Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019(COVID-19)is crucial for understanding the pathogenic mechanism of ...Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019(COVID-19)is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity.In this study,we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19samples including severe,moderate,and convalescent samples from three severely/critically ill and four moderately ill patients.We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19,with an increased proportion of monocytes and seriously reduced diversity.In addition,we discovered two novel severe-disease-specific monocyte subsets:Mono 0 and Mono 5.These subsets expressed amphiregulin(AREG),epiregulin(EREG),and cytokine interleukin-18(IL-18)gene,exhibited an enriched erythroblastic leukemia viral oncogene homolog(ErbB)signaling pathway,and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics.We also found metabolic changes in Mono 0 and Mono 5,including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1(HIF-1)signaling pathway.Notably,one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples.In conclusion,our study discovered two novel severedisease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19.Overall,this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.展开更多
The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019(COVID-19).Data on 104 patients admitted to hospit...The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019(COVID-19).Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected.Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients.The least absolute shrinkage and selection operator(LASSO)logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients.The concordance index(C-index)was used to assess the discrimination of the model,and internal validation was performed through bootstrap resampling.A novel predictive nomogram was constructed by incorporating these features.Of the 104 patients included in the study(median age 55 years),75(72.1%)had improved short-term outcomes,while 29(27.9%)showed no signs of improvement.There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes.After a multi-step screening process,prognostic factors were selected and incorporated into the nomogram construction,including immunoglobulin A(IgA),C-reactive protein(CRP),creatine kinase(CK),acute physiology and chronic health evaluation II(APACHE II),and interaction between CK and APACHE II.The C-index of our model was 0.962(95%confidence interval(CI),0.931-0.993)and still reached a high value of 0.948 through bootstrapping validation.A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve.The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient,which may facilitate personalized counselling and treatment.展开更多
This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and co...This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and consensuses.The Chinese Society of Hepatology,Chinese Medical Association(CMA)and the Society of Infectious Diseases,CMA organized relevant native experts to establish this Guideline of Prevention and Treatment for Chronic Hepatitis B(1st version)in 2005,and made the first revision in 2010.In the past 5 years,great progress has been made in the native and foreign fundamental and clinical research with respect to CHB,necessitating additional revision of this guideline.展开更多
Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China...Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.展开更多
Background and Aims:It is critical but challenging to predict the prognosis of hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).This study systematically summarized and evaluated the quality and perf...Background and Aims:It is critical but challenging to predict the prognosis of hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).This study systematically summarized and evaluated the quality and performance of available clinical prediction models(CPMs).Methods:A keyword search of articles on HBV-ACLF CPMs published in PubMed from January 1995 to April 2020 was performed.Both the quality and performance of the CPMs were assessed.Results:Fifty-two CPMs were identified,of which 31 were HBV-ACLF specific.The modeling data were mostly derived from retrospective(83.87%)and single-center(96.77%)cohorts,with sample sizes ranging from 46 to 1,202.Three-month mortality was the most common endpoint.The Asian Pacific Association for the Study of the Liver consensus(51.92%)and Chinese Medical Association liver failure guidelines(40.38%)were commonly used for HBV-ACLF diagnosis.Serum bilirubin(67.74%),the international normalized ratio(54.84%),and hepatic encephalopathy(51.61%)were the most frequent variables used in models.Model discrimination was commonly evaluated(88.46%),but model calibration was seldom performed.The model for end-stage liver disease score was the most widely used(84.62%);however,varying performance was reported among the studies.Conclusions:Substantial limitations lie in the quality of HBV-ACLF-specific CPMs.Disease severity of study populations may impact model performance.The clinical utility of CPMs in predicting short-term prognosis of HBV-ACLF remains to be undefined.展开更多
Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin...Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice.Methods:In this prospective,multicenter,observational,non-interventional cohort study,patients were assessed for up to 1 year after peg-IFNαtreatment cessation.Treating physicians established the dosing and treatment duration according to Chinese clinical practice.Effectiveness of peg-IFNαtreatment was measured by the percentage of:patients with HBV DNA<2000 IU/mL and loss of hepatitis B surface antigen(commonly known as HBsAg);HBV DNA level at end of treatment(EOT),and 6 months and 1 year posttreatment;and time course change in quantitative HBV DNA and HBsAg.Results:At EOT,6 months posttreatment,and 1 year posttreatment,the percentage of patients with HBV DNA<2000 IU/mL was 90.0%,81.8%,and 82.2%,and that of patients with HBsAg loss was 6.5%,9.4%,and 9.5%,respectively.The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment.The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment.The incidence of adverse events was 52.0%.Conclusions:Peg-IFNαhas the potential to provide functional cure(HBsAg loss)for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China.展开更多
Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease.As a dengue non-endemic country,China has experienced several dengue outbreaks in recent years.However,dengue patients in China display c...Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease.As a dengue non-endemic country,China has experienced several dengue outbreaks in recent years.However,dengue patients in China display clinical characteristics that are distinct from those of patients in dengue-endemic countries.To standardize the diagnosis and treatment of dengue fever,the experts at the Society of Infectious Diseases,Society of Tropical Medicine and Parasitology of the Chinese Medical Association,and the Society of Emergency Medicine of China Association of Chinese Medicine have developed a guideline after reviewing the following guidelines and data:guidelines for diagnosis,treatment,prevention,and control of dengue(World Health Organization,2009);the guidelines for diagnosis and treatment of dengue(National Health and Family Planning Commission of the People’s Republic of China,2014,Edition 2);health industry standard of the People’s Republic of China“diagnosis for dengue fever(WS216-2018)”;and systemic reports on dengue.The new guideline includes eight aspects:introduction,terminology,epidemiology and prevention,etiology and pathogenesis,clinical features,diagnosis,treatment,and problems to be solved.展开更多
End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decom...End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decompensation.Consequently,infections are among the most common complications of disease progression.There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus.This consensus assembled up-to-date knowledge and experience across Chinese colleagues,providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.展开更多
Background:Bacterial infections are common in patients with decompensated cirrhosis,largely owing to bacterial translocation and cirrhosis-associated immune dysfunction.This study aims to determine the reliability for...Background:Bacterial infections are common in patients with decompensated cirrhosis,largely owing to bacterial translocation and cirrhosis-associated immune dysfunction.This study aims to determine the reliability for classifying infections in patients with decompensated cirrhosis based on the Centers for Disease Control and Prevention(CDC)criteria.Methods:The patients with decompensated cirrhosis with suspicious infection in a registered prospective cohort of cirrhosis from May 1,2014 to February 25,2015 in the ward of First Affiliated Hospital of Zhejiang University were retrospectively identified.Agreement assessment was conducted focusing on site of infection,the possibility of infection,and pathogens of infection on both system level and specific diagnosis level.A subgroup analysis was performed based on with/without acute-on-chronic liver failure(ACLF).Results:A total of 402 infectious episodes among 351 patients were enrolled for consistency analysis.The overall agreement for site of infection was 94%(378/402)(k=0.90,95%CI 0.86–0.94)on system level and 86%(346/402)(k=0.84,95%CI 0.80–0.88)on specific diagnosis level.On possibility of infection,the overall agreement was 81%(306/378)(weighted k=0.71,95%CI 0.65–0.77),with 84%(224/267)(weighted k=0.75,95%CI 0.63–0.87)in patients with ACLF and 80%(70/88)(weighted k=0.68,95%CI 0.60–0.76)in patients without ACLF,respectively.On pathogens of infection,the overall agreement was 72%(60/83)(k=0.70,95%CI 0.60–0.80)among most frequent infections.Conclusion:The agreement for classifying infections in patients with decompensated cirrhosis based on CDC criteria is acceptable overall,suggesting that it can be a useful tool for clinical management in patients with decompensated cirrhosis with suspicious infections.展开更多
The current epidemic situation of coronavirus disease 2019(COVID-19)still remains severe.As the National Clinical Research Center for Infectious Diseases,The First Affiliated Hospital of the Zhejiang University School...The current epidemic situation of coronavirus disease 2019(COVID-19)still remains severe.As the National Clinical Research Center for Infectious Diseases,The First Affiliated Hospital of the Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang Province.Based on the present expert consensus carried out by the National Health Commission and National Administration of Traditional Chinese Medicine,our team summarized and established an effective treatment strategy centered on“Four-Anti and Two-Balance”for clinical practice.The“Four-Anti and Two-Balance”strategy includes antivirus,anti-shock,antihypoxemia,and anti-secondary infection,and maintaining of water,electrolyte and acid/base balance and microecological balance.Simultaneously,an integrated multidisciplinary personalized treatment is recommended to improve therapeutic effects.The importance of early viral detection,dynamic monitoring of inflammatory indexes,and chest radiographs has been emphasized in clinical decision-making.Sputum was observed with the highest positive rate by reverse transcription-polymerase chain reaction(RTPRC).Viral nucleic acids could be detected in 10%of the patients’blood samples at the acute phase and 50%of patients had positive RT-PCR results in their feces.We also isolated live viral strains from feces,indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identify cytokine storms and for the application of the artificial liver blood purification system.The“Four-Anti and Two-Balance”strategy effectively increased cure rates and reduced mortality.Early antiviral treatment alleviated disease severity and prevented illness progression.We found that