1.Introduction。There is abundant evidence that the amount of habitual physical activity(PA)and the level of cardiorespiratory fitness(CRF)are inversely related to developing chronic diseases,including cardiovascular(...1.Introduction。There is abundant evidence that the amount of habitual physical activity(PA)and the level of cardiorespiratory fitness(CRF)are inversely related to developing chronic diseases,including cardiovascular(CV)disease(CVD).Relative to the CV and all-cause mortality reductions associated with exercise,intensity and duration also appear to be inversely related.For example,the mortality reductions that are associated with a regular 5-min run~a 15-min walk,and a 25-min run~a 105-min walk.1 In addition,at comparable levels of total energy expenditure,vigorous exercise seems to be more effective than moderate-intensity exercise in reducing CV risk.2 Vigorous exercise training is also more effective than moderate intensity training at increasing CRF,expressed as metabolic equivalents or METs,which has been shown to confer a lower risk of mortality.3 Accordingly,the optimal physiologic,clinical,and survival benefits of exercise are most likely to be achieved by progressing from moderate intensity exercise(usually defined as 40%-59%of functional capacity or 55%-69%of the maximal heart rate)to vigorous training regimens,corresponding to≥60%of functional capacity or 70%-89%of the measured maximal heart rate.展开更多
AIM:To systematically review the data on distinctive aspects of peptic ulcer disease(PUD),Dieulafoy’s lesion(DL),and Mallory-Weiss syndrome(MWS)in patients with advanced alcoholic liver disease(a ALD),including alcoh...AIM:To systematically review the data on distinctive aspects of peptic ulcer disease(PUD),Dieulafoy’s lesion(DL),and Mallory-Weiss syndrome(MWS)in patients with advanced alcoholic liver disease(a ALD),including alcoholic hepatitis or alcoholic cirrhosis.METHODS:Computerized literature search performed via Pub Med using the following medical subject heading terms and keywords:"alcoholic liver disease","alcoholic hepatitis","alcoholic cirrhosis","cirrhosis","liver disease","upper gastrointestinal bleeding","nonvariceal upper gastrointestinal bleeding","PUD",‘‘DL’’,‘‘Mallory-Weiss tear",and"MWS’’.RESULTS:While the majority of acute gastrointestinal(GI)bleeding with a ALD is related to portal hypertension,about 30%-40%of acute GI bleeding in patients with a ALD is unrelated to portal hypertension.Such bleeding constitutes an important complication of a ALD because of its frequency,severity,and associated mortality.Patients with cirrhosis have a markedly increased risk of PUD,which further increases with the progression of cirrhosis.Patients with cirrhosis or a ALD and peptic ulcer bleeding(PUB)have worse clinical outcomes than other patients with PUB,including uncontrolled bleeding,rebleeding,and mortality.Alcohol consumption,nonsteroidal anti-inflammatory drug use,and portal hypertension may have a pathogenic role in the development of PUD in patients with a ALD.Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients.The frequency of bleeding from DL appears to be increased in patients with a ALD.DL may be associated with an especially high mortality in these patients.MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism,and is associated with a ALD.Patients with a ALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics.Preendoscopic management of acute GI bleeding in patients with a ALD unrelated to portal hypertension is similar to the management of a ALD patients with GI bleeding from portal hypertension,because clinical distinction before endoscopy is difficult.Most patients require intensive care unit admission and attention to avoid over-transfusion,to correct electrolyte abnormalities and coagulopathies,and to administer antibiotic prophylaxis.Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal.Prompt endoscopy,after initial resuscitation,is essential to diagnose and appropriately treat these patients.Generally,the same endoscopic hemostatic techniques are used in patients bleeding from PUD,DL,or MWS in patients with a ALD as in the general population.CONCLUSION:Nonvariceal upper GI bleeding in patients with a ALD has clinically important differences from that in the general population without a ALD,including:more frequent and more severe bleeding from PUD,DL,or MWS.展开更多
AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy(PHG) based on a systematic literature review.METHODS: Computerized search of the literature ...AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy(PHG) based on a systematic literature review.METHODS: Computerized search of the literature was performed via Pub Med using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG.PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepaticportosystemic-shunt or liver transplantation is highly successful ultimate therapies because they reduce the underlying portal hypertension.CONCLUSION: PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.展开更多
Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic ...Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.展开更多
A 68-year-old man presented with progressive right lower quadrant abdominal pain and tenderness without rebound tenderness, and with constipation during the prior 9 mo. Abdomino-pelvic computed tomography and magnetic...A 68-year-old man presented with progressive right lower quadrant abdominal pain and tenderness without rebound tenderness, and with constipation during the prior 9 mo. Abdomino-pelvic computed tomography and magnetic resonance imaging demonstrated a dilated appendix forming a fistula to the sigmoid colon. Open laparotomy revealed a bulky abdominal tumor involving appendix, cecum, and sigmoid, and extending up to adjacent viscera, without ascites or peritoneal implants. The abdominal mass was removed en bloc, including resection of sigmoid colon, cecum(with preservation of ileocecal valve), appendix, right vas deferens, testicular vessels, and minimal amounts of anterior abdominal wall; and shaving off of small parts of the walls of the urinary bladder and small bowel. Gross and microscopic pathologic examination revealed an appendix-to-sigmoid malignant fistula secondary to perforation of mucinous adenocarcinoma of the appendix with minimal local spread(stage T4). However, the surgical margins were clear, all 13 resected lymph nodes were cancer-free, and pseudomyxoma peritonei or peritoneal implants were not present. The patient did well during 1 year of follow-up with no clinical or radiologic evidence of local recurrence, metastases, or pseudomyxoma peritonei despite presenting with extensive stage T4 cancer that was debulked without administering chemotherapy, and despite presenting with malignant appendiceal perforation. This case illustrates the non-aggressive biologic behavior of this low-grade malignancy. The fistula may have prevented free spillage of cancerous cells and consequent distant metastases by containing the appendiceal contents largely within the colon.展开更多
