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A series of ten novel chalcone incorporated quinazoline derivatives (11a–11j) were designed and synthesized. All the synthesized compounds were evaluated for their anticancer activities against four human cancer cell lines (A549, HT-29, MCF-7 and A375). Among them, four compounds, 11f, 11g, 11i and 11j showed more potent anticancer activity than the control drug, Combretastatin – A4.

Abstract Background Small intestinal bacterial overgrowth (SIBO) is a condition in which excessive levels of bacteria, mainly the colonic-type species are present in the small intestine. Recent data suggest that SIBO may contribute to the pathophysiology of Irritable bowel syndrome (IBS). The purpose of this study was to identify potential predictors of SIBO in patients with IBS. Methods Adults with IBS based on Rome II criteria who had predominance of bloating and flatulence underwent a glucose breath test (GBT) to determine the presence of SIBO. Breath samples were obtained at baseline and at 30, 45, 60, 75 and 90 minutes after ingestion of 50 g of glucose dissolved in 150 mL of water. Results of the glucose breath test, which measures hydrogen and methane levels in the breath, were considered positive for SIBO if 1) the hydrogen or methane peak was >20 ppm when the baseline was Results Ninety-eight patients were identified who underwent a GBT (mean age, 49 y; 78% female). Thirty-five patients (36%) had a positive GBT result suggestive of SIBO. A positive GBT result was more likely in patients >55 years of age (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.4-9.0) and in females (OR, 4.0; 95% CI, 1.1-14.5). Hydrogen was detected more frequently in patients with diarrhea-predominant IBS (OR, 8; 95% CI, 1.4-45), and methane was the main gas detected in patients with constipation-predominant IBS (OR, 8; 95% CI, 1.3-44). There was no significant correlation between the presence of SIBO and the predominant bowel pattern or concurrent use of tegaserod, proton pump inhibitors, or opiate analgesics. Conclusions Small intestinal bacterial overgrowth was present in a sizeable percentage of patients with IBS with predominance of bloating and flatulence. Older age and female sex were predictors of SIBO in patients with IBS. Identification of possible predictors of SIBO in patients with IBS could aid in the development of successful treatment plans.

Abstract Background Gastroparesis has a number of etiologies. The main ones are secondary to a complication from diabetes mellitus, related to post vagotomy or post gastric surgical resections, or idiopathic when the etiology is unclear. Gastroparesis secondary to a demyelinating disease of the brain is unusual. Case presentation A 22-year-old woman was referred for acute onset of intractable nausea and vomiting. She also had cerebellar deficits, dysphagia and paresthesias. Magnetic resonance imaging (MRI) of the brain revealed an isolated area of demyelination in the medullary region. Another 24-year-old woman had a similar presentation with right hemiplegia and MRI of the brain revealed a distal medullary region. Both these patients had an abnormal gastric emptying test. Gastroparesis and neurological deficits improved with intravenous corticosteroids. While the former patient has had no further recurrences, the latter patient developed multiple sclerosis within three months of presentation. Conclusion A demyelinating disease is a rare cause gastropareis, but should be suspected when symptoms of gastroparesis are associated with neurological deficits. MRI might help in the diagnosis and intravenous coriticosteroids can address the underlying disease process and improve gastric emptying, especially when used early during the course of the disease.

Abstract Background Fecal leukocyte test (FLT) is widely used to screen for invasive diarrheas including C. difficile associated diarrhea (CDAD), which account for more than 25 % of all antibiotic associated diarrhea. Method 263 stool samples from patients with suspected CDAD were studied simultaneously for fecal leukocyte test (FLT) and Clostridium difficile toxin assay (CDTA). FLT was performed by the Giemsa technique and CDTA was performed by enzyme immuno assay (EIA). Results Sensitivity, specificity, positive predictive value and negative predictive value of FLT as compared to CDTA were 30%, 74.9%, 13.2% and 89.3% respectively. Conclusion Considering the poor sensitivity of FLT, and the comparable cost and time of obtaining a CDTA at our institution, we conclude that FLT is not a good screening test for CDAD. Possible reasons for FLT being a poor predictor of CDTA are discussed.

