Israel Medical Association Journal

Background: Epidemiological studies have demonstrated an association between sleep deprivation (SD) and ischemic heart disease.

Objectives: To determine the effect of SD on the endothelial function and on the inflammatory profile of young healthy men following 24 hours of work without sleep.

Methods: Fourteen healthy men (age 31.3 ± 2.4 years) participated in our prospective study. Endothelial function was evaluated by the brachial artery method, measuring flow medicated percent change (FMD%) of the brachial artery by a linear array ultrasound early in the morning. Interleukin 1 (IL-1) and interleukin 6 (IL-6) were measured in saliva by ELISA.

Results: Basic FMD% was 6.7 ± 6.8%, and following SD 1.7 ± 3.3% (P = 0.009). A 5.0 ± 6.1% decrease was measured after SD. IL-1 levels increased after SD from 36 ± 21 pg/ml to 47 ± 24 pg/ml (P = 0.004), and IL-6 levels increased from 22 ± 07 pg/ml to 36 ± 11 pg/ml (P = 0.0005). A negative correlation was found between the change (decrease) in FMD% and the change (increase) in IL-1 level (r = -0.813; P = 0.001). A negative correlation was found between the decrease in FMD% and the increase in IL-6 level (r = -0.735; P = 0.003).

Conclusions: SD led to endothelial dysfunction with increase in markers of inflammation (IL-1 and IL-6), with an inverse correlation between the change (decrease) in endothelial function and the change (increase) in IL-1 and in IL-6.

Anifrolumab is a monoclonal antibody approved by the U.S. Food and Drug Administration in 2021 for the treatment of moderate-to-severe systemic lupus erythematosus (SLE) (excluding renal or neurological involvement). The drug inhibits the type 1 interferon receptor. Its safety and efficacy were evaluated through three placebo-controlled studies [1]. Clinical studies have demonstrated the beneficial effects of anifrolumab as an adjunct to standard therapy for SLE with cutaneous manifestations. Common side effects include upper respiratory tract infections, infusion-related reactions, herpes zoster, and hypersensitivity phenomena. Importantly, no serious skin reactions have been previously associated with the use of anifrolumab [2].

To the best of our knowledge, this is the first reported case of drug-induced bullous pemphigoid (DIBP) following treatment with anifrolumab.

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: Pyogenic flexor tenosynovitis (PFT) is a common and severe hand infection. Patients who present early can be treated with intravenous antibiotics.

Objectives: To determine whether PFT caused by animal bites and treated with antibiotics leads to a different outcome than other disease etiologies due to the extensive soft tissue insult and different bacterial flora.

Methods: We conducted a retrospective cohort study of 43 consecutive patients who presented with PFT between 2013 and 2020. The 10 patients who presented with PFT following an animal bite were compared to those who presented with PFT caused by any other etiology.

Results: Patients who were bitten pursued medical attention sooner: 1.9 ± 1.4 days compared with 5.3 ± 4.7 days (P = 0.001). Despite the quicker presentation, patients from the study group received similar antibiotic types and duration as controls. All patients were initially treated with intravenous antibiotics under surveillance of a hand surgeon. One patient (10%) from the study group and four controls (12%) were treated surgically (P = 1). Average follow-up was 17 ± 16 days. At the end of follow-up, one (10%) patient from the study group and three (9%) controls sustained mild range of motion limitation and one (3%) patient from the control group had moderate limitations (P = 0.855).

Conclusions: Intravenous antibiotic treatment, combined with an intensive hand surgeon follow-up, is a viable option for the treatment of PFT caused by animal bites.

Background: Advancements in artificial intelligence (AI) and natural language processing (NLP) have led to the development of language models such as ChatGPT. These models have the potential to transform healthcare and medical research. However, understanding their applications and limitations is essential.

Objectives: To present a view of ChatGPT research and to critically assess ChatGPT's role in medical writing and clinical environments.

Methods: We performed a literature review via the PubMed search engine from 20 November 2022, to 23 April 2023. The search terms included ChatGPT, OpenAI, and large language models. We included studies that focused on ChatGPT, explored its use or implications in medicine, and were original research articles. The selected studies were analyzed considering study design, NLP tasks, main findings, and limitations.

