Israel Medical Association Journal

Background: The field of artificial intelligence (AI) is poised to significantly influence the future of medicine. With the accumulation of vast databases and recent advancements in computer science methods, AI's capabilities have been demonstrated in numerous areas, from diagnosis and morbidity prediction to patient treatment. Establishing an AI research and development unit within a medical center offers multiple advantages, particularly in fostering research and tapping into the immediate potential of AI at the patient's bedside.

Objectives: To outline the steps taken to establish a center for AI and big data within an innovation center at a tertiary hospital in Israel.

Methods: We conducted a retrospective analysis of projects developed in the field of AI at the Artificial Intelligence Center at the Rabin Medical Center, examining trends, clinical domains, and the predominant sectors over a specific period.

Results: Between 2019 and 2023, data from 49 AI projects were gathered. A substantial and consistent growth in the number of projects was observed. Following the inauguration of the Artificial Intelligence Center we observed an increase of over 150% in the volume of activity. Dominant sectors included cardiology, gastroenterology, and anesthesia. Most projects (79.6%) were spearheaded by physicians, with the remainder by other hospital sectors. Approximately 59.2% of the projects were applied research. The remainder were research-based or a mix of both.

Conclusions: Developing technological projects based on in-hospital medical data, in collaboration with clinicians, is promising. We anticipate the establishment of more centers dedicated to medical innovation, particularly involving AI.

Artificial intelligence (AI) has emerged as a transformative group of technologies in the field of medicine. Specifically in cardiology, numerous applications have materialized, and these are developing exponentially. AI-based risk prediction models leverage machine learning algorithms and large datasets to probe multiple variables, aid in the identification of individuals at high risk for adverse events, facilitate early interventions, and enable personalized risk assessments. Unique algorithms analyze medical images, such as electrocardiograms, echocardiograms, and cardiac computed tomography scans to enable rapid detection of abnormalities and aid in the accurate identification of cardiac pathologies. AI has also shown promise in guiding treatment decisions during coronary catheterization. In addition, AI has revolutionized remote patient monitoring and disease management by means of wearable and implantable sensing technologies. In this review, we discussed the field of cardiovascular genetics and personalized medicine, where AI holds great promise. While the applications of AI in cardiology are promising, challenges such as data privacy, interpretability of the findings, and multiple matters regarding ethics need to be addressed. We presented a succinct overview of the applications of AI in cardiology, highlighting its potential to revolutionize risk prediction, diagnosis, treatment, and personalized patient care.

In recent years, we have been experiencing a technological revolution, which signifies an ethical and societal transformation. Artificial intelligence (AI) based technologies have gradually permeated all aspects of life and solidified their position. Within this context, the emergence of these technologies offers new opportunities in the medical field, including palliative care, which is aimed at alleviating suffering and improving the quality of life for terminally ill patients and their families. In Israel, the Dying Patient Act of 2005 (the law), which promotes values such as the sanctity of life and individual autonomy, allows terminally ill patients to determine their preferred treatment, and withhold life-saving treatment under certain circumstances. The law represents a significant step toward improving care for terminally ill patients, reducing pain and suffering, and respecting the patient's wishes and worldviews in their final days. However, the practical implementation of the law has encountered numerous challenges, ranging from lack of familiarity among doctors and healthcare professionals and the requirement to determining life expectancy to fulfilling the law's purpose. These challenges are associated with ethical, cultural, and religious perspectives. In this article, we describe how AI-based technologies hold immense potential in applying the law and providing palliative care based on their predictive capabilities, prognostic accuracy, and optimization of treatment as well as communication between patients and healthcare providers. However, as an innovative, developing, and complex technology, it is crucial not to overlook the ethical, societal, and legal challenges inherent in implementing and using AI-based technologies in the context of palliative care.

Background: Small left atria (LA) is associated with an increased risk of mortality.

Objectives: To determine whether the attributed risk of mortality is influenced by the underlying etiologies leading to decreased volumes.