Introduction Primary biliary cholangitis (PBC) is associated with an increased risk of developing fractures. Current guidelines recommend measures that can help prevent the development of fractures in these patients. The purpose of this study was to trend the rates of hospitalizations related to fractures and their burden on healthcare. Methods We performed a retrospective, cohort study of adults hospitalized in the United States with PBC between 2010 and 2014. Patients were identified using the Nationwide Inpatient Sample (NIS). Temporal analysis of PBC patients with a co-diagnosis of hip, vertebral, or wrist fractures (the study group) was performed with regards to the total number of inpatient admissions, inpatient mortality, length of stay, and total charges associated with hospitalization. Descriptive analyses were performed using the  t -test for continuous data and the  chi-square test for categorical data. Results During the five-year study period, there were 308,753 hospitalizations for PBC. There has been a downward trend (p=0.02) in fracture-related admissions among patients with PBC during this study period. Length of stay was higher in the PBC-fracture group (10.85 days vs 7.36 days; p<0.001). Total hospitalization charges were higher among the PBC-fracture patients when compared to the control group ($98,444 vs $72,964; p=0.004). Conclusion There has been a gradual reduction in the rate of fracture-related hospitalizations in patients with PBC. However, patients with PBC who have fractures have increased the utilization of health care resources as compared to their cohort admitted for reasons other than for a fracture., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Ansari et al.)

Hemophagocytic lymphohistiocytosis is a syndrome characterized by excessive immune activation. Timely diagnosis can be challenging, and prompt treatment is the only hope for survival. We present an adult patient with a history of alcohol dependence, who presented with fatigue, bilateral lower extremity edema, and orange-colored urine. Clinical workup revealed abnormal liver function tests, elevated ferritin, cytopenia, and lymphadenopathy. Eventually, he was diagnosed with hemophagocytic lymphohistiocytosis. This case report encourages gastroenterologists to maintain a high index of suspicion when a patient presents with liver failure, hyperferritinemia, and cytopenia because they may be the first healthcare professionals to evaluate these patients., (© 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

This study aimed to determine the rate and safety of immediate esophageal dilation for esophageal food bolus impaction (EFBI) and evaluate its impact on early recurrence (i.e. prior to interval esophageal dilation) from a large Midwest US cohort. We also report practice patterns among community and academic gastroenterologists practicing in similar settings. We identified adult patients with a primary discharge diagnosis for EFBI from January 2012 to June 2018 using our institutional database. Pregnant patients, incarcerated patients, and patients with esophageal neoplasm were excluded. The primary outcome measured was rate of complications with immediate esophageal dilation after disimpaction of EFBI. Secondary outcomes were recurrence of food bolus impaction prior to scheduled interval endoscopy for dilation, practice patterns between academic and private gastroenterologists, and adherence to follow-up endoscopy. Two-hundred and fifty-six patients met our inclusion criteria. Esophageal dilation was performed in 46 patients (18%) at the time of disimpaction. A total of 45 gastroenterologists performed endoscopies for EFBI in our cohort. Twenty-five (62%) did not perform immediate esophageal dilation, and only 5 (11%) performed immediate dilation on greater than 50% of cases. Academic gastroenterologists performed disimpaction of EFBI for 102 patients, immediate dilation as performed in 20 patients and interval dilation was recommended in 82 patients. Of these 82, only 31 patients (38%) did not return for interval dilation. Four patients who did not undergo immediate dilation, presented with recurrent EFBI prior to interval dilation, within 3 months. None of the patients had complications. Complications with immediate esophageal dilation after disimpaction of EFBI are infrequent but are rarely performed. Failure of immediate dilation increases the risk of EFBI recurrence. Given poor patient adherence to interval dilation, immediate dilation is recommended., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The aim of this study was to determine the recent trends of the rates of hospitalization, mortality of hospitalized patients, and associated health care utilization in patients with acute pancreatitis (AP)., Methods: We identified adult patients with primary discharge diagnosis of AP from the National Inpatient Sample database. Patients with chronic pancreatitis and/or pancreatic cancer were excluded. Primary outcomes included age-adjusted incidence of AP and in-hospital mortality based on US standard population derived from the 2000 census data. Secondary outcomes were length of stay, inflation-adjusted hospital costs in 2014 US dollars, and procedural rates. Subgroup analysis included disease etiologies, age, race, sex, hospital region, hospital size, and institution type., Results: From 2001 to 2014, the rate of primary discharge diagnosis for AP increased from 65.38 to 81.88 per 100,000 US adults per year. In-hospital case fatality decreased from 1.68% to 0.69%. Mortality rate is higher in patients with AP who are older than 65 years (3.4%). Length of stay decreased, with a median of 3.8 days; cost per hospitalization decreased since 2007 from $7602 to $6766 in 2014., Conclusions: The rate of hospitalization related to AP in the United States continues to increase. Mortality, length of stay, and cost per hospitalization decrease. The increase in volume of hospitalization might contribute to an overall increase in health care resource utilization.

