Fulminant myocarditis(FM) has unacceptable high mortality. This study aimed to evaluate the therapeutic efficacy of a life support-based comprehensive treatment regimen(LSBCTR), a completely novel treatment regimen, f...Fulminant myocarditis(FM) has unacceptable high mortality. This study aimed to evaluate the therapeutic efficacy of a life support-based comprehensive treatment regimen(LSBCTR), a completely novel treatment regimen, for FM. A total of 169 FM patients recruited from January 2008 to December 2018 were divided into two groups: patients receiving LSBCTR(81 cases),which includes(i) mechanical life support(positive pressure respiration, intra-aortic balloon pump with or without extracorporeal membrane oxygenation),(ii) immunomodulation therapy using sufficient doses of glucocorticoids and immunoglobulins, and(iii) application of neuraminidase inhibitors, and those receiving conventional treatment(88 cases). The endpoints were in-hospital death and heart-transplantation. Of all the population, 44 patients(26.0%) died in hospitals. Inhospital mortality was 3.7%(3/81) for LSBCTR group and 46.6%(41/88) for traditional treatment(P<0.001). Early application of LSBCTR, mechanical life support, neuraminidase inhibitors, and immunomodulation therapy significantly contributed to reduction in in-hospital mortality. This study describes a novel treatment regimen for FM patients that dramatically reduces inhospital mortality. Its generalization and clinical application will efficiently save lives although further optimization is needed.This study offers an insight that virus infection induced inflammatory waterfall results in cardiac injury and cardiogenic shock and is the therapeutic target.展开更多
AIM:To compare the incidence of early portal or splenic vein thrombosis(PSVT) in patients treated with irregular and regular anticoagulantion after splenectomy with gastroesophageal devascularization.METHODS:We retros...AIM:To compare the incidence of early portal or splenic vein thrombosis(PSVT) in patients treated with irregular and regular anticoagulantion after splenectomy with gastroesophageal devascularization.METHODS:We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010.Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation,respectively.Group A(153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin(LMWH) irregularly.Group B(148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery,followed by oral warfarin and aspirin for one month regularly.The target prothrombin time/international normalized ratio(PT/INR) was 1.25-1.50.Platelet and PT/INR were monitored.Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy.RESULTS:The patients' data were collected and analyzed retrospectively.Among the patients,94 developed early postoperative mural PSVT,including 63 patients in group A(63/153,41.17%) and 31 patients in group B(31/148,20.94%).There were 50(32.67%) patients in group A and 27(18.24%) in group B with mural PSVT in the main trunk of portal vein.After the administration of thrombolytic,anticoagulant and antiaggregation therapy,complete or partial thrombus dissolution achieved in 50(79.37%) in group A and 26(83.87%) in group B.CONCLUSION:Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization,and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy.Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT.展开更多
Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-on...Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock,with mortality rates as high as 50%–70%. Most importantly, there are no treatment options, guidelines or an expert consensus statement. Here, we provide the first expert consensus, the Chinese Society of Cardiology Expert Consensus Statement on the Diagnosis and Treatment of Fulminant Myocarditis, based on data from our recent clinical trial(NCT03268642). In this statement, we describe the clinical features and diagnostic criteria of fulminant myocarditis, and importantly, for the first time,we describe a new treatment regimen termed life support-based comprehensive treatment regimen. The core content of this treatment regimen includes(i) mechanical life support(applications of mechanical respirators and circulatory support systems,including intraaortic balloon pump and extracorporeal membrane oxygenation),(ii) immunological modulation by using sufficient doses of glucocorticoid, immunoglobulin and(iii) antiviral reagents using neuraminidase inhibitor. The proper application of this treatment regimen may and has helped to save the lives of many patients with fulminant myocarditis.展开更多