AIM To systematically review safety/efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography(ERCP) performed during pregnancy, considering fetal viability, fetal teratogenicity, premature delivery, and f...AIM To systematically review safety/efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography(ERCP) performed during pregnancy, considering fetal viability, fetal teratogenicity, premature delivery, and future postpartum development of the infant.METHODS Systematic computerized literature search performed using PubMed with the key words "ERCP" and "pregnancy". Two clinicians independently reviewed the literature, and decided on which articles to incorporate in this review based on consensus and preassigned priorities. Large clinical trials, meta-analyses, systematic reviews, and controlled trials were assigned higher priority than review articles or small clinical series, and individual case reports were assigned lowest priority. Dr. Cappell has formal training and considerable experience in conducting systematic reviews, with 4 published systematic reviews in peer-reviewed journals indexed in PubM ed during the last 2 years, and with a PhD in neurophysiology that involved 5 years of training and research in biomedical statistics.RESULTS Advances in imaging modalities, including abdominal ultrasound, MRCP, and endoscopic ultrasound, have generally obviated the need for diagnostic ERCP in nonpregnant and pregnant patients. Clinical experience with performing ERCP during pregnancy is burgeoning, with > 500 cases of therapeutic ERCP reported in the literature, aside from a national registry study of 58 patients. These studies show that therapeutic ERCP has a very high rate of technical success in clearing the bile duct of gallstones, and has a relatively low and acceptable rate of maternal and fetal complications. The great majority of births after therapeutic ERCP are full-term, have normal birth weights, and are healthy. A recent trend is performing ERCP without radiation to eliminate radiation teratogenicity. Systematic literature review reveals 147 cases of ERCP without fluoroscopy in 8 clinical series. These studies demonstrate extremely high technical success in endoscopically removing choledocholithiasis, favorable maternal outcomes with rare maternal ERCP complications, and excellent fetal outcomes. ERCP without fluoroscopy generally confirms proper biliary cannulation by aspiration of yellow bile per sphincterotome or leakage of yellow bile around an inserted guide-wire.CONCLUSION This systematic literature review reveals ERCP is relatively safe and efficacious during pregnancy, with relatively favorable maternal and fetal outcomes after ERCP. Recommendations are provided about ERCP indications, special ERCP techniques during pregnancy, and prospects for future research.展开更多
Endoscopic-retrograde-cholangiopancreatography(ERCP) is now a vital modality with primarily therapeutic and occasionally solely diagnostic utility for numerous biliary/pancreatic disorders. It has a significantly stee...Endoscopic-retrograde-cholangiopancreatography(ERCP) is now a vital modality with primarily therapeutic and occasionally solely diagnostic utility for numerous biliary/pancreatic disorders. It has a significantly steeper learning curve than that for other standard gastrointestinal(GI) endoscopies, such as esophagogastroduodenoscopy or colonoscopy, due to greater technical difficulty and higher risk of complications. Yet, GI fellows have limited exposure to ERCP during standard-three-year-GI-fellowships because ERCP is much less frequently performed than esophagogastroduodenoscopy/colonoscopy. This led to adding an optional year of training in therapeutic endoscopy. Yet many graduates from standard three-year-fellowships without advanced training intensely pursue independent/unsupervised ERCP privileges despite inadequate numbers of performed ERCPs and unacceptably low rates of successful selective cannulation of desired(biliary or pancreatic) duct. Hospital credentialing committees have traditionally performed ERCP credentialing, but this practice has led to widespread flouting of recommended guidelines(e.g., planned privileging of applicant with 20% successful cannulation rate, or after performing only 7 ERCPs);and intense politicking of committee members by applicants, their practice groups, and potential competitors. Consequently, some gastroenterologists upon completing standard fellowships train and learn ERCP 'on the job' during independent/unsupervised practice, which can result in bad outcomes: high rates of failed bile duct cannulation. This severe clinical problem is indicated by publication of ≥ 12 ERCP competency studies/guidelines during last 5 years. However, lack of mandatory, quantitative, ERCP credentialing criteria has permitted neglect of recommended guidelines. This work comprehensively reviews literature on ERCP credentialing;reviews rationales for proposed guidelines;reports problems with current system;and proposes novel criteria for competency. This work advocates for mandatory, national, written,minimum, quantitative, standards, including cognitive skills(possibly assessed by a nationwide examination), and technical skills, assessed by number performed(≥ 200-250 ERCPs), types of ERCPs, success rate(approximately ≥ 90%cannulation of desired duct), and letters of recommendation by program director/ERCP mentor. Mandatory criteria should ideally not be monitored by a hospital committee subjected to intense politicking by applicants, their employers, and sometimes even competitors, but an independent national entity,like the National Board of Medical Examiners/American Board of Internal Medicine.展开更多
AIM: To devise a simplified and efficient method for long-term culture and maintenance of embryonic stem cells requiring less frequent passaging. METHODS: Mouse embryonic stem cells(ESCs) labeled with enhanced yellow ...AIM: To devise a simplified and efficient method for long-term culture and maintenance of embryonic stem cells requiring less frequent passaging. METHODS: Mouse embryonic stem cells(ESCs) labeled with enhanced yellow fluorescent protein were cultured in three-dimensional(3-D) self-assembling scaffolds and compared with traditional two-dimentional(2-D) culture techniques requiring mouse embryonic fibroblast feeder layers or leukemia inhibitory factor. 3-D scaffolds encapsulating ESCs were prepared by mixing ESCs with polyethylene glycol tetra-acrylate(PEG-4-Acr) and thiolfunctionalized dextran(Dex-SH). Distribution of ESCs in 3-D was monitored by confocal microscopy. Viability and proliferation of encapsulated cells during long-term culture were determined by propidium iodide as well as direct cell counts and PrestoB lue(PB) assays. Genetic expression of pluripotency markers(Oct4, Nanog, Klf4, and Sox2) in ESCs grown under 2-D and 3-D cultureconditions was examined by quantitative real-time polymerase chain reaction. Protein expression of selected stemness markers was determined by two different methods, immunofluorescence staining(Oct4 and Nanog) and western blot analysis(Oct4, Nanog, and Klf4). Pluripotency of 3-D scaffold grown ESCs was analyzed by in vivo teratoma assay and in vitro differentiation via embryoid bodies into cells of all three germ layers. RESULTS: Self-assembling scaffolds encapsulating ESCs for 3-D culture without the loss of cell viability were prepared by mixing PEG-4-Acr and Dex-SH(1:1 v/v) to a final concentration of 5%(w/v). Scaffold integrity was dependent on the degree of thiol substitution of Dex-SH and cell concentration. Scaffolds prepared using Dex-SH with 7.5% and 33% thiol substitution and incubated in culture medium maintained their integrity for 11 and 13 d without cells and 22 ± 5 d and 37 ± 5 d with cells, respectively. ESCs formed compact colonies, which progressively increased in size over time due to cell proliferation as determined by confocal microscopy and PB staining. 3-D scaffold cultured ESCs expressed significantly higher levels(P < 0.01) of Oct4, Nanog, and Kl4, showing a 2.8, 3.0 and 1.8 fold increase, respectively, in comparison to 2-D grown cells. A similar increase in the protein expression levels of Oct4, Nanog, and Klf4 was observed in 3-D grown ESCs. However, when 3-D cultured ESCs were subsequently passaged in 2-D culture conditions, the level of these pluripotent markers was reduced to normal levels. 3-D grown ESCs produced teratomas and yielded cells of all three germ layers, expressing brachyury(mesoderm), NCAM(ectoderm), and GATA4(endoderm) markers. Furthermore, these cells differentiated into osteogenic, chondrogenic, myogenic, and neural lineages expressing Col1, Col2, Myog, and Nestin, respectively. CONCLUSION: This novel 3-D culture system demonstrated long-term maintenance of mouse ESCs without the routine passaging and manipulation necessary for traditional 2-D cell propagation.展开更多
