Rachel Gingold-Belfer

Popeye domain-containing 1 is down-regulated in failing human hearts.

Congestive heart failure, a complex disease of heterogeneous etiology, involves alterations in the expression of multiple genes. The Popeye domain-containing (POPDC) family of three novel muscle-restricted genes (POPDC1-3) is evolutionarily conserved and developmentally regulated. In mice, POPDC1 has been shown to play an important role in skeletal and cardiac muscles subjected to injury or stress. However, it has never been explored in human hearts. In biopsies from non-failing and failing human hearts, we examined the cellular distribution of POPDC1 as well as the expression patterns of POPDC1-3 mRNAs. POPDC1 was visualized by immunohistochemistry and estimated by Western immunoblotting. The mRNA levels of POPDC1-3 and ß myosin heavy chain (MYHC7) were assessed using reverse transcription/quantitative polymerase chain reaction. POPDC1 was predominantly localized in the sarcolemma with an enhanced expression in the intercalated discs. In failing hearts, many cardiomyocytes appeared deformed and POPDC1 labeling was deranged. The three POPDC mRNAs were expressed in the four heart chambers with higher transcript levels in the ventricles compared to the atria. Heart failure concurred with reduced levels of POPDC1 mRNA and protein in the left ventricle. Correlation analyses of mRNA levels among the failing heart specimens indicated the coordinated regulation of POPDC1 with POPDC3 and of POPDC2 with MYHC7. It can be concluded that POPDC gene expression is modified in end-stage heart failure in humans in a manner suggesting regulatory and/or functional differences between the three family members and that POPDC1 is particularly susceptible to this condition.

Long-term treatment outcome of patients with gastric vascular ectasia treated with argon plasma coagulation.

Background Gastric vascular ectasia (VE) is an uncommon cause of upper gastrointestinal bleeding. Long-term data on the efficacy of argon plasma coagulation (APC) for the treatment of gastric VE are lacking. Methods We retrospectively identified consecutive patients, between January 2005 and December 2010, treated with APC for an index diagnosis of gastric VE. Clinical and endoscopic features and APC treatment success were recorded. Treatment success was determined by resolution of symptoms and stabilization of the hemoglobin level at 30% above baseline. Results A total of 62 patients [28 (45.2%) male] with a mean age of 72.6±12.8 years, who had undergone 159 upper endoscopies (mean 2.6, range 1–10), including 140 APC sessions (mean 2.3, range 1–10), were identified. The duration of follow-up was 46.9±26.5 months. Treatment success was achieved in 16 (25.8%) patients. Predictors of success included older age, focal pattern, lack of comorbid liver failure or collagen vascular disease, use of antiplatelet or anticoagulant drugs, and lower baseline hemoglobin level. Of the patients, 26 (41.9%) died during follow-up. Conclusion APC is safe and effective for the initial management of gastric VE; however, most patients do not experience long-term resolution of upper gastrointestinal bleeding and anemia.

Gastric mucin expression in first-degree relatives of gastric cancer patients.

Objectives There are currently no accepted clinical guidelines for the surveillance of first-degree relatives (FDRs) of gastric cancer patients. The existence of intestinal metaplasia, as well as altered mucin expression, might be associated with an increased risk for gastric cancer. In the present study we aimed to investigate the mucin phenotype of individuals with a family history of gastric cancer. Methods We included FDRs of gastric cancer patients. Individuals with functional chest pain served as controls. Upper endoscopy including extensive biopsy according to the Olga protocol was performed. Immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 was performed. Sera were assayed for pepsinogen I and II. Helicobacter status was determined through Giemsa staining and serological tests. Results Forty FDRs and eight controls were included; the mean age was 46.7±12.0 years. In both the study group and the control group there were no gross endoscopic findings and no histological evidence of intestinal metaplasia. Superficial MUC1 expression was significantly increased in the study group (47.5 vs. 0%; P=0.01). There was no difference in the expression of deep MUC1, MUC2, MUC5AC, or MUC6 between the groups, nor was there a difference in pepsinogen I/II levels or Helicobacter pylori exposure (35.0 vs. 25.0%; P=0.46). Conclusion Despite normal appearing mucosa and the absence of intestinal metaplasia according to histological analysis, FDRs of gastric cancer patients show increased expression of MUC1, which may serve as a predictor of future intestinal metaplasia, dysplasia, and cancer. Further studies are needed to verify these findings and their implications.

