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BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).
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Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Inibidores do Citocromo P-450 CYP3A/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Adulto , Idoso , Antivirais/efeitos adversos , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Humanos , Análise de Intenção de Tratamento , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Gravidade do Paciente , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ritonavir/efeitos adversos , SARS-CoV-2 , Tempo para o Tratamento , Falha de Tratamento , Carga ViralRESUMO
BACKGROUND: GeneXpert MTB/RIF (Xpert) assay was applied widely to detect Mycobacterium tuberculosis (MTB) and rifampicin resistance. METHODS: Retrospectively investigated the association among treatment histories, phenotypic drug susceptibility testing (pDST) results, and clinical outcomes of patients infected with probe A absent mutation isolate confirmed by Xpert. RESULTS: 63 patients with only probe A absent mutation and 40 with additional pDST results were analyzed. 24 (60.0%) patients had molecular-phenotypic discordant rifampicin (RIF) susceptibility testing results, including 12 (12/13, 92.3%) new tuberculosis (TB) patients and 12 (12/27, 44.4%) retreated ones. 28 (28/39, 71.8%) retreated patients received first-line treatment regime within two years with failed outcomes. New patients had better treatment outcomes than retreated ones (successful: 83.3% VS. 53.8%; P value = 0.02). The clinical results of RIF-susceptible TB confirmed by pDST were not better than RIF-resistant TB (successful: 62.5% VS. 50.0%; P value = 0.43). INH-resistant TB and INH-susceptible TB had similar treatment outcomes too (successful: 61.5% VS. 50.0%; P value = 0.48). 11 (11/12, 91.7%) new patients treated with the short treatment regimen (STR) had successful outcomes. CONCLUSIONS: More than half of mono probe A absent isolates had RIF molecular-phenotypic discordance results, especially in new patients. Probe A mutations were significantly associated with unsuccessful clinical outcomes, whether the pDST results were RIF susceptible or not. STR was the best choice for new patients. TRIAL REGISTRATION: retrospectively registered in Wuhan Jinyintan Hospital (No. 2021-KY-16).
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Humanos , Rifampina/farmacologia , Rifampina/uso terapêutico , Mycobacterium tuberculosis/genética , Testes de Sensibilidade Microbiana , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Mutação , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. METHODS: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. FINDINGS: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. INTERPRETATION: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. FUNDING: National Key R&D Program of China.
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Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , China/epidemiologia , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Tosse/epidemiologia , Tosse/virologia , Surtos de Doenças , Dispneia/epidemiologia , Dispneia/virologia , Feminino , Febre/epidemiologia , Febre/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Prognóstico , Radiografia Torácica , Estudos Retrospectivos , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/virologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: The clinical correlates, prognosis and determinants of acute kidney injury (AKI) in patients with coronavirus disease 2019 (Covid-19) remain largely unclear. METHODS: We retrospectively reviewed medical records of all adult patients with laboratory-confirmed Covid-19 who were admitted to the intensive care unit (ICU) between January 23rd 2020 and April 6th 2020 at Wuhan JinYinTan Hospital and The First Affiliated Hospital of Guangzhou Medical University. RESULTS: Among 210 patients, 131 were males (62.4%). The median Age was 64 years (IQR: 56-71). Of 92 (43.8%) patients who developed AKI during hospitalization, 13 (14.1%), 15 (16.3%) and 64 (69.6%) were classified as being at stage 1, 2 and 3, respectively. 54 patients (58.7%) received continuous renal replacement therapy. Age, sepsis, nephrotoxic drug, invasive mechanical ventilation and elevated baseline serum creatinine levels were associated with the occurrence of AKI. Renal recovery during hospitalization was identified among 16 patients with AKI (17.4%), who had a significantly shorter time from admission to AKI diagnosis, lower incidence of right heart failure and higher ratio of partial pressure of oxygen to the fraction of inspired oxygen. Of 210 patients, 93 deceased within 28 days of ICU admission. AKI stage 3, critical disease, greater Age and the lowest ratio of partial pressure of oxygen to the fraction of inspired oxygen being < 150 mmHg were independently associated with death. CONCLUSIONS: Among patients with Covid-19, the incidence of AKI was high. Our findings of the risk factors of the development of AKI and factors associated with renal function recovery may inform clinical management of patients with critical illness of Covid-19.
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Injúria Renal Aguda/virologia , Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , China , Estado Terminal , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2RESUMO
Photocatalytic conversion of CO2 to CH4, a carbon-neutral fuel, represents an appealing approach to remedy the current energy and environmental crisis; however, it suffers from the large production of CO and H2 by side reactions. The design of catalytic sites for CO2 adsorption and activation holds the key to address this grand challenge. In this Article, we develop highly selective sites for photocatalytic conversion of CO2 to CH4 by isolating Cu atoms in Pd lattice. According to our synchrotron-radiation characterizations and theoretical simulations, the isolation of Cu atoms in Pd lattice can play dual roles in the enhancement of CO2-to-CH4 conversion: (1) providing the paired Cu-Pd sites for the enhanced CO2 adsorption and the suppressed H2 evolution; and (2) elevating the d-band center of Cu sites for the improved CO2 activation. As a result, the Pd7Cu1-TiO2 photocatalyst achieves the high selectivity of 96% for CH4 production with a rate of 19.6 µmol gcat-1 h-1. This work provides fresh insights into the catalytic site design for selective photocatalytic CO2 conversion, and highlights the importance of catalyst lattice engineering at atomic precision to catalytic performance.
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BACKGROUND: To explore the efficacy of a prediction model based on diffusion-weighted imaging (DWI) features extracted from deep learning (DL) and radiomics combined with clinical parameters and apparent diffusion coefficient (ADC) values to identify microsatellite instability (MSI) in endometrial cancer (EC). METHODS: This study included a cohort of 116 patients with EC, who were subsequently divided into training (n = 81) and test (n = 35) sets. From DWI, conventional radiomics features and convolutional neural network-based DL features were extracted. Random forest (RF) and logistic regression were adopted as classifiers. DL features, radiomics features, clinical variables, ADC values, and their combinations were applied to establish DL, radiomics, clinical, ADC, and combined models, respectively. The predictive performance was evaluated through the area under the receiver operating characteristic curve (AUC), total integrated discrimination index (IDI), net reclassification index (NRI), calibration curves, and decision curve analysis (DCA). RESULTS: The optimal predictive model, based on an RF classifier, comprised four DL features, three radiomics features, two clinical variables, and an ADC value. In the training and test sets, this model exhibited AUC values of 0.989 (95% CI: 0.935-1.000) and 0.885 (95% CI: 0.731-0.967), respectively, demonstrating different degrees of improvement compared with the clinical, DL, radiomics, and ADC models (AUC-training = 0.671, 0.873, 0.833, and 0.814, AUC-test = 0.685, 0.783, 0.708, and 0.713, respectively). The NRI and IDI analyses revealed that the combined model resulted in improved risk reclassification of the MSI status compared to the clinical, radiomics, DL, and ADC models. The calibration curves and DCA indicated good consistency and clinical utility of this model, respectively. CONCLUSIONS: The predictive model based on DWI features extracted from DL and radiomics combined with clinical parameters and ADC values could effectively assess the MSI status in EC.
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Aprendizado Profundo , Imagem de Difusão por Ressonância Magnética , Neoplasias do Endométrio , Instabilidade de Microssatélites , Radiômica , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Estudos Retrospectivos , Curva ROCRESUMO
OBJECTIVE: To investigate if the addition of bedaquiline and clofazimine to a treatment regimen for multidrug-resistant tuberculosis (MDR-TB) could improve patient outcomes. METHODS: A prospective, randomized, controlled study was conducted in patients with MDR-TB. Treatment was for 18 months. Patients in the experimental group received bedaquiline and clofazimine in addition to their regular treatment regimen whereas patients in the control group did not. RESULTS: 68 patients with MDR-TB were randomised to treatment, 34 to each group. At the end of treatment, cure rates were statistically significantly greater for the experimental group compared with the control group (82% vs. 56%). There was no difference between groups in the number of severe adverse events (3[9%]) in both groups and none were skin-related. CONCLUSIONS: The addition of bedaquiline and clofazimine to the treatment regimen significantly improves outcomes for patients with MDR-TB. Clinicians should be aware of the clinical benefits of this addition but be mindful of contraindications and adverse effects.
