to improve prognosis. Pathogen determination through blood culture is the gold standard for diagnosis but has limitations due to low sensitivity. Recently, circulating DNAs derived from pathogenic organisms were found in the plasma of patients with sepsis and were further proved to be more sensitive biomarkers for the diagnosis of the pathogen origin in sepsis. However, the fundamental molecular characteristics of circulating DNA in patients with sepsis remain unclear. Here, we used specific PCR and Sanger sequencing to verify the microbiology culture results via the corresponding plasma circulating DNA. We analyzed the composition and molecular characteristics of circulating DNA in septic patients using next-generation sequencing technology. We showed the presence of pathogen-derived circulating DNA in the plasma of patients with sepsis. The sizes of circulating DNA fragments derived from pathogenic bacteria showed a skewed unimodal distribution, while those derived from host cells showed a normal unimodal distribution. Lengths of fragments at peak concentration for both origins ranged from 150 bp to 200 bp, and reads mapping to pathogenic bacteria genome distributed uniformly on the reference. Our findings have improved our understanding of microbial circulating DNA in patients with sepsis as a potential methodology for the accurate diagnosis of sepsis, especially in light of an urgent need for such a diagnosis associated with the COVID-19 infection.


Assuntos
Infecções Bacterianas/microbiologia , Ácidos Nucleicos Livres/sangue , DNA Bacteriano/sangue , Sepse/microbiologia , Adulto , Idoso , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Betacoronavirus , Ácidos Nucleicos Livres/análise , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Técnicas de Cultura , DNA Bacteriano/análise , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Pandemias , Pneumonia Viral , Reação em Cadeia da Polimerase , Sepse/complicações , Sepse/diagnóstico , Análise de Sequência de DNA
10.
PLoS One ; 15(10): e0239802, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002041

RESUMO

BACKGROUND: To date, several clinical laboratory parameters associated with Coronavirus disease 2019 (COVID-19) severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19. METHODS AND FINDINGS: We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] ×109 cells/L), and lower lymphocyte, CD4 and CD8 T cell counts with MMD (95% CI) of -0.39 (-0.47, -0.31) ×109 cells/L, -204.9 (-302.6, -107.1) cells/µl and -123.6 (-170.6, -76.6) cells/µl, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml). CONCLUSIONS: Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Betacoronavirus , Proteína C-Reativa/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Interleucina-6/sangue , Contagem de Linfócitos , Estudos Observacionais como Assunto , Pandemias , Índice de Gravidade de Doença , Troponina I/sangue
12.
Intern Med ; 59(19): 2353-2358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32999264

RESUMO

Objective Liver injury is a notable complication of coronavirus disease 2019 (COVID-19). This study aimed to clarify the clinical features and liver injury in Japanese patients with COVID-19. Methods We conducted a multicenter retrospective cohort study. All consecutive patients with COVID-19 who visited or were admitted to our hospital before May 12, 2020, were enrolled. Their demographics, symptoms, laboratory findings, comorbidities, concomitant drugs, treatment, and clinical course were reviewed. We defined liver injury as alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) levels over the upper limit of normal. Results Twenty-two patients with COVID-19 (median age, 47 years old; men/women, 13/9) were enrolled. Two patients had underlying liver diseases, and two were diagnosed as having COVID-19 without any symptoms. Elevated ALT and GGT levels were found in 12 and 12 patients, respectively, and liver injury was observed in 15 patients (68.2%). Compared with the patients without liver injury, those with liver injury had a significantly higher fever during the clinical course (median, 37.5°C vs. 38.8°C, p=0.006). A significant correlation was found between the highest serum liver values and the highest body temperature in each patient. Among the 22 patients, 4 required artificial respiratory support, and 2 died thereafter. Liver injury was not associated with the severity or mortality of COVID-19. Conclusion Elevated levels of liver enzymes in the Japanese patients with COVID-19 were associated with the highest body temperature during the clinical course but not with the severity or mortality of COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Hepatopatias/virologia , Pneumonia Viral/complicações , Adulto , Alanina Transaminase/sangue , Betacoronavirus , Temperatura Corporal , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Estudos Retrospectivos , gama-Glutamiltransferase/sangue
13.
Urol Clin North Am ; 47(4): 457-467, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008496

