Israel Medical Association Journal

Background: Ischemic stroke is associated with increased risk of morbidity and mortality in future vascular events.

Objectives: To investigate whether CHA₂DS₂-VASc scores aid in risk stratification of middle-aged patients without atrial fibrillation (AF) experiencing ischemic stroke.

Methods: We analyzed data of 2628 patients, aged 40–65 years with no known AF who presented with acute ischemic stroke between January 2020 and February 2022. We explored the association between CHA₂DS₂-VASc scores categorized by subgroups (score 2–3, 4–5, or 6–7) with major adverse cardiac and cerebrovascular events (MACCE) including recurrent stroke, myocardial infarction, coronary revascularization, or all-cause death during a median follow-up of 19.9 months.

Results: Mean age was 57 years (30% women); half were defined as low socioeconomic status. Co-morbidities included hypertension, diabetes, obesity, and smoking in 40–60% of the patients. The incidence rate of MACCE per 100 person-years was 6.7, 12.2, and 21.2 in those with score 2–3, 4–5, and 6–7, respectively. In a multivariate cox regression model, compared to patients with score 2–3 (reference group), those with score 4–5 and 6–7 had an adjusted hazard ratio (95% confidence interval [95%CI]) for MACCE of 1.74 (95%CI 1.41–2.14) and 2.87 (95%CI 2.10–3.93), respectively. The discriminative capacity of CHA₂DS₂-VASc score for overall MACCE was modest (area under curve 0.63; 95%CI 0.60–0.66), although better for myocardial infarction 0.69 (95% CI 0.61–0.77).

Conclusions: CHA₂DS₂-VASc score may predict future MACCE in middle-aged patients with ischemic stroke and no history of AF.

In this special issue of Israel Medical Association Journal (IMAJ) we expose readers to the topic of artificial intelligence (AI) in medicine. AI has become a powerful tool, which enables healthcare professionals to personalize treatment based on many factors, including genetic analyses of tumors, and to consider other co-morbidities affecting a specific patient. AI gives physicians the ability to analyze huge amounts of data and to combine data from different sources. AI can be implemented make a diagnosis based on computed tomography (CT) scans and magnetic resonance imaging (MRI) scans using deep machine learning and data that are stored in the memory of mega computers. AI assists in tailoring more precise surgery to train surgeons before surgery and to support surgeons during procedures. This advancement may benefit surgical procedures by making them more accurate and faster without cutting unnecessary tissues (e.g., nerves and blood vessels); thus, patients face fewer complications, lower rates of infection, and more operation theater time. In this issue, we include three original studies that describe the use of AI in academia and eight review articles that discuss applications of AI in different specialties in medicine. One of the review articles addresses ethical issues and concerns that are raised due to the more advanced use of AI in medicine.

Background: Laryngopharyngeal reflux (LPR) refers to the backflow of acidic stomach content into the larynx, pharynx, and upper aerodigestive tract. The diagnosis of LPR is based on the patient's history and findings of the laryngoscopy associated with LPR. Other possible manifestations consistent with LPR symptoms include laryngeal cancer, vocal fold granulomas, Reinke's space edema, and vocal polyps. In this study, we compared the characteristics of patients with LPR symptoms and incidental laryngeal findings (ILF) in the laryngoscopic evaluation to those without ILF (WILF).

Objectives: Determine the characteristics of LPR-symptomatic patients with ILF versus WILF.

Methods: In this retrospective study, we examined 160 medical charts from patients referred to the otolaryngology clinic at Galilee Medical Center for LPR evaluation 2016–2018. The reflux symptoms index (RSI), reflux finding score (RFS), and demographics of the patient were collected. All patients with a positive RSI score for LPR (RSI > 9) were included, and the profiles of patients with versus without ILF on laryngoscopy examination were compared.

Results: Of the 160 patients, 20 (12.5%) had ILF during laryngoscopy. Most had vocal cord findings such as leukoplakia (20%), polyps (15%), and nodules (20%). Hoarseness, throat clearing, swallowing difficulty, breathing difficulties, and total RSI score were significantly higher in patients with ILF.

