Objective We aimed to compare the clinical outcomes of intravenous urography-assisted fluoroscopy-guided shockwave lithotripsy for radiolucent ureteral stones and standard shockwave lithotripsy for radiopaque ureteral...Objective We aimed to compare the clinical outcomes of intravenous urography-assisted fluoroscopy-guided shockwave lithotripsy for radiolucent ureteral stones and standard shockwave lithotripsy for radiopaque ureteral stones.Methods We retrospectively reviewed 734 patients with ureteral stones treated by fluoroscopy-guided shockwave lithotripsy between March 2014 and March 2021.The primary outcome was a stone-free rate with one session within 30 days,defined as no residual stones without auxiliary treatment.The multivariate analysis was used to examine whether the intravenous urography use predicted treatment success.Furthermore,we compared the outcomes using propensity score matching.Results Ninety-eight patients underwent the intravenous urography use protocol(Group I),and the remaining 636 patients underwent the non-intravenous urography protocol(Group N).Stone-free rates with one session within 30 days were 38%and 32%in groups I and N,respectively(p=0.3).No statistical differences were observed in the conversion rate to ureteroscopy(p=0.3)or complication rate(p=0.7)between Group I and Group N.One patient who developed skin redness was considered a complication of the contrast medium.Propensity score matching examined 88 matched pairs.Treatment success was obtained in 31(35%)patients in Group I and 33(38%)patients in Group N(p=0.9)within 30 days with one session.Conclusion Radiolucent stones can be safely and effectively treated by shockwave lithotripsy with intravenous urography.展开更多
BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world ...BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.展开更多
BACKGROUND Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes.Various therapies including albumin infusion,volume expanders...BACKGROUND Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes.Various therapies including albumin infusion,volume expanders(VEs),and vasoactive agents are used to manage patients with cirrhosis.Despite numerous clinical trials,a comprehensive meta-analysis comparing the effectiveness of albumin infusion against alternative treatments is limited.This study provides the current and comprehensive synthesis of evidence,offering key insights for optimizing therapeutic strategies in patients with liver cirrhosis.AIM To systematically update available data on therapies of liver cirrhosis,we performed a meta-analysis to evaluate and compare the clinical efficacy of albumin infusion vs other VEs and vasoactive agents in patients with liver cirrhosis.METHODS A literature search from the PubMed and Embase databases(inception till June 2024)focused on hyponatremia(primary outcome)and various outcomes such as gastrointestinal bleeding,hepatic encephalopathy,severe infection,post-paracentesis-induced circulatory dysfunction(PICD),ascites reappearance,spontaneous bacterial peritonitis,hepatorenal syndrome,renal impairment,hospital stay,mortality,and safety was performed.The primary analysis pooled studies that compared albumin infusion with control.In the subgroup analysis,comparisons were made within the stratified treatment categories included in the control group.RESULTS Of the 2957 studies retrieved,31 studies(27 randomized controlled trials and 4 observational studies)comprising 6255 patients were included.Albumin use was significant in reducing odds of hyponatremia[odds ratio(OR)=0.67;95%confidence interval(95%CI)=0.53-0.85]and PICD(OR=0.38;95%CI=0.20-0.71),whereas the reduction in severe infection(OR=0.55;95%CI=0.28-1.07)did not reach statistical significance.In the subgroup analysis,albumin demonstrated a favorable improvement in lowering the incidence of hyponatremia vs inactive/standard medical therapy(OR=0.54;95%CI=0.27-1.09).For PICD,albumin use was significant compared with other VEs(OR=0.31;95%CI=0.11-0.85)but not with vasoconstrictors(OR=0.63;95%CI=0.21-1.91).In the overall subgroup analysis,a significant reduction was observed in hyponatremia(OR=0.67;95%CI=0.53-0.85)and PICD(OR=0.38;95%CI=0.20-0.71).CONCLUSION Human albumin has been shown to significantly reduce the incidence of hyponatremia and PICD in patients with liver cirrhosis,whereas its effect on severe infection remains suggestive but not statistically significant.展开更多
