Israel Medical Association Journal

Background: Botulinum toxin (BT) can alleviate limb dystonia, but limited insurance coverage hinders its utilization.

Objectives: To compare the therapeutic efficacy of BT injections for spasticity and dystonia of the limbs.

Methods: BT injections of hypertonic limbs were administered under ultrasound guidance between 2019 and 2024 for either limb dystonia or limb spasticity.

Results: Of 74 patients included, 57 were diagnosed with spasticity and 17 with dystonia. In total, 276 therapeutic cycles were administered. The dropout rates were 45.6% in the spasticity group and 41.2% in the dystonia group (P = 0.48). There was no significant difference in subjective motor improvement between dystonia and spasticity (P = 0.16). Dystonia patients reported significantly better pain relief (98.5 ± 4.9% vs. 72.4 ± 35.6% respectively, P < 0.001). Notably, 74.3% of dystonia treatments reported moderate or marked improvement, whereas only 54.0% of spasticity treatments did (P > 0.05), based on patient the global impression of change (PGI-C) scale. Side effects were infrequent.

Conclusions: BT injections for limb spasticity and dystonia are partially effective. Nonetheless, the dropout rate is high. While BT injections are more effective in relieving pain for dystonia compared to spasticity, disease severity gradually improves over time in treated patients with spasticity but not with dystonia.

Background: Acute cholecystitis (ACC) is one of the most common diagnoses encountered in surgical wards. A number of treatment modalities are available, and various guidelines have been developed to help decision making. Many factors influence treatment strategies, including patient age and frailty. Due to the increasing proportion of older patients, consideration into the best treatment modalities for this population are warranted.

Objectives: To determine outcomes of elderly patients with ACC according to different treatment strategies.

Methods: A retrospective analysis of consecutive patients aged ≥ 80 years who were admitted with a diagnosis of ACC between 2015 and 2019 to a single academic center. Patients were divided into three groups according to treatment: percutaneous cholecystostomy tube placement, cholecystectomy, intravenous antibiotic treatment only.

Results: Overall, 466 patients were included in the cohort. The majority (approximately 75%) were treated with antibiotics only, 17% underwent percutaneous cholecystostomy, and 8% underwent laparoscopic cholecystectomy. One-year mortality was 28.1%. The highest mortality rate was 41.6% in the cholecystostomy group (P = 0.002). In multivariable analysis age, functional status, C-reactive protein, and albumin levels were found to be independent risk factors for 1-year mortality (hazard ratio [HR] 1.08, 0.56, 0.98, 0.4, respectively). Cholecystostomy increased risk of one-year mortality compared to cholecystectomy and antibiotics alone (HR 0.61, 0.23, respectively).

Conclusions: The use of cholecystostomy for ACC in older adults is an independent risk factor for 1-year mortality. Its use in older adults should be reserved for carefully selected cases.

Background: The prognostic significance of diabetes mellitus (DM) on hospitalization outcomes of patients with acute decompensated heart failure (ADHF) remains inconclusive.

Objectives: To comprehensively assess the clinical outcomes of patients with and without DM hospitalized for ADHF.

Methods: This single center retrospective cohort study included consecutive hospitalized patients with a principal diagnosis of ADHF between 1 January 2010 and 31 December 2019. Patients were categorized into diabetic and non-diabetic groups. The primary outcomes assessed were in-hospital mortality, 1-year overall mortality, and readmission rate within a year of follow-up.

Results: The final analysis involved 787 ADHF patients, with 62% having a pre-existing diagnosis of DM. Despite a higher burden of co-morbidities in diabetic patients, there were no differences in clinical outcomes when compared to non-diabetic counterparts. Specifically, there were no differences in overall hospital mortality (10% vs. 10%, P = 0.675), 1-year mortality (22% vs. 25%, P = 0.389), and re-admissions (51% vs. 56%, P = 0.154). Notably, the 1-year mortality among diabetic patients was not influenced by HbA1c levels documented before or during admission.