Coronary artery vasospasm(CAVS)plays an important role in acute chest pain syndrome caused by transient and partial or complete occlusion of the coronary arteries.Pathophysiology of the disease remains incompletely un...Coronary artery vasospasm(CAVS)plays an important role in acute chest pain syndrome caused by transient and partial or complete occlusion of the coronary arteries.Pathophysiology of the disease remains incompletely understood,with autonomic and endothelial dysfunction thought to play an important role.Due to the dynamic nature of the disease,its exact prevalence is not entirely clear but is found to be more prevalent in East Asian and female population.Cigarette smoking remains a prominent risk factor,although CAVS does not follow traditional coronary artery disease risk factors.Many triggers continue to be identified,with recent findings identifying chemotherapeutics,allergens,and inflammatory mediators as playing some role in the exacerbation of CAVS.Provocative testing with direct visualization is currently the gold-standard for diagnosis,but non-invasive tests,including the use of biomarkers,are being increasingly studied to aid in the diagnosis.Treatment of the CAVS is an area of active research.Apart from risk factor modification,calcium channel blockers are currently the first line treatment,with nitrates playing an important adjunct role.High-risk patients with life-threatening complications should be considered for implantable cardioverter defibrillator(ICD),although timing criteria for escalated therapy require further investigation.The role of pharmaceuticals targeting oxidative stress remains incompletely understood.展开更多
Objective To assess the influence of age on the error of estimate （EE） of maximal oxygen uptake （VO2max） using sex and population specific-equations in cycle ergometer exercise testing, since estimated VO2 max is ...Objective To assess the influence of age on the error of estimate （EE） of maximal oxygen uptake （VO2max） using sex and population specific-equations in cycle ergometer exercise testing, since estimated VO2 max is associated with a substantial EE, often exceeding 20%, possibly due to intrinsic variability of mechanical efficiency. Methods 1850 adults （68% men）, aged 18 to 91 years, underwent maximal cycle ergometer cardiopulmonary exercise testing. Cardiorespiratory fitness （CRF） was assessed relative to sex and age [younger （18 to 35 years）, middle-aged （36 to 60 years） and older （〉 60 years）]. VO2max [mL.（kg.min）-1] was directly measured by assessment of gas exchange and estimated using sex and population specific-equations. Measured and estimated values of VO2max and related EE were compared among the three age- and sex-specific groups. Results Directly measured VO2max of men and women were 29.5 ± 10.5 mL.（kg.min）-1 and 24.2 ± 9.0 mL.（kg·min） -1 （P 〈 0.01）. EE [mL·（kg·min）-1] and percent errors （%E） for men and women had similar values, 0.5 ± 3.2 and 0.4 ± 2.9 mL·（kg·min）-1, and -0.8 ± 13.1% and -1.7 ± 15.4% （P 〉 0.05）, respectively. EE and %E for each age-group were, respectively, for men： younger = 1.9 ± 4.1 mL·（kg·min）-1 and 3.8 ± 10.5%, middle-aged = 0.6 ± 3.1 mL.（kg·min）-1 and 0.4 ± 10.3%, older = -0.2 ± 2.7 mL·（kg·min） -1 and -4.2 ± 16.6% （P 〈 0.01）; and for women： younger = 1.2 ± 3.1 mL.（kg.min）-1 and 2.7 ±10.0%, middle-aged = 0.7 ± 2.8 mL·（kg·min）-1 and 0.5 ± 11.1%, older = -0.8 ± 2.3 mL-（kg·min）-1 and -9.5 ± 22.4% （P 〈 0.01）. Conclusion VO2max were underestimated in younger age-groups and were overestimated in older age groups. Age significantly influences the magnitude of the EE of VO2max in both men and women and should be considered when CRF is estimated using population specific equations, rather than directly measured.展开更多
BACKGROUND Hereditary hemochromatosis(HH)has an increased risk of hepatocellular cancer(HCC)both due to genetic risks and iron overload as iron overload can be carcinogenic;HH impacts the increasing risk of HCC,not on...BACKGROUND Hereditary hemochromatosis(HH)has an increased risk of hepatocellular cancer(HCC)both due to genetic risks and iron overload as iron overload can be carcinogenic;HH impacts the increasing risk of HCC,not only through the development of cirrhosis but concerning hepatic iron deposition,which has been studied further recently.AIM To evaluate HH yearly trends,patient demographics,symptoms,comorbidities,and hospital outcomes.The secondary aim sheds light on the risk of iron overload for developing HCC in HH patients,independent of liver cirrhosis complications.The study investigated HH(without cirrhosis)as an independent risk factor for HCC.METHODS We analyzed data from National Inpatient Sample(NIS)Database,the largest national inpatient data collection in the United States,and selected HH and HCC cohorts.HH was first defined in 2011 International Classification of Disease-9th edition(ICD-9)as a separate diagnosis;the HH cohort is extracted from January 2011 to December 2019 using 275.01(ICD-9)and E83.110(ICD-10)diagnosis codes of HH.Patients were excluded from the HH cohort if they had a primary or secondary diagnostic code of cirrhosis(alcoholic,non-alcoholic,and biliary),viralhepatitis,alcoholic liver disease,non-alcoholic fatty liver disease(NAFLD),and non-alcoholic steatohepatitis(NASH).We removed these patients from the HH cohort to rule out bias or ICD-10 diagnostic errors.The HCC cohort is selected from January 2011 to December 2019 using the ICD-9 and ICD-10 codes of HCC.We selected a non-HCC cohort with the 1:1 fixed ratio nearest neighbor(greedy)propensity score method using the patients'age,gender,and race.We performed multivariate analysis for the risk factors of HCC in the HCC and non-HCC matched cohort.We further analyzed HH without cirrhosis(removing HH patients with a diagnosis of cirrhosis)as an independent risk factor of HCC after adjusting all known risk factors of HCC in the multivariate model.RESULTS During the 2011-2019 period,a total of 18031 hospitalizations with a primary or secondary diagnosis of HH(excluding liver diseases)were recorded in the NIS database.We analyzed different patients’characteristics,and we found increments in inpatient population trend with a Ptrend<0.001 and total hospital cost of care trend from$42957 in 2011 to$66152 in 2019 with a Ptrend<0.001 despite no change in Length