Advanced intrahepatic cholangiocarcinoma(ICC)has a dismal prognosis.Here,we report the efficacy and safety of combining toripalimab,lenvatinib,and gemcitabine plus oxaliplatin(GEMOX)as first-line therapy for advanced ...Advanced intrahepatic cholangiocarcinoma(ICC)has a dismal prognosis.Here,we report the efficacy and safety of combining toripalimab,lenvatinib,and gemcitabine plus oxaliplatin(GEMOX)as first-line therapy for advanced ICC.Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine(1 g/m2)on Days 1 and 8 and oxaliplatin(85 mg/m2)Q3W for six cycles along with intravenous toripalimab(240 mg)Q3W and oral lenvatinib(8 mg)once daily for one year.The expression of programmed death-ligand 1(PD-L1)and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing(WES)analysis.The primary endpoint was the objective response rate(ORR).Secondary outcomes included safety,overall survival(OS),progression-free survival(PFS),disease control rate(DCR)and duration of response(DoR).As of July 1,2022,the median follow-up time was 23.5 months,and the ORR was 80%.Twenty-three patients achieved partial response,and one achieved complete response.Patients(21/30)with DNA damage response(DDR)-related gene mutations showed a higher ORR,while patients(14/30)with tumor area positivity≥1(PD-L1 staining)showed a trend of high ORR,but without significant difference.The median OS,PFS,and DoR were 22.5,10.2,and 11.0 months,respectively.The DCR was 93.3%.Further,56.7%of patients experienced manageable grade≥3 adverse events(AEs),commonly neutropenia(40.0%)and leukocytopenia(23.3%).In conclusion,toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC.A phase-III,multicenter,double-blinded,randomized study to validate our findings was approved by the National Medical Products Administration(NMPA,No.2021LP01825).展开更多
Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcit...Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcitabine,and oxaliplatin)regimen in advanced NKTL.Nine patients underwent six 21-day cycles of anti-PD-1 antibody(day 1),pegaspargase 2000 U/m2(day 1),gemcitabine 1 g/m2(days 1 and 8)and oxaliplatin 130 mg/m2(day 1),followed by anti-PD-1 antibody maintenance every 3 weeks.Programmed death-ligand 1(PD-L1)expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing(NGS)analysis.Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography(18FDG-PET)and computed tomography or magnetic resonance imaging.Eight patients exhibited significant responses,comprising of seven complete remissions and one partial remission(overall response rate:88.9%).After a median follow-up of 10.6 months,6/9 patients(66.7%)remained in complete remission.The most common grade 3/4 adverse events were anemia(33.3%),neutropenia(33.3%),and thrombocytopenia(33.3%);all of which were manageable and resolved.Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression(5/6,83.3%).NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy.Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D,TET2,and BCORL1 might indicate a poor response to immunochemotherapy.In conclusion,the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL.PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.展开更多
Background Acute severe biliary pancreatitis （ASBP） is a severe and fatal disease, and the expenditure is huge and therapeutic effects are still not satisfactory. This study aimed to improve the therapeutic effects ...Background Acute severe biliary pancreatitis （ASBP） is a severe and fatal disease, and the expenditure is huge and therapeutic effects are still not satisfactory. This study aimed to improve the therapeutic effects and reduce the expenditure of ASBP treatment.Methods One hundred and five patients diagnosed with ASBP were referred to our department from January 2004 to July 2009. Diagnosis was based on the 2007 criteria of the Chinese Society of Surgery. Patients were divided into two groups; the E group： 50 patients who underwent endoscopic retrograde choledochopancreatography （ERCP） ＋ endoscopic sphincterotomy （EST） ＋ endoscopic lithotripsy basket （ESR） ＋endoscopic retrograde biliary drainage （ERBD）and enteral nutrition （EN）, and the R group： 55 patients who underwent traditional treatment without ERCP. Subsequently,subjective symptoms, signs, biochemical analysis, serum endotoxin, tumor necrosis factor a, grades by computed tomography （CT）, cost of hospitalization and length of stay were compared between the two groups.Results All enrolled patients complied well with all therapeutic regimens. Endoscopic therapy that combined EN could significantly improve symptoms, clinical signs, laboratory values, tumor necrosis factor a and endotoxin while significantly reducing hospital expenditure and length of hospital stay. The experimental findings revealed that there were obvious advantages in the E group compared with the R group.Conclusions Endoscopic therapy combined with EN is an effective, safe and economic therapeutic regimen of ASBP.展开更多
