Israel Medical Association Journal

Background: Current guidelines for the treatment of heart failure with reduced ejection fraction (HFrEF) are based on studies that have excluded or underrepresented older patients.

Objectives: To assess the value of guideline directed medical therapy (GDMT) in HFrEF patients 80 years of age and older.

Methods: A single-center retrospective study included patients hospitalized with a first and primary diagnosis of acute decompensated heart failure (ADHF) and ejection fraction (EF) of ≤ 40%. Patients 80 years of age and older were stratified into two groups: GDMT, defined as treatment at hospital discharge with at least two drugs of the following groups: beta-blockers, angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or mineralocorticoid antagonists; and a personalized medicine group, which included patients who were treated with up to one of these drug groups. The primary outcomes were 90-day all-cause mortality, 90-day rehospitalization, and 3-years mortality.

Results: The study included 1152 patients with HFrEF. 254 (22%) patients who were at least 80 years old. Of the group, 123 were GDMT at discharge. When GDMT group was compared to the personalized medicine group, there were no statistically significant differences in terms 90-day mortality (17% vs. 13%, P = 0.169), 90-day readmission (51 % vs. 45.6%, P = 0.27), or 3-year mortality (64.5% vs. 63.3%, P = 0.915).

Conclusions: Adherence to guidelines in the older adult population may not have the same effect as in younger patients who were studied in the randomized clinical trials. Larger prospective studies are needed to further address this issue.

Background: There is an increasing use of anti-protein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs); however, real-world data is lacking.

Objectives: To define the demographic and clinical characteristics of patients treated with anti-PCSK9 mAbs. To evaluate efficacy, tolerability, and differences between the approved agents.

Methods: A retrospective cohort study was conducted of patients treated at the lipid clinic at Rabin Medical Center (Beilinson Campus), Israel, from January 2016 to December 2019. Data from electronic records were evaluated for demographic and clinical characteristics, indication for use, response of lowering low-density lipoprotein cholesterol (LDL-C)/non-high-density lipoprotein cholesterol (non-HDL-C) levels and reaching target levels, side effects, tolerability, differences between the agents, and doses.

Results: The study cohort included 115 patients. Two-thirds (n=75) were at high cardiovascular risk, the rest at very high risk (n=40). The major indication for treatment was statin intolerance (n=97, 84%). Most patients (n=102, 88%) were treated by anti-PCSK9 mAbs agents only. LDL-C and non-HDL-C levels were decreased by 47% and 39%, respectively (156 + 49 to 81 + 39 and 192 + 53 to 116 + 42 mg/dl), within 6 months and remained stable. Two-thirds (n=76) of the patients reached their lipid target levels. No clinically significant differences were observed between the agents in efficacy or tolerability.

Conclusions: In a real-world setting, anti-PCSK9 mAbs are used primarily as a single agent in high-risk and very high-risk cardiovascular populations with statin intolerance. They are well tolerated and effective in reduction of LDL-C levels. Further studies are needed to clarify comparisons between agents and doses.

Worldwide, students of healthcare professions attend clinical rotations at medical facilities. Much research, and consequently scientific publications, is produced during their studies, bearing the fruits of student–faculty collaboration. To the best of our knowledge, no previous contract has been proposed detailing the fine print to pre-determine mutual responsibilities and privileges of students and faculty. Our objective was to present such a contract to the relevant students and faculty. We conducted a literature review to study existing proposals and solutions for this dilemma. Appropriate guidelines were also scanned. We included a proposal for a standard contract as the basis for student–faculty agreement for conducting research and publishing collaborative work. Questions regarding the relative contribution of students and subsequent authorship often arise. Vague rules and absent regulations in this realm can, at times, can be disadvantageous to students. We foresee a future role for our proposed agreement.

Mesenteric venous thrombosis (MVT) refers to acute, subacute, or chronic thrombosis and occlusion of the mesenteric veins. MVT is an uncommon disorder, with an estimated incidence of is 2.7 per 100,000 patient-years. It accounts for 1 in 5000 to 15,000 inpatient admissions [1,2].

Intravesicular administration of Bacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has long been used as adjuvant therapy for treatment of non-muscle invasive bladder carcinoma. BCG is usually well tolerated; however, infectious complications can range from 1–5% of cases. Infectious complications of BCG [1] can be divided into localized disease, which is considered a late onset disease occurring 3 months following treatment such as cystitis, Epididymo-orchitis, and pyelonephritis. Another form is a systemic disease, which is an early onset manifestation including sepsis syndrome that usually occurs directly after treatment and is the most common form of disseminated BCG infection.

