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1.
Infect Dis Ther ; 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34687442

RESUMO

INTRODUCTION: To assess the long-term consequences of coronavirus disease (COVID-19) among health care workers (HCWs) in China (hereafter surviving HCWs). METHODS: A total of 303 surviving HCWs were included. Lung (pulmonary function test, 6-min walk test [6MWT], chest CT), physical (St. George's Respiratory Questionnaire [SGRQ], Modified Medical Research Council dyspnea scale [mMRC], and Borg scale), and psychiatric functions (Essen Trauma Inventory) were evaluated during the 1-year follow-up. RESULTS: Surviving HCWs had an abnormal diffusion capacity 1 year post-discharge. Participants with a reduced carbon monoxide diffusing capacity (DLCO) comprised 43.48%. The proportion of HCWs with a median 6MWT distance below the lower limit of the normal was 19.4%. An abnormal CT pattern was observed in 37.5% of the HCWs. The SGRQ, mMRC, and Borg scores of surviving HCWs, especially those with critical/severe disease, were significantly higher than those in the normal population. Probable post-traumatic stress disorder (PTSD) was reported in 21.9% of the surviving HCWs. Diffusion capacity impairment was associated with women. Critical/severe illness and nurses were associated with impaired physical function. CONCLUSIONS: Most surviving HCWs, especially female HCWs, still had an abnormal diffusion capacity at 1 year. The physical and psychiatric functions of surviving HCWs were significantly worse than those of the healthy population. Long-term follow-up of pulmonary, physical, and psychiatric functions for surviving HCWs is required.

2.
Front Immunol ; 12: 710904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421916

RESUMO

Although studies in oncology have well explored the pharmacological effects of Birc5, little is known about its role in allogeneic T-cell responses. Therefore, the present study used a mouse model of acute heart allograft rejection to investigate the protective effect and mechanism of conditional knockout of Birc5 in T cells. Survivin (encoded by Birc5) was up-regulated in T cells activated in vivo and in vitro. Deletion of Birc5 in T cells attenuated acute heart allograft rejection by reducing the ratio of effector to naive T cells and Th1 to Tregs. In addition, deletion of Birc5 had no noticeable effect on proliferation but on apoptosis and the secretion of IFN-γ. The results revealed a significant increase in the percentage of Annexin V positive CD4+ T cells in the Birc5-/- group, compared to the WT. Moreover, there was significant increase in early apoptotic alloreactive T cells in Birc5 -/- mice and this was partly mediated by caspase-3. Furthermore, treatment with YM155 inhibited acute heart allograft rejection in vivo and increased T-cell apoptosis in healthy human PBMCs in vitro. The results highlight a potential therapeutic target for the prevention and treatment of acute transplant rejection.

3.
Int J Biol Sci ; 17(9): 2193-2204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239349

RESUMO

The functions of dual-specificity phosphatase 9 (DUSP9) in hepatic steatosis and metabolic disturbance during nonalcoholic fatty liver disease were discussed in our prior study. However, its roles in the pathophysiology of pressure overload-induced cardiac hypertrophy remain to be illustrated. This study attempted to uncover the potential contributions and underpinning mechanisms of DUSP9 in cardiac hypertrophy. Utilizing the gain-and-loss-of-functional approaches of DUSP9 the cardiac phenotypes arising from the pathological, echocardiographic, and molecular analysis were quantified. The results showed increased levels of DUSP9 in hypertrophic mice heart and angiotensin II treated cardiomyocytes. In accordance with the results of cellular hypertrophy in response to angiotensin II, cardiac hypertrophy exaggeration, fibrosis, and malfunction triggered by pressure overload was evident in the case of cardiac-specific conditional knockout of DUSP9. In contrast, transgenic mice hearts with DUSP9 overexpression portrayed restoration of the hypertrophic phenotypes. Further explorations of molecular mechanisms indicated the direct interaction of DUSP9 with ASK1, which further repressed p38 and JNK signaling pathways. Moreover, blocking ASK1 with ASK1-specific inhibitor compensated the pro-hypertrophic effects induced by DUSP9 deficiency in cardiomyocytes. The main findings of this study suggest the potential of DUSP9 in alleviating cardiac hypertrophy at least partially by repressing ASK1, thereby looks promising as a prospective target against cardiac hypertrophy.