RESUMO

Biochemically recurrent prostate cancer represents a stage of prostate cancer where conventional (continued on next page) computed tomography and technetium Tc 99m bone scan imaging are unable to detect disease after curative intervention despite rising prostate-specific antigen. There is no clear standard of care and no systemic therapy has been shown to improve survival. Immunotherapy-based treatments potentially are attractive options relative to androgen deprivation therapy due to the generally more favorable side-effect profile. Biochemically recurrent prostate cancer patients have a low tumor burden and likely lymph node-based disease, which may make them more likely to respond to immunotherapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Imunoterapia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/patologia , Idoso , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Seleção de Pacientes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Medição de Risco , Papel (figurativo) , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
14.
Urol Clin North Am ; 47(4): 523-536, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008501

RESUMO

Personalized medicine uses a patient's genotype, environment, and lifestyle choices to create a tailored diagnosis and therapy plan, with the goal of minimizing side effects, avoiding lost time with ineffective treatments, and guiding preventative strategies. Although most precision medicine strategies are still within the laboratory phase of development, this article reviews the promising technologies with the greatest potential to improve the diagnosis and treatment options for male infertility, including sperm cell transplantation, genomic editing, and new biomarker assays, based on the latest proteomic and epigenomic studies.


Assuntos
Genômica , Infertilidade Masculina/genética , Infertilidade Masculina/terapia , Medicina de Precisão/métodos , Biomarcadores/sangue , Terapia Combinada , Previsões , Humanos , Infertilidade Masculina/diagnóstico , Masculino , Proteômica , Medição de Risco , Resultado do Tratamento
15.
Colomb Med (Cali) ; 51(2): e4272, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33012887

RESUMO

In the past four months SARS-CoV-2 has reached most countries in the world. Public health strategies based on widespread testing and proper isolation of positive cases have shown to be helpful to reduce local transmission of SARS-CoV-2. Confirmatory tests, that identify viral RNA, and screening serological tests that identify viral antigens or host antibodies against viral proteins are part of the tools that nations can use to fight infectious disease epidemics. Understanding how each test works can provide insights about their test characteristics and how they can be used for different clinical and public health goals. Testing is a key strategy to reduce viral transmission, not only for this epidemic, but also for others to come.


Assuntos
Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Antígenos Virais/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Humanos , América Latina/epidemiologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Saúde Pública , RNA Viral/isolamento & purificação
17.
Trials ; 21(1): 828, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023671