Immunohistochemistry staining for mismatch repair proteins: the endoscopic biopsy material provides useful and coherent results☆☆☆

Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) in patients with colorectal cancer can be performed on endoscopic biopsy material or the surgical resection material. Data are continuing to accumulate regarding the deleterious effect of neoadjuvant chemoradiation on MMRP expression. However, despite continuing rise in the use of endoscopic biopsies for IHC, most pathology departments still use mainly the surgical materials for IHC testing. In this study we compared the quality of stains among 96 colon cancer subjects with paired endoscopic and surgical material available for MLH1, MSH2, MSH6, and PMS2 stains (96 × 4, yielding 384 paired stains). Each slide received both a quantitative score (immunoreactivity [0-3] × percent positivity [0-4]) and a qualitative score (absent; weak and focal; strong). The quantitative scores of all MMRP were significantly higher among the endoscopic material (P<.001 for all). In 358 pairs (93.2%), both the endoscopic and operative material stained either strong (322, 83.9%) or absent (36, 9.4%). In 26 pairs (6.8%), the endoscopic material stained strong, whereas the operative material stained focal and weak. No endoscopic biopsy materials stained focal and weak. Our findings indicate that the biopsy material may provide more coherent results. Although these results may indicate that biopsy material provides coherent and useful results, it is yet to be determined if the demonstrated differences pose a real clinical problem in interpreting final results of IHC staining of such kind. Hence, we suggest that when available, the endoscopic material rather than the operative one should serve as the primary substrate for IHC staining.

Utilization of Influenza Immunization in Adults with Crohnʼs Disease—A Longitudinal, Population-Based Study

Background:The incidence of vaccine-preventable disease is increasing. Several guidelines recommend annual influenza vaccination for patients with inflammatory bowel disease. Methods:Using the Business Objects database of Clalit Health Services in the Tel Aviv district we identified all patients older than 18 years with a diagnosis of Crohns disease (CD) on December 31, 2005. This cohort was followed until December 31, 2012. Subjects without inflammatory bowel disease older than 50 years served as controls. The uptake of annual influenza vaccination was recorded. Results:The study included 515 patients with CD (267 [51.8%] men, age 48.9 ± 17.5 years, disease duration 142.7 ± 56.9 months) and 2960 controls (1262 [42.6%] men, P < 0.01, age 68.9 ± 11.1 years, P < 0.01). The mean number of influenza vaccines received from 2006 to 2012 was 2.08 ± 2.46 and 3.40 ± 2.71 in CD and controls, respectively (P < 0.01). Uptake was higher in patients with CD aged 50 to 59 years and 60 to 69 years, compared with controls (0.45 ± 0.04 versus 0.24 ± 0.01, P < 0.01 and 0.64 ± 0.06 versus 0.50 ± 0.01, P = 0.04, respectively). Vaccination uptake increased significantly over time in both groups (P < 0.01). Predictors of vaccination in CD included age, female sex, immunosuppression, and cardiovascular disease. Conclusions:Uptake of influenza vaccination in CD has increased over the past 7 years, and among subjects older than 50 years, uptake remains higher in age-matched controls. Nevertheless, overall uptake remains low, particularly in young males.

Effect of Postprandial Administration of Esomeprazole on Reflux Symptoms in Gastroesophageal Reflux Disease: A Randomized, Controlled Trial.

Background: Esomeprazole is commonly administered with food; however, clinical data to support this practice are lacking. We aimed to determine the effect of postprandial ingestion of esomeprazole on reflux symptoms among patients with gastroesophageal reflux disease (GERD). Methods: Consecutive patients with GERD adequately controlled with esomeprazole 40 mg daily, entered a 2-week lead-in period during which esomeprazole was administered 30 min before breakfast. Patients were then randomized to continue preprandial ingestion or to ingest esomeprazole following a standardized meal. Outcomes included GERD frequency and severity indices, GERD-health-related quality of life (GERD-HRQL) questionnaire and Short Form 36 (SF-36). Results: Thirty-two patients (17 [53.1%] men, aged 53.5 ± 17.2 years) were included, and 16 (50%) switched to postprandial ingestion of esomeprazole. GERD frequency and severity decreased in both groups (Δ9.0 ± 7.2 vs. Δ10.0 ± 8.1, p = 0.29; Δ6.6 ± 6.8 vs. Δ10.2 ± 7.4, p = 0.57 in postprandial group vs. controls, for frequency and severity, respectively). GERD-HRQL improved in both study groups to a similar degree (Δ10.7 ± 10.5 vs. Δ10.0 ± 13.8, p = 0.97). All SF-36 subscores increased in both groups to a similar degree. In a mixed linear model, there were no differences between the study groups in the changes observed in GERD frequency (p = 0.49), severity (p = 0.32), and GERD-HRQL (p = 0.98) during the study period. Conclusion: Switching to postprandial administration of esomeprazole is not associated with deterioration in reflux symptoms among patients with GERD. Esomeprazole seems to remain efficacious when administered after meals.

Increasing Serum Albumin Level Shortly After Gastrostomy Tube Insertion Predicts Longer Survival in Elderly Patients With Dementia.

