Israel Medical Association Journal

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.

Sulfonylureas have been used to treat patients with diabetes for the last 80 years. The main side effect of this drug class is hypoglycemia, which might be severe and protracted. With the emergence of new medications with improved safety and better efficacy in preventing diabetes complications and cardiovascular morbidity and mortality, the use of these agents is waning.

Sulfonylureas are historically classified into two generations. The generation first includes drugs such as tolbutamide and chlorpropamide, which are no longer used. The second generation includes glibenclamide and glimepiride, which have different pharmacokinetic properties and active metabolites.

In this case report, we present a patient with diabetes and end-stage renal disease (ESRD) who developed prolonged hypoglycemia following the unauthorized use of a food supplement containing the first-generation sulfonylurea - tolbutamide.

A 26-year-old female at 28 weeks of gestation with her fourth pregnancy presented with a 24-hour history of diffuse abdominal pain and distension. In addition, she had nausea, vomiting, and constipation. The pain did not respond to analgesics. She had poor prenatal care during her pregnancy. She had previously had three cesarean deliveries. The first cesarean delivery was due to non-progressive second stage of labor, the second was preterm due to abdominal pain and suspected uterine rupture, and the last was due to the previous cesarean deliveries. In her last previous pregnancy, she presented with recurrent milder abdominal pain, which resolved spontaneously.

On examination, she was afebrile, with normal blood pressure and heart rate. Her abdomen was distended, tympanic, and mildly tender to palpation with no tenderness on the cesarean scar and no peritoneal signs. Her laboratory testing was normal except for mild hypokalemia.

Contactin associated protein-like 2 (CASPR2) and leucine-rich glioma-inactivated protein 1 (LGI1) voltage gated potassium channel (VGKC) proteins are found in both the central and peripheral nervous systems [1]. Antibodies against these proteins are associated with encephalopathy, seizures, peripheral nerve hyper-excitability, autonomic dysfunction, hyponatremia, pain, and insomnia in varying severity and combination [1].

Morvan syndrome, first described in 1890, combines symptoms of peripheral nervous system (PNS), central nervous system (CNS), and autonomic nervous system dysfunction. It was later found to be associated with VGKC-complex antibodies, mainly against CASPR2 or LGI1 or both.

Our patient had a history of anti-LGI1 positive limbic encephalitis, which presented years later with anti-CASPR2 positive Morvan syndrome.

Global developmental delay (GDD), defined as a significant delay in two or more developmental domains (e.g., gross/fine motor, cognitive, speech/language, personal/social, activities of daily living), affects 1–3% of children. According to the Israeli Ministry of Health, thyroid function studies are not indicated in children with GDD unless there are systemic features suggestive of thyroid dysfunction (https://www.health.gov.il/hozer/mr36_2012.pdf). This approach also exists in other countries with newborn screening programs for congenital hypothyroidism.

We present the case of an infant with GDD, who despite normal newborn screening tests, underwent a repeated extended thyroid function analysis (including T₃ levels) leading to a diagnosis of Allan-Herndon-Dudley syndrome, a rare genetic neurodevelopmental syndrome.

Familial spastic paraparesis is a non-progressive disorder. However, clinical experience shows that after trauma, disease, surgery, or limb fracture that force a patient's long immobilization, a significant functional deterioration is observed. I describe two patients with Silver syndrome who experienced such functional deterioration after sustaining a simple fracture. A description of Silver syndrome and a biographical sketch of Dr. Silver, who explained the disorder in 1966, are given.

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].

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.

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: 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: 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.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders. Acute cholangitis (AC) is a life-threatening illness.

Objective: To determine whether NAFLD is a risk factor for the severity of AC.

Methods: We retrospectively studied hospitalized patients with a diagnosis of AC over 5 years. Patients were divided into a NAFLD group and a non-NAFLD group. We compared the two groups with regard to demographic characteristics, co-morbidities, laboratory data, and severity of AC (including Charlson Comorbidity Index [CCI] and Tokyo Consensus meeting criteria).

