Israel Medical Association Journal

Background: There is an unmet need for real-world data regarding laboratory results, co-morbidities, and medication use prior to the first symptoms of amyotrophic lateral sclerosis (ALS). Researchers must identify specific subpopulations at risk for developing ALS and understand pathogenic mechanisms preceding the clinical presentation of ALS as well as possible subclinical disease manifestations.

Objectives: To valuate the role of laboratory results, co-morbidities, and medication use prior to the first symptoms of patients with ALS in Israel so that specific subpopulations at risk for developing ALS can be identified and for possible subclinical disease manifestations. To understand pathogenic mechanisms preceding the clinical presentation of ALS.

Methods: At the ALS clinic at Tel Aviv Sourasky Medical Center, 259 ALS patients insured by Maccabi Healthcare Services and seen between January 1998 and December 2017 were included. Comparisons of demographics, co-morbidities, medications taken, history of trauma, and laboratory tests prior to disease onset were performed between patients and 1295 matched controls.

Results: Prior to disease presentation, ALS patients had a higher frequency of hypertension and cardiovascular disease; presented more frequently with trauma and viral infections; more frequently used analgesics, non-steroidal anti-inflammatory drugs, narcotics, antibiotics, and antiviral medications; and had higher creatine kinase levels.

Conclusions: ALS patients showed higher frequency of cardiovascular disease prior to diagnosis, as well as higher frequency of trauma, infections, and pain medication usage.

Background: Several studies have shown that patients with fibromyalgia present with neuroendocrine, inflammatory, and coagulation features linked to cardiovascular disease development. However, the exact profile of cardiovascular risk factors and events in fibromyalgia remains to be defined.

Objectives: To compare the profile of cardiovascular risk factors and events between fibromyalgia outpatients and the general population in Italy.

Methods: Cardiovascular risk factors and events in fibromyalgia females were collected using the criteria adopted in the CUORE Project.

Results: The study comprised 62 female fibromyalgia patients and 4093 female controls from 35 to 75 years of age. The prevalence of hypertension, diabetes, atrial fibrillation, transient ischemic attack, and cardiovascular total burden was significantly higher in fibromyalgia females than in the general Italian population. No difference was found in blood fasting glucose, triglycerides, total and fractionated cholesterol levels, body mass index, and metabolic syndrome (MetS). The MetS rate was underestimated for methodological aspects.

Conclusions: Fibromyalgia is associated with an increased cardiovascular burden, probably through a specific risk factor profile.

Congenital cardiac tumors are rare in neonates. A rhabdomyoma, the most common neonatal cardiac tumor, tends to regress in the first year of life. Indications for intervention include hemodynamic compromise and intractable arrhythmias. To the best of our knowledge, rhabdomyoma-induced ischemia has not yet been reported. We report a case of a neonate with multiple rhabdomyomas with myocardial infarction related to compression of a coronary artery.

Background: Signet ring cell carcinoma (SRCC) is classified as an undifferentiated gastric carcinoma with poor prognosis. Early SRCCs are associated with improved prognosis.

Objectives: To describe the outcomes of incidental SRCC.

Methods: In this case series, 900 medical charts of patients with SRCC were screened to identify patients with incidental SRCC, defined as diagnosed in random, non-focal-lesion-targeted biopsies.

Results: Six patients were diagnosed with incidental SRCC and underwent gastrectomy. The final pathology of five patients revealed one or more small foci of early SRCC without lymphovascular invasion. Only one patient had no evidence of malignancy. The median follow-up after surgery was 4.2 years (50 months, range 37–90 months). No deaths or recurrences were recorded during the follow-up period. These results resemble the reported survival rate for early SRCC.

Conclusions: An aggressive surgical approach in incidental gastric SRCC patients is recommended, as they have a chance for long-term survival.

Biological therapies with monoclonal antibodies have revolutionized the management of many inflammatory and autoimmune diseases. Combining biological treatments is very rarely indicated and may theoretically result in severe adverse effects, specifically, an increased tendency toward infectious diseases. We present the case of a woman in whom combination therapy with canakinumab for familial Mediterranean fever (FMF) and mepolizumab for chronic eosinophilic pneumonia was successfully employed.

Background: Perianal abscesses require immediate incision and drainage (I&D). However, prompt bedside drainage is controversial as it may compromise exposure and thorough anal examination.

Objectives: To examine outcomes of bedside I&D of perianal abscesses in the emergency department (ED) vs. the operating room (OR).