4.
BMC Med ; 19(1): 163, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34256745

RESUMO

BACKGROUND: Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China. METHODS: We conducted an ambidirectional cohort study in "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ2, and Fisher's exact test were used to assess the variance between two or more groups where appropriate. RESULTS: Of 333 HCWs with severe COVID-19, the HCWs' median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3+ T cells and CD4+ T cells. CONCLUSION: The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19 , COVID-19 , Teste de Esforço , Pessoal de Saúde/estatística & dados numéricos , SARS-CoV-2/imunologia , Adulto , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/reabilitação , Teste Sorológico para COVID-19/métodos , Teste Sorológico para COVID-19/estatística & dados numéricos , China/epidemiologia , Teste de Esforço/métodos , Teste de Esforço/estatística & dados numéricos , Feminino , Seguimentos , Estado Funcional , Humanos , Interleucina-6/sangue , Masculino , Alta do Paciente/estatística & dados numéricos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue
5.
Transl Psychiatry ; 11(1): 374, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226510

RESUMO

Suffering from COVID-19 and witnessing the suffering and deaths of patients with COVID-19 may place frontline healthcare workers (HCWs) at particularly high risk for posttraumatic stress disorder (PTSD); however, few data are available on the clinical characteristics of PTSD among frontline HCWs who survived COVID-19 ("surviving HCWs" hereafter). The present study examined the prevalence, correlates, and clinical symptoms of possible PTSD in surviving HCWs 6 months after the COVID-19 outbreak in China. A total of 291 surviving HCWs and 42 age- and gender-matched COVID-19-free frontline HCWs (control group) were recruited and administered the Chinese Essen Trauma Inventory, which was used to assess the presence of possible PTSD according to DSM-IV-TR criteria. Survivors' clinical data and characteristics of exposure to COVID-19 were collected via self-report questionnaires. Surviving HCWs had significantly higher rates of possible PTSD than controls (19.9% vs. 4.8%, P = 0.017). Correlates of PTSD in survivors were ICU admission (OR = 8.73, P = 0.003), >10 respiratory symptoms during the most symptomatic period of COVID-19 (OR = 3.08, P = 0.006), the residual symptom of dizziness (OR = 2.43, P = 0.013), the residual symptom of difficult breathing (OR = 2.23, P = 0.027), life in danger due to COVID-19 (OR = 16.59, P = 0.006), and exposure to other traumatic events (OR = 2.94, P = 0.035). Less commonly seen PTSD symptoms in survivors were having nightmares about the event (34.5%), suddenly feeling like they were living through the event suddenly (25.9%), being unable to remember an important part of the event (32.8%), and overalertness (31.0%). Nearly one-fifth of the surviving HCWs had possible PTSD 6 months after the COVID-19 outbreak. Mental health services for this vulnerable population should include periodic screening for PTSD, expanded social support, and, when necessary, psychotherapy and psychopharmacological treatment.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , China/epidemiologia , Surtos de Doenças , Pessoal de Saúde , Humanos , Prevalência , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/epidemiologia
6.
Cell Death Dis ; 12(6): 501, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006836

RESUMO

Regulatory T cells play a crucial role in orchestrating immune response and maintaining immune tolerance, and the expression of the Foxp3 gene is indispensable to the differentiation of regulatory T cells. IL-4 shows strong inhibitory effects on Foxp3 expression and regulatory T cells differentiation, but the detailed mechanisms are still unclear. Here, we revealed that epigenetic modulations are key to this process. Specifically, the inhibition was found to be STAT6 dependent, and HDAC9 was involved with the process of histone deacetylation at the Foxp3 locus, subsequently decreasing chromatin accessibility and Foxp3 gene transcription. Pan-histone deacetylation inhibitors, especially sodium butyrate, notably abolished the inhibitory effects of IL-4 and ameliorated allergic airway inflammation in mouse models. Our research provides important mechanistic insights into how IL-4 inhibits regulatory T cells differentiation and suggests the therapeutic potential of the sodium butyrate in allergic airway disease.


Assuntos
Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Interleucina-4/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Linfócitos T Reguladores/citologia , Animais , Diferenciação Celular/fisiologia , Epigênese Genética , Feminino , Humanos , Camundongos , Linfócitos T Reguladores/imunologia
7.
Curr Med Res Opin ; 37(6): 917-927, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33729889

RESUMO

BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources. METHODS: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses. RESULTS: Eight factors, namely, Oxygen saturation, blood Urea nitrogen, Respiratory rate, admission before the date the national Maximum number of daily new cases was reached, Age, Procalcitonin, C-reactive protein (CRP), and absolute Neutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71; p < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts. CONCLUSIONS: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.