Monoclonal antibodies(mAbs)require a high level of purity for regulatory approval and safe administration.High-molecular weight(HMW)species are a common impurity associated with mAb therapies.Hydrophobic interaction c...Monoclonal antibodies(mAbs)require a high level of purity for regulatory approval and safe administration.High-molecular weight(HMW)species are a common impurity associated with mAb therapies.Hydrophobic interaction chromatography(HIC)resins are often used to remove these HMW impurities.Determination of a suitable HIC resin can be a time and resource-intensive process.In this study,we modeled the chromatographic behavior of seven mAbs across 13 HIC resins using measurements of surface hydrophobicity,surface charge,and thermal stability for mAbs,and hydrophobicity and zeta-potential for HIC resins with high fit quality(adjusted R2>0.80).We identified zeta-potential as a novel key modeling parameter.When using these models to select a HIC resin for HMW clearance of a test mAb,we were able to achieve 60%HMW clearance and 89%recovery.These models can be used to expedite the downstream process development for mAbs in an industry setting.展开更多
BACKGROUND Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease(MS-IBD). This study hypothesized that as a standard of treatment and the pr...BACKGROUND Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease(MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes.AIM To investigate the effectiveness of conventional therapy for MS-IBD.METHODS A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn's disease(CD) and ulcerative colitis(UC). Corticosteroids(prednisone, hydrocortisone, budesonide, prednisolone,dexamethasone), 5-aminosalicylic acid(5-ASA) derivatives(mesalazine and sulfasalazine) and immunosuppressants [azathioprine(AZA), methotrexate(MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine(6-MP)] were considered conventional therapy. The exclusion criteria were sample size below50; narrative reviews; specific subpopulations(e.g., pregnant women,comorbidities); studies on postoperative IBD; and languages other than English,Spanish, French or Portuguese. The primary outcome measures were clinical remission(induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria.RESULTS The search strategy identified 1995 citations, of which 27 were considered eligible(7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected(AZA and 6-MP showed no advantage over placebo,MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses). Only one meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus vs placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials(RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing,one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence.CONCLUSION High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.展开更多
Herein, we present a case of gastric adenocarcinoma of fundic gland type(GA-FG) spreading to heterotopic gastric glands(HGG) in the submucosa. A 58-year-old man with epigastric pain was referred to our hospital and un...Herein, we present a case of gastric adenocarcinoma of fundic gland type(GA-FG) spreading to heterotopic gastric glands(HGG) in the submucosa. A 58-year-old man with epigastric pain was referred to our hospital and underwent an esophagogastroduodenoscopy. A Borrmann type II gastric cancer at the antrum and a 10 mm submucosal tumor-like lesion in the lesser curvature of the upper third of the stomach were detected. Histological examination of the biopsy specimens obtained from the submucosal tumorlike lesion suggested a GA-FG. Therefore, endoscopic submucosal dissection was performed as excisional biopsy, and histopathological examination of the resected specimen confirmed a GA-FG and HGG proximal to the GA-FG. Although the GA-FG invaded the submucosal layer slightly, the submucosal lesion of the GA-FG had a poor stromal reaction and was located just above the HGG in the submucosa. Therefore, wefinally diagnosed the lesion as a GA-FG invading the submucosal layer by spreading to HGG.展开更多
BACKGROUND Anal fistula is a pathological connection between the anal canal and perianal skin,which most commonly develops from an infected anal crypt.While the majority of anal fistulas are idiopathic,they are also a...BACKGROUND Anal fistula is a pathological connection between the anal canal and perianal skin,which most commonly develops from an infected anal crypt.While the majority of anal fistulas are idiopathic,they are also associated with Crohn’s disease(CD)and other inflammatory conditions.The prevalence of anal fistula is estimated to be 1-2 per 10000 patients,but population-based studies on anal fistula epidemiology are limited and outdated.AIM To assess the prevalence of anal fistula and relevant comorbidities,with and without CD in the United Kingdom and Europe.METHODS A retrospective population-representative observational cohort study was performed in The Health Improvement Network(THIN),a United Kingdom primary care database.Mid-year point prevalence of anal fistula was calculated on the first of July for each year between 2014 and 2017.Estimates were calculated for anal fistula overall and by CD status and standardized to the United Kingdom and European population.Prevalence of relevant comorbidities