AIM To investigate predictive and prognostic value of serum alpha-fetoprotein(AFP) level and its dynamic changes in patients with advanced gastric cancer with elevated serum AFP(AFPAGC).METHODS One hundred and five pa...AIM To investigate predictive and prognostic value of serum alpha-fetoprotein(AFP) level and its dynamic changes in patients with advanced gastric cancer with elevated serum AFP(AFPAGC).METHODS One hundred and five patients with AFPAGC were enrolled in the study, and all of them underwent at least one cycle of systemic chemotherapy at our institute and had serum AFP ≥ 20 ng/m L at diagnosis or recurrence. Clinicopathologic features, serum AFP level at diagnosis and changes during treatment, first-line chemotherapy regimens, efficacy and toxicity, and survival information were collected. A Person's χ~2 or Fisher's exact test was used to measure the differences between variables. Survival prognostic factors were investigated using the Kaplan-Meier method and Cox regression.RESULTS Median serum AFP level was 161.7 ng/m L(range, 22.9-2557110 ng/m L). Objective response rates(ORR) was significantly lower in the AFP ≥ 160 ng/m L group than in the AFP < 160 ng/m L group(30.4% vs 68.3%, P < 0.001). ORR to doublet regimens was significantly lower in the AFP ≥ 160 ng/m L group, whereas ORR to triplet regimens was similar between the two groups. Liver metastasis rate was significantly higher in the AFP ≥ 160 ng/m L group than in the AFP < 160 ng/m L(69.8% vs 50.0%, P < 0.001). Overall survival(OS) in the two cohorts did not show any significant difference(P = 0.712). Dynamic changes of AFP were consistent with response to chemotherapy, and median OS of patients with a serum AFP decline ≥ 50% and those with a serum AFP decline < 50% was 17.5 m and 10.0 m, respectively(P = 0.003). Hepatic(P = 0.005), peritoneal(P < 0.001), non-regional lymph node metastasis(P < 0.001), and portal vein tumor thrombus(PVTT)(P = 0.042) were identified as independent prognostic factors for AFPAGC. CONCLUSION Real-time examination of AFP has great predictive and prognostic value for managing AFPAGC. For those with markedly elevated AFP, triplet regimens may be a better choice.展开更多
AIM To evaluate the outcomes of furazolidone-and amoxicillin-based quadruple therapy for treatment of Helicobacter pylori(H. pylori) infection and identify predictors of failed eradication.METHODS Patients with H. pyl...AIM To evaluate the outcomes of furazolidone-and amoxicillin-based quadruple therapy for treatment of Helicobacter pylori(H. pylori) infection and identify predictors of failed eradication.METHODS Patients with H. pylori infection treated with furazolidone, amoxicillin, bismuth, and proton pump inhibitor therapy(January 2015 to December 2015) who received the ^(13)C-urea breath test > 4 wk after treatment were evaluated. Demographic and clinical data including prior H. pylori treatment attempts, medication adherence, alcohol and cigarette consumption during therapy, and treatment-related adverse events were recorded by reviewing medical records and telephone surveys. H. pylori eradication rates for overall and subgroups were evaluated. Multivariate analysis was performed to identify independent predictors of failed H. pylori eradication.RESULTS Of the 992 patients treated and retested for H. pylori infection, the overall eradication rate was 94.5% [95% confidence interval(CI): 94.1%-95.9%]. H. pylori eradication rate of primary therapy was 95.0%(95%CI: 93.5%-96.5%), while that of rescue therapy was 91.3%(95%CI: 86.8%-95.8%). Among the 859 patients who completed the study protocol, 144(17%) reported treatment-related adverse events including 24(3%) leading to premature discontinuation. On multivariate analysis, poor medication adherence [adjusted odds ratio(AOR) = 6.7, 95%CI: 2.8-15.8], two or more previous H. pylori treatments(AOR = 7.4, 95%CI: 2.2-24.9), alcohol consumption during therapy(AOR = 4.4, 95%CI: 1.5-12.3), and possibly smoking during therapy(AOR = 1.9, 95%CI: 0.9-4.3) were associated with failed H. pylori eradication. CONCLUSION Furazolidone-and amoxicillin-based quadruple therapy for H. pylori infection in an area with a high prevalence of clarithromycin resistance demonstrated high eradication rates as primary and rescue therapies with a favorable safety profile. Patient education targeting abstinence from alcohol during therapy and strict medication adherence may further optimize H. pylori eradicat展开更多
Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combinat...Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents(DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5 A inhibitors and HCV NS5 B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatmentnave patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in nullresponders and in patients with cirrhosis. Interferonfree regimens in combination with ribavirin and/or two or more DAAs could be used for treatment-nave, treatm展开更多
