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Cystic fibrosis patients on cystic fibrosis transmembrane conductance regulator modulators have a reduced incidence of cirrhosis

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World Journal of Hepatology 2022年第2期14卷 411-419页

作者： Mitchell L ramsey michael r wellner Kyle Porter Stephen E Kirkby Susan S Li Luis F Lara Sean G Kelly A James Hanje Lindsay A Sobotka Department of Gastroenterology Hepatology and NutritionThe Ohio State University Wexner Medical CenterColumbusOH 43210United States Department of Gastroenterology Hepatology and NutritionThe Ohio State Wexner Medical CenterColumbusOH 43210United States Department of Biostatistics The Ohio State UniversityColumbusOH 43210United States Department of Pulmonary and Critical Care Medicine The Ohio State University Wexner Medical CenterColumbusOH 43210United States Department of Internal Medicine The Ohio State University Wexner Medical CenterColumbusOH 43210United States Department of Gastroenterology Hepatology and NutritionThe Ohio State UniversityColumbusOH 43210United States

BACKGrOUND Cystic fibrosis transmembrane conductance regulator(CFTr)modulators significantly improve pulmonary function in patients with cystic fibrosis(CF)but the effect on hepatobiliary outcomes remains *** hypothesized that CF patients on CFTr modulators would have a decreased incidence of cirrhosis compared to patients not on CFTr modulators or on *** To investigate the effect of CFTr modulators on the development of cirrhosis in patients with *** A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of *** were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol *** were grouped by use of CFTr modulators,ursodiol,dual therapy,or no *** primary outcome was development of ***-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment *** A total of 7201 patients were included,of which 955(12.6%)used a CFTr modulator,529(7.0%)used ursodiol,105(1.4%)used combination therapy,and 5612(74.3%)used neither *** incidence of cirrhosis was 0.1%at 1 year and 0.7%at 4 years in untreated patients,5.9%and 10.1%in the Ursodiol group,and 1.0%and 1.0%in patients who received both *** patient treated with CFTr modulators alone developed *** on CFTr modulators alone had lower cirrhosis incidence than untreated patients(P=0.05),patients on Ursodiol(Prapy(P=0.003).The highest incidence of cirrhosis was found among patients treated with Ursodiol alone,compared to untreated patients(Pr patients on Ursodiol and CFTr modulators(P=0.01).CONCLUSION CFTr modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

关键词： Cirrhosis Ursodiol Transmembrane Cystic fibrosis Market scan Cystic fibrosis related liver disease

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On the rate of convergence of the maximum likelihood estimator of a k-monotone density

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Science China Mathematics 2009年第7期52卷 1525-1538页

作者： wellner Jon A Department of Statistics University of Washington

Bounds for the bracketing entropy of the classes of bounded k-monotone functions on [0,A] are obtained under both the Hellinger distance and the Lp(Q) distance,where 1 p < ∞ and Q is a probability measure on [0,A].Th... 详细信息

Bounds for the bracketing entropy of the classes of bounded k-monotone functions on [0,A] are obtained under both the Hellinger distance and the Lp(Q) distance,where 1 p robability measure on [0,A].The result is then applied to obtain the rate of convergence of the maximum likelihood estimator of a k-monotone density.

关键词： bracketing metric entropy maximum likelihood estimator Hellinger distance 62G05 46B50

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High-grade pancreatic intraepithelial lesions： prevalence and implications in pancreatic neoplasia

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Hepatobiliary & Pancreatic Diseases International 2017年第2期16卷 202-208页

作者： Jean r Park Feng Li Veeral M Oza Brett C Sklaw Kevin M Cronley michael wellner Benjamin Swanson Somashekar G Krishna Division of Hospital Medicine The Ohio State University Wexner Medical Center Columbus Ohio USA Division of Gastroenterology Hepatology and Nutrition The Ohio State University Wexner Medical Center Columbus Ohio USA Department of Pathology The Ohio State University Wexner Medical Center Columbus Ohio USA