Results: In all, 298 of 419 hospitalized patients diagnosed with AC met the inclusion criteria. Of these, 73/298 (24.5%) were in the NAFLD group. NAFLD group patients were younger and more likely to be diabetic and obese than the non-NAFLD group. Participants in the NAFLD presented with higher serum C-reactive protein and higher liver enzymes (P < 0.05, for each parameter) and with more events of organ dysfunction (P < 0.001) and bacteremia (P < 0.005). Regarding the severity of AC according to Tokyo Consensus, among the NAFLD group more patients presented with Grade II (39.7 vs. 33.3%, P < 0.001) and Grade III (23.3 vs. 18.3, P < 0.001) cholangitis. More Grade I cholangitis was found among the non-NAFLD group (48.4 vs. 37%, P < 0.001). Multivariate logistic regression analysis showed that NAFLD was independently associated with severe AC, Grade III (odds ratio 3.25, 95% confidence interval 1.65–6.45, P = 0.038).

Conclusions: NAFLD is an independent risk factor for the severity of AC.

Background: The cornea is one of the most densely innervated in the body. Pterygium surgery includes removal of the pterygium tissue from the cornea and conjunctiva followed by autologous conjunctival grafting.

Objectives: To examine the change in corneal and conjunctival sensation post-pterygium surgery.

Methods: This prospective study included patients with primary pterygium. We collected and analyzed demographic data, visual acuity (VA), refraction, quantified sensation, and corneal tomography. Comparison in sensation in the cornea, conjunctiva, and conjunctival autograft was recorded the day of surgery and at least 6 months postoperatively.

Results: Nine patients participated in the study. Mean follow-up time was 9 months (9 ± 3.3, 6–12.4). No complications were documented during or following surgery and no recurrences were found. Statistically significant increases in corneal sensation in the nasal corneal and in the nasal conjunctival areas were noted by the end of follow-up compared to before surgery (P = 0.05, paired samples t-test). There was a significant correlation between the increase in nasal corneal and conjunctival sensation with improved Schirmer testing outcomes and tear break-up time after surgery (P = 0.05, P = 0.01, Pearson correlation). There was a positive correlation between the changes in nasal corneal sensation after surgery and improved changes in VA (P = 0.02, Pearson correlation).

Conclusions: We found improvement in sensation 9 months after pterygium surgery, which may be due to reinnervation of the cornea and conjunctival autograft from the neighboring non-injured nerve fibers. Larger studies with confocal microscopy should be conducted for further analysis.

Background: Thiamine is an essential co-factor for aerobic intracellular respiration, nerve conduction, and muscle contraction. Thiamine deficiency is common in the intensive care unit (ICU). Delirium is a frequent unwanted symptom among critical ill patients. Although the exact cause of ICU-associated delirium is unknown, abnormal nutrition and thiamine deficiency may contribute to the etiology.

Objectives: To compare the prevalence of delirium among ICU patients who received thiamine with those who did not and to compare morbidity and mortality.

Methods: A retrospective study was conducted among ICU patients admitted 2014–2018. Routine thiamine administration began in 2016. Collected data included patient demographics, medical history, indication for ICU admission, hospital admission times, ventilation days, inotropic therapy, hemodialysis, tracheostomy, 28-day mortality, and need for anti-psychotic therapy. Group A received thiamine, group B did not. All data were statistically analyzed according to type.

Results: The study included 930 patients: 465 patients in group A and 465 in group B. At admission and throughout the hospitalization severity of disease parameters was worse in group A compared to group B, including acute physiology and chronic health evaluation (APACHE) score, admission lactate level, ventilation days, inotropic support, renal replacement therapy, tracheostomy, and ICU hospitalization. Group A had fewer delirium events without difference of maximal delirium score. No difference in mortality rate was observed.

Conclusions: Thiamine administration was associated with lower delirium prevalence despite longer ICU admission times and higher disease severity parameters at admission and during ICU stay.