To review possible mechanisms and therapeutics for acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, se...To review possible mechanisms and therapeutics for acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide(NO) through the inducible NO synthase(i NOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In con-scious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.展开更多
Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus ca...Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine(XELOX)and epirubicin,oxaliplatin,plus capecitabine(EOX)regimens in treating AGC.Methods:This phase III trial enrolled previously untreated patients with AGC whowere randomly assigned to receive the XELOXor EOXregimen.The primary endpoint was non-inferiority in progression-free survival(PFS)for XELOX as compared with EOX on an intention-to-treat basis.Results:Between April 10,2015 andAugust 20,2020,448AGCpatientswere randomized to receive XELOX(n=222)or EOX(n=226).The median PFS(mPFS)was 5.0 months(95%confidence interval[CI]=4.5-6.0 months)in the XELOX arm and 5.5 months(95%CI=5.0-6.0 months)in the EOX arm(hazard ratio[HR]=0.989,95%CI=0.812-1.203;P_(non-inferiority)=0.003).There was no significant difference inmedian overall survival(mOS)(12.0 vs.12.0months,P=0.384)or objective response rate(37.4%vs.45.1%,P=0.291)between the two groups.In patients with poorly differentiated adenocarcinoma and liver metastasis,the EOX arm had a significantly longer mOS(P=0.021)and a trend of longer mPFS(P=0.073)than the XELOX arm.The rate of grade 3/4 adverse events(AEs)was 42.2%(90/213)in the XELOX arm and 72.5%(156/215)in the EOX arm(P=0.001).The global health-related quality of life(QoL)score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy.Conclusions:This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients.However,the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.展开更多
Background A phase Ⅲ trial involving docetaxel, cisplatin, and fluorouracil （DCF） in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but wi...Background A phase Ⅲ trial involving docetaxel, cisplatin, and fluorouracil （DCF） in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but with a high rate of hematologic toxicity. To reduce toxicity while maintaining the efficacy of DCF, we reduced the doses of docetaxel （D） and cis-platinum （CDDP）, and administered 5-fluorouracil （5-FU） via a continuous intravenous （CIV） infusion.Methods Chemotherapy-naive patients with gastric adenocarcinomas received D （60 mg/m2 1 hour on day 1）, CDDP （30 mg/m2on days 1 and 2）, and 5-FU （1500 mg·m-2·24 h-1 CIV on days 1 and 8 every 3 weeks）. The primary endpoint was the response rate.Results Fourteen patients were enrolled. Based on the efficacy evaluation following at least 2 cycles of treatment, there was 7.1% complete remission （CR）, 71% partial remission （PR）, 14% stable disease （NC/SD）, and 7.1% progressive disease （PD）. The median survival time was 13 months. Nine patients （64%） had grade Ⅲ-Ⅳ neutropenia, and 4 patients （29%） had grade Ⅳ neutropenia, among whom 1 had grade Ⅳ neutropenia with grade Ⅲ nausea and vomiting.Conclusion The modified DCF regimen is highly active and has a favorable toxicity profile in Chinese patients with gastric cancer.展开更多
基金supported by the National Basic Research Program of China (2012CB518004)the key project of the National Natural Science Foundation of China (81630010, 81790624)National Key Research and Development Program of China (SQ2017YFSF090157)
文摘Fulminant myocarditis(FM) has unacceptable high mortality. This study aimed to evaluate the therapeutic efficacy of a life support-based comprehensive treatment regimen(LSBCTR), a completely novel treatment regimen, for FM. A total of 169 FM patients recruited from January 2008 to December 2018 were divided into two groups: patients receiving LSBCTR(81 cases),which includes(i) mechanical life support(positive pressure respiration, intra-aortic balloon pump with or without extracorporeal membrane oxygenation),(ii) immunomodulation therapy using sufficient doses of glucocorticoids and immunoglobulins, and(iii) application of neuraminidase inhibitors, and those receiving conventional treatment(88 cases). The endpoints were in-hospital death and heart-transplantation. Of all the population, 44 patients(26.0%) died in hospitals. Inhospital mortality was 3.7%(3/81) for LSBCTR group and 46.6%(41/88) for traditional treatment(P<0.001). Early application of LSBCTR, mechanical life support, neuraminidase inhibitors, and immunomodulation therapy significantly contributed to reduction in in-hospital mortality. This study describes a novel treatment regimen for FM patients that dramatically reduces inhospital mortality. Its generalization and clinical application will efficiently save lives although further optimization is needed.This study offers an insight that virus infection induced inflammatory waterfall results in cardiac injury and cardiogenic shock and is the therapeutic target.
