BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resist...BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resistance(HOMA-IR)andβ-cell function(HOMA-β)in patients with T2D in a meta-analysis.METHODS Randomized controlled trials(RCTs)comparing SGLT2 inhibitors to placebo in T2D patients,with a minimum treatment duration of 12 weeks,were searched using the PubMed,EMBASE,and Cochrane Library databases.Risk of bias was assessed using the Cochrane Risk of Bias Tool,and the certainty of evidence was evaluated using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)system.Changes in HOMA-IR and HOMA-βwere the outcomes analyzed.Meta-analyses were performed using a random-effects model by incorporating the potential influences of heterogeneity.RESULTS Of 1388 articles identified,24 RCTs met the inclusion criteria.23 of the included studies were double-blind RCTs with low risk of bias.Pooled results including 2272 patients showed that SGLT2 inhibitors significantly reduced HOMA-IR compared to placebo[mean difference(MD)=-0.81,95%confidence interval(CI):-1.11 to-0.52,P<0.001;I2=82%],indicating reduced insulin resistance.Addi-tionally,meta-analysis with 2845 patients suggested that SGLT2 inhibitors significantly increased HOMA-β(MD=7.90,95%CI:5.44-10.37,P<0.001;I2=74%)compared to placebo in patients with T2D,indicating improvedβ-cell function.Based on GRADE assessment,the certainty of evidence was rated moderate for both outcomes due to heterogeneity.Subgroup analyses showed that HOMA-βincreased more substantially in non-Asian studies than in Asian studies(P for subgroup difference<0.01).Subgroup analyses according to the individual medications of SGLT2 inhibitors all showed significant improvement of HOMA-IR and HOMA-β(P all<0.05).No significant publication bias was detected(P for Egger’s test all>0.05).CONCLUSION SGLT2 inhibitors are associated with improvements in insulin resistance andβ-cell function in patients with T2D,although the certainty of evidence is moderate due to heterogeneity.展开更多
BACKGROUND Cirrhosis is a progressive condition characterized by fibrosis that can lead to severe complications and increased mortality.The mac-2 binding protein glyco-sylation isomer(M2BPGi)is a prominent biomarker f...BACKGROUND Cirrhosis is a progressive condition characterized by fibrosis that can lead to severe complications and increased mortality.The mac-2 binding protein glyco-sylation isomer(M2BPGi)is a prominent biomarker for predicting hepatocellular carcinoma(HCC)and cirrhosis-induced esophageal varices(EV).AIM To investigate thresholds of M2BPGi associated with HCC,EV,and decomp-ensation in patients with cirrhosis.METHODS This was a prospective study.A total of 153 patients with cirrhosis who met the inclusion criteria were enrolled.The patients were diagnosed with HCC and EV according to the Baveno VII and European Association for the Study of the Liver guidelines.Baseline serum M2BPGi levels were assessed along with other routine tests.The data analysis aimed to determine the cutoff values of M2BPGi for pre-dicting EV and HCC.RESULTS In the study 85.6%of patients were Child-Pugh B and C.M2BPGi mean cutoff index was 7.1±3.7,showing no significant etiological differences.However,M2BPGi levels varied significantly among Child-Pugh classes,EV classifications,and between patients with and without HCC(P<0.01).M2BPGi cutoff values for predicting HCC,EV,and decompensated cirrhosis were 6.50,6.64,and 5.25,respectively.Mul-tivariate analysis confirmed M2BPGi as an independent risk factor for EV[adjusted odds ratio(aOR):1.3,95%CI:1.08-1.64]and liver decompensation(aOR:2.11,95%CI:1.37-3.83).Area under the curve of M2BPGi for HCC differ-entiation was 0.71.An algorithm combining alpha-fetoprotein(AFP)and M2BPGi detected 26 of 28 HCC cases with 98.04%accuracy vs 10 cases by AFP alone.CONCLUSION Serum M2BPGi predicted cirrhosis complications,including decompensation and varices,especially in HCC.Combined with AFP,it enhanced HCC detection.Future liver biopsy studies are needed for tissue confirmation.展开更多
BACKGROUND The Mac-2 binding protein glycosylated isomer(M2BPGi)is a serum marker for fibrosis that correlates with the fibrosis stages in various liver diseases.AIM To examine the M2BPGi’s threshold for staging fibr...BACKGROUND The Mac-2 binding protein glycosylated isomer(M2BPGi)is a serum marker for fibrosis that correlates with the fibrosis stages in various liver diseases.AIM To examine the M2BPGi’s threshold for staging fibrosis in patients with chronic hepatitis B(CHB),and its changes during treatment.METHODS This was a prospective,longitudinal study.A total of 348 eligible patients were recruited from the Hepatology Department,Medic Medical Center between March 2020 and December 2023.Liver enzyme tests,platelet counts,M2BPGi levels,and FibroScan were conducted at baseline and at 3-month intervals until six months post-treatment.Correlation plots of M2BPGi,FibroScan,and the other parameters were generated.Receiver operating characteristic curves were constructed for M2BPGi and the other parameters to evaluate their performance.RESULTS M2BPGi levels correlated well with FibroScan results and increased as the fibrosis stage advanced.The median M2BPGi levels at the different stages of fibrosis showed statistically significant differences.The cut-off values of M2BPGi for diagnosing significant fibrosis(F≥2),advanced fibrosis(F3),and cirrhosis(F4)were determined to be 1.08,1.4,and 1.52,respectively.In the context of fibrosis regression in CHB patients during the first 6-month of treatment,M2BPGi levels appeared to decrease before this pattern occurred in the FibroScan results.CONCLUSION M2BPGi levels were strongly correlated with FibroScan.M2BPGi can be used to assess liver fibrosis,and to serve as a tool for monitoring fibrosis regression in CHB patients undergoing treatment.展开更多
