Israel Medical Association Journal

Background: Prophylactic intravenous antibiotics are not routinely administered prior to direct peroral cholangiopancreatoscopy. The frequency of post-procedure bacteremia has not been well studied.

Objectives: To evaluate the risk of bacteremia following endoscopic retrograde cholangiopancreatography (ERCP) with cholangiopancreatoscopy. To assess the prevalence of other infectious complications and the effect of real-life practices regarding prophylactic antibiotic administration.

Methods: We conducted a retrospective analysis on consecutive patients (2016–2022) who underwent cholangiopancreatoscopy using the single-operator SpyGlass System (Boston Scientific Corporation, USA). Prophylactic antibiotic treatment was administered based on clinical discretion. Demographic and clinical data, including procedure indication, procedure reports, blood culture results, pre- and post-procedure antibiotic treatment, hospital length, mortality, and infectious and non-infectious complications, were collected.

Results: Our single-center cohort included 75 patients who underwent ERCP with direct cholangiopancreatoscopy. We involved 63 patients in the analysis. In 17/63 patients (27%), post-procedural blood cultures were drawn based on clinical suspicion of infection. Positive cultures were found in 4/17 (23.5%) of all cultures and 4/63 (6.3%) of the entire cohort; 2/63 (3.2%) had clinically significant bacteremia. Antibiotic prophylaxis was administered to 35 patients (55.6%), with no evidence of significant reduction in bacteremia, cholangitis, hospitalization length, or mortality rates when compared to patients who did not receive prophylactic antibiotics (P > 0.05). Post-procedural cholangitis was observed in 5/63 patients (7.9%). There were no cases of acute cholecystitis or liver abscess.

Conclusions: The prevalence of bacteremia and cholangitis following ERCP with direct cholangiopancreatoscopy was 6.3% and 7.9%, respectively. Prophylactic antibiotics did not reduce post-procedural infectious adverse events.

Celiac disease (CD) is diagnosed by demonstrating gluten-induced villous atrophy on duodenal biopsy in patients with positive serology. Duodenal histology remains the gold standard, although pediatric guidelines allow a no-biopsy approach in highly seropositive children. Video capsule endoscopy (VCE) can visualize mucosal changes typical of active CD, such as flattening of mucosal folds, fissuring, scalloping, ulcerations, throughout the small bowel, overcoming the regular endoscopy capability of reaching the proximal duodenum and missing distal and patchy lesions. In this review, I discussed whether VCE can replace duodenal biopsy for diagnosing celiac disease. I summarized diagnostic yield, sensitivity/specificity, and clinical contexts favoring VCE as well as its limitations and potential future role (including artificial intelligence enhancement). I found that video capsule endoscopy is a valuable adjunctive tool to diagnose CD, but currently it complements, rather than outright replaces, duodenal biopsy.

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by persistent respiratory symptoms and airflow obstruction determined by spirometry, including emphysema, chronic bronchitis, and small airway disease. Traditional treatment settings for COPD exacerbations typically involve in-hospital care. However, hospital-at-home (HaH) programs have emerged as an innovative model to provide hospital-level care at a patient's home. I synthesized available randomized controlled trials (RCTs) and compared the outcomes of COPD management in HaH and in-hospital settings. I searched for English language medical literature studies of COPD patients in HaH programs compared to in-hospital. Searches were performed in PubMed, EMBASE, Scopus, and CENTRAL. Outcomes were compared, meta-analyses were performed, and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. Heterogeneity was evaluated and I² statistic was used to measure the proportion of inconsistency in individual studies. Potential publication bias was also calculated. Seven controlled studies representing 19 sub-studies (data sets) were selected according to the inclusion criteria. The OR of the HaH and in-hospital comparison was 0.542, 95%CI 0.379–0.774, P = 0.001. The different clinical outcomes of HaH were better or similar to those at regular hospitals, but with higher patient preference (OR 0.316, 95%CI 0.198–0.506). Heterogeneity and inconsistency were small, with no significant publication bias. HaH may be recommended for COPD patients' hospitalization when needed according to the specific indications and patients matching HaH criteria.

I read with great interest the comprehensive and interesting paper by Hazzan and colleagues in the Israel Medical Association Journal (IMAJ) [1]. The authors examined the difference in the results between morning and afternoon shifts of colonoscopy procedures. Not to my surprise, they found that more polyps were found in the morning shifts than in those in the afternoon. I believe, as do the authors, that the higher quality of the colonoscopy, the better its efficacy in detecting polyps and preventing colorectal cancer (CRC).

Background: Hyponatremia is common among hospitalized children, including those with community acquired pneumonia. The prevalence and severity of hyponatremia were reported to correlate with disease. However, data regarding the association between hyponatremia and causative infectious pathogens are limited and results are inconsistent.