including lymphogranuloma venereum,hidradenitis suppurativa,anal presentation of sexually transmitted diseases,diabetes mellitus,and radiation in the pelvic area was reported.RESULTS The United Kingdom-standardized overall point prevalence of anal fistula was 1.80(95%CI:1.65-1.94)per 10000 patients in 2017,while the Europe standardized estimate was 1.83(95%CI:1.68-1.98)per 10000 patients.Both these standardized point prevalence estimates ranged from 1.89 to 2.36 between 2014-2016.The United Kingdom-standardized point prevalence of anal fistula without CD was 1.35(95%CI:1.23-1.48)per 10000 patients,while the Europe-standardized estimate was 1.39(95%CI:1.26-1.52)per 10000 patients.In contrast,the standardized point prevalence estimate of anal fistula with CD was lower for both United Kingdom and Europe(0.44;95%CI United Kingdom:0.37-0.52,95%CI Europe:0.37-0.51)per 10000 patients in 2017.In 2017,19%of anal fistula patients without CD and 13%of anal fistula patients with CD had at least one relevant comorbidity.These results show that anal fistulas are infrequent in the general population.24.5%of prevalent anal fistulas are associated with CD,but other potentially etiological comorbidities are rare.CONCLUSION This real-world evidence study estimated the United Kingdom-standardized prevalence of anal fistula was 1.80 per 10000 patients in 2017.Approximately 25%of cases may be associated with CD,while other comorbidities are rare.展开更多
BACKGROUND Anorectal malignant melanoma(AMM)is a rare disorder with an extremely poor prognosis.Although there is currently no consensus on the treatment methods for AMM,surgical procedures have been the most common t...BACKGROUND Anorectal malignant melanoma(AMM)is a rare disorder with an extremely poor prognosis.Although there is currently no consensus on the treatment methods for AMM,surgical procedures have been the most common treatment methods used until now.We recently encountered a case of AMM that we diagnosed using endoscopic submucosal dissection(ESD).To our knowledge,this is the first case of ESD for AMM,suggesting that ESD can potentially be a diagnostic and treatment method for AMM.CASE S UMA/MARY A 77-year-old woman visited our hospital with a chief complaint of anal bleeding and a palpable rectal mass.Colonoscopy revealed a 20-mm protruded lesion in the lower rectum.After obtaining biopsy specimens from the lesion,although a malignant rectal tumor was suspected,a definitive diagnosis was not made.Endoscopic ultrasonography revealed tumor invasion into the submucosal layer but not the muscular layer.Therefore,we performed an excisional biopsy using ESD.Immunohistochemical examination of the ESD-resected specimen revealed tumor cells positive for Human Melanin Black-45,Melan-A,and S-100.Moreover,the tumor cells lacked melanin pigment;thus,a diagnosis of amelanotic AMM was made.Although the AMM had massively invaded the submucosal layer and both lymphatic and venous invasion were present,we closely monitored the patient without any additional therapy on the basis of her request.Six months after ESD,local recurrence was detected,and the patient consented to wide local excision.CONCL USION It is suggested that ESD is a potential diagnostic and treatment method for AMM.展开更多
In this paper, a grid-based distributed hydrological model BTOPMC （Block-wise use of TOPMODEL） is introduced, which was developed from the original TOPMODEL. In order to broaden the model＇s application to arid regi...In this paper, a grid-based distributed hydrological model BTOPMC （Block-wise use of TOPMODEL） is introduced, which was developed from the original TOPMODEL. In order to broaden the model＇s application to arid regions, improvement methodology is also implemented. The canopy interception and soil infiltration processes were incorporated into the original BTOPMC to model event-based runoff simulation in large arid regions. One designed infiltration model with application of time compression approximation method is emphasized and validated for improving model＇s performance for event hydrological simulations with a case study of Lushi River basin.展开更多
AIM To investigate the pathophysiology of the digestive tract in patients with liver cirrhosis.METHODS In 42 cirrhotic patients and 20control subjects, the following fecal proteinswere measured by enzyme-linkedimmunos...AIM To investigate the pathophysiology of the digestive tract in patients with liver cirrhosis.METHODS In 42 cirrhotic patients and 20control subjects, the following fecal proteinswere measured by enzyme-linkedimmunosorb6nt assay: albumin (Alb ),transferrin (Tf), and al-antitrypsin (a,-AT) as amarker for intestinal protein l0ss, hemoglobin(Hb) for bleeding, PMN-eIastase for intestinalinflammation, and secretory lgA for intestinalimmunity.RESULTS The fecaI concentrations of Hb, Alb,Tf, al-AT, and PMN’eIastase were increased