BACKGROUND Mac-2 binding protein glycosylation isomer(M2BPGi)serves as a marker of activated hepatic stellate cells and as such holds potential as a biomarker for liver fibrosis.In Viet Nam,metabolic dysfunction-assoc...BACKGROUND Mac-2 binding protein glycosylation isomer(M2BPGi)serves as a marker of activated hepatic stellate cells and as such holds potential as a biomarker for liver fibrosis.In Viet Nam,metabolic dysfunction-associated steatotic liver disease(MASLD)is rising in prevalence and there is an urgent need for better clinical management,particularly in early detection methods that will improve overall prognosis.AIM To examine M2BPGi cut-off values for staging liver fibrosis in patients with MASLD and risk factors associated with disease progression.METHODS A total of 301 individuals with ultrasound-confirmed or FibroScan-confirmed diagnosis of fatty liver were enrolled in the study.The participants were stratified according to fibrosis stage,measured via magnetic resonance elastography.M2-BPGi,Fibrosis-4(FIB-4)Index score,and routine parameters of liver function were assessed to statistically investigate the correlation of M2BPGi levels in various fibrosis stages and to identify risk factors associated with fibrosis severity.RESULTS M2BPGi levels positively correlated with fibrosis stages,with cut-off indexes of 0.57 for F0-1,0.68 for F2-3,and 0.78 for F4.M2BPGi levels in the F0-1 group were significantly different from those in both the F2-3 group(P=0.038)and the F4 group(P=0.0051);the F2-3 and F4 groups did not show a significant difference(P=0.39).Females exhibited significantly higher M2BPGi levels than males for all fibrosis stages,particularly in the F2-3 group(P=0.01)and F4 group(P=0.0006).In the F4(cirrhosis)group,individuals with diabetes had significantly higher M2BPGi levels than those without.M2BPGi,hemoglobin A1c,and FIB-4 score were identified as independent risk factors for greater fibrosis and cirrhosis.CONCLUSION M2BPGi levels varied significantly throughout fibrosis progression,from early MASLD to cirrhosis,with sex correlation.M2BPGi holds promise as an early biomarker for fibrosis characterization in MASLD adult patient populations.展开更多
BACKGROUND Cytomegalovirus(CMV)prophylaxis with valganciclovir and ganciclovir is associated with elevated neutropenia and leukopenia risk in kidney transplant recipients,although the impact of these events on healthc...BACKGROUND Cytomegalovirus(CMV)prophylaxis with valganciclovir and ganciclovir is associated with elevated neutropenia and leukopenia risk in kidney transplant recipients,although the impact of these events on healthcare resource utilization(HCRU)and clinical outcomes is unclear.AIM To quantify clinical events and HCRU associated with neutropenia and leukope-nia among adults receiving valganciclovir and/or ganciclovir post-kidney trans-plantation.METHODS Adult kidney transplant recipients receiving valganciclovir and/or ganciclovir prophylaxis were identified in the TriNetX database from 2012 to 2021.Patient characteristics were evaluated in the 1-year period pre-first transplant.HCRU and adjusted event rates per person-year were evaluated in follow-up year 1 and years 2-5 after first kidney transplantation among cohorts with vs without neutropenia and/or leukopenia.RESULTS Of 15398 identified patients,the average age was 52.39 years and 58.70%were male.Patients with neutropenia and/or leukopenia had greater risk of clinical events for CMV-related events,opportunistic infections,use of granulocyte colony stimulating factor,and hospitalizations(relative risk>1 in year 1 and years 2-5).Patients with vs without neutropenia and/or leukopenia had higher HCRU in year 1 and years 2-5 post kidney transplantation,including the mean number of inpatient admissions(year 1:3.47 vs 2.76;years 2-5:2.70 vs 2.29)and outpatient visits(48.97 vs 34.42;31.73 vs 15.59,respectively),as well as the mean number of labs(1654.55 vs 1182.27;622.37 vs 327.89).CONCLUSION Adults receiving valganciclovir and/or ganciclovir prophylaxis post-kidney transplantation had greater risk of neutropenia and/or leukopenia,which were associated with higher clinical event rates and HCRU up to 5 years post-transplantation.These findings suggest the need for alternative prophylaxis options with lower myelosup-pressive effects to improve patient outcomes.展开更多
Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC...Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.展开更多
BACKGROUND Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome(IBS-D);however,the certainty of evidence is low.Wellpowered randomized controlled dose-ranging trials a...BACKGROUND Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome(IBS-D);however,the certainty of evidence is low.Wellpowered randomized controlled dose-ranging trials are warranted on promising single-strain candidates.AIM To investigate the clinical efficacy of Lactiplantibacillus plantarum(L.plantarum)Lpla33(DSM34428)in adults with IBS-D.METHODS This is a randomized,double-blind,placebo-controlled,multi-center,and doseranging study.Three hundred and seven adults,18-70 years of age,with IBS-D,according to Rome IV criteria,were allocated(1:1:1)to receive placebo or L.plantarum Lpla33 at 1×10^(9)(1B)or 1×10^(10)(10B)colony-forming units/d over an 8-wk intervention period.The primary outcome was the change in IBS severity scoring system(IBS-SSS)total score after 8 wk,while secondary and exploratory outcomes included abdominal pain severity,IBS related quality of life,stool and microbial profile,and perceived stress.RESULTS IBS-SSS was significantly reduced,after 8 wk,in participants receiving L.plantarum 1B(-128.45±83.30;P<0.001)and L.plantarum 10B(-156.77±99.06;P<0.001),compared to placebo(-58.82±74.75).Further,a dose-ranging effect was observed,with a greater absolute reduction in the L.plantarum 10B group(P<0.05).A reduction in sub-scores related to abdominal pain,abdominal distension,bowel habits,and quality of life was observed in both L.plantarum groups compared to placebo(P<0.001).Further,62.5%and 88.4%of participants administered L.plantarum 1B and 10B,respectively,were classified as stool consistency responders based on a reduction in diarrheal stool form,as compared to 26.3%in the placebo group(P<0.001).In contrast,no significant shifts were observed in microbial diversity.CONCLUSION L.plantarum Lpla33(DSM34428)is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.展开更多
In the November 27,2010 issue of the World Journal of Hepatology (WJH),three case reports were published which involved patients who had consumed various dietary supplements and conventional foods generally marketed a...In the November 27,2010 issue of the World Journal of Hepatology (WJH),three case reports were published which involved patients who had consumed various dietary supplements and conventional foods generally marketed as weight loss products.The reference to Herbalife products as contaminated and generally com-parable to all dietary supplements or weight loss prod-ucts is not scientifically supported.The authors provided an insufficient amount of information regarding patient histories,concomitant medications and other com-pounds,dechallenge results,and product specifications and usage.This information is necessary to fully assess the association of Herbalife products in the WJH case reports.Therefore,the article does not objectively sup-port a causal relationship between the reported cases of liver injury and Herbalife products or ingredients.展开更多
Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract(IND-2) add-on therapy in type 2 diabetes mellitus(T2DM) patients who were on insulin treatment in prospect...Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract(IND-2) add-on therapy in type 2 diabetes mellitus(T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial.Methods: T2DM patients(n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar(FBS) level between 100-140 mg/dL received IND-2 capsules(700 mg, thrice a day) for 16 weeks.The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16.Secondary end-points include post-prandial blood sugar level, glycosylated Hb(HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks.Safety and adverse events(AEs) were also assessed during the study.Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after addon therapy of IND-2.However, add-on therapy of IND-2 significantly reduced(P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline.Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoproteincholesterol levels were significantly increased(P<0.01) after IND-2 add-on therapy.Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16.Additionally, add-on therapy of IND-2 did not produce any serious adverse events.Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia.Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM.展开更多
The present manuscript deals with theoretical and experimental studies of the effect of inclined scraper on removal raw cotton from mesh surface. The mathematical model of the problem and theoretical studies of the mo...The present manuscript deals with theoretical and experimental studies of the effect of inclined scraper on removal raw cotton from mesh surface. The mathematical model of the problem and theoretical studies of the motion of cotton mass on plane of scraper is derived taking into account material point by accomplishing plane motion in the mesh surface. Graphs of the experiment shows that performance of scraper inclined to the radius of the disk by the value α=30° to the surface mesh β=110°, optimally allows to reduce the formation of technological defects of raw cotton. The presence of zero-pressure portion on the mesh surface of separator may provide complete removal of cotton from its surface and to eliminate grid clogging.展开更多
BACKGROUND Cytomegalovirus(CMV)infections in the population are mostly subclinical,inapparent,or latent.However,it is rare in brain tissue.Most reported CMV encephalitis cases were patients with immunodeficiency.The d...BACKGROUND Cytomegalovirus(CMV)infections in the population are mostly subclinical,inapparent,or latent.However,it is rare in brain tissue.Most reported CMV encephalitis cases were patients with immunodeficiency.The diagnosis and detection rate of CMV encephalitis in patients with normal immune function needs to be further improved.CASE SUMMARY An 86-year-old male was admitted due to a sudden onset of unconsciousness for 3 h.The patient developed status epilepticus and was relieved after antiepileptic treatment.Encephalitis was considered due to the high signals of diffusionweighted imaging sequences in the right central region by magnetic resonance imaging.Metagenomic next-generation sequencing(mNGS)of blood and cerebrospinal fluid revealed CMV,with unique reads number being 614 and 1,respectively.Simultaneous quantitative PCR results showed CMV positive in blood samples and negative in cerebrospinal fluid samples.The patient was finally diagnosed as CMV encephalitis with status epilepticus.After the antiviral,hormonal,andγ-globulin pulse therapy,the patient’s condition improved,and he was finally discharged.CONCLUSION mNGS could be a reliable approach for the diagnosis of CMV encephalitis,with high efficiency,sensitivity,and specificity.展开更多
AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV...AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression.RESULTS SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.展开更多
Purpose： To evaluate the efficacy and safety of the glycoside fraction of fenugreek （Trigonellafoenum-graecum） seeds （Fenu-FG） on physiologi- cal parameters related to muscle anabolism, androgenic hormones, and b...Purpose： To evaluate the efficacy and safety of the glycoside fraction of fenugreek （Trigonellafoenum-graecum） seeds （Fenu-FG） on physiologi- cal parameters related to muscle anabolism, androgenic hormones, and body fat in healthy male subjects during an 8-week resistance training program using a prospective, randomized, double-blind, placebo controlled design. Methods： Sixty healthy male subjects were randomized to ingest capsules of Fenu-FG （1 capsule of 300 rag, twice per day） or the matching placebo at a 1：1 ratio. The subjects participated in a supervised 4-day per week resistance-training program for 8 weeks. The outcome measurements were recorded at recruitment （baseline） and at the end of the treatment （8 weeks）. The efficacy outcome included serum testosterone （total and free） levels, muscle strength and repetitions to failure, metabolic markers for anabolic activity （serum creatinine and blood urea nitrogen）, and % body fat. The standard safety measurements such as adverse events monitoring, vital signs, hematology, biochemistry, and urinalysis were performed. Results： Fenu-FG supplementation demonstrated significant anabolic and androgenic activity as compared with the placebo. Fenu-FG treated subjects showed significant improvements in body fat without a reduction in muscle strength or repetitions to failure. The Fenu-FG supplemen- tation was found to be safe and well-tolerated. Conclusion： Fenu-FG supplementation showed beneficial effects in male subjects during resistance training without any clinical side effects.展开更多
To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed. METHODSOutcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 201...To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed. METHODSOutcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response (SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response (FVR) was defined as undetectable HCV RNA at week-4 (telaprevir) or week-8 (boceprevir). RESULTSThe median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis (FIB-4 ≥ 3.25). Only 42% (94/223) of patients achieved SVR24 on an intention-to-treat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio (OR) = 5.92, 95% confidence interval (CI): 2.34-14.96], HCV sub-genotype 1b (OR = 2.81, 95%CI: 1.45-5.44), platelet count (OR = 1.10, per x 10<sup>4</sup> cells/μL, 95%CI: 1.05-1.16), and IL28B CC genotype (OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 10<sup>3</sup>/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25% (27/104) of patients with an end-of-treatment response and was associated with non-FVR (OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a (OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25 (OR = 2.77; 95%CI: 1.07-7.22). CONCLUSIONThe SVR rate was 42% with telaprevir- or boceprevir-based triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.展开更多
