Israel Medical Association Journal

Higher potency bisphosphonates, typically intravenous formulations, are given at lower doses for postmenopausal women. The treatment has improved compliance compared to daily oral therapy. Since bisphosphonates are exclusively excreted via the kidneys, intravenous formulation has been associated with deterioration of renal function, specifically in the setting of preexisting renal disease or concomitant use of nephrotoxic agents [1].

Celiac disease (CD) is an immune-based reaction to dietary gluten. CD can present with a diverse array of symptoms. Many CD patients have no symptoms at all. Thus, a great number of atypical cases of CD remain undiagnosed, leading to a risk of long-term complications. Some atypical symptoms of CD such as pregnancy complications, infertility, recurrent abortions, intrauterine growth restriction, preterm delivery, and severe preeclampsia have been investigated in undiagnosed and diagnosed pregnant women with CD. Nutrient deficiency and autoimmune pathogenic mechanisms have been hypothesized to be the explanation of these adverse pregnancy outcomes. Recently, an association between obstetric complications and anti-tissue transglutaminase antibodies titers in women with CD has been reported. While the adverse effects of CD on the reproductive system are well investigated, there are only a few reports in the literature on the effect of pregnancy and puerperium on CD. We reviewed the published literature on the adverse effects and pathophysiology of CD in reproductive disorders and the effect of pregnancy and puerperium on the manifestation of CD.

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.

On Saturday, 7 October 2023, the Jewish holiday of Simchat Torah, our entire country woke to a reality of the worst terror attacks it has ever known, despite its long history of wars and terror. These horrific attacks included killing and burning babies, children, women, men, and the elderly; raping women; beheading babies; destroying settlements; and kidnapping more than 240 civilians and soldiers. The severe traumatic events created different circles of those exposed to trauma. In each group, the intensity of the trauma was different and had different characteristics.

Background: Helicobacter pylori (H. pylori) prevalence varies according to both geographical region and ethnicity. The interplay between these two factors has been poorly studied.

Objectives: To determine the positivity rate of H. pylori infection among Jewish and Arab patients who live in a mixed urban center in Israel.

Methods: Between November 2009 and September 2014, dyspeptic patients referred to a gastroenterology clinic in Lod, Israel, were enrolled in a prospective study. For each patient, clinical and epidemiological data were collected and a noninvasive or endoscopy-based test for H. pylori was performed.

Results: A total of 429 consecutive patients (322 Jewish and 107 Arabs), mean age 45 years (range 15–91 years) were included; 130 males. Overall positivity for H. pylori was 42.4% (182/429). The positivity rate of H. pylori was 38.8% for Jews (125/322) and 53.2% for Arabs (57/107) in Lod (P < 0.01). When immigrants were excluded, the difference in H. pylori positivity did not reach statistical significance (45.0% [77/171] vs. 53.2% [57/107], P = 0.217, in Jews and Arabs, respectively).

Conclusions: H. pylori infection was more common in Arabs that Jews in the mixed city of Lod, Israel. This finding may suggest that non-environmental factors were responsible for the observed difference in H. pylori positivity.

Background: Low-risk venous thromboembolism (VTE) patients are advised to be discharged from the emergency department (ED) on direct oral anticoagulants (DOACs) treatment. There is no data on whether this recommendation is followed in Israel.

Objectives: To characterize newly diagnosed VTE patients who were discharged from the ED, their anticoagulation treatment at the ED, the recommended discharge protocol, and patient adherence.

Methods: We conducted a retrospective cohort study, which included all newly diagnosed VTE patients who were discharged from the ED. Collected data included demographic and clinical background; anticoagulation treatment at the ED, recommended discharge protocol and its subsequent adherence, patient subsequent, recommended hematological evaluation, and adverse events.

Results: The study group included 443 patients, 89% with deep vein thrombosis (DVT). Approximately three-quarters were treated with anticoagulants in the ED, 98% with enoxaparin. At discharge, anticoagulants were recommended for all; 49% continued enoxaparin, 47% DOACs, and 4% warfarin. After 4 weeks, 67% were treated with DOACs, 22% with enoxaparin, 5% with warfarin. Approximately 6% discontinued all treatment. After 12 weeks, 90% of the patients who were taking DOACs adhered to the protocol, whereas only 70% and 50% among the enoxaparin and warfarin users, respectively, did. Only 56% were referred for hematological evaluation. The 12-week rate of adverse reactions was approximately 2%. The use of DOACs and the recommendation for further hematological evaluation increased over time.

Conclusions: Clinician training regarding discharge of VTE patients from the ED should continue.

Background: Younger patient age and relatively good prognosis have been described as factors that may increase caregiver motivation in treating patients with septic shock in the intensive care unit (ICU).

Objectives: To examine whether clinical teams tended to achieve unnecessarily higher map arterial pressure (MAP) values in younger patients.

Methods: We conducted a population-based retrospective cohort study of patients presenting with septic shock who were treated with noradrenaline and hospitalized in a general ICU between 2006 and 2018. The patients were classified into four age groups: 18-45 (n=129), 46-60 (n=96), 61-75 (n=157), and older than 75 years (n=173). Adjusted linear mixed models and locally weighted scatterplot smoothing (LOWESS) curves were used to assess associations and potential non-linear relationships, respectively, of age group with MAP and noradrenaline dosage.