Objectives: To investigate the associations between sodium levels, severity and causative pathogen in children with pneumonia.

Methods: A retrospective study of all children (< 18 years) hospitalized with pneumonia from 1 January 2018 to 31 December 2020. Admission sodium levels were compared to the presumed etiological pathogens, clinical parameters, and inflammatory markers.

Results: Among 751 (52% males) children, 10 (1%) had sodium levels < 130 mEq/L, 187 (25%) had mildly decreased levels 130–134 mEq/L, and the remaining 554 (74%) had normal levels 135–145 mEq/L. Sodium levels < 130 mEq/L were found in 7/236 (3%) of the patients with presumed bacterial pneumonia, in 0/20 of patients with presumed atypical-bacterial, and in only 3/495 (0.6%) of the patients with a presumed viral infection, P < 0.001. Sodium levels < 135 mEq/L conferred an odds ratio of 3.1 (95% confidence interval [95%CI] 2.1–4.3) and levels < 130 mEq/L an odds ratio of 6.8 (95%CI 1.8–33.0) for bacterial infection, P < 0.001 for both. Hyponatremia was also inversely associated with high white blood cell counts, absolute neutrophil cell counts, and C-reactive protein levels.

Conclusions: Hyponatremia was common among children hospitalized with pneumonia and was associated with elevated inflammatory markers and presumed bacterial pneumonia.

Colorectal cancer (CRC) is a major health concern, ranking as the third most common cancer in the United States. Screening programs, especially colonoscopy, play a crucial role in preventing CRC by removing and detecting polyps or early-stage cancers. Despite inherent risks, colonoscopy's effectiveness in saving lives is significant. In this review, we analyzed the outcomes of screening colonoscopies in an asymptomatic population for 15 years, focusing on detection rates and complications. We compared the data with previous meta-analyzes to evaluate changes in efficacy and safety. We conducted a systematic search of medical literature databases (1 January 2012 to 31 December 2023) for English-language studies on CRC screening colonoscopy. Our inclusion criteria comprised complete articles with over 500 participants with extractable data and a focus on screening colonoscopy outcomes in average-risk populations. In total, 2,897,025 people were screened, most (99.6%) were asymptomatic and were an average-risk population. Colonoscopy was complete and reached the cecum in 97–99% of the procedures. CRC was found in 0.5% (95% confidence interval [95%CI] 0.4–0.7%) of the participants. Advanced adenoma was found in 7.6% (95%CI 6.2–9.3%) of the cases. Complications were rare. Perforation developed in 0.022% of the cases and bleeding in 0.148%. Our findings exhibited a significant increase in the detection yield of adenomas and advanced adenomas with low complication rates, which shows that colonoscopy is feasible and suitable for screening for CRC in asymptomatic people.

The emergence of the hybrid hospital represents a paradigm shift, blending the physical and virtual realms to optimize healthcare delivery. Telehealth made its significant entrance into the health systems during the coronavirus disease 2019 (COVID-19) pandemic. The use of a variety of telehealth initiatives increased during the COVID-19 pandemic. Approximately 8% of primary care visits in the United States are by telehealth. Despite the rapid growth of telehealth, several barriers persist. Technological limitations, regulatory challenges, and resistance to change among both healthcare providers and patients pose hurdles to the widespread adoption of telehealth services. A significant concern in the healthcare digital evolution is the digital divide. Socioeconomic factors, such as limited access to high-speed internet and digital devices, can exacerbate existing healthcare disparities. An important part of the hybrid hospital is home hospitalization, which is an alternative to regular hospitalization. This method opens access to big, tertiary, academic centers to remote populations and advances treatment equity. Home hospitalization has become available in several countries such as Australia, China, and the United States, with impressive results for peripheral, remote populations. According to the McKenzie Report, virtual hospitals have the potential to ease busy health systems, make more hospital beds available, decrease the need for building physical hospitals, and save millions of dollars. Hybrid hospitals and telehealth are here to stay. The medical community should study the risks and opportunities and establish guidelines for proper, quality, and safe management.

Mucin gene 5AC (MUC5AC), a secreted mucin, is the most important component of the gastric mucus unstirred, protecting layer, preventing the enzymatic attack of acid and pepsin, toxins, and microorganisms. We investigated the effect of Helicobacter pylori (H. pylori) infection on MUC5AC expression in the gastric mucosa. English language medical literature searches were conducted for gastric MUC5AC expression in H. pylori infected patients compared to uninfected people, or cases after eradication. PubMed, EMBASE, Scopus, and CENTRAL databases were searched. Meta-analysis was performed and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. Heterogeneity was evaluated and I² statistic was used to measure the proportion of inconsistency in individual studies.