in13 (3l%), 8(19%), l0(24%), 6(14%), and 1l(26%) cases among 42 patients, resPectiveIy.F6cal concentration of secretory IgA wasdecreased in 7 (l7%) of 42 patients. However,these fecal concentrations were not related tothe severity or etiology of liver cirrhosis. Theserum Alb level was significantIy decreased inpatients with intestinal protein Ioss c0mpared tothat in patients without intestinal protein loss.CONCLUSION These findings suggest that: rob6sides the weIl’known pathological conditions,Such as bleeding and protein loss, intestinaIinflammati0n and decreased intestinaI immunityare found in cirrhotic patients, @ intestinalprotein loss contributes to hypoalbuminemia incirrhotic patients, and @ intestinaI inflammationshouId not b6 0verlooked in cirrhotic patients,since it may contribute to or cause intestinalprotein Ioss and oth6r various pathologicalconditions.展开更多
We investigated the biodegradation of 2-nitrophenol （2-NP）, 4-nitrophenol （4-NP）, and 2,4-dinitrophenol （2,4-DNP） in the rhizosphere of Spirodela polyrrhiza plants by conducting degradation experiments with thre...We investigated the biodegradation of 2-nitrophenol （2-NP）, 4-nitrophenol （4-NP）, and 2,4-dinitrophenol （2,4-DNP） in the rhizosphere of Spirodela polyrrhiza plants by conducting degradation experiments with three river water samples supplemented with each nitrophenol （NP）. We then isolated NP-degrading bacteria both from the S. polyrrhiza roots and from the river water. In the river water samples, removal of the three NP was accelerated in the presence of S. polyrrhiza plants. The three NPs persisted in an autoclaved solution with sterile plants suggests that NP removal was accelerated largely by bacterial NP biodegradation rather than by adsorption and uptake by the plants. We isolated 8 strains of NP-degrading bacteria： 6 strains from the S. polyrrhiza roots and 2 strains from river water without the plants. The 2-NP- and 2,4-DNP-degrading bacteria were isolated only from the S. polyrrhiza roots. The 4-NP- degrading bacteria different from those isolated from the river water samples were also found on S. polyrrhiza roots. The 2-NP- and 4-NP-degrading strains isolated from the roots utilized the corresponding NP （0.5 mmol/L） as the sole carbon and energy source. The 2,4-DNP-degrading strains isolated from the roots showed substantial 2,4-DNP-degrading activity, but the presence of other carbon and energy sources was required for their growth. The isolated NP-degrading bacteria from the roots must have contributed to the accelerated degradation of the three NPs in the rhizosphere of S. polyrrhiza. Our results suggested that rhizoremediation with S. polyrrhiza may be effective for NP-contaminated surface water.展开更多
AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following...AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg(n = 201), vonoprazan 10 mg(n = 202), or vonoprazan 20 mg(n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events(AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen Ⅰ/Ⅱ levels, and gastric mucosa histopathology results.RESULTS Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg(P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg(5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan(P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSION Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.展开更多
文摘Objective We aimed to compare the clinical outcomes of intravenous urography-assisted fluoroscopy-guided shockwave lithotripsy for radiolucent ureteral stones and standard shockwave lithotripsy for radiopaque ureteral stones.Methods We retrospectively reviewed 734 patients with ureteral stones treated by fluoroscopy-guided shockwave lithotripsy between March 2014 and March 2021.The primary outcome was a stone-free rate with one session within 30 days,defined as no residual stones without auxiliary treatment.The multivariate analysis was used to examine whether the intravenous urography use predicted treatment success.Furthermore,we compared the outcomes using propensity score matching.Results Ninety-eight patients underwent the intravenous urography use protocol(Group I),and the remaining 636 patients underwent the non-intravenous urography protocol(Group N).Stone-free rates with one session within 30 days were 38%and 32%in groups I and N,respectively(p=0.3).No statistical differences were observed in the conversion rate to ureteroscopy(p=0.3)or complication rate(p=0.7)between Group I and Group N.One patient who developed skin redness was considered a complication of the contrast medium.Propensity score matching examined 88 matched pairs.Treatment success was obtained in 31(35%)patients in Group I and 33(38%)patients in Group N(p=0.9)within 30 days with one session.Conclusion Radiolucent stones can be safely and effectively treated by shockwave lithotripsy with intravenous urography.