of Stay over the last decade.The multivariate analyses showed that HH without cirrhosis(aOR,28.8;95%CI,10.4–80.1;P<0.0001),biliary cirrhosis(aOR,19.3;95%CI,13.4–27.6;P<0.0001),non-alcoholic cirrhosis(aOR,17.4;95%CI,16.5–18.4;P<0.0001),alcoholic cirrhosis(aOR,16.9;95%CI,15.9–17.9;P<0.0001),hepatitis B(aOR,12.1;95%CI,10.85–13.60;P<0.0001),hepatitis C(aOR,8.58;95%CI,8.20–8.98;P<0.0001),Wilson disease(aOR,4.27;95%CI,1.18–15.41;P<0.0001),NAFLD or NASH(aOR,2.96;95%CI,2.73–3.20;P<0.0001),alpha1-antitrypsin deficiency(aOR,2.10;95%CI,1.21–3.64;P<0.0001),diabetes mellitus without chronic complications(aOR,1.17;95%CI,1.13–1.21;P<0.0001),and blood transfusion(aOR,1.80;95%CI,1.69–1.92;P<0.0001)are independent risk factor for liver cancer.CONCLUSION Our study showed an increasing trend of in-hospital admissions of HH patients in the last decade.These trends were likely related to advances in diagnostic approach,which can lead to increased hospital utilization and cost increments.Still,the length of stay remained the same,likely due to a big part of management being done in outpatient settings.Another vital part of our study is the significant result that HH without cirrhosis is an independent risk factor for HCC with adjusting all known risk factors.More prospective and retrospective large studies are needed to re-evaluate the HH independent risk in developing HCC.展开更多
Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure （HF）. We examined relationships between maximal o...Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure （HF）. We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, fianctional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction （n = 25, age 75 ：i： 7 years） were compared to 25 healthy ageand gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake （VO2p^ak）, oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go （GUG）, Comfortable Gait Speed （CGS）, Unipedal Stance （US）], and self-reported physical activity （PA）. Results Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.展开更多
PURPOSE: To evaluate the benefit of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) in eyes with diffuse diabetic macular edem a refractory to laser photocoagulation.DESIGN: Prospective...PURPOSE: To evaluate the benefit of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) in eyes with diffuse diabetic macular edem a refractory to laser photocoagulation.DESIGN: Prospective, consecutive, interve ntional case series. METHODS: Diabetic patients with biomicroscopic, angiographi c, and tomographic evidence of diabetic macular edema persisting for at least 3 months after numerous sessions of macular photocoagulation were evaluated for in clusion. Patients with biomicroscopic evidence of epiretinal membrane or taut po sterior hyaloid, previous vitreoretinal surgery, or active proliferative diabeti c retinopathy were excluded. The main outcome measures were macular thickness, a s measured by optical coherence tomography (OCT) and visual acuity (VA). RESULTS : PPV with ILM removal was performed in 11 eyes of 10 patients (four men, six wo men; mean age=58.2 years). Six-month follow-up data were available for 10 eyes (91%). At 6 months postoperatively, central macular thickness had improved by at least 20%in eight of 11 eyes (mean preoperative thickness of 421 μm compare d with mean postoperative thickness of 188 μm; P=.007). Mean VA improved from 2 0/352 to 20/94 at 6 months (P=.002). By the most recent visit (range=6-20 month s postoperatively), VA had improved by at least 2 Snellen lines in 6 of 10 eyes treated with surgery alone. CONCLUSIONS: The early results of this ongoing study suggest that PPV with ILM removal may provide anatomic and visual benefit in so me eyes with chronic diabetic macular edema unresponsive or unamenable to additi onal laser photocoagulation.展开更多
We examined the incidence, presentation, and outcome of patients who developed gastrointestinal bleeding after percutaneous coronary intervention for acute myocardial infarction in the Primary Angioplasty in Myocardia...We examined the incidence, presentation, and outcome of patients who developed gastrointestinal bleeding after percutaneous coronary intervention for acute myocardial infarction in the Primary Angioplasty in Myocardial Infarction trials. Of the 3,130 patients, 71(2.3%) developed gastrointestinal bleeding, which was more likely to occur in elderly patients. Gastrointestinal bleeding was independently associated with a prolonged hospital stay and greater in-hospital and 6-month mortality.展开更多
BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation(TPIAT),systematic evidence of its outcomes remains limited.AIM To evaluate the outcomes of TPIAT.METHODS We searched PubMed,E...BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation(TPIAT),systematic evidence of its outcomes remains limited.AIM To evaluate the outcomes of TPIAT.METHODS We searched PubMed,EMBASE,and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes.Data were extracted and analyzed using comprehensive meta-analysis software.The random-effects model was used for all variables.Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic.Publication bias was assessed using Egger’s test.RESULTS Twenty-one studies published between 1980 and 2017 examining 1011 patients were included.Eighteen studies were of adults,while three studied pediatric populations.Narcotic independence was achieved in 53.5%[95% Confidence Interval(CI):45-62,P<0.05,I2=81%]of adults compared to 51.9%(95%CI:17-85,P<0.05,I2=84%)of children.Insulinindependence post-procedure was achieved in 31.8%(95%CI:26-38,P<0.05,I2=64%)of adults with considerable heterogeneity compared to 47.7%(95%CI:20-77,P<0.05,I2=82%)in children.Glycated hemoglobin(HbA1C)12 mo post-surgery was reported in four studies with a pooled value of 6.76%(P=0.27).Neither stratification by age of the studied population nor metaregression analysis considering both the study publication date and the islet-cell-equivalent/kg weight explained the marked heterogeneity between studies.CONCLUSION These results indicate acceptable success for TPIAT.Future studies should evaluate the discussed measures before and after surgery for comparison.展开更多
Heart failure (HF) is a common disease associated with increasing age. B-type natriuretic peptide (BNP), is a cardiac neurohormone, and is released as prepro BNP and then enzyrnatically cleaved to the Ntenninal-proBNP...Heart failure (HF) is a common disease associated with increasing age. B-type natriuretic peptide (BNP), is a cardiac neurohormone, and is released as prepro BNP and then enzyrnatically cleaved to the Ntenninal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP have been used to identify patients with I-IF. The BNP assay is currently used as a diagnostic and prognostic aid in HF. In general, a BNP level below 100 pg/mL excludes acutely decompensated HF and levels ＞ 500 pg/ml indicate decompensation. Recombinant human BNP (hBNP, nesiritide) is an approved intravenous treatment for acute,decompensated -HF. Nesiritide given in supraphysiologic doses causes vasodilation, natriuresis, diuresis, and improved symptoms over the course of a 48-hour infusion. This paper will sort out the literature concerning the use of this peptide both as a diagnostic test and as an intravenous therapy.展开更多