Methods: We retrospectively evaluated patients with an available LA volume index (LAVI) as measured by echocardiography who came to our institution between 2011 and 2016. Individuals with small LA (LAVI < 16 ml/m²) were included and divided according to the etiology of the small LA (determined or indeterminate) and investigated according to the specific etiology.

Results: The cohort consisted of 288 patients with a mean age of 56 ± 18 years. An etiology for small LA was determined in 84% (n=242). The 1-year mortality rate of the entire cohort was 20.5%. Patients with indeterminate etiology (n=46) demonstrated a lower mortality rate compared with determined etiologies (8.7% vs. 22.7%, P = 0.031). However, following propensity score adjustments for baseline characteristics, there was no significant difference between the groups (P = 0.149). The only specific etiology independently associated with 1-year mortality was the presence of space occupying lesions (odds ratio 3.26, 95% confidence interval 1.02–10.39, P = 0.045).

Conclusions: Small LA serve as a marker for negative outcomes, and even in cases of undetected etiology, the prognosis remains poor. The presence of small LA should alert the physician to a high risk of mortality, regardless of the underlying disease.

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.

Ruxolitinib is an inhibitor of the cytosolic tyrosine kinase Janus kinase (JAK) family of proteins (JAK1/2), which is widely used to treat various myeloid neoplasms that are characterized by constant activation of the JAK-STAT signaling pathway.

Many side effects are associated with ruxolitinib, including anemia, thrombocytopenia, increased rate of infections (especially herpes zoster), and mild hypercalcemia noted in 15.4% of patients [1]. The possible mechanism causing hypercalcemia may involve altered bone and mineral metabolism with secondary hyperparathyroidism, as described for other kinase inhibitors [2].

Background: Severe asthma affects up to 20,000 citizens of Israel. Novel biological therapies, which individually have been proven to reduce asthma morbidity in clinical trials, have become available in recent years. Comparative data among different drugs are scarce.

Objectives: To describe and compare the clinical outcomes of biological therapies in severe asthma patients treated at Shamir Medical Center.

Methods: We conducted a cohort study based on a review of cases treated with monoclonal antibodies for severe asthma at our center. Data were extracted for demographics, eosinophil count, lung function (FEV1), exacerbation rate, and median dose of oral prednisone. Between-drug comparison was conducted by repeated measures ANOVA.

Results: The cohort included 62 patients receiving biological therapy. All biologic drugs were found to reduce exacerbation rate [F(1, 2) = 40.4, P < 0.0001] and prednisone use [F(1, 4) = 16, P < 0.001] significantly. ANOVA revealed no difference of efficacy endpoints between the different drugs. Eosinophil count was significantly reduced post-biologic treatment in the anti-interleukin-5 agents (P < 0.001) but not under treatment with omalizumab and dupilumab.

Conclusions: All of the biological therapies were effective for improving clinical outcomes. None of the agents was clearly superior to any other. These data emphasize the need for severe asthma patients to be seen by pulmonary medicine specialists and offered, where appropriate, biological therapies.

Background: Benign tracheal stenosis has emerged as a therapeutic challenge for physicians involved in the care of survivors of critical care units. Although the traditional mainstay of open surgical reconstructive treatment is still considered the gold standard, endoscopic therapies such as laser re-canalization, balloon dilation, or stenting are commonly practiced in invasive bronchology. Recurrent obstructing granulomas pose a challenge for bronchoscopists. Mitomycin C (MyC) is a cytotoxic agent that is isolated from Streptomyces caespitosus and acts by inhibiting DNA and RNA synthesis through alkylation and cross-linkages. Topical MyC is commonly used in indirect laryngoscopies for the treatment of granulation tissue in the trachea by using saturated pledgets.

Objectives: To describe fiberoptic bronchoscopic submucosal injection of MyC as a treatment for recurrent bening tracheal stenosis.