Conclusions: The clinical outcomes of patients hospitalized with ADHF did not differ by the presence of diabetes. Instead, our findings emphasize the importance of early heart failure prevention and subsequent hospitalization. Considering the evolving landscape of disease-modifying therapies for heart failure, achieving this goal becomes increasingly feasible.

Background: The coronavirus disease 2019 (COVID-19) pandemic showed the need to evaluate disease severity promptly at the time of hospital admission. 

Objectives: To establish an admission protocol, which included clinical and laboratory findings. 

Methods: We conducted a retrospective study at Wolfson Medical Center, Israel, for a period of 19 months (2020–2021). We established a protocol for patients who were admitted with COVID-19 infection. The protocol parameters included demographic data, co-morbidities, immune status, oxygen level at room air on admission, oxygen demand, lymphopenia, C-reactive protein (CRP) level, lactate dehydrogenase, D-DIMER, creatinine, aspartate transferase, alanine aminotransferase, and ferritin. Based on this protocol, we defined the severity of COVID-19 at the beginning of hospitalization and started treatment without delay. This protocol included ferritin levels as a guide to severity and outcome of patients. A database was established for all the parameters of the patients included in the study. 

Results: The study included 407 patients; 207 males (50.9%), 200 females (49.1%). The age range was 18–101 years. Hyperferritinemia (> 1000 ng/dl) was one of the strongest and most significant predictors for severe disease in these patients (P < 0.001). Lymphopenia, high levels of CRP, alanine aminotransferase, aspartate transferase, lactate dehydrogenase, and creatinine also correlated with severe disease, complications, and death. 

Conclusions: Abnormal ferritin levels were a very significant and clear indicator of the development of severe COVID-19. The addition of ferritin levels to our protocol aided in finding which patients were at increased risk for morbidity and mortality.

Background: The coronavirus disease 2019 (COVID-19) pandemic posed significant challenges to healthcare systems worldwide, including a surge in the use of extracorporeal membrane oxygenation (ECMO).

Objectives: To compare outcomes and costs of COVID-19 and non-COVID-19 adult patients treated with ECMO in the intensive care unit (ICU) at Tel Aviv Sourasky Medical Center.

Methods: We conducted a retrospective study. Clinical outcomes, ECMO duration, ICU and hospital length of stay (LOS), and healthcare costs were examined and compared between the two groups.

Results: A total of 119 patients were treated with ECMO between 2016 and 2023; 56 (47.1%) diagnosed with COVID-19. The study found no significant difference in mortality rates between COVID-19 and non-COVID-19 patients. However, COVID-19 patients experienced significantly longer ECMO durations and ICU LOS. Hospitalization and ECMO operation costs were notably higher for COVID-19 patients, but overall admission costs were lower compared to non-COVID-19 patients, with cost of surgical interventions, consultations and imaging contributing to the price gap.

Conclusions: Despite longer durations of ECMO and LOS, the economic burden of ECMO in COVID-19 patients was significantly lower than non-COVID-19 patients. Strict patient selection should be utilized, a fortiori during times of surge-capacity.

Background: Galactin-3 has been found to be involved in oocyte maturation, folliculogenesis, implantation, and placentation. The expression of Galactin-3 in the endometrium of women who have successfully undergone in vitro fertilization (IVF) has been suggested as a potential biomarker for predicting successful embryo implantation.

Objectives: To evaluate the expression of Galactin-3 in the sera and follicular fluid of women during IVF cycles.

Methods: This prospective research included 21 women undergoing IVF treatments. Blood samples were taken at four points: day 2 before starting stimulation, trigger day, day of oocyte retrieval, and day of the β-human chorionic gonadotropin level test. In addition, follicular fluid samples were taken on the day of oocyte retrieval. Galactin-3 protein levels were measured in serum and follicular fluid using enzyme-linked immunosorbent assay.

Results: Galactin-3 levels on the stimulation day were positively correlated to estradiol levels on the day of the trigger (0.59, P = 0.02). Among women who achieved pregnancy compared to those who did not, Galectin-3 serum levels were higher on the day of the trigger (17.93 ± 4.35 ng/ml vs. 11.01 ± 3.73 ng/ml, P = 0.015).

