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.

Background: Long-term outcome data for bariatric surgery in patients with severe obesity (SO) (body mass index [BMI] ³ 50 kg/m²) are scarce.

Objectives: To compare perioperative morbidity and long-term outcomes between patients with SO and non-SO (NSO).

Methods: Patients with SO who underwent primary bariatric surgery with a follow-up ³ 5 years were age- and gender-matched with NSO patients in a retrospective, case-control study. Data included demographics, BMI, co-morbidities, early outcomes, current and nadir weight, co-morbidity status, and general satisfaction.

Results: Of 178 patients, 49.4% were male, mean age 44.5 ± 14 years. Mean preoperative BMI was 54.7 ± 3.6 and 41.8 ± 3.8 kg/m² in SO and NSO, respectively (P = 0.02). Groups were similar in preoperative characteristics. Depression/anxiety was more prevalent in NSO (12.4% vs. 3.4%, P = 0.03). Obstructive sleep apnea was higher in SO (21.3% vs. 10.1%, P = 0.04). Sleeve gastrectomy was performed most often (80.9%), with a tendency toward bypass in SO (P = 0.05). Early complication rates were: 13.5% in SO and 12.4% in NSO (P = 0.82). Mean follow-up was 80.4 ± 13.3 months. BMI reduction was higher in SO (31.8 ± 5.9 vs. 26.8 ± 4.2 kg/m², P < 0.001) and time to nadir weight was longer (22.1 ± 21.3 vs. 13.0 ± 12.0 months, P = 0.001). Co-morbidity improvement and satisfaction were similar.

Conclusions: Patients with SO benefited from bariatric surgery with reduced BMI and fewer co-morbidities. No added risk of operative complications was found compared to patients with NSO.

Background: There is an unmet need for real-world data regarding laboratory results, co-morbidities, and medication use prior to the first symptoms of amyotrophic lateral sclerosis (ALS). Researchers must identify specific subpopulations at risk for developing ALS and understand pathogenic mechanisms preceding the clinical presentation of ALS as well as possible subclinical disease manifestations.

Objectives: To valuate the role of laboratory results, co-morbidities, and medication use prior to the first symptoms of patients with ALS in Israel so that specific subpopulations at risk for developing ALS can be identified and for possible subclinical disease manifestations. To understand pathogenic mechanisms preceding the clinical presentation of ALS.

Methods: At the ALS clinic at Tel Aviv Sourasky Medical Center, 259 ALS patients insured by Maccabi Healthcare Services and seen between January 1998 and December 2017 were included. Comparisons of demographics, co-morbidities, medications taken, history of trauma, and laboratory tests prior to disease onset were performed between patients and 1295 matched controls.

Results: Prior to disease presentation, ALS patients had a higher frequency of hypertension and cardiovascular disease; presented more frequently with trauma and viral infections; more frequently used analgesics, non-steroidal anti-inflammatory drugs, narcotics, antibiotics, and antiviral medications; and had higher creatine kinase levels.

Conclusions: ALS patients showed higher frequency of cardiovascular disease prior to diagnosis, as well as higher frequency of trauma, infections, and pain medication usage.

Background: A limited program for kidney donation from uncontrolled donation after cardiocirculatory determination of death (uDCDD) was implemented at four hospitals in Israel in close cooperation with Magen David Adom (MDA), the national emergency medical service.

Objectives: To assess the outcome of transplantations performed between January 2017 and June 2022.

Methods: Donor data included age, sex, and cause of death. Recipient data included age, sex, and yearly serum creatinine levels. A retrospective study of out-of-hospital cardiac arrest cases treated by MDA during 2021 were analyzed to assess their compatibility as potential uDCDD donors.

Results: In total, 49 potential donors were referred to hospitals by MDA. Consent was obtained in 40 cases (83%), organ retrieval was performed in 28 cases, and 40 kidneys were transplanted from 21 donors (75% retrieval rate). At 1-year follow-up, 36 recipients had a functioning graft (4 returned to dialysis) and mean serum creatinine 1.59 ± 0.92 mg% (90% graft survival). Outcome after transplantation showed serum creatinine levels (mg%) at 2 years 1.41 ± 0.83, n=26; 3 years 1.48 ± 0.99, n=16; 4 years 1.07 ± 1.06, n=7; and 5 years 1.12 ± 0.31, n=5. One patient died of multiple myeloma at 3 years. The MDA audit revealed an unutilized pool of 125 potential cases, 90 of whom were transported to hospitals and 35 were declared dead at the scene.