Methods: The authors report their successful experience with submucosal intralesional injection of MyC in the management of recurrent obstructing granulomas/stenosis using the flexible fiberoptic bronchoscope in a series of 10 patients between 2005 and 2019.

Results: The results suggest that intralesional injection of MyC using the flexible bronchoscope after the endoscopic treatment of the stenotic lesion may reduce the rate of subsequent formation of granulation tissue and scarring without side effects.

Conclusions: The efficacy of MyC injection should be studied prospectively.

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

Background: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment.

Objectives: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development.

Methods: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD.

Results: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e’ septal (P < 0.001).

Conclusions: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment

Background: The effect of weight reduction following bariatric surgery is already well known.

Objectives: To investigate the effects of abdominoplasty on metabolic markers indicative of weight loss.

Methods: The authors prospectively enrolled consecutive obese patients after laparoscopic sleeve gastrectomy. They were candidates for post-bariatric surgery abdominoplasty. The authors measured metabolic markers one day prior to surgery, 24 hours after, and 3 months following surgery. They recorded medical and demographic parameters.

Results: Sixteen patients were recruited for participation in the study. Mean age was 47 years and 88% of the patients were female. Bariatric surgery achieved a mean decline in body mass index of 13.8 kg/m². All patients underwent abdominoplasty. Leptin and insulin levels were slightly increased at 3 months postoperative. No significant changes were observed in glucose, hemoglobin, or triglycerides throughout the study.

Conclusions: In a cohort of obese patients undergoing laparoscopic sleeve gastrectomy followed by abdominoplasty, no significant changes were noted in a patient’s metabolic profiles. The results suggest that abdominoplasty has no effect on the metabolic markers tested in contrast to other reports; however, the cosmetic, behavioral, and psychological advantages of abdominoplasty are well established.

Background: C-reactive protein (CRP) blood level is associated with clinical outcomes of several diseases. However, the independent predictive role of CRP in the heterogeneous population of patients admitted to internal medicine wards is not known. 

Objectives: To determine whether single CRP levels at admission independently predicts clinical outcome and flow of patients in general medicine wards.

Methods: This study comprised 275 patients (50.5% female) with a mean age of 68.25 ± 17.0 years, hospitalized with acute disease in a general internal medicine ward. The association between admission CRP levels and clinical outcomes including mortality, the need for mechanical ventilation, duration of hospitalization, and re-admission within 6 months was determined.

Results: A significant association was found between CRP increments of 80 mg/L and risk for the major clinical outcomes measured. The mortality odds ratio (OR) was 1.89 (95% confidence interval (95%CI, 1.37–2.61, P < 0.001), mechanical ventilation OR 1.67 (95%CI, 1.10–2.34, P = 0.006), re-admission within 6 months OR 2.29 (95%CI, 1.66–3.15 P < 0.001), and prolonged hospitalization >7 days OR 2.09 (95%CI, 1.59–2.74, P < 0.001). Lower increments of10 mg/L in CRP levels were associated with these outcomes although with lower ORs. Using a stepwise regression model for admission CRP levels resulted in area under the receiver operating characteristics curves between 0.70 and 0.76 for these outcomes.

Conclusions: A single admission CRP blood level is independently associated with major parameters of clinical outcomes in acute care patients hospitalized in internal medicine wards.

Background: The MitraClip procedure is becoming an acceptable alternative for high-risk patients with mitral regurgitation (MR) due to functional (FMR) or degenerative (DMR) disease and suitable mitral anatomy.

Objectives: To evaluate the results of MitraClip at our institute in carefully selected patients.

Methods: We conducted a retrospective analysis of medical records and echocardiography data from January 2012 to December 2017.

