Israel Medical Association Journal

Background: Direct oral anticoagulants (DOACs) have significantly transformed anticoagulant therapy, improving effectiveness, safety, and convenience in managing thromboembolic conditions. However, concerns persist regarding drug-related problems (DRPs) associated with DOACs, necessitating the establishment of multidisciplinary antithrombotic stewardship programs to optimize the selection, dosing, and monitoring of DOACs.

Objectives: To evaluate the incidence and types of DRPs associated with DOACs, the frequency of clinical pharmacist consultations, the acceptance rates of the clinical pharmacist recommendations, and physicians' adherence to appropriate DOACs prescribing practices.

Methods: A retrospective cohort study was conducted over 4 months in the internal medicine departments at Shamir Medical Center (Assaf Harofeh), Israel. The study included patients aged 18 years and older who were prescribed DOACs (apixaban, rivaroxaban, and dabigatran). Data on patient characteristics and clinical outcomes were collected from electronic medical records. A clinical pharmacist reviewed and reassessed the appropriateness of DOAC prescribing.

Results: During the study period, 415 patients receiving DOACs were identified. Among them, 28.4% had inappropriate DOAC prescriptions leading to 128 recommended interventions. The most common DRP was underdosing (29.7%) followed by unjustified antiplatelet use (26.6%). Clinical pharmacists performed 85.9% of the interventions, with a physician acceptance rate of 72.7%. Patients with inappropriate DOAC prescriptions exhibited increased trends in thromboembolic events and in-hospital mortality.

Conclusions: Despite over a decade of clinical experience with DOACs, DRPs remain a significant challenge. Implementing antithrombotic stewardship programs is critical for optimizing DOACs use, reducing DRPs, and enhancing patient safety.

Methotrexate, a folate analog antimetabolite, is one of the oldest cytotoxic drugs still in use. It is active against a variety of malignancies including bladder and breast cancer, head and neck tumors, gestational choriocarcinoma, osteogenic sarcoma, lymphomas, and leukemias.

Methotrexate is given mostly intravenously (IV), usually at standard doses (milligrams). It can also be delivered in much higher doses (grams), which is known as high-dose methotrexate (HDMTX). The intrathecal (IT) route is used particularly in children with acute lymphoblastic leukemia (ALL) and in adults with meningeal carcinomatosis. The drug may be administered orally as well, mainly in non-oncological conditions such as rheumatoid arthritis and other autoimmune diseases.

Immune thrombocytopenia (ITP), driven by autoantibodies targeting platelet antigens, is an acquired disorder posing considerable challenges, particularly in pregnancy, where its prevalence escalates to 1–3 per 10,000 women, a tenfold increase compared to the general population [1]. Predominantly characterized by a heightened risk of bleeding, particularly during pregnancy, the incidence of significant hemorrhagic events stands at approximately 18%, mostly non-severe [1]. Despite its rarity, thrombosis can manifest as a complication, especially when accompanied by antiphospholipid antibodies, which amplify the propensity for arterial and venous thrombotic events alongside obstetric complications and thrombocytopenia [2,3].

In this case report, we present the case of a young female with primary unexplained infertility, complicated by ITP and antiphospholipid syndrome (APS), predisposing her to increased bleeding and thrombotic risks. During a multidisciplinary consultation, the medical staff navigated the intricate landscape of fertility treatments and pregnancy options, carefully considering the delicate balance between risks and benefits to optimize patient outcomes.

A 70-year-old female with a 10-year history of dermatomyositis involving the skin, muscles, and gastrointestinal system was diagnosed based on proximal muscle weakness, typical dermatomyositis-specific rashes, elevated creatine kinase, and muscle biopsy findings consistent with dermatomyositis. Myositis-specific autoantibodies were negative.

The patient initially received treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) but experienced gastrointestinal intolerance to both methotrexate and azathioprine. Subsequently, she was managed with intravenous immunoglobulin (IVIg) for 4 years; however, due to a relapse of muscle involvement, rituximab was initiated and has been administered for the past 3 years.