Introduction: Functional dyspepsia (FD) is widespread with 20% prevalence worldwide and a significant economic burden due to health care cost and constraints on daily activities of patients. Despite extensive investigation, the underlying causes of dyspepsia in a majority of patients remain unknown. Common complaints include abdominal discomfort, pain, burning, nausea, early satiety, and bloating. Motor dysfunction of the gut was long considered a major cause, but recent investigations suggest immune-based pathophysiological and molecular events in the duodenum are more probable contributing factors. Areas Covered: Inflammatory mediators and immune cells including duodenal eosinophils, intraepithelial lymphocytes, and T-cells have been implicated in the underlying cause of disease process, as have genetic factors. In this article, we critically reviewed findings, identified gaps in knowledge and suggested future directions for further investigation to identify targets and develop better therapeutic approaches. Expert commentary: Impaired gastric accommodation, slow gastric emptying, and increased visceral sensitivity have long been thought of as main causal factors of FD. However, more recent identification of eosinophilic degranulation and recruitment of T cells that induce mild duodenal inflammation are giving rise to new insights into immune-mediated pathophysiology. These insights offer promising avenues to explore for immune-mediated therapy in the future.

Granular cell tumors (GCTs) have been described as neoplasms of Schwann cell origin. They are often benign and notably uncommon in the gastrointestinal tract. Recently, their incidence has become more common, likely as a result of increased colonoscopy screenings. Very few data exist regarding their potential for malignancy, but malignant GCTs have been reported. Here, we report the case of a young female patient who was diagnosed with an atypical GCT on the ileocecal valve with an overlying tubular adenoma which was found incidentally on colonoscopy. This represents the first known report of a GCT with atypical features on the ileocecal valve, as well as a rare case of overlying adenomatous changes. Due to the paucity of cases, there is no clear modus operandi for their management. Furthermore, it is not clear whether surgical or endoscopic interventions or simple observation may be most appropriate. Further studies are needed to evaluate the potential for malignancy of this tumor, as well as its management.

Context: Endoscopic ultrasonography guided fine needle aspiration (EUS-FNA) is a front line test used for the diagnosis of solid as well as cystic lesions of the pancreas. This procedure is fairly well tolerated and associated with minimal complications. Local complications such as perforation and pancreatitis have been reported with EUS-FNA, albeit rarely. Although pancreatic duct injury can occur during EUS-FNA, symptomatic pancreatic duct leak as a complication of this procedure has never been reported., Case Report: We present a 67-year-old patient who developed symptomatic ascites after EUS-FNA of a pancreatic neck lesion that required several paracenteses. Analysis of the ascitic fluid revealed that the fluid amylase and lipase levels were very high consistent with pancreatic ascites. An endoscopic retrograde pancreatography was subsequently performed that documented the presence of a pancreatic duct leak in the neck. The pancreatic duct leak and the ascites resolved after placing a pancreatic duct stent., Conclusion: A clinically significant pancreatic leak can occur as a rare complication of EUS-FNA that can be effectively managed by endoscopic retrograde pancreatography and placement of a transpapillary pancreatic duct stent.