Sedation practices vary according to countries with different health system regulations, the procedures done, and local circumstances. Interestingly, differences in the setting in which the practice of gastroenterolog...Sedation practices vary according to countries with different health system regulations, the procedures done, and local circumstances. Interestingly, differences in the setting in which the practice of gastroenterology and endoscopy takes place (university-based vs academic practice) as well as other systematic practice differences influence the attitude of endoscopists concerning sedation practices. Conscious sedation using midazolam and opioids is the current standard method of sedation in diagnostic and therapeutic endoscopy. Interestingly, propofol is a commonly preferred sedation method by endoscopists due to higher satisfaction rates along with its short half-life and thus lower risk of hepatic encephalopathy. On the other hand, midazolam is the benzodiazepine of choice because of its shorter duration of action and better pharmacokinetic profile compared with diazepam. The administration of sedation under the supervision of a properly trained endoscopist could become the standard practice and the urgent development of an updated international consensus regarding the use of sedative agents like propofol is needed.展开更多
文摘1.Introduction。There is abundant evidence that the amount of habitual physical activity(PA)and the level of cardiorespiratory fitness(CRF)are inversely related to developing chronic diseases,including cardiovascular(CV)disease(CVD).Relative to the CV and all-cause mortality reductions associated with exercise,intensity and duration also appear to be inversely related.For example,the mortality reductions that are associated with a regular 5-min run~a 15-min walk,and a 25-min run~a 105-min walk.1 In addition,at comparable levels of total energy expenditure,vigorous exercise seems to be more effective than moderate-intensity exercise in reducing CV risk.2 Vigorous exercise training is also more effective than moderate intensity training at increasing CRF,expressed as metabolic equivalents or METs,which has been shown to confer a lower risk of mortality.3 Accordingly,the optimal physiologic,clinical,and survival benefits of exercise are most likely to be achieved by progressing from moderate intensity exercise(usually defined as 40%-59%of functional capacity or 55%-69%of the maximal heart rate)to vigorous training regimens,corresponding to≥60%of functional capacity or 70%-89%of the measured maximal heart rate.
文摘AIM:To systematically review the data on distinctive aspects of peptic ulcer disease(PUD),Dieulafoy’s lesion(DL),and Mallory-Weiss syndrome(MWS)in patients with advanced alcoholic liver disease(a ALD),including alcoholic hepatitis or alcoholic cirrhosis.METHODS:Computerized literature search performed via Pub Med using the following medical subject heading terms and keywords:"alcoholic liver disease","alcoholic hepatitis","alcoholic cirrhosis","cirrhosis","liver disease","upper gastrointestinal bleeding","nonvariceal upper gastrointestinal bleeding","PUD",‘‘DL’’,‘‘Mallory-Weiss tear",and"MWS’’.RESULTS:While the majority of acute gastrointestinal(GI)bleeding with a ALD is related to portal hypertension,about 30%-40%of acute GI bleeding in patients with a ALD is unrelated to portal hypertension.Such bleeding constitutes an important complication of a ALD because of its frequency,severity,and associated mortality.Patients with cirrhosis have a markedly increased risk of PUD,which further increases with the progression of cirrhosis.Patients with cirrhosis or a ALD and peptic ulcer bleeding(PUB)have worse clinical outcomes than other patients with PUB,including uncontrolled bleeding,rebleeding,and mortality.Alcohol consumption,nonsteroidal anti-inflammatory drug use,and portal hypertension may have a pathogenic role in the development of PUD in patients with a ALD.Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients.The frequency of bleeding from DL appears to be increased in patients with a ALD.DL may be associated with an especially high mortality in these patients.MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism,and is associated with a ALD.Patients with a ALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics.Preendoscopic management of acute GI bleeding in patients with a ALD unrelated to portal hypertension is similar to the management of a ALD patients with GI bleeding from portal hypertension,because clinical distinction before endoscopy is difficult.Most patients require intensive care unit admission and attention to avoid over-transfusion,to correct electrolyte abnormalities and coagulopathies,and to administer antibiotic prophylaxis.Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal.Prompt endoscopy,after initial resuscitation,is essential to diagnose and appropriately treat these patients.Generally,the same endoscopic hemostatic techniques are used in patients bleeding from PUD,DL,or MWS in patients with a ALD as in the general population.CONCLUSION:Nonvariceal upper GI bleeding in patients with a ALD has clinically important differences from that in the general population without a ALD,including:more frequent and more severe bleeding from PUD,DL,or MWS.
文摘AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy(PHG) based on a systematic literature review.METHODS: Computerized search of the literature was performed via Pub Med using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG.PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepaticportosystemic-shunt or liver transplantation is highly successful ultimate therapies because they reduce the underlying portal hypertension.CONCLUSION: PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.
文摘Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.
文摘A 68-year-old man presented with progressive right lower quadrant abdominal pain and tenderness without rebound tenderness, and with constipation during the prior 9 mo. Abdomino-pelvic computed tomography and magnetic resonance imaging demonstrated a dilated appendix forming a fistula to the sigmoid colon. Open laparotomy revealed a bulky abdominal tumor involving appendix, cecum, and sigmoid, and extending up to adjacent viscera, without ascites or peritoneal implants. The abdominal mass was removed en bloc, including resection of sigmoid colon, cecum(with preservation of ileocecal valve), appendix, right vas deferens, testicular vessels, and minimal amounts of anterior abdominal wall; and shaving off of small parts of the walls of the urinary bladder and small bowel. Gross and microscopic pathologic examination revealed an appendix-to-sigmoid malignant fistula secondary to perforation of mucinous adenocarcinoma of the appendix with minimal local spread(stage T4). However, the surgical margins were clear, all 13 resected lymph nodes were cancer-free, and pseudomyxoma peritonei or peritoneal implants were not present. The patient did well during 1 year of follow-up with no clinical or radiologic evidence of local recurrence, metastases, or pseudomyxoma peritonei despite presenting with extensive stage T4 cancer that was debulked without administering chemotherapy, and despite presenting with malignant appendiceal perforation. This case illustrates the non-aggressive biologic behavior of this low-grade malignancy. The fistula may have prevented free spillage of cancerous cells and consequent distant metastases by containing the appendiceal contents largely within the colon.
