Israel Medical Association Journal

Over the last decade the use of artificial intelligence (AI) has reformed academic research. While clinical diagnosis of psoriasis and psoriatic arthritis is largely straightforward, the determining factors of a clinical response to therapy, and specifically to biologic agents, have not yet been found. AI may meaningfully impact attempts to unravel the prognostic factors that affect response to therapy, assist experimental techniques being used to investigate immune cell populations, examine whether these populations are associated with treatment responses, and incorporate immunophenotype data in prediction models. The aim of this mini review was to present the current state of the AI-mediated attempts in the field. We executed a Medline search in October 2023. Selection and presentation of studies were conducted following the principles of a narrative–review design. We present data regarding the impact AI can have on the management of psoriatic disease by predicting responses utilizing clinical or biological parameters. We also reviewed the ways AI has been implemented to assist development of models that revolutionize the investigation of peripheral immune cell subsets that can be used as biomarkers of response to biologic treatment. Last, we discussed future perspectives and ethical considerations regarding the use of machine learning models in the management of immune-mediated diseases.

Background: The use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) is emerging for lowering low-density lipoprotein cholesterol (LDL-C). However, real-world data is lacking for their use among elderly patients.

Objective: To define the characteristics of elderly patients treated with PCSK9 mAbs and to evaluate the efficacy and tolerability compared with younger patients.

Methods: We conducted a retrospective cohort study of elderly patients (≥ 75 years at enrollment) treated with PCSK9 mAbs for primary and secondary cardiovascular prevention. Data were retrieved for demographic and clinical characteristics; indications for treatment; agents and dosages; concomitant lipid lowering treatment; LDL-C levels at baseline, 6, 12 months, and at the end of follow up. Data also included achieving LDL-C target levels and adverse effects.

Results: The cohort included 91 elderly patients and 92 younger patients, mean age 75.2 ± 3.76 and 58.9 ± 7.4 years (P < 0.0001). Most patients (82%, 80%) were in high/very high-risk categories. For almost all (98%, 99%), the indication was statin intolerance, with PCSK9 mAb monotherapy the most prevalent regimen. The average follow-up was 38.1 ± 20.5 and 30.9 ± 15.8 months (P = 0.0258). Within 6 months the LDL-C levels were reduced by 57% in the elderly group and by 59% in the control group (P = 0.2371). Only 53% and 57% reached their LDL-C target levels. No clinically significant side effects were documented.

Conclusion: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.

A dramatic portrait bust of the physician Gabriele da Fonseca (1586? to 1668) at prayer is considered by art historians to be one of the finest late works of Gian Lorenzo Bernini (1598–1680), the preeminent sculptor of 17th century Rome. This statue is of medical as well as artistic interest. First, Fonseca is shown wearing his physician’s robe, thus celebrating his successful career as a leading medical figure in Rome, holding both Papal and university appointments at the highest level. In addition, the positioning of the statue in a special chapel designed by Bernini highlights Fonseca’s role as an influential participant in the introduction of quinine into Europe as a cure for malaria. Last, an examination of the statue’s hands identifies a number of pathologies and anatomical anomalies that raise interesting questions, regrettably unanswerable given the information presently available, concerning Fonseca’s illnesses and cause of death.

On 7 October 2023, a large-scale invasion by armed Hamas terrorists occurred in southern Israel. Approximately 1500 militants breached the Gaza security barrier using tractors, RPGs, and explosives. Concurrently, the terrorists utilized various means including armed vehicles, motorized paragliders, sea incursions, and a massive rocket attack launched toward Israel. On entering Israeli territory, the militants dispersed and targeted several towns, kibbutzim (collective communities), and Israel Defense Forces (IDF) military bases near Gaza. This strategy resulted in a death toll exceeded 1300 civilians and soldiers. In addition, more than 240 individuals were abducted. This attack occurred in one day. In this article, we introduce the Israeli National Institute of Forensic Medicine, which specialized in forensic analysis during mass casualty incidents, and pivotal role it played on 7 October. We present a detailed discussion on methods, challenges, and adaptations the institute took in response to the event of 7 October.