基金Supported by Takeda Pharmaceuticals USA,Inc.Medical writing support was provided by Luke Humphreys,PhD,of Oxford PharmaGenesis,Oxford,UK and was funded by Takeda Development Center Americas,Inc.
文摘BACKGROUND Data regarding complex Crohn’s perianal fistulas(CPF)epidemiology are limited,and optimal treatment strategies are elusive.An improved understanding of how CPF treatment options are used in the real-world setting and factors associated with CPF development,treatment failure,and reasons for undergoing multiple surgeries may help to inform optimal patient management strategies,reduce treatment burden,and improve outcomes in patients with CPF.AIM To describe the epidemiology,treatments,outcomes,and associated risk/protective factors for complex CPF.METHODS Electronic databases(MEDLINE,EMBASE,EBM Reviews,EconLit)were searched.Two reviewers independently used populations,interventions,comparators,outcomes,study designs,and time criteria to identify relevant studies.Observational studies published in English from January 1,2015 to February 17,2022 with>50 patients were included,even if complex CPF was not defined.Items of interest included complex CPF definitions,epidemiology,treatment patterns,morbidity,mortality,and risk factors associated with complex CPF development,treatment failure,and undergoing multiple surgeries.Data were reported using descriptive statistics.RESULTS Overall,140 studies were included.Complex CPF definitions were heterogeneous and rarely reported(24 studies).Hence,data mostly related to CPF in general.CPF prevalence was variable(range:1.5%-81.0%).Incidence was wide-ranging and mostly reported cumulatively at 1-year post-Crohn’s disease diagnosis(range:3.5%-50.1%).Overall healing and failure rates after treatment were in the range of 10.5%-80.2%and 3.6%-83.0%,respectively.Abscesses were the most frequently reported morbidity(n=18).No CPF-related deaths were reported.No consistent risk or protective factors were identified.CONCLUSION Epidemiology,treatment patterns,and risk factors for CPF vary,likely due to inconsistent CPF and clinical outcome definitions.Standardization would facilitate comparability,which may inform optimal complex CPF treatment strategies.