Hypereosinophilia is defined as the absolute eosinophilic count of above 1500 cells/µL in the peripheral blood on two separate tests taken during one month and/or the pathological confirmation of hypereosinophilia. There are many conditions that are associated with increased eosinophil counts including: parasitic infections, drug reactions, eosinophilic granulomatosis with polyangiitis, allergic reactions, drug reaction with eosinophilia and systemic symptoms (DRESS), primary immunodeficiencies (PID), eosinophilic gastrointestinal diseases (EGID), familial hypereosinophilia, and neoplasms [1]. Molecular classification may be an adjuvant in the classification of hypereosinophilia [2]. Our patient presented with hypereosinophilia as part of a paraneoplastic syndrome.

Candida species inhabit the gastrointestinal tract. Isolation of Candida from the respiratory tract has been found and reflects colonization, particularly among mechanically ventilated patients [1]. However, the existence of candida as a respiratory pathogen was previously doubted. Candida pneumonia is a rare and challenging-to-diagnose entity. We present a histopathologically confirmed case of necrotizing Candida pneumonia and lung abscess in a solid organ transplant recipient.

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.

Myelodysplastic syndrome (MDS) is frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory responses of the immune system. The biological linkage between MDS clones and the occurrence of autoimmune manifestations is mirrored by the response of the latter to MDS modifying therapeutic approaches [1]. We encountered a rare case of MDS coexisting with antiphospholipid syndrome (APS), which was effectively treated with a hypomethylating agent followed by allogenic bone marrow transplantation.

Background: Multiple myeloma (MM) accounts for approximately 10% of hematological malignancies. The monoclonal immunoglobulin G kappa (IgG-κ) daratumumab can bind to CD38 on MM cells and be detected in serum immunofixation (IF), causing pitfalls in M-protein quantification.

Objectives: To determine the efficacy of mitigating the interference of IgG MM treated with daratumumab.

Methods: Levels of Ig, free light chains (FLC) kappa (κ) and lambda (λ), serum protein electrophoresis (SPE)/IF, and Hydrashift 2/4 assays were assessed following manufacturer's instructions in three patients.

Results: Patient 1 was a 70-year-old male diagnosed with IgG-λ MM. The IF distinguished two monoclonal bands (IgG-κ and IgG-λ). With the Hydrashift assay, the daratumumab–anti-daratumumab immune complex shifted the IgG-κ to the α zone, suggesting that the monoclonal IgG-κ band corresponded to daratumumab. Patient 2 was a 63-year-old male with IgG-κ MM who was receiving daratumumab once every other week. SPE/IF assay revealed a faint monoclonal IgG-κ band in the g zone. A stronger monoclonal band was observed after administration. The IgG-κ band disappeared on the Hydrashift assay, while the daratumumab–anti-daratumumab complex appeared as a broad smear in the α-region. Patient 3, a 63-year-old male diagnosed with IgG-λMM, was receiving daratumumab once every other month. The IF assay showed two distinct bands (IgG-κ and IgG-λ) post-daratumumab administration. The shift to the α zone of the IgG-κ bands on the Hydrashift assay confirmed that the additional band observed post-infusion was due to the daratumumab.

Conclusions: The Hydrashift assay can help distinguish daratumumab from endogenous M-spike.

Background: Rare incidence cases are part of the routine work of pediatric surgeons. Cecal anomalies in children are an example of such cases.

Objectives: To describe the presentation, workup, management and outcome of rare cecal anomalies in children and to analyze the skills needed for their successful treatment.

Methods: A retrospective chart review was conducted of all cases of cecal anomalies managed by the pediatric surgical service at a tertiary hospital from June 2017 to January 2020. Data regarding demographics, clinical presentation, radiological studies, surgical treatment, pathology, complications, and outcome were collected.

Results: Five cases of cecal anomalies were encountered over a period of 32 months, including a cecal volvulus, cecal duplication, cecal intussusception, and two cecal masses (one ulcerated lipoma and one polyp). All patients, except the patient with cecal duplication, presented acutely and were managed surgically. Long-term follow-up of 17–24 months was unremarkable in all cases.

Conclusions: A wide knowledge base, careful judgment, and creativity enable pediatric surgeons to successfully treat rare conditions such as rare cecal anomalies. These skills should be part of the education of pediatric surgery trainees.

Background: The hepatobiliary system is a sterile micro-environment. Bacterial infection in this system is most commonly associated with anaerobes as well as gram-positive and gram-negative bacteria. Biliary infections with Staphylococcus aureus are poorly characterized.

Objectives: To depict the clinical characteristics and outcome of patients with S. aureus infection of the hepatobiliary system.

Methods: Medical records of patients with bile cultures positive for S. aureus from January 2006 to November 2020 were extracted from the computerized database of a hospital in Israel.

