Israel Medical Association Journal

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: Unfractionated heparin is the preferred anticoagulant used during open heart surgeries, including left ventricular assist device (LVAD) implantation. In cases in which patients are heparin-induced thrombocytopenia positive (HIT+), the accepted practice has been to substitute heparin with bivalirudin. This practice may be associated with significant bleeding and adverse outcomes.

Objectives: To review our experience with HIT+ patients who were heparin-induced thrombocytopenia with thrombosis negative (HITT-) and who underwent HeartMate 3 LVAD implantation using heparin intraoperatively rather than bivalirudin.

Methods: From 2016 to 2022, 144 adult patients were implanted with HeartMate 3 LVAD at our center. Among them, 7 were detected as HIT+ but HITT- and therefore were prescribed intraoperatively with heparin and treated pre- and postoperatively with bivalirudin. We reviewed the preoperative, intraoperative, and postoperative characteristics as well as short-term mortality and the complication rates of these HIT+ patients.

Results: The median age of our cohort was 56 years (51–60), 71% were male (n=5), all were INTERMACS Level 1, and most were bridged to transplant (n=6, 86%). The 30-day mortality rate post-implantation was 0%. The average 24-hour chest drain postoperative output was 1502.86 ± 931.34 ml. There were no intraoperative pump thromboses, perioperative thromboses, cerebrovascular accidents, or gastrointestinal bleeding within the first 24 hours postoperative. One patient required a revision due to bleeding.

Conclusions: Intraoperative unfractionated heparin may be administered to patients who are HIT+ and HITT- while undergoing LVAD implantation. However, further investigation is required.

Cognitive impairment due to different types of anemia is well-known. We reviewed the links between different types of anemia and the mechanism of cognition impairment as well as the direct involvement of micronutrients such as iron, vitamin B12, folic acid, and copper on cognitive function. Anemia can lead to cognitive impairment, yet the current health policy usually requires patient involvement in the treatment decision-making. Therefore, can an anemic patient be a partner to shared decision-making concerning the recommended treatment?

Background: At the beginning of 2020, the coronavirus disease 2019 (COVID-19) pandemic presented a new burden on healthcare systems.

Objectives: To evaluate the impact of the COVID-19 pandemic on the outcome of non-COVID patients in Israel.

Methods: We conducted a retrospective observational cohort study at a tertiary medical center in Israel. From December 2018 until June 2022, 6796 patients were hospitalized in the internal medicine wards. Patients were grouped based on their admission date: admitted during COVID waves (waves group), admitted between waves (interim group), and admitted during the same months in the previous year (former-year group).

Results: Mortality during hospitalization and 30-day mortality were higher in the waves group compared to the interim and former-year groups (41.4% vs. 30.5% and 24%, 19.4% vs. 17.9% and 12.9%, P < 0.001). In addition, 1-year mortality was higher in the interim group than in the waves and former-year group (39.1 % vs. 32.5% and 33.4%, P = 0.002). There were significant differences in the readmissions, both at 1 year and total number. The waves group had higher rates of mechanical ventilation and noradrenaline administration during hospitalization. Moreover, the waves group exhibited higher troponin levels, lower hemoglobin levels, and more abnormalities in liver and kidney function.

Conclusions: Hospitalized non-COVID patients experienced worse outcomes during the peaks of the pandemic compared to the nadirs and the preceding year, perhaps due to the limited availability of resources. These results underscore the importance of preparing for large-scale threats and implementing effective resource allocation policies.

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: The French AmbUlatory Cesarean Section (FAUCS) technique was introduced to the Galilee Medical Center in September 2021. FAUCS was performed electively for interested women who meet the criteria.

Objectives: To evaluate the learning curve of senior surgeons performing FAUCS, the procedure short-term outcomes, and complications.

Methods: This retrospective study included 50 consecutive women who underwent FAUCS from September 2021 until March 2022 at our facility. Preoperative, intraoperative, postoperative, and demographic data were retrieved from patient electronic charts.