Conclusions: Evaluation of LPR symptoms may provide otolaryngologists with a tool to identify patients with other findings on fiberoptic laryngoscopy. A laryngoscopic examination should be part of the examination of every patient with LPR to enable diagnosis of incidental findings.

Gastric perforation secondary to foreign body ingestion is rare. While obvious signs of acute abdomen usually lead to a prompt diagnosis by emergency department (ED) staff, this can be delayed in non-responsive or mentally disabled patients. An altered pain perception has been described in schizophrenia, as part of a complex phenomenon, which is thought to be unrelated to changes in nociceptive pathways. Cognitive impairment and negative symptoms may strongly influence the patient’s expression of pain [1].

On 7 October 2023, a large-scale invasion by armed Hamas terrorists occurred in southern Israel. Approximately 1500 militants breached the Gaza security barrier using tractors, RPGs, and explosives. Concurrently, the terrorists utilized various means including armed vehicles, motorized paragliders, sea incursions, and a massive rocket attack launched toward Israel. On entering Israeli territory, the militants dispersed and targeted several towns, kibbutzim (collective communities), and Israel Defense Forces (IDF) military bases near Gaza. This strategy resulted in a death toll exceeded 1300 civilians and soldiers. In addition, more than 240 individuals were abducted. This attack occurred in one day. In this article, we introduce the Israeli National Institute of Forensic Medicine, which specialized in forensic analysis during mass casualty incidents, and pivotal role it played on 7 October. We present a detailed discussion on methods, challenges, and adaptations the institute took in response to the event of 7 October.

Background: With age, colorectal cancer (CRC) prevalence rises. The elderly (> 75 years), and the very elderly (> 85 years) are especially vulnerable. The advantages of screening must be assessed in the context of diminished life span and co-morbidities.

Objective: To compare CRC findings in colonoscopies that were performed following a positive fecal occult blood test/fecal immunochemical test (FOBT/FIT) in both elderly and very elderly age groups with those of younger patients.

Methods: We identified colonoscopies conducted between 1998 and 2019 following a positive stool test for occult blood in asymptomatic individuals. A finding of malignancy was compared between the two patient age groups. Furthermore, a sub-analysis was performed for positive malignancy findings in FOBT/FIT among patients > 85 years compared to younger than < 75 years.

Results: We compared the colonoscopy findings in 10,472 patients: 40–75 years old (n=10,146) vs. 76–110 years old (n=326). There was no significant difference in prevalence of CRC detection rate between the groups following positive FOBT/FIT (2.1% vs. 2.7%, P = 0.47). Similar results for non-significant differences were obtained in the sub-analysis compared to malignancy detection rates in the very elderly 0% (n=0) vs. 2.1% for < 75 years old (n=18), P = 0.59.

Conclusions: Although the prevalence of CRC increases with age, no significant increase in the detection rate of CRC by FOBT was found in either the elderly or very elderly age groups. Screening colonoscopies in elderly patients should be performed only after careful consideration of potential benefits, risks, and patient preferences.

Recent studies using propensity score matching have clearly indicated that contrast nephropathy following computed tomography occurs in hospitalized patients with advanced chronic kidney disease (eGFR < 30 ml/min/1.73 m²) and that this iatrogenic complication is likely underestimated because of concomitant renal functional recovery, unrelated to the imaging procedure. These findings should be considered regarding contrast-enhanced studies in such patients.

Background: The DES-obstructive sleep apnea (DES-OSA) score uses morphological characteristics to predict the presence and severity of obstructive sleep apnea syndrome (OSAS).

Objectives: To validate DES-OSA scores on the Israeli population. To identify patients requiring treatment for OSAS. To evaluate whether additional parameters could improve the diagnostic value of DES-OSA scores.

Methods: We performed a prospective cohort study on patients attending a sleep clinic. Polysomnography results were examined independently by two physicians. DES-OSA scores were calculated. STOP and Epworth questionnaires were administered, and data on cardiovascular risk was extracted.