基金Supported by National Natural Science Foundation of China,No.82070604 and No.82270618the Shanghai Municipal Key Clinical Specialty,China,No.shslczdzk01103。
文摘BACKGROUND Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes.Various therapies including albumin infusion,volume expanders(VEs),and vasoactive agents are used to manage patients with cirrhosis.Despite numerous clinical trials,a comprehensive meta-analysis comparing the effectiveness of albumin infusion against alternative treatments is limited.This study provides the current and comprehensive synthesis of evidence,offering key insights for optimizing therapeutic strategies in patients with liver cirrhosis.AIM To systematically update available data on therapies of liver cirrhosis,we performed a meta-analysis to evaluate and compare the clinical efficacy of albumin infusion vs other VEs and vasoactive agents in patients with liver cirrhosis.METHODS A literature search from the PubMed and Embase databases(inception till June 2024)focused on hyponatremia(primary outcome)and various outcomes such as gastrointestinal bleeding,hepatic encephalopathy,severe infection,post-paracentesis-induced circulatory dysfunction(PICD),ascites reappearance,spontaneous bacterial peritonitis,hepatorenal syndrome,renal impairment,hospital stay,mortality,and safety was performed.The primary analysis pooled studies that compared albumin infusion with control.In the subgroup analysis,comparisons were made within the stratified treatment categories included in the control group.RESULTS Of the 2957 studies retrieved,31 studies(27 randomized controlled trials and 4 observational studies)comprising 6255 patients were included.Albumin use was significant in reducing odds of hyponatremia[odds ratio(OR)=0.67;95%confidence interval(95%CI)=0.53-0.85]and PICD(OR=0.38;95%CI=0.20-0.71),whereas the reduction in severe infection(OR=0.55;95%CI=0.28-1.07)did not reach statistical significance.In the subgroup analysis,albumin demonstrated a favorable improvement in lowering the incidence of hyponatremia vs inactive/standard medical therapy(OR=0.54;95%CI=0.27-1.09).For PICD,albumin use was significant compared with other VEs(OR=0.31;95%CI=0.11-0.85)but not with vasoconstrictors(OR=0.63;95%CI=0.21-1.91).In the overall subgroup analysis,a significant reduction was observed in hyponatremia(OR=0.67;95%CI=0.53-0.85)and PICD(OR=0.38;95%CI=0.20-0.71).CONCLUSION Human albumin has been shown to significantly reduce the incidence of hyponatremia and PICD in patients with liver cirrhosis,whereas its effect on severe infection remains suggestive but not statistically significant.
文摘Monoclonal antibodies(mAbs)require a high level of purity for regulatory approval and safe administration.High-molecular weight(HMW)species are a common impurity associated with mAb therapies.Hydrophobic interaction chromatography(HIC)resins are often used to remove these HMW impurities.Determination of a suitable HIC resin can be a time and resource-intensive process.In this study,we modeled the chromatographic behavior of seven mAbs across 13 HIC resins using measurements of surface hydrophobicity,surface charge,and thermal stability for mAbs,and hydrophobicity and zeta-potential for HIC resins with high fit quality(adjusted R2>0.80).We identified zeta-potential as a novel key modeling parameter.When using these models to select a HIC resin for HMW clearance of a test mAb,we were able to achieve 60%HMW clearance and 89%recovery.These models can be used to expedite the downstream process development for mAbs in an industry setting.
文摘BACKGROUND Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease(MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes.AIM To investigate the effectiveness of conventional therapy for MS-IBD.METHODS A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn's disease(CD) and ulcerative colitis(UC). Corticosteroids(prednisone, hydrocortisone, budesonide, prednisolone,dexamethasone), 5-aminosalicylic acid(5-ASA) derivatives(mesalazine and sulfasalazine) and immunosuppressants [azathioprine(AZA), methotrexate(MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine(6-MP)] were considered conventional therapy. The exclusion criteria were sample size below50; narrative reviews; specific subpopulations(e.g., pregnant women,comorbidities); studies on postoperative IBD; and languages other than English,Spanish, French or Portuguese. The primary outcome measures were clinical remission(induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria.RESULTS The search strategy identified 1995 citations, of which 27 were considered eligible(7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected(AZA and 6-MP showed no advantage over placebo,MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses). Only one meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus vs placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials(RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing,one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence.CONCLUSION High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.
文摘Herein, we present a case of gastric adenocarcinoma of fundic gland type(GA-FG) spreading to heterotopic gastric glands(HGG) in the submucosa. A 58-year-old man with epigastric pain was referred to our hospital and underwent an esophagogastroduodenoscopy. A Borrmann type II gastric cancer at the antrum and a 10 mm submucosal tumor-like lesion in the lesser curvature of the upper third of the stomach were detected. Histological examination of the biopsy specimens obtained from the submucosal tumorlike lesion suggested a GA-FG. Therefore, endoscopic submucosal dissection was performed as excisional biopsy, and histopathological examination of the resected specimen confirmed a GA-FG and HGG proximal to the GA-FG. Although the GA-FG invaded the submucosal layer slightly, the submucosal lesion of the GA-FG had a poor stromal reaction and was located just above the HGG in the submucosa. Therefore, wefinally diagnosed the lesion as a GA-FG invading the submucosal layer by spreading to HGG.