Results: The mean duration of surgery was 53.26 ± 11.62 minutes. This time decreased as the surgical team's experience increased: from a mean 58.26 ± 12.25 minutes for the first 15 procedures to a mean 51.17 ± 9.73 minutes for subsequent procedures. The mean visual analogue scale score for 24 hours was 1.08 ± 0.84 (on a 10-point scale). The rate of neonatal cord pH < 7.2 was 6%, and there were 11.3% cases of vacuum assisted fetal extraction. In total, 44% of the women were able to mobilize and urinate spontaneously by 4–6 hours. Complications included bladder injury (n=1), endometritis (n=1), and incisional hematoma (n=1). Overall, the maternal satisfaction rate was high; 94% of the women would recommend FAUCS to others.

Conclusions: FAUCS is a feasible procedure with a high satisfaction rate. Following the first 15 procedures performed by one surgical team, the operative time decreased considerably. Further randomized controlled studies are needed to compare this procedure to regular cesarean section and evaluate neonatal outcomes.

Background: Computed tomography (CT) is the main diagnostic modality for detecting pancreatic adenocarcinoma.

Objectives: To assess the frequency of missed pancreatic adenocarcinoma on CT scans according to different CT protocols.

Methods: The medical records of consecutive pancreatic adenocarcinoma patients were retrospectively collected (12/2011–12/2015). Patients with abdominal CT scans performed up to a year prior to cancer diagnosis were included. Two radiologists registered the presence of radiological signs of missed cancers. The frequency of missed cancers was compared between portal and pancreatic/triphasic CT protocols.

Results: Overall, 180 CT scans of pancreatic adenocarcinoma patients performed prior to cancer diagnosis were retrieved; 126/180 (70.0%) were conducted using pancreatic/triphasic protocols and 54/180 (30.0%) used portal protocols. The overall frequency of missed cancers was 6/180 (3.3%) in our study population. The frequency of missed cancers was higher with the portal CT protocols compared to the pancreatic/triphasic protocols: 5/54 (9.3%) vs. 1/126 (0.8%), P = 0.01. CT signs of missed cancers included small hypodense lesions, peri-pancreatic fat stranding, and dilated pancreatic duct with a cut-off sign.

Conclusions: The frequency of missed pancreatic adenocarcinoma is higher on portal CT protocols. Physicians should consider the cancer miss rate on different CT protocols.

Nocardia species are gram-positive aerobic bacteria, usually acquired by inhalation or traumatic percutaneous inoculation [1,2]. It is a rare opportunistic infection that mainly occurs in immunocompromised hosts, patients with human immunodeficiency virus (HIV), organ transplant recipients, and long-term corticosteroid treated patients [1,2]. It is associated with high morbidity and mortality rates. The increased use of tumor necrosis factor (TNF) inhibitors has been accompanied by increased risk of different opportunistic infections including reactivation of tuberculosis, viral hepatitis B and C, listeria, fungal and bacterial infections [3,4]. To date, there are scarce case reports regarding nocardial infection with anti-TNF, particularly during the first 6 months of treatment.

We present a case of nocardial tenosynovitis of the hand in a patient with psoriatic arthropathy who was followed in our rheumatology clinic in Meir medical center in Israel after treatment with an anti TNF therapy.

Uveal melanoma (UM) affects approximately six individuals per million per year in the United States, with similar rates in Mediterranean countries. Although it appears to have a low prevalence, it is the most common primary intraocular malignancy in adults. Clinically, it presents in most patients as a painless loss or distortion of vision, although it may also be accidentally discovered at routine ophthalmic examination. Associated risk factors include fair skin tone, light eye color, presence of a choroidal nevus, oculodermal melanocytosis (nevus of ota), dysplastic nevus syndrome, and germline BRCA-associated protein 1 mutations (BAP1 mutations) [1].

Background: Influenza and coronavirus disease 2019 (COVID-19) are respiratory diseases with similar modes of transmission. In December 2021, influenza re-emerged after it had been undetected since March 2020 and the Omicron variant replaced the Delta variant. Data directly comparing the two diseases are scarce.

Objectives: To compare the outcomes of patients with both the Omicron variant and influenza during 2021–2022.

Methods: We performed a retrospective study conducted in Beilinson hospital, Israel, from December 2021 to January 2022. We included all hospitalized patients with either laboratory-confirmed COVID-19 or influenza. The primary outcome was 30-day mortality.

Results: We identified 167 patients diagnosed with Omicron and 221 diagnosed with Influenza A. The median age was 71 years for Omicron and 65 years for influenza. Patients with Omicron had a significantly higher Charlson Comorbidity Index score (4 vs. 3, P < 0.001). Patients with Omicron developed more respiratory failure that needed mechanical ventilation (7% vs. 2%, P = 0.05) and vasopressors (14% vs. 2%, P < 0.001) than patients with influenza. In a multivariate model, 30-day mortality was lower in patients diagnosed with influenza than in patients diagnosed with Omicron (19/221 [9%] vs. 44/167 [26%], hazard ratio 0.45, 95% confidence interval 0.25–0.81).

Conclusions: Patients diagnosed with Omicron had higher mortality than patients diagnosed with seasonal influenza. This finding could be due to differences in co-morbidities, the virus pathogenicity, and host responses to infection.

Background: Data are scarce on the immunogenicity of coronavirus disease 2019 vaccines in patients with autoimmune rheumatic diseases (ARD).

Objectives: To measure the immunoglobulin G (IgG) response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and to evaluate clinical characteristics associated with seropositivity.

Methods: Samples were collected after the second and third doses of the three different types of vaccines in ARD patients. Seroconversion rates and IgG antibody S1/S2 titers were measured.

Results: The type of ARD diagnosis and previous treatment had no significant impact on the serum IgG antibody levels measured after the second (P = 0.489 and P = 0.330, respectively) and boost dose (P = 0.441 and P = 0.446, respectively). What made a significant difference regarding serum IgG antibody levels after the second dose was the type of SARS-CoV-2 vaccine. The difference was highly statistically significant for all vaccine types (P = 0.001 with the highest odds ratio for the mRNA vaccine). After the boost with the mRNA vaccine, all patients achieved a high level of serum IgG antibody levels (t = 10.31, P = 0.001). No ARD patients experienced serious post-vaccinal reactions. Eight patients developed COVID-19 before the boost dose.

Conclusions: In ARDs patients, the highest level of serum IgG antibody against S1/S2 proteins was achieved with the mRNA vaccine, irrespective of the therapy applied or the type of the disease. We recommend a booster dose with mRNA vaccine in all ARDs for the highest SARS-CoV-2 protection without serious post-vaccinal reactions observed.

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.

Fibromyalgia syndrome is a chronic widespread musculoskeletal pain syndrome primarily characterized by fatigue, sleep disturbances, and cognitive impairment. Its etiology remains elusive despite ongoing research and has multifactorial elements. It has been shown that traumatic events and neuro-inflammation, autoimmunity, and genetic factors contribute to the pathogenesis of fibromyalgia syndrome.

Recent evidence has pointed to a bi-directional link between cardiovascular disease, traditional cardiovascular risk factors, and metabolic syndrome (MetS), together with the presence of fibromyalgia [1].

Background: Among the most frequent complications following transcatheter aortic valve replacement (TAVR) is hemostasis imbalance that presents either as thromboembolic or bleeding. Deviations in platelet count (PC) and mean platelet volume (MPV) are markers of hemostasis imbalance.

Objectives: To determine the predictive value of pre- and post-procedural PC and MPV fL 1-year all-cause mortality in patients who underwent TAVR.

Methods: In this population-based study, we included 236 TAVR patients treated at the Tzafon Medical Center between 1 June 2015 and 31 August 2018. Routine blood samples for serum PC levels and MPV fL were taken just before the TAVR and 24-hour post-TAVR. We used backward regression models to evaluate the predictive value of PC and MPV in all-cause mortality in TAVR patients.

Results: In this study cohort, MPV levels 24-hour post-TAVR that were greater than the cohort median of 9 fL (interquartile range 8.5–9.8) were the strongest predictor of 1-year mortality (hazard ratio 1.343, 95% confidence interval 1.059–1.703, P-value 0.015). A statistically significant relationship was seen in the unadjusted regression model as well as after the adjustment for clinical variables.

Conclusions: Serum MPV levels fL 24-hour post-procedure were found to be meaningful markers in predicting 1-year all-cause mortality in patients after TAVR.