lopinavir/ritonavir combined with abidol showed antiviral effects against COVID-19.Shock and hypoxemia were usually caused by cytokine storms.The artificial liver blood purification system was able to rapidly remove inflammatory mediators and block the cytokine storm.Moreover,it also contributed to the balance of fluids,electrolytes,and acids/bases and thus improved treatment efficacy during critical illness.For cases of severe illness,early and also short periods of moderate glucocorticoid administration was supported.Patients with an oxygenation index below 200mmHg were transferred to the intensive care unit.Conservative oxygen therapy was preferred and noninvasive ventilation(NIV)was not recommended.Patients with mechanical ventilation were strictly supervised with cluster ventilator-associated pneumonia prevention strategies.Antimicrobial prophylaxis was prescribed rationally and was not recommended,except for patients with a long course of disease,repeated fever,and elevated procalcitonin,similarly secondary fungal infections were of concern.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased genus such as Lactobacillus and Bifidobacterium.Nutritional and gastrointestinal function should;therefore,be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infections due to bacterial translocation.Anxiety and fear were common in patients with COVID-19.Therefore,we established a dynamic assessment and warning for psychological crises.We also integrated Chinese medicine in the treatment to promote rehabilitation.We optimized nursing processes for severe patients to promote their rehabilitation.Since viral clearance patterns after severe acute respiratory syndrome coronavirus 2 infections remained unclear,2 weeks quarantine for discharged patients was required,and a regular following-up was also needed.These Zhejiang experiences and suggestions have been implemented in our center and achieved good results.However,since COVID-19 was a newly emerging disease,more work is warranted to further improve strategies of prevention,diagnosis,and treatment for COVID-19.展开更多
基金supported by the National Science and Technology Major Project(2017ZX10204401001002)the National Key Research and Development Project of China(2017ZX10204401001002008)+1 种基金the Key Research and Development Project of Zhejiang Province(2020C03123)Zhejiang Provincial Nature Science Foundation of China(LED20H19001)。
文摘Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019(COVID-19)is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity.In this study,we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19samples including severe,moderate,and convalescent samples from three severely/critically ill and four moderately ill patients.We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19,with an increased proportion of monocytes and seriously reduced diversity.In addition,we discovered two novel severe-disease-specific monocyte subsets:Mono 0 and Mono 5.These subsets expressed amphiregulin(AREG),epiregulin(EREG),and cytokine interleukin-18(IL-18)gene,exhibited an enriched erythroblastic leukemia viral oncogene homolog(ErbB)signaling pathway,and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics.We also found metabolic changes in Mono 0 and Mono 5,including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1(HIF-1)signaling pathway.Notably,one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples.In conclusion,our study discovered two novel severedisease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19.Overall,this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.
基金supported by the research on the prevention and clinical treatment in patients with COVID-19(2020C03123)a funding of the Zhejiang Provincial Department of Science and Technology+1 种基金the National Natural Science Foundation of China(81790631)the National Key Research and Development Program of China(2018YFC2000500).
文摘The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019(COVID-19).Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected.Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients.The least absolute shrinkage and selection operator(LASSO)logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients.The concordance index(C-index)was used to assess the discrimination of the model,and internal validation was performed through bootstrap resampling.A novel predictive nomogram was constructed by incorporating these features.Of the 104 patients included in the study(median age 55 years),75(72.1%)had improved short-term outcomes,while 29(27.9%)showed no signs of improvement.There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes.After a multi-step screening process,prognostic factors were selected and incorporated into the nomogram construction,including immunoglobulin A(IgA),C-reactive protein(CRP),creatine kinase(CK),acute physiology and chronic health evaluation II(APACHE II),and interaction between CK and APACHE II.The C-index of our model was 0.962(95%confidence interval(CI),0.931-0.993)and still reached a high value of 0.948 through bootstrapping validation.A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve.The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient,which may facilitate personalized counselling and treatment.
文摘This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and consensuses.The Chinese Society of Hepatology,Chinese Medical Association(CMA)and the Society of Infectious Diseases,CMA organized relevant native experts to establish this Guideline of Prevention and Treatment for Chronic Hepatitis B(1st version)in 2005,and made the first revision in 2010.In the past 5 years,great progress has been made in the native and foreign fundamental and clinical research with respect to CHB,necessitating additional revision of this guideline.
基金Ascletis BioScience Co.,Ltd.provided financial support for this study
文摘Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.
基金the Chinese National Natural Science Foundation(Nos.81670567 and 81870425)the Fundamental Research Funds for the Central Universities.
