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: 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: 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.

Hypokalemia is a frequently encountered electrolyte disturbance, particularly among hospitalized patients. It often arises from increased potassium excretion (via the kidney or gastrointestinal tract) or intracellular shifts [1]. Hypokalemic periodic paralysis (HPP) is an uncommon cause of hypokalemia, with the most common reported mutation found in the dihydropyridine-sensitive calcium channel in skeletal muscles (CACNA1S gene) [2]. We present a case of a young woman with HPP associated with a novel mutation in the chloride voltage-gated channel 1 (CLCN1) gene.

Kidney involvement in systemic sclerosis (SSc) is common with altered kidney function present in approximately half of the patients [1]. Scleroderma renal crisis (SRC), the most severe kidney manifestation, occurs in about 20% of patients with this autoimmune disorder [1]. SRC mainly affects patients with the diffuse cutaneous systemic sclerosis (dcSSc) subtype of the disease, and particularly in those who are seropositive to anti RNA polymerase III antibodies [2]. In recent years, the prevalence of SRC has decreased following the initiation of medication therapy with angiotensin-converting-enzyme inhibitors (ACE-i). Previously, SRC mortality rates were as high as 78%. Contemporary studies in the post-ACE-i era suggest lower rates, with mortality rate ranging from 30% to 36% [3]. Nevertheless, progression to end-stage renal disease (ESRD) is evident and may require renal replacement therapies (RRTs). While renal transplant rates in SSc have increased, they constitute a small proportion of SSc-SRC patients (3–8%) and SSc-ESRD patients (4–17%).

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].

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.

Background: Preeclampsia is a unique vascular disease during pregnancy that generally appears after 20 of weeks gestation or until 6 weeks after delivery. Left undiagnosed, preeclampsia can lead rapidly to death of both mother and fetus.

Objectives: To verify the efficacy of peripheral blood inflammatory markers (BIMs)in diagnosing preeclampsia and compare them with results from other studies.

Methods: Our retrospective case-control study comprised two patient groups. Pregnant women with preeclampsia and pregnant women without preeclampsia were compared for BIMs: neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV). The primary endpoint of our research was to assess the predictive power of BIMs for preeclampsia diagnosis.

Results: The sample size was calculated based on expected differences of BIMs between the control and study groups. Comparison of quantitative variables was conducted with independent sample t-test or alternatively by Wilcoxon rank sum test. The MPV values were slightly higher in the preeclampsia group, but not statistically significant. NLR and PLR did differentiate between study and control groups.

Conclusions: The diagnostic accuracy of BIMs is unsatisfactory for preeclampsia diagnosis. Discrepancies concerning these values need to be clarified. Further large prospective studies are necessary to validate the potential factor accuracy in preeclampsia diagnosis.

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.

Reversible cerebral vasoconstriction syndrome (RCVS) comprises a group of conditions characterized by reversible vasoconstrictions of cerebral arteries. Clinical manifestations include sudden-onset severe headaches with or without additional neurologic signs and symptoms [1].

The incidence of RCVS is 2.7 cases per million adults. It predominantly affects women, and about 9% of all RCVS cases occur during the postpartum period [2,3]. Other possible precipitating factors, such as subarachnoid hemorrhage, ischemic stroke, intracranial hemorrhage, and exposure to vasoactive drugs, have also been reported in association with RCVS [2]. The exact pathophysiology of RCVS is not well understood, although hormonal influences have been suggested as possible contributing factors.

Alkalosis-induced cerebral vasoconstriction is described but not well understood. Hyperventilation is commonly used in neurologic patients to decrease intracranial pressure and cerebral blood flow. Hyperventilation causes cerebral vasoconstriction directly by hypocapnia and may indirectly affect through alkalosis.

We present a case of RCVS in a postpartum patient admitted to the intensive care unit (ICU) with severe metabolic alkalosis necessitating hemodialysis.

Background: Exclusive breastfeeding is recommended through six months as it supports infant growth and development. Yet, many mothers do not exclusively breastfeed in early postpartum.

Objectives: To examine factors associated with exclusive breastfeeding at hospital discharge among culturally diverse women.

Methods: This cross-sectional study used data of women who gave birth at a major medical center in Israel in 2015–2017. Descriptive statistics and regression analysis were conducted to examine maternal characteristics and associated breastfeeding outcomes by hospital discharge.

