Israel Medical Association Journal

Background: Wilson disease (WD) is an autosomal recessive disease characterized by a defect in hepatocellular copper transport with a wide spectrum of clinical manifestations and reported prevalence.

Objectives: To study the epidemiology and clinical manifestations of WD between two ethnic groups, Jewish and Bedouins, with different marriage patterns, in southern Israel.

Methods: We conducted a retrospective study investigating the clinical course and laboratory characteristics of children diagnosed with WD who were treated at Soroka University Medical Center.

Results: Sixteen patients were diagnosed between 2000 and 2021 (8 males, 50%), 14 were of Bedouins origin. The total cohort prevalence was 1:19,258 while the prevalence of the disease was significantly higher among Bedouins compared to Jews (1:10,828 vs.1:78,270, P-value = 0.004). The median age at diagnosis was 10.2 years, without a significant difference between the groups. The most common presenting symptom was hepatic manifestations: 81.2% had elevated transaminases, 12.5% had jaundice, 25% had neurological symptoms, one had a Kayser-Fleischer ring, and one had psychosis. The mean ceruloplasmin level was 3.0 mg/dl. During follow-up, nine patients normalized transaminases with treatment, while three required liver transplantation. There was no significant difference in the clinical presentation and disease course between the two ethnic groups.

Conclusions: Our cohort showed a high prevalence of WD compared to previous studies, especially among the Bedouin population, which has a high consanguinity rate. The prognosis of WD in our population is similar to other studies and depends mainly on treatment compliance.

Background: Cardiovascular disease (CVD) events are rare in premenopausal women. Nevertheless, women with depression have a higher prevalence of CVD. Patients with depression present with endothelial dysfunction and impaired ability to regenerate endothelial progenitor cells (EPCs).

Objectives: To understand the association between depression and CVD, especially in young women.

Methods: We collected peripheral blood samples from 30 premenopausal women diagnosed with major depression and 28 aged-matched healthy women. From these blood samples, we extracted RNA and conducted RNA sequencing to obtain comprehensive gene expression profiles. Gene expression analysis was performed to identify differences between the two groups.

Results: We detected 6540 differentially expressed genes between the two groups, of which 5577 were downregulated and 963 up regulated. Of these genes, we detected a significant decrease of CD144 (VE-Cadherin) (P = 0.0001), CD146 (MCAM) (P = 0.0001) and CD133 (PROM1) (P = 0.00009), all known to enhance EPCs and regeneration of damaged blood vessels. A significant increase was found in the expression of CD31 (PECAM1) (P = 0.0003) and CD45 (PTPRC) (P = 0.00001), both known to promote atherogenesis and thrombogenesis with platelet and T lymphocyte activation.

Conclusions: Young premenopausal women with depression had an impaired ability to grow colony forming units of endothelial progenitor cells (CFU-EPCs). Young women with depression are more vulnerable genetically to develop CVD because of the downregulated genes of the stem cells endothelial vascular regeneration and upregulation of genes coding for platelet and T lymphocyte activation, thus accelerating the atherosclerotic and atherothrombotic pathway.

Rehabilitation plays a crucial role in improving clinical outcomes for cardiac patients. The accessibility of traditional cardiac rehabilitation programs is often hindered by factors such as cost and geographical distance. In recent years, wearable monitor-based remote rehabilitation has emerged as a potential solution to improve accessibility. In this systematic review, we assessed the recent literature on remote cardiac rehabilitation utilizing wearable monitors. We conducted a comprehensive literature review using the MEDLINE database, focusing on all studies published in English until June 2023. The search utilized the keywords cardiac rehabilitation and remote monitoring to identify relevant studies on clinical outcomes, wellbeing, and adherence. Filters were applied to include human subjects only. Reviews, meta-analyses, and systematic reviews were used to expand the search, but excluded from the primary selection process. A total of 14 relevant papers were included following the selection process: nine randomized controlled trials and five cohort studies. The synthesis of articles found that remote cardiac rehabilitation monitored by wearable devices is as safe and effective as conventional rehabilitation and more effective than medical observation only. In addition, it enhances the availability of cardiac rehabilitation in cases of limited accessibility. Several limitations require further research including expanding the demographic diversity of the participants and improving the ease of use of the technology. While remote cardiac rehabilitation monitored by wearable devices shows promise, further research is needed to expand the participant pool and refine the wearable monitor technology's usability.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive, soft-tissue sarcoma. The treatment is surgical and includes wide local excision (WLE) or Mohs micrographic Surgery (MMS). There is no consensus regarding the preferred type of surgery.

