Israel Medical Association Journal

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

Background: Coronary heart disease (CHD) patients are considered high cardiovascular risks. Guidelines recommend low-density lipoprotein cholesterol (LDL-C) target levels below 55 mg/dl with > 50% reduction from baselines. These levels can be reached by a combination of statins, ezetimibe, and anti-protein convertase subtilisin/kexin type 9 (anti-PCSK9) agents. Our clinical impression was that CHD patients do not reach LDL-C target levels, despite the wide availability.

Objectives: To evaluate whether hospitalization would result in changes in lipid lowering regimens and short-term compliance.

Methods: We conducted a retrospective cohort study using data of CHD patients who were admitted to internal medicine wards at Clalit Health Services medical centers because of anginal syndrome during 2020–2022. The data were evaluated for demographic and clinical characteristics; LDL-C level at admission, 6 months previously, and 3 months and 6–9 months after discharge; rates of reaching LDL-C target levels; and lipid lowering treatment at admission, discharge, and 6–9 months after.

Results: The cohort included 10,540 patients. One-third and three-quarters did not have lipids level measurements up to 6 months before and during hospitalization, respectively. Only one-fifth of the patients reached LDL-C values before and during admission (median LDL-C 72 mg/dl; range 53–101). Approximately half were treated with high-dose potent statins. Only 10% were treated with ezetimibe. Hospitalization did not have a clinically significant effect on short-term lipid lowering treatment or LDL-C levels.

Conclusions: Gaps were noted between guidelines and clinical practice for reaching LDL-C target levels. Further education and strict policy are needed.

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%).

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.

Background: Left ventricular assist devices (LVAD) are a staple element in contemporary treatment of advanced heart failure. LVAD surgeries are mostly done in heart transplantations centers, as a destination therapy or as a bridge to heart transplantation.

Objectives: To describe our step-by-step experience in establishing and implementing a new LVAD program in a non-heart transplant center. To give insight to our short- and long-term results of our first 25 LVAD patients.

Methods: Preliminary steps included identifying the need for a new program and establishing the leading team. Next is defining protocols for pre-operative evaluation, operating room, post-operative management, and outpatient follow-up. The leading team needs to educate other relevant units in the hospital that will be involved in the care of these patients. It is essential to work in collaboration with a heart transplant center from the very beginning. Patient selection is of major importance especially in the early experience. Initially “low risk” patients should be enrolled.

Results: We describe our first 25 LVAD patients. Our first five patients all survived beyond 2 years, with no major complications. Overall, there was one operative death due to massive GI bleeding. There were four late deaths due to septic events.

Conclusions: Establishing a new LVAD program can be successful also with small- and medium-size programs. With careful and meticulous planning LVAD implantation can be extended to more centers thus offering an excellent solution for advanced heart failure patients.

Among patients admitted with acute decompensated heart failure (ADHF), deterioration of renal function with resulting acute kidney injury (AKI) is reported in up to 70% of patients with cardiogenic shock. Twenty percent of heart failure patients with AKI progress to dialysis (AKI-D). Optimal timing for initiation of renal replacement therapies (RRT) has been researched; however, minimal studies discuss guidelines for weaning from RRT [1]. Electronic monitoring of urine output (UO) may serve as a tool to aid in withdrawal from RRT. We present a case of ADHF with severe AKI requiring continuous renal replacement therapy (CRRT) where real-time electronic monitoring of UO was implemented for the first time to guide de-escalation therapy from CRRT until successful withdrawal.

Background: Long-term support with a HeartMate 3 (HM3) left ventricular assist device (LVAD) has improved outcomes of patients with end-stage heart failure. However, there is a paucity of data on the outcomes of patients who underwent concomitant cardiac surgical procedure (CCSP) during HM3-LVAD implantation.

Objectives: To assess our single-center experience with patients who underwent CCSP during the implantation of an HM3-LVAD.

Methods: From December 2016 until April 2022, 131 adult patients underwent HM3-LVAD implantation. A total of 23 patients underwent CCSP during the HM3-LVAD implantation+CCSP, and 108 underwent only HM3-LVAD implantation (HM3-only).