Results: Among 10,978 women, 17.8% (n=1958) exclusively breastfed, 57.9% (n=6357) partially breastfed, and 24.3% (n=2663) did not breastfeed. Among Israeli-born and former Soviet Union-born Jewish women, breastfeeding intention (odds ratio [OR] 19.59, 95% confidence interval [95%CI] 10.27–37.35 and OR 15.92, 95%CI 5.79–43.80, respectively) and early breastfeeding (OR 2.415, 95%CI 1.91–3.05 and OR 2.04, 95%CI 1.57–2.64, respectively) were associated with exclusive breastfeeding. The only significant factor associated with exclusive breastfeeding among refugees and Israeli-born Muslim women was early breastfeeding (OR 1.61, 95%CI 1.20–2.16). For Ethiopian-born Jewish women, not married (OR 0.330, 95%CI 0.114–0.955) and cesarean delivery (OR 0.481, 95%CI 0.232–0.998) were negatively associated with exclusive breastfeeding.

Conclusions: Despite having access to the same hospital-based breastfeeding support, there were differences among ethno-culturally diverse women in Israel. In this study, we identified maternal characteristics associated with early breastfeeding among women of diverse ethno-cultural backgrounds. Study findings highlight the importance of ethno-cultural considerations in breastfeeding practices and inform health professionals of factors associated with exclusive breastfeeding in early postpartum.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune demyelinating disorder of the central nervous system. Optic neuritis (ON) is the most common clinical manifestation of MOGAD in adults. In 2023, new MOGAD diagnostic criteria were proposed, highlighting the importance of supplemental criteria when MOG-immunoglobulin G (IgG) titers are unavailable.

Objective: To investigate the applicability of the 2023 MOGAD criteria in patients diagnosed with MOGAD and treated before the availability of MOG-IgG titers.

Methods: We conducted a retrospective chart review of patients classified as MOGAD between 2010 and 2023 at Rabin Medical Center. Patient demographics as well as clinical and imaging data were collected, including visual acuity, expanded disability status score, core demyelinating events, antibody status, and brain and optic nerve magnetic resonance imaging data. Patients fulfilling the 2023 MOGAD criteria were reported as definite MOGAD.

Results: Fifteen patients met the 2023 MOGAD diagnostic criteria despite lack of MOG-IgG titer. The most common supplemental criterion meeting the 2023 MOGAD criteria was optic disc edema (n=12, 80%), followed by longitudinal optic nerve involvement (53%), bilateral ON (40%), and perineural optic sheath enhancement (33%).

Conclusions: All patients with a clinical diagnosis of MOG-ON in our cohort fulfilled the 2023 MOGAD criteria despite the lack of antibody titers. The 2023 MOGAD criteria can be reliably applied to Israeli cohorts, prior to availability of MOGAD IgG titers, with particular attention to additional supplemental criteria. Since the 2023 MOGAD criteria were published, MOGAD IgG titers have been added to routine testing at our facility.

Long-term sperm preservation plays a pivotal role in providing a lifeline for individuals grappling with medical and fertility challenges; thus, enabling them to pursue their aspirations of parenthood. While the significance of frozen sperm is unquestionable, it is vital to address the persistently low utilization and disposal rates of stored samples over time and resulting in an unintended accumulation of unclaimed doses. This accumulation not only carries significant medical, legal, and financial burdens for the institutions responsible, such as sperm banks, but also raises complex ethical considerations, particularly concerning potential biological paternity. These multifaceted considerations are particularly relevant within Israel's publicly funded healthcare system, accentuating the need for clearly defined preservation criteria in cases where an immediate clinical necessity is not readily apparent. We highlight the important clinical, ethical, and economic aspects of preserving the potential for biological paternity and efficiently managing the resources and responsibilities associated with long-term sperm preservation.

We read with interest the retrospective study by Ohana Sarna and colleagues [1] titled Clinical Characteristics, Etiology, and Outcomes of Hypothermia in Well-appearing Children Referred to the Emergency Department. The study comprised 99 children younger than 16 years of age who presented to pediatric emergency department (PED) with hypothermia (temperature of < 36.5°C). The authors evaluated the incidence of serious bacterial infection (SBI) in 15 infants aged 0–3 months, 71 children aged 3–36 months, and 13 children older than 36 months. They concluded that the incidence of SBI in infants younger than 3 months of age was low and the older children had a benign course and outcome. As pediatric endocrinologists, we would like to mention another important cause of hypothermia, especially in infants but also in children: congenital and acquired hypothyroidism.