Assuntos
COVID-19 , Medição de Risco/métodos , COVID-19/epidemiologia , COVID-19/mortalidade , China , Hospitalização/estatística & dados numéricos , Humanos , Itália , Fatores de Risco
8.
Med (N Y) ; 2(4): 435-447.e4, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33521746

RESUMO

Background: To develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC). Methods: We performed a retrospective cohort study from a total of 13,138 inpatients with COVID-19 in Hubei, China, and Milan, Italy. Among them, 9,810 patients with ≥2 CBC records from Hubei were assigned to the training cohort. CBC parameters were analyzed as potential predictors for all-cause mortality and were selected by the generalized linear mixed model (GLMM). Findings: Five risk factors were derived to construct a composite score (PAWNN score) using the Cox regression model, including platelet counts, age, white blood cell counts, neutrophil counts, and neutrophil:lymphocyte ratio. The PAWNN score showed good accuracy for predicting mortality in 10-fold cross-validation (AUROCs 0.92-0.93) and subsets with different quartile intervals of follow-up and preexisting diseases. The performance of the score was further validated in 2,949 patients with only 1 CBC record from the Hubei cohort (AUROC 0.97) and 227 patients from the Italian cohort (AUROC 0.80). The latent Markov model (LMM) demonstrated that the PAWNN score has good prediction power for transition probabilities between different latent conditions. Conclusions: The PAWNN score is a simple and accurate risk assessment tool that can predict the mortality for COVID-19 patients during their entire hospitalization. This tool can assist clinicians in prioritizing medical treatment of COVID-19 patients. Funding: This work was supported by National Key R&D Program of China (2016YFF0101504, 2016YFF0101505, 2020YFC2004702, 2020YFC0845500), the Key R&D Program of Guangdong Province (2020B1111330003), and the medical flight plan of Wuhan University (TFJH2018006).

9.
Curr Med Sci ; 41(1): 1-13, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582899

RESUMO

Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×109/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO2 >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.


Assuntos
COVID-19/terapia , Oxigenação por Membrana Extracorpórea/métodos , Adulto , Idoso , COVID-19/mortalidade , Estudos de Casos e Controles , China , Estado Terminal , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
10.
J Am Heart Assoc ; 10(4): e014311, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33522247

RESUMO

Background Heart pathological hypertrophy has been recognized as a predisposing risk factor for heart failure and arrhythmia. DUSP (dual-specificity phosphatase) 26 is a member of the DUSP family of proteins, which has a significant effect on nonalcoholic fatty liver disease, neuroblastoma, glioma, and so on. However, the involvement of DUSP26 in cardiac hypertrophy remains unclear. Methods and Results Our study showed that DUSP26 expression was significantly increased in mouse hearts in response to pressure overload as well as in angiotensin II-treated cardiomyocytes. Cardiac-specific overexpression of DUSP26 mice showed attenuated cardiac hypertrophy and fibrosis, while deficiency of DUSP26 in mouse hearts resulted in increased cardiac hypertrophy and deteriorated cardiac function. Similar effects were also observed in cellular hypertrophy induced by angiotensin II. Importantly, we showed that DUSP26 bound to transforming growth factor-ß activated kinase 1 and inhibited transforming growth factor-ß activated kinase 1 phosphorylation, which led to suppression of the mitogen-activated protein kinase signaling pathway. In addition, transforming growth factor-ß activated kinase 1-specific inhibitor inhibited cardiomyocyte hypertrophy induced by angiotensin II and attenuated the exaggerated hypertrophic response in DUSP26 conditional knockout mice. Conclusions Taken together, DUSP26 was induced in cardiac hypertrophy and protected against pressure overload induced cardiac hypertrophy by modulating transforming growth factor-ß activated kinase 1-p38/ c-Jun N-terminal kinase-signaling axis. Therefore, DUSP26 may provide a therapeutic target for treatment of cardiac hypertrophy and heart failure.


Assuntos
Cardiomegalia/tratamento farmacológico , Fosfatases de Especificidade Dupla/farmacologia , Regulação da Expressão Gênica , MAP Quinase Quinase Quinases/genética , Fosfatases da Proteína Quinase Ativada por Mitógeno/farmacologia , Miócitos Cardíacos/metabolismo , Animais , Cardiomegalia/genética , Cardiomegalia/metabolismo , Modelos Animais de Doenças , Ecocardiografia , MAP Quinase Quinase Quinases/biossíntese , Camundongos , Camundongos Knockout , Miócitos Cardíacos/patologia , RNA/genética , Transdução de Sinais
11.
Cell ; 184(3): 775-791.e14, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33503446

RESUMO

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.


Assuntos
COVID-19/metabolismo , Regulação da Expressão Gênica , Proteoma/biossíntese , Proteômica , SARS-CoV-2/metabolismo , Autopsia , COVID-19/patologia , COVID-19/terapia , Feminino , Humanos , Masculino , Especificidade de Órgãos
12.
Cell Metab ; 33(2): 258-269.e3, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421384

RESUMO

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.


Assuntos
Corticosteroides/uso terapêutico , COVID-19/tratamento farmacológico , Linfócitos/citologia , Neutrófilos/citologia , Corticosteroides/efeitos adversos , Área Sob a Curva , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Humanos , Hiperglicemia/complicações , Hiperglicemia/patologia , Tempo de Internação , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
13.
J Thorac Dis ; 12(11): 6663-6669, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33282367

RESUMO

Background: The pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) creates many challenges for the healthcare sector. Currently, little is known of how the pandemic has impacted patients with cardiovascular disease. The primary focus of this study was to determine whether emergency cardiovascular surgeries can be carried out safely during the COVID-19 pandemic. Methods: Between 17 January 2020 and 11 February 2020, 13 patients were admitted to Wuhan Union Hospital for emergency cardiovascular surgery. During this time, Wuhan was a COVID-19 epicenter, and Wuhan Union Hospital is a sentinel hospital located in this area. These patients' epidemiological histories, clinical records, laboratory assessments, imaging findings, and surgical outcomes were retrospectively reviewed. Throat swabs were collected from some patients preoperatively and all patients postoperatively for reverse transcription polymerase chain reaction (RT-PCR) testing to determine whether these patients had COVID-19. Results: This cohort included 5 cases of acute aortic dissection, 3 cases of congenital heart disease, 2 cases of dilated cardiomyopathy with end-stage heart failure, 1 case of aortocoronary fistula that had undergone previous surgery, 1 case of subacute infective endocarditis with cerebral infarction, and 1 case of multivessel coronary disease. Six patients were suspected COVID-19 cases (46.2%). There were no confirmed COVID-19 cases in this cohort. None of the patients in this cohort died and none developed severe acute respiratory syndrome, renal failure, or septic shock after surgery. No cross-infection occurred with other patients or medical staff who came into close contact with this cohort. Conclusions: Emergency surgery is crucial and unavoidable for many patients with acute and severe cardiovascular disease, regardless of the pandemic. Our study indicates that, with adequate preparation and the provision of appropriate treatment, satisfactory outcomes can be achieved for such patients.

14.
Interact Cardiovasc Thorac Surg ; 31(6): 834-840, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33150432

RESUMO

OBJECTIVES: Our goal was to compare the short-term outcomes of Stanford type A aortic dissection (TAAD), during the coronavirus disease 2019 (COVID-19) pandemic with those during normal times and summarize our perioperative management experience of patients with TAAD in the context of COVID-19. METHODS: From 17 January 2020 to 8 March 2020, a total of 27 patients with TAAD were operated on in 8 cardiovascular surgery centres in Hubei Province (COVID-19 group). The data from 91 patients with TAAD from the same centres during the same period last year were extracted from the Hubei Cardiac Surgery Registration System (control group). A propensity score matched subgroup of 26 pairs (1:2) was identified. Perioperative data and short-term outcomes were assessed. RESULTS: Nine patients in the COVID-19 group were categorized as suspicious for the disease (9/27, 33.3%), and others were excluded (18/27, 66.7%). No one was laboratory confirmed preoperatively. The average waiting, cross-clamp and circulatory arrest times were longer in the COVID-19 group (22.9 ± 8.3 vs 9.7 ± 4.0 h, P < 0.001; 135 ± 36 vs 103 ± 45 min, P = 0.003; 24 ± 9 vs 17 ± 8 min, P < 0.001, respectively). The 30-day or in-hospital deaths were 3.8% in both groups (P = 1.0). The COVID-19 group was associated with longer ventilation and intensive care unit times (81 ± 71 vs 45 ± 19 h, P < 0.001; 7.4 ± 3.8 vs 4.5 ± 2.7 days; P < 0.001, respectively). There were no statistical differences between the 2 groups in the incidence of complications such as stroke, neurological deficit, acute kidney injury, pulmonary infection and reoperation. Serum antibody tests for those patients showed 7 out of 9 suspected cases were Immunoglobulin G positive. No cross-infection occurred in other patients or associated medical staff. CONCLUSIONS: With adequate preparation and appropriate protection, satisfactory early outcomes can be achieved after emergency operations for patients with TAAD during the COVID-19 pandemic.


Assuntos
Aneurisma Dissecante/cirurgia , COVID-19/epidemiologia , Pandemias , Pontuação de Propensão , SARS-CoV-2 , Procedimentos Cirúrgicos Vasculares/métodos , Aneurisma Dissecante/epidemiologia , China/epidemiologia , Comorbidade , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento
16.
Cell Metab ; 32(4): 537-547.e3, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32861268

RESUMO

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.


Assuntos
Acidose/induzido quimicamente , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Metformina/efeitos adversos , Pneumonia Viral/complicações , Acidose Láctica/induzido quimicamente , Idoso , COVID-19 , China/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hospitalização , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos
17.
Lancet Haematol ; 7(9): e671-e678, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32659214

RESUMO

BACKGROUND: COVID-19 is an ongoing global pandemic. Changes in haematological characteristics in patients with COVID-19 are emerging as important features of the disease. We aimed to explore the haematological characteristics and related risk factors in patients with COVID-19. METHODS: This retrospective cohort study included patients with COVID-19 admitted to three designated sites of Wuhan Union Hospital (Wuhan, China). Demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records and compared between patients with moderate, severe, and critical disease (defined according to the diagnosis and treatment protocol for novel coronavirus pneumonia, trial version 7, published by the National Health Commission of China). We assessed the risk factors associated with critical illness and poor prognosis. Dynamic haematological and coagulation parameters were investigated with a linear mixed model, and coagulopathy screening with sepsis-induced coagulopathy and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation scoring systems was applied. FINDINGS: Of 466 patients admitted to hospital from Jan 23 to Feb 23, 2020, 380 patients with COVID-19 were included in our study. The incidence of thrombocytopenia (platelet count <100 × 109 cells per L) in patients with critical disease (42 [49%] of 86) was significantly higher than in those with severe (20 [14%] of 145) or moderate (nine [6%] of 149) disease (p<0·0001). The numbers of lymphocytes and eosinophils were significantly lower in patients with critical disease than those with severe or moderate disease (p<0·0001), and prothrombin time, D-dimer, and fibrin degradation products significantly increased with increasing disease severity (p<0·0001). In multivariate analyses, death was associated with increased neutrophil to lymphocyte ratio (≥9·13; odds ratio [OR] 5·39 [95% CI 1·70-17·13], p=0·0042), thrombocytopenia (platelet count <100 × 109 per L; OR 8·33 [2·56-27·15], p=0·00045), prolonged prothrombin time (>16 s; OR 4·94 [1·50-16·25], p=0·0094), and increased D-dimer (>2 mg/L; OR 4·41 [1·06-18·30], p=0·041). Thrombotic and haemorrhagic events were common complications in patients who died (19 [35%] of 55). Sepsis-induced coagulopathy and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation scores (assessed in 12 patients who survived and eight patients who died) increased over time in patients who died. The onset of sepsis-induced coagulopathy was typically before overt disseminated intravascular coagulation. INTERPRETATION: Rapid blood tests, including platelet count, prothrombin time, D-dimer, and neutrophil to lymphocyte ratio can help clinicians to assess severity and prognosis of patients with COVID-19. The sepsis-induced coagulopathy scoring system can be used for early assessment and management of patients with critical disease. FUNDING: National Key Research and Development Program of China.


