Israel Medical Association Journal

In the last hundred years, the science of fracture repair has significantly changed. Management has moved from a simple metabolic and hormonal concept of bone regeneration to an inflammatory concept and now to a more complicated immunological description. Fracture repair has been considered age-dependent and related to diabetes, nutrition, hormone connection, autoimmune diseases, rheumatic arthritis, and nicotine. Recently a new branch of medicine, osteoimmunology, which deals with the mechanism of fracture repair, has been introduced.

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: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

Background: Cloacal malformation represents the rarest and most complex congenital anorectal malformation in females and is characterized by the convergence of urinary, gynecological, and intestinal systems within a single common channel. Three-dimensional computed tomography reconstruction (3D CT cloacagram) has emerged as a valuable method for anatomical assessment and preoperative planning.

Objectives: To evaluate our experience with 3D CT cloacagram and assess its results.

Methods: This retrospective case series included all patients with cloacal malformation who underwent preoperative 3D CT cloacagram at a single institution during 2019–2023. Collected data included patient characteristics, timing of the 3D CT cloacagram, results of the 3D CT cloacagram, comparison with endoscopic results, surgical procedures, and postoperative outcome.

Results: Six patients with cloacal malformation were included in this study, including two with posterior cloaca. The median common channel length on 3D CT cloacagram was 24.5 mm (range 9–48 mm) and the median urethral length was 15.5 mm (range 13-24 mm). The surgical approach involved a combined abdominoperineal approach in three patients and posterior sagittal anorectal vaginal urethral plasty in one patient. Two patients were awaiting surgical reconstruction at the time of publication.

Conclusions: Our implementation of 3D cloacagram has facilitated precise measurements of both the urethra and common channel lengths, two key factors in formulating surgical strategies for cloacal reconstruction. Moreover, this technique has markedly improved our capacity for surgical planning contributing to colorectal, gynecological, and urological perspectives.

Background: Breech presentation is a major indication for cesarean delivery (CD); however, the ideal timing of breech CD is debatable.

Objectives: To study the influence of gestational age at the time of CD in breech presentation on maternal and fetal complications.

Methods: We conducted a retrospective study including term singleton CDs of breech presentation between February 2020 and January 2022 at a tertiary medical center. Maternal and neonatal outcomes were compared by gestational age at the time of CD. Logistic regression models were constructed to adjust for confounders.

Results: The study population included 468 CDs, 227 (48.5%) were at 37 + 0 to 38 + 6 weeks, 168 (36%) were at 39 + 0 to 39 + 6 weeks (comparison group), and 73 (15.5%) were at ≥ 40 weeks at the time of delivery. The rate of emergent CDs was significantly higher in both study groups. The composite of maternal adverse outcomes was also significantly higher at ≥ 40 weeks of gestation. Using logistic regression model, associations remained significant. The adjusted odds ratios (OR) for emergent CDs at 37 + 0 to 38 + 6 weeks and at ≥ 40 weeks were 1.65 (P = 0.018) and 2.407 (P = 0.004), respectively. Adjusted OR for maternal adverse outcomes at ≥ 40 weeks was 2.094 (P = 0.018). Higher rates of emergent CDs in both study groups compared to the comparison group was noted. A composite of maternal adverse outcomes was significantly higher at ≥ 40 weeks of gestation. This association remained significant after controlling for potential confounders.

Conclusions: CDs at 39 + 0 to 39 + 6 weeks are associated with better maternal outcomes and lower rates of emergent CDs.

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: Coronary heart disease (CHD) patients are considered high cardiovascular risks. Guidelines recommend low-density lipoprotein cholesterol (LDL-C) target levels below 55 mg/dl with > 50% reduction from baselines. These levels can be reached by a combination of statins, ezetimibe, and anti-protein convertase subtilisin/kexin type 9 (anti-PCSK9) agents. Our clinical impression was that CHD patients do not reach LDL-C target levels, despite the wide availability.

Objectives: To evaluate whether hospitalization would result in changes in lipid lowering regimens and short-term compliance.

Methods: We conducted a retrospective cohort study using data of CHD patients who were admitted to internal medicine wards at Clalit Health Services medical centers because of anginal syndrome during 2020–2022. The data were evaluated for demographic and clinical characteristics; LDL-C level at admission, 6 months previously, and 3 months and 6–9 months after discharge; rates of reaching LDL-C target levels; and lipid lowering treatment at admission, discharge, and 6–9 months after.

Results: The cohort included 10,540 patients. One-third and three-quarters did not have lipids level measurements up to 6 months before and during hospitalization, respectively. Only one-fifth of the patients reached LDL-C values before and during admission (median LDL-C 72 mg/dl; range 53–101). Approximately half were treated with high-dose potent statins. Only 10% were treated with ezetimibe. Hospitalization did not have a clinically significant effect on short-term lipid lowering treatment or LDL-C levels.

Conclusions: Gaps were noted between guidelines and clinical practice for reaching LDL-C target levels. Further education and strict policy are needed.

Background: Serum ferritin is a sensitive inflammatory biomarker reflecting cell damage and oxidative stress in inflammatory rheumatic diseases. The use of ferritin for assessment of systemic sclerosis (SSc) activity, severity, and prognosis has not been fully elucidated.

Objectives: To assess the correlation between serum ferritin levels and SSc disease parameters, complications, and outcome.

