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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Esophageal diverticulum: New perspectives in the era of minimally invasive endoscopic treatment

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World Journal of gastroenterology 2019年第12期25卷 1457-1464页

作者： Hiroki Sato Manabu Takeuchi Satoru Hashimoto Ken-ichi Mizuno Koichi Furukawa Akito Sato Junji Yokoyama Shuji Terai division of gastroenterology Niigata University Medical and Dental Hospital division of gastroenterology Nagaoka Red Cross Hospital division of gastroenterology Niigata City General Hospital division of gastroenterology Nagaoka Chuo General Hospital

Esophageal diverticula are rare conditions that cause esophageal symptoms, such as dysphagia, regurgitation, and chest pain. They are classified according to their location and characteristic pathophysiology into three types: epiphrenic diverticulum, Zenker's diverticulum, and Rokitansky diverticulum. The former two disorders take the form of protrusions, and symptomatic cases require interventional treatment. However, the esophageal anatomy presents distinct challenges to surgical resection of the diverticulum, particularly when it is located closer to the oral orifice. Since the condition itself is not malignant,minimally invasive endoscopic approaches have been developed with a focus on alleviation of symptoms. Several types of endoscopic devices and techniques are currently employed, including peroral endoscopic myotomy(POEM). However,the use of minimally invasive endoscopic approaches, like POEM, has allowed the development of new disorder called iatrogenic esophageal diverticula. In this paper, we review the pathophysiology of each type of diverticulum and the current state-of-the-art treatment based on our experience.

关键词： Diverticulum Esophagus Epiphrenic diverticulum Zenker's diverticulum Rokitansky diverticulum Iatrogenic disease Esophageal achalasia Peroral endoscopic myotomy Diverticulectomy

Clinical features and long-term outcomes of patients with colonic oligopolyposis of unknown etiology

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World Journal of gastroenterology 2022年第48期28卷 6950-6961页

作者： Dan Feldman Linda Rodgers-Fouche Stephanie Hicks Daniel C Chung division of gastroenterology Massachusetts General HospitalBostonMassachusetts 02114United States Center for Cancer Risk Assessment Massachusetts General HospitalBostonMassachusetts 02114United States division of gastroenterology and Center for Cancer Risk Assessment Massachusetts General HospitalHarvard Medical SchoolBostonMassachusetts 02114United States

BACKGROUND Colonic adenomatous polyposis of unknown etiology(CPUE)is an adenomatous polyposis phenotype that resembles Familial Adenomatous Polyposis(FAP)even though no germline pathogenic variant is *** We sought to better characterize the clinical features and outcomes in a cohort of CPUE *** This is a retrospective case series of patients 18 years old or older with adenomatous oligopolyposis(between 10-100 adenomas)and negative genetic testing,identified through the Hereditary Gastrointestinal Cancer Database at massachusetts general hospital,a tertiary academic referral center.A retrospective chart review was performed with a focus on demographics,alcohol and tobacco use,medication use,familial malignancy and polyp burden,genetic testing information,endoscopic surveillance data including the corresponding histopathology,colonic and extracolonic malignancies,mortality events,and their *** correlation and Pearson Chi-square test(or Fisher's exact test)were used for continuous and categorical variables *** CPUE patients were primarily male(69%)and presented for genetic counseling at 63.7 *** 2 patients(2.9%)reported a first-degree relative with *** an average surveillance period of 12.3 years,0.5 colonoscopies per year were *** developed 2.3 new adenomas per year.4(5.7%)were diagnosed with colorectal cancer(CRC)at a mean age of 66 years,and 3 were diagnosed prior to the onset of oligopolyposis.7(10%)required colectomy due to advanced dysplasia or polyp *** respect to upper gastrointestinal manifestations,1 patient had a gastric adenoma,but there were no cases of gastric or small bowel *** surveillance,10(14%)patients died at a mean age of 72,and none were due to *** CPUE is distinct from familial adenomatous polyposis(FAP)syndrome and the use of FAP surveillance guidelines may result in unnecessarily frequent upper and lower endoscopies.