Abstract： The shortest path problem in a network G is to find shortest paths between some specified source vertices and terminal vertices when the lengths of edges are given. The structure of the optimal solutions se...Abstract： The shortest path problem in a network G is to find shortest paths between some specified source vertices and terminal vertices when the lengths of edges are given. The structure of the optimal solutions set on the shortest paths is studied in this paper. First, the conditions of having unique shortest path between two distinguished vertices 8 and t in a network G are discussed; Second, the structural properties of 2-transformation ^-G graph G on the shortest-paths for G are presented heavily.展开更多
Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with...Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with men who require 58 μg to achieve similar responses. In children the current desmopressin dose recommendation to treat primary nocturnal enuresis (PNE) is the same for boys and girls. This post hoc analysis of data from a randomised, doubleblind single-dose study of 84 children with PNE aged 6 - 12 years explored gender differences in sensitivity to desmopressin in children. Following water loading to suppress endogenous AVP, placebo or desmopres-sin 30, 60, 120, 240, 360 or 480 μg was administered when urinary production reached >0.13 mL/min/kg. The endpoints of urinary osmolality and duration of urinary-concentrating action (DOA) (above three thresholds: 125, 200 and 400 mOsm/kg) were analysed to compare efficacy in boys and girls, in each treatment group. The DOA and urinary osmolality were similar in both genders in the desmopressin 120 - 480 μg groups. Boys receiving desmopressin ODT 30 - 60 μg tended to increased urinary osmolality and experienced 1 - 2 hours longer DOA than girls. The same pattern of higher values in boys compared with girls was seen for all measures of urinary osmolality. Conclusion: In a limited sample of pre-pubertal children the antidiuretic response to desmopressin was largely similar between genders, in contrast to findings in adults.展开更多
Background: Iopromide (Ultravist®) has been shown to be a very safe CM agent in previous post-marketing surveillance studies on Western and Asian populations. Our study aimed to analyse data pertaining to the s...Background: Iopromide (Ultravist®) has been shown to be a very safe CM agent in previous post-marketing surveillance studies on Western and Asian populations. Our study aimed to analyse data pertaining to the safety, tolerability and diagnostic image quality of Iopromide in an unselected sub-set of the Chinese population. Methods: we analysed data for Chinese ambulatory and in-patients who received Iopromide for an imaging procedure (in accordance with the local package insert and routine clinical practice), as part of an international post-marketing surveillance study. Use of premedication was at the discretion of the attending physician. Patient demographics, clinical history, type of examination, contrast quality and tolerability, including pre-specified adverse drug reactions, were recorded. All statistical analyses were descriptive. Results: case report forms for 20,000 Chinese patients (61.3% men) were analysed, of whom 153 patients (0.77%) had risk factors for idiosyncratic contrast media reactions (at-risk group). Use of premedication, most commonly corticosteroids, was recorded for 5658 patients (28.3%) and 86 at-risk patients (56.2% of the at-risk group), respectively. The mean (±standard deviation) dose of iodine administered was 29 ± 5.5 g. During the physician’s evaluation of image parameters, contrast quality was considered to be “good” (64.7%) or “excellent” (29.3%) in the majority of patients. 571 patients (2.9%) experienced at least one adverse drug reaction [most frequently nausea (0.70%) and dysgeusia (0.62%)], which were typically transient and of mild intensity. Two serious adverse drug reactions were reported [edema (n = 1), decreased blood pressure and dyspnea (n = 1)]. The incidence of adverse drug reactions was increased in the at-risk group versus the overall patient population, and tended to reduce with premedication (mainly corticosteroids). Conclusions: Iopromide was well tolerated and proved to be an efficient contrast agent in a large, non-selected sub-set of Chinese patients undergoing different types of diagnostic imaging procedures.展开更多
BACKGROUND Understanding the treatment landscape of inflammatory bowel diseases(IBD)is essential for improving disease management and patient outcomes.Brazil is the largest Latin American country,and it presents socio...BACKGROUND Understanding the treatment landscape of inflammatory bowel diseases(IBD)is essential for improving disease management and patient outcomes.Brazil is the largest Latin American country,and it presents socioeconomic and health care differences across its geographical regions.This country has the highest increase in IBD incidence and prevalence in Latin America,but information about the clinical and treatment characteristics of IBD is scarce.AIM To describe the sociodemographic,clinical,and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast,South and Northeast/Midwest regions.METHODS Multicenter,cross-sectional study with a 3-year retrospective chart review component.Patients with moderate-to-severe Crohn’s disease(CD)or ulcerative colitis(UC)were consecutively enrolled between October 2016 and February 2017.Active CD at enrollment was defined as a Harvey Bradshaw Index≥8 or a CD Activity Index≥220 or a calprotectin level>200μg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year;active UC was defined as a partial Mayo score≥5.Descriptive statistics were used to analyze all variables.RESULTS In a total of 407 included patients,CD was more frequent than UC,both overall(264 CD/143 UC patients)and by region(CD:UC ratios of 2.1 in the Southeast,1.6 in the South and 1.2 in the Northeast/Midwest).The majority of patients were female(54.2%of CD;56.6%of UC),and the mean ages were 45.9±13.8 years(CD)and 42.9±13.0 years(UC).The median disease duration was 10.0(range:0.5-45)years for both IBD types.At enrollment,44.7%[95%confidence interval(CI):38.7-50.7]of CD patients and 25.2%(95%CI:18.1-32.3)of UC patients presented with active disease.More than 95%of IBD patients were receiving treatment at enrollment;CD patients were commonly treated with biologics(71.6%)and immunosuppressors(67.4%),and UC patients were commonly treated with mesalazine[5-Aminosalicylic acid(5-ASA)]derivates(69.9%)and immunosuppressors(44.1%).More than 50%of the CD patients had ileocolonic disease,and 41.7%presented with stricturing disease.One-quarter of CD patients had undergone CD-related surgery in the past 3 years,and this proportion was lower in the Northeast/Midwest region(2.9%).CONCLUSION In Brazil,there are regional variations in IBD management.CD outweighs UC in both frequency and disease activity.However,one-quarter of UC patients have active disease,and most are receiving 5-ASA treatment.展开更多