RESUMO

OBJECTIVES: Primary objectives • To assess the time from randomisation until an improvement within 84 days defined as two points on a seven point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of SARS-CoV-2 infection or standard of care. Secondary objectives • To assess overall survival, and the overall survival rate at 28 56 and 84 days. • To assess SARS-CoV-2 viral clearance and load as well as antibody titres. • To assess the percentage of patients that required mechanical ventilation. • To assess time from randomisation until discharge. TRIAL DESIGN: Randomised, open-label, multicenter phase II trial, designed to assess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group 4) following treatment with anti-SARS-CoV-2 convalescent plasma or standard of care. PARTICIPANTS: High-risk patients >18 years of age hospitalized with SARS-CoV-2 infection in 10-15 university medical centres will be included. High-risk is defined as SARS-CoV-2 positive infection with Oxygen saturation at ≤ 94% at ambient air with additional risk features as categorised in 4 groups: • Group 1, pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less. • Group 2, chronic immunosuppression not meeting the criteria of group 1. • Group 3, age ≥ 50 - 75 years meeting neither the criteria of group 1 nor group 2 and at least one of these criteria: Lymphopenia < 0.8 x G/l and/or D-dimer > 1µg/mL. • Group 4, age ≥ 75 years meeting neither the criteria of group 1 nor group 2. Observation time for all patients is expected to be at least 3 months after entry into the study. Patients receive convalescent plasma for two days (day 1 and day 2) or standard of care. For patients in the standard arm, cross over is allowed from day 10 in case of not improving or worsening clinical condition. Nose/throat swabs for determination of viral load are collected at day 0 and day 1 (before first CP administration) and subsequently at day 2, 3, 5, 7, 10, 14, 28 or until discharge. Serum for SARS-Cov-2 diagnostic is collected at baseline and subsequently at day 3, 7, 14 and once during the follow-up period (between day 35 and day 84). There is a regular follow-up of 3 months. All discharged patients are followed by regular phone calls. All visits, time points and study assessments are summarized in the Trial Schedule (see full protocol Table 1). All participating trial sites will be supplied with study specific visit worksheets that list all assessments and procedures to be completed at each visit. All findings including clinical and laboratory data are documented by the investigator or an authorized member of the study team in the patient's medical record and in the electronic case report forms (eCRFs). INTERVENTION AND COMPARATOR: This trial will analyze the effects of convalescent plasma from recovered subjects with SARS-CoV-2 antibodies in high-risk patients with SARS-CoV-2 infection. Patients at high risk for a poor outcome due to underlying disease, age or condition as listed above are eligible for enrollment. In addition, eligible patients have a confirmed SARS-CoV-2 infection and O2 saturation ≤ 94% while breathing ambient air. Patients are randomised to receive (experimental arm) or not receive (standard arm) convalescent plasma in two bags (238 - 337 ml plasma each) from different donors (day 1, day 2). A cross over from the standard arm into the experimental arm is possible after day 10 in case of not improving or worsening clinical condition. MAIN OUTCOMES: Primary endpoints: The main purpose of the study is to assess the time from randomisation until an improvement within 84 days defined as two points on a seven-point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of a SARS-CoV-2 infection or standard of care. Secondary endpoints: • Overall survival, defined as the time from randomisation until death from any cause 28-day, 56-day and 84-day overall survival rates. • SARS-CoV-2 viral clearance and load as well as antibody titres. • Requirement mechanical ventilation at any time during hospital stay (yes/no). • Time until discharge from randomisation. • Viral load, changes in antibody titers and cytokine profiles are analysed in an exploratory manner using paired non-parametric tests (before - after treatment). RANDOMISATION: Upon confirmation of eligibility (patients must meet all inclusion criteria and must not meet exclusion criteria described in section 5.3 and 5.4 of the full protocol), the clinical site must contact a centralized internet randomization system ( https://randomizer.at/ ). Patients are randomized using block randomisation to one of the two arms, experimental arm or standard arm, in a 1:1 ratio considering a stratification according to the 4 risk groups (see Participants). BLINDING (MASKING): The study is open-label, no blinding will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total number of 174 patients is required for the entire trial, n=87 per group. TRIAL STATUS: Protocol version 1.2 dated 09/07/2020. A recruitment period of approximately 9 months and an overall study duration of approximately 12 months is anticipated. Recruitment of patients starts in the third quarter of 2020. The study duration of an individual patient is planned to be 3 months. After finishing all study-relevant procedures, therapy, and follow-up period, the patient is followed in terms of routine care and treated if necessary. Total trial duration: 18 months Duration of the clinical phase: 12 months First patient first visit (FPFV): 3rd Quarter 2020 Last patient first visit (LPFV): 2nd Quarter 2021 Last patient last visit (LPLV): 3rd Quarter 2021 Trial Report completed: 4th Quarter 2021 TRIAL REGISTRATION: EudraCT Number: 2020-001632-10, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE , registered on 04/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). The eCRF is attached (Additional file 3).


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus , Infecções por Coronavirus , Pandemias , Plasma/imunologia , Pneumonia Viral , Idoso , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Ensaios Clínicos Fase II como Assunto , Convalescença , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Imunização Passiva/métodos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Estudos Multicêntricos como Assunto , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco Ajustado , Índice de Gravidade de Doença
18.
Saudi Med J ; 41(10): 1090-1097, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33026050

RESUMO

OBJECTIVES: To elucidate the risk factors for hospital admission among COVID-19 patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective study was conducted at the Prince Sultan Military Medical City, Riyadh, Saudi Arabia between May 2020 and July 2020. Out of 7,260 COVID-19 patients, 920 were identified as T2DM. After the exclusion process, 806 patients with T2DM were included in this analysis. Patients' data were extracted from electronic medical records. A logistic regression model was performed to estimate the risk factors of hospital admission. Results: Of the total of 806 COVID-19 patients with T2DM, 48% were admitted in the hospital, 52% were placed under home isolation. Older age between 70-79 years (OR [odd ratio] 2.56; p=0.017), ≥80 years (OR 6.48; p=0.001) were significantly more likely to be hospitalized compared to less than 40 years. Similarly, patients with higher HbA1c level of ≥9% compared to less than 7%; (OR 1.58; p=0.047); patients with comorbidities such as, hypertension (OR 1.43; p=0.048), cardiovascular disease (OR 1.56; p=0.033), cerebrovascular disease (OR 2.38; p=0.016), chronic pulmonary disease (OR 1.51; p=0.018), malignancy (OR 2.45; p=0.025), chronic kidney disease (CKD) IIIa, IIIb, IV (OR 2.37; p=0.008), CKD V (OR 5.07; p=0.007) were significantly more likely to be hospitalized. Likewise, insulin-treated (OR 1.46; p=0.03) were more likely to require hospital admission compared to non-insulin treated patients. CONCLUSION: Among COVID-19 patients with diabetes, higher age, high HbA1c level, and presence of other comorbidities were found to be significant risk factors for the hospital admission.