Over the last year, the patient achieved remission in muscle involvement but experienced worsening dermatomyositis-specific skin manifestations, including heliotrope rash, Gottron signs, and holster sign [Figure 1A], accompanied by severe pruritus that significantly impaired her quality of life. The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score reached 17. Her skin condition remained refractory despite treatment with topical steroids and calcineurin inhibitors.

Recent publications based on newly available list of surgeries performed in Nazi concentration camps raised the question of motivation for thousands of procedures on internees incarcerated from occupied Europe. The performance of major surgeries would be suspicious in their intent, indicating, if not directly proving, their intention as an exercise for junior physicians or medical students. The concept of the Revier (infirmary) is discussed. The Revier (also known as Krankenrevier or infirmary) in Nazi concentrations camps was located next to the extermination unit. Procedures performed at the Revier were considered non-therapeutic, as the victims had a minimal chance of survival without appropriate postoperative facilities. A review of medical documents of major concentration camps (Auschwitz, Mauthausen, Gusen, Ebensee) indicates the criminal intention of the authorities. This unusual type of crime was raised in post-war trials, but no specific legal code was nominated.

Obesity is a growing global health concern, with its prevalence contributing to the rise of multiple chronic conditions, including autoimmune diseases. In this review I explore the intricate relationship between obesity and autoimmunity, focusing on how excess adiposity can affect immune responses and promote the development of autoimmune disorders. Obesity alters adipose tissue architecture, promoting chronic low-grade inflammation and triggering the release of pro-inflammatory cytokines, which contribute to immune system dysregulation. Adipose tissue is no longer seen as merely an energy store but as an active endocrine organ that interacts with the immune system. The review delves into mechanisms such as the role of adipokines, altered T cell function, and the recruitment of immune cells to inflamed adipose tissue, which together exacerbate autoimmune risk in obese individuals. Genetic and environmental factors also play a critical role in these processes, as polymorphisms and high-fat diets have been shown to influence both obesity and autoimmune susceptibility. Last, the review explores potential therapeutic strategies, such as lifestyle interventions and targeting obesity-driven inflammatory pathways, which could mitigate autoimmunity. Understanding the connection between obesity and autoimmunity offers insights into more effective interventions for patients suffering from these intertwined conditions.

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by persistent respiratory symptoms and airflow obstruction determined by spirometry, including emphysema, chronic bronchitis, and small airway disease. Traditional treatment settings for COPD exacerbations typically involve in-hospital care. However, hospital-at-home (HaH) programs have emerged as an innovative model to provide hospital-level care at a patient's home. I synthesized available randomized controlled trials (RCTs) and compared the outcomes of COPD management in HaH and in-hospital settings. I searched for English language medical literature studies of COPD patients in HaH programs compared to in-hospital. Searches were performed in PubMed, EMBASE, Scopus, and CENTRAL. Outcomes were compared, meta-analyses were performed, and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. Heterogeneity was evaluated and I² statistic was used to measure the proportion of inconsistency in individual studies. Potential publication bias was also calculated. Seven controlled studies representing 19 sub-studies (data sets) were selected according to the inclusion criteria. The OR of the HaH and in-hospital comparison was 0.542, 95%CI 0.379–0.774, P = 0.001. The different clinical outcomes of HaH were better or similar to those at regular hospitals, but with higher patient preference (OR 0.316, 95%CI 0.198–0.506). Heterogeneity and inconsistency were small, with no significant publication bias. HaH may be recommended for COPD patients' hospitalization when needed according to the specific indications and patients matching HaH criteria.

Plastic and reconstructive surgery is a specialty that has an important place in the surgical field. Plastic surgeons cooperate with all surgical disciplines to solve complex multidisciplinary surgical cases. This issue of the Israel Medical Association Journal (IMAJ) covers some of the groundbreaking treatments being performed by plastic surgeons in Israel.