基金funded by Takeda Pharmaceuticals International Inc.
文摘BACKGROUND Anal fistula is a pathological connection between the anal canal and perianal skin,which most commonly develops from an infected anal crypt.While the majority of anal fistulas are idiopathic,they are also associated with Crohn’s disease(CD)and other inflammatory conditions.The prevalence of anal fistula is estimated to be 1-2 per 10000 patients,but population-based studies on anal fistula epidemiology are limited and outdated.AIM To assess the prevalence of anal fistula and relevant comorbidities,with and without CD in the United Kingdom and Europe.METHODS A retrospective population-representative observational cohort study was performed in The Health Improvement Network(THIN),a United Kingdom primary care database.Mid-year point prevalence of anal fistula was calculated on the first of July for each year between 2014 and 2017.Estimates were calculated for anal fistula overall and by CD status and standardized to the United Kingdom and European population.Prevalence of relevant comorbidities including lymphogranuloma venereum,hidradenitis suppurativa,anal presentation of sexually transmitted diseases,diabetes mellitus,and radiation in the pelvic area was reported.RESULTS The United Kingdom-standardized overall point prevalence of anal fistula was 1.80(95%CI:1.65-1.94)per 10000 patients in 2017,while the Europe standardized estimate was 1.83(95%CI:1.68-1.98)per 10000 patients.Both these standardized point prevalence estimates ranged from 1.89 to 2.36 between 2014-2016.The United Kingdom-standardized point prevalence of anal fistula without CD was 1.35(95%CI:1.23-1.48)per 10000 patients,while the Europe-standardized estimate was 1.39(95%CI:1.26-1.52)per 10000 patients.In contrast,the standardized point prevalence estimate of anal fistula with CD was lower for both United Kingdom and Europe(0.44;95%CI United Kingdom:0.37-0.52,95%CI Europe:0.37-0.51)per 10000 patients in 2017.In 2017,19%of anal fistula patients without CD and 13%of anal fistula patients with CD had at least one relevant comorbidity.These results show that anal fistulas are infrequent in the general population.24.5%of prevalent anal fistulas are associated with CD,but other potentially etiological comorbidities are rare.CONCLUSION This real-world evidence study estimated the United Kingdom-standardized prevalence of anal fistula was 1.80 per 10000 patients in 2017.Approximately 25%of cases may be associated with CD,while other comorbidities are rare.
文摘BACKGROUND Anorectal malignant melanoma(AMM)is a rare disorder with an extremely poor prognosis.Although there is currently no consensus on the treatment methods for AMM,surgical procedures have been the most common treatment methods used until now.We recently encountered a case of AMM that we diagnosed using endoscopic submucosal dissection(ESD).To our knowledge,this is the first case of ESD for AMM,suggesting that ESD can potentially be a diagnostic and treatment method for AMM.CASE S UMA/MARY A 77-year-old woman visited our hospital with a chief complaint of anal bleeding and a palpable rectal mass.Colonoscopy revealed a 20-mm protruded lesion in the lower rectum.After obtaining biopsy specimens from the lesion,although a malignant rectal tumor was suspected,a definitive diagnosis was not made.Endoscopic ultrasonography revealed tumor invasion into the submucosal layer but not the muscular layer.Therefore,we performed an excisional biopsy using ESD.Immunohistochemical examination of the ESD-resected specimen revealed tumor cells positive for Human Melanin Black-45,Melan-A,and S-100.Moreover,the tumor cells lacked melanin pigment;thus,a diagnosis of amelanotic AMM was made.Although the AMM had massively invaded the submucosal layer and both lymphatic and venous invasion were present,we closely monitored the patient without any additional therapy on the basis of her request.Six months after ESD,local recurrence was detected,and the patient consented to wide local excision.CONCL USION It is suggested that ESD is a potential diagnostic and treatment method for AMM.
