Israel Medical Association Journal

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.

Romidepsin is an intravenously administered antineoplastic agent, which acts by inhibiting histone deacetylases, thus preventing removal of acetyl groups from histones. The accrual of acetyl groups on histones causes cell cycle arrest and apoptotic cell death. It was approved for use in the United States in 2009 for treatment of refractory or relapsed cutaneous and peripheral T cell lymphomas [1-3].

The most common side effects are mild to moderate in severity and include nausea, vomiting, fatigue, fever, myelosuppression (e.g., anemia, neutropenia, thrombocytopenia), elevated liver enzymes, constipation, and rash. More severe adverse events can include marked neutropenia, thrombocytopenia, serious infections such as line sepsis, acute renal failure, tumor lysis syndrome, and cardiac arrhythmias [1].

The health of survivors of the Shoah has been investigated, both at early and late stages in their lives. There have been findings of multiple morbidities, but survivors have enjoyed slightly prolonged longevity when compared to the general population [1]. Less attention has been granted to investigations and descriptions of illnesses that presented inside the ghettos and the Nazi camps. Some of the surviving records from those sites have yet to be interpreted. Documented diagnoses of both insulin dependent and mature onset diabetes mellitus and of malignancy has been conspicuously absent. We present our meta-analysis and interpretations of surviving medical documents covering a large population of prisoners from a range of ghettos and concentration camps and specifically note the absence of recorded incidence of malignancy and a relatively low incidence of diabetes mellitus.

Background: Myalgic encephalomyelits/chronic fatigue syndrome (ME/CFS) is an acquired disease with symptoms of fatigue and pain. In pathogenesis, the induction of autoantibodies (AAB) against G-protein coupled receptors (GPCR), such as β-adrenergic receptors (β-AdR), has been suspected. GPCR-AAB correlate with symptom severity and autonomic dysfunction in ME/CFS.

Objectives: To describe symptoms and treatment of a patient presenting with infection-triggered ME/CFS demonstrating that levels of β-AdR-AAB underlie modulation over time, correlating with the severity of symptoms.

Methods: At T1 and T2, GPCR-AAB were measured and questionnaires assessing symptom severity were completed. TSHDS-IgM-AAB were tested, and SF density was analyzed via skin probe.

Results: At T2, elevated levels of β-AdR-AAB were found, corresponding with an aggravation of fatigue and pain symptoms. Elevated TSHDS-IgM-AAB were found, which corresponded with reduced fiber density from the skin probe.

Conclusions: The levels of β-AdR-AAB in post-infectious ME/CFS can be modulated. Future studies might target interventions to reduce these AAB.

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 developed countries, amblyopia has an estimated prevalence rate of 1–4%, depending on the socioeconomic gradient. Previous studies performed on pediatric populations in Ethiopia demonstrated amblyopia rates up to 16.7.

Objectives: To assess rates of amblyopia, refractive errors, strabismus, and other eye pathologies among Ethiopian-born children and adolescents who immigrated to Israel compared to Israeli-born children.

Methods This observational cross-sectional study included children and adolescents 5–19 years of age who immigrated to Israel up to 2 years before data collection and lived in an immigration center. Demographic data and general health status of the children were obtained from the parents, and a comprehensive ophthalmologic examination was performed. Results were compared to Israeli-born children.

Results: The study included 223 children and adolescents: 87 Ethiopian-born and 136 Israeli-born. The rate of amblyopia in the Ethiopian-born group vs. Israeli-born was 3.4% and 4.4%, respectively. Even after controlling for age, there was still no significant difference between the two groups (P > 0.99).

Conclusions: Despite originating from a country with limited resources and fewer medical facilities, the amblyopia rate in Jewish Ethiopian immigrants was not higher, and even mildly lower, compared to Israeli-born children.

Background: The global refugee crises have raised concerns among medical communities worldwide; nonetheless, access to healthcare has rarely been studied even though refugees are a medically high-risk group.

Objectives: To compare pediatric department admission rates from the pediatric emergency department (PED) of refugees and Israelis.

Methods: We compared data from refugee and Israeli children admitted to the pediatric department at Wolfson Medical Center in Israel between 2013–2017.