We also calculated a potential publication bias. In all, 11 studies representing 13 sub-studies were selected according to the inclusion criteria. The OR of MUC5AC expression in a random effect analysis was 0.217, 95%CI 0.124–0.377, P < 0.0001, significantly lower in H. pylori gastritis than in normal mucosa. When only studies with high-quality scores were calculated, OR was 0.239, 95%CI 0.137–0.419, P < 0.0001. Heterogeneity and inconsistency were small, with no significant publication bias. MUC5AC expression is lower in H. pylori infected mucosa, which may significantly affect the effective colonization and survival of the bacterium and persistent chronic inflammation.

Background: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link.

Objectives: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship.

Methods: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors.

Results: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls.

Conclusions: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Background: Ventricular assist devices (VADs) play a critical and increasing role in treating end-stage heart failure in pediatric patients. A growing number of patients are supported by VADs as a bridge to heart transplantation. Experience with VADs in the pediatric population is limited, and experience in Israel has not been published.

Objectives: To describe this life-saving technology and our experience with VAD implantation in children with heart failure, including characteristics and outcomes.

Methods: We conducted a retrospective chart review of all patients who underwent VAD implantation at Schneider Children's Medical Center from 2018 to 2023.

Results: We analyzed results of 15 children who underwent VAD implantation. The youngest was 2.5 years old and weighed 11 kg at implantation. In eight patients, HeartMate 3, a continuous-flow device, was implanted. Seven patients received Berlin Heart, a pulsatile-flow device. Three children required biventricular support; 11 underwent heart transplants after a median duration of 169 days. Two patients died due to complications while awaiting a transplant; two were still on VAD support at the time of submission of this article. Successful VAD support was achieved in 86.6% of patients. In the last 5 years,79%  of our heart transplant patients received VAD support prior to transplant.

Conclusions: Circulatory assist devices are an excellent bridge to transplantation for pediatric patients reaching end-stage heart failure. VADs should be carefully selected, and implantation techniques tailored to patient's weight and diagnosis at a centralized pediatric cardiac transplantation center. Israeli healthcare providers should be cognizant of this therapeutic alternative.

Background: Up to half the patients diagnosed with acute coronavirus disease 2019 (COVID-19) presented with gastrointestinal symptoms. Gastric mucosal cells, enterocytes, and colonocytes express the viral entry receptor angiotensin-converting enzyme 2 (ACE2) and coreceptor transmembrane protease serine 2 (TMPRSS2) and are prone to infection. Direct infection of gastrointestinal epithelial cells has been demonstrated. COVID-19 disease was first diagnosed in Israel at the end of February 2020 with 842,536 confirmed cases and 6428 deaths by the end of June 2021. In our multicenter, retrospective cohort study, we looked for gastrointestinal signs and symptoms in two periods and correlated them with mortality. Period 1 included the first and second waves and the original virus. Period 2 represented the third wave and the alpha variant.

Objectives: To reveal gastrointestinal signs and symptoms in two periods and correlate them with mortality.

Methods: From 22,302 patients hospitalized in general medical centers, we randomly selected 3582 from Period 1 and 1106 from Period 2. The study was performed before vaccinations were available.

Results: Gastrointestinal signs and symptoms, diarrhea, vomiting, abdominal pain, and taste/smell loss were significantly more prevalent during Period 1. Thirty-day mortality and in-hospital mortality were significantly higher in Period 2 than in Period 1, 25.20% vs. 13.68%, and 21.17% vs. 12.87%, respectively (P < 0.001).

Conclusions: Thirty-day mortality and in-hospital mortality rates were 1.84 and 1.64 times higher from 6 November 2020 to 15 January 2021, the alpha variant, and in negative correlation with gastrointestinal symptoms.

Background: Polymyositis (PM) and dermatomyositis (DM) are inflammatory mediated myopathies characterized by progressive symmetric proximal muscle weakness and associated with extra-muscular involvement. Central nervous system complications are rarely reported with these diseases.

Objectives: To investigate the association between dementia and PM/DM.

Methods: A retrospective cohort study was conducted using a database from Clalit Health Care, the largest health maintenance organization in Israel. Patients with a first recorded diagnosis of PM/DM were included and were compared with age- and sex-matched controls by a ratio of 1:5. The prevalence of dementia among PM/DM patients compared to controls was assessed using a univariate and a multivariable model. Binary logistic regression analysis was conducted to assess the association of different factors with dementia within the PM/DM cohort.

Results: The study included 2085 PM/DM cases (17.0%) and 10,193 age- and sex-matched controls (83.0%). During the follow-up time, 36 PM/DM patients were diagnosed with dementia compared to 160 controls, with a univariate hazard ratio (HR) of 1.10 (95% confidence interval [95%CI] 0.77–1.58). Within the PM/DM cohort, significant predictors for the development of dementia included increased age at diagnosis (5 years increment; OR 1.86, 95%CI 1.57–2.21, P < 0.001) and treatment with glucocorticoids (OR 5.40, 95%CI 1.67–17.67, P = 0.005).

Conclusions: In our cohort, inflammatory myopathies were not associated with dementia. Age and treatment with glucocorticoids were associated with dementia. If dementia is diagnosed in patients with inflammatory myopathies, other systemic causes should be investigated.

Background: Mucins, heavily glycosylated glycoproteins, are synthesized by mucosal surfaces and play an important role in healthy and malignant states. Changes in mucin synthesis, expression, and secretion may be a primary event or may be secondary to inflammation and carcinogenesis.

Objectives: To assess current knowledge of mucin expression in the small bowel of celiac disease (CD) patients and to determine possible associations between mucin profile and gluten-free diet.

Method: Medical literature searches of articles in English were conducted using the terms mucin and celiac. Observational studies were included. Pooled odds ratios and 95% confidence intervals were calculated.

Results: Of 31 articles initially generated by a literature search, 4 observational studies that fulfilled the inclusion criteria remained eligible for meta-analysis. These studies included 182 patients and 148 controls from four countries (Finland, Japan, Sweden, United States). Mucin expression was significantly increased in small bowel mucosa of CD patients than in normal small bowel mucosa (odds ratio [OR] 7.974, 95% confidence interval [95%CI] (1.599–39.763), P = 0.011] (random-effect model). Heterogeneity was significant: Q = 35.743, df (Q) = 7, P < 0.0001, I² = 80.416%. ORs for MUC2 and MUC5AC expression in the small bowel mucosa of untreated CD patients were 8.837, 95%CI 0.222–352.283, P = 0.247 and 21.429, 95%CI 3.883–118.255, P < 0.0001, respectively.

Conclusions: Expression of certain mucin genes in the small bowel mucosa of CD patients is increased and may serve as a diagnostic tool and assist in surveillance programs.

Background: Fibromyalgia syndrome (FMS) is estimated to affect 2–4% of the general population. While FMS has some known environmental and genetic risk factors, the disorder has no clear etiology. A common coexisting disorder with FMS is small fiber neuropathy (SFN). High levels of serum immunoglobulin M (IgM) binding to trisulfated-heparin-disaccharide (TS-HDS) were recently found to be associated with SFN.

Objectives: To evaluate potential differences in anti-TS-HDS antibody titers in women with FMS compared to healthy controls.

Methods: In this cross-sectional study, we evaluated 51 female participants: 30 with a diagnosis of FMS and 21 healthy controls who had been recruited at the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. All of the participants were older than 18 years of age. Anti-TS-HDS IgM levels were measured in their sera using the enzyme immunoassay technique.

Results: The mean anti-TS-HDS IgM levels were significantly lower in the FMS group, compared with the control group (7.7 ± 5 vs. 13.2 ± 8.6 U/ml, respectively; P = 0.013).

Conclusions: There is a possible association between FMS and anti-TS-HDS IgM. This association might be the missing link for the coexistence of SFN and FMS, but further study should be performed to assess this association and this auto-antibody characteristic.

Pneumonia patients are susceptible to autonomic nervous system changes. Ultrashort HRV (usHRV) is the measurement of cyclic changes in heart rate over a period < 5 minutes.

Objectives: To describe usHRV in patients with pneumonia and assess the correlation with mortality.

Methods: We conducted a retrospective analysis, which included patients diagnosed with pneumonia in the emergency department (ED). UsHRV indices were calculated from a 10-second ED electrocardiogram and correlated with mortality utilizing logistic and Cox regressions.

Results: The study comprised 240 patients. Mortality rates over 30, 90, and 365 days were 13%, 18%, and 30%, respectively. usHRV frequency-domain parameters had significant univariate correlations with mortality. Normalized low frequency (LF) and high frequency (HF) were correlated with 30-, 90-, and 365-day mortality in an opposite direction (odds ratio [OR] 0.094, P = 0.028 vs. OR 4.589, P =0.064; OR 0.052, P = 0.002 vs. OR 6.975, P =0.008; OR 0.055, P < 0.001 vs. OR 7.931, P < 0.001; respectively). Survival analysis was conducted for a follow-up median period of 5.86 years (interquartile range 0.65–9.77 years). Univariate Cox proportional hazard regression revealed time-domain indices with significant correlation with survival (SDNN and RMSSD; hazard ratio [HR] 1.005, 1.005; P = 0.032, P = 0.005; respectively) as well as frequency-domain parameters (normalized LF, HF, LF/HF ratio, and total power; HR 0.102, 5.002, 0.683, 0.997, respectively; P < 0.001).

Conclusions: usHRV may predict mortality in pneumonia patients and serve as a novel risk stratification tool.