Israel Medical Association Journal

Background: Diagnosing occult stress urinary incontinence (OSUI) prior to surgical intervention for pelvic organ prolapse (POP) repair may allow for adding an anti-incontinence procedure and thus prevent postoperative SUI.

Objectives: To compare preoperative detection rates for OSUI by either a multichannel urodynamic investigation or by a plain pelvic examination.

Methods: We retrospectively evaluated the medical charts of all women who underwent urodynamic investigation prior to surgical repair of advanced POP at our institution between 1 January 2006 and 31 December 2012.

Results: In total, 720 women underwent surgical POP repair during the study period, of whom 54 (7.5%) were diagnosed with OSUI preoperatively. Of these patients, 54 (100%) were detected by multichannel urodynamic investigation while only 27 (50%) were detected by a plain pelvic examination (P = 0.001). Bladder fullness during the pelvic examination was associated with higher detection rates for OSUI (P = 0.001). Women with OSUI who underwent concomitant tension-free vaginal tape and POP repair procedures did not develop de novo SUI or obstructive voiding symptoms (OVS) postoperatively.

Conclusions: Preoperative multichannel urodynamic investigation has significantly higher detection rates for OSUI than a plain pelvic examination. Utilizing this modality resulted in no cases of de novo SUI or OVS postoperatively.

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.

Hypereosinophilia is defined as the absolute eosinophilic count of above 1500 cells/µL in the peripheral blood on two separate tests taken during one month and/or the pathological confirmation of hypereosinophilia. There are many conditions that are associated with increased eosinophil counts including: parasitic infections, drug reactions, eosinophilic granulomatosis with polyangiitis, allergic reactions, drug reaction with eosinophilia and systemic symptoms (DRESS), primary immunodeficiencies (PID), eosinophilic gastrointestinal diseases (EGID), familial hypereosinophilia, and neoplasms [1]. Molecular classification may be an adjuvant in the classification of hypereosinophilia [2]. Our patient presented with hypereosinophilia as part of a paraneoplastic syndrome.

Candida species inhabit the gastrointestinal tract. Isolation of Candida from the respiratory tract has been found and reflects colonization, particularly among mechanically ventilated patients [1]. However, the existence of candida as a respiratory pathogen was previously doubted. Candida pneumonia is a rare and challenging-to-diagnose entity. We present a histopathologically confirmed case of necrotizing Candida pneumonia and lung abscess in a solid organ transplant recipient.

Background: Salmonella, Shigella, and Campylobacter are highly prevalent among children. Reports on risk factors of patients infected with all three pathogens, not simultaneously, are scarce.

Objectives: To identify risk factors for multiple infection with Salmonella, Shigella, and Campylobacter in the same child.

Methods: Using the Israel Sentinel Laboratory-Based Surveillance Network, we conducted a retrospective observational case-case–control study among children aged 0–9 years. A case was defined as a child infected with Salmonella, Shigella, and Campylobacter at different occasions between January 1999 and December 2020. A control was defined as a child infected with a single pathogen once, during the same period. Logistic regression models were applied to determine the association between multiple infections and demographic characteristics.

Results: We identified 109 cases (0.1%) infected with Salmonella, Shigella, and Campylobacter, and 86,511 controls (99.9%) infected with only one bacteria type. In a multivariable analysis, we showed that being Jewish (odds ratio [OR] 2.4, 95% confidence interval [95%CI] 1.3–4.4), having residency in Jerusalem (OR 3.2, 95%CI 1.3–7.7), or in the southern district (OR 3.7, 95%CI 1.5–8.8) were independent risk factors for multiple infection.

Conclusions: Although very rare, non-simultaneous infection with multiple bacteria does occur in Israel. National and local authorities should promote programs to encourage proper hygiene practices, which are culture-adjusted.

Background: Patients with juvenile myoclonic epilepsy (JME) are especially prone to having antiseizure medications (ASMs) withdrawal seizures (WS).

Objectives: To clarify whether WS in JME patients are caused by a high tendency of non-adherence from seizure-free patients or by a constitutive increased sensitivity to drug withdrawal.

Methods: Epilepsy patients followed in a tertiary epilepsy clinic between 2010 and 2013 were included in the study. WS prevalence was compared between drug-responsive and drug-resistant JME patients and patients with other types of epilepsy.

Results: The study included 23 JME patients (16 drug-responsive and 7 drug-resistant) and 138 patients with other epilepsies (74 drug-responsive and 64 drug-resistant). JME patients were younger and included more women than non-JME patients. Significantly more WS were seen in JME than in non-JME patients (P = 0.01) and in the drug-resistant fraction of JME patients in comparison to drug-resistant non-JME patients (P = 0.02). On logistic regression, the type of epilepsy, but not the patient’s sex, was found to significantly predict WS. No significant difference was found in the prevalence of WS between drug-responsive and drug-resistant JME patients. The main ASM discontinued in JME was valproic acid (VPA), especially in women.

Conclusion: Our findings suggest a higher sensitivity of JME patients to withdrawal of medications. It is important to educate JME patients about treatment adherence and to explain to their physicians how to carefully reduce or replace ASMs to mitigate the morbidity and mortality related to ASM withdrawal

Background: Risk factors for severe coronavirus disease-2019 (COVID-19) infection include old age, chronic illness, and neurological conditions. In contrast, high vitamin D levels are known to augment immune activity and to reduce the severity of viral infections. Recently, a possible association between the likelihood of COVID-19 infection, COVID-19 severity, and vitamin D blood levels was reported.

