Israel Medical Association Journal

Twenty-five years ago, we, the undersigned together with the chairman of the Israel Medical Association at the time, Prof. Yoram Blachar, and the Secretary General of the Israel Medical Association, Adv. Leah Wapner, joined forces to found an Israeli medical journal in English. The purpose of this journal was to present to the world Israeli clinical medicine and medical research. That journal is none other than the Israel Medical Association Journal (IMAJ), and in 2023 its 300th issue was published. In 2024 we keep going, taking pride in the fact that every one of those past 300 issues has been published and dispatched on time, without delay, regardless of any circumstances.

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.

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.

Background: Due to the high variability in malignancy rate among cytologically indeterminate thyroid nodules (Bethesda categories III–V), the American Thyroid Association recommends that each center define its own categorical cancer risk.

Objectives: To assess cancer risk in patients with cytologically indeterminate thyroid nodules who were operated at our center.

Methods: In a retrospective study, we analyzed the pathology results of all the patients whose fine needle aspiration results showed Bethesda III–V cytology and who subsequently underwent total thyroidectomy or lobectomy from December 2013 to September 2017.

Results: We analyzed 56 patients with indeterminate cytology on fine needle aspiration. Twenty-nine (52%) were defined as Bethesda III, 19 (34%) Bethesda IV, and 8 (14%) Bethesda V category. Malignancy rates were 38%, 58%, and 100% for Bethesda categories III, IV, and V, respectively. Most malignancies in Bethesda categories III and IV were follicular in origin (follicular thyroid carcinoma and follicular type papillary thyroid carcinoma), while 100% of the patients with Bethesda category V were diagnosed with classical papillary thyroid carcinoma. No correlation was found between sonographic and cytological criteria of nodules with Bethesda categories III and IV and rates of malignancy.

Conclusions: We found higher than expected rates of malignancy in indeterminate cytology. This finding reinforces the guidelines of the American Thyroid Association to establish local malignancy rates for thyroid nodules with indetermined cytology.

Overuse of healthcare services is a common phenomenon defined as: “a healthcare service that is provided under circumstances in which its potential for harm exceeds the possible benefit.” It is expressed in the gap between desired services and available ones and is accompanied by high financial and human life costs. One-fifth to one-third of patients receives unnecessary, ineffective, or potentially harmful treatments or services. One of the greatest challenges to understanding overuse is the lack of definition for appropriate use. Apart from the physical and mental damage caused by overuse or improper use of medical services, this phenomenon has many implications, such as increasing waiting times for services, creating long queues, and incurring considerable financial costs as over 10% of hospital expenses are used to correct medical errors or preventable infections. Government intervention through economic arrangements such as deductibles and pre-authorization of services by the insurer are partially effective in reducing the overuse of health services. Additional solutions include ensuring safety and quality of care as well as shared decision-making.

Diagnosis and treatment of posterior hip pain has increased due to advancements in clinical, anatomical, biomechanical, and related pathological understandings of the hip. Due to its complexity and close anatomical relationship with many osseous, neurovascular, and musculotendinous structures, posterior hip pain must be appropriately categorized based on its origin. Therefore, it is crucial that clinicians are able to determine whether patient complaints are of extra-articular or intra-articular nature so that they can implement the optimal treatment plan. In the current review article, we discussed posterior hip pain with an emphasis on the main differential diagnoses of deep gluteal syndrome, ischiofemoral impingement, and hamstring tear/hamstring syndrome. For the appropriate diagnosis and etiology of posterior hip pain, a thorough and conclusive clinical history is imperative. Physicians should rule out the possibility of spinal involvement by physical examination and if necessary, by magnetic resonance imaging (MRI). Furthermore, because of the vicinity to other, non-orthopedic structures, an obstetric and gynecologic history, general surgery history, and urologic history should be obtained. Following the collection of patient history clinicians should adhere to an established and efficient order of evaluation starting with standing then to seated, supine, lateral, and prone testing. Imaging assessment of posterior hip pain begins with a standard anterior-posterior pelvic radiograph, in addition to frog-leg lateral. MRI is pivotal for assessing soft tissue-related extra-articular causes of hip in patients with posterior hip pain. Non-surgical treatment is preferred in most cases of deep gluteal syndrome, ischiofemoral impingement, pudendal nerve entrapment, and proximal hamstring pathologies. Surgical treatment is saved as a last resort option in cases of failed non-surgical treatment

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: 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: The most common complication after tonsillectomy is bleeding. We investigated whether performing the procedure during the summer or the winter affects the bleeding rate.

Objectives: To investigate whether there is an association between meteorological conditions and the occurrence of post-tonsillectomy hemorrhage (PTH) in the southern Israel Negev region.

Methods: All patients who underwent tonsillectomy from 2001–2013 at the Soroka Medical Center were included. We collected patient demographic data and indications for surgery. Meteorological data were obtained from a weather station operated by the Israel Ministry of Environmental Protection.

Results: Of 4438 patients who underwent tonsillectomy, with or without adenoidectomy, 432 (9.73%) experienced hemorrhage. Patients who suffered from PTH were significantly older: median age 9.61 years vs.4.7 years, P < 0.0001. When comparing patients without PTH to those who bled within 0–3 days after surgery, there was a higher risk for bleeding during the warmer seasons: relative risk (RR) 1.38, 95% confidence interval ([95%CI] 1.07–1.77), RR 1.45 (95%CI 1.17–1.80), and 1.62 (95%CI 1.27–2.06) comparing the winter to spring, summer, and fall, respectively. A statistically significant positive association was also found with the average temperature on the day of surgery. Bleeding more than 3 days after surgery was less likely in summer: RR 0.82, 95%CI 0.69–0.97. We found no association with temperature on the day of surgery and PTH after postoperative day 3.

Conclusions: Seasonality, and to an extent temperature, seem to play only a minor role in PTH.

Background: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.

Objectives: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. 

Methods: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. 

Results: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.

Conclusions: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported. 

 

Background: Determining the prognosis of patients with heart failure is essential for patient management and clinical trial conduct. The relative value of traditional prognostic criteria remains unclear and the assessment of long-term prognosis for individual patients is problematic.

Objectives: To determine the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of patients with idiopathic dilated cardiomyopathy.

Methods: We investigated the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of individual patients in a large, representative, contemporary cohort of idiopathic dilated cardiomyopathy (IDCM) patients referred to Johns Hopkins from 1997 to 2004 for evaluation of cardiomyopathy. In all patients a baseline history was taken, and physical examination, laboratory studies, echocardiogram, right heart catheterization and endomyocardial biopsy were performed.

Results: In 171 IDCM patients followed for a median 3.5 years, there were 50 long-term event-free survivors (LTS) (median survival 6.4 years) and 34 patients died or underwent ventricular assist device placement or transplantation within 5 years (NLTS; non-long-term survivors) (median time to event 1.83 years. Established risk factors (gender, race, presence of diabetes, serum creatinine, sodium) and the use of accepted heart failure medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers) were similar between the two groups. Although LTS had younger age, higher ejection fraction (EF) and lower New York Heart Association (NYHA) class at presentation, the positive predictive value of an EF< 25% was 64% (95% CI 41%–79%) and of NYHA class > 2 was 53% (95% CI 36–69%). A logistic model incorporating these three variables incorrectly classified 29% of patients.

Conclusions: IDCM exhibits a highly variable natural history and standard clinical predictors have limited ability to classify IDCM patients into broad prognostic categories. These findings suggest that there are important host-environmental factors still unappreciated in the biology of IDCM.