Results: A total of 39 MitraClip procedures in 37 patients (aged 75 ± 12 years, 9 women) was performed. Twenty-four patients presented with FMR, 12 with DMR, and 1 with combined pathology. One-day post-procedure MR was moderate to low in 86.1% of patients, with immediate device success in 88.8%. MR at 1 year was moderate to low in 79% at 1 year. Survival at 1 year was 86% and at 2 years 69.4%. Peri-procedural (< 1 week) death and MitraClip failure occurred in one and three patients, respectively. New York Heart Association score improved to class 1 or 2 in 37% of patients at 1 year vs. one patient at baseline. Post-procedural systolic pulmonary pressure was reduced from 53 (range 48–65) to 43 (range 36–52) mmHg at 1 month with a subsequent plateau at follow-up, to 41 (34–57) mmHg at 6 months, and to 47 (38–50) at 12 months.

Conclusions: MitraClip in severe MR resulted in modest improvement in functional status and pulmonary pressure with a small risk of immediate procedural complications. Outcomes are encouraging considering the natural course of MR and the risks of surgical intervention.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) (such as canagliflozin, empagliflozin, and dapagliflozin) are widely used to treat patients with type 2 diabetes mellitus (T2DM) to improve glycemic, cardiovascular and renal outcomes. However, based on post-marketing data, a warning label was added regarding possible occurrence of acute kidney injury (AKI).

Objectives: To describe the clinical presentation of T2DM patients treated with SGLT2i who were evaluated for AKI at our institution and to discuss the potential pathophysiologic mechanisms.

Methods: A retrospective study of a computerized database was conducted of patients with T2DM who were hospitalized or evaluated for AKI while receiving SGLT2i, including descriptions of clinical and laboratory characteristics, at our institution.

Results: We identified seven patients in whom AKI occurred 7–365 days after initiation of SGLT2i. In all cases, renin-angiotensin-aldosterone system blockers had also been prescribed. In five patients, another concomitant nephrotoxic agent (injection of contrast-product, use of nonsteroidal anti-inflammatory drugs or cox-2 inhibitors) or occurrence of an acute medical event potentially associated with AKI (diarrhea, sepsis) was identified. In two patients, only the initiation of SGLT2i was evident. The mechanisms by which AKI occurs under SGLT2i are discussed with regard to the associated potential triggers: altered trans-glomerular filtration or, alternatively, kidney medullary hypoxia.

Conclusions: SGLT2i are usually safe and provide multiple benefits for patients with T2DM. However, during particular medical circumstances, and in association with usual co-medications, particularly if baseline glomerular filtration rate is decreased, patients treated with SGLT2i may be at risk of AKI, thus warranting caution when prescribed.

Background: Sonographic assessment of the fetal kidneys is an integral part of the prenatal anatomical survey.

Objectives: To evaluate the fetal renal to abdominal (RTA) ratio throughout pregnancy and to investigate whether this ratio can be a potential diagnostic landmark for congenital anomalies of the kidney and urinary tract (CAKUT).

Methods: Measurements of the anterior-posterior diameters of the fetal kidney and fetal abdomen (APAD) were obtained prospectively. The RTA was calculated as the ratio between them in in two groups: normal population vs. CAKUT cases. RTA in CAKUT cases was compared to RTA in a normal population.

Results: The study group was comprised of 210 women. The mean gestational age for the fetuses was 31 ± 5.6 weeks (range 14–40 weeks). Fetal RTA ratio was found to be 0.28 ± 0.03 throughout pregnancy from early second trimester to term, with high reproducibility of measurements. During the study period the RTA was evaluated in nine cases referred for suspected CAKUT. All cases demonstrated a different ratio according to the renal anomaly. High ratio was observed in one case of overgrowth syndrome (Beckwith Wiedenmann syndrome; 0.47), three cases of infantile polycystic kidney (0.45–0.47), and three cases of a solitary kidney (0.31–0.35), while cases of dysplastic kidneys revealed a low ratio (0.14–0.18).

Conclusions: Prenatal RTA ratio is constant throughout gestation. An abnormal ratio should lead to meticulous renal investigation to rule out kidney disease.