Objective: To assess the possible association between vitamin D long-term supplementation and COVID-19 symptomatic severity and complications of COVID-19 infection in elderly psychiatric inpatients, a high at-risk group.

Methods: We conducted a retrospective case series study. Data of 14 elderly COVID-19 positive inpatients, presenting with dementia or schizophrenia and other medical conditions were extracted from medical records. All patients maintained a 800 IU daily dose of vitamin D prior to the infection.

Results: Most of the inpatients were asymptomatic or presented very few symptoms. No need for intensive care unit intervention or deaths were reported. Cognitive functioning of the patients remained unchanged.

Conclusions: Pre-existing vitamin D supplementation may reinforce immunity and reduce COVID-19 severity in elderly psychiatric inpatients.

Background: Cystic periventricular leukomalacia (cPVL) is a strong indicator of subsequent motor and developmental impairments in premature infants. There is a paucity of publications on biomarkers of cPVL.

Objectives: To determine C-reactive protein (CRP) levels during the first week of life of preterm infants who later developed cPVL and to identify the association between CRP levels with perinatal factors.

Methods: We retrospectively included infants ≤ 32 weeks gestation and/or birth weights ≤ 1500 grams; 17 with a cranial ultrasound diagnosis of cPVL and 54 with normal ultrasounds. Serum CRP levels were measured during days 1-7 (CRP^1–7d) of life and subdivided into two timing groups: days 1–3 (CRP^1–3d) and days 4-7 (CRP^4–7d).

Results: The cPVL group had significantly higher mean CRP^4–7d levels compared to controls (12.75 ± 21.2 vs. 2.23 ± 3.1, respectively, P = 0.03), while CRP^1–3d levels were similar. CRP^1–7d levels were significantly correlated with maximal fraction of inspired oxygen during the first 12 hours of life (FiO₂-12h, r = 0.51, P < 0.001]. Additional risk factors were not associated with CRP levels.

Conclusions: Our finding of elevated CRP^4-7d levels and later development of cPVL supports earlier studies on the involvement of inflammation in the pathogenesis of cPVL. Whether CRP could serve as a biomarker of cPVL and its correlation with outcomes, awaits further trials. Furthermore, the correlation between FiO₂-12h and CRP^1–7d levels suggest that hypoxia and/or hyperoxia may serve as a trigger in the activation of inflammation during the first days of life of preterm infants

Background: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust.

Objectives: To describe changes in teaching during the first phase of the COVID-19 pandemic.

Methods: We described the steps implemented at the Technion–Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem. 

Results: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs. 

Conclusions: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching

Background: Takotsubo syndrome (TTS) is a non-ischemic cardiomyopathy characterized by an acute reversible left ventricular dysfunction with typical apical ballooning, usually with subsequent complete spontaneous recovery. TTS may be triggered by several physical and emotional stressors. The name Covidsubo was recently adopted to describe this emerging entity. TTS during quarantine may be a reasonable outcome of the overwhelming stress and fear of this pandemic. However, according to the current literature, conflicting results have been reported regarding the incidence of this syndrome during the first wave of the pandemic, and further studies are needed. High index of suspicion is needed to identify patients during the next waves of the pandemic, particularly given the need for minimizing imaging modalities and contact with the patients.

Objectives: To describe two cases of TTS triggered by quarantine during the coronavirus disease-2019 (COVID-19) pandemic.

Methods: Two patients (age 81 years and 70 years) were admitted to our medical center with severe chest pain with normal blood pressure and heart rate.

Results: TTS should always be in the differential diagnosis in patients presenting with chest pain suspected to be from coronary origin. Based on the typical clinical, echocardiographic, and angiographic findings, we assumed TTS.

Conclusions: The only prominent stressor in the two cases in this article was the stress accompanying quarantine.

Background: Takotsubo syndrome (TTS) is a non-ischemic cardiomyopathy characterized by an acute reversible left ventricular dysfunction with typical apical ballooning, usually with subsequent complete spontaneous recovery. TTS shares several features with acute coronary syndrome (ACS), including clinical presentation, ECG changes, and elevated troponin.

Objectives: To identify different features that may help differentiate between TTS and ACS with presentation based on presenting symptoms and physical examination.

Methods: We compared 35 patients who TTS had been diagnosed with 60 age- and sex- matched patients with ACS (both ST and non-ST segment elevation myocardial infarction) who were hospitalized in Galilee Medical Center through 2011-2015.Basic characteristics and clinical features of the two groups were compared using appropriate statistical tests.

Results: Of the patients with TTS, 21 (60%) reported an emotional trigger (60%) before admission, although they did not have increased prevalence of psychiatric disease compared to ACS patients (5.7% vs. 5%, P = 0.611). There was no difference in the type of chest pain or accompanied symptoms between the groups. Of notice, ECG changes in the TTS group were prominent in the anterior leads, and the patients presented with higher heart rate (86 ± 17 vs. 79 ± 15, P = 0.029) and lower systolic blood pressure (129 ± 26 vs. 142 ± 30, P = 0.034) on admission compared to the ACS group.

Conclusions: There was no reliable feature that could distinguish TTS from ACS based on clinical presentation. TTS should always be in the differential diagnosis in patients with acute chest pain, especially in elderly women