Conclusions: Transplant outcomes were encouraging, suggesting that more intensive implementation of the program may increase the number of kidneys transplanted, thus shortening recipient waiting lists.

Background: Among chronic kidney disease (CKD) patients, baseline neutrophil gelatinase-associated lipocalin (NGAL) may reflect the severity of renal impairment. No data exists on serial changes in serum NGAL levels in CKD patients before and after percutaneous coronary intervention (PCI).

Objectives: To evaluate serial serum NGAL levels relation to contrast induced acute kidney injury (CI-AKI) following PCI.

Methods: The study included 58 patients with CKD who underwent elective PCI. Plasma NGAL measurements were performed before (pre-NGAL) and 24 hours following (post-NGAL) PCI. Patients were followed for CI-AKI and changes in NGAL levels. Receiver operator characteristic identified the optimal sensitivity and specificity for pre-NGAL levels compared with post-NGAL for patients with CI-AKI.

Results: Overall CI-AKI incidence was 33%. Both pre-NGAL (172 vs. 119 ng/ml, P < 0.001) and post-NGAL (181 vs. 121 ng/ml, P < 0.001) levels were significantly higher in patients with CI-AKI, but no significant changes were detected. Pre-NGAL levels were similar to post-NGAL levels in predicting CI-AKI (area under the curve 0.753 vs. 0.745). Optimal cutoff value for pre-NGAL was 129 ng/ml (sensitivity of 73% and specificity of 72%, P < 0.001). Post-NGAL levels > 141 ng/ml were independently associated with CI-AKI (hazard ratio [HR] 4.86, 95% confidence interval [95%CI] 1.34–17.64, P = 0.02) with a strong trend for post-NGAL levels > 129 ng/ml (HR 3.46, 95%CI 1.23–12.81, P = 0.06).

Conclusions: In high-risk patients, pre-NGAL levels may predict CI-AKI. Further studies on larger populations are needed to validate the use of NGAL measurements in CKD patients.

Background: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer.

Objectives: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia.

Methods: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130–134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications.

Results: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22–6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08–6.28.

Conclusions: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.

Optic neuritis is an inflammation of the optic nerve and has several causes. The hallmarks of clinical manifestation are pain on movement of the eyes and decreased vision. Typical optic neuritis is an idiopathic demyelinating condition that is often associated with multiple sclerosis, affects young women, is unilateral, and has a good prognosis.

Background: APOE genotype strongly affects plasma lipid levels and risk for cardiovascular disease and cognitive decline. Studies of apo-e allelic and APOE genotype frequencies among several populations have revealed interesting ethnic variations that might affect cardiovascular morbidity and cognition deterioration.

Objectives: To evaluate apo-e allelic frequency among Israeli newborns based on known variances in apo-e allelic frequencies in different countries.

Methods: We examined 498 consecutive neonates born at Tel Aviv Sourasky Medical Center. Umbilical cord blood was sampled for genotyping and lipids. Birth weights were recorded. Demographics and parental risk factors for atherosclerosis were obtained from the mothers.

Results: Most parents were native-born Israelis. Other countries of origin of grandparents were Morocco, Russia, and Iraq. The prevalence of APOE genotypes in Israel is APOE 2/2: 1.4%, APOE 2/3: 8.2%, APOE 3/3: 77.7%, and APOE 4/4: 11.8%. There were no associations of APOE genotype with parental country of origin. However, there was a tendency for APOE 3/4 to be more frequent in newborns of parents of Asian and African origin. Genotype 3/3 was more frequent in newborns whose parents came from Europe and America (78%) compared to those from Asia or Africa (69%).

Conclusions: It is important to determine risk factors such as APOE genotype for evaluation of premature atherosclerosis. Determining genetic and environmental risk factors may facilitate earlier treatment and prevent heart and brain atherosclerosis. APOE genotypes did not appear to affect total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels in newborns.

Background: Little is known about the success of multidisciplinary thyroid eye disease (TED) clinic.

Objectives: To present the characteristics, treatments, and outcomes of patients treated in a multidisciplinary TED clinic.

Methods: A medical record review of all patients who attended a TED clinic was performed. Data included demographics, medical history, laboratory tests, visual function tests, ocular examinations, clinical activity score (CAS), and assessment of quality-of-life (QOL).

Results: Clinic visits included 132 patients seen during 385 appointments at a TED clinic (mean 12 appointments per patient). Management of TED included medical treatments for 48 patients (36.3%) and surgical treatment for 56 (42.4%). There was a positive significant correlation between the CAS and thyroid-stimulating immunoglobulin (TSI) activity at the first visit and at the last follow-up visit (P < 0.01 and P < 0.02, respectively). However, no correlation was found between the CAS and the thyroid-stimulating hormone levels or between the free triiodothyronine (fT3) and fT4 levels at the first or last visit. There was a significant negative correlation between the CAS and color vision (-0.347, P < 0.01, Pearson correlation) at the first visit, but not between the CAS and visual acuity and visual field at either the first or last visit. Changes in the QOL and the CAS scores were significantly negatively correlated (-0.240, P < 0.01).

Conclusions: Treatment and management decisions for TED should be based on multiple parameters including clinical examinations by ophthalmologists and endocrinologists, laboratory tests, and CAS and QOL scores.

Background: Handheld ultrasound devices present an opportunity for prehospital sonographic assessment of trauma, even in the hands of novice operators commonly found in military, maritime, or other austere environments. However, the reliability of such point-of-care ultrasound (POCUS) examinations by novices is rightly questioned. A common strategy being examined to mitigate this reliability gap is remote mentoring by an expert.

Objectives: To assess the feasibility of utilizing POCUS in the hands of novice military or civilian emergency medicine service (EMS) providers, with and without the use of telementoring. To assess the mitigating or exacerbating effect telementoring may have on operator stress.

Methods: Thirty-seven inexperienced physicians and EMTs serving as first responders in military or civilian EMS were randomized to receive or not receive telementoring during three POCUS trials: live model, Simbionix trainer, and jugular phantom. Salivary cortisol was obtained before and after the trial. Heart rate variability monitoring was performed throughout the trial.

Results: There were no significant differences in clinical performance between the two groups. Iatrogenic complications of jugular venous catheterization were reduced by 26% in the telementored group (P < 0.001). Salivary cortisol levels dropped by 39% (P < 0.001) in the telementored group. Heart rate variability data also suggested mitigation of stress.

Conclusions: Telementoring of POCUS tasks was not found to improve performance by novices, but findings suggest that it may mitigate caregiver stress.

Background: Recent studies show a high risk of developing malignancy in patients with Fanconi anemia. The most common solid tumor in this condition is head and neck squamous cell carcinoma (HNSCC) and there is often uncertainty and about disease behavior as well as chemotherapy and radiation response.

Objectives: To describe and characterize HNSCC among Fanconi anemia patients on the Israeli Fanconi Registry

Methods: Our study population included patients in Israel's inherited bone marrow failure registry who were diagnosed with Fanconi anemia between1980 and 2016. Demographic, clinical, and laboratory data were collected from patient charts.

Results: From the collected data, HNSCC was confirmed in 6/111 (5.4%) Fanconi anemia patients; 1 (17%) had classic HNSCC risk factors of tobacco abuse and 4 (56%) had undergone primary surgery. The 3 (50%) receiving concurrent chemoradiotherapy had mild side effects, while half developed metachronous primary malignancy, and all developed > 2 primary malignancies. The overall median survival of the patients in our study was 14 (0.5–57) months.

Conclusions: Fanconi anemia patients have a very high risk of developing HNSCC. Proactive screening for malignancies is needed for the head and neck regions. We also found that chemoradiotherapy can be used safely in high-stage cancers.

Background: Changes accommodating requirements of religious authorities in Israel resulted in the Brain and Respiratory Death Determination Law (BRDDL), which came into effect in 2009. These included considering patient wishes regarding the brain respiratory death determination (BRDD), mandatory performance of apnea and ancillary testing, establishment of an accreditation committee, and accreditation required for physicians performing BRDD.

Objectives: To assess the impact of the legislation from 2010–2019.

Methods: Data collected included the number of formal BRDDs and accredited physicians. Obstacles to declaring brain death and interventions applied were identified.

Results: Obstacles included lack of trained physicians to perform BRDD and interpret ancillary test results, inability to perform apnea or ancillary testing, and non-approach to next-of-kin objecting to BRDD. Interventions included physician training courses, additional ancillary test options, and legal interpretation of patient wishes for non-determination of BRD. As a result, the number of non-determinations related to next-of-kin objecting decreased (26 in 2010 to 5 in 2019), inability to perform apnea or ancillary testing decreased (33 in 2010 to 2 in 2019), and number of physicians receiving accreditation increased (210 in 2010 to 456 in 2019). Last, the consent rate for organ donation increased from 49% to 60% in 2019.

Conclusions: The initial decrease in BRDDs has reversed, thus enabling more approaches for organ donation. The increased consent rate may reflect in part the support of the rabbinate and confidence of the general public that BRDD is performed and monitored according to strict criteria.

Background: Self-management, an active life routine, and adherence to physical activity are effective in the management of low back pain (LBP). However, delivering effective education and reassurance to patients can be a difficult for practitioners. The enhanced transtheoretical model intervention (ETMI) has shown to be successful and cost effective. The intervention focuses on educating practitioners to reassure patients, empower them to increase physical activity, and improve their self-efficacy.

Objectives: To assess whether ETMI can be implemented among primary care practitioners and to examine whether it reduces pain, disability, and fear avoidance as well as decreasing healthcare utilization. This protocol outlines the methodology for the implementation of ETMI through a hybrid implementation–effectiveness design.

Methods: Two qualitative and mixed-method studies provided a basis for an implementation prospective cohort study. Discussions are followed by a prospective cohort study with pre-and post-intervention measures as well as descriptions retrieving economic and therapeutic outcome data from the Maccabi Healthcare Services (MHS) databases. In addition, a fourth qualitative study was conducted at the midpoint of the implementation to evaluate the process by measuring the perceptions and practice of practitioners. The intervention group was 220 primary care practitioners and their patients (~n=10,000) from the central district of MHS. The control data was provided by other care districts with similar socioeconomic makeup (~n=40,000).

Conclusions: We evaluated the process and outcomes of the implementation of ETMI. We investigated the relationship between the care received (ETMI against treatment as usual) and healthcare utilization, costs, and patient-clinical outcomes.

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on healthcare systems worldwide. The fear of seeking medical attention to avoid the possibility of being infected may have altered the course of some diseases.

Objectives: To describe our experience with the management of patients with acute cholecystitis during the pandemic at our medical center.

Methods: We compared patients treated for acute cholecystitis between 1 March and 31 August 2020 (Group I) to patients admitted with the same diagnosis during the same months in 2019 (Group II). We evaluated demographics, presenting symptoms, laboratory and imaging findings at presentation, the disease's clinical course, management, and outcome.

Results: Group I consisted of 101 patients and group II included 94 patients. No differences were noted for age (66 years, IQR 48–78 vs. 66 years, IQR 47–76; P = 0.50) and sex (57.4% vs. 51.1% females; P = 0.39) between the two groups. The delay between symptom onset and hospital admission was longer for Group I patients (3 days, IQR 2–7 vs. 2 days, IQR 1–3; P = 0.002). Moderate to severe disease was more commonly encountered in Group I (59.4% vs. 37.2%, P = 0.003). Group I patients more often failed conservative management (36% vs. 6%, P = 0.001) and had a higher conversion rate to open surgery (15.4% vs. 0%, P = 0.025).

Conclusions: Patients presenting with acute cholecystitis during the COVID-19 pandemic more often presented late to the emergency department and more showed adverse outcomes