Results: Our study included 27 articles that examined ChatGPT's performance in various tasks and medical fields. These studies covered knowledge assessment, writing, and analysis tasks. While ChatGPT was found to be useful in tasks such as generating research ideas, aiding clinical reasoning, and streamlining workflows, limitations were also identified. These limitations included inaccuracies, inconsistencies, fictitious information, and limited knowledge, highlighting the need for further improvements.

Conclusions: The review underscores ChatGPT's potential in various medical applications. Yet, it also points to limitations that require careful human oversight and responsible use to improve patient care, education, and decision-making.

Paraneoplastic syndromes are reported in 8–15% of patients diagnosed with cancer [1]. They are defined as syndromes that occur due to an underlying malignancy, which has yet to be diagnosed, or at the time of the diagnosis and less frequently following the diagnosis of a malignancy. Several mechanisms are involved including autocrine and paracrine mediators, hormones, peptides, cytotoxic lymphocytes, and cytokines [1,2].

Recognizing myocarditis is a diagnostic and therapeutic challenge due to the heterogeneity of its clinical presentation and the wide range of etiologies. There is a lack of uniformity among position papers and guidelines from various professional societies regarding the definition and diagnostic workout, including recommendations for performing endomyocardial biopsy (EMB) and medical management, especially the use of immunosuppressive regimens [1-3]. Moreover, there is significant variability among medical centers in Israel in the diagnostic and therapeutic approaches to acute myocarditis. The purpose of this position paper is to present ways to standardize the management of acute myocarditis in Israel [4] by providing up-to-date definitions of the clinical categories of myocarditis, diagnostic criteria, and therapeutic approaches that correspond to the realities of our healthcare system.

In the position statement on the definition and diagnosis of acute myocarditis on page XXX of this issue of the Israel Medical Association Journal (IMAJ), we discussed contemporary criteria for definition of acute myocarditis and inflammatory cardiomyopathy [1-6]. We also addressed current diagnostic methods including indications for endomyocardial biopsy (EMB) [7-21]. In this position statement, we discuss the management approaches during hospitalization and following hospital discharge, including specific forms of myocarditis and recommendations for returning to physical activity after myocarditis [21-36].

Background: The DES-obstructive sleep apnea (DES-OSA) score uses morphological characteristics to predict the presence and severity of obstructive sleep apnea syndrome (OSAS).

Objectives: To validate DES-OSA scores on the Israeli population. To identify patients requiring treatment for OSAS. To evaluate whether additional parameters could improve the diagnostic value of DES-OSA scores.

Methods: We performed a prospective cohort study on patients attending a sleep clinic. Polysomnography results were examined independently by two physicians. DES-OSA scores were calculated. STOP and Epworth questionnaires were administered, and data on cardiovascular risk was extracted.

Results: We recruited 106 patients, median age 64 years, 58% male. DES-OSA scores were positively correlated with apnea-hypopnea index (AHI) (P < 0.001) and were significantly different between the OSAS severity groups. Interobserver agreement for calculating DES-OSA was very high between the two physicians (intraclass correlation coefficient 0.86). DES-OSA scores ≤ 5 were associated with high sensitivity and low specificity (0.90 and 0.27, respectively) for moderate to severe OSAS. In univariate analysis, only age was significantly correlated with the presence of OSAS (OR 1.26, P = 0.01). Age older than 66 years as a single point in the DES-OSA score slightly improved the sensitivity of the test.

Conclusions: DES-OSA is a valid score based solely on physical examination, which may be useful for excluding OSAS requiring therapy. DES-OSA score ≤ 5 effectively ruled out moderate to severe OSAS. Age older than 66 years as an extra point improved the sensitivity of the test.

Background: Epidemiological studies have shown a connection between ethnic origin and the incidence and outcome of systemic lupus erythematosus (SLE).

Objective: To evaluate the SLE outcomes among Ashkenazi Jews, non-Ashkenazi Jews, and Arabs.