Results: We recruited 106 patients, median age 64 years, 58% male. DES-OSA scores were positively correlated with apnea-hypopnea index (AHI) (P < 0.001) and were significantly different between the OSAS severity groups. Interobserver agreement for calculating DES-OSA was very high between the two physicians (intraclass correlation coefficient 0.86). DES-OSA scores ≤ 5 were associated with high sensitivity and low specificity (0.90 and 0.27, respectively) for moderate to severe OSAS. In univariate analysis, only age was significantly correlated with the presence of OSAS (OR 1.26, P = 0.01). Age older than 66 years as a single point in the DES-OSA score slightly improved the sensitivity of the test.

Conclusions: DES-OSA is a valid score based solely on physical examination, which may be useful for excluding OSAS requiring therapy. DES-OSA score ≤ 5 effectively ruled out moderate to severe OSAS. Age older than 66 years as an extra point improved the sensitivity of the test.

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: Trabecular bone score (TBS) reflects vertebrae microarchitecture and assists in fracture risk assessment. The International Society of Clinical Densitometry postulates that the role of TBS in monitoring antiresorptive therapy is unclear. Whether changes in TBS correlate with bone resorption measured by bone turnover markers is not known.

Objectives: To determine whether longitudinal changes in TBS correlate with C-terminal telopeptide (CTX) of type I collagen.

Methods: Examinees with two bone mineral density (BMD) measurements were detected via the institutional database. Over 5.8% change in TBS was considered least significant and patients were grouped accordingly (increment, decrement, or unchanged). CTX, BMD, co-morbidities, incident fractures, and medication exposure were compared between the groups by Kruskal-Wallis. The correlation between TBS and BMD change and CTX in a continuous model was analyzed by Pearson's correlation coefficient.

Results: In total, 110 patients had detailed medical records. In 74.5%, TBS change was below least significant change. Two other TBS categories, fracture incidence or medication exposure, did not differ by CTX. In the continuous model, BMD and TBS change was positively correlated (r = 0.225, P = 0.018). A negative correlation was observed between BMD change and CTX. The decrease in BMD level was associated with higher CTX (r = -0.335, P = 0.004). No correlation was observed between CTX and TBS.

Conclusions: No correlation between TBS dynamics and bone resorption marker was found. Clinical interpretation and implication of longitudinal TBS changes should be further explored.

Background: Cancellation of transesophageal echocardiography (TEE) tests leads to inefficient use of echocardiography laboratory (echo lab) time and wastes resources.

Objectives: To identify the causes of same-day TEE cancellations in hospitalized patients, to formulate a TEE order screening protocol, and to evaluate its efficacy at implementation.

Methods: We performed a prospective analysis of inpatients referred to a single tertiary hospital echo lab for TEE study by inpatient wards. A comprehensive screening protocol emphasizing active participation of all links directly involved in the chain of inpatient TEE referral was developed and implemented. Comparison of pre- and post-implementation of the new screening protocol on two consecutive periods of 6 months on TEE cancellation rates out of total ordered TEEs stratified by cause categories was performed.

Results: In total, 304 inpatient TEE procedures were ordered during the initial observation period; 54(17.8%) were canceled on the same day. The most common cancellation reasons were equally respiratory distress and patient not in fasted state (20.4% of total cancellations and 3.6% of all scheduled TEEs for each cause). Following implementation of the new screening process, total TEEs ordered (192) and cancelled (16) dropped significantly. A decrease in the rate of each cancellation category was observed, with statistical significance achieved for the overall cancellation rate (8.3% vs. 17.8%, P = 0.003), but not for the individual cancellation categories in split analysis.

Conclusions: A concerted effort to implement a comprehensive screening questionnaire significantly reduced same-day cancellations of scheduled TEEs.

Background: The neutrophil to lymphocyte ratio (NLR) has demonstrated prognostic value in various malignant conditions, including gastric adenocarcinoma. However, chemotherapy may affect NLR.