Assuntos
Infecções por Coronavirus/patologia , Transtornos Hemorrágicos/patologia , Pneumonia Viral/patologia , Adulto , Idoso , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/classificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/patologia , Eosinófilos/citologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Transtornos Hemorrágicos/complicações , Humanos , Modelos Lineares , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias/classificação , Pneumonia Viral/classificação , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Tempo de Protrombina , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Trombocitopenia/complicações , Trombocitopenia/patologia
18.
Theranostics ; 10(18): 8051-8060, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724457

RESUMO

Background: The immune checkpoint cytotoxic T lymphocyte antigen-4 (CTLA-4), induced upon T cell activation but degraded quickly, has been targeted in the clinical therapy of advanced cancers and autoimmune diseases. However, whether inhibiting CTLA-4 degradation ameliorates transplant rejection remains unknown. Methods: The CTLA-4 expression in activated murine T cells treated with the inhibitors mediating protein degradation was detected by flow cytometry (FCM). CD45.1 mice, which received TEa T cells and underwent heart transplantation, were administrated with the inhibitor. Subsequently, CTLA-4 expression of TEa T cells was analyzed. Murine skin and heart transplantation models were built, then the survival and histopathology of the allografts, and T cell subsets in the spleens of each group were compared. Results: Chloroquine (CQ) was identified as an inhibitor of CTLA-4 degradation, which augmented both surface and total CTLA-4 expression in T cells. It considerably prolonged the skin and heart allograft survival time and reduced the infiltration of inflammatory cells in allografts. Besides decreasing the frequencies of the CD4+ and CD8+ effector T cells, especially IFN-γ producing T cells, CQ also increased the proportion of regulatory T cells in the spleen. The CTLA-4 blockade abrogated the benefits of CQ on the survival of heart allografts. Moreover, CQ enhanced CTLA-4 expression in activated human T cells and reduced the secretion of IFN-γ in human mixed lymphocyte reaction. Conclusion: Targeting CTLA-4 degradation provides a novel means to prevent transplant rejection and induce transplant tolerance.


Assuntos
Antígeno CTLA-4/agonistas , Cloroquina/farmacologia , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/efeitos adversos , Transplante de Pele/efeitos adversos , Animais , Autofagia/efeitos dos fármacos , Antígeno CTLA-4/metabolismo , Linhagem Celular , Cloroquina/uso terapêutico , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos , Interferon gama/antagonistas & inibidores , Interferon gama/metabolismo , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Lisossomos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Transgênicos , Proteólise/efeitos dos fármacos
20.
Aging (Albany NY) ; 12(12): 11636-11652, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32541091

RESUMO

Chronic allograft dysfunction (CAD) resulting from fibrosis is the major limiting factor for long-term survival of lung transplant patients. Myofibroblasts promote fibrosis in multiple organs, including the lungs. In this study, we identified PLK1 as a promoter of myofibroblast differentiation and investigated the mechanism by which its inhibition alleviates transplant-associated obliterative bronchiolitis (OB) during CAD. High-throughput bioinformatic analyses and experiments using the murine heterotopic tracheal transplantation model revealed that PLK1 is upregulated in grafts undergoing CAD as compared with controls, and that inhibiting PLK1 alleviates OB in vivo. Inhibition of PLK1 in vitro reduced expression of the specific myofibroblast differentiation marker α-smooth muscle actin (α-SMA) and decreased phosphorylation of both MEK and ERK. Importantly, we observed a similar phenomenon in human primary fibroblasts. Our results thus highlight PLK1 as a promising therapeutic target for alleviating transplant-associated OB through suppression of TGF-ß1-mediated myofibroblast differentiation.


Assuntos
Bronquiolite Obliterante/patologia , Proteínas de Ciclo Celular/metabolismo , Rejeição de Enxerto/patologia , Transplante de Pulmão/efeitos adversos , Miofibroblastos/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Actinas/metabolismo , Aloenxertos/citologia , Aloenxertos/efeitos dos fármacos , Aloenxertos/patologia , Animais , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/prevenção & controle , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Doença Crônica/prevenção & controle , Biologia Computacional , Modelos Animais de Doenças , Fibrose , Técnicas de Silenciamento de Genes , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Voluntários Saudáveis , Humanos , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos , Miofibroblastos/efeitos dos fármacos , Células NIH 3T3 , Via de Pentose Fosfato/efeitos dos fármacos , Fosforilação , Cultura Primária de Células , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Pteridinas/farmacologia , Pteridinas/uso terapêutico , RNA-Seq , Traqueia/citologia , Traqueia/efeitos dos fármacos , Traqueia/patologia , Traqueia/transplante , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
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