Results: A total of 104,244 patients (aged 0–18 years) came to the PED. Admission rate to the pediatric department for refugees was 695/2541 (27%) compared to 11,858/101,703 (11.7%) Israeli patients (P < 0.001). Hospital stay for patients 0–2-years of age was 3.22 ± 4.80 days for refugees vs. 2.78 ± 3.17 for Israelis (P < 0.03). Re-admission rate within 7 days was 1.3% for refugees and 2.6% for Israelis (P < 0.05). Dermatological diseases (e.g., impetigo and cellulitis) were more frequent in refugees (23.30% vs. 13.15%, P < 0.01); however, acute gastroenteritis and respiratory diagnoses were more common in Israelis (18.52% vs. 11.72%, P < 0.05 and 14.84% vs. 6.26%, P < 0.01, respectively). Neurological diseases (e.g., febrile convulsions) were also more frequent in Israelis (7.7% vs. 3%, P < 0.05). Very significantly, 23% of refugees had no healthcare coverage, while only 0.2% of the Israelis had none (P < 0.001).

Conclusions: We found significant morbidity in refugees compared to the local Israeli pediatric population, highlighting the need for different approaches for each population.

Background: Cannabis consumption is suspected of causing arrhythmias and potentially sudden death.

Objectives: To investigate prevalence and temporal relationships between cannabis use and onset of symptomatic arrhythmias among cancer patients using Belong.life, a digital patient powered network application.

Methods: Real-world data (RWD) were obtained through Belong.Life, a mobile application for cancer patients who use cannabis routinely. Patients replied anonymously and voluntarily to a survey describing their demographics, medical history, and cannabis use.

Results: In total, 354 cancer patients (77% female, 71% 50–69 years of age) replied: 33% were smokers and 49% had no co-morbidities. Fifteen had history of arrhythmias and two had a pacemaker; 64% started cannabis before or during chemotherapy and 18% had no chemotherapy. Cannabis indication was symptom relief in most patients. The mode of administration included oil, smoking, or edibles; only 35% were prescribed by a doctor. Cannabis type was delta 9-tetrahydrocannabinol > 15% in 43% and cannabidiol in 31%. After starting cannabis, 24 patients (7%) experienced palpitations; 13 received anti-arrhythmic drugs and 6 received anticoagulation. Eleven needed further medical investigation. Three were hospitalized. One had an ablation after starting cannabis and one stopped cannabis due to palpitations. Seven patients (2%) reported brady-arrhythmias after starting cannabis, but none needed pacemaker implantation.

Conclusions: RWD showed that in cancer patients using cannabis, the rate of reported symptomatic tachy- and brady-arrhythmias was significant (9%) but rarely led to invasive treatments. Although direct causality cannot be proven, temporal relationship between drug use and onset of symptoms suggests a strong association.

Background: The two cerebral hemispheres influence the immune response differently. While the left hemisphere enhances cellular immunity, the right hemisphere inhibits it.

Objectives: To determine whether immune and inflammatory markers correlated with stroke severity and hospitalization duration as a function of stroke side.

Methods: The study included 137 patients with unilateral ischemic stroke. The medical records were reviewed for demographic and clinical laboratory data, including C-reactive protein (CRP), white blood cell (WBC) count, its differential stroke side and stroke severity according to the National Institute of Health Stroke Scale (NIHSS), and length of hospital stay (LOS). We examined differences between right side (RS) and left side (LS) stroke on immune and inflammatory markers and compared correlations between these markers and NIHSS and LOS as a function of stroke side.

Results: RS stroke patients had higher CRP and monocytes than LS stroke patients. In RS stroke patients, CRP, total WBC, and lymphocyte levels positively correlated with both NIHSS and LOS, whereas levels of neutrophils were positively correlated with NIHSS alone. No correlations were found for LS stroke patients.

Conclusions: Immune-inflammatory markers correlated with stroke severity and LOS only in patients with RS stroke. Neuroimmunological processes influence short-term clinical outcomes after stroke, especially considering the differential effects of the hemispheres on immunity. Prospective studies that evaluate long-term clinical outcomes are needed. Testing the effects of anti-inflammatory treatments on prognosis of RS stroke patients should be considered.

Background: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer.

Objectives: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia.

Methods: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130–134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications.

Results: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22–6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08–6.28.

Conclusions: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.

Background: Massive, non-compressible bleeding is a leading cause of preventable trauma mortality. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a minimally invasive procedure in which a balloon catheter is maneuvered into the aorta to temporarily occlude large vessels and enable stabilization of the exsanguinating patient.

Objectives: To present experiences in assimilating REBOA at a single level 1 trauma center in Israel, to evaluate the technical aspects of the procedure, and to describe patient characteristics and outcomes.

Methods: This retrospective cohort study comprised civilians admitted with hemorrhagic shock to our trauma department who were treated with REBOA between November 2017 and July 2021. Descriptive statistics of the patients, characteristics of the injuries and patient outcomes are presented.

