Israel Medical Association Journal

In September 2020, a 37-year-old man without significant medical history or medication use presented to the emergency department with shortness of breath. The patient denied any history of shortness of breath, travel history, recent sick contacts, or history of lung disease. On arrival, the patient was afebrile with a respiratory rate of 26 breaths per minute (b/m), oxygen saturation 82% on ambient air, blood pressure 130\80 mmHg, and heart rate 130 beats per minute (bpm). He was started on three liters per minute oxygen therapy, which improved his saturation to 90%. Physical examination was remarkable for tachypnea and diffuse bilateral inspiratory lung crackles. Electrocardiogram revealed sinus tachycardia.

Fetal hydrops is a life-threatening condition defined as abnormal accumulation of fluid in two or more fetal compartments: ascites, pleural effusion, pericardial effusion, or generalized skin edema [1]. Fetal hydrops may also be associated with polyhydramnios and placental edema [2].

Based on pathophysiology results, fetal hydrops is classified as either immune or non-immune. The frequency of immune fetal hydrops has decreased dramatically since the development of Rh (D) immunization given to mothers at risk. Nonimmune hydrops fetalis (NIHF) accounts for almost 90% of cases [1]. The etiology of NIHF is further classified as cardiovascular (17–35%), chromosomal (7–16%), hematologic (4–12%), infectious (5–7%), and unknown (15–25%). Inborn errors of metabolism account for only 1–2% of NIHF cases [1]. NIHF is commonly progressive. Complete resolution of NIHF before birth is rare.

Ruxolitinib is an inhibitor of the cytosolic tyrosine kinase Janus kinase (JAK) family of proteins (JAK1/2), which is widely used to treat various myeloid neoplasms that are characterized by constant activation of the JAK-STAT signaling pathway.

Many side effects are associated with ruxolitinib, including anemia, thrombocytopenia, increased rate of infections (especially herpes zoster), and mild hypercalcemia noted in 15.4% of patients [1]. The possible mechanism causing hypercalcemia may involve altered bone and mineral metabolism with secondary hyperparathyroidism, as described for other kinase inhibitors [2].

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: 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.

Background: Fibromyalgia syndrome (FMS) is estimated to affect 2–4% of the general population. While FMS has some known environmental and genetic risk factors, the disorder has no clear etiology. A common coexisting disorder with FMS is small fiber neuropathy (SFN). High levels of serum immunoglobulin M (IgM) binding to trisulfated-heparin-disaccharide (TS-HDS) were recently found to be associated with SFN.

Objectives: To evaluate potential differences in anti-TS-HDS antibody titers in women with FMS compared to healthy controls.

Methods: In this cross-sectional study, we evaluated 51 female participants: 30 with a diagnosis of FMS and 21 healthy controls who had been recruited at the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. All of the participants were older than 18 years of age. Anti-TS-HDS IgM levels were measured in their sera using the enzyme immunoassay technique.

Results: The mean anti-TS-HDS IgM levels were significantly lower in the FMS group, compared with the control group (7.7 ± 5 vs. 13.2 ± 8.6 U/ml, respectively; P = 0.013).

Conclusions: There is a possible association between FMS and anti-TS-HDS IgM. This association might be the missing link for the coexistence of SFN and FMS, but further study should be performed to assess this association and this auto-antibody characteristic.

Fibromyalgia is one of the most significant causes of chronic widespread musculoskeletal pain, heavily burdening both individual patients and the healthcare system. Hence, reducing the prevalence of the disorder is of paramount importance. Unfortunately, the etiology and the exact risk factors leading to the development of fibromyalgia are not clearly known, making its prevention difficult and challenging. Nevertheless, there are numerous risk markers that are associated with an increased probability of the disease, such as obesity, psychological and physical stress, exposure to traumatic life events, certain infectious disorders, and co-morbid rheumatic and psychiatric disorders. It is reasonable to assume that targeting preventable risk markers may suppress consequent emergence of fibromyalgia, but studies investigating primary prevention on fibromyalgia are scarce. In this review, we examined several studies that discuss proven methods to prevent fibromyalgia, including maintenance of a normal body mass index, regular physical exercise, and psychological techniques such as cognitive behavioral therapy.

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.

Background: The coronavirus disease 2019 (COVID-19) pandemic has severe consequences in terms of mortality and morbidity. Knowledge of factors that impact COVID-19 may be useful in the search for treatments.

Objectives: To determine the effect of glucose-6-phosphate dehydrogenase (G6PD) deficiency on morbidly and mortality associated with COVID-19.

Methods: All patients admitted to Hadassah Hebrew University Medical Center between 01 March 2020 and 03 May 2021 with a diagnosis of COVID-19 were included. We retrospectively retrieved demographic, clinical, and laboratory data from the hospital’s electronic medical records. The main outcomes were mortality, intensive care unit (ICU) admission, and severity of COVID-19.

Results: The presence of G6PD deficiency emerged as an independent protective predictor for ICU admission (odds ratio [OR] 0.258, 95% confidence interval [95%CI] 0.077–0.619, P = 0.003) and the development of critical illness (OR 0.121, 95%CI 0.005–0.545, P = 0.006). Moreover, patients with G6PD deficiency had a trend toward lower mortality rates that did not reach statistical significance (OR 0.541, 95%CI 0.225–1.088, P = 0.10).

Conclusions: Patients with G6PD deficiency were less likely to have a severe disease, had lower rates of ICU admission, and trended toward lower mortality rates.