文摘Background and Aims:It is critical but challenging to predict the prognosis of hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).This study systematically summarized and evaluated the quality and performance of available clinical prediction models(CPMs).Methods:A keyword search of articles on HBV-ACLF CPMs published in PubMed from January 1995 to April 2020 was performed.Both the quality and performance of the CPMs were assessed.Results:Fifty-two CPMs were identified,of which 31 were HBV-ACLF specific.The modeling data were mostly derived from retrospective(83.87%)and single-center(96.77%)cohorts,with sample sizes ranging from 46 to 1,202.Three-month mortality was the most common endpoint.The Asian Pacific Association for the Study of the Liver consensus(51.92%)and Chinese Medical Association liver failure guidelines(40.38%)were commonly used for HBV-ACLF diagnosis.Serum bilirubin(67.74%),the international normalized ratio(54.84%),and hepatic encephalopathy(51.61%)were the most frequent variables used in models.Model discrimination was commonly evaluated(88.46%),but model calibration was seldom performed.The model for end-stage liver disease score was the most widely used(84.62%);however,varying performance was reported among the studies.Conclusions:Substantial limitations lie in the quality of HBV-ACLF-specific CPMs.Disease severity of study populations may impact model performance.The clinical utility of CPMs in predicting short-term prognosis of HBV-ACLF remains to be undefined.
基金The authors wish to thank all of the investigators and participating study sites,which are listed in Supplemental Table 1,as well as all the patients who participated in this studyThe authors also wish to thank Michelle Belanger,MD,of Edanz Medical Writing for providing medical writing assistance,which was funded by Shanghai Roche Pharmaceuticals Ltd.The study was funded by Shanghai Roche Pharmaceuticals Ltd
文摘Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice.Methods:In this prospective,multicenter,observational,non-interventional cohort study,patients were assessed for up to 1 year after peg-IFNαtreatment cessation.Treating physicians established the dosing and treatment duration according to Chinese clinical practice.Effectiveness of peg-IFNαtreatment was measured by the percentage of:patients with HBV DNA<2000 IU/mL and loss of hepatitis B surface antigen(commonly known as HBsAg);HBV DNA level at end of treatment(EOT),and 6 months and 1 year posttreatment;and time course change in quantitative HBV DNA and HBsAg.Results:At EOT,6 months posttreatment,and 1 year posttreatment,the percentage of patients with HBV DNA<2000 IU/mL was 90.0%,81.8%,and 82.2%,and that of patients with HBsAg loss was 6.5%,9.4%,and 9.5%,respectively.The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment.The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment.The incidence of adverse events was 52.0%.Conclusions:Peg-IFNαhas the potential to provide functional cure(HBsAg loss)for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China.
基金supported byNational KeyR&DProgramof China(2020YFC1200100)National Science and Technology Major Project of China(2017ZX10305501-003)+2 种基金Special Program of Science and Technology of Guangdong Province(2013A020229001,2013A020229002)The Major Program of Guangzhou Healthcare Collaborative Innovation(201508020263,201803040006)Pilot Project of Guangzhou Clinical Medicine Research And Transformation Center(2014Y2-00550).
文摘Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease.As a dengue non-endemic country,China has experienced several dengue outbreaks in recent years.However,dengue patients in China display clinical characteristics that are distinct from those of patients in dengue-endemic countries.To standardize the diagnosis and treatment of dengue fever,the experts at the Society of Infectious Diseases,Society of Tropical Medicine and Parasitology of the Chinese Medical Association,and the Society of Emergency Medicine of China Association of Chinese Medicine have developed a guideline after reviewing the following guidelines and data:guidelines for diagnosis,treatment,prevention,and control of dengue(World Health Organization,2009);the guidelines for diagnosis and treatment of dengue(National Health and Family Planning Commission of the People’s Republic of China,2014,Edition 2);health industry standard of the People’s Republic of China“diagnosis for dengue fever(WS216-2018)”;and systemic reports on dengue.The new guideline includes eight aspects:introduction,terminology,epidemiology and prevention,etiology and pathogenesis,clinical features,diagnosis,treatment,and problems to be solved.
文摘End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decompensation.Consequently,infections are among the most common complications of disease progression.There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus.This consensus assembled up-to-date knowledge and experience across Chinese colleagues,providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.
基金This work was supported by Chinese National Natural Science Foundation(No.81870425)the 13-5 State S&T Projects of China(2018ZX10302-206)and Fundamental Research Funds for the Central Universities.