文摘AIM To systematically review safety/efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography(ERCP) performed during pregnancy, considering fetal viability, fetal teratogenicity, premature delivery, and future postpartum development of the infant.METHODS Systematic computerized literature search performed using PubMed with the key words "ERCP" and "pregnancy". Two clinicians independently reviewed the literature, and decided on which articles to incorporate in this review based on consensus and preassigned priorities. Large clinical trials, meta-analyses, systematic reviews, and controlled trials were assigned higher priority than review articles or small clinical series, and individual case reports were assigned lowest priority. Dr. Cappell has formal training and considerable experience in conducting systematic reviews, with 4 published systematic reviews in peer-reviewed journals indexed in PubM ed during the last 2 years, and with a PhD in neurophysiology that involved 5 years of training and research in biomedical statistics.RESULTS Advances in imaging modalities, including abdominal ultrasound, MRCP, and endoscopic ultrasound, have generally obviated the need for diagnostic ERCP in nonpregnant and pregnant patients. Clinical experience with performing ERCP during pregnancy is burgeoning, with > 500 cases of therapeutic ERCP reported in the literature, aside from a national registry study of 58 patients. These studies show that therapeutic ERCP has a very high rate of technical success in clearing the bile duct of gallstones, and has a relatively low and acceptable rate of maternal and fetal complications. The great majority of births after therapeutic ERCP are full-term, have normal birth weights, and are healthy. A recent trend is performing ERCP without radiation to eliminate radiation teratogenicity. Systematic literature review reveals 147 cases of ERCP without fluoroscopy in 8 clinical series. These studies demonstrate extremely high technical success in endoscopically removing choledocholithiasis, favorable maternal outcomes with rare maternal ERCP complications, and excellent fetal outcomes. ERCP without fluoroscopy generally confirms proper biliary cannulation by aspiration of yellow bile per sphincterotome or leakage of yellow bile around an inserted guide-wire.CONCLUSION This systematic literature review reveals ERCP is relatively safe and efficacious during pregnancy, with relatively favorable maternal and fetal outcomes after ERCP. Recommendations are provided about ERCP indications, special ERCP techniques during pregnancy, and prospects for future research.
文摘Endoscopic-retrograde-cholangiopancreatography(ERCP) is now a vital modality with primarily therapeutic and occasionally solely diagnostic utility for numerous biliary/pancreatic disorders. It has a significantly steeper learning curve than that for other standard gastrointestinal(GI) endoscopies, such as esophagogastroduodenoscopy or colonoscopy, due to greater technical difficulty and higher risk of complications. Yet, GI fellows have limited exposure to ERCP during standard-three-year-GI-fellowships because ERCP is much less frequently performed than esophagogastroduodenoscopy/colonoscopy. This led to adding an optional year of training in therapeutic endoscopy. Yet many graduates from standard three-year-fellowships without advanced training intensely pursue independent/unsupervised ERCP privileges despite inadequate numbers of performed ERCPs and unacceptably low rates of successful selective cannulation of desired(biliary or pancreatic) duct. Hospital credentialing committees have traditionally performed ERCP credentialing, but this practice has led to widespread flouting of recommended guidelines(e.g., planned privileging of applicant with 20% successful cannulation rate, or after performing only 7 ERCPs);and intense politicking of committee members by applicants, their practice groups, and potential competitors. Consequently, some gastroenterologists upon completing standard fellowships train and learn ERCP 'on the job' during independent/unsupervised practice, which can result in bad outcomes: high rates of failed bile duct cannulation. This severe clinical problem is indicated by publication of ≥ 12 ERCP competency studies/guidelines during last 5 years. However, lack of mandatory, quantitative, ERCP credentialing criteria has permitted neglect of recommended guidelines. This work comprehensively reviews literature on ERCP credentialing;reviews rationales for proposed guidelines;reports problems with current system;and proposes novel criteria for competency. This work advocates for mandatory, national, written,minimum, quantitative, standards, including cognitive skills(possibly assessed by a nationwide examination), and technical skills, assessed by number performed(≥ 200-250 ERCPs), types of ERCPs, success rate(approximately ≥ 90%cannulation of desired duct), and letters of recommendation by program director/ERCP mentor. Mandatory criteria should ideally not be monitored by a hospital committee subjected to intense politicking by applicants, their employers, and sometimes even competitors, but an independent national entity,like the National Board of Medical Examiners/American Board of Internal Medicine.
基金Oakland University and Oakland University-William Beaumont Institute for Stem Cell and Regenerative Medicine(OU-WB ISCRM)
文摘AIM: To devise a simplified and efficient method for long-term culture and maintenance of embryonic stem cells requiring less frequent passaging. METHODS: Mouse embryonic stem cells(ESCs) labeled with enhanced yellow fluorescent protein were cultured in three-dimensional(3-D) self-assembling scaffolds and compared with traditional two-dimentional(2-D) culture techniques requiring mouse embryonic fibroblast feeder layers or leukemia inhibitory factor. 3-D scaffolds encapsulating ESCs were prepared by mixing ESCs with polyethylene glycol tetra-acrylate(PEG-4-Acr) and thiolfunctionalized dextran(Dex-SH). Distribution of ESCs in 3-D was monitored by confocal microscopy. Viability and proliferation of encapsulated cells during long-term culture were determined by propidium iodide as well as direct cell counts and PrestoB lue(PB) assays. Genetic expression of pluripotency markers(Oct4, Nanog, Klf4, and Sox2) in ESCs grown under 2-D and 3-D cultureconditions was examined by quantitative real-time polymerase chain reaction. Protein expression of selected stemness markers was determined by two different methods, immunofluorescence staining(Oct4 and Nanog) and western blot analysis(Oct4, Nanog, and Klf4). Pluripotency of 3-D scaffold grown ESCs was analyzed by in vivo teratoma assay and in vitro differentiation via embryoid bodies into cells of all three germ layers. RESULTS: Self-assembling scaffolds encapsulating ESCs for 3-D culture without the loss of cell viability were prepared by mixing PEG-4-Acr and Dex-SH(1:1 v/v) to a final concentration of 5%(w/v). Scaffold integrity was dependent on the degree of thiol substitution of Dex-SH and cell concentration. Scaffolds prepared using Dex-SH with 7.5% and 33% thiol substitution and incubated in culture medium maintained their integrity for 11 and 13 d without cells and 22 ± 5 d and 37 ± 5 d with cells, respectively. ESCs formed compact colonies, which progressively increased in size over time due to cell proliferation as determined by confocal microscopy and PB staining. 3-D scaffold cultured ESCs expressed significantly higher levels(P < 0.01) of Oct4, Nanog, and Kl4, showing a 2.8, 3.0 and 1.8 fold increase, respectively, in comparison to 2-D grown cells. A similar increase in the protein expression levels of Oct4, Nanog, and Klf4 was observed in 3-D grown ESCs. However, when 3-D cultured ESCs were subsequently passaged in 2-D culture conditions, the level of these pluripotent markers was reduced to normal levels. 3-D grown ESCs produced teratomas and yielded cells of all three germ layers, expressing brachyury(mesoderm), NCAM(ectoderm), and GATA4(endoderm) markers. Furthermore, these cells differentiated into osteogenic, chondrogenic, myogenic, and neural lineages expressing Col1, Col2, Myog, and Nestin, respectively. CONCLUSION: This novel 3-D culture system demonstrated long-term maintenance of mouse ESCs without the routine passaging and manipulation necessary for traditional 2-D cell propagation.