The aim of this prospective observational pilot study was to observe the impact of orbital atherectomy (OA) on the coronary microcirculation via coronary flow reserve (CFR) measurements. Fifteen subjects who had succe...The aim of this prospective observational pilot study was to observe the impact of orbital atherectomy (OA) on the coronary microcirculation via coronary flow reserve (CFR) measurements. Fifteen subjects who had successful OA and stent placement with no procedural complication were enrolled at 3 hospitals in the U.S. Baseline and hyperemic velocities were 16 ± 5.2 and 36 ± 14 cm/sec, respectively. The average CFR post-procedure was within the normal range at 2.23 ± 0.33. The observation of normal CFR following OA may be attributed to the orbital action of the device that allows for continuous flow during treatment, minimizing a bolus embolization effect which can impact microvascular function.展开更多
文摘BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resistance(HOMA-IR)andβ-cell function(HOMA-β)in patients with T2D in a meta-analysis.METHODS Randomized controlled trials(RCTs)comparing SGLT2 inhibitors to placebo in T2D patients,with a minimum treatment duration of 12 weeks,were searched using the PubMed,EMBASE,and Cochrane Library databases.Risk of bias was assessed using the Cochrane Risk of Bias Tool,and the certainty of evidence was evaluated using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)system.Changes in HOMA-IR and HOMA-βwere the outcomes analyzed.Meta-analyses were performed using a random-effects model by incorporating the potential influences of heterogeneity.RESULTS Of 1388 articles identified,24 RCTs met the inclusion criteria.23 of the included studies were double-blind RCTs with low risk of bias.Pooled results including 2272 patients showed that SGLT2 inhibitors significantly reduced HOMA-IR compared to placebo[mean difference(MD)=-0.81,95%confidence interval(CI):-1.11 to-0.52,P<0.001;I2=82%],indicating reduced insulin resistance.Addi-tionally,meta-analysis with 2845 patients suggested that SGLT2 inhibitors significantly increased HOMA-β(MD=7.90,95%CI:5.44-10.37,P<0.001;I2=74%)compared to placebo in patients with T2D,indicating improvedβ-cell function.Based on GRADE assessment,the certainty of evidence was rated moderate for both outcomes due to heterogeneity.Subgroup analyses showed that HOMA-βincreased more substantially in non-Asian studies than in Asian studies(P for subgroup difference<0.01).Subgroup analyses according to the individual medications of SGLT2 inhibitors all showed significant improvement of HOMA-IR and HOMA-β(P all<0.05).No significant publication bias was detected(P for Egger’s test all>0.05).CONCLUSION SGLT2 inhibitors are associated with improvements in insulin resistance andβ-cell function in patients with T2D,although the certainty of evidence is moderate due to heterogeneity.
文摘BACKGROUND Cirrhosis is a progressive condition characterized by fibrosis that can lead to severe complications and increased mortality.The mac-2 binding protein glyco-sylation isomer(M2BPGi)is a prominent biomarker for predicting hepatocellular carcinoma(HCC)and cirrhosis-induced esophageal varices(EV).AIM To investigate thresholds of M2BPGi associated with HCC,EV,and decomp-ensation in patients with cirrhosis.METHODS This was a prospective study.A total of 153 patients with cirrhosis who met the inclusion criteria were enrolled.The patients were diagnosed with HCC and EV according to the Baveno VII and European Association for the Study of the Liver guidelines.Baseline serum M2BPGi levels were assessed along with other routine tests.The data analysis aimed to determine the cutoff values of M2BPGi for pre-dicting EV and HCC.RESULTS In the study 85.6%of patients were Child-Pugh B and C.M2BPGi mean cutoff index was 7.1±3.7,showing no significant etiological differences.However,M2BPGi levels varied significantly among Child-Pugh classes,EV classifications,and between patients with and without HCC(P<0.01).M2BPGi cutoff values for predicting HCC,EV,and decompensated cirrhosis were 6.50,6.64,and 5.25,respectively.Mul-tivariate analysis confirmed M2BPGi as an independent risk factor for EV[adjusted odds ratio(aOR):1.3,95%CI:1.08-1.64]and liver decompensation(aOR:2.11,95%CI:1.37-3.83).Area under the curve of M2BPGi for HCC differ-entiation was 0.71.An algorithm combining alpha-fetoprotein(AFP)and M2BPGi detected 26 of 28 HCC cases with 98.04%accuracy vs 10 cases by AFP alone.CONCLUSION Serum M2BPGi predicted cirrhosis complications,including decompensation and varices,especially in HCC.Combined with AFP,it enhanced HCC detection.Future liver biopsy studies are needed for tissue confirmation.
文摘BACKGROUND The Mac-2 binding protein glycosylated isomer(M2BPGi)is a serum marker for fibrosis that correlates with the fibrosis stages in various liver diseases.AIM To examine the M2BPGi’s threshold for staging fibrosis in patients with chronic hepatitis B(CHB),and its changes during treatment.METHODS This was a prospective,longitudinal study.A total of 348 eligible patients were recruited from the Hepatology Department,Medic Medical Center between March 2020 and December 2023.Liver enzyme tests,platelet counts,M2BPGi levels,and FibroScan were conducted at baseline and at 3-month intervals until six months post-treatment.Correlation plots of M2BPGi,FibroScan,and the other parameters were generated.Receiver operating characteristic curves were constructed for M2BPGi and the other parameters to evaluate their performance.RESULTS M2BPGi levels correlated well with FibroScan results and increased as the fibrosis stage advanced.The median M2BPGi levels at the different stages of fibrosis showed statistically significant differences.The cut-off values of M2BPGi for diagnosing significant fibrosis(F≥2),advanced fibrosis(F3),and cirrhosis(F4)were determined to be 1.08,1.4,and 1.52,respectively.In the context of fibrosis regression in CHB patients during the first 6-month of treatment,M2BPGi levels appeared to decrease before this pattern occurred in the FibroScan results.CONCLUSION M2BPGi levels were strongly correlated with FibroScan.M2BPGi can be used to assess liver fibrosis,and to serve as a tool for monitoring fibrosis regression in CHB patients undergoing treatment.