Background: Most endosonographers use an EUS needle with an internal stylet during EUS-guided FNA (EUS-FNA). Reinserting the stylet into the needle after every pass is tedious and time-consuming, and there are no data to suggest that it improves the quality of the cytology specimen., Objective: To compare the samples obtained by EUS-FNA with and without a stylet for (1) the degree of cellularity, adequacy, contamination, and amount of blood and (2) the diagnostic yield of malignancy., Design: Prospective,single-blind, randomized, controlled trial., Setting: Two tertiary care referral centers., Patients: Patients referred for EUS-FNA of solid lesions., Intervention: Patients underwent EUS-FNA of the solid lesions, and 2 passes each were made with a stylet and without a stylet in the needle. The order of the passes was randomized, and the cytopathologists reviewing the slides were blinded to the stylet status of passes., Main Outcome Measurements: Degree of cellularity, adequacy, contamination, amount of blood, and the diagnostic yield of malignancy in the specimens., Results: A total of 101 patients with 118 lesions were included in final analysis; 236 FNA passes were made, each with and without a stylet. No significant differences were seen in the cellularity (P = .98), adequacy of the specimen (P = .26), contamination (P = .92), or significant amount of blood (P = .61) between specimens obtained with and without a stylet. The diagnostic yield of malignancy was 55 of 236 specimens (23%) in the with-stylet group compared with 66 of 236 specimens (28%) in the without-stylet group (P = .29)., Limitations: Endosonographers were not blinded to the stylet status of the passes., Conclusions: Using a stylet during EUS-FNA does not confer any significant advantage with regard to the quality of the specimen obtained or the diagnostic yield of malignancy. (, Clinical Trial Registration Number: NCT 01213290)., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background & Aims: The risks of dysplasia and esophageal adenocarcinoma (EAC) are not clear for patients with nondysplastic Barrett's esophagus (NDBE); the rate of progression has been overestimated in previous studies. We studied the incidences of dysplasia and EAC and investigated factors associated with progression of BE., Methods: The BE study is a multicenter outcomes project of a large cohort of patients with BE. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Patients followed up for at least 1 year after the index endoscopy examination were included, whereas those diagnosed with dysplasia and EAC within 1 year of diagnosis with BE (prevalent cases) were excluded. Of 3334 patients with BE, 1204 met the inclusion criteria (93.7% Caucasian; 88% male; mean age, 59.3 y) and were followed up for a mean of 5.52 years (6644.5 patient-years)., Results: Eighteen patients developed EAC (incidence, 0.27%/y; 95% confidence interval [CI], 0.17-0.43) and 32 developed HGD (incidence, 0.48%/y; 95% CI, 0.34-0.68). The incidence of HGD and EAC was 0.63%/y (95% CI, 0.47-0.86). There were 217 cases of low-grade dysplasia (incidence, 3.6%/y; 95% CI, 3.2-4.1). Five and 10 years after diagnosis, 98.6% (n = 540) and 97.1% (n = 155) of patients with NDBE were cancer free, respectively. The length of the BE was associated significantly with progression (EAC <6 cm, 0.09%/y vs EAC ≥ 6 cm, 0.65%/y; P = 0.001)., Conclusions: There is a lower incidence of dysplasia and EAC among patients with NDBE than previously reported. Because most patients are cancer free after a long-term follow-up period, surveillance intervals might be lengthened, especially for patients with shorter segments of BE., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Inconclusive findings on abdominal computerized tomography (CT) scans such as "enlarged or prominent pancreas" are commonly reported; however, their clinical significance is not clearly understood. The objective was to evaluate the efficacy of endoscopic ultrasound (EUS) in a cohort of patients with indeterminate findings on CT. We undertook a retrospective, single-center study at a tertiary care university hospital. About 107 consecutive patients (56 men) underwent EUS evaluation for inconclusive CT findings. The main intervention was EUS with fine needle aspiration (FNA) The main outcome measurement was to describe lesions identified by EUS in this cohort of patients. About 22 patients (21%) had pancreatic adenocarcinoma, 14 (13%) had chronic pancreatitis, 28 (26%) had benign lesions, and 35 patients (33%) had a normal EUS exam. Pancreatic cancer was more likely to be found on EUS in patients with significant weight loss (OR 10.1; 95% CI: 3.3-30.60), hyperbilirubinemia (OR 9; 95% CI: 3-26.0), or common bile duct (CBD) dilatation (OR 3.2; 95% CI: 1.25-8.5). The limitations of the study were that we were unable to control the uniformity of CT interpretation because the scans were reviewed by multiple radiologists. There were also limited follow-up data on patients who had benign lesions or normal EUS. In conclusion, EUS is an effective modality for evaluating pancreatic lesions in patients with inconclusive findings on abdominal CT. This assists in the prompt diagnosis and institution of appropriate treatment strategies for a variety of pancreatic diseases including cancer. In the setting of inconclusive CT findings, patients with hyperbilirubinemia, significant weight loss, or CBD dilatation should undergo EUS evaluation as they are at a higher risk of having underlying pancreatic cancer.

