Israel Medical Association Journal

Background: The coronavirus disease 2019 (COVID-19) pandemic has disrupted healthcare systems globally, affecting chronic disease management like osteoporosis and the prevention of fragility hip fractures. We hypothesized that it led to suboptimal prevention of secondary femoral neck fractures, reduced treatment frequency, and delayed treatment initiation.

Objectives: To evaluate the treatment initiation rate for secondary prevention of femoral neck fractures, comparing pre-COVID-19, COVID-19, and post-COVID periods, considering patient demographics.

Methods: This retrospective diagnostic cohort study used automated electronic medical records database from Clalit Health Services. Data regarding patients with hip fractures from January 2017 through September 2021 were extracted from the database. Treatment for osteoporosis included one of the following treatments: alendronate, risedronate, zoledronate, abaloparatide, denosumab, romosozumab, and teriparatide. The primary outcome variable in the study is the time taken to initiate appropriate therapy for the secondary prevention of femoral neck fractures.

Results: Treatment frequency decreased over time, with rates declining from 40.4% in 2019 to 33.5% in 2021 (P-value < 0.05). However, the percentage of prompt care management (within 3 months) increased between 2020 and 2021 (47.3%–62.5%) and between 2019 and 2021 (48.7%–62.5%), P < 0.05.

Conclusions: The COVID-19 pandemic reduced the rate of appropriate treatment initiation following hip fractures. However, adherence to timely treatment within 3 months of the fracture has improved. The findings highlight the effectiveness of the health system response in managing crises and ensuring the timely delivery of critical treatment.

Background: Carbohydrate counting (CC), a recommended method for managing insulin bolus in patients with Type 1 diabetes mellitus (T1DM), depends on patient cognitive ability and motivation, and often does not account for ethnic foods. We have developed a simplified, accessible, patient-specific carbohydrate counting tool (SCC) to serve our very diverse population.

Objective: To retrospectively evaluate the long-term efficacy of the SCC with an emphasis on patients with moderate to poor glycemic control.

Method: The SCC tool is tailored to each patient’s insulin:carbohydrate ratio (I:C), insulin sensitivity (IS), and dietary pattern. It includes two tables written in the patient's preferred language. The first lists the units of insulin needed to correct pre-meal blood glucose to target glucose. The second contains a list of food items derived from participant's personal eating habits, carbohydrate content, and the number of insulin units needed.

At a median follow-up period of 6 months, we examined the change in hemoglobin A1c (HbA1c) in 212 patients with T1DM who utilized the SCC.

Results: At follow-up, HbA1c in the study population decreased by 1.07% (22.43 mmol/mol) (95% confidence interval 0.8–1.3, P < 0.001). The variables sex and diabetes duration were nearly statistically significant in relation to the change in HbA1c levels (P = 0.059, P = 0.056).

Conclusions: While not influenced by age, sex, ethnicity, socioeconomic status, education, insulin delivery method, duration of diabetes, or residence, the SCC tool is designed to help adult patients with T1DM with moderate to poor glycemic control.

Background: Flumazenil has been available since 1991 for the treatment of acute benzodiazepine overdose, yet many physicians remain reluctant to use it.

Objectives: To evaluate the frequency of flumazenil use for benzodiazepine overdose at a large, urban, tertiary care center. To assess its effectiveness and associated adverse events.

Methods: The study was conducted in an emergency department with approximately 220,000 annual visits. Medical records of patients who received a medical toxicology consultation and were treated with flumazenil between 1 January 2019, and 31 December 2023 were reviewed. Data collected included patient demographics, medical history, substances involved, presence of seizures, indications for flumazenil use, clinical response, and adverse effects.

Results: Of 263 patients evaluated for suspected benzodiazepine overdose and referred to medical toxicology, 79 received flumazenil and comprised the study cohort. Among them, 64 cases involved intentional overdose. Indications for flumazenil administration included severe overdose with impaired consciousness and ventilatory failure (37 patients) or without ventilatory failure (42 patients). Co-ingestion of tricyclic antidepressants was documented in 4 patients and other antidepressants or antipsychotics in 35. Clinical improvement, including enhanced consciousness and/or reduced need for mechanical ventilation, was observed in all 79 patients. No adverse effects, including seizures, were reported.