文摘Coronary artery vasospasm(CAVS)plays an important role in acute chest pain syndrome caused by transient and partial or complete occlusion of the coronary arteries.Pathophysiology of the disease remains incompletely understood,with autonomic and endothelial dysfunction thought to play an important role.Due to the dynamic nature of the disease,its exact prevalence is not entirely clear but is found to be more prevalent in East Asian and female population.Cigarette smoking remains a prominent risk factor,although CAVS does not follow traditional coronary artery disease risk factors.Many triggers continue to be identified,with recent findings identifying chemotherapeutics,allergens,and inflammatory mediators as playing some role in the exacerbation of CAVS.Provocative testing with direct visualization is currently the gold-standard for diagnosis,but non-invasive tests,including the use of biomarkers,are being increasingly studied to aid in the diagnosis.Treatment of the CAVS is an area of active research.Apart from risk factor modification,calcium channel blockers are currently the first line treatment,with nitrates playing an important adjunct role.High-risk patients with life-threatening complications should be considered for implantable cardioverter defibrillator(ICD),although timing criteria for escalated therapy require further investigation.The role of pharmaceuticals targeting oxidative stress remains incompletely understood.
文摘Objective To assess the influence of age on the error of estimate （EE） of maximal oxygen uptake （VO2max） using sex and population specific-equations in cycle ergometer exercise testing, since estimated VO2 max is associated with a substantial EE, often exceeding 20%, possibly due to intrinsic variability of mechanical efficiency. Methods 1850 adults （68% men）, aged 18 to 91 years, underwent maximal cycle ergometer cardiopulmonary exercise testing. Cardiorespiratory fitness （CRF） was assessed relative to sex and age [younger （18 to 35 years）, middle-aged （36 to 60 years） and older （〉 60 years）]. VO2max [mL.（kg.min）-1] was directly measured by assessment of gas exchange and estimated using sex and population specific-equations. Measured and estimated values of VO2max and related EE were compared among the three age- and sex-specific groups. Results Directly measured VO2max of men and women were 29.5 ± 10.5 mL.（kg.min）-1 and 24.2 ± 9.0 mL.（kg·min） -1 （P 〈 0.01）. EE [mL·（kg·min）-1] and percent errors （%E） for men and women had similar values, 0.5 ± 3.2 and 0.4 ± 2.9 mL·（kg·min）-1, and -0.8 ± 13.1% and -1.7 ± 15.4% （P 〉 0.05）, respectively. EE and %E for each age-group were, respectively, for men： younger = 1.9 ± 4.1 mL·（kg·min）-1 and 3.8 ± 10.5%, middle-aged = 0.6 ± 3.1 mL.（kg·min）-1 and 0.4 ± 10.3%, older = -0.2 ± 2.7 mL·（kg·min） -1 and -4.2 ± 16.6% （P 〈 0.01）; and for women： younger = 1.2 ± 3.1 mL.（kg.min）-1 and 2.7 ±10.0%, middle-aged = 0.7 ± 2.8 mL·（kg·min）-1 and 0.5 ± 11.1%, older = -0.8 ± 2.3 mL-（kg·min）-1 and -9.5 ± 22.4% （P 〈 0.01）. Conclusion VO2max were underestimated in younger age-groups and were overestimated in older age groups. Age significantly influences the magnitude of the EE of VO2max in both men and women and should be considered when CRF is estimated using population specific equations, rather than directly measured.
文摘BACKGROUND Hereditary hemochromatosis(HH)has an increased risk of hepatocellular cancer(HCC)both due to genetic risks and iron overload as iron overload can be carcinogenic;HH impacts the increasing risk of HCC,not only through the development of cirrhosis but concerning hepatic iron deposition,which has been studied further recently.AIM To evaluate HH yearly trends,patient demographics,symptoms,comorbidities,and hospital outcomes.The secondary aim sheds light on the risk of iron overload for developing HCC in HH patients,independent of liver cirrhosis complications.The study investigated HH(without cirrhosis)as an independent risk factor for HCC.METHODS We analyzed data from National Inpatient Sample(NIS)Database,the largest national inpatient data collection in the United States,and selected HH and HCC cohorts.HH was first defined in 2011 International Classification of Disease-9th edition(ICD-9)as a separate diagnosis;the HH cohort is extracted from January 2011 to December 2019 using 275.01(ICD-9)and E83.110(ICD-10)diagnosis codes of HH.Patients were excluded from the HH cohort if they had a primary or secondary diagnostic code of cirrhosis(alcoholic,non-alcoholic,and biliary),viralhepatitis,alcoholic liver disease,non-alcoholic fatty liver disease(NAFLD),and non-alcoholic steatohepatitis(NASH).We removed these patients from the HH cohort to rule out bias or ICD-10 diagnostic errors.The HCC cohort is selected from January 2011 to December 2019 using the ICD-9 and ICD-10 codes of HCC.We selected a non-HCC cohort with the 1:1 fixed ratio nearest neighbor(greedy)propensity score method using the patients'age,gender,and race.We performed multivariate analysis for the risk factors of HCC in the HCC and non-HCC matched cohort.We further analyzed HH without cirrhosis(removing HH patients with a diagnosis of cirrhosis)as an independent risk factor of HCC after adjusting all known risk factors of HCC in the multivariate model.RESULTS During the 2011-2019 period,a total of 18031 hospitalizations with a primary or secondary diagnosis of HH(excluding liver diseases)were recorded in the NIS database.We analyzed different patients’characteristics,and we found increments in inpatient population trend with a Ptrend<0.001 and total hospital cost of care trend from$42957 in 2011 to$66152 in 2019 with a Ptrend<0.001 despite no change in Length of Stay over the last decade.The multivariate analyses showed that HH without cirrhosis(aOR,28.8;95%CI,10.4–80.1;P<0.0001),biliary cirrhosis(aOR,19.3;95%CI,13.4–27.6;P<0.0001),non-alcoholic cirrhosis(aOR,17.4;95%CI,16.5–18.4;P<0.0001),alcoholic cirrhosis(aOR,16.9;95%CI,15.9–17.9;P<0.0001),hepatitis B(aOR,12.1;95%CI,10.85–13.60;P<0.0001),hepatitis C(aOR,8.58;95%CI,8.20–8.98;P<0.0001),Wilson disease(aOR,4.27;95%CI,1.18–15.41;P<0.0001),NAFLD or NASH(aOR,2.96;95%CI,2.73–3.20;P<0.0001),alpha1-antitrypsin deficiency(aOR,2.10;95%CI,1.21–3.64;P<0.0001),diabetes mellitus without chronic complications(aOR,1.17;95%CI,1.13–1.21;P<0.0001),and blood transfusion(aOR,1.80;95%CI,1.69–1.92;P<0.0001)are independent risk factor for liver cancer.CONCLUSION Our study showed an increasing trend of in-hospital admissions of HH patients in the last decade.These trends were likely related to advances in diagnostic approach,which can lead to increased hospital utilization and cost increments.Still,the length of stay remained the same,likely due to a big part of management being done in outpatient settings.Another vital part of our study is the significant result that HH without cirrhosis is an independent risk factor for HCC with adjusting all known risk factors.More prospective and retrospective large studies are needed to re-evaluate the HH independent risk in developing HCC.
