Israel Medical Association Journal

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.

Background: Pelvic organ prolapse in pregnancy is rare. Consequent complications include cervical infection, spontaneous abortion, and premature birth. Conservative management by means of a pessary have been described as improving maternal symptomatology and minimizing gestational risk. The delivery mode is controversial.

Objective: To describe the clinical courses of patients diagnosed with pelvic organ prolapse during pregnancy, and to present our multidisciplinary approach.

Methods: In this retrospective case series, we summarized the obstetrical outcomes of women diagnosed with pelvic organ prolapse during pregnancy in a single university-affiliated hospital.

Results: We identified eight women with advanced uterine prolapse at a mean age of 30.3 years. Seven were diagnosed with advanced uterine prolapse (Pelvic Organ Prolapse Quantification [POPQ] stage ≥ 3). All were treated by pessary placement, which was tolerable and provided symptomatic relief. The pessary type was chosen according to the prolapse stage. In women with cervical prolapse POPQ stage > 2 and cervical edema, a support pessary was less beneficial. However, the prolapse was well-controlled with a space-filling Gellhorn pessary. Low complication rates were associated with vaginal deliveries. The few complications that were reported included minor cervical laceration, postpartum hemorrhage, and retained placenta.

Conclusions: Treatment of pelvic organ prolapse during pregnancy must be individualized and requires a multidisciplinary approach of urogynecologists, obstetricians, dietitians, pelvic floor physiotherapists, and social workers. Conservative management, consisting of insertion of a vaginal pessary when prolapse symptoms appeared, provided adequate support for the pelvic floor, improved symptomatology, and minimized pregnancy complications. Vaginal delivery was feasible for most of the women.

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.

The use of smaller-diameter, pencil-point spinal needles has increased to reduce post-dural puncture headaches in obstetric patients. However, this therapy has also led to more needle deformation and breakage. While risk factors and prevention are described, there is limited literature on management when breakage occurs.

The utilization of neuraxial techniques for labor analgesia and cesarean delivery has experienced a consistent increase in recent years [1]. Spinal anesthesia has emerged as the preferred technique for cesarean deliveries due to its advantages, including a reduction in morbidity and mortality, decreased complications related to airway management, reduced bleeding, improved bonding with the baby, and better outcomes for newborns [2]. While the adoption of smaller diameter, non-cutting bevel spinal needles has successfully reduced the incidence of post-dural puncture headaches in obstetric patients, it has also given rise to complications such as spinal needle deformation and breakage [3,4]. The current understanding of the incidence of neuraxial needle breakage remains limited, with estimated incidences reported between approximately 1 in 5,000 to 1 in 11,000 spinal anesthesia procedures performed [4]. Although numerous case reports have documented broken needles during attempted neuraxial anesthesia, the existing literature predominantly focuses on associated risk factors and preventive measures for this complication [3]. However, there is a lack of literature regarding the subsequent management once this adverse event has transpired. In this report, we present a case involving a broken spinal needle during an attempt to perform spinal anesthesia for an urgent cesarean delivery. By sharing this case, we shed light on the management strategies and considerations following such an event.

The prevalence of difficult-to-treat rheumatoid arthritis (D2T RA) varies between 5% and 25%, with females comprising the majority of patients and no difference in patient age between D2T and non-D2T RA cohorts. While several attempts to subclassify D2T RA patients into defined subgroups have been tried, the inclusion of an individual D2T RA patient to one of the predefined subgroups can be difficult or impossible as multiple factors are usually involved in the mechanisms of rheumatoid arthritis (RA) refractoriness, with the complex interplay of inflammatory, structural, social, and psychological factors being unique for each patient. More severe disease at presentation, including seropositivity and early erosion formation, and insufficiently aggressive initial treatment can both contribute to the eventual development of D2T RA. No single test or study can replace the holistic clinical approach to the diagnosis and understanding of the causation of D2T RA. Traditional in-depth clinical history and thorough clinical examination remain sine qua non in managing D2T RA patients. Multifaceted contributions of inflammatory and non-inflammatory components create the uniqueness of D2T RA and dictate a comprehensive approach to the management, including both pharmacologic and non-pharmacological therapeutic strategies. Mean annual total costs for D2T RA patients have been estimated as being about twice as high as that of patients with non-D2T RA.

The emergence of the hybrid hospital represents a paradigm shift, blending the physical and virtual realms to optimize healthcare delivery. Telehealth made its significant entrance into the health systems during the coronavirus disease 2019 (COVID-19) pandemic. The use of a variety of telehealth initiatives increased during the COVID-19 pandemic. Approximately 8% of primary care visits in the United States are by telehealth. Despite the rapid growth of telehealth, several barriers persist. Technological limitations, regulatory challenges, and resistance to change among both healthcare providers and patients pose hurdles to the widespread adoption of telehealth services. A significant concern in the healthcare digital evolution is the digital divide. Socioeconomic factors, such as limited access to high-speed internet and digital devices, can exacerbate existing healthcare disparities. An important part of the hybrid hospital is home hospitalization, which is an alternative to regular hospitalization. This method opens access to big, tertiary, academic centers to remote populations and advances treatment equity. Home hospitalization has become available in several countries such as Australia, China, and the United States, with impressive results for peripheral, remote populations. According to the McKenzie Report, virtual hospitals have the potential to ease busy health systems, make more hospital beds available, decrease the need for building physical hospitals, and save millions of dollars. Hybrid hospitals and telehealth are here to stay. The medical community should study the risks and opportunities and establish guidelines for proper, quality, and safe management.

Background: Data regarding the management of adnexal torsion (AT) during the coronavirus disease 2019 (COVID-19) pandemic are scarce.

Objectives: To study the effects of actions to limit the spread of COVID-19 on AT management.

Methods: We conducted a retrospective cohort study of all women who underwent laparoscopy for suspected AT between March 2011 and February 2021. We compared the COVID-19 pandemic period, (15 March 2020–2 August 2021, group A) to a parallel period (2019–2020, group B), and a 9-year period preceding the pandemic (March 2011–February 2020, group C).

Results: We performed 97 laparoscopies in group A, 82 in group B, and 635 in group C. The proportion of women presenting following in vitro fertilization treatment was lower (odds ratio [OR] 0.22, 95% confidence interval ]95%CI] (0.06–0.86), P < 0.023). Time from admission to decision to operate was shorter (2.7 vs. 3.9 hours, P = 0.028) in group A than group B. Time from admission to surgery was shorter (9.1 vs. 12.5 hours, P = 0.005) and the rate of surgically confirmed AT was lower (59 [60.8%] vs. 455 [71.7%], P = 0.030, OR 0.61, 95%CI 0.39–0.95) in group A than group C. Among surgically confirmed AT cases only, mean time from admission to decision was shorter in group A than group B (2.6 vs. 4.6 hours, P = 0.014).

Conclusions: We identified differences in time from admission to clinical decision and from admission to surgery among women with suspected AT during the COVID-19 pandemic.

Background: Cesarean delivery (CD) is one of the most common surgeries performed worldwide, with increasing yearly rates. Although neuraxial techniques remain the preferred anesthesia method for CD, maternal thrombocytopenia remains a prominent contraindication. Formation of spinal\epidural hematomas are extremely rare, however the minimal thrombocyte count required for safe neuraxial anesthesia is still under debate. Although transfusion of thrombocytes for the purpose of neuraxial anesthesia is still not recommended, patients with severe thrombocytopenia (less than 50 × 10³/uL) are given thrombocyte transfusion for surgical hemostasis.

Objectives: To evaluate the anesthetic approach to caesarean deliveries in parturients with severe thrombocytopenia who received thrombocyte transfusion aimed for improved surgical hemostasis.

Methods: We conducted a single center, retrospective cohort study.

Results: A total of five cases were found, four of which were given spinal anesthesia immediately following thrombocyte transfusion. One patient was denied spinal anesthesia because her thrombocyte count following transfusion failed to reach safe levels. None of our cases had anesthesia-related complications recorded.

Conclusions: We examined the anesthetic management parturients with severe thrombocytopenia who needed cesarean delivery and were transfused with thrombocytes for surgical hemostasis. In such cases, spinal anesthesia may be considered due to the serious risks associated with general anesthesia.

Background: Cesarean deliveries (CD) are commonly performed using neuraxial anesthesia. The use of neuraxial morphine has proven beneficial in terms of postoperative pain management; however, its effect on postoperative urine retention remains unclear.

Objectives: To determine whether morphine injection into the neuraxis during CD influences postoperative urinary retention rate.

Methods: We conducted a retrospective case-control observational study of patients undergoing CD. We compared patients using morphine injected into the intrathecal or epidural spaces (November 2020 to October 2021) to a historical cohort of patients undergoing CD without morphine (November 2019 to October 2020). The primary outcome was the rate of postoperative overt urinary retention necessitating bladder catheterization.

Results: The study group comprised 283 patients, and 313 patients in the control group were eligible for analysis. No differences were found with respect to the baseline demographic and indication for CD. The number of postpartum urinary bladder catheterizations due to urine retention was higher in the study group (5% vs. 1%, P-value = 0.003). No cases of 30-day readmission were recorded. Moreover, patients treated with neuraxial morphine required fewer repeat doses of postoperative anesthesia (oral analgesia 7.4 vs. 10.1, intravenous analgesia 0.29 vs. 0.31, oral opioids 0.06 vs. 3.70, intravenous opioids 0.01 vs. 0.45, P-value < 0.001 for all)

Conclusions: While neuraxial morphine used during CD appears to be safe and effective, the risk of postoperative urinary retention seems to be increased due to its use. Cases of overt urinary retention treated by bladder catheterization does not lead to short-term complications.

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.

Fibromyalgia is a pain-related condition common in women and is present in about 5% of the population [1]. Its treatment involves physical exercise, psychotherapy (mainly behavioral–cognitive therapy), and antidepressant/anticonvulsant use as class IA evidence treatments [1]. Although in several cases this treatment fails or loses effectiveness over time, necessitating novel therapeutical agents.

Naltrexone is an opioid antagonist drug used for opioid addiction therapy. It also has anti-inflammatory and analgesic properties when used in low dosages [2]. Our group recently wrote a systematic review of low-dose naltrexone (LDN) for treating rheumatic diseases, including fibromyalgia [3]. In all seven published articles on LDN for fibromyalgia, a benefit was observed in pain reduction and improvements in fibromyalgia questionnaires [3]. To the best of our knowledge, no study using LDN as the first option of treatment has been conducted. Therefore, in this study we aimed to evaluate the effects of LDN as the first line of therapy in patients with fibromyalgia.

Idiopathic eosinophilic vasculitis is a newly recognized form of hypereosinophilic syndrome. While little is understood about the condition, criteria for its definition have been proposed. We aimed to determine whether three patients with eosinophilia and vasculitis could be retrospectively diagnosed with this condition. We performed a retrospective descriptive analysis on three cases with hypereosinophilia and vasculitis who were treated in Sheba Medical Center, Sourasky Medical Center, and Meir Medical Center in Israel between 2009 and 2021. A thorough review of all three cases was conducted. The findings were compared to the suggested criteria for idiopathic eosinophilic vasculitis.

All patients shared the symptoms of progressive limb ischemia, eosinophilic rash, and peripheral neuropathy that are consistent with vasculitis. No lower or upper respiratory abnormalities or the presence of anti-neutrophil cytoplasmic antibodies (ANCA) autoantibodies associated with eosinophilic granulomatosis with polyangiitis were detected. Primary monoclonal abnormalities, drug interactions, infections, allergy, and other secondary causes of hypereosinophilia were excluded. After a thorough review, we suggest that our three patients with previously unexplained hypereosinophilia and vasculitis fit the diagnosis of idiopathic eosinophilic vasculitis. These results highlight the existence of this novel condition and the importance of its recognition and consideration as part of the differential diagnosis in patients with marked eosinophilia and vasculitis. Further research for elucidating the mechanisms and treatment approach for this potentially severe condition is urgently needed.

Mucin gene 5AC (MUC5AC), a secreted mucin, is the most important component of the gastric mucus unstirred, protecting layer, preventing the enzymatic attack of acid and pepsin, toxins, and microorganisms. We investigated the effect of Helicobacter pylori (H. pylori) infection on MUC5AC expression in the gastric mucosa. English language medical literature searches were conducted for gastric MUC5AC expression in H. pylori infected patients compared to uninfected people, or cases after eradication. PubMed, EMBASE, Scopus, and CENTRAL databases were searched. Meta-analysis was performed and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. Heterogeneity was evaluated and I² statistic was used to measure the proportion of inconsistency in individual studies.

We also calculated a potential publication bias. In all, 11 studies representing 13 sub-studies were selected according to the inclusion criteria. The OR of MUC5AC expression in a random effect analysis was 0.217, 95%CI 0.124–0.377, P < 0.0001, significantly lower in H. pylori gastritis than in normal mucosa. When only studies with high-quality scores were calculated, OR was 0.239, 95%CI 0.137–0.419, P < 0.0001. Heterogeneity and inconsistency were small, with no significant publication bias. MUC5AC expression is lower in H. pylori infected mucosa, which may significantly affect the effective colonization and survival of the bacterium and persistent chronic inflammation.