基金Supported by Grants from Beijing Municipal Health Bureau,No.2011-2-18
文摘AIM:To compare the incidence of early portal or splenic vein thrombosis(PSVT) in patients treated with irregular and regular anticoagulantion after splenectomy with gastroesophageal devascularization.METHODS:We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010.Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation,respectively.Group A(153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin(LMWH) irregularly.Group B(148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery,followed by oral warfarin and aspirin for one month regularly.The target prothrombin time/international normalized ratio(PT/INR) was 1.25-1.50.Platelet and PT/INR were monitored.Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy.RESULTS:The patients' data were collected and analyzed retrospectively.Among the patients,94 developed early postoperative mural PSVT,including 63 patients in group A(63/153,41.17%) and 31 patients in group B(31/148,20.94%).There were 50(32.67%) patients in group A and 27(18.24%) in group B with mural PSVT in the main trunk of portal vein.After the administration of thrombolytic,anticoagulant and antiaggregation therapy,complete or partial thrombus dissolution achieved in 50(79.37%) in group A and 26(83.87%) in group B.CONCLUSION:Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization,and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy.Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT.
基金funded by the National Key Basic Research Project (2012CB518004)Natural Science Fund Key Project (81630010)
文摘Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock,with mortality rates as high as 50%–70%. Most importantly, there are no treatment options, guidelines or an expert consensus statement. Here, we provide the first expert consensus, the Chinese Society of Cardiology Expert Consensus Statement on the Diagnosis and Treatment of Fulminant Myocarditis, based on data from our recent clinical trial(NCT03268642). In this statement, we describe the clinical features and diagnostic criteria of fulminant myocarditis, and importantly, for the first time,we describe a new treatment regimen termed life support-based comprehensive treatment regimen. The core content of this treatment regimen includes(i) mechanical life support(applications of mechanical respirators and circulatory support systems,including intraaortic balloon pump and extracorporeal membrane oxygenation),(ii) immunological modulation by using sufficient doses of glucocorticoid, immunoglobulin and(iii) antiviral reagents using neuraminidase inhibitor. The proper application of this treatment regimen may and has helped to save the lives of many patients with fulminant myocarditis.
基金National Natural Science Foundation of China(81972232,81830102,82150004)Clinical Research Plan of SHDC(SHDC‑2020CR1003A,SHDC-2020CR1022B)+3 种基金National Key Research and Development Program of China(2019YFC1316000,2019YFC1315800,and 2019YFC1315802)the Key Disease Joint Research Program of Xuhui District(XHLHGG202103),the Clinical Medicine Research Pilot Project of Shanghai Medical School of Fudan University(2020,21DGF501035/00)the Shanghai Municipal Natural Science Foundation(20JC1419103,21ZR1412200)Beijing Mutual Care Public Welfare Foundation(GDXZ-08-05)Sanming Project of Medicine in Shenzhen(SZSM202003009),and Shanghai Municipal Key Clinical Specialty Construction Project(shslczdzk02401).