文摘Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure （HF）. We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, fianctional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction （n = 25, age 75 ：i： 7 years） were compared to 25 healthy ageand gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake （VO2p^ak）, oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go （GUG）, Comfortable Gait Speed （CGS）, Unipedal Stance （US）], and self-reported physical activity （PA）. Results Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.
文摘PURPOSE: To evaluate the benefit of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) in eyes with diffuse diabetic macular edem a refractory to laser photocoagulation.DESIGN: Prospective, consecutive, interve ntional case series. METHODS: Diabetic patients with biomicroscopic, angiographi c, and tomographic evidence of diabetic macular edema persisting for at least 3 months after numerous sessions of macular photocoagulation were evaluated for in clusion. Patients with biomicroscopic evidence of epiretinal membrane or taut po sterior hyaloid, previous vitreoretinal surgery, or active proliferative diabeti c retinopathy were excluded. The main outcome measures were macular thickness, a s measured by optical coherence tomography (OCT) and visual acuity (VA). RESULTS : PPV with ILM removal was performed in 11 eyes of 10 patients (four men, six wo men; mean age=58.2 years). Six-month follow-up data were available for 10 eyes (91%). At 6 months postoperatively, central macular thickness had improved by at least 20%in eight of 11 eyes (mean preoperative thickness of 421 μm compare d with mean postoperative thickness of 188 μm; P=.007). Mean VA improved from 2 0/352 to 20/94 at 6 months (P=.002). By the most recent visit (range=6-20 month s postoperatively), VA had improved by at least 2 Snellen lines in 6 of 10 eyes treated with surgery alone. CONCLUSIONS: The early results of this ongoing study suggest that PPV with ILM removal may provide anatomic and visual benefit in so me eyes with chronic diabetic macular edema unresponsive or unamenable to additi onal laser photocoagulation.
文摘We examined the incidence, presentation, and outcome of patients who developed gastrointestinal bleeding after percutaneous coronary intervention for acute myocardial infarction in the Primary Angioplasty in Myocardial Infarction trials. Of the 3,130 patients, 71(2.3%) developed gastrointestinal bleeding, which was more likely to occur in elderly patients. Gastrointestinal bleeding was independently associated with a prolonged hospital stay and greater in-hospital and 6-month mortality.
文摘BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation(TPIAT),systematic evidence of its outcomes remains limited.AIM To evaluate the outcomes of TPIAT.METHODS We searched PubMed,EMBASE,and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes.Data were extracted and analyzed using comprehensive meta-analysis software.The random-effects model was used for all variables.Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic.Publication bias was assessed using Egger’s test.RESULTS Twenty-one studies published between 1980 and 2017 examining 1011 patients were included.Eighteen studies were of adults,while three studied pediatric populations.Narcotic independence was achieved in 53.5%[95% Confidence Interval(CI):45-62,P<0.05,I2=81%]of adults compared to 51.9%(95%CI:17-85,P<0.05,I2=84%)of children.Insulinindependence post-procedure was achieved in 31.8%(95%CI:26-38,P<0.05,I2=64%)of adults with considerable heterogeneity compared to 47.7%(95%CI:20-77,P<0.05,I2=82%)in children.Glycated hemoglobin(HbA1C)12 mo post-surgery was reported in four studies with a pooled value of 6.76%(P=0.27).Neither stratification by age of the studied population nor metaregression analysis considering both the study publication date and the islet-cell-equivalent/kg weight explained the marked heterogeneity between studies.CONCLUSION These results indicate acceptable success for TPIAT.Future studies should evaluate the discussed measures before and after surgery for comparison.
文摘Heart failure (HF) is a common disease associated with increasing age. B-type natriuretic peptide (BNP), is a cardiac neurohormone, and is released as prepro BNP and then enzyrnatically cleaved to the Ntenninal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP have been used to identify patients with I-IF. The BNP assay is currently used as a diagnostic and prognostic aid in HF. In general, a BNP level below 100 pg/mL excludes acutely decompensated HF and levels ＞ 500 pg/ml indicate decompensation. Recombinant human BNP (hBNP, nesiritide) is an approved intravenous treatment for acute,decompensated -HF. Nesiritide given in supraphysiologic doses causes vasodilation, natriuresis, diuresis, and improved symptoms over the course of a 48-hour infusion. This paper will sort out the literature concerning the use of this peptide both as a diagnostic test and as an intravenous therapy.
文摘Sedation practices vary according to countries with different health system regulations, the procedures done, and local circumstances. Interestingly, differences in the setting in which the practice of gastroenterology and endoscopy takes place (university-based vs academic practice) as well as other systematic practice differences influence the attitude of endoscopists concerning sedation practices. Conscious sedation using midazolam and opioids is the current standard method of sedation in diagnostic and therapeutic endoscopy. Interestingly, propofol is a commonly preferred sedation method by endoscopists due to higher satisfaction rates along with its short half-life and thus lower risk of hepatic encephalopathy. On the other hand, midazolam is the benzodiazepine of choice because of its shorter duration of action and better pharmacokinetic profile compared with diazepam. The administration of sedation under the supervision of a properly trained endoscopist could become the standard practice and the urgent development of an updated international consensus regarding the use of sedative agents like propofol is needed.