Background: Acute appendicitis (AA) is a medical emergency. The standard of care for AA had been surgical appendectomy. Recently, non-operative management (NOM) has been considered, mainly for uncomplicated AA.

Objectives: To evaluate AA NOM trends over two decades.

Methods: We conducted a retrospective cohort study based on Israel’s National Hospital Discharges Database (NHDD). Inclusion criteria were AA admissions from 1 January 2000 to 31 December 2019, with either primary discharged diagnosis of AA, or principal procedure of appendectomy. Predefined groups were children (5 ≤ 18 years) and adults (≥ 18 years). We compared the last decade (2010–2019) with the previous one (2000–2009).

Results: The overall AA incidence rate over two decades was 126/100,000/year; higher in children 164/100,000/year than 113/100,000/year in adults. Surgery was the predominant AA treatment in 91.9%; 93.7% in children and 91.1% in adults. There was an increase in AA NOM rates when comparing the previous decade (5.6%) to the past decade (10.2%); 3.2% vs. 9.1% in children and 6.8% vs. 10.7% in adults, respectively. Annual trends revealed a mild increase in AA NOM rates. Delayed appendectomy (within 90 days of AA NOM) was 19.7% overall; 17.3% in adults and 26.3% in children.

Conclusions: There was an increase in AA NOM rates during the last decade in the overall population. Since 2015, there has been a noticeable increase in AA NOM rates, probably associated with World Society of Emergency Surgery Jerusalem guidelines. Surgery is still the predominant treatment for AA despite the increasing trend in NOM.

Takotsubo syndrome (TTS) often develops following stressors such as cardiac surgery. It may be fatal in rare cases. Our 70-year-old female patient presented with a rare case of tricuspid valve papillary fibroelastoma, which was complicated by fatal TTS after successful resection. The patient had a right atrial mass that was investigated with computed tomography and transesophageal echocardiography (TTE). She was scheduled for surgery. Pathology findings were consistent with papillary fibroelastoma of the tricuspid valve. Three weeks after successful surgery, the patient was admitted due to cardiogenic shock with echocardiographic findings of apical ballooning and left ventricular outflow tract obstruction consistent with TTS. The patient died one hour after her admission despite optimal medical therapy.

Background: Clinical dysentery causes hundreds of thousands of deaths annually worldwide. However, current recommendations reserve antibiotics for those either clinically sick or with highly suspected cases of shigellosis. This treatment stems from rising antibiotic resistance. Children diagnosed with clinical dysentery in the pediatric emergency department (PED) are regarded more cautiously.

Objectives: To explore the use of antibiotics in children diagnosed with clinical dysentery in the PED.

Methods: A retrospective case study of children with clinical dysentery at a single PED during the years 2015 and 2018. Demographics as well as clinical findings were compared to culture results and antibiotic treatment.

Results: The study included 281 children who were diagnosed with clinical dysentery during the study period; 234 (83%) were treated with antibiotics. However, cultures were positive in only 162 cases (58%). Only 32% were Shigella spp. Younger age, fever, and leukocytosis were related to antibiotic treatment.

Conclusions: The diagnosis of clinical dysentery is misgiven commonly in the PED leading to widespread use of antibiotics when not indicated. This treatment may impact antibiotic resistance patterns. Further studies and interventions are necessary to create clear guidelines in the PED setting.

Background: Higher body mass index (BMI) has been shown to be a protective factor from mortality in sepsis patients. Yet, whether this effect is different in the very elderly is currently unknown.

Objective: To investigate the relationship between BMI and sepsis outcomes in patients older and younger than 80 years of age.

Methods: A retrospective analysis of consecutive patients admitted with sepsis to Shamir Medical Center, Israel, was conducted. We compared patients older than and younger than 80 years of age with a BMI higher and lower than 25 kg/m² for hospitalization outcomes.

Results: Patients older than 80 years presented with multiple co-morbidities compared to younger patients, but with no difference between BMI groups. Similarly, hospitalization outcomes of functional deterioration, discharge to long-term care facilities, and readmission were not significantly different between BMI groups in the same age category. Mortality was significantly different between BMI groups in patients older than 80 years of age, with higher mortality in BMI < 25 kg/m²: in-hospital mortality (23.4% vs. 14.9%, P < 0.001), 30-day mortality (27.6% vs. 17.9%, P < 0.001), and 90-day mortality (43.4% vs. 28.9%, P < 0.001). This difference was not significant between the groups younger than 80 years old. On logistic regression, BMI over 25 kg/m² was protective in all mortality categories. Nevertheless, there was no significant interaction between age over 80 years to BMI over 25 kg/m² in all mortality outcomes.

Conclusions: Among patients hospitalized with sepsis, higher BMI is a protective factor against mortality in both elderly and younger patients.

Acute cholecystitis is a common surgical diagnosis. If not addressed properly, it can potentially lead to sepsis, perforation of the gallbladder, and even death.

The most frequent pathogens isolated from bile cultures of patients with cholecystitis are anaerobes and Enterbacterales such as E. coli, Klebsiella species, and Streptococcus species [1].

Streptococcus gordonii belongs to the Viridians streptococci group of oral bacteria and is commonly associated with dental caries. S. gordonii has been previously reported as the causative pathogen in both endocarditis and spondylodiskitis [2]. However, it has rarely been associated with biliary infections. In this report, we presented a patient diagnosed with cholecystitis associated with S. gordonii infection.