文摘Advanced intrahepatic cholangiocarcinoma(ICC)has a dismal prognosis.Here,we report the efficacy and safety of combining toripalimab,lenvatinib,and gemcitabine plus oxaliplatin(GEMOX)as first-line therapy for advanced ICC.Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine(1 g/m2)on Days 1 and 8 and oxaliplatin(85 mg/m2)Q3W for six cycles along with intravenous toripalimab(240 mg)Q3W and oral lenvatinib(8 mg)once daily for one year.The expression of programmed death-ligand 1(PD-L1)and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing(WES)analysis.The primary endpoint was the objective response rate(ORR).Secondary outcomes included safety,overall survival(OS),progression-free survival(PFS),disease control rate(DCR)and duration of response(DoR).As of July 1,2022,the median follow-up time was 23.5 months,and the ORR was 80%.Twenty-three patients achieved partial response,and one achieved complete response.Patients(21/30)with DNA damage response(DDR)-related gene mutations showed a higher ORR,while patients(14/30)with tumor area positivity≥1(PD-L1 staining)showed a trend of high ORR,but without significant difference.The median OS,PFS,and DoR were 22.5,10.2,and 11.0 months,respectively.The DCR was 93.3%.Further,56.7%of patients experienced manageable grade≥3 adverse events(AEs),commonly neutropenia(40.0%)and leukocytopenia(23.3%).In conclusion,toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC.A phase-III,multicenter,double-blinded,randomized study to validate our findings was approved by the National Medical Products Administration(NMPA,No.2021LP01825).
基金supported by the Chinese National Natural Science Funds(82041009,31925013,31671457,91753139,and 31871405)Zhejiang University Joint Pingduoduo“Virus Infectious Disease Prevention and Control funds”,a special program from the Ministry of Science and Technology of China(2016YFA0502500)+2 种基金Jiangsu Provincial Distinguished Young Scholars award(BK20180043)the Zhejiang Natural Science Fund(LD19C070001),the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003)A project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcitabine,and oxaliplatin)regimen in advanced NKTL.Nine patients underwent six 21-day cycles of anti-PD-1 antibody(day 1),pegaspargase 2000 U/m2(day 1),gemcitabine 1 g/m2(days 1 and 8)and oxaliplatin 130 mg/m2(day 1),followed by anti-PD-1 antibody maintenance every 3 weeks.Programmed death-ligand 1(PD-L1)expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing(NGS)analysis.Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography(18FDG-PET)and computed tomography or magnetic resonance imaging.Eight patients exhibited significant responses,comprising of seven complete remissions and one partial remission(overall response rate:88.9%).After a median follow-up of 10.6 months,6/9 patients(66.7%)remained in complete remission.The most common grade 3/4 adverse events were anemia(33.3%),neutropenia(33.3%),and thrombocytopenia(33.3%);all of which were manageable and resolved.Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression(5/6,83.3%).NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy.Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D,TET2,and BCORL1 might indicate a poor response to immunochemotherapy.In conclusion,the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL.PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.
文摘Background Acute severe biliary pancreatitis （ASBP） is a severe and fatal disease, and the expenditure is huge and therapeutic effects are still not satisfactory. This study aimed to improve the therapeutic effects and reduce the expenditure of ASBP treatment.Methods One hundred and five patients diagnosed with ASBP were referred to our department from January 2004 to July 2009. Diagnosis was based on the 2007 criteria of the Chinese Society of Surgery. Patients were divided into two groups; the E group： 50 patients who underwent endoscopic retrograde choledochopancreatography （ERCP） ＋ endoscopic sphincterotomy （EST） ＋ endoscopic lithotripsy basket （ESR） ＋endoscopic retrograde biliary drainage （ERBD）and enteral nutrition （EN）, and the R group： 55 patients who underwent traditional treatment without ERCP. Subsequently,subjective symptoms, signs, biochemical analysis, serum endotoxin, tumor necrosis factor a, grades by computed tomography （CT）, cost of hospitalization and length of stay were compared between the two groups.Results All enrolled patients complied well with all therapeutic regimens. Endoscopic therapy that combined EN could significantly improve symptoms, clinical signs, laboratory values, tumor necrosis factor a and endotoxin while significantly reducing hospital expenditure and length of hospital stay. The experimental findings revealed that there were obvious advantages in the E group compared with the R group.Conclusions Endoscopic therapy combined with EN is an effective, safe and economic therapeutic regimen of ASBP.