Objectives: To compare the outcomes of the two types of surgery (WLE and MMS).

Methods: This retrospective cohort study was based on the medical records of 59 patients with DFSP treated at Sheba Medical Center (using the WLE method) or Assuta Medical Center (using the MMS method) between 1995 and 2018. The data included demographics, clinical presentations, imaging, types of wound closures, pathological margin status, surgical defect sizes, recurrences, and follow-up.

Results: Of the 59 included patients, 18 (30.5%) underwent WLE and 41 (69.5%) underwent MMS. The mean age at diagnosis was 40.1 ± 14.4 years. The male-to-female ratio was 1.5:1. The main tumor location was the trunk (50% for WLE and 41.5% for MMS). The main type of closure for both procedures was primary closure. In 72.2% of WLE and 78.8% of MMS cases, the margins were free. The difference between the final surgical defect and the original tumor size was statistically significantly smaller in patients who underwent MMS. The median duration of follow-up was 6.6 years. There was no significant difference in the rate of recurrence.

Conclusions: MMS enables better tissue preservation and results in a minor surgical defect compared to WLE, with no difference in tumor recurrence between the two methods.

Almost three-quarters of a century ago an American surgeon named Frederick Edward Mohs, had the idea of excising skin cancers and examining the margins before the closure of the surgical wound. In this manner he thought the patient would get better treatment with the best cosmetic result.

Mohs micrographic surgery (MMS) in its present format has been used as a surgical method for treating skin cancers for the last 70 years. The method became popular with American dermatologists 54 years ago when the original Mohs technique was modified into its fresh tissue modality [2] and in the rest of the Western world and Israel more than 35 years ago. Variations of MMS started to appear and indications for surgery also expanded. At the beginning, MMS was indicated mainly for basal and squamous cell carcinomas–nonmelanoma skin cancers (NMSC). Knowledge has been collected and today the method is applicable for a variety of other skin cancers such as melanoma in situ, microcystic adnexal carcinoma, dermatofibrosarcoma protuberans (DFSP), and other adnexal and spindle cell tumors. In this issue of the Israel Medical Association Journal (IMAJ), Landov and colleagues [3] showed the value of MMS for the treatment of DFSP.

Background: One-third of patients with acute decompensated heart failure (ADHF) develop worsening kidney function, known as type I cardiorenal syndrome (CRS). CRS is linked to higher mortality rates, prolonged hospital stays, and increased readmissions.

Objectives: To explore the impact of real-time monitoring of urinary output (UO) trends on personalized pharmacologic management, fluid balance, and clinical outcomes of patients with ADHF admitted to a cardiac intensive care unit.

Methods: Our study comprised 35 patients who were hospitalized with ADHF and continuously monitored for UO (UO_elec). Standard diuretic and fluid protocols were implemented after 2 hours of oliguria, and patient outcomes were compared to a historical matched control (HMC) group. Patients were assessed for daily and cumulative fluid balance (over 72 hours) as well as for the occurrence of acute kidney injury (AKI).

Results: Significantly more patients in the UO_elec group demonstrated negative fluid balance daily and cumulatively over time in the intensive care unit compared to the HMC group: 91% vs. 20%, respectively (P < 0.0001 for 72-hour cumulative fluid balance). The incidence of AKI was significantly lower in the UO_elec monitoring cohort compared to the HMC: 23% vs. 57%, respectively (P = 0.003). Moreover, higher AKI resolution, and lower peak serum creatinine levels were demonstrated in the UO_elec group vs. the HMC group.

Conclusions: Implementing real-time monitoring of UO in ADHF patients allowed for early response to oliguria and goal-directed adjustment to treatment. This finding ultimately led to reduced congestion and contributed to early resolution of AKI.

Background: The coronavirus disease 2019 (COVID-19) pandemic posed significant challenges to healthcare systems worldwide, including a surge in the use of extracorporeal membrane oxygenation (ECMO).

Objectives: To compare outcomes and costs of COVID-19 and non-COVID-19 adult patients treated with ECMO in the intensive care unit (ICU) at Tel Aviv Sourasky Medical Center.

Methods: We conducted a retrospective study. Clinical outcomes, ECMO duration, ICU and hospital length of stay (LOS), and healthcare costs were examined and compared between the two groups.

Results: A total of 119 patients were treated with ECMO between 2016 and 2023; 56 (47.1%) diagnosed with COVID-19. The study found no significant difference in mortality rates between COVID-19 and non-COVID-19 patients. However, COVID-19 patients experienced significantly longer ECMO durations and ICU LOS. Hospitalization and ECMO operation costs were notably higher for COVID-19 patients, but overall admission costs were lower compared to non-COVID-19 patients, with cost of surgical interventions, consultations and imaging contributing to the price gap.