基金21st Century Center Of Excellence (COE) Program supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan
文摘In this paper, a grid-based distributed hydrological model BTOPMC （Block-wise use of TOPMODEL） is introduced, which was developed from the original TOPMODEL. In order to broaden the model＇s application to arid regions, improvement methodology is also implemented. The canopy interception and soil infiltration processes were incorporated into the original BTOPMC to model event-based runoff simulation in large arid regions. One designed infiltration model with application of time compression approximation method is emphasized and validated for improving model＇s performance for event hydrological simulations with a case study of Lushi River basin.
文摘AIM To investigate the pathophysiology of the digestive tract in patients with liver cirrhosis.METHODS In 42 cirrhotic patients and 20control subjects, the following fecal proteinswere measured by enzyme-linkedimmunosorb6nt assay: albumin (Alb ),transferrin (Tf), and al-antitrypsin (a,-AT) as amarker for intestinal protein l0ss, hemoglobin(Hb) for bleeding, PMN-eIastase for intestinalinflammation, and secretory lgA for intestinalimmunity.RESULTS The fecaI concentrations of Hb, Alb,Tf, al-AT, and PMN’eIastase were increased in13 (3l%), 8(19%), l0(24%), 6(14%), and 1l(26%) cases among 42 patients, resPectiveIy.F6cal concentration of secretory IgA wasdecreased in 7 (l7%) of 42 patients. However,these fecal concentrations were not related tothe severity or etiology of liver cirrhosis. Theserum Alb level was significantIy decreased inpatients with intestinal protein Ioss c0mpared tothat in patients without intestinal protein loss.CONCLUSION These findings suggest that: rob6sides the weIl’known pathological conditions,Such as bleeding and protein loss, intestinaIinflammati0n and decreased intestinaI immunityare found in cirrhotic patients, @ intestinalprotein loss contributes to hypoalbuminemia incirrhotic patients, and @ intestinaI inflammationshouId not b6 0verlooked in cirrhotic patients,since it may contribute to or cause intestinalprotein Ioss and oth6r various pathologicalconditions.
基金supported by Japan Science and Technology Agency (JST)the National Natural Science Foundation of China (NSFC) Project as the Japan-China Joint Research Program on Science and Technology (S&T) for Environmental Conservation and Construction of a Society with Less Environmental Burden with the research theme of Development of remediation technique for water environmental pollution using microorganisms and aquatic plants with purification ability-enhanced rhizosphere
文摘We investigated the biodegradation of 2-nitrophenol （2-NP）, 4-nitrophenol （4-NP）, and 2,4-dinitrophenol （2,4-DNP） in the rhizosphere of Spirodela polyrrhiza plants by conducting degradation experiments with three river water samples supplemented with each nitrophenol （NP）. We then isolated NP-degrading bacteria both from the S. polyrrhiza roots and from the river water. In the river water samples, removal of the three NP was accelerated in the presence of S. polyrrhiza plants. The three NPs persisted in an autoclaved solution with sterile plants suggests that NP removal was accelerated largely by bacterial NP biodegradation rather than by adsorption and uptake by the plants. We isolated 8 strains of NP-degrading bacteria： 6 strains from the S. polyrrhiza roots and 2 strains from river water without the plants. The 2-NP- and 2,4-DNP-degrading bacteria were isolated only from the S. polyrrhiza roots. The 4-NP- degrading bacteria different from those isolated from the river water samples were also found on S. polyrrhiza roots. The 2-NP- and 4-NP-degrading strains isolated from the roots utilized the corresponding NP （0.5 mmol/L） as the sole carbon and energy source. The 2,4-DNP-degrading strains isolated from the roots showed substantial 2,4-DNP-degrading activity, but the presence of other carbon and energy sources was required for their growth. The isolated NP-degrading bacteria from the roots must have contributed to the accelerated degradation of the three NPs in the rhizosphere of S. polyrrhiza. Our results suggested that rhizoremediation with S. polyrrhiza may be effective for NP-contaminated surface water.
文摘AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg(n = 201), vonoprazan 10 mg(n = 202), or vonoprazan 20 mg(n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events(AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen Ⅰ/Ⅱ levels, and gastric mucosa histopathology results.RESULTS Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg(P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg(5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan(P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSION Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.