关键词： Colonic polyposis of unknown etiology Multigene cancer panel Colorectal cancer Colectomy Surveillance Mortality

hospital readmissions in decompensated cirrhotics: Factors pointing toward a prevention strategy

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World Journal of gastroenterology 2017年第37期23卷 6868-6876页

作者： Siamak M Seraj Emily J Campbell Sarah K Argyropoulos Kara Wegermann Raymond T Chung James M Richter massachusetts general hospital Division of Gastroenterology Duke University hospital Department of Medicine Harvard Medical School

AIM To reduce readmissions and improve patient outcomes in cirrhotic patients through better understanding of readmission *** We performed a single-center retrospective study of patients admitted with decompensated cirrhosis from January 1, 2011 to December 31, 2013(n = 222). Primary outcomes were time to first readmission and 30-d readmission rate due to complications of cirrhosis. Clinical and demographic data were collected to help describe predictors of readmission, along with care coordination measures such as post-discharge status and outpatient follow-up. Univariate and multivariateanalyses were performed to describe variables associated with *** One hundred thirty-two patients(59.4%) were readmitted at least once during the study period. Median time to first and second readmissions were 54 and 93 d, respectively. Thirty and 90-d readmission rates were 20.7 and 30.1 percent, respectively. Predictors of 30-d readmission included education level, hepatic encephalopathy at index, ALT more than upper normal limit and Medicare coverage. There were no statistically significant differences in readmission rates when stratified by discharge disposition, outpatient follow-up provider or time to first outpatient *** Readmissions are challenging aspect of care for cirrhotic patients and risk continues beyond 30 d. More initiatives are needed to develop enhanced, longitudinal post-discharge systems.

关键词： Chronic disease Re-hospitalizations Liver disease Readmissions Cirrhosis Chronic care

Management of inflammatory bowel disease with Clostridium difficile infection

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World Journal of gastroenterology 2017年第27期23卷 4986-5003页

作者： Julie D’Aoust Robert Battat Talat Bessissow division of Internal Medicine Jewish General Hospital division of gastroenterology Jewish General Hospital division of gastroenterology Mc Gill University Health Centre

To address the management of Clostridium difficile (C. difficile) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare. METHODSA systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBD-related hospitalizations. RESULTSIn those with IBD, CDI is associated with increased morbidity, including subsequent escalation in IBD medical therapy, urgent colectomy and increased hospitalization, as well as excess mortality. Vancomycin-containing regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid, immunomodulator, or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI, while immunomodulators and biologics are not. CONCLUSIONStrong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However, based on expert opinion and observational data, initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.

关键词： Biologic therapy Clostridium difficile Inflammatory bowel disease Ulcerative colitis Crohn’s disease Corticosteroids

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阿司匹林用于结直肠癌预防(英文)

化学进展 2013年第9期25卷 1450-1453页

作者： Andrew T.Chan division of gastroenterology Massachusetts General Hospital

一直以来,实验室研究、流行病学调查和最近的随机对照临床试验都表明阿司匹林可以降低结直肠癌的风险。出于对潜在的副作用如胃肠道出血的考虑,此前美国预防医学工作组的专家曾经建议对于处于平均风险的普通人群不要常规使用阿司匹林来... 详细信息

一直以来,实验室研究、流行病学调查和最近的随机对照临床试验都表明阿司匹林可以降低结直肠癌的风险。出于对潜在的副作用如胃肠道出血的考虑,此前美国预防医学工作组的专家曾经建议对于处于平均风险的普通人群不要常规使用阿司匹林来预防结直肠癌。然而,最近的高质量证据表明,阿司匹林不仅可以预防结直肠癌,对其它癌症也有预防作用。因此,值得重新考虑阿司匹林是否可常规用于癌症预防这个问题。本文总结了这些支持阿司匹林化学预防功效的有力证据,认为阿司匹林广泛的抗癌效应加上它在预防心血管疾病中的作用可能推动阿司匹林在众多患者中的长期应用。

关键词：阿司匹林结直肠癌随机对照试验非阿司匹林非甾体抗炎药化学预防

Endoscopic hemoclip treatment for bleeding peptic ulcer

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World Journal of gastroenterology 2000年第1期6卷 53-56页

作者： Lai YC Yang SS Wu CH Chen TK division of gastroenterology Cathay General HospitalTaipei division of gastroenterology Cathay General HospitalTaipei Medical FacultyChina Medical CollegeTaichungTaiwanChina

AIM To evaluate the efficacy of endoscopichemoclip in the treatment of bleeding *** Totally,40 patients with F1a andFib hemorrhagic activity of peptic ulcers wereenrolled in this uncontrolled prospective studyfor endoscopic hemoclip *** used anewly developed rotatable clip-device for theapplication of hemoclip(MD850)to *** was repeated if there wasany sign or suspicion of rebleeding,and re-clipping was performed if necessary *** Initial hemostatic rate by clippingwas 95%,and rebleeding rate was only 8%.Ultimate hemostatic rates were 87%,96%,and93% in the Fla and Flb subgroups,and totalcases,*** patients with shock onadmission,hemoclipping achieved ultimatehemostasis of 71% and 83% in F1a and F1bsubgroups,*** reached100% in patients without shock regardless ofhemorrhagic activity being F1a or *** number of clips used per case was 3.0(range 2-5).Spurting bleeders required moreclips on average than did oozing bleeders(3.4versus 2.8).We observed no obviouscomplications,no tissue injury,or impairmentof ulcer healing related to *** Endoscopic hemoclip placementis an effective and safe *** theimprovement of the clip and application device,the procedure has become easier and much *** hemoclipping deservesfurther study in the treatment of bleeding pepticulcers.