Objectives: To evaluate the prognostic value of NLR as an accessory decision-making tool in terms of operating patients after neoadjuvant chemotherapy in patients with resectable gastric cancer.

Methods: We collected oncologic, perioperative, and survival data of patients with gastric adenocarcinoma who underwent curative intent gastrectomy and D2 lymphadenectomy between 2009 and 2016. The NLR was calculated from preoperative laboratory tests and classified as high (> 4) and low (≤ 4). The t-test, chi-square, Kaplan-Meier analysis, and Cox multivariate regression models were used to assess associations of clinical, histologic, and hematological variables with survival.

Results: For 124 patients the median follow-up was 23 months (range 1–88). High NLR was associated with greater rate of local complication (r=0.268, P < 0.01). The rate of major complications (Clavien-Dindo ≥ 3) was higher in the high NLR group (28% vs. 9%, P = 0.022). Among the 53 patients who received neoadjuvant chemotherapy, those with low NLR had significantly improved disease-free survival (DFS) (49.7 vs. 27.7 months, P = 0.025). Low NLR was not significantly associated with overall survival (mean survival, 51.2 vs. 42.3 months, P = 0.19). Multivariate regression identified NLR group (P = 0.013), male gender (P = 0.04), and body mass index (P = 0.026) as independently associated with DFS.

Conclusions: Among gastric cancer patients planned for curative intent surgery who underwent neoadjuvant chemotherapy, NLR may have prognostic value, particularly regarding DFS and postoperative complications.

Thyroid storm-related heart failure is a rare, life threatening complication of hyperthyroidism. In refractory cases, urgent thyroidectomy is required for definitive control of thyrotoxicosis. venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a supportive measure for cardiorespiratory failure requiring continuous anticoagulation to prevent clotting. We presented two cases of thyrotoxic cardiac failure that necessitated VA-ECMO. One of the patients was successfully treated with thyroidectomy while on VA-ECMO. To the best of our knowledge, only two such cases have previously been reported.

Gallbladder metastasis is an extremely rare entity [1]. It is mainly secondary to melanoma but has also been reported as originating from breast cancer, renal cell carcinoma, and gastric cancer. Its diagnosis is often late in the advanced stage of the disease with the involvement of other organ systems [2].

We present a case of a patient who developed gastric cancer gallbladder metastasis. These findings are usually incidental on pathology of cholecystectomy specimens [1]. In our case, the metastatic lesion was demonstrated on magnetic resonance imaging (MRI) prior to surgery. Of note, the lesion had a similar enhancement pattern to the primary tumor.

Background: Children with forearm fractures who present to the emergency department (ED) often need a closed reduction. In our institution, until 2017, pediatric trauma patients presented to the general trauma ED (GTED) where no sedation services for pediatric patients were available. From 2017, patients presented to the pediatric emergency department (PED) where closed reductions were performed under sedation when appropriate.

Objectives: To compare GTED and PED with regard to length of stay (LOS) and hospitalization rates of pediatric patients with forearm fractures who needed a closed reduction.

Methods: Our retrospective observational study was conducted at a regional hospital. The study population consisted of all patients younger than 18 years of age who presented to the ED with a forearm fracture that needed a closed reduction. The primary outcome measure was the hospitalization rate. The secondary outcome measure was LOS in the ED.

Results: The study comprised 165 patients with forearm fractures who needed a closed reduction; 79 presented to the GTED, and 96 presented to the PED. Hospitalization rates were lower for patients undergoing closed reduction under sedation in the PED compared to the GTED (6.3% and 21.5%, respectively; P = 0.003). Median ED LOS was longer among patients undergoing sedation in the PED compared to the GTED (237 vs. 168 minutes respectively, P < 0.0001).

Conclusions: Sedation for forearm fracture reduction in a hospital’s PED was associated with a decrease of more than three times in hospitalization rate. Despite the need for more resources, PED LOS was only mildly increased.