文摘Background:Bacterial infections are common in patients with decompensated cirrhosis,largely owing to bacterial translocation and cirrhosis-associated immune dysfunction.This study aims to determine the reliability for classifying infections in patients with decompensated cirrhosis based on the Centers for Disease Control and Prevention(CDC)criteria.Methods:The patients with decompensated cirrhosis with suspicious infection in a registered prospective cohort of cirrhosis from May 1,2014 to February 25,2015 in the ward of First Affiliated Hospital of Zhejiang University were retrospectively identified.Agreement assessment was conducted focusing on site of infection,the possibility of infection,and pathogens of infection on both system level and specific diagnosis level.A subgroup analysis was performed based on with/without acute-on-chronic liver failure(ACLF).Results:A total of 402 infectious episodes among 351 patients were enrolled for consistency analysis.The overall agreement for site of infection was 94%(378/402)(k=0.90,95%CI 0.86–0.94)on system level and 86%(346/402)(k=0.84,95%CI 0.80–0.88)on specific diagnosis level.On possibility of infection,the overall agreement was 81%(306/378)(weighted k=0.71,95%CI 0.65–0.77),with 84%(224/267)(weighted k=0.75,95%CI 0.63–0.87)in patients with ACLF and 80%(70/88)(weighted k=0.68,95%CI 0.60–0.76)in patients without ACLF,respectively.On pathogens of infection,the overall agreement was 72%(60/83)(k=0.70,95%CI 0.60–0.80)among most frequent infections.Conclusion:The agreement for classifying infections in patients with decompensated cirrhosis based on CDC criteria is acceptable overall,suggesting that it can be a useful tool for clinical management in patients with decompensated cirrhosis with suspicious infections.
基金This study was supported by the Zhejiang Provincial Key Research and Development Program(2020C03123).
文摘The current epidemic situation of coronavirus disease 2019(COVID-19)still remains severe.As the National Clinical Research Center for Infectious Diseases,The First Affiliated Hospital of the Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang Province.Based on the present expert consensus carried out by the National Health Commission and National Administration of Traditional Chinese Medicine,our team summarized and established an effective treatment strategy centered on“Four-Anti and Two-Balance”for clinical practice.The“Four-Anti and Two-Balance”strategy includes antivirus,anti-shock,antihypoxemia,and anti-secondary infection,and maintaining of water,electrolyte and acid/base balance and microecological balance.Simultaneously,an integrated multidisciplinary personalized treatment is recommended to improve therapeutic effects.The importance of early viral detection,dynamic monitoring of inflammatory indexes,and chest radiographs has been emphasized in clinical decision-making.Sputum was observed with the highest positive rate by reverse transcription-polymerase chain reaction(RTPRC).Viral nucleic acids could be detected in 10%of the patients’blood samples at the acute phase and 50%of patients had positive RT-PCR results in their feces.We also isolated live viral strains from feces,indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identify cytokine storms and for the application of the artificial liver blood purification system.The“Four-Anti and Two-Balance”strategy effectively increased cure rates and reduced mortality.Early antiviral treatment alleviated disease severity and prevented illness progression.We found that lopinavir/ritonavir combined with abidol showed antiviral effects against COVID-19.Shock and hypoxemia were usually caused by cytokine storms.The artificial liver blood purification system was able to rapidly remove inflammatory mediators and block the cytokine storm.Moreover,it also contributed to the balance of fluids,electrolytes,and acids/bases and thus improved treatment efficacy during critical illness.For cases of severe illness,early and also short periods of moderate glucocorticoid administration was supported.Patients with an oxygenation index below 200mmHg were transferred to the intensive care unit.Conservative oxygen therapy was preferred and noninvasive ventilation(NIV)was not recommended.Patients with mechanical ventilation were strictly supervised with cluster ventilator-associated pneumonia prevention strategies.Antimicrobial prophylaxis was prescribed rationally and was not recommended,except for patients with a long course of disease,repeated fever,and elevated procalcitonin,similarly secondary fungal infections were of concern.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased genus such as Lactobacillus and Bifidobacterium.Nutritional and gastrointestinal function should;therefore,be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infections due to bacterial translocation.Anxiety and fear were common in patients with COVID-19.Therefore,we established a dynamic assessment and warning for psychological crises.We also integrated Chinese medicine in the treatment to promote rehabilitation.We optimized nursing processes for severe patients to promote their rehabilitation.Since viral clearance patterns after severe acute respiratory syndrome coronavirus 2 infections remained unclear,2 weeks quarantine for discharged patients was required,and a regular following-up was also needed.These Zhejiang experiences and suggestions have been implemented in our center and achieved good results.However,since COVID-19 was a newly emerging disease,more work is warranted to further improve strategies of prevention,diagnosis,and treatment for COVID-19.