关键词： Subject headings endoscopic hemoclipping gastrointestinal hemorrhage/therapy peptic ulcer hemostasis

Why are we performing fewer cholecystectomies for mild acute biliary pancreatitis?Trends and predictors of cholecystectomy from the National Readmissions Database(2010–2014)

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gastroenterology Report 2019年第5期7卷 331-337,I0002页

作者： Sushil Kumar Garg Fateh Bazerbachi Shashank Sarvepalli Shounak Majumder Shanthi Swaroop Vege division of gastroenterology and Hepatology Mayo ClinicRochesterMNUSA division of gastroenterology Massachusetts General HospitalBostonMAUSA Department of hospital Medicine Cleveland ClinicClevelandOHUSA

Background:Current guidelines recommend cholecystectomy for patients with mild acute biliary pancreatitis(MABP)during the index admission because it is associated with better *** this study,we aimed to assess national trends in cholecystectomy during index admissions for MABP and to identify factors associated with cholecystectomy completion and 30-day ***:Using diagnostic codes and the National Readmissions Database,we identified patients admitted with MABP between 2010 and *** in cholecystectomy rates were computed on the basis of various *** conducted a multivariable analysis to identify factors associated with 30-day readmission and cholecystectomy during the same ***:We identified 255,695 unique index MABP cases(41.3%male)and the 30-day readmission rate was 12.6%.Overall,43.8%underwent cholecystectomy and 25%underwent endoscopic retrograde cholangiopancreatography(ERCP)with *** observed a decreasing trend in both procedures during the study period(P<0.001).In multivariate analysis,odds of 30-day readmission were reduced for patients undergoing ERCP with sphincterotomy(odds ratio,0.78;95%confidence interval,0.74–0.84)or cholecystectomy(odds ratio,0.37;95%confidence interval,0.35–0.39).Conclusions:For patients with MABP,cholecystectomy or ERCP with sphincterotomy during the index admission decreased the risk of 30-day *** this benefit and national guidelines recommending cholecystectomy during the index MABP admission,the rate of cholecystectomies performed nationally decreased during the study *** research is needed to understand the implications and reasons underlying this deviation from guidelines.

关键词： cholecystectomy mild acute biliary pancreatitis National Readmissions Database endoscopic retrograde cholangiopancreatography

Risk factors and metabolic abnormality of patients with non-alcoholic fatty liver disease: Either non-obese or obese Chinese population

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Hepatobiliary & Pancreatic Diseases International 2018年第1期17卷 45-48页

作者： Shou-Wu Lee Teng-Yu Lee Sheng-Shun Yang Chun-Fang Tung Hong-Zen Yeh Chi-Sen Chang division of gastroenterology Department of Internal Medicine Taichung Veterans General Hospital

Background: Non-alcoholic fatty liver disease(NAFLD) occurs not only in obese individuals but also in non-obese ones. The aim of this study was to focus on the association between NAFLD and metabolic events in a non-obese or obese Chinese ***: Data collected from subjects registered at Taichung Veterans general hospital from January to December 2009 were analyzed. The exclusion criteria were alcoholics, chronic hepatitis B or C. Patients included in analyses were assigned to four groups according to sonography of their liver(normal or NAFLD), and body mass index(BMI) levels(non-obese if BMI < 25 kg/m~2 or obese if BMI ≥ 25 kg/m~2).Results: There were 745, 208, 770 and 285 patients enrolled in four groups labeled non-obese normal liver(group A), non-obese NAFLD(group B), obese normal liver(group C) and obese NAFLD(group D),respectively. The highest ratio of metabolic syndrome existed in the group B(26.9%), followed by group A(11.7%), group D(10.9%) and finally the group C(5.2%). The positive association with NAFLD in non-obese individuals was significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02) and glucose(OR = 1.02; 95% CI:1.01–1.03), while the positive association with NAFLD in obese subjects was only significant in triglyceride(OR = 1.01; 95% CI: 1.01–1.02). The positive association was most significant in all cases(adjusted OR = 2.41; 95% CI: 1.78–3.24), especially in non-obese individuals(OR = 2.81; 95% CI: 1.92–4.12).Conclusions: Non-obese NAFLD subjects displayed a higher proportion of metabolic abnormality. Hyperlipidemia and hyperglycemia had the most positive strength association with NAFLD.

关键词： Fatty liver Non-alcoholic fatty liver disease Obese Chinese population