Background: Low-risk venous thromboembolism (VTE) patients are advised to be discharged from the emergency department (ED) on direct oral anticoagulants (DOACs) treatment. There is no data on whether this recommendation is followed in Israel.

Objectives: To characterize newly diagnosed VTE patients who were discharged from the ED, their anticoagulation treatment at the ED, the recommended discharge protocol, and patient adherence.

Methods: We conducted a retrospective cohort study, which included all newly diagnosed VTE patients who were discharged from the ED. Collected data included demographic and clinical background; anticoagulation treatment at the ED, recommended discharge protocol and its subsequent adherence, patient subsequent, recommended hematological evaluation, and adverse events.

Results: The study group included 443 patients, 89% with deep vein thrombosis (DVT). Approximately three-quarters were treated with anticoagulants in the ED, 98% with enoxaparin. At discharge, anticoagulants were recommended for all; 49% continued enoxaparin, 47% DOACs, and 4% warfarin. After 4 weeks, 67% were treated with DOACs, 22% with enoxaparin, 5% with warfarin. Approximately 6% discontinued all treatment. After 12 weeks, 90% of the patients who were taking DOACs adhered to the protocol, whereas only 70% and 50% among the enoxaparin and warfarin users, respectively, did. Only 56% were referred for hematological evaluation. The 12-week rate of adverse reactions was approximately 2%. The use of DOACs and the recommendation for further hematological evaluation increased over time.

Conclusions: Clinician training regarding discharge of VTE patients from the ED should continue.

There are numerous experimental studies on the effect of immune modulation on the skeleton but few clinical ones.

In this letter, we supplement the previous information on enhanced bone healing. A new branch of medicine, osteoimmunology, describes fracture healing as an active immune system process evolving in a cascade of repairs.

Background: The French AmbUlatory Cesarean Section (FAUCS) technique was introduced to the Galilee Medical Center in September 2021. FAUCS was performed electively for interested women who meet the criteria.

Objectives: To evaluate the learning curve of senior surgeons performing FAUCS, the procedure short-term outcomes, and complications.

Methods: This retrospective study included 50 consecutive women who underwent FAUCS from September 2021 until March 2022 at our facility. Preoperative, intraoperative, postoperative, and demographic data were retrieved from patient electronic charts.

Results: The mean duration of surgery was 53.26 ± 11.62 minutes. This time decreased as the surgical team's experience increased: from a mean 58.26 ± 12.25 minutes for the first 15 procedures to a mean 51.17 ± 9.73 minutes for subsequent procedures. The mean visual analogue scale score for 24 hours was 1.08 ± 0.84 (on a 10-point scale). The rate of neonatal cord pH < 7.2 was 6%, and there were 11.3% cases of vacuum assisted fetal extraction. In total, 44% of the women were able to mobilize and urinate spontaneously by 4–6 hours. Complications included bladder injury (n=1), endometritis (n=1), and incisional hematoma (n=1). Overall, the maternal satisfaction rate was high; 94% of the women would recommend FAUCS to others.

Conclusions: FAUCS is a feasible procedure with a high satisfaction rate. Following the first 15 procedures performed by one surgical team, the operative time decreased considerably. Further randomized controlled studies are needed to compare this procedure to regular cesarean section and evaluate neonatal outcomes.

Background: The administration of antenatal corticosteroids (ACS) is standard practice for management of threatened preterm birth. Its benefit, especially in small for gestational age (SGA) late preterm, is unclear.

Objectives: To evaluate the impact of ACS on perinatal outcome of late preterm SGA neonates.

Methods: We conducted a retrospective cohort study of all women carrying a singleton gestation who had late preterm delivery (34–36 gestational weeks) of SGA neonates at a single tertiary university-affiliated medical center (July 2012–December 2017). Exclusion criteria included termination of pregnancy, intrauterine fetal death, and birth weight ≥ 10th percentile. Outcomes were compared between ACS and non-ACS treatment prior to delivery. Neonatal composite outcome included neonatal intensive care unit (NICU) admission, respiratory distress syndrome, mechanical ventilation, and transient tachypnea.