Conclusions: These findings may imply a potential role of Galectin-3 on the success of IVF treatments, underscoring the potential importance of inflammatory processes in fertility.

Background: Diabetic ketoacidosis (DKA) poses a significant medical emergency in both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients. Recent attention has focused on the emergence of euglycemic DKA associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors.

Objectives: To understand the epidemiology and outcomes of DKA, particularly in T2DM patients.

Methods: We conducted a retrospective cohort analysis of 204 patients admitted with DKA to Shamir Medical Center (2013–2021). We assessed demographics, clinical characteristics, and outcomes. Patients were stratified by diabetes type and SGLT2 inhibitor treatment status.

Results: Among the 204 patients with DKA, 38.2% had T2DM. Patients with T2DM exhibited older age, higher co-morbidity burden, and greater prevalence of microvascular complications compared to T1DM patients. Mortality rates were notably higher among T2DM patients, despite similar DKA severity at presentation, including in-hospital mortality rates of 6.4% vs. 0%, P < 0.05, and 90-day mortality rates of 7.7% vs. 0%, P < 0.05. T2DM was independently associated with adverse hospitalization outcomes, including a composite of rehospitalization, prolonged hospital stays, and mortality (odds ratio 2.68, 95% confidence interval 1.302–5.557). SGLT2 inhibitor treatment did not affect hospitalization outcomes of patients with T2DM.

Conclusions: Our findings underscore the importance of recognizing DKA as a substantial complication in diabetic patients, particularly those with T2DM. Vigilance in management, adherence to DKA guidelines, and awareness of triggers such as SGLT2 inhibitors are crucial for improving outcomes in this population.

Background: On 7 October 2023, Hamas lunched a massive terror attack against Israel. The first weeks after were characterized with great uncertainty, insecurity, and fear.

Objectives: To evaluate the effect of the first 2 months of the Iron Swords war on obstetrical emergency attendance and the corresponding perinatal outcomes.

Methods: We conducted a single center retrospective cohort study of all singleton births between 7 October and 7 December 2023. Prenatal emergency labor ward admission numbers and obstetric outcomes during the first 2 months of the war were compared to the combined corresponding periods for the years 2018–2022.

Results: During the initial 2 months of the conflict 1379 births were documented. The control group consisted of 7304 deliveries between 2018 and 2022. There was a decrease in daily emergency admissions to the labor ward during the first 5 weeks of the conflict compared to the corresponding periods in the preceding years (51.8 ± 15.0 vs. 57.0 ± 13.0, P = 0.0458). A notable increase in stillbirth rates was observed in the study group compared to the control group (5/1379 [0.36%] vs. 7/7304 [0.1%]; P = 0.014). Both groups exhibited similar gestational ages at birth, rates of preterm and post-term delivery, neonatal birthweights, mode of delivery, and induction of labor rates.

Conclusions: In the initial weeks following Hamas's attack on Israel, there was a notable decrease in admissions to the prenatal emergency labor ward. This decline coincided with an increase in the rate of stillbirths among a population not directly involved in the conflict.

Background: Heart failure (HF) is an emerging pandemic associated with increased mortality, recurrent hospitalizations, and reduced quality of life. Guideline-directed medical therapy has been shown to improve outcomes, particularly in patients with HF with reduced ejection fraction (HFrEF). The main goal of HF clinics is optimizing medical therapy.

Objectives: To assess the impact of our HF clinic on medical therapy and clinical outcomes.

Methods: We obtained demographic, echocardiographic, and clinical data of patients listed in our HF clinic during a 4-year period. Medical therapy was evaluated based on patient reports and documented data. Recurrent admissions for HF were documented.

Results: A total of 317 patients (74.1% male, median age 66 years, IQR 55–74) were listed in the clinic with a total of 1140 visits. Of these patients, 62.5% had HFrEF, 20.5% presented with mildly reduced ejection fraction, and 17% showed preserved ejection fraction at the time of the first visit. The use of sodium glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists was optimized in 92% and 91% of the patients, respectively. In the subgroup of patients with HFrEF, the use of angiotensin-receptor antagonist/neprilysin inhibitor increased from 22.6% to 87.9% (P < 0.001) and SGLT2 inhibitor use increased from 49.2% to 92% (P < 0.001). During the follow-up period (2.2 years, IQR 1.1–3.1), 203 patients (64%) were readmitted to the hospital for HF at least once. The rate of readmissions decreased over time.