基金Supported by the National Key Research and Development Program of China,No.2017YFC1308900Beijing Natural Science Foundation,No.7161002Capital Health Improvement and Research Funds,No.2016-1-1021
文摘AIM To investigate predictive and prognostic value of serum alpha-fetoprotein(AFP) level and its dynamic changes in patients with advanced gastric cancer with elevated serum AFP(AFPAGC).METHODS One hundred and five patients with AFPAGC were enrolled in the study, and all of them underwent at least one cycle of systemic chemotherapy at our institute and had serum AFP ≥ 20 ng/m L at diagnosis or recurrence. Clinicopathologic features, serum AFP level at diagnosis and changes during treatment, first-line chemotherapy regimens, efficacy and toxicity, and survival information were collected. A Person's χ~2 or Fisher's exact test was used to measure the differences between variables. Survival prognostic factors were investigated using the Kaplan-Meier method and Cox regression.RESULTS Median serum AFP level was 161.7 ng/m L(range, 22.9-2557110 ng/m L). Objective response rates(ORR) was significantly lower in the AFP ≥ 160 ng/m L group than in the AFP < 160 ng/m L group(30.4% vs 68.3%, P < 0.001). ORR to doublet regimens was significantly lower in the AFP ≥ 160 ng/m L group, whereas ORR to triplet regimens was similar between the two groups. Liver metastasis rate was significantly higher in the AFP ≥ 160 ng/m L group than in the AFP < 160 ng/m L(69.8% vs 50.0%, P < 0.001). Overall survival(OS) in the two cohorts did not show any significant difference(P = 0.712). Dynamic changes of AFP were consistent with response to chemotherapy, and median OS of patients with a serum AFP decline ≥ 50% and those with a serum AFP decline < 50% was 17.5 m and 10.0 m, respectively(P = 0.003). Hepatic(P = 0.005), peritoneal(P < 0.001), non-regional lymph node metastasis(P < 0.001), and portal vein tumor thrombus(PVTT)(P = 0.042) were identified as independent prognostic factors for AFPAGC. CONCLUSION Real-time examination of AFP has great predictive and prognostic value for managing AFPAGC. For those with markedly elevated AFP, triplet regimens may be a better choice.
基金Supported by the Zhejiang Science and Technology Project,No.LGF18H160012
文摘AIM To evaluate the outcomes of furazolidone-and amoxicillin-based quadruple therapy for treatment of Helicobacter pylori(H. pylori) infection and identify predictors of failed eradication.METHODS Patients with H. pylori infection treated with furazolidone, amoxicillin, bismuth, and proton pump inhibitor therapy(January 2015 to December 2015) who received the ^(13)C-urea breath test > 4 wk after treatment were evaluated. Demographic and clinical data including prior H. pylori treatment attempts, medication adherence, alcohol and cigarette consumption during therapy, and treatment-related adverse events were recorded by reviewing medical records and telephone surveys. H. pylori eradication rates for overall and subgroups were evaluated. Multivariate analysis was performed to identify independent predictors of failed H. pylori eradication.RESULTS Of the 992 patients treated and retested for H. pylori infection, the overall eradication rate was 94.5% [95% confidence interval(CI): 94.1%-95.9%]. H. pylori eradication rate of primary therapy was 95.0%(95%CI: 93.5%-96.5%), while that of rescue therapy was 91.3%(95%CI: 86.8%-95.8%). Among the 859 patients who completed the study protocol, 144(17%) reported treatment-related adverse events including 24(3%) leading to premature discontinuation. On multivariate analysis, poor medication adherence [adjusted odds ratio(AOR) = 6.7, 95%CI: 2.8-15.8], two or more previous H. pylori treatments(AOR = 7.4, 95%CI: 2.2-24.9), alcohol consumption during therapy(AOR = 4.4, 95%CI: 1.5-12.3), and possibly smoking during therapy(AOR = 1.9, 95%CI: 0.9-4.3) were associated with failed H. pylori eradication. CONCLUSION Furazolidone-and amoxicillin-based quadruple therapy for H. pylori infection in an area with a high prevalence of clarithromycin resistance demonstrated high eradication rates as primary and rescue therapies with a favorable safety profile. Patient education targeting abstinence from alcohol during therapy and strict medication adherence may further optimize H. pylori eradicat
文摘Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents(DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5 A inhibitors and HCV NS5 B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatmentnave patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in nullresponders and in patients with cirrhosis. Interferonfree regimens in combination with ribavirin and/or two or more DAAs could be used for treatment-nave, treatm
基金Supported by Grants from the National Science Council,Far Eastern Medical FoundationTzu Chi Charitable Foundation
文摘To review possible mechanisms and therapeutics for acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide(NO) through the inducible NO synthase(i NOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In con-scious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.