Results: The median age was 59 ± 11 years (range 54-67), 82% (n=108) were male, and 76% (n=100) were implanted as a bridge-to-transplant. The concomitant procedures performed during the implantation included 8 aortic valve repairs/replacements, 14 tricuspid valve repairs, 4 patent foramen ovales or atrial septal defect closures, and 3 other cardiac procedures. The mean cardiopulmonary bypass time was 113 ± 58 minutes for the HM3-only group and 155 ± 47 minutes for the HM3+CCSP group (P = 0.007). The mortality rates at 30 days, 6 months, and 12 months post-implantation were 2 (9%), 5 (22%), and 6 (26%) respectively for the HM3+CCSP group, and 7 (6%), 18 (17%), and 30 (28%) for the HM3-only group (P = 0.658, 0.554, and 1.000).

Conclusions: Our experience demonstrated no significant difference in the 30-day, 6-month, and 12-month mortality rates for patients who underwent a CCSP during HM3-LVAD implantation compared to patients who did not undergo CCSP during HM3-LVAD implantation.

Background: Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult. Unnecessary antibiotic use contributes to unwanted side effects, such as allergic reactions and diarrhea. It also may increase antibiotic resistance. 

Objectives: To evaluate the effect of a machine learning algorithm on the clinical evaluation of bacterial pharyngitis in children.

Methods: We assessed 54 children aged 2–17 years who presented to a primary healthcare clinic with a sore throat and fever over 38°C from 1 November 2021 to 30 April 2022. All children were tested with a streptococcal rapid antigen detection test (RADT). If negative, a throat culture was performed. Children with a positive RADT or throat culture were considered GAS-positive and treated antibiotically for 10 days, as per guidelines. Children with negative RADT tests throat cultures were considered positive for viral pharyngitis. The children were allocated into two groups: Group A streptococcal pharyngitis (GAS-P) (n=36) and viral pharyngitis (n=18). All patients underwent a McIsaac score evaluation. A linear support vector machine algorithm was used for classification.

Results: The machine learning algorithm resulted in a positive predictive value of 80.6 % (27 of 36) for GAS-P infection. The false discovery rates for GAS-P infection were 19.4 % (7 of 36).

Conclusions: Applying the machine-learning strategy resulted in a high positive predictive value for the detection of streptococcal pharyngitis and can contribute as a medical decision aid in the diagnosis and treatment of GAS-P.

Hearing and vestibular function may be affected by gout and/or hyperuricemia. We performed a systematic review of the literature on ear involvement in patients with gout and hyperuricemia. We selected 24 articles: 8 case reports and 16 original articles. Case reports mainly focused on the presence of tophi in the middle ear, which was resolved with surgical treatment. Seven articles studied the hearing function in relationship to serum uric acid and 10 articles studied the occurrence of vertigo, with one of them studying both aspects. Regarding results on vertigo, five studies showed an association with uric acid elevation, three with lowering of uric acid, and two found no differences. Concerning hearing loss, five studies detected poor hearing function in association with high uric acid levels while other two did not.) Most of the studies showed an association of hearing loss with high uric acid/gout. Regarding vestibular function, the results are too heterogeneous to make any conclusions.

Since the introduction of the international study group (ISG) criteria for the diagnosis of Behçet's disease (BD) in the early 1990s by Yazici and colleagues [1] and the international criteria for BD (ICBD) by Davatchi and colleagues in 2014 [2], great progress has been achieved in the diagnosis of BD with fairly high sensitivity and specificity rates. However, a small, but very challenging and unique minority might not fulfill these criteria, at least at presentation. These patients are most challenging as they may present with life-threatening vascular or neurological manifestations. If the diagnosis BD is delayed, the risk for morbidity and even mortality might be increased. Therefore, we should aim for early diagnosis and prompt treatment.

Background: Hypothermia, as a sign of serious bacterial infection (SBI) in children and infants older than 90 days is poorly characterized, especially in the post-pneumococcal vaccine era.

Objectives: To assess the prevalence of SBI in children and infants presenting to the pediatric emergency department (PED) with reported or documented hypothermia.