Conclusions: An HF clinic plays an important role in optimizing medical therapy and reducing readmissions.

Background: Pseudomonas aeruginosa (PSA) is an infectious pathogen associated with acute appendicitis; however, it is not consistently addressed by empirical antibiotic therapy, despite potential complications.

Objectives: To investigate the incidence, predictors, and outcomes of PSA-associated acute appendicitis in children.

Methods: We conducted a retrospective analysis involving pediatric patients who underwent acute appendicitis surgery and had positive peritoneal cultures. Clinical, microbiological, and intraoperative data were extracted from medical records.

Results: Among 2523 children with acute appendicitis, 798 (31.6%) underwent peritoneal cultures, revealing 338 positive cases (42.3%), with PSA detected in 77 cases (22.8%). Children with PSA were three times more likely to exhibit high intraoperative grading ≥ 3 (93.4% vs. 76.8%, 95% confidence interval [95%CI] 1.2–8.3, P = 0.023) and nearly four times more likely to have polymicrobial cultures (88.3% vs. 62.1%, 95%CI 1.8–8.0, P < 0.001) than those without PSA in peritoneal cultures. Duration of symptoms did not predict PSA isolation (P = 0.827). Patients with PSA had longer median hospital stays (8 days, interquartile range [IQR] 7–10) than those with other pathogens (7 days, IQR 5–9) (P = 0.004). Antibiotic treatment duration, intensive care unit admission rates, readmission, and mortality were similar between the two groups (P = 0.893, 0.197, 0.760, and 0.761, respectively).

Conclusions: PSA is a common pathogen in children diagnosed with acute appendicitis and positive peritoneal cultures. The likelihood of isolating PSA increases with high-grade intraoperative assessment and in the presence of multiple pathogens in peritoneal cultures, suggests antipseudomonal treatment.

Background: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications.

Objectives: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM.

Methods: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared.

Results: The cohort included 89 women: 49 with HbA1c 6–8%, 29 with HbA1c 8–10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes.

Conclusions: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

Background: Cardiac implantable electronic devices (CIEDs) are increasingly being used; thus, there is an increasing need for transvenous lead extraction (TLE).

Objectives: To summarize our experience with TLE at single referral center in northern Israel.

Methods: The study included all patients who underwent TLE at our center between 2019 and 2022, regardless of the indication.

Results: The cohort included 50 patients. The mean age was 69 ± 10.36 years; 78% were males. A total of 99 electrodes were targeted. The mean number of electrodes was 1.96 (range 1–4) per patient. The time between lead implantation and extraction ranged between 1.1 and 34 years with an average of 8.14 ± 5.71 years (median of 7.5 years). Complete lead removal was achieved in 98% of patients and in 98.99% of leads. The complete procedural success rate as well as the clinical procedural success rate was 96%. The procedural failure rate was 4% (1 patient died 2 days after the index procedure and 1 patient remained with large portion of lead). The indication for TLE was infection in 78% of the cohort group. Powered mechanical sheaths were used in 36 patients (72%), laser sheaths in 27 (54%), and a combination of laser and mechanical sheaths in 16 (32%).

Conclusions: The clinical and procedural success rates of TLE, primarily for CEID-related infection, were high. A combination of laser and mechanical sheaths was needed in one-third of patients.

Background: Ischemic stroke is associated with increased risk of morbidity and mortality in future vascular events.

Objectives: To investigate whether CHA₂DS₂-VASc scores aid in risk stratification of middle-aged patients without atrial fibrillation (AF) experiencing ischemic stroke.

Methods: We analyzed data of 2628 patients, aged 40–65 years with no known AF who presented with acute ischemic stroke between January 2020 and February 2022. We explored the association between CHA₂DS₂-VASc scores categorized by subgroups (score 2–3, 4–5, or 6–7) with major adverse cardiac and cerebrovascular events (MACCE) including recurrent stroke, myocardial infarction, coronary revascularization, or all-cause death during a median follow-up of 19.9 months.

