Israel Medical Association Journal

Background: The increasing use of micromobility solutions (MMS), including electric scooters, electric, and non-motorized bicycles, has revolutionized urban transportation. We addressed the rising incidence of injuries related to pedestrian-MMS accidents, with a specific focus on pedestrian injuries.

Objectives: To improve clinician comprehension of patient characteristics and injuries associated with pedestrian-MMS accidents and to provide insights for injury prevention, policy making, and urban planning.

Methods: We conducted a retrospective analysis, June 2017 to January 2023, of pedestrians who were admitted to the emergency department post-MMS accidents. Data included patient characteristics, type of MMS, time of the accident, and outcome variables including type of injury, hospitalization, and surgical treatment.

Results: The study cohort included 498 pedestrians (57.7% women), with a mean age of 42.3 ± 21.8 years. Nighttime accidents were 53.2% of cases. Fractures were the dominant type of injury (18.3% of the total cohort). Age, particularly those ≥ 60 years, significantly (P < 0.05) influenced fracture, hospitalization, and surgery rates (30.6%, 22.4%, and 12.6%, respectively). The odds ratio of having a fracture for pedestrians ≥ 60 years was 5.35 (P = 0.008). Interestingly, the type of MMS did not significantly affect outcomes.

Conclusions: Age emerged as a critical factor in injury severity, emphasizing the need for age-specific safety measures in urban environments. The type of MMS did not show a significant influence on outcomes, emphasizing the importance of a comprehensive regulation of all MMS types. The high rate of accidents during nighttime calls for focused interventions during this period to prevent accidents.

Background: Giant cell arteritis (GCA) is a large vessel vasculitis predominantly affecting patients over 50 years, typically managed with glucocorticoids, with treatment varying on individual patient needs. While effective for GCA, long-term glucocorticoids use poses significant risks, including the development of osteoporosis, a metabolic bone disease common in older individuals. This overlap poses a significant clinical challenge, as the treatment for GCA inadvertently raises the risk of osteoporosis and necessitates careful balance to manage both conditions effectively.

Objectives: To investigate the occurrence of osteoporosis and other co-morbid conditions in patients with GCA treated with glucocorticoids.

Methods: A retrospective cross-sectional analysis of GCA patients examined the correlation between GCA and osteoporosis by searching the Clalit Health Service database for patients over 50 years of age from January 2002 to January 2018. In addition, we conducted a logistic regression analysis stratifying for other co-morbidities to evaluate the independent association between GCA and osteoporosis.

Results: In total, 6607 GCA patients were compared with 36,066 age- and sex-matched controls. The study revealed a higher prevalence of osteoporosis in the GCA group (43%) compared to controls (27%) (odds ratio [OR] 2.06, 95% confidence interval [95%CI] 1.95–2.17). In addition, hypertension, hyperlipidemia, diabetes mellitus, and ischemic heart disease were more prevalent among GCA patients. After stratifying for cardiovascular co-morbidities, GCA remained independently associated with osteoporosis (OR 2.1, 95%CI 1.96–2.26, P < 0.001).

Conclusions: Glucocorticoid-treated GCA is independently associated with osteoporosis. Healthcare providers must consider this added aspect of GCA for the treatment and management of patients.

Background: The prognostic significance of diabetes mellitus (DM) on hospitalization outcomes of patients with acute decompensated heart failure (ADHF) remains inconclusive.

Objectives: To comprehensively assess the clinical outcomes of patients with and without DM hospitalized for ADHF.

Methods: This single center retrospective cohort study included consecutive hospitalized patients with a principal diagnosis of ADHF between 1 January 2010 and 31 December 2019. Patients were categorized into diabetic and non-diabetic groups. The primary outcomes assessed were in-hospital mortality, 1-year overall mortality, and readmission rate within a year of follow-up.

Results: The final analysis involved 787 ADHF patients, with 62% having a pre-existing diagnosis of DM. Despite a higher burden of co-morbidities in diabetic patients, there were no differences in clinical outcomes when compared to non-diabetic counterparts. Specifically, there were no differences in overall hospital mortality (10% vs. 10%, P = 0.675), 1-year mortality (22% vs. 25%, P = 0.389), and re-admissions (51% vs. 56%, P = 0.154). Notably, the 1-year mortality among diabetic patients was not influenced by HbA1c levels documented before or during admission.

Conclusions: The clinical outcomes of patients hospitalized with ADHF did not differ by the presence of diabetes. Instead, our findings emphasize the importance of early heart failure prevention and subsequent hospitalization. Considering the evolving landscape of disease-modifying therapies for heart failure, achieving this goal becomes increasingly feasible.

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on patient populations can be divided to direct consequences of the disease and indirect implications of changes imposed on the national healthcare systems. The impact of the later survival of chronic hemodialysis patients is still unknown.

Objectives: To examine the impact of quarantine on health outcomes of dialysis patients.

Methods: In a retrospective case-controlled study, we compared chronic hemodialysis patients from two separate timeframes: during a quarantine period and a parallel time without quarantine.