Methods: Retrospective data analysis was conducted of all well-appearing children aged 0–16 years who presented with a diagnosis of hypothermia at two tertiary PEDs from 2010 to 2019.

Results: The study comprised 99 children, 15 (15.2%) age 0–3 months, 71 (71.7%) 3–36 months, and 13 (13.1%) > 36 months. The youngest age group had increased length of stay in the hospital (P < 0.001) and increased rates of pediatric intensive care unit admissions (P < 0.001). Empirical antibiotic coverage was initiated in 80% of the children in the 0–3 months group, 21.1% in the 3–36 months group, and 15.4% in > 36 months (P < 0.001). Only one case of SBI was recorded and no bacteremia or meningitis. Hypothermia of unknown origin was the most common diagnosis in all age groups (34%, 42%, 46%), respectively, followed by bronchiolitis (26%) and hypoglycemia (13.3%) for 0–3 month-old children, unspecified viral infection (20%) and otitis media (7%) for 3–36-month old, and unspecified viral infection (23%) and alcohol intoxication (15.2%) in > 36 months.

Conclusion: There is a low incidence of SBI in well-appearing children presenting to the PED with hypothermia and a benign course and outcome in those older than 3 months.

Takotsubo syndrome (TTS) or Takotsubo cardiomyopathy (TCM) is a cardiomyopathy that develops rapidly and is usually caused by mental or physical stress. It is usually a transient cardiomyopathy. The presumed cause of the onset of the syndrome is the increase and extreme secretion of adrenaline and norepinephrine due to extreme stress. An infectious disease such as sepsis can also be the cause [1].

One of the most widespread diagnostic tools is the revised version of Mayo Clinic Diagnostic Criteria for TTS (2008) [2], which incorporates transient wall-motion abnormalities, absence of a potential coronary culprit, myocarditis, and pheochromocytoma. The prognosis for TTS is usually favorable and resolves with complete recovery in 4–8 weeks in more than 90% of patients.

Since 1980 dermatologists have been interested in the exceptional healing reported by patients who underwent treatments at the Dead Sea. Tens of thousands of patients have visited this area and more than 10,000 cases have been the subject of clinical and laboratory studies since this natural therapeutic option was discovered for psoriasis management. Through evaluation of the published articles on climatotherapy, we tried to reach a global assessment of the usefulness of this approach and to discover whether this treatment still can be recommended in the era of biologic treatments. I conducted a review of the available literature on clinical trials through PubMed, Medline, and Google Scholar using the terms psoriasis and Dead Sea. I found 26 studies published between 1982 and 2021. Assessment of patients showed major improvement through several selected parameters. Length of the stay and medical supervision positively influenced the major outcomes observed. Duration of improvement and possible long-term side effects of this natural treatment still need to be more precisely determined. Exposure to the unique climatic factors of the region, essentially the sun and the sea, induces fast and significant results with high clearance rates of psoriasis plaques. Dead Sea climatotherapy still has its place for the control of psoriasis symptoms.

In this special issue of Israel Medical Association Journal (IMAJ) we expose readers to the topic of artificial intelligence (AI) in medicine. AI has become a powerful tool, which enables healthcare professionals to personalize treatment based on many factors, including genetic analyses of tumors, and to consider other co-morbidities affecting a specific patient. AI gives physicians the ability to analyze huge amounts of data and to combine data from different sources. AI can be implemented make a diagnosis based on computed tomography (CT) scans and magnetic resonance imaging (MRI) scans using deep machine learning and data that are stored in the memory of mega computers. AI assists in tailoring more precise surgery to train surgeons before surgery and to support surgeons during procedures. This advancement may benefit surgical procedures by making them more accurate and faster without cutting unnecessary tissues (e.g., nerves and blood vessels); thus, patients face fewer complications, lower rates of infection, and more operation theater time. In this issue, we include three original studies that describe the use of AI in academia and eight review articles that discuss applications of AI in different specialties in medicine. One of the review articles addresses ethical issues and concerns that are raised due to the more advanced use of AI in medicine.

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.