Results: The study included 22 patients (median age 30.1 years, 21 male). The mean systolic blood pressure (SBP) before REBOA inflation was 59.6 ± 11.4 mmHg, and the mean SBP measured after the procedure was 115.2 ± 26.3 mmHg. In 20 patients (91%), the SBP was normalized (> 90 mmHg) shortly after inflation of the balloon, and they survived the treatment in the trauma department; 15 (75%) survived the first 30 days. 

Conclusions: REBOA is an effective method for the initial resuscitation and hemorrhage control of patients with massive, non-compressible bleeding and is relatively easy to assimilate in a hospital. The achievement of immediate normalization of SBP enables medical personnel to correct physiological parameters and obtain accurate imaging before proceeding to the operating theater. 

Triclosan (5-chloro-2-[2, 4-dichlorophenoxy] phenol) is an antibacterial and antifungal agent found in numerous consumer products. It has been in use for more than four decades and is present in soaps, shampoos, deodorants, toothpastes, mouth washes, and cleaning supplies [1]. Presently, triclosan is being incorporated into an increasing number of products including toys, bedding, clothes, and trash bags ]1]. On contact, triclosan penetrates the skin and enters the bloodstream. Due to its high hydrophobicity, triclosan accumulates in fatty tissues and is found in human samples (urine, breast milk, and serum) [1]. At high concentrations, triclosan acts as a biocide with multiple cytoplasmic and membrane targets [3].

Optic neuritis is an inflammation of the optic nerve and has several causes. The hallmarks of clinical manifestation are pain on movement of the eyes and decreased vision. Typical optic neuritis is an idiopathic demyelinating condition that is often associated with multiple sclerosis, affects young women, is unilateral, and has a good prognosis.

Background: During coronavirus disease 2019 (COVID-19) pandemic, less isolation of common winter viruses was reported in the southern hemisphere.

Objectives: To evaluate annual trends in respiratory disease-related admissions in a large Israeli hospital during and before the pandemic.

Methods: A retrospective analysis of medical records from November 2020 to January 2021 (winter season) was conducted and compared to the same period in two previous years. Data included number of admissions, epidemiological and clinical presentation, and isolation of respiratory pathogens.

Results: There were 1488 respiratory hospitalizations (58% males): 632 in 2018–2019, 701 in 2019–2020, and 155 in 2020–2021. Daily admissions decreased significantly from a median value of 6 (interquartile range [IQR] 4–9) and 7 per day (IQR 6–10) for 2018–2019 and 2019–2020, respectively, to only 1 per day (IQR 1–3) in 2020–2021 (P-value < 0.001). The incidence of all respiratory viruses decreased significantly during the COVID-19 pandemic, with no hospitalizations due to influenza and only one with respiratory syncytial virus. There was also a significant decline in respiratory viral and bacterial co-infections during the pandemic (P-value < 0.001).

Conclusions: There was a significant decline in pediatric respiratory admission rates during the COVID-19 pandemic. Possible etiologies include epidemiological factors such as mask wearing and social distancing, in addition to biological factors such as viral interference. A herd protection effect of adults and older children wearing masks may also have had an impact.

Background: Existing cardiac disease contributes to poor outcome in patients with coronavirus disease 2019 (COVID-19). Little information exists regarding COVID-19 infection in patients with a cardiac implantable electronic device (CIED).

Objectives: To assess the association between CIEDs and severity of COVID-19 infection.

Methods: We performed a retrospective analysis including 13,000 patients > 18 years old with COVID-19 infection between January and December 2020. Patients with COVID-19 who had a permanent pacemaker or defibrillator were matched 1:4 based on age and sex followed by univariate and multivariate analyses. Baseline characteristics and clinical outcomes were assessed.

Results: Forty patients with CIED and 160 patients without CIED were included in the current analysis. Mean age was 72.6 ± 13 years, and approximately 50% were females. Majority of the patients in the study arm had a pacemaker (63%), whereas only 15 patients (37%) had a defibrillator. Patients with COVID-19 and CIED presented more often with atrial fibrillation, coronary artery disease, heart failure, hypertension, diabetes, and chronic kidney disease. They were more likely to be hospitalized in the intensive care unit (ICU) and required more ventilatory support (35% vs. 18.3%). Thirty-day mortality (22.5% vs. 13.8%) and 1-year mortality (25% vs. 15%) were higher among patients with COVID-19 and CIED.

Conclusions: Patients with COVID-19 and CIED had a significantly higher prevalence of co-morbidities that were associated with increased mortality. Although,CIED by itself was not found as an independent risk factor for morbidity and mortality, it may serve as a warning for severe illness with COVID-19.