Methods: We conducted a retrospective review of all patients presented to the ED with a perianal abscesses between January 2018 and March 2020. Patients with Crohn’s disease, horseshoe or recurrent abscesses were excluded.

Results: The study comprised 248 patients; 151 (60.89%) underwent I&D in the OR and 97 (39.11%) in the ED. Patients elected to bedside I&D had smaller abscess sizes (P = 0.01), presented with no fever, and had lower rates of inflammatory markers. The interval time from diagnosis to intervention was significantly shorter among the bedside I&D group 2.13 ± 2.34 hours vs. 10.41 ± 8.48 hours (P < 0.001). Of patients who underwent I&D in the OR, 7.3% had synchronous fistulas, whereas none at bedside had (P = 0.007). At median follow-up of 24 months, recurrence rate of abscess and fistula formation in patients treated in the ED were 11.3% and 6.2%, respectively, vs. 19.9% and 15.23% (P = 0.023, 0.006). Fever (OR 5.71, P = 0.005) and abscess size (OR 1.7, P = 0.026) at initial presentation were risk factors for late fistula formation.

Conclusions: Bedside I&D significantly shortens waiting time and does not increase the rates of long-term complications in patients with small primary perianal abscesses.

Background: Depression has been shown to be associated with cervical tumors (CTs), an association mostly demonstrated in studies in which temporality could not have been ascertained.

Objectives: To study the association between depression and CTs and the influence of co-morbidities of this association in a large cohort study.

Methods: A retrospective computer-based cohort study was conducted. The cohort included 357,450 female members of Maccabi Healthcare Services. The cohort was classified as depressed or non-depressed using the International Classification of Diseases 9/10 codes. For each subgroup, demographic characteristics, behavioral characteristics, co-morbidities, and CTs diagnosis were obtained. The burden of co-morbidities was defined as the sum of major co-morbidities. We used zero-inflated negative binomial regression analysis due to over-dispersion to estimate the relative risk (RR) for CTs with 95% confidence interval (95%CI).

Results: Depression was diagnosed in 15,789 women. Among this group, CTs were diagnosed in 1585 (10.0%). Among the 341,661 non-depressed, CTs were diagnosed in 4185 (1.2%). After adjustment to age and socioeconomic status, the association between depression and CTs was RR=9.2 (95%CI 8.7–9.9, P-value < 0.0001). The association between depression and CTs increased as the burden of clinical conditions increased (P-value < 0.0001).

Conclusions: Women with depression are at a higher risk for CTs, especially among those who have several co-morbidities. Tighter gynecology surveillance is crucial among these women.

Carpal tunnel syndrome (CTS) is a collection of symptoms and signs caused by compression of the median nerve as it travels through the carpal tunnel. Symptoms include paresthesia and/or numbness in the median nerve distribution, aching in the thenar eminence, and weakness at later stages. CTS is the most common entrapment neuropathy with a prevalence of 1–5%, and even higher among females, manual workers, and the elderly. Therefore, many patients with signs and symptoms of CTS refer to their primary care physician who should recognize, diagnose, and provide initial treatment.

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: Among chronic kidney disease (CKD) patients, baseline neutrophil gelatinase-associated lipocalin (NGAL) may reflect the severity of renal impairment. No data exists on serial changes in serum NGAL levels in CKD patients before and after percutaneous coronary intervention (PCI).

Objectives: To evaluate serial serum NGAL levels relation to contrast induced acute kidney injury (CI-AKI) following PCI.

Methods: The study included 58 patients with CKD who underwent elective PCI. Plasma NGAL measurements were performed before (pre-NGAL) and 24 hours following (post-NGAL) PCI. Patients were followed for CI-AKI and changes in NGAL levels. Receiver operator characteristic identified the optimal sensitivity and specificity for pre-NGAL levels compared with post-NGAL for patients with CI-AKI.

Results: Overall CI-AKI incidence was 33%. Both pre-NGAL (172 vs. 119 ng/ml, P < 0.001) and post-NGAL (181 vs. 121 ng/ml, P < 0.001) levels were significantly higher in patients with CI-AKI, but no significant changes were detected. Pre-NGAL levels were similar to post-NGAL levels in predicting CI-AKI (area under the curve 0.753 vs. 0.745). Optimal cutoff value for pre-NGAL was 129 ng/ml (sensitivity of 73% and specificity of 72%, P < 0.001). Post-NGAL levels > 141 ng/ml were independently associated with CI-AKI (hazard ratio [HR] 4.86, 95% confidence interval [95%CI] 1.34–17.64, P = 0.02) with a strong trend for post-NGAL levels > 129 ng/ml (HR 3.46, 95%CI 1.23–12.81, P = 0.06).