Goal: To identify factors influencing survival after percutaneous endoscopic gastrostomy (PEG) tube insertion in elderly patients with severe dementia. Background: Use of PEG in patients with dementia raises medical and ethical questions. Study: The cohort included 189 patients aged ≥64 years with severe dementia who underwent PEG tube insertion in 2002 to 2011 at a tertiary hospital and were followed through 2014. Data were collected on background diseases, laboratory tests conducted 14 (±10) days before and 90 (±10) days after PEG, and date of death. Multivariate Cox regression analysis was performed and cumulative survival curves plotted. Results: Mean baseline serum albumin level was significantly lower in patients who died ⩽30 days after PEG (n=32, 16.9%) than patients who survived longer (2.9±0.5 vs. 3.3±0.5 g/dL, P<0.001), and significantly higher in patients who survived 1 year after PEG (n=96, 50.8%) than patients who died earlier (3.4±0.5 vs. 3.1±0.5 g/dL, P=0.002). No significant differences were found for the other laboratory parameters. After adjustment for background diseases, serum albumin level above the median (3.3 g/dL) was the only predictor of survival (hazard ratio 0.51; 95% confidence interval, 0.37-0.72; P<0.001). Patients with stable/increased serum albumin levels at 90 days after PEG (n=80, 42.3%) survived longer than patients with decreased levels. The only predictor of survival after adjustment for age and background diseases was a stable/increased albumin level at 90 days (hazard ratio 0.59; 95% confidence interval, 0.42-0.85; P=0.004). Conclusions: Survival after PEG tube insertion is associated with a higher serum albumin level at baseline and a stable/increased serum albumin level during follow-up.

Attitudes and practice related to Helicobacter pylori infection among primary care physicians.

Objectives Helicobacter pylori infection is a major public health concern and primary care physicians (PCPs) are at the forefront of H. pylori management. We aimed to assess PCP attitudes related to H. pylori and identify areas where PCP practice deviates from the accepted guidelines. Methods A 13-item multiple-choice internet-based questionnaire was distributed to PCPs on a national level. Five questions were related to H. pylori detection, two were related to treatment, three were related to gastric cancer, and three were related to screening. The Maastricht IV/Florence Consensus Report was used as the benchmark for correct responses. Results A total of 314 PCP responses were included [140 (52%) men, age 48.2±12.9 years]. Of the total, 292 (93.0%) prescribed clarithromycin-based triple therapy for first-line treatment, 95 (30.3%) prescribed levofloxacin or bismuth-based protocols for second-line treatment, and 137 (43.6%) routinely confirmed eradication. Screening relatives of gastric cancer patients and screening before NSAID treatment was reported by 87 (30.9%) and 39 (14.1%) PCPs, respectively. Of all, 130 (45.0%) believed that the organism is definitely carcinogenic and only 188 (65.0%) agreed that H. pylori eradication reduces the risk of developing gastric cancer. Adherence with guidelines was associated with younger age, central urban clinic location, and a high volume of H. pylori patients. Conclusion Overall PCP adherence to H. pylori management guidelines is low. Public health agencies should advance educational initiatives aimed at closing these gaps.

Colonic carriage of Streptococcus bovis and colorectal neoplasia: a prospective 17-year longitudinal case-control study.

Background Patients with Streptococcus bovis infective endocarditis have an increased prevalence of advanced colonic neoplasia; however, an association with fecal carriage of the organism is unclear. S. bovis has been shown to promote colonic neoplasia in preclinical studies. The aim of this study was to examine the effect of S. bovis fecal carriage on the long-term risk of colonic neoplasia. Patients and methods Patients were prospectively recruited before colonoscopy. S. bovis was detected by culture in stool, colonic fluid aspirates, and biopsies. Patients continued colonoscopic surveillance at intervals according to accepted guidelines. The National Cancer Registry was checked for diagnoses of colorectal cancer on 31 December 2014. Results A total of 118 patients were recruited [75 (72.8%) men, aged 64.5±9.3 years] including 15 with S. bovis. The mean duration of follow-up was 190.7±123.5 months. Colonic neoplasia was detected at colonoscopy in six (40.0%) and 49 (47%) patients with and without S. bovis, respectively (P=0.78). At the end of follow-up, colorectal cancer had developed in one (6.7%) S. bovis-positive and six (5.8%) S. bovis-negative patients (P=1.00). Conclusion Fecal carriage of S. bovis at baseline is not associated with an increased long-term risk of developing colonic neoplasia in this longitudinal study.

Optimization of 13C-urea breath test threshold levels for the detection of Helicobacter pylori infection in a national referral laboratory

Threshold values for 13C‐urea breath test (13C‐UBT) positivity may be affected by various sociodemographic, host, bacterial, and laboratory factors. Manufacturer recommended cutoffs for 13C‐UBT assays may not be applicable in all settings. Optimizing 13C‐UBT cutoffs may have profound public health ramifications. We aimed to determine the optimal threshold for 13C‐UBT positivity in our population.