BACKGrOUND： High-grade pancreatic intraepithelial neoplasia（Pan IN-3）, a precursor of pancreatic ductal adenocarcinoma（PDAC）, is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of Pan IN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms（IPMNs）.METHODS： A retrospective review of a tertiary care center pathology database（1/2000-6/2014） was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were ***： A total of 458 patients who underwent primary pancreatic resection were included. “Pan IN-3” lesions were found in 74（16.2%） patients who either had PDAC（n=67） or main duct（MD）-IPMN（n=7）. Among IPMN-MDs, Pan IN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival（OS） for pancreata with Pan IN-3 lesions was significantly better than those without（OS 1.12 years, interquartile range [IQr] 0.72, 2.05 years vs OS 0.86 years, IQr 0.64,1.60 years respectively; P=0.04）. Multivariate Cox regression analysis demonstrated that the presence of Pan IN-3 lesions was associated with a reduced risk of death（Hr=0.43; 95% CI： 0.23-0.82; P=0.01）.CONCLUSIONS： Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without Pan IN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.

关键词： pancreatic intraepithelial neoplasia intraductal papillary mucinous neoplasms pancreatic neoplasia pancreatic ductal adenocarcinoma

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Impact of postoperative TNM stages after neoadjuvant therapy on prognosis of adenocarcinoma of the gastro-oesophageal junction tumours

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World Journal of Gastroenterology 2018年第13期24卷 1429-1439页

作者： michael Thomaschewski richard Hummel Ekaterina Petrova Juliana Knief Ulrich Friedrich wellner Tobias Keck Dirk Bausch Department of Surgery University Medical Center Schleswig-Holstein Campus Lübeck Department of Pathology University Medical Center Schleswig-Holstein Campus Lübeck

AIM To compare prognostic relevance of postoperative tumour/node/metastasis(TMN) stages between patients with and without neoadjuvant treatment. METHODS Data from patients with adenocarcinoma of the gastrooesophageal junction(AEG) who had undergone surgical resection at a single German university centre were retrospectively analysed. Patients with or without neoadjuvant preoperative treatment were selected by exact matching based on preoperative staging. Standard assessment of preoperative(c)TNM stage was based on endoscopic ultrasound and computed tomography of the thorax and abdomen, according to the American Joint Committee on Cancer/Union for International Cancer Control classification system. Patients with cT1cN0cM0 and cT2cN0cM0 stages were excluded from the study, as these patients are generally not recommended for pretreatment. Longterm survival among the various postoperative TNM stages was compared between the groups of patients with or without neoadjuvant treatment. For statistical assessments, a P-value of ≤ 0.05 was considered *** The study included a total of 174 patients. The group of patients who had received preoperative neoadjuvant treatment included more cases of AEG(Siewert) type 1 carcinoma(P rformed more frequently among these patients(P roups(with or without preoperative neoadjuvant treatment) had comparable preoperative T stages, but the group of patients with preoperative neoadjuvant treatment presented a higher rate of preoperative N-positive disease(P = 0.020). Overall long-term survival was not different between the two groups of patients according to tumours of different AEG classifications, receipt of oesophagectomy or gastrectomy, nor between patients with similar postoperative TNM stage, resection margin and grading. However, an improvement of long-term survival was found for patients with nodal down-staging after neoadjuvant therapy(P = 0.053).CONCLUSI

关键词： Adenocarcinoma of the gastro-oesophageal junction American Joint Committee on Cancer/Union for International Cancer Control TNM system Neoadjuvant therapy Oesophageal cancer

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rare cause of dysphagia after esophageal variceal banding: A case report

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World Journal of Gastrointestinal Endoscopy 2019年第4期11卷 292-297页

作者： Lindsay A Sobotka Mitchell L ramsey michael wellner Sean G Kelly Department of Gastroenterology Hepatology and Nutrition The Ohio State University Wexner Medical Center