Conclusions: In this retrospective cohort, flumazenil was administered without serious adverse events and was associated with improved alertness and ventilation. While caution is required, particularly in mixed overdoses, flumazenil may have a role in managing benzodiazepine-induced respiratory depression when guided by toxicology consultation.

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.

In the 1950s, ionizing radiation to the scalp was commonly used in Israel as a treatment for tinea capitis. Decades later, epidemiological studies identified an increased incidence of head and neck malignancies, particularly basal cell carcinoma, as well as intracranial tumors such as meningiomas among individuals who underwent this therapy in childhood. In addition to the oncologic risk, irradiated scalp skin presents significant reconstructive challenges due to chronic skin atrophy, hypovascularity, fibrosis, and impaired wound healing. In this study, we present our clinical experience with a modified, skin-sparing surgical protocol for managing reconstruction post excision of non-melanoma skin cancer of the scalp in patients previously irradiated for tinea capitis. The surgical strategy is tailored according to lesion size, depth, periosteal involvement, and scalp tissue quality. It incorporates components of the reconstructive ladder as appropriate. We present three representative cases highlighting key surgical challenges and considerations in this complex population.

Scleromyxedema is a rare, chronic cutaneous mucinosis characterized clinically by diffuse indurated plaques, numerous waxy papules, and potential for systemic involvement, including neurological, pulmonary, and gastrointestinal complications. It can significantly impact the clinical course and patient prognosis [1].

Histologically, scleromyxedema typically manifests in two main forms. The classic form, the most common variant, is characterized by dense mucin deposition within the dermis, an increase in fibroblasts, and thickened collagen. The granuloma annulare-like variant, accounting for approximately 23% of cases, mimics granuloma annulare and is characterized by interstitial granulomatous infiltration and, in some cases, palisaded granulomas within the dermis. This unusual variant presents a significant diagnostic challenge due to its overlap with other granulomatous conditions, potentially causing diagnostic delays [2].

The lack of standardized treatment regimens makes managing scleromyxedema complex. Intravenous immunoglobulin (IVIG) has emerged as a leading therapeutic option, demonstrating efficacy in controlling both cutaneous and systemic manifestations. Other options include systemic steroids, thalidomide, retinoids, and melphalan [3].

These cases underscore the challenges of recognizing the clinical and histologic variability of scleromyxedema, which may lead to a delay in the diagnosis. Early diagnosis is critical given the potential for systemic involvement (neurological, gastrointestinal, and muscular) and the association of scleromyxedema with monoclonal gammopathy of undetermined significance (MGUS), which might progress to multiple myeloma. Consequently, timely hematologic evaluation and ongoing surveillance are warranted.

Background: Radiofrequency-skin interaction is considered self-limited for treating acquired pigmentation such as melasma. Alternatively, skin perforation with microneedling radiofrequency (MNRF) may increase skin bioavailability for depigmenting-mediated ingredients or drugs for the treatment of melasma.

Objectives: To examine the clinical feasibility of topical tranexamic acid (TA) mediated with MNRF-assisted transepidermal delivery in patients with mixed melasma.

Methods: The study protocol included 14 women with centrofacial or malar pattern of distribution of melasma (skin types II-VI; age 35–48 years). Patients underwent four treatments at 3-week intervals between treatments. Treatment protocol included non-insulated MNFR (Intensif, EndyMed Ltd, Caesarea, Israel) followed by TA (hexakapron 4%) solution application. The improvement was evaluated based on clinical photographs (Quantificare, Biot, France) and modified Melasma Area and Severity Index (mMASI) scores. Baseline Photographs were analyzed 3 months after the last treatment.

Results: In 13 patients (93%), mMASI scores were significantly lower after 3 months (mean 3.6) than at baseline (5.22). In one patient, mMASI was higher at 3 months compared to baseline. Overall, mMASI improved by 31% (P < 0.01). Physician and patient satisfaction was high. Minimal adverse reactions were recorded.