文摘BACKGROUND Mac-2 binding protein glycosylation isomer(M2BPGi)serves as a marker of activated hepatic stellate cells and as such holds potential as a biomarker for liver fibrosis.In Viet Nam,metabolic dysfunction-associated steatotic liver disease(MASLD)is rising in prevalence and there is an urgent need for better clinical management,particularly in early detection methods that will improve overall prognosis.AIM To examine M2BPGi cut-off values for staging liver fibrosis in patients with MASLD and risk factors associated with disease progression.METHODS A total of 301 individuals with ultrasound-confirmed or FibroScan-confirmed diagnosis of fatty liver were enrolled in the study.The participants were stratified according to fibrosis stage,measured via magnetic resonance elastography.M2-BPGi,Fibrosis-4(FIB-4)Index score,and routine parameters of liver function were assessed to statistically investigate the correlation of M2BPGi levels in various fibrosis stages and to identify risk factors associated with fibrosis severity.RESULTS M2BPGi levels positively correlated with fibrosis stages,with cut-off indexes of 0.57 for F0-1,0.68 for F2-3,and 0.78 for F4.M2BPGi levels in the F0-1 group were significantly different from those in both the F2-3 group(P=0.038)and the F4 group(P=0.0051);the F2-3 and F4 groups did not show a significant difference(P=0.39).Females exhibited significantly higher M2BPGi levels than males for all fibrosis stages,particularly in the F2-3 group(P=0.01)and F4 group(P=0.0006).In the F4(cirrhosis)group,individuals with diabetes had significantly higher M2BPGi levels than those without.M2BPGi,hemoglobin A1c,and FIB-4 score were identified as independent risk factors for greater fibrosis and cirrhosis.CONCLUSION M2BPGi levels varied significantly throughout fibrosis progression,from early MASLD to cirrhosis,with sex correlation.M2BPGi holds promise as an early biomarker for fibrosis characterization in MASLD adult patient populations.
文摘BACKGROUND Cytomegalovirus(CMV)prophylaxis with valganciclovir and ganciclovir is associated with elevated neutropenia and leukopenia risk in kidney transplant recipients,although the impact of these events on healthcare resource utilization(HCRU)and clinical outcomes is unclear.AIM To quantify clinical events and HCRU associated with neutropenia and leukope-nia among adults receiving valganciclovir and/or ganciclovir post-kidney trans-plantation.METHODS Adult kidney transplant recipients receiving valganciclovir and/or ganciclovir prophylaxis were identified in the TriNetX database from 2012 to 2021.Patient characteristics were evaluated in the 1-year period pre-first transplant.HCRU and adjusted event rates per person-year were evaluated in follow-up year 1 and years 2-5 after first kidney transplantation among cohorts with vs without neutropenia and/or leukopenia.RESULTS Of 15398 identified patients,the average age was 52.39 years and 58.70%were male.Patients with neutropenia and/or leukopenia had greater risk of clinical events for CMV-related events,opportunistic infections,use of granulocyte colony stimulating factor,and hospitalizations(relative risk>1 in year 1 and years 2-5).Patients with vs without neutropenia and/or leukopenia had higher HCRU in year 1 and years 2-5 post kidney transplantation,including the mean number of inpatient admissions(year 1:3.47 vs 2.76;years 2-5:2.70 vs 2.29)and outpatient visits(48.97 vs 34.42;31.73 vs 15.59,respectively),as well as the mean number of labs(1654.55 vs 1182.27;622.37 vs 327.89).CONCLUSION Adults receiving valganciclovir and/or ganciclovir prophylaxis post-kidney transplantation had greater risk of neutropenia and/or leukopenia,which were associated with higher clinical event rates and HCRU up to 5 years post-transplantation.These findings suggest the need for alternative prophylaxis options with lower myelosup-pressive effects to improve patient outcomes.
基金supported in part by the National Natural Sci-ence Foundation of China(81472284 and 81672699)Shanghai Pujiang Program(16PJD004)
文摘Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.
文摘BACKGROUND Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome(IBS-D);however,the certainty of evidence is low.Wellpowered randomized controlled dose-ranging trials are warranted on promising single-strain candidates.AIM To investigate the clinical efficacy of Lactiplantibacillus plantarum(L.plantarum)Lpla33(DSM34428)in adults with IBS-D.METHODS This is a randomized,double-blind,placebo-controlled,multi-center,and doseranging study.Three hundred and seven adults,18-70 years of age,with IBS-D,according to Rome IV criteria,were allocated(1:1:1)to receive placebo or L.plantarum Lpla33 at 1×10^(9)(1B)or 1×10^(10)(10B)colony-forming units/d over an 8-wk intervention period.The primary outcome was the change in IBS severity scoring system(IBS-SSS)total score after 8 wk,while secondary and exploratory outcomes included abdominal pain severity,IBS related quality of life,stool and microbial profile,and perceived stress.RESULTS IBS-SSS was significantly reduced,after 8 wk,in participants receiving L.plantarum 1B(-128.45±83.30;P<0.001)and L.plantarum 10B(-156.77±99.06;P<0.001),compared to placebo(-58.82±74.75).Further,a dose-ranging effect was observed,with a greater absolute reduction in the L.plantarum 10B group(P<0.05).A reduction in sub-scores related to abdominal pain,abdominal distension,bowel habits,and quality of life was observed in both L.plantarum groups compared to placebo(P<0.001).Further,62.5%and 88.4%of participants administered L.plantarum 1B and 10B,respectively,were classified as stool consistency responders based on a reduction in diarrheal stool form,as compared to 26.3%in the placebo group(P<0.001).In contrast,no significant shifts were observed in microbial diversity.CONCLUSION L.plantarum Lpla33(DSM34428)is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.
文摘In the November 27,2010 issue of the World Journal of Hepatology (WJH),three case reports were published which involved patients who had consumed various dietary supplements and conventional foods generally marketed as weight loss products.The reference to Herbalife products as contaminated and generally com-parable to all dietary supplements or weight loss prod-ucts is not scientifically supported.The authors provided an insufficient amount of information regarding patient histories,concomitant medications and other com-pounds,dechallenge results,and product specifications and usage.This information is necessary to fully assess the association of Herbalife products in the WJH case reports.Therefore,the article does not objectively sup-port a causal relationship between the reported cases of liver injury and Herbalife products or ingredients.