Methods: We conducted a retrospective study of patients who were diagnosed with SLE and followed in lupus clinics at two large tertiary medical centers. The data were obtained from patient medical records. Patients were stratified into three ethnic origins: Ashkenazi Jews, non-Ashkenazi Jews, and Arabs. The primary outcomes were all-cause mortality, development of end-stage kidney disease (ESKD), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K ≤ 4 at last visit.

Results: We included 570 patients in this study. The Arab group showed the highest number of SLE classification criteria at diagnosis and last encounters compared to non-Ashkenazi and Ashkenazi Jewish groups (6.0 vs. 5.0 and 4.0, respectively at diagnosis, P < 0.001; 8.0 vs. 7.0 and 6.0 at last visit, P = 0.01). In multivariate models, Arab patients had three times higher risk of all-cause mortality than Ashkenazi Jews (hazard ratio 2.99, 95% confidence interval [95%CI] 1.32–6.76, P = 0.009). ESKD was similar among the study groups. Low disease activity (SLEDAI 2K ≤ 4) at last visit was lower in the Arab group than the Ashkenazi Jews (odds ratio 0.50, 95%CI 0.28–0.87, P = 0.016), depicting a medium-to-high disease activity among the former.

Conclusions: Physicians should consider the influence of the ethnicity of the SLE patient when deciding on their care plan.

Serum sickness is an immune-complex-mediated hypersensitivity reaction that classically presents with fever, rash, polyarthritis, or poly arthralgias. Damage is caused by formation or deposition of antigen-antibody complexes in vessels or tissues. Deposition of immune complexes causes complement activation and/or recruitment of neutrophils by interaction of immune complexes with Fc immunoglobulin G receptors. The condition was first recognized as an entity in the early 1900s in patients who had received heterologous antisera, which was historically used to treat infectious diseases. The symptoms typically occur one to two weeks after exposure to an offending agent and resolve within several weeks of discontinuation [1].

The coronavirus disease 2019 (COVID-19) pandemic has resulted in more than four million deaths globally. In addition to the lower respiratory system, a wide range of major organ injuries have been reported among patients infected with COVID-19. These injuries include cardiac involvement. The spectrum of cardiac manifestations includes cardiac injury, heart failure, cardiogenic shock, acute coronary syndrome, myocarditis, tachyarrhythmias, and bradyarrhythmia [1]. Different degrees of atrioventricular blocks have been reported [2].

The pathogenesis of these complications is not fully understood. Differentmechanisms are proposed, including direct myocyte injury, interstitial inflammation and fibrosis, cytokine storm, plaque destabilization, and and/or hypoxia [3]. Many countries have worked toward mass vaccination using the Pfizer BioNTech (BNT162b2) COVID-19 vaccine, including Israel. We report a case of high degree atrioventricular block (AVB) following vaccination with the COVID-19 BNT162b2 vaccine.

Background: Medical organizations worldwide aim for equity and diversity in the medical profession to improve care quality. Data on whether the caregiver gender affects outcomes in the prehospital setting are essential but scarce compared to available in-hospital studies.

Objective: To analyze the rates of missed injuries in the prehospital setting and determine whether these rates were associated with the gender of the on-field physician or paramedic.

Methods: A retrospective record review was conducted, which included trauma records documented in two trauma registries, the prehospital Israel Defense Forces-Trauma Registry (IDF-TR), and the in-hospital Israeli National Trauma Registry (INTR). Missed injuries were defined as injuries documented in the INTR but not in the IDF-TR. A multivariable regression analysis was performed to assess the association between provider’s gender and missed injuries.

Results: Of 490 casualties, 369 (75.3%) were treated by teams that included only male paramedics or physicians. In 386 (78.8%) cases, a physician was a part of the prehospital team. In all, 94 (19.2%) casualties sustained injuries that were missed by the prehospital medical team. Missed injuries were not associated with the gender of the paramedic or physician (odds ratio 1.242, 95% confidence interval 0.69–2.193).

Conclusions: No association was found between the gender of the medical provider in the prehospital setting and the rate of missed injuries. These results should encourage prehospital emergency medical systems to aim for a balanced and diverse caregiver population.

Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses