Israel Medical Association Journal

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.

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.

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].

Thyroid storm-related heart failure is a rare, life threatening complication of hyperthyroidism. In refractory cases, urgent thyroidectomy is required for definitive control of thyrotoxicosis. venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a supportive measure for cardiorespiratory failure requiring continuous anticoagulation to prevent clotting. We presented two cases of thyrotoxic cardiac failure that necessitated VA-ECMO. One of the patients was successfully treated with thyroidectomy while on VA-ECMO. To the best of our knowledge, only two such cases have previously been reported.

The interplay between post-traumatic stress disorder (PTSD) and autoimmunity is well known. One of the contributors leading to immune disorders is autonomic dysregulation, which is characterized by attenuated parasympathetic and elevated sympathetic systems. In this review, we described evidence regarding the relationship between stress, PTSD, autonomic dysfunction, and autoimmunity. Stress is a physiological response, which is functional for our being. The implication of dysfunction in stress response may be a cause of disease development. We described the fundamental role of the pathological high levels of stress in PTSD as a mediator factor that contributes to autonomic dysfunction, which as a result may lead to autoimmunity. Systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes are some of the autoimmune diseases PTSD patients are at higher risk of developing. Notably, some autoimmune diseases are shown to increase the susceptibility to develop PTSD, which may indicate a bidirectional influence. In addition, we elaborated on stress as a major component in both fibromyalgia and PTSD, as there are overlaps between the pathogenesis of fibromyalgia and PTSD. Underlying chronic low-grade inflammation, which characterizes PTSD patients, may be a potential target and biomarker in treating PTSD patients. We believe that chronic low-grade inflammation, high concentrations of cytokines, and other inflammatory biomarkers, which characterize PTSD patients, may be potential targets and biomarkers in the treatment of PTSD patients and part of the PTSD diagnostic criteria.

Background: Higher body mass index (BMI) has been shown to be a protective factor from mortality in sepsis patients. Yet, whether this effect is different in the very elderly is currently unknown.

Objective: To investigate the relationship between BMI and sepsis outcomes in patients older and younger than 80 years of age.

Methods: A retrospective analysis of consecutive patients admitted with sepsis to Shamir Medical Center, Israel, was conducted. We compared patients older than and younger than 80 years of age with a BMI higher and lower than 25 kg/m² for hospitalization outcomes.

Results: Patients older than 80 years presented with multiple co-morbidities compared to younger patients, but with no difference between BMI groups. Similarly, hospitalization outcomes of functional deterioration, discharge to long-term care facilities, and readmission were not significantly different between BMI groups in the same age category. Mortality was significantly different between BMI groups in patients older than 80 years of age, with higher mortality in BMI < 25 kg/m²: in-hospital mortality (23.4% vs. 14.9%, P < 0.001), 30-day mortality (27.6% vs. 17.9%, P < 0.001), and 90-day mortality (43.4% vs. 28.9%, P < 0.001). This difference was not significant between the groups younger than 80 years old. On logistic regression, BMI over 25 kg/m² was protective in all mortality categories. Nevertheless, there was no significant interaction between age over 80 years to BMI over 25 kg/m² in all mortality outcomes.

Conclusions: Among patients hospitalized with sepsis, higher BMI is a protective factor against mortality in both elderly and younger patients.

Background: National registries for acromegaly and population-based data make an important contribution to disease understanding and management. Data concerning the epidemiology of acromegaly in Israel is scanty.

Objectives: To evaluate the epidemiology of acromegaly in different industrial areas in northern Israel.

Methods: Data from adult patients diagnosed with acromegaly from 2000 to 2020, living in Haifa and the western Galilee District were collected using the electronic database and medical records from Clalit Health Services. The prevalence of acromegaly in three distinct areas and overall were reported. In addition, other epidemiological data including associated co-morbidities, pituitary tumor size, and treatment modalities were collected.

Results: We identified 77 patients with a confirmed diagnosis of acromegaly. The overall prevalence was 155 cases/10⁶ inhabitants without statistically significant differences between the three areas. The mean age at diagnosis was 50 ± 1.8 years and the male to female ratio was 1.1. Macroadenoma and microadenoma were identified in 44 (57%) and 25 (33%), respectively. The frequency rate of acromegaly-associated co-morbidities such as diabetes, hypertension, carpal tunnel syndrome, and osteoporosis was similar to previously reported studies. The mean body mass index (BMI) was 29 ± 5.6 kg/m² .Obesity, with a BMI ≥ of 30 kg/m², was found in 29 patients (38%). The majority of patients underwent transsphenoidal surgery 67 (87%). Normalized insulin-like growth factor 1 was reported in 64 (83%).