Results: Overall, 228 women met inclusion criteria; 102 (44.7%) received ACS and 126 did not (55.3%). Median birth weight among the non-ACS group was significantly higher (1896.0 vs. 1755.5 grams P < 0.001). Rates of NICU and jaundice requiring phototherapy were higher among the ACS group (53.92% vs. 31.74%, P = 0.01; 12.74% vs. 5.55%, P = 0.05, respectively). Composite neonatal outcome was significantly higher among the ACS group (53.92% vs. 32.53%, odds ratio [OR] 2.42, 95% confidence interval [95%CI] 1.41–4.15, P = 0.01). After adjustment for potential confounders, this association remained significant (OR 2.15, 95%CI 1.23–3.78, P = 0.007).

Conclusions: ACS given during pregnancy did not improve respiratory outcome for SGA late preterm neonates. ACS may be associated with a worse outcome.

Background: Congestive heart failure (CHF) with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF) is a common diagnosis in patients hospitalized in the department of internal medicine. Recently, the therapeutic regimens were updated, as the sodium-glucose cotransporter-2 (SGLT2) inhibitors became an integral part of the therapeutic regimen for either HFrEF or HFpEF.

Objectives: To define the demographic and clinical characteristics of CHF patients hospitalized in the department of medicine.

Methods: We conducted a retrospective cohort study that included all patients hospitalized in the departments of medicine at the Rabin Medical Center, Israel, between 2016 and 2019. Demographic and clinical background, in-hospital procedures, discharge regimens, and outcome parameters were evaluated according to HFrEF/HFpEF.

Results: The cohort included 4458 patients. The majority (97%) presented with a preexisting diagnosis, whereas HF was an active condition in only half of them. The rates of HFrEF/HFpEF were equal. In most cases, the trigger of the exacerbation could not be determined; however, infection was the most common cause. There were basic differences in the demography, clinical aspects, and therapeutic regimens at discharge between HFrEF and HFpEF. Both conditions were associated with high in hospital mortality (8%) and re-admissions rates (30 days [20%], 90 days [35%]) without any difference between them.

Conclusions: HFrEF/HFpEF patients differed by demographics and co-morbidities. They were equally represented among patients admitted to medical wards and had similar prognosis. For both diagnoses, hospitalization should be considered for updating therapeutic regimens, especially with SGLT2 inhibitors.

Migraine is very common headache disorder, usually starting at a young age with a higher prevalence in females. In this narrative review, we summarize the prevalence, burden, and socio-demographic characteristics of migraineurs worldwide and specifically in Israel. We searched standard electronic bibliographic databases, including MEDLINE (via PubMed), Embase, Google Scholar, and Up to Date using combinations of search terms and reviewed the articles we found. The factors reviewed included prevalence and incidence, burden, sex differences, age distribution, cognitive function, socioeconomic status, religion, country of origin, and urban vs. rural dwelling.

A review of the literature on the effect of immune modulation on the skeleton shows disappointing results.

Background: Little is known about phenotypical variations among ethnic groups in patients with Parkinson's disease (PD) in Israel. Clinical characteristics of non-Ashkenazi Jews (NAJ) are scantly described.

Objectives: To describe clinical aspects of PD in ethnic groups in Israel, focusing on NAJ and Ashkenazi Jews (AJ).

Methods: In this cross-sectional retrospective study, we collected demographic, genetic, and clinical characteristics of patients from different ethnic Jewish backgrounds. Ethnic groups included AJ; North African Jews (NAFJ); oriental Jews (OJ) originating from Iran, Iraq, and Buchara; Balkan Jews; Yemenite Jews (YJ); and Jews of mixed origin. Clinical characteristics included hyposmia, urinary complaints, constipation, and rapid eye movement sleep behavioral disorder. Cognitive complaints, motor features, levodopa-induced dyskinesia, and motor fluctuations were collected. Motor part of the MDS-UPDRS and Hoehn and Yahr scores were collected.

Results: The study comprised 174 PD Jewish patients (63.2% AJ, 56.4% males). The age at onset was 65.3 ± 10.2 years; 106 patients (60.9%) were genotyped (17 glucocerebrosidase [16.0%], 13 leucine-rich repeat kinase 2 [LRRK2] [12.3%]). Rates of hyposmia were significantly higher in AJ than NAJ (56.6% vs. 39.5%, respectively, P = 0.003). No significant differences were found in motor features in all variables. Of 13 AJ patients carrying the LRRK2 mutation, only one had hyposmia. Three patients with LRRK2 were NAJ.