Results: The cohort included 555 patients. An inverse relation was observed between average MAP value and age. Among patients aged 18–45 years, the average MAP was 4.7 mmHg higher (95% confidence interval 3.4–5.9) than among patients aged > 75 years (P-value <0.001) after adjustment for sex, death in the intensive care unit, and Sequential Organ Failure Assessment scores.

Conclusions: Among patients with septic shock, the titration of noradrenaline by staff led to a higher average MAP for younger patients. Although the MAP target is equal for all age groups, staff may administer noradrenaline treatment according to a higher target of MAP due to attitudes toward patients of different ages, despite any evidence that such practice is beneficial.

Background: The continuity equation (CE) used for evaluating aortic stenosis (AS) is based on values obtained from transthoracic echocardiography (TTE) with the assumption that the left ventricular outflow tract (LVOT) has a circular shape. Transesophageal echocardiography (TEE) may be used for accurate measurement of the LVOT cross-sectional area (CSA). Previous studies have focused on fusion from TEE for LVOT-CSA measurement and TTE for velocity time integrals (VTI) calculations.

Objectives: To assess aortic valve area (AVA) using parameters obtained exclusively from TEE as an alternative approach.

Methods: Thirty patients with equivocal AS based on TTE were evaluated using TEE for further assessment.

Results: The mean pressure gradient across the aortic valve (AV) was 38 ± 5.9 and 37.9 ± 7.6 mmHg in TTE and TEE, respectively, P = 0.42. LVOT-CSA was larger in TEE (3.6 ± 0.3 vs. 3.4 ± 0.3 cm², P = 0.049). VTI over the AVA was similar (98.54 ± 22.8 and 99.52 ± 24.52 cm in TTE and TEE, respectively, P = 0.608), while VTI across the LVOT was higher when measured by TTE (24.06 ± 5.8 vs. 22.03 ± 4.3 cm, P < 0.009). Using the CE, AVA was 0.82 ± 0.3 vs. 0.83 ± 0.17 cm² in TEE vs. TTE, respectively, P = 0.608. Definitive grading was achieved in all patients (26 patients defined with severe AS and 4 with moderate).

Conclusions: In equivocal cases of AS, full assessment using TEE may be a reliable modality for decision making.

Background: In the past decade, numerous new imaging and laboratory tests have been implemented that significantly contribute to improved medical diagnostic capabilities. However, inappropriate utilization, which occurs on a large scale, has significant ramifications for both patient care and health systems.

Objectives: To assess the impact of a novel clinical decision support system (CDSS) applied to our electronic medical records on abdominal ultrasonography utilization pattern.

Methods: We conducted a retrospective cohort study comparing patterns of abdominal ultrasound utilization in cases of liver enzyme elevation, with and without CDSS, between February and May in 2017 (before CDSS implementation) and during the same months in 2018 (after CDSS implementation). The following parameters were collected: number of tests ordered according to the guidelines, tests with a diagnostic value, and order forms completed with any data or a diagnostic question. The comparison was conducted using chi-square test.

Results: Of 152 abdominal ultrasound tests, 72 were ordered in the pre-implementation period and 80 in the post-implementation period. The system failed to reach statistical significance regarding the rates of ordered tests according to the guidelines and/or tests with a diagnostic value. However, the use of the CDSS had a statistically significant impact regarding completing the order form with data, including a specific diagnostic question.

Conclusions: The effect of the system on the efficiency of test utilization was partial. However, our findings strongly suggested that CDSS has the potential to promote proper usage of complementary technologies.

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.

In the acute settings of generalized myasthenia gravis (MG) treatment options include plasma exchange (PLEX), intravenous immunoglobulin (IVIG), and pyridostigmines. A thymoma is associated with the disease in up to 20% of cases [1,2].

In cases where a thymoma is detected, surgical treatment to remove the tumor is recommended in certain age groups. At present, there are no clear guidelines regarding the optimal time to perform thymectomy after diagnosis of acute crisis or from the last treatment to thymectomy. Treatment is at the clinician's discretion.

A 42-year-old healthy man collapsed suddenly in the street while walking. The patient received 2 minutes of basic life support until an automatic external defibrillator was brought and detected ventricular fibrillation (VF), which was successfully terminated by a single shock. The patient regained consciousness and was transferred to the hospital.

The patient’s physical examination was normal with no neurologic deficit. Blood pressure was 147/102 mmHg. Brain computed tomography showed normal findings. The first troponin I measurement within 1 hour of the event was in the normal range (19.6 ng/L, normal < 20 ng/L) and rose to 99.9 ng/L after 3 hours.

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?

There are numerous experimental studies on the effect of immune modulation on the skeleton but few clinical ones.

In this letter, we supplement the previous information on enhanced bone healing. A new branch of medicine, osteoimmunology, describes fracture healing as an active immune system process evolving in a cascade of repairs.

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.