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Clofazimina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Clofazimina/uso terapêutico , Antituberculosos/uso terapêutico , Estudos Prospectivos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
SETTING: The shorter treatment regimen (STR) for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) has achieved successful outcomes in many countries. However, there are few studies on high-dose gatifloxacin-based STR with adverse drug reactions (ADRs) and management. DESIGN: A prospective observational study was conducted with MDR/RR-TB patients who were treated with a standardized 9 or 12 - month regimen: including gatifloxacin (Gfx), clofazimine (Cfz), ethambutol (EMB), and pyrazinamide (PZA), and supplemented by amikacin (Am), isoniazid (INH), and prothionamide (Pto) during an intensive phase of 4 or 6 - month. Monitored ADRs monthly until treatment completion and then followed up every three months for one year. RESULTS: Among the 42 eligible patients, 35 (83.3%) completed treatment successfully, 1 (2.4%) lost to follow-up (LTFU), and 6 (14.3%) failed due to ADRs, with no death. The most important ADR was drug-induced liver damage, which occurred in 24 out of 42 (57.1%) patients and resulted in 4 (9.5%) failed treatments and 4 (9.5%) adjusted treatments. QT interval prolongation occurred in 17 out of 42 (40.5%) patients, 9 (21.4%) of them with the corrected QT interval according to Fridericia (QTcF) > 500 ms resulting in 7 (16.7%) adjusted treatments. CONCLUSIONS: This study confirmed the effectiveness of the high-dose gatifloxacin-based STR but severe ADRs, especially hepatotoxicity and QT interval prolongation should never be ignored.
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Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/efeitos adversos , Gatifloxacina , Humanos , Isoniazida/efeitos adversos , Pirazinamida/efeitos adversos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
BACKGROUND: Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear. METHODS: We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. RESULTS: Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13 days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28-day survival rate. CONCLUSIONS: In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.
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COVID-19 , Coinfecção , Infecção Hospitalar , Adulto , Antibacterianos/uso terapêutico , Coinfecção/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Humanos , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities which are indicators of higher mortality especially in severe cases. METHODS: We studied patients with proven COVID-19 disease in the intensive care unit of Jinyintan Hospital, Wuhan, China from 30 to 2019 to 31 March 2020. RESULTS: Of 180 patients, 89 (49.44 %) had died, 85 (47.22 %) had been discharged alive, and 6 (3.33 %) were still hospitalised by the end of data collection. A D-dimer concentration of > 0.5 mg/L on admission was significantly associated with 30 day mortality, and a D-dimer concentration of > 5 mg/L was found in a much higher proportion of non-survivors than survivors. Sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) scoring systems were dichotomised as < 4 or ≥ 4 and < 5 or ≥ 5, respectively, and the mortality rate was significantly different between the two stratifications in both scoring systems. Enoxaparin was administered to 68 (37.78 %) patients for thromboembolic prophylaxis, and stratification by the D-dimer concentration and DIC score confirmed lower mortality in patients who received enoxaparin when the D-dimer concentration was > 2 than < 2 mg/L or DIC score was ≥ 5 than < 5. A low platelet count and low serum calcium concentration were also related to mortality. CONCLUSIONS: A D-dimer concentration of > 0.5 mg/L on admission is a risk factor for severe disease. A SIC score of > 4 and DIC score of > 5 may be used to predict mortality. Thromboembolic prophylaxis can reduce mortality only in patients with a D-dimer concentration of > 2 mg/L or DIC score of ≥ 5.
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In patients with critically ill COVID-19 pneumonia, lower airways are filled with plenty of highly viscous exudates or mucus, leading to airway occlusion. The estimation of airway opening pressures and effective mucus clearance are therefore two issues that clinicians are most concerned about during mechanical ventilation. In this study we retrospectively analyzed respiratory data from 24 critically ill patients with COVID-19 who received invasive mechanical ventilation and recruitment maneuver at Jinyintan Hospital in Wuhan, China. Among 24 patients, the mean inspiratory plateau pressure was 52.4 ± 4.4 cmH2O (mean ± [SD]). Particularly, the capnograms presented an upward slope during the expiratory plateau, indicting the existence of airway obstruction. A computational model of airway opening was subsequently introduced to investigate possible fluid dynamic mechanisms for the extraordinarily high inspiratory plateau pressures among these patients. Our simulation results showed that the predicted airway opening pressures could be as high as 40-50 cmH2O and the suction pressure could exceed 20 kPa as the surface tension and viscosity of secretion simulants markedly increased, likely causing the closures of the distal airways. We concluded that, in some critically ill patients with COVID-19, limiting plateau pressure to 30 cmH2O may not guarantee the opening of airways due to the presence of highly viscous lower airway secretions, not to mention spontaneous inspiratory efforts. Active airway humidification and effective expectorant drugs are therefore strongly recommended during airway management.