文摘Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract(IND-2) add-on therapy in type 2 diabetes mellitus(T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial.Methods: T2DM patients(n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar(FBS) level between 100-140 mg/dL received IND-2 capsules(700 mg, thrice a day) for 16 weeks.The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16.Secondary end-points include post-prandial blood sugar level, glycosylated Hb(HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks.Safety and adverse events(AEs) were also assessed during the study.Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after addon therapy of IND-2.However, add-on therapy of IND-2 significantly reduced(P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline.Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoproteincholesterol levels were significantly increased(P<0.01) after IND-2 add-on therapy.Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16.Additionally, add-on therapy of IND-2 did not produce any serious adverse events.Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia.Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM.
文摘The present manuscript deals with theoretical and experimental studies of the effect of inclined scraper on removal raw cotton from mesh surface. The mathematical model of the problem and theoretical studies of the motion of cotton mass on plane of scraper is derived taking into account material point by accomplishing plane motion in the mesh surface. Graphs of the experiment shows that performance of scraper inclined to the radius of the disk by the value α=30° to the surface mesh β=110°, optimally allows to reduce the formation of technological defects of raw cotton. The presence of zero-pressure portion on the mesh surface of separator may provide complete removal of cotton from its surface and to eliminate grid clogging.
文摘BACKGROUND Cytomegalovirus(CMV)infections in the population are mostly subclinical,inapparent,or latent.However,it is rare in brain tissue.Most reported CMV encephalitis cases were patients with immunodeficiency.The diagnosis and detection rate of CMV encephalitis in patients with normal immune function needs to be further improved.CASE SUMMARY An 86-year-old male was admitted due to a sudden onset of unconsciousness for 3 h.The patient developed status epilepticus and was relieved after antiepileptic treatment.Encephalitis was considered due to the high signals of diffusionweighted imaging sequences in the right central region by magnetic resonance imaging.Metagenomic next-generation sequencing(mNGS)of blood and cerebrospinal fluid revealed CMV,with unique reads number being 614 and 1,respectively.Simultaneous quantitative PCR results showed CMV positive in blood samples and negative in cerebrospinal fluid samples.The patient was finally diagnosed as CMV encephalitis with status epilepticus.After the antiviral,hormonal,andγ-globulin pulse therapy,the patient’s condition improved,and he was finally discharged.CONCLUSION mNGS could be a reliable approach for the diagnosis of CMV encephalitis,with high efficiency,sensitivity,and specificity.
基金Supported by Janssen Scientific Affairs and National Institutes of Health,Nos.DA031095 and DK090317
文摘AIM To assess the real-world effectiveness and cost of simeprevir(SMV), and/or sofosbuvir(SOF)-based therapy for chronic hepatitis C virus(HCV) infection.METHODS The real-world performance of patients treated with SMV/SOF ± ribavirin(RBV), SOF/RBV, and SOF/RBV with pegylated-interferon(PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response-the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response(SVR) 12]-were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression.RESULTS SVR 12 rates were as follows: 86%(95%CI: 80%-91%)among 178 patients on SMV/SOF ± RBV; 62%(95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78%(95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR 12 were $174442(standard deviation: ± $18588) for SMV/SOF ± RBV; $223003(± $77946) for SOF/RBV; and $126496(± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio(OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin(OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR 12(OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION SVR 12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.
基金supported by the Indus Biotech Private Ltd.,Pune with no role in the collection,analysis,and interpretation of data and the writing of the report
文摘Purpose： To evaluate the efficacy and safety of the glycoside fraction of fenugreek （Trigonellafoenum-graecum） seeds （Fenu-FG） on physiologi- cal parameters related to muscle anabolism, androgenic hormones, and body fat in healthy male subjects during an 8-week resistance training program using a prospective, randomized, double-blind, placebo controlled design. Methods： Sixty healthy male subjects were randomized to ingest capsules of Fenu-FG （1 capsule of 300 rag, twice per day） or the matching placebo at a 1：1 ratio. The subjects participated in a supervised 4-day per week resistance-training program for 8 weeks. The outcome measurements were recorded at recruitment （baseline） and at the end of the treatment （8 weeks）. The efficacy outcome included serum testosterone （total and free） levels, muscle strength and repetitions to failure, metabolic markers for anabolic activity （serum creatinine and blood urea nitrogen）, and % body fat. The standard safety measurements such as adverse events monitoring, vital signs, hematology, biochemistry, and urinalysis were performed. Results： Fenu-FG supplementation demonstrated significant anabolic and androgenic activity as compared with the placebo. Fenu-FG treated subjects showed significant improvements in body fat without a reduction in muscle strength or repetitions to failure. The Fenu-FG supplemen- tation was found to be safe and well-tolerated. Conclusion： Fenu-FG supplementation showed beneficial effects in male subjects during resistance training without any clinical side effects.
基金Supported by Janssen Scientific Affairs,LLC(partially)to Andrea D Branch to conduct the studyNational Institute of Health(NIH),Nos.DK090317 and DA031095(partially)to Andrea D Branch to conduct the study
文摘To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed. METHODSOutcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response (SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response (FVR) was defined as undetectable HCV RNA at week-4 (telaprevir) or week-8 (boceprevir). RESULTSThe median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis (FIB-4 ≥ 3.25). Only 42% (94/223) of patients achieved SVR24 on an intention-to-treat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio (OR) = 5.92, 95% confidence interval (CI): 2.34-14.96], HCV sub-genotype 1b (OR = 2.81, 95%CI: 1.45-5.44), platelet count (OR = 1.10, per x 10<sup>4</sup> cells/μL, 95%CI: 1.05-1.16), and IL28B CC genotype (OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 10<sup>3</sup>/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25% (27/104) of patients with an end-of-treatment response and was associated with non-FVR (OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a (OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25 (OR = 2.77; 95%CI: 1.07-7.22). CONCLUSIONThe SVR rate was 42% with telaprevir- or boceprevir-based triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.