BACKGrOUND Esophageal varices are a result of progressive liver disease and portal hypertension. Treatment can be performed with band ligation versus nonselective beta blockers depending on the size of varices, ability to tolerate medications and history of variceal bleeding. Band ligation is an effective intervention with rare but serious complications including bleeding, ulcers and rarely obstruction. Few cases of esophageal obstruction and necrosis caused by banding have been reported, each with varied management from conservative treatment to band *** SUMMArY An 89 years old woman with a past medical history of nonalcoholic steatohepatitis cirrhosis presented to the hospital with an inability to swallow one day after screening esophagogastroduodenoscopy where band ligation of esophageal varices was performed for primary prophylaxis. The patient was not able to tolerate her oral secretions. Initial blood work revealed a Model of End Organ Liver Disease score of 7. She was treated with sublingual nitroglycerin for esophageal spasm, a known complication after esophageal banding. When she failed to improve, esophagogastroduodenoscopy was performed and revealed the mucosa surrounding the banded varix was necrosed and blocking the lumen of the esophagus. The band was purposefully dislodged, revealing distal ulceration and stricturing. Within 72 h after band removal, she was tolerating an oral diet. Endoscopy performed 2 wk later revealed an intrinsic stenosis,measuring 8 mm in diameter by 1 cm in length, which was *** Esophageal obstruction is a complication of variceal banding that should be considered in patients with inability to tolerate oral diet after banding.

关键词： Case report Esophageal varices Band ligation Esophageal necrosis Esophageal obstruction

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公路路面结构寿命研究

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重庆交通大学学报（自然科学版） 2018年第10期37卷 31-36页

作者： Frohmut wellner 梁乃兴德累斯顿工业大学城市与公路研究所重庆交通大学土木工程学院重庆400074

现行路面结构设计及材料组成设计对交通荷载增长及环境气候变化等影响因素考虑不够,针对这一问题,分析了沥青、沥青混合料、沥青路面层间联结强度等对沥青路面疲劳寿命的影响作用,及对路面结构设计和材料组成设计的影响作用,并提出了解... 详细信息

现行路面结构设计及材料组成设计对交通荷载增长及环境气候变化等影响因素考虑不够,针对这一问题,分析了沥青、沥青混合料、沥青路面层间联结强度等对沥青路面疲劳寿命的影响作用,及对路面结构设计和材料组成设计的影响作用,并提出了解决的途径。研究为路面结构分析设计提出了一个新的思路。

关键词：道路工程路面结构寿命沥青层间联结

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路表温度对沥青路面疲劳损伤的影响

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公路交通科技 2013年第1期30卷 1-5,16页

作者：韦璐 Sascha KAYSEr Frohmut wellner 安徽建筑工业学院土木工程学院安徽合肥230601 德累斯顿工业大学城市和路面工程研究所德国德累斯顿01069

为准确评价温度影响下沥青路面结构的抗疲劳性能,解决采用某单一固定温度预估疲劳损伤不够精确的问题,以德国德累斯顿工业大学提出的路面温度场预估模型为例,基于Miner疲劳累积损伤定理,分析路表不同温度及其组合对沥青路面疲劳损伤的... 详细信息

为准确评价温度影响下沥青路面结构的抗疲劳性能,解决采用某单一固定温度预估疲劳损伤不够精确的问题,以德国德累斯顿工业大学提出的路面温度场预估模型为例,基于Miner疲劳累积损伤定理,分析路表不同温度及其组合对沥青路面疲劳损伤的影响。通过大量实测的路表温度数据,确定不同的路表温度组合及其组合内温度区间的温度代表值,研究路面结构疲劳损伤变化的规律。分析结果表明:采用由多个温度区间组成的路表温度组合预估疲劳损伤比用某单一固定路表温度预估更精确;组成路表温度组合的温度区间划分越多,路面结构疲劳损伤预估的精度越高;温度区间划分越少,区间内选取不同的温度代表值预估路面结构疲劳损伤差异越大;温度区间内温度代表值取区间上限高温,对沥青路面结构疲劳损伤的影响远比区间下限低温影响大。

关键词：道路工程沥青路面计算机仿真路表温度组合疲劳损伤温度区间

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国际常用块材铺设路面的性能(摘要)

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建筑砌块与砌块建筑 2011年第6期 38-38,40页