Assuntos
Fatores Etários , Doença Crônica/epidemiologia , Infecções por Coronavirus , Diabetes Mellitus Tipo 2 , Hemoglobina A Glicada/análise , Hospitalização/estatística & dados numéricos , Pandemias , Pneumonia Viral , Adulto , Idoso , Betacoronavirus/isolamento & purificação , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Arábia Saudita/epidemiologia
19.
BMJ Case Rep ; 13(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028572

RESUMO

A 13-year-old boy presented to hospital with 3-day self-limited fever, followed by dry cough, persistent asthenia and impaired general condition of 2 weeks' duration. Blood analyses showed a severe inflammatory status and chest X-ray images were consistent with bilateral COVID-19 pneumonia. He developed an acute respiratory failure that required paediatric intensive care admission and non-invasive ventilation. A targeted COVID-19 treatment was initiated with hydroxicloroquine, corticosteroids, enoxaparine and a single dose of tocilizumab. Repeated serological tests and real-time reverse transcription PCR for SARS-CoV-2 were negative. Other infectious pathogens were also ruled out. Thoracic high resolution CT showed an intense bilateral pulmonary dissemination with lytic vertebral bone lesions. After diagnostic investigations, Ewing's sarcoma with metastatic pulmonary dissemination was diagnosed. Nowadays, in the context of SARS-CoV-2 community pandemic, we cannot forget that COVID-19 clinical presentation is not specific and other entities can mimic its clinical features.


Assuntos
Infecções por Coronavirus/diagnóstico , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Pneumonia Viral/diagnóstico , Sarcoma de Ewing , Tomografia Computadorizada por Raios X/métodos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Exame de Medula Óssea/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/secundário , Masculino , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos
20.
Tohoku J Exp Med ; 252(2): 109-119, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33028754

RESUMO

Coronavirus disease 2019 (COVID-19) is associated with various symptoms and changes in hematological and biochemical variables. However, clinical features, which can differentiate COVID-19 from non-COVID-19, are not clear. We therefore examined the key clinical features of COVID-19 and non-COVID-19 patients. This study included 60 COVID-19 patients and 100 non-COVID-19 patients, diagnosed by PCR, and no significant differences in the age and sex were seen between the two groups. The frequencies of fatigue, loose stool, diarrhea, nasal obstruction, olfactory dysfunction, taste dysfunction, underlying hyperlipidemia, and the prescription of angiotensin II receptor blocker (ARB) were significantly higher in COVID-19 patients than those in non-COVID-19 patients. The counts of leucocytes, neutrophils, lymphocytes, eosinophils, monocytes, and basophils and the levels of chloride and calcium in blood of COVID-19 patients were significantly lower than those of non-COVID-19 patients. The frequencies of atypical lymphocytes and the levels of lactate dehydrogenase (LDH) and potassium were significantly higher in COVID-19 than those in non-COVID-19. The C-reactive protein (CRP) level in COVID-19 patients was significantly lower than that in non-COVID-19 patients, when we compared CRP levels among patients with elevated CRP. This study is the first to indicate that electrolyte levels and the frequency of atypical lymphocytes in COVID-19 are significantly different from those in non-COVID-19. Fatigue, loose stool, diarrhea, nasal obstruction, olfactory dysfunction, and taste dysfunction were the key symptoms of COVID-19. Furthermore, hyperlipidemia and ARB may be risk factors of COVID-19. In conclusion, leucocytes, leucocyte fractions, CRP, LDH, and electrolytes are useful indicators for COVID-19 diagnosis.


Assuntos
Infecções por Coronavirus/diagnóstico , Eletrólitos/sangue , Linfócitos/virologia , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Proteína C-Reativa/análise , Criança , Diagnóstico Diferencial , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/virologia , Pandemias , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Avaliação de Sintomas , Distúrbios do Paladar/virologia , Adulto Jovem
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