Results: Mean age was 57 years (30% women); half were defined as low socioeconomic status. Co-morbidities included hypertension, diabetes, obesity, and smoking in 40–60% of the patients. The incidence rate of MACCE per 100 person-years was 6.7, 12.2, and 21.2 in those with score 2–3, 4–5, and 6–7, respectively. In a multivariate cox regression model, compared to patients with score 2–3 (reference group), those with score 4–5 and 6–7 had an adjusted hazard ratio (95% confidence interval [95%CI]) for MACCE of 1.74 (95%CI 1.41–2.14) and 2.87 (95%CI 2.10–3.93), respectively. The discriminative capacity of CHA₂DS₂-VASc score for overall MACCE was modest (area under curve 0.63; 95%CI 0.60–0.66), although better for myocardial infarction 0.69 (95% CI 0.61–0.77).

Conclusions: CHA₂DS₂-VASc score may predict future MACCE in middle-aged patients with ischemic stroke and no history of AF.

Background: Hypothermia, as a sign of serious bacterial infection (SBI) in children and infants older than 90 days is poorly characterized, especially in the post-pneumococcal vaccine era.

Objectives: To assess the prevalence of SBI in children and infants presenting to the pediatric emergency department (PED) with reported or documented hypothermia.

Methods: Retrospective data analysis was conducted of all well-appearing children aged 0–16 years who presented with a diagnosis of hypothermia at two tertiary PEDs from 2010 to 2019.

Results: The study comprised 99 children, 15 (15.2%) age 0–3 months, 71 (71.7%) 3–36 months, and 13 (13.1%) > 36 months. The youngest age group had increased length of stay in the hospital (P < 0.001) and increased rates of pediatric intensive care unit admissions (P < 0.001). Empirical antibiotic coverage was initiated in 80% of the children in the 0–3 months group, 21.1% in the 3–36 months group, and 15.4% in > 36 months (P < 0.001). Only one case of SBI was recorded and no bacteremia or meningitis. Hypothermia of unknown origin was the most common diagnosis in all age groups (34%, 42%, 46%), respectively, followed by bronchiolitis (26%) and hypoglycemia (13.3%) for 0–3 month-old children, unspecified viral infection (20%) and otitis media (7%) for 3–36-month old, and unspecified viral infection (23%) and alcohol intoxication (15.2%) in > 36 months.

Conclusion: There is a low incidence of SBI in well-appearing children presenting to the PED with hypothermia and a benign course and outcome in those older than 3 months.

Background: Pregnant women are at higher risk for severe coronavirus disease 2019 (COVID-19). Since the release of the BNT162b2 messenger RNA vaccine (Pfizer/BioNTech), there has been accumulated data about the three vaccine doses. However, information regarding obstetric and neonatal outcomes of pregnant women vaccinated with the third (booster) vaccine is limited and primarily retrospective.

Objectives: To evaluate the obstetric and early neonatal outcomes of pregnant women vaccinated during pregnancy with the COVID-19 booster vaccine compared to pregnant women vaccinated only by the first two doses.

Methods: We conducted a cross-sectional study of pregnant women who received the BNT162b2 vaccine during pregnancy. Obstetric and neonatal outcomes were compared between pregnant women who received only the first two doses of the vaccine to those who also received the booster dose.

Results: Overall, 139 pregnant women were vaccinated during pregnancy with the first two doses of the vaccine and 84 with the third dose. The third dose group received the vaccine earlier during their pregnancy compared to the two doses group (21² vs. 31⁵ weeks, respectively, P < 0.001). No differences in obstetric and early neonatal outcomes between the groups were found except for lower rates of urgent cesarean delivery in the third dose group (adjusted odds ratio 0.21; 95% confidence interval 0.048–0.926, P = 0.039).

Conclusions: Compared to the first two doses of the BNT162b2 vaccine given in pregnancy, the booster vaccination is safe and not associated with an increased rate of adverse obstetric and early neonatal outcomes.