作者： Frohmut wellner 刘畅德国德累斯顿工程大学

用块状材料铺设路面的方法,是铺筑道路路面最古老的方法之一,最早已知用块材铺设路面的技术,至今已有约5000到8000年。因此,人们可以通过路面所用新、旧块材的多种路面建造方案,来窥探社会变迁的过程;同时也证明了块材路面适用于行驶机... 详细信息

用块状材料铺设路面的方法,是铺筑道路路面最古老的方法之一,最早已知用块材铺设路面的技术,至今已有约5000到8000年。因此,人们可以通过路面所用新、旧块材的多种路面建造方案,来窥探社会变迁的过程;同时也证明了块材路面适用于行驶机动车的道路。

关键词：道路路面块材铺设摘要性能国际块状材料建造方案

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Applicability of in Vitro Models in Predicting the in Vivo Bioavailability of Lycopene and β-Carotene from Differently Processed Soups

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Food and Nutrition Sciences 2012年第4期3卷 477-489页

作者： Marie Alminger Cecilia Svelander Anna wellner rebeca Martinez-Tomas Lucy Bialek Elvira Larque Francisca Perez-Llamas Department of Chemical and Biological Engineering Food ScienceChalmers University of TechnologyGoteborgSweden Physiology Department Faculty of BiologyUniversity of MurciaMurciaSpain Unilever Discover r&D Unilever Food and Health Research InstituteVlaardingenThe Netherlands

Presently, there is no clear consensus on the best approach to estimate carotenoid bioavailability. The best alternative would be to use human studies, but they are labour-intensive and expensive and can only be used to investigate a limited number of samples. Hence, a number of in vitro: models have been developed to study pre-absorptive processes and factors affecting bioavailability. The question is, however, how well the results obtained by the various methods correlate to each other and to the in vivo situation. In the present paper, we have compared in vivo data from two human studies on differently processed soups containing carrots, tomato and broccoli, with results obtained by in vitro characterisation of the same soups. In vitro bioaccessibility was estimated by a static in vitro digestion investigating matrix release and micellarization of carotenoids and by uptake studies in a human intestinal cell line (Caco-2). In vivo data was obtained from clinical studies measuring total plasma carotenoid concentrations in human subjects after 4 weeks daily consumption of the soups. Comparison of the in vitro and in vivo results indicate that the combination of a two-step in vitro digestion and Caco-2 cells seems to be a useful tool for estimation of β-carotene bioaccessibility and screening of factors governing the release of β-carotene from this type of food. For lycopene the in vitro and in vivo results were less consistent, suggesting that reliable prediction of lycopene bioavailability might be more problematic.

关键词： In Vitro Digestion Human Uptake Caco-2 Cells β-Carotene Lycopene Carotene Bioavailability

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Arguments for an individualized closure of the pancreatic remnant after distal pancreatic resection

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World Journal of Gastrointestinal Surgery 2012年第5期4卷 114-120页

作者： Ulrich Friedrich wellner Frank Makowiec Olivia Sick Ulrich Theodor Hopt Tobias Keck Department of General and Visceral Surgery University of Freiburg

AIM:To analyze risk factors for postoperative pancreatic fistula(POPF) rate after distal pancreatic resection(DPr).METHODS:We performed a retrospective analysis of 126 DPrs during 16 *** primary endpoint was clinically relevant pancreatic ***:Over the years,there was an increasing rate of operations in patients with a high-risk pancreas and a significant change in operative *** was the most prominent factor for perioperative *** risk factors for pancreatic fistula were high body mass index(BMI) [odds ratio(Or) = 1.2(CI:1.1-1.3),P = 0.001],high-risk pancreatic pathology [Or = 3.0(CI:1.3-7.0),P = 0.011] and direct closure of the pancreas by hand suture [Or = 2.9(CI:1.2-6.7),P = 0.014].Of these,BMI and hand suture closure were independent risk factors in multivariate *** hand suture closure was a risk factor in the low-risk pancreas subgroup,high BMI further increased the fistula rate for a high-risk ***:We propose a risk-adapted and indication-adapted choice of the closure method for the pancreatic remnant to reduce pancreatic fistula rate.

关键词： Distal pancreatic resection Postoperative pancreatic fistula Body mass index

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