Conclusions: Hyposmia is less prevalent in PD patients of NAJ origin than in AJ. The rate of hyposmia in NAFJ patients is particularly low. The rate of other non-motor features is similar between NAJ and AJ patients.

Background: Morbidly adherent placentation (MAP) increases the risk for obstetric hemorrhage. Cesarean hysterectomy is the prevalent perioperative approach. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive and relatively simple endovascular procedure to temporarily occlude the aorta and control below diaphragm bleeding in trauma. It has been effectively used to reduce obstetric hemorrhage.

Objectives: To evaluate whether REBOA during cesarean delivery (CD) in women with morbidly adherent placentation is a safe and effective treatment modality.

Methods: We introduced REBOA for CD with antepartum diagnosis of MAP in 2019 and compared these patients (RG) to a standard approach group (SAG) treated in our center over the preceding year, as a control. All relevant data were collected from patient electronic files.

Results: Estimated blood loss and transfusion rates were significantly higher in SAG; 54.5% of SAG patients received four RBC units or more vs. one administered in RG. No fresh frozen plasma, cryoprecipitate, or platelets were administered in RG vs. mean 3.63, 6, and 3.62 units, respectively in SAG. Ten SAG patients (90.9%) underwent hysterectomy vs. 3 RG patients (30%). Five SAG patients (45%) required post-surgical intensive care unit (ICU) admission vs. no RG patients. Bladder injury occurred in five SAG cases (45%) vs. 2 RG (20%). One RG patient had a thromboembolic event. Perioperative lactate levels were significantly higher in SAG patients.

Conclusions: Use of REBOA during CD in women with MAP is safe and effective in preventing massive bleeding, reducing the rate of hysterectomy, and improving patient outcome.

The health of survivors of the Shoah has been investigated, both at early and late stages in their lives. There have been findings of multiple morbidities, but survivors have enjoyed slightly prolonged longevity when compared to the general population [1]. Less attention has been granted to investigations and descriptions of illnesses that presented inside the ghettos and the Nazi camps. Some of the surviving records from those sites have yet to be interpreted. Documented diagnoses of both insulin dependent and mature onset diabetes mellitus and of malignancy has been conspicuously absent. We present our meta-analysis and interpretations of surviving medical documents covering a large population of prisoners from a range of ghettos and concentration camps and specifically note the absence of recorded incidence of malignancy and a relatively low incidence of diabetes mellitus.

Background: Acute coronary syndrome (ACS) represents a spectrum of ischemic myocardial disease including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Various prognostic scores were developed for patients presenting with NSTEMI-ACS. Among these scores, the GRACE risk score offers the best discriminative performance for prediction of in-hospital and 6-month mortality. However, the GRACE score is limited and cannot be used in several ethnic populations. Moreover, it is not predictive of clinical outcomes other than mortality.

Objective: To assess the prognostic value of traditional cardiovascular risk factors and laboratory biomarkers in predicting 6-month major adverse cardiac and cerebrovascular events (MACCE), including hospitalization, recurrent percutaneous coronary intervention (PCI), stroke, and cardiovascular mortality in patients with NSTEMI treated with PCI.

Methods: This retrospective study included consecutive patients admitted with an initial diagnosis of NSTEMI to the cardiac intensive care unit (CICU) at the Tzafon Medical Center, Israel, between April 2015 and August 2018 and treated by PCI within 48 hours of admission.

Results: A total of 223 consecutive patients with NSTEMI treated by PCI were included in the study. Logarithm_ebrain natriuretic peptide (LogₑBNP), prior MI, and Hb levels were found to be significant predictors of any first MACCE. Only logₑBNP was found to be an independent predictor of a first MACCE event by multivariate logistic regression analysis.

Conclusions: LogₑBNP is an independent predictor of worse prognosis in patients with NSTEMI. Routine evaluation of BNP levels should be considered in patients admitted with NSTEMI.