Israel Medical Association Journal

One of the most wonderful things in the practice of medicine is the endless opportunities to learn new things and encounter novel medical conditions and their manifestations. However, not all new experiences are necessarily welcomed. As we recently discovered, there are some medical encounters that no physician should ever face, because no patient should have to endure these encounters. That is, no person, and certainly no child, should ever go through the kind of cruel captivity we recently encountered following the horrific events of 7 October 2023 in Israel.

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.

Anti-tumor necrosis factor-alpha (anti-TNFα) medications are the most frequently used biologicals to treat inflammatory bowel disease (IBD). Little is known about the ocular side effects of this drug category. We present a case series of six young patients with Crohn disease (CD) and no previous ophthalmologic manifestations who developed blepharitis after commencing treatment with anti-TNFα therapy. Six otherwise healthy patients with CD, with no history of allergies or prior ocular complaints, developed blepharitis at a median of 7.5 months after the initiation of anti-TNFα therapy. All ophthalmic findings were treated topically. The ocular symptoms of two of the patients resolved shortly after discontinuation of the anti-TNFα treatment. The other four presented with relapsing-remitting symptoms. Blepharitis is a common ocular disease in the general population and an extra-intestinal manifestation in patients with IBD. It may be an adverse effect of anti-TNFα therapy in this patient population.

Background: In 2019, 1 mg subcutaneous semaglutide was registered for the treatment of diabetes in Israel. Recognition of its effect on weight has led to its use as a treatment for obesity.

Objectives: To explore physicians’ pre-therapy considerations, therapy practices, and attitudes regarding subcutaneous semaglutide for weight loss.

Methods: A 22-item questionnaire was disseminated to physicians who prescribed semaglutide 1-mg for weight loss using an authorized off-label path.

Results: In total, 127 physicians completed the questionnaire. As for pretreatment requirements, in the absence of diabetes, 30% requested a minimal body mass index of 30 kg/m². Additional requirements were documented lifestyle-change effort (67%) and prior weight loss medication use (13%). Half of the physicians regarded calorie restriction, and 23% considered physical activity as necessary for weight loss while on therapy. As for dose, most physicians (78%) started with a 0.25-mg weekly injection, 57% doubled the dose monthly, and all others recommended doubling when side effects subsided. Regarding weight loss goal, 43% of the physicians set a personal goal with each patient while 26% limited the goal to 10% of initial weight. Fewer than 50% of physicians discussed treatment duration with their patients, and 52% of patients discontinued therapy in the first 3 months. The main reasons for discontinuation were price, lack of effect, and fear of long-term side effects.

Conclusions: The diverse approaches regarding off-label use of semaglutide for weight reduction highlight the necessity to guide physicians and standardize treatment regimen.

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: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients.

Objectives: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications.

Methods: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel.

Results: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15–53, range 3–60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12–80). The median time from HSCT to LTx was 96 months (IQR 63–120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications.

Conclusions: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

Takotsubo syndrome (TTS) often develops following stressors such as cardiac surgery. It may be fatal in rare cases. Our 70-year-old female patient presented with a rare case of tricuspid valve papillary fibroelastoma, which was complicated by fatal TTS after successful resection. The patient had a right atrial mass that was investigated with computed tomography and transesophageal echocardiography (TTE). She was scheduled for surgery. Pathology findings were consistent with papillary fibroelastoma of the tricuspid valve. Three weeks after successful surgery, the patient was admitted due to cardiogenic shock with echocardiographic findings of apical ballooning and left ventricular outflow tract obstruction consistent with TTS. The patient died one hour after her admission despite optimal medical therapy.

Endovascularly retrieved clots may be a potential resource for diagnosing stroke etiology. This method may influence secondary prevention treatment. We measure thrombin activity eluted by serially washing clots. We concluded that an assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

Retroperitoneal infiltration, also known as retroperitoneal fibrosis (RPF), is a rare condition, which mostly occurs in men over the age of 40 years. This condition involves inflammation of the soft tissue of the retroperitoneal cavity, most commonly around the infrarenal abdominal aorta, iliac arteries, ureters, and abdominal organs. Clinical manifestations consist of severe pain in the lower back, abdomen, or flank, which may radiate to the inguinal region. Pain may be acute at the onset and can be mistaken for renal colic. Renal and ureteral involvement is common and can develop into acute kidney injury and hypertensive crises.

Background: The 2015 American Thyroid Association (ATA2015) and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS) are two widely used thyroid sonographic systems.

Objectives: To compare the two systems for accuracy of cancer risk prediction.

Methods: Preoperative ultrasound images from 265 patients who underwent thyroidectomy at our hospital from January 2012 to March 2019 were retrospectively categorized by the ACR TI-RADS and ATA2015 systems. Diagnostic performances were compared.

Results: Of 238 nodules assessed, 115 were malignant. Malignancy risks for the five ACR TI-RADS categories were 0%, 7.5%, 11.4%, 59.6%, and 90.0%. Malignancy risks for the five ATA2015 categories were 0%, 6.8%, 17.0%, 55.5%, and 92.1%. The proportion of total nodules biopsied was higher with the ATA2015 system than the ACR TI-RADS system: 88.7% vs. 66.3%. Proportions of malignant nodules and benign nodules biopsied were higher with ATA2015 than with ACR TI-RADS: 93.3% vs. 87.8% and 84.4% vs. 46.3%, respectively. Specificity and sensitivity rates were 53.6% and 84.3%, respectively, for ACR TI-RADS, and 15.5% and 93.3%, respectively, for ATA2015. The two systems showed similarly accurate diagnostic performance (AUC > 0.88). False negative rates for ACR TI-RADS and ATA2015 were 15.6% and 6.6%, respectively. Rates of missed aggressive cancer were similar for the two systems: 3.4% and 3.7%, respectively.

Conclusion: ACR TI-RADS was superior to ATA2015 in specificity and avoiding unnecessary biopsies. ATA2015 yielded better sensitivity and a lower false negative rate. Identification of aggressive cancers was identical in the two systems

Background: The coronavirus disease-2019 (COVID-19) pandemic had enormous impact on many aspects of our society, including huge medical, social, and economic challenges.

Objective: To evaluate the impact of the first wave of the COVID-19 pandemic and the related movement restrictions on the incidence of hip fractures in different age groups.

Methods: This single center retrospective observational study included all patients over 60 years old admitted to our hospital with the diagnosis of hip fracture during March and April 2020. Exclusion criteria were periprosthetic or pathologic fractures and multitrauma. We collected the same data on all patients with hip fractures admitted during March and April of 2018 and 2019.

Results: Mean patient age increased from 81.7 to 85.0 years. Only two of 49 patients tested positive for COVID-19. The data show a decrease of 38% in fracture load, but a striking decrease of 85% and 59% among sexagenarians and septuagenarian, respectively. There was no decrease among nonagenarians. Early mortality, both at 30 days and 90 days, was twice as common during the pandemic. However, stratification by age group demonstrated that the risks of early mortality were the same as previous years. Mean waiting time for surgery decreased from 27.5 to 18.9 hours. Patient discharge to home over a rehabilitation facility increased from 9% to 17%.

Conclusions: The COVID-19 pandemic affected the epidemiology of hip fractures in the elderly. The incidence of fractures and age distribution were significantly different from other years. Discharge destinations were also affected. The management of hip fracture patients was not compromised.

Coronavirus disease-2019 (COVID‐19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic. In October 2020, the U.S. Centers for Disease Control and Prevention (CDC) published 27 cases [1] describing the new multi-system inflammatory syndrome in adults (MIS-A). Nine of the cases were reported directly to the CDC, 7 from published case reports and another 11 patients found in three distinct case series

Background: Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50%

Objectives: To evaluate which IPF patients have better prognosis following LTx.

Methods: A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis.

Results: Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates.

Conclusions: IPF patients with higher mean PHT, older age (> 65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.

Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses

Background: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA.

Objectives: To evaluate SC tocilizumab in a real-life clinical setting.

Methods: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed.

Results: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively.

Conclusions: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.