Conclusions: Despite longer durations of ECMO and LOS, the economic burden of ECMO in COVID-19 patients was significantly lower than non-COVID-19 patients. Strict patient selection should be utilized, a fortiori during times of surge-capacity.

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.

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: 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: Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease associated with a heavy burden of morbidity and cost.

Objectives: To provide standardized estimates of trends in HS incidence and prevalence among patients in Israel between 2016 and 2019.

Methods: We conducted a population-based analysis of routinely collected electronic health records data from Clalit Health Services, the largest nationwide public health service provider in Israel. Age- and sex-adjusted rates were reported by using the standard European population as a reference.

Results: The study included 3488 HS incident cases. The mean ± SD age of onset was 30.3 years and was similar in males and females. HS was more common among Jews with low and medium socioeconomic status. The annual HS incidence rate increased throughout the study period. HS prevalence increased from 0.12% in 2016 to 0.17% in 2019.

Conclusions: HS prevalence and incidence rates steadily rose among the Israeli population between 2016 and 2019. Awareness of these findings can help provide an optimal allocation of healthcare resources by policymakers and health service providers and prevent delays in diagnosis.

Background: Condylar hyperplasia is a non-neoplastic overgrowth of the mandibular condyle. The disorder is progressive and causes gradual jaw deviation, facial asymmetry, and dental malocclusion. The only treatment capable of stopping hyperplastic growth is surgical condylectomy to remove the upper portion of the condyle containing the deranged growth center. When this procedure is conducted in proportion to the length of the healthy side it may also correct the jaw deviation and facial asymmetry.

Objectives: To assess the degree to which condylectomy corrects the asymmetry and to determine the proportion of patients after condylectomy who were satisfied with the esthetic result and did not desire further corrective surgery.

Methods: We conducted a retrospective analysis of medical records of patients who underwent condylectomy that was not followed by corrective orthognathic surgery for at least 1 year to determine the degree of correction of chin deviation and lip cant. Patient satisfaction from treatment or desire and undergo further corrective surgery was reported.

Results: Chin deviation decreased after condylectomy from a mean of 4.8⁰ to a mean of 1.8⁰ (P < 0.001). Lip cant decreased after condylectomy from a mean of 3.5⁰ to a mean of 1.5⁰ (P < 0.001). Most patients (72%) were satisfied with the results and did not consider further corrective orthognathic surgery.

Conclusions: Proportional condylectomy could be a viable treatment to both arrest the condylar overgrowth and achieve some correction of the facial asymmetry.

In this review, I described the development of the healthcare system in Theresienstadt during the Holocaust, from the establishment of the camp in late 1941 through 1945. Despite the horrific conditions, the Jews established a highly organized and relatively efficient system that was able to deliver excellent medical care to those eligible to receive care. The major factors that enabled development of the system included the heroic efforts of the high-level providers, the trust of patients, a public health approach to prevent epidemics and the perceived propaganda value of a good healthcare system to the Nazi oppressor. There were many challenges, particularly an informal triage policy that largely excluded medical care from the elderly (above age 60 years), mentally ill, and disabled. There were often difficult relations between caregivers related to ageism, gender, and national origin of the providers. Despite these adversities and the eventual futility due to the murder of the vast majority of the inhabitants, the Jews in Theresienstadt clung to life and tried their best to conduct a civilized society, in a large part through the delivery of excellent medical care.

Background: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA).

Objectives: To demonstrate the utility of the Western blotting (WB)-based amyloid typing method in patients diagnosed with cardiac amyloidosis where the type of amyloid was not obvious based on the clinical context.

Methods: Congo red positive endomyocardial biopsy specimens were studied in patients where the type of amyloid was uncertain. Amyloid proteins were extracted and identified by WB. Mass spectrometry (MS) of the electrophoretically resolved protein-in-gel bands was used for confirmation of WB data.

Results: WB analysis allowed differentiation between AL, AA, and ATTR in cardiac biopsies based on specific immunoreactivity of the electrophoretically separated proteins and their characteristic molecular weight. The obtained results were confirmed by MS.

Conclusions: WB-based amyloid typing method is cheaper and more readily available than the complex and expensive gold standard techniques such as MS analysis or immunoelectron microscopy. Notably, it is more sensitive and specific than the commonly used immunohistochemical techniques and may provide an accessible diagnostic service to patients with amyloidosis in Israel.

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.