Results: The study included 344 hemodialysis patients. Baseline characteristics were compared between those enrolled in 2015 and those enrolled in 2020. Despite comparable clinical parameters, a statistically significant increase in the 6-month mortality rate was observed in 2020 (1.2% vs. 6.7%, P = 0.01), primarily attributed to sepsis. Notably, no deaths were attributed to COVID-19 in 2020. Interdialytic weight gain and dialysis quality remained similar between the two groups, with a mild trend toward excessive weight gain in 2020. Secondary outcomes after 6 months did not significantly differ, except for lower sodium values in 2015 compared to 2020.

Conclusions: Dialysis patients experienced disproportionate effects from the COVID-19 pandemic, even with continuous care and no direct virus-related fatalities. The findings showed unintended consequences of quarantine measures, highlighting adverse impact on both physical and mental health. Recognizing and addressing these consequences are imperative for minimizing their impact in future pandemics, emphasizing the importance of proactive measures in healthcare planning.

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.

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: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. There is an under-representation of non-Caucasians in epidemiologic studies of HS. The characteristics of HS in Israeli Arabs have not yet been studied.

Objectives: To investigate the demographic and clinical profile of HS in the Israeli Arab population.

Methods: A retrospective analysis was conducted in two cohorts of patients with HS in Israel. The patients were derived from the database of a large health management organization (n=4191, 639 Arabs; population-based) and a major tertiary medical center (n=372, 49 Arabs). Demographic and clinical data were compared between ethnic groups.

Results: The prevalence of HS in Israeli Arabs was found to be 0.5%, fivefold higher than in Jews. Arab patients were younger (35.3 vs. 40.5 years, P < 0.001) and mostly male (52% vs. 35.7%, p < 0.001), with lower rates of co-morbidities, including smoking (40.8% vs. 55.7%, p < 0.001), hyperlipidemia, and depression as well as a higher rate of dissecting cellulitis (10.2% vs. 1.9%, p = 0.008). HS was more severe in Arabs, but of shorter duration, with mainly axillary involvement (79.6% vs. 57.9%, p = 0.004). Treatment with hormones was more common in Jews, and with biologic agents in Arabs.

Conclusions: The findings suggest a different phenotype of HS in Arabs, warranting further study.

Background: The Gaza–Israeli conflict poses challenges for unbiased reporting due to its complexity and media bias. We explored recent scientific publications to understand scholarly discourse and potential biases surrounding this longstanding geopolitical issue.

Objectives: To conduct a descriptive bibliometric analysis of PubMed articles regarding the recent Gaza–Israeli conflict.

Methods: We reviewed 1628 publications using keywords and medical subject headings (MeSH) terms related to Gaza, Hamas, and Israel. We focused on articles written in English. A team of researchers assessed inclusion criteria, resolving disagreements through a third researcher.

Results: Among 37 publications, Lancet, BMJ, and Nature were prominent journals. Authors from 12 countries contributed, with variety of publication types (46% correspondence, 32% news). Pro-Gaza perspectives dominated (43.2%), surpassing pro-Israel (21.6%) and neutral (35.1%) viewpoints. Pro-Gaza articles exhibited higher Altmetric scores, indicating increased social media impact. Pro-Israel publications were predominantly authored by Israelis.

Conclusions: The prevalence of pro-Gaza perspectives underscores challenges in maintaining impartiality. Higher social media impact for pro-Gaza publications emphasizes the need for nuanced examination. Addressing bias is crucial for a comprehensive understanding of this complex conflict and promoting balanced reporting.

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: The chloride intracellular channel (CLIC) protein family consists of six members in humans. CLICs are unique due to their metamorphic property, displaying both soluble and integral membrane forms. The transmembrane conformation was shown to give rise to ion-channel activity in vitro. In recent years, CLICs were implicated in a growing number of physiological processes in various organ systems and associated with distinct disease states. Indeed, the founding member of the family, CLIC5, was shown to be involved in hereditary deafness and various types of cancer. Nevertheless, the natural interactants and endogenous ligands of CLIC5 have not been discovered yet.

Objectives: To find ligands that affect the biochemical properties and activity of CLIC5. We hypothesized that such ligands could serve as important tools for resolving the long-sought cellular roles of CLICs and may offer novel therapeutic avenues for CLIC-associated conditions.

Methods: Using molecular biology and biochemical methods, CLIC5 was overexpressed in Escherichia coli and purified. Next, a high-throughput differential scanning fluorimetry thermal shift assay (TSA) was established and the interaction of approximately 500 natural compounds was examined.

Results: The TSA-based screening approach developed here allows to evaluate the effect of approximately 100 compounds in parallel within approximately 1 hour. Our proof-of-concept screening yielded 11 potential hits, significantly affecting the thermal stability of CLIC5. By examining the dose-dependence of this effect, we identified a specific interaction of CLIC5 with curcumin.

Conclusions: Using the approach we developed, large libraries of small molecules can be screened efficiently to identify novel CLIC5 interactants. Considering the participation of CLIC5 in various physiological and pathological processes, uncovering ligands that inhibit or activate CLIC5 may provide tools to modulate its activity and possibly to ameliorate CLIC5-related pathologies in the future.

Background: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and tenderness with associated neuropsychological symptoms such as fatigue, unrefreshing sleep, cognitive dysfunction, anxiety, and depression. Osteoporosis is defined as a reduction of bone density. Previous studies to determine an association of FMS with osteoporosis showed mixed results, partially due to small sample sizes and lack of statistical power.

Objectives: To evaluate the association of FMS with osteoporosis.

Methods: We conducted a case-control study utilizing the database from Israel’s largest health maintenance organization. FMS patients were compared to age- and sex-matched controls. Data were analyzed using chi-square and t-tests. Multivariable logistic regression models assessed the association between osteoporosis and FMS. Spearman’s rho test was used for correlation.

Results: We utilized data from 14,296 FMS patients and 71,324 age- and sex-matched controls. Spearman's rho test showed a significant correlation between FMS and osteoporosis (correlation coefficient 0.55, P < 0.001). A logistic regression for osteoporosis showed an odds ratio [OR] of 1.94 (95% confidence interval [95%CI] 1.83–2.06, P < 0.001) for FMS compared to controls and found higher body mass index to be slight protective (OR 0.926, 95%CI 0.92–0.93, P < 0.001).

Conclusions: There is a significant correlation between FMS and osteoporosis. Early detection of predisposing factors for osteoporosis in FMS patients and implementation of suitable treatments and prevention measures (such as dietary supplements, resistance or weight bearing exercise, and bone-mineral enhancing pharmacological therapy) may reduce both occurrence rate and severity of osteoporosis and its complications, such as fractures.

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.

Background: Dysphagia is a common symptom with diverse etiologies and refers to disorders of the process of swallowing food or fluids. Many studies have reported the anatomical and functional differences between men and women in swallowing in healthy patients; however, sex discrepancies in symptomatic patients have not often been studied.

Objectives: To compare the performance of men and women with dysphagia using videofluoroscopy.

Methods: To compare the performance of men and women with dysphagia using videofluoroscopy.

Results: A total of 203 patients met the inclusion criteria, 106 men (52%) and 97 women (48%). Men complained significantly more about choking on liquids (P = 0.002) and in swallowing pills (P = 0.004) compared to women. Men had more abnormalities in the pharyngeal phase (P = 0.015) and at the upper esophageal sphincter (P = 0.056). The prevalence of aspiration, penetration, and barium residue in the hypopharynx and in the vallecula were significantly greater in men as well.

Conclusions: In patients with dysphagia, women had fewer subjective symptoms and performed better than men in videofluoroscopy especially in the pharyngeal phase. These differences are probably due to different anatomical and functional swallowing characteristics. A better understanding of these discrepancies can be useful in offering tailored treatment in clinical practice.

Background: Secondary immune thrombocytopenic purpura (ITP) associated with coronavirus disease 2019 (COVID-19) is a rare but serious complication of the pandemic. Diagnostic criteria include clinical and laboratory findings. Early treatment is often effective, but rare severe bleeding and death can occur. An autoimmune mechanism is likely.

Objectives: To determine a role for molecular mimicry in producing disease.

Methods: Hexapeptide and heptapeptide matches between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and platelet N-glycosylated proteins and other human proteins were assessed.

Results: Shared viral and platelet glycoprotein peptides were found. Copy frequency of these peptides in the human proteome was low for many of the candidate molecular mimics.

Conclusions: The data support a contribution of molecular mimicry in COVID-19 ITP autoimmunity and offer avenues for in vitro diagnostic assay development. The continuation of the pandemic necessitates additional understanding of COVID-19 ITP as well as studies on diagnosis and mitigation.

Background: Pilonidal disease in the natal cleft is treated traditionally by a wide and deep excision of the affected area. There is growing awareness, however, to the advantages of minimally invasive surgeries.

Objectives: To compare the efficacy of wide excision operations and minimal trephine surgery in patients with primary pilonidal disease.

Methods: In this retrospective study we examined surgical and inpatient records of 2039 patients who underwent surgery for primary pilonidal disease in five private hospitals between 2009 and 2012. Most procedures were of lay-open, primary midline closure, and minimal surgery types. Pilonidal recurrence rates were evaluated in a subset of 1260 patients operated by 53 surgeons each performing one type of surgery, regardless of patient characteristics or disease severity.

Results: With a mean follow-up of 7.2 years, 81.5%, 85%, and 88% of patients were disease-free after minimally invasive surgery, wide excision with primary closure, and lay-open surgery, respectively, with no statistically significant difference in recurrence rates. Minimal surgeries were usually performed under local anesthesia and involved lower pain levels, less need for analgesics, and shorter hospital stays than wide excision operations, which were normally performed under general anesthesia. The use of drainage, antibiotics, or methylene blue had no effect on recurrence of pilonidal disease.

Conclusions: Minimally invasive surgeries have the advantage of reducing the extent of surgical injury and preserving patient’s quality of life. They should be the treatment of choice for primary pilonidal disease