Conclusions: MNRF-assisted transepidermal delivery with topical TA is a safe and effective modality for the treatment of melasma.

Nail psoriasis (NP) is a common manifestation of psoriasis, affecting up to 80–90% of patients with psoriatic arthritis and up to 60% of those with cutaneous psoriasis. Isolated NP also occurs in 5–10% of cases. It significantly impacts quality of life and may indicate or precede psoriatic arthritis. In this review, we summarized the clinical features of NP, highlighting patterns of matrix and nail bed involvement, and discussed differential diagnosis with onychomycosis. We outlined current topical, intralesional, systemic, and non-pharmacological treatment options, and proposed an evidence-based approach to diagnosis and management.

Psoriasis is a chronic immuno-inflammatory skin disorder characterized by rapid keratinocyte proliferation, forming thick, red patches with silvery scales. It affects 2–3% of the population, impacting skin, nails, and joints. Pathogenesis involves genetic, environmental, and immunological factors [1]. Triggers such as infections (especially Streptococcus), skin injuries, medications, stress, and alcohol can initiate or worsen the condition [1]. Psoriasis may follow a stable course or present in cycles of flare-ups and remissions. Skin involvement may manifest in any body area but is most common on the knees, elbows, trunk, and scalp [1]. Nail involvement appears in up to 60% of those with cutaneous psoriasis and 80% of those with psoriatic arthritis (PsA), with an 80–90% lifetime incidence [2,3]. Isolated nail psoriasis (NP), defined as nail changes without cutaneous psoriasis or with limited body surface involvement (< 5%), occurs in 5–10% of patients [4,5].

Infantile hemangioma (IH) is the most common benign vascular tumor in infancy. Recent advances, particularly in beta-blocker therapy, have significantly improved the management of IHs. Early identification and treatment of IH may help reduce morbidity and associated complications. In this review, experts in pediatric dermatology in Israel who have experience in treating IH formulated national guidelines for the diagnosis and treatment of IHs, providing evidence-based recommendations for selecting appropriate therapeutic approaches. These Israeli national guidelines provide a structured approach to the diagnosis and treatment of IH, emphasizing early referral, appropriate treatment selection, and careful monitoring. The guidelines serve as a critical resource for pediatricians and dermatologists, ensuring optimal patient outcomes while minimizing complications.

Background: Uninterrupted antithrombotic treatment (ATT) during cardiac implantable electronic device (CIED) implantation increases bleeding and device-related infections (DRI) risk. The wide-awake-local-anesthesia-no-tourniquet (WALANT) technique, using large-volume local anesthesia and adrenaline, is successful in hand surgeries but its potential to mitigate bleeding risk in CIED implantations remains unknown.

Objectives: To investigate whether WALANT protocol for CIED implantations reduces clinically significant pocket hematoma in patients with a high bleeding risk or is a contraindication for interrupting ATT.

Methods: We conducted a prospective, double-blind, randomized controlled trial with CIED surgery patients on uninterrupted ATT. They received WALANT protocol (lidocaine 1% with adrenaline 1:100,000) or standard protocol (lidocaine 1%). Following implantation, patients were blindly monitored in the ward and pacemaker clinic. Patients were monitored for bleeding outcomes post-implantation.

Results: Forty-six consecutive patients (73.6 ± 9 years, 72% male) were enrolled. In the WALANT group (n=24) no intra-pocket pro-hemostatic agents were needed, compared to 45% in the control group (P = 0.0002). Postoperative pressure dressings were used in 12.5% vs. 68% (P = 0.0002). WALANT patients had smaller hematoma areas (median 3.7 cm² IQR [1–39] vs. 46 cm² [IQR 24–76], P = 0.0004) 1-day postoperative. ATT interruption occurred in 12.5% vs. 18% (P = 0.7). Superficial skin infection rates were 4% vs. 9% (P = 0.6). No DRI occurred. No WALANT-related side effects were observed.

Conclusions: WALANT protocol in CIED implantation with uninterrupted ATT reduced pro-hemostatic agents, pressure-dressing need, and hematoma size. Larger studies are needed to assess its impact on infection rates.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive, soft-tissue sarcoma. The treatment is surgical and includes wide local excision (WLE) or Mohs micrographic Surgery (MMS). There is no consensus regarding the preferred type of surgery.