Spontaneous pneumomediastinum (SPM) is a rare and benign clinical entity characterized by free air around mediastinal structures. Precipitating factors include violent cough, asthma, inhalational drugs, labor and exercise. We report a case of SPM due to achalasia which to the best of our knowledge, has never been reported. In achalasia, Valsalva maneuver might accompany severe vomiting. This causes alveolar rupture due to elevated intrabronchial and intra-alveolar pressure. Air tracks along the mediastinal spaces cause SPM. In our patient, there was no evidence of esophageal perforation. Tension pneumomediastinum and pneumothorax are complications of SPM.

Context: Atypical antipsychotic agents are associated with diabetes mellitus and pancreatitis. Aripiprazole, a new antipsychotic, has never been implicated to cause either diabetes mellitus or pancreatitis. We present a patient who developed diabetes mellitus after being started on aripiprazole., Case Report: A 33 year-old male with schizophrenia presented with fatigue, dyspepsia and epigastric pain. Patient was found to have hyperglycemia, diabetic ketoacidosis, and hyperlipasemia. Imaging studies of the pancreas were normal. Patient was started on aripiprazole treatment 18 months prior to this episode and had experienced progressive weight gain since then. Work up for other causes of pancreatitis was negative., Conclusions: Diabetes mellitus in this patient was probably a complication of aripiprazole due to progressive weight gain. In the absence of radiologic evidence of pancreatitis, hyperlipasemia was probably secondary to diabetic ketoacidosis. Possible causes of hyperlipasemia and its significance in diabetic ketoacidosis are discussed.

Despite widespread use for treatment of asthma and allergies, glucocorticoids may cause allergic reactions, even anaphylaxis. The incidence of adverse reactions to systemic glucocorticoids is 0.3%. The most commonly reported corticosteroids causing anaphylaxis like reactions are hydrocortisone, prednisone, and methylprednisolone. Most authors agree that allergic reactions to systemic corticosteroids are possibly immunoglobulin E mediated. We report a patient with asthma, aspirin allergy, and nasal polyps who developed bronchospasm following the administration of intravenous methylprednisolone sodium succinate during an acute asthmatic attack. We discuss the differential diagnosis of worsening asthma despite adequate treatment, and suggest corticosteroid-induced bronchospasm in our patient. Corticosteroid-induced bronchospasm should be considered when asthmatics fail to improve, or frankly deteriorate with systemic corticosteroid therapy, particularly when a history of aspirin allergy is present. TEACHING POINT: Know the differential diagnosis for worsening of asthma despite adequate treatment. Consider corticosteroid-induced bronchospasm when asthmatics fail to improve, or frankly deteriorate with systemic corticosteroid therapy. Corticosteroid-induced bronchospasm is more commonly seen in asthmatics with a history of aspirin allergy.