Conclusions: In high-risk patients, pre-NGAL levels may predict CI-AKI. Further studies on larger populations are needed to validate the use of NGAL measurements in CKD patients.

Metastatic pulmonary calcinosis (MPC) is characterized by deposits of calcium in normal pulmonary parenchyma. Diffuse pulmonary calcinosis commonly occurs in hypercalcemia and/or hyperphosphatemia and is more commonly related to renal failure than primary hyperparathyroidism, skeletal metastases, or multiple myeloma [1]. Calcium depositions favor alkaline tissue and are thus more common in the upper lobes of the lung, which have a higher ventilation to perfusion ratio and a low capillary pCO₂, resulting in an alkaline pH [2]. Therefore, the most common radiographic manifestation consists of poorly defined nodular opacities bilaterally in the upper lung zones [3].

Background: Loss of consciousness (LOC) is one of the most common reasons for seeking neurological advice in clinics and emergency departments. There is considerable difficulty in determining the nature of the events according to patient reports, and collateral history is often difficult to interpret due to multiple versions and observer interpretations.

Objectives: To examine the utility and validity of incidental video recordings (IVR) in the differential diagnosis of LOC.

Methods: In this retrospective study, I included patients with a documented IVR description. Results were divided into three categories: definite approval (IVR conclusion was decisive and congruent with the gold standard test), partial approval (IVR conclusion was decisive and diagnosis was confirmed by treatment response or clinical course), and inconclusive (IVR conclusion was not decisive, no gold standard test was performed, or the gold standard test was either not decisive or incongruent with the IVR).

Results: I evaluated the results of 31 patients with IVR documentation. Overall, in 18 patients (58%), the IVR conclusion was decisive and congruent with the gold standard test. In 8 patients (25.8%), the IVR conclusion was decisive and congruent with the clinical course or treatment response. In 5 patients (16.1%) the IVR was regarded as inconclusive.

Conclusions: IVR have a substantial yield and are highly accurate in the differential diagnosis of LOC, mainly differentiating between epileptic seizures and psychogenic nonepileptic seizures, yet it is utilized in a minority of the patients in real life.

Background: In late 2019, a new strain of coronavirus (coronavirus disease 2019 [COVID-19]) spread rapidly throughout the world. The American Society of Plastic Surgeons reported a pandemic-related surge in the demand for aesthetic surgery compared to the same popularity of procedures prior to the pandemic.

Objectives: To determine whether this phenomenon also occurred in Israel.

Methods: We collected data from three leading private medical centers in Tel Aviv. Data were compared for the years 2019 and 2020 by surgical procedure. Number of orthopedic, gynecologic, and hand procedures served as control data.

Results: We present a detailed pandemic-related timeline relevant to aesthetic surgery in Israel. Overall, the demand for aesthetic surgery increased, with a marked trend toward body contouring procedures.

Conclusions: The Israeli aesthetic surgery market was affected by the COVID-19 pandemic, with a post-closure surge. The popularity and number of procedures are unique to the Israeli market.

The interplay between post-traumatic stress disorder (PTSD) and autoimmunity is well known. One of the contributors leading to immune disorders is autonomic dysregulation, which is characterized by attenuated parasympathetic and elevated sympathetic systems. In this review, we described evidence regarding the relationship between stress, PTSD, autonomic dysfunction, and autoimmunity. Stress is a physiological response, which is functional for our being. The implication of dysfunction in stress response may be a cause of disease development. We described the fundamental role of the pathological high levels of stress in PTSD as a mediator factor that contributes to autonomic dysfunction, which as a result may lead to autoimmunity. Systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes are some of the autoimmune diseases PTSD patients are at higher risk of developing. Notably, some autoimmune diseases are shown to increase the susceptibility to develop PTSD, which may indicate a bidirectional influence. In addition, we elaborated on stress as a major component in both fibromyalgia and PTSD, as there are overlaps between the pathogenesis of fibromyalgia and PTSD. Underlying chronic low-grade inflammation, which characterizes PTSD patients, may be a potential target and biomarker in treating PTSD patients. We believe that chronic low-grade inflammation, high concentrations of cytokines, and other inflammatory biomarkers, which characterize PTSD patients, may be potential targets and biomarkers in the treatment of PTSD patients and part of the PTSD diagnostic criteria.

Background: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings.

Objectives: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine.

Methods: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models.

Results: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038).

Conclusions: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.