Methods: Demographic, clinical, and laboratory data, including blood levels of ferritin, were collected from files of patients with SSc who were treated at the Rheumatology Institute at Rambam Health Care Campus from January 2004 to July 2021. The study compared SSc patients with elevated levels of ferritin to those with normal levels.

Results: We extracted data of 241 SSc patients (80% female, 60% with diffuse SSc, mean age 54 ± 15.4 years, mean disease duration 6.8 ± 4.5 years). During follow-up, 39% died. Elevated ferritin levels positively correlated with male sex; short disease duration; lung, heart, and kidney involvement; higher modified Rodnan skin score; anemia; elevated levels of creatinine kinase, C-reactive protein, creatinine, and troponin; reduced pulmonary function tests (forced vital capacity and diffusion capacity of the lung for carbon monoxide); and left ventricular ejection fraction. There were no correlations between ferritin levels and pulmonary hypertension or gastrointestinal involvement. Levels of ferritin negatively correlated with anti-centromere antibodies.

Conclusions: In SSc, ferritin can serve as a marker for ongoing systemic inflammation and prognosis, particularly in patients with lung and heart involvement. Further studies on serial ferritin measurement in the management of SSc patients are warranted.

We report a rare case of an epidural abscess caused by Aggregatibacter aphrophilus in a 69-year-old healthy woman. The patient, presented with neck pain, high fever, and chills following dental treatment. A magnetic resonance imaging (MRI) scan revealed an epidural abscess with moderate spinal cord compression at the C4–C5 level. Surgical intervention and antibiotic therapy with ceftriaxone led to complete recovery. This case underscores the significance of considering A. aphrophilus as a potential pathogen in patients with neck pain and fever post-dental procedures and as a cause of abscesses in apparently healthy patients.

A. aphrophilus, a gram-negative coccobacillus, is part of the HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella), a group of bacteria mainly known for its association with endocarditis [1]. However, A. aphrophilus is an uncommon pathogen for epidural abscesses [2]. Our case illustrates its potential to cause an epidural abscess after dental manipulation.

In 2013, the idea of the hyperferritinemic syndrome was introduced to suggest the possible inflammatory properties of ferritin in contributing to the pathogenesis of four diseases, namely Still’s disease, macrophage activation syndrome (MAS), septic shock, and catastrophic antiphospholipid syndrome [1]. Based on this concept, ex vivo and in vitro studies were performed reporting the inflammatory properties of the heavy subunit of ferritin (FeH) in inducing the commitment of macrophages toward an inflammatory phenotype, production of pro-inflammatory cytokines, and the direct stimulation of NLRP3 and NF-kB pathway [2,4]. In addition, recent in vivo studies have established the pathogenic role of hyperferritinemia [4-6], mainly triggering a Still’s disease-like phenotype in a wild type murine model by the aberrant activation of immune cells and production of inflammatory mediators [5]. Moreover, the hyperferritinemic syndrome arena has seen many recent developments due to the rapid accrual of knowledge in coronavirus disease 2019 (COVID-19) [6,7]. Specifically, the appearance of hyperferritinemia is increasingly recognized to be associated with a more severe patient phenotype at higher risk of poor prognosis due to the appearance of the cytokine storm syndrome [8], which is a hyper-inflammatory state due to overwhelming massive release of inflammatory mediators and rapidly evolving to multiorgan failure [9].

In this case report, we elucidated the complex etiology of new-onset ascites through the unusual presentation of a 32-year-old female with abdominal swelling, oliguria, and acute renal failure. This patient's ascites was attributed to urinary bladder rupture, a rare but critical consideration in differential diagnoses. Highlighting the significance of this case, bladder rupture without recent trauma history, especially post-gynecological surgery, poses a diagnostic challenge due to its rarity and potential for severe morbidity and mortality if not promptly recognized and managed. Our patient's journey, from initial symptoms to the eventual discovery of bladder rupture, underscores the necessity of considering this diagnosis in similar clinical scenarios. The case uniquely demonstrates pseudo-renal failure, a phenomenon resulting from reversed dialysis across the peritoneal membrane, which further complicated the diagnostic process.

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.

War is a chaotic situation for most of the public sectors in the countries involved. These sectors also include the medical systems, especially medical education, of which medical communication is often neglected or forgotten due to objective and subjective causes on either side of the involved countries. By planning lessons on various aspects of medicine for countries at war and close mentoring and utilization of modern communications technologies, these difficulties can be minimized without jeopardizing the quality of medical studies nor medical communication. In this perspective article, we describe the objective and subjective measures taken by our team to achieve these goals during the Iron Swords war in our region.

Background: Local anesthetics are used in various sites and mechanisms to maximize perioperative analgesia and reduce opioid use and side effects. Pain management in the bariatric setting is challenging and the efficacy of local anesthetics intraoperatively is under current evaluation.

Objectives: To determine the safety and efficacy of a new intra-abdominal anesthetic technique performed during laparoscopic bariatric operations: visceral block.

Methods: During this prospective randomized double-blinded pilot study, 16 patients undergoing bariatric surgery were treated with the injection of ropivacaine to the anterior esophagogastric junction fat, and 15 were injected with saline as control.

Results: The procedure was shown to be safe, and no adverse events nor side effects were encountered. A non-statistically significant trend toward the use of a non-opioid analgesia was documented during the first postoperative hours.

Conclusions: Visceral block is a safe and feasible intraoperative procedure. A trend toward its efficacy warrants future larger scale studies.