基金National Key Research and Development Program of China,Grant/Award Number:2017YFC1308900The clinical research and cultivation project of shanghai Shenkang hospital development center,Grant/Award Number:SHDC12017×01Sun Yat-sen University Xie Tong Chuang Xin Program,Grant/Award Number:ZLYXXTCX201504。
文摘Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine(XELOX)and epirubicin,oxaliplatin,plus capecitabine(EOX)regimens in treating AGC.Methods:This phase III trial enrolled previously untreated patients with AGC whowere randomly assigned to receive the XELOXor EOXregimen.The primary endpoint was non-inferiority in progression-free survival(PFS)for XELOX as compared with EOX on an intention-to-treat basis.Results:Between April 10,2015 andAugust 20,2020,448AGCpatientswere randomized to receive XELOX(n=222)or EOX(n=226).The median PFS(mPFS)was 5.0 months(95%confidence interval[CI]=4.5-6.0 months)in the XELOX arm and 5.5 months(95%CI=5.0-6.0 months)in the EOX arm(hazard ratio[HR]=0.989,95%CI=0.812-1.203;P_(non-inferiority)=0.003).There was no significant difference inmedian overall survival(mOS)(12.0 vs.12.0months,P=0.384)or objective response rate(37.4%vs.45.1%,P=0.291)between the two groups.In patients with poorly differentiated adenocarcinoma and liver metastasis,the EOX arm had a significantly longer mOS(P=0.021)and a trend of longer mPFS(P=0.073)than the XELOX arm.The rate of grade 3/4 adverse events(AEs)was 42.2%(90/213)in the XELOX arm and 72.5%(156/215)in the EOX arm(P=0.001).The global health-related quality of life(QoL)score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy.Conclusions:This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients.However,the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.
文摘Background A phase Ⅲ trial involving docetaxel, cisplatin, and fluorouracil （DCF） in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but with a high rate of hematologic toxicity. To reduce toxicity while maintaining the efficacy of DCF, we reduced the doses of docetaxel （D） and cis-platinum （CDDP）, and administered 5-fluorouracil （5-FU） via a continuous intravenous （CIV） infusion.Methods Chemotherapy-naive patients with gastric adenocarcinomas received D （60 mg/m2 1 hour on day 1）, CDDP （30 mg/m2on days 1 and 2）, and 5-FU （1500 mg·m-2·24 h-1 CIV on days 1 and 8 every 3 weeks）. The primary endpoint was the response rate.Results Fourteen patients were enrolled. Based on the efficacy evaluation following at least 2 cycles of treatment, there was 7.1% complete remission （CR）, 71% partial remission （PR）, 14% stable disease （NC/SD）, and 7.1% progressive disease （PD）. The median survival time was 13 months. Nine patients （64%） had grade Ⅲ-Ⅳ neutropenia, and 4 patients （29%） had grade Ⅳ neutropenia, among whom 1 had grade Ⅳ neutropenia with grade Ⅲ nausea and vomiting.Conclusion The modified DCF regimen is highly active and has a favorable toxicity profile in Chinese patients with gastric cancer.