Conclusions: A high prevalence of acromegaly was found in northern Israel. The pituitary microadenoma frequency rate is the highest reported.

Background: Pregnant women with Marfan syndrome (MS) have a high risk of aortic dissection around delivery and their optimal management requires a multi-disciplinary approach, including proper cardio-obstetric care and adequate pain management during labor, which may be difficult due to the high prevalence of dural ectasia (DE) in these patients.

Objectives: To evaluate the multidisciplinary management of MS patients during labor.

Methods: Nineteen pregnant women (31 pregnancies) with MS were followed by a multi-disciplinary team (cardiologist, obstetrician, anesthesiologist) prior to delivery.

Results:^. Two patients had kyphoscoliosis; none had previous spine surgery nor complaints compatible with DE. In eight pregnancies (7 patients), aortic root diameter (ARd) before pregnancy was 40 to 46 mm. In this high-risk group, one patient underwent elective termination, two underwent an urgent cesarean section (CS) under general anesthesia, and five had elective CS; two under general anesthesia (GA), and three under spinal anesthesia. In 23 pregnancies (12 patients), ARd was < 40 mm. In this non-high-risk group three pregnancies (1 patient) were electively terminated. Of the remaining 20 deliveries (11 patients), 14 were vaginal deliveries, 9 with epidural analgesia and 5 without. Six patients had a CS; four under GA and two2 under spinal anesthesia. There were no epidural placement failures and no failed responses. There were 2 cases of aortic dissection, unrelated to the anesthetic management.

Conclusions: The optimal anesthetic strategy during labor in MS patients should be decided by a multi-disciplinary team. Anesthetic complications due to DE were not encountered during neuraxial block

Background: Consent rates for organ donation remain one of the most important factors determining the number of organs available for transplantation. Trauma casualties constitute a substantial part of the deceased organ donor pool and have unique characteristics that distinguish them from the general donor population. However, this group has not been extensively studied.

Objectives: To identify donor factors associated with positive familial consent for solid organ donation among trauma casualties.

Methods: This retrospective study included all trauma casualties who were admitted to the Rabin Medical Center, Beilinson hospital, during the period from January 2008 to December 2017, who were potential organ donors. Data collected included demographic features, the nature of the injury, surgical interventions, and which organs were donated. Data was collected from the Rabin Medical Center Trauma Registry.

Results: During the study period 24,504 trauma patients were admitted and 556 died over their hospital course. Of these 76 were potential donors, of whom 32 became actual donors and donated their organs. Two factors showed a statistically significant correlation to donation, namely female gender (P = 0.018) and Jewish religion of the deceased (P = 0.032).

Conclusions: Only a small group of in hospital trauma deaths were potential solid organ donors (13.7%) and less than half of these became actual donors. Consent rates were higher when the deceased was female or Jewish

Background: Patients with critical limb ischemia (CLI) involving the below-the-knee (BTK) arteries are at increased risk of limb loss. Despite improvement in endovascular modalities, it is still unclear whether an aggressive approach results in improved limb salvage.

Objectives: To assess whether an aggressive approach to BTK arterial disease results in improved limb salvage.

Methods: A comparative study of two groups was conducted. Group 1 included patients treated between 2012 and 2014, primarily with transfemoral angioplasty of the tibial arteries. Group 2 included patients treated between 2015–2019 with a wide array of endovascular modalities (stents, multiple tibial artery and pedal angioplasty, retrograde access). Primary endpoint was freedom from amputation at 4 years.

Results: A total of 529 BTK interventions were performed. Mean age was 71 ± 10.6 years, 382 (79%) were male. Patients in group 1 were less likely to be taking clopidogrel (66% vs. 83%, P < 0.01) and statins (72 % vs. 87%, P < 0.01). Several therapeutic modalities were used more often in group 2 than in group 1, including pedal angioplasty (24 vs. 43 %, P = 0.01), tibial and pedal retrograde access (0 vs. 10%, P = 0.01), and tibial stenting (3% vs. 25%, P = 0.01). Revascularization of two or more tibial arteries was performed at a higher rate in group 2 (54% vs. 50%, P = 0.45). Estimated freedom from amputation at 40 months follow-up was higher in group 2 (53% vs. 63%, P = 0.05).