文摘Abstract： The shortest path problem in a network G is to find shortest paths between some specified source vertices and terminal vertices when the lengths of edges are given. The structure of the optimal solutions set on the shortest paths is studied in this paper. First, the conditions of having unique shortest path between two distinguished vertices 8 and t in a network G are discussed; Second, the structural properties of 2-transformation ^-G graph G on the shortest-paths for G are presented heavily.
文摘Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with men who require 58 μg to achieve similar responses. In children the current desmopressin dose recommendation to treat primary nocturnal enuresis (PNE) is the same for boys and girls. This post hoc analysis of data from a randomised, doubleblind single-dose study of 84 children with PNE aged 6 - 12 years explored gender differences in sensitivity to desmopressin in children. Following water loading to suppress endogenous AVP, placebo or desmopres-sin 30, 60, 120, 240, 360 or 480 μg was administered when urinary production reached >0.13 mL/min/kg. The endpoints of urinary osmolality and duration of urinary-concentrating action (DOA) (above three thresholds: 125, 200 and 400 mOsm/kg) were analysed to compare efficacy in boys and girls, in each treatment group. The DOA and urinary osmolality were similar in both genders in the desmopressin 120 - 480 μg groups. Boys receiving desmopressin ODT 30 - 60 μg tended to increased urinary osmolality and experienced 1 - 2 hours longer DOA than girls. The same pattern of higher values in boys compared with girls was seen for all measures of urinary osmolality. Conclusion: In a limited sample of pre-pubertal children the antidiuretic response to desmopressin was largely similar between genders, in contrast to findings in adults.
文摘Background: Iopromide (Ultravist®) has been shown to be a very safe CM agent in previous post-marketing surveillance studies on Western and Asian populations. Our study aimed to analyse data pertaining to the safety, tolerability and diagnostic image quality of Iopromide in an unselected sub-set of the Chinese population. Methods: we analysed data for Chinese ambulatory and in-patients who received Iopromide for an imaging procedure (in accordance with the local package insert and routine clinical practice), as part of an international post-marketing surveillance study. Use of premedication was at the discretion of the attending physician. Patient demographics, clinical history, type of examination, contrast quality and tolerability, including pre-specified adverse drug reactions, were recorded. All statistical analyses were descriptive. Results: case report forms for 20,000 Chinese patients (61.3% men) were analysed, of whom 153 patients (0.77%) had risk factors for idiosyncratic contrast media reactions (at-risk group). Use of premedication, most commonly corticosteroids, was recorded for 5658 patients (28.3%) and 86 at-risk patients (56.2% of the at-risk group), respectively. The mean (±standard deviation) dose of iodine administered was 29 ± 5.5 g. During the physician’s evaluation of image parameters, contrast quality was considered to be “good” (64.7%) or “excellent” (29.3%) in the majority of patients. 571 patients (2.9%) experienced at least one adverse drug reaction [most frequently nausea (0.70%) and dysgeusia (0.62%)], which were typically transient and of mild intensity. Two serious adverse drug reactions were reported [edema (n = 1), decreased blood pressure and dyspnea (n = 1)]. The incidence of adverse drug reactions was increased in the at-risk group versus the overall patient population, and tended to reduce with premedication (mainly corticosteroids). Conclusions: Iopromide was well tolerated and proved to be an efficient contrast agent in a large, non-selected sub-set of Chinese patients undergoing different types of diagnostic imaging procedures.
文摘BACKGROUND Understanding the treatment landscape of inflammatory bowel diseases(IBD)is essential for improving disease management and patient outcomes.Brazil is the largest Latin American country,and it presents socioeconomic and health care differences across its geographical regions.This country has the highest increase in IBD incidence and prevalence in Latin America,but information about the clinical and treatment characteristics of IBD is scarce.AIM To describe the sociodemographic,clinical,and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast,South and Northeast/Midwest regions.METHODS Multicenter,cross-sectional study with a 3-year retrospective chart review component.Patients with moderate-to-severe Crohn’s disease(CD)or ulcerative colitis(UC)were consecutively enrolled between October 2016 and February 2017.Active CD at enrollment was defined as a Harvey Bradshaw Index≥8 or a CD Activity Index≥220 or a calprotectin level>200μg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year;active UC was defined as a partial Mayo score≥5.Descriptive statistics were used to analyze all variables.RESULTS In a total of 407 included patients,CD was more frequent than UC,both overall(264 CD/143 UC patients)and by region(CD:UC ratios of 2.1 in the Southeast,1.6 in the South and 1.2 in the Northeast/Midwest).The majority of patients were female(54.2%of CD;56.6%of UC),and the mean ages were 45.9±13.8 years(CD)and 42.9±13.0 years(UC).The median disease duration was 10.0(range:0.5-45)years for both IBD types.At enrollment,44.7%[95%confidence interval(CI):38.7-50.7]of CD patients and 25.2%(95%CI:18.1-32.3)of UC patients presented with active disease.More than 95%of IBD patients were receiving treatment at enrollment;CD patients were commonly treated with biologics(71.6%)and immunosuppressors(67.4%),and UC patients were commonly treated with mesalazine[5-Aminosalicylic acid(5-ASA)]derivates(69.9%)and immunosuppressors(44.1%).More than 50%of the CD patients had ileocolonic disease,and 41.7%presented with stricturing disease.One-quarter of CD patients had undergone CD-related surgery in the past 3 years,and this proportion was lower in the Northeast/Midwest region(2.9%).CONCLUSION In Brazil,there are regional variations in IBD management.CD outweighs UC in both frequency and disease activity.However,one-quarter of UC patients have active disease,and most are receiving 5-ASA treatment.
文摘The aim of this prospective observational pilot study was to observe the impact of orbital atherectomy (OA) on the coronary microcirculation via coronary flow reserve (CFR) measurements. Fifteen subjects who had successful OA and stent placement with no procedural complication were enrolled at 3 hospitals in the U.S. Baseline and hyperemic velocities were 16 ± 5.2 and 36 ± 14 cm/sec, respectively. The average CFR post-procedure was within the normal range at 2.23 ± 0.33. The observation of normal CFR following OA may be attributed to the orbital action of the device that allows for continuous flow during treatment, minimizing a bolus embolization effect which can impact microvascular function.