The articles show the wide and complex range of issues where plastic surgery is needed, including hospital-based breast reconstructions, oncologic resections, and innovative lymphedema surgery, as well as aesthetic procedures. The efforts of plastic surgeons have been especially highlighted due to the Iron Swords war, which started on 7 October 2023. Injuries included complex burns and amputations that required attention under fire. In addition, advances were achieved through cutting‑edge reconstructive microsurgical traumatic solutions. Together, these articles highlight how Israeli teams have leveraged experience in trauma, high‑volume civilian and military caseloads and innovative inspirations that have generated knowledge that may be broadly applicable to surgeons worldwide.

Burn injuries pose a significant challenge in mass casualty scenarios. They require rapid and effective intervention to optimize patient outcomes. In this case report, we present the management of three severely burned patients following the October 7th terrorist attack in Israel. Our objective is to highlight the role of NexoBrid® (MediWound Ltd, Yavne, Israel) enzymatic debridement [1] as a primary intervention and discuss the challenges encountered in a mass casualty setting.

During these challenging times, following the October 7th terrorist attacks and the ongoing Iron Swords war, there is a greater need to strengthen the Israeli Society of Plastic and Aesthetic Surgery. Prof. Josef Haik, chair of the Israeli Society of Plastic and Aesthetic Surgery, leads this effort. In addition, it is vital to highlight Israel's contributions to the global Plastic and Aesthetic Surgery community and to encourage collaboration with the nursing division for plastic surgery and burns. Our department is involved in presenting our findings and collaborating with colleagues. In this article, we outlined five main topics: the role of plastic surgery in wartime, reconstructive plastic surgery, aesthetic plastic surgery, microsurgery, and innovation in plastic surgery.

Background: Modern medicine has improved survival rates in burn care. However, this progress has led to a new challenge of sepsis, which has become the leading cause of death in burn patients, accounting for over 50% of mortality. The diagnosis and treatment of sepsis in the burn care unit pose significant challenges due to the hypermetabolic state of the patient, which can mask septic signs and symptoms. This situation underscores the urgent need for improved strategies in sepsis management in burn patients.

Objectives: To assess the predictors of morbidity and mortality among severe burn patients.

Methods: Rambam Health Care Campus is the referral center for burn patients in northern Israel. We reviewed 5 years of patient records, noting information regarding sepsis, laboratory results, infections, and overall morbidity and mortality. In addition, a comparative cohort of burn patient records without sepsis was compared.

Results: Thirty patients had recorded sepsis. Total and direct bilirubin were associated with higher mortality (P < 0.05). Elevated white blood cell count and platelet count at admission were also associated with mortality (P < 0.05). The most prominent burn areas were the arms, head, and legs. The leading cause of injury was fire, followed by an explosion. Burns of total body surface area ≥ 40% was associated with sepsis.

Conclusions: Sepsis is a complex challenge when diagnosing and treating burned patients. Identifying specific traits and prognostic factors is crucial to adequately treat these patients. Research in burn care and sepsis management is essential.

Background: Soft-tissue defects of the lower limb pose a reconstructive challenge. Soft tissue loss with exposed bone, tendon, or cartilage often requires free flap reconstruction. Dermal substitutes are used for treatment of extensive burns to replace damaged skin and may be ideal for lower limb reconstruction in selected cases.

Objectives: To present our experience with reconstruction of lower limb wounds using Integra® Bilayer Wound Matrix (Integra LifeSciences Corp., Plainsboro, NJ, USA) and MatriDerm® (MedSkin Solutions Dr. Suwelack AG, Billerbeck, Germany).

Methods: This single center retrospective study comprised 10 patients who underwent reconstruction of extensive tissue defects of the distal lower limbs with dermal matrices and split-thickness skin grafts.

Results: All patients were successfully reconstructed and resumed normal ambulation. Six patients had complete and four partial graft takes that was treated conservatively until full wound healing. Older patients with medical co-morbidities or history of wound infection were more likely to have partial graft take. One postoperative infection was recorded in the study.

Conclusions: Dermal substitutes are easy to apply and safe, show minimal donor site morbidity, provide good functional and aesthetic outcomes, and should be used for reconstruction of complex lower limb wounds.

Background: The forehead and scalp play a crucial role in the aesthetic appearance of the face. Extensive oncological resections that result in significant defects create challenges for reconstruction and require various surgical techniques.

Objective: To present the planning and surgical technique required for a simple, reproducible one-stage flap to reconstruct an extensive forehead defect.

Methods: A cohort of six patients underwent reconstruction of large anterior forehead or scalp defects using a one-stage axial fasciocutaneous flap. All procedures were conducted under general anesthesia. The defects resulted from tumor resections. The sizes ranged from 5.5 cm to 11 cm. The flap was used to reconstruct various forehead and anterior scalp regions.

Results: All the flaps were successful. The aesthetic outcomes were favorable, and no significant complications were noted.

Conclusions: The extended forehead flap is a versatile option for safe, simple, and reproducible one-stage reconstruction of large forehead and anterior scalp defects that yields satisfactory aesthetic results.

Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin tumor with an increasing incidence in Western countries. Predominantly affecting older individuals, MCC represents less than 1% of malignant skin tumors.

Objectives: To characterize the clinical presentation, therapeutic interventions, and follow-up outcomes of MCC patients. To promote heightened clinical awareness regarding the early recognition and diagnosis of MCC.

Methods: We conducted a retrospective cohort study analyzing medical records of MCC patients at the Shaare Zedek Medical Center between 2015–2022. From 19 initially identified patients, 17 met the inclusion criteria. Data collection included demographic, epidemiological, clinical, and pathological characteristics.

Results: The study included 17 patients, predominantly of Jewish origin, with a mean age of 70.06 years; 58.8% female. Medical co-morbidities included 64.7% hypertension and 35.3% diabetes. MCC tumors were predominantly left-sided (58.8%), with varied locations including limbs, trunk, and face. Surgical treatment consisted of excision and primary closure (64.7%) or skin grafting (23.5%). The average tumor diameter was 3.41 cm clinically and 3.83 cm pathologically. Lymph node involvement occurred in 29.4% of cases; 23.5% showed metastatic disease at diagnosis, with metastases diffused in different body areas. Kaplan-Meier survival analysis showed no statistically significant differences across most variables, except for a significantly lower survival rate in patients with ischemic heart disease (P = 0.009).

Conclusions: Our study reveals unique characteristics of MCC, predominance of female patients, and a slightly younger average diagnosis age compared to existing literature. The 2-year survival rate in our cohort was 82%. The study underscores the importance of early detection and diagnosis of MCC, thereby enhancing clinical awareness and improving patient outcomes.

Background: The incidence of autologous breast reconstruction has been steadily increasing in recent years. Deep inferior epigastric perforator (DIEP) flap reconstruction is considered the gold standard for breast reconstruction despite its demanding technical expertise, time intensiveness, and rigorous postoperative monitoring.

Methods: We retrospectively collected data from 102 DIEP flaps utilized for breast reconstruction in 70 patients treated at private clinics between 2013 and 2024. All surgeries were performed by a single, experienced surgeon.

Results: The mean age at surgery was 42.2 ± 8 years. Immediate reconstructions were conducted in 34 patients (48%); 46% of patients had prior radiation therapy. Only one patient received adjuvant radiation therapy. Free DIEP flaps vascularized by one (53%), two (32%), or three (10%) perforators were preferentially anastomosed to the internal mammary vessels. One patient underwent a muscle-sparing procedure due to the absence of available perforators. Total flap failure occurred in four cases (3.9%), three occurred as a unilateral loss in patients who underwent bilateral reconstruction. Postoperative revisions of the microvascular anastomosis were performed in three patients, with successful flap salvage in two (67%). Fat necrosis was diagnosed in 26 breasts (25%), only a minority of cases required follow-up surgery. All patients were managed completely in a private clinic, with none requiring hospitalization in the public system.

Conclusions: Free DIEP flap breast reconstruction necessitates meticulous surgical planning, a well-coordinated surgical team, and close postoperative monitoring. Nevertheless, this surgery can be safely and effectively performed in a private clinic setting, with complication rates comparable to that of the public setting.