Conclusions: An aggressive, multimodality approach in treating BTK arteries results in improved limb salvage.

Background: There are several methods for primary breast reconstruction following oncologic resection, including alloplastic and autologous-based reconstruction. Major complications that can lead to re-operation and reconstruction failure occur in up to 25% of the patients and necessitate salvage procedures.

Objectives: To present the authors' experience using a pedicled latissimus dorsi (LD) flap for the salvage of complicated and impending failed breast reconstruction.

Methods: A retrospective cohort study was conducted of all patients who underwent breast reconstruction salvage by means of an LD flap in our institution during a 5-year period. Demographic, oncologic, surgical, and postoperative data were collected and analyzed.

Results: Seventeen patients underwent breast reconstruction salvage with the LD flap. Fourteen patients had alloplastic reconstruction and three patients had autologous reconstruction. Postoperative complications included wound infection in three patients, minor wound dehiscence in two, and donor site seroma in two. One case of postoperative infection required re-operation with exchange of the implant with a tissue expander. All breast reconstructions were salvaged using the LD flap. Only one patient complained of functional limitations in using the arm of the harvested LD.

Conclusions: The LD flap is a valuable and reliable flap for alloplastic or autologous breast reconstruction salvage and has a high rate of salvage success despite the challenging surgical environment. This flap offers a good cosmetic reconstruction outcome with relatively low donor-site morbidity and high patient satisfaction.

Background: Drooling is the unintentional loss of saliva from the mouth, usually caused by poor coordination of the swallowing mechanism. It is commonly seen in patients with chronic neurologic disorders, such as Parkinson's disease, amyotrophic lateral sclerosis (ALS), cerebral palsy, and stroke, as well as in patients with cognitive impairment and dementia.

Objectives: To evaluate the efficacy and safety of ultrasound-guided botulinum toxin injections into the parotid and submandibular salivary glands for the treatment of drooling.

Methods: We conducted a retrospective analysis of the medical records of 12 consecutive patients treated with botulinum toxin injections into the parotid and submandibular glands for the first time. The primary outcome variable was the subjective improvement of drooling on a 5-point scale. Secondary outcome variables were duration of the therapeutic effect, request to undergo additional treatment, and adverse events.

Results: Of 12 patients, 8 (67%) reported considerable improvement after treatment, 3 reported slight improvement, and 1 reported development of dry mouth. All patients stated that they felt the effects 1 week after the injections; the mean duration of the therapeutic effect was 4.5 months (range 3–9 months). One patient suffered from local hematoma and ecchymosis that did not require medical care. Another patient complained of difficulty swallowing, which did not require medical treatment and resolved spontaneously within 1 month.

Conclusions: Ultrasound-guided botulinum toxin injections into the parotid and submandibular glands seem to be a safe and effective therapy for the treatment of drooling. Further long-term prospective studies with varying doses are warranted.

Background: Cardiac damage caused by oncological therapy may manifest early or many years after the exposure.

Objectives: To determine the differences between sub-acute and late-onset cardiotoxicity in left ventricular ejection fraction (LVEF) recovery as well as long-term prognosis.

Methods: We studied 91 patients diagnosed with impaired systolic function and previous exposure to oncological therapy. The study population was divided according to sub-acute (from 2 weeks to ≤ 1 year) and late-onset (> 1 year) presentation cardiotoxicity. Recovery of LVEF of at least 50% was defined as the primary end point and total mortality was the secondary end point.

Results: Fifty-three (58%) patients were classified as sub-acute, while 38 (42%) were defined as late-onset cardiotoxicity. Baseline clinical characteristics were similar in the two groups. The mean LVEF at presentation was significantly lower among patients in the late-onset vs. sub-acute group (28% vs. 37%, respectively, P < 0.001). Independent predictors of LVEF recovery were trastuzumab therapy and a higher baseline LVEF. Although long-term mortality rates were similar in the groups with sub-acute and late-onset cardiotoxicity, improvement of LVEF was independently associated with reduced mortality.

Conclusions: Our findings suggest that early detection and treatment of oncological cardiotoxicity play an important role in LVEF recovery and long-term prognosis.