Objectives: To compare the outcomes of the two types of surgery (WLE and MMS).

Methods: This retrospective cohort study was based on the medical records of 59 patients with DFSP treated at Sheba Medical Center (using the WLE method) or Assuta Medical Center (using the MMS method) between 1995 and 2018. The data included demographics, clinical presentations, imaging, types of wound closures, pathological margin status, surgical defect sizes, recurrences, and follow-up.

Results: Of the 59 included patients, 18 (30.5%) underwent WLE and 41 (69.5%) underwent MMS. The mean age at diagnosis was 40.1 ± 14.4 years. The male-to-female ratio was 1.5:1. The main tumor location was the trunk (50% for WLE and 41.5% for MMS). The main type of closure for both procedures was primary closure. In 72.2% of WLE and 78.8% of MMS cases, the margins were free. The difference between the final surgical defect and the original tumor size was statistically significantly smaller in patients who underwent MMS. The median duration of follow-up was 6.6 years. There was no significant difference in the rate of recurrence.

Conclusions: MMS enables better tissue preservation and results in a minor surgical defect compared to WLE, with no difference in tumor recurrence between the two methods.

Background: Coronary heart disease (CHD) patients are considered high cardiovascular risks. Guidelines recommend low-density lipoprotein cholesterol (LDL-C) target levels below 55 mg/dl with > 50% reduction from baselines. These levels can be reached by a combination of statins, ezetimibe, and anti-protein convertase subtilisin/kexin type 9 (anti-PCSK9) agents. Our clinical impression was that CHD patients do not reach LDL-C target levels, despite the wide availability.

Objectives: To evaluate whether hospitalization would result in changes in lipid lowering regimens and short-term compliance.

Methods: We conducted a retrospective cohort study using data of CHD patients who were admitted to internal medicine wards at Clalit Health Services medical centers because of anginal syndrome during 2020–2022. The data were evaluated for demographic and clinical characteristics; LDL-C level at admission, 6 months previously, and 3 months and 6–9 months after discharge; rates of reaching LDL-C target levels; and lipid lowering treatment at admission, discharge, and 6–9 months after.

Results: The cohort included 10,540 patients. One-third and three-quarters did not have lipids level measurements up to 6 months before and during hospitalization, respectively. Only one-fifth of the patients reached LDL-C values before and during admission (median LDL-C 72 mg/dl; range 53–101). Approximately half were treated with high-dose potent statins. Only 10% were treated with ezetimibe. Hospitalization did not have a clinically significant effect on short-term lipid lowering treatment or LDL-C levels.

Conclusions: Gaps were noted between guidelines and clinical practice for reaching LDL-C target levels. Further education and strict policy are needed.

The prevalence of difficult-to-treat rheumatoid arthritis (D2T RA) varies between 5% and 25%, with females comprising the majority of patients and no difference in patient age between D2T and non-D2T RA cohorts. While several attempts to subclassify D2T RA patients into defined subgroups have been tried, the inclusion of an individual D2T RA patient to one of the predefined subgroups can be difficult or impossible as multiple factors are usually involved in the mechanisms of rheumatoid arthritis (RA) refractoriness, with the complex interplay of inflammatory, structural, social, and psychological factors being unique for each patient. More severe disease at presentation, including seropositivity and early erosion formation, and insufficiently aggressive initial treatment can both contribute to the eventual development of D2T RA. No single test or study can replace the holistic clinical approach to the diagnosis and understanding of the causation of D2T RA. Traditional in-depth clinical history and thorough clinical examination remain sine qua non in managing D2T RA patients. Multifaceted contributions of inflammatory and non-inflammatory components create the uniqueness of D2T RA and dictate a comprehensive approach to the management, including both pharmacologic and non-pharmacological therapeutic strategies. Mean annual total costs for D2T RA patients have been estimated as being about twice as high as that of patients with non-D2T RA.

Background: Pyogenic flexor tenosynovitis (PFT) is a common and severe hand infection. Patients who present early can be treated with intravenous antibiotics.