Results: We analyzed the results of 28 cases that were found in the database. The mean age of study patients was 62.2 ± 19 years. Hypertension, dyslipidemia, chronic kidney disease, diabetes, and benign prostatic hypertrophy were the most common co-morbidities (57.1%, 32.1%, 25%, 25%, and 25%, respectively). Fourteen of the methicillin-resistant S. aureus (MRSA) bile cultures (82.3%) were a result of primary S. aureus biliary infections (no other source for S. aureus infection) and the remainder were of a secondary infection. Eight of the MRSA cultures (47.1%) were from hospital acquired infections. Increased hospital mortality in patients with S. aureus hepatobiliary infection was associated with hypertension (P = 0.04), bedridden status (P = 0.01), and nursing home residence (P = 0.003).

Conclusions: Hepatobiliary infection with S. aureus can manifest in a variety of ways. S. aureus should be especially considered in patients who are bedridden, present with hypertension, or live in nursing homes because of their association with in-hospital mortality resulting from this entity.

Background: Contact dermatitis is an inflammatory skin disorder characterized by an erythematous pruritic rash. The disorder can be either irritant or allergic. Allergic contact dermatitis is diagnosed by patch testing along with patient history.

Objectives: To review the results of patch tests conducted thought 2 years and to present real-life data characterizing clinical features and comparing prevalent local allergens to the ones common worldwide.

Methods: The retrospective cohort included 517 participants (384 females and 133 males) who underwent patch testing during a 2-year period. For each patient, clinical and demographic data were collected, and statistical analysis was conducted.

Results: We found that 261 patients had a positive test for at least one allergen. More females tested positive than males (52.9% vs. 43.6%). Test indications other than dermatitis were associated with a negative result. Hands, head, and neck were the most prevalent body parts affected. Patients with a background of atopic dermatitis had a higher rate of contact sensitization (69 vs. 43). Patients with a specific suspected offending allergen had significantly higher contact sensitizations. The most common allergen was nickel.

Conclusions: Patch testing should be conducted in patients with relevant dermatological findings accompanied by taking a thorough medical history. Clinicians should be updated on emerging allergens and exposure trends.

Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin's lymphoma. There are limited data on the management of PCNSL outside of clinical trials.

Objectives: To report experience with three main high-dose methotrexate (HDMTX)-based protocols for PCNSL treatment at one medical center.

Methods: We conducted a retrospective review of the medical records of patients diagnosed with PCNSL who were treated at Soroka Medical Center between 2007 and 2019.

Results: The study included 36 patients, median age 64.9 years; 33 patients received a HDMTX backbone induction therapy, 21 (58.3%) received consolidation treatment in addition. In the entire cohort, 25 patients (75.7%) achieved complete remission (CR, CRu-unconfirmed), with mean progression-free survival (PFS) 32 ± 6.9 months and median overall survival (OS) 59.6 ± 12.4 months. More aggressive regiment such as combination of rituximab, HDMTX, cytarabine and thiotepa had better responses 5 (100%) CR, but also a higher incidence of side effects such as neutropenic fever 5 (100%). In subgroup analysis by age (younger vs. older than 60 years), the PFS was 24.2 vs. 9.3 months, and OS was 64.1 vs. 19.4 months, respectively.

Conclusions: A difference in CR and PFS favored a more aggressive protocol, but the toxicity of the multiagent combinations was significantly higher. The prognosis in younger was better than in older patients, with higher rates of CR, PFS, and OS, although not statistically significant. Overall treatment outcomes are encouraging; however, there is a real need for an adaptive approach for older patients and balancing among the effectiveness and side effects.

Background: Gestational hypertensive (GH) disorders remain a major obstetric problem.

Objective: To evaluate the incidence of gestational hypertensive disorders among participants undergoing intrauterine insemination (IUI) after exposure to various levels of sperm from sperm donation (SD).

Methods: A retrospective case-control study was conducted at a single tertiary medical center between 2011 and 2019. Participants conceived via IUI using SD from a single sperm bank and had a successful singleton birth. Group 1 conceived during 1–2 cycles of IUI from the same sperm donor; whereas Group 2 after 3+ cycles.

Results: Overall 171 patients (Group 1 = 81, Group 2 = 90) met inclusion criteria. Participants showed no differences in age, chronic medical conditions, or history of pregnancy complications. The groups differed in gravidity and parity. The factors positively associated with Group 1 included either preeclampsia or GH (11 [13.5%] vs. 1 [1.1%], P = 0.001) and GH alone (8 [9.9%] vs. 1 [1.1%], P = 0.014). Newborns from Group 1 had a statistically significant lower birth weight than those from Group 2 (3003 grams ± 564.21 vs. 3173 grams ± 502.59, P = 0.039). GH was more prevalent in Group 1 (P = 0.008) than a control group of 45,278 participants who conceived spontaneously. No significant differences were observed between Group 2 and the control group.

Conclusions: The incidence of GH and preeclampsia in participants was higher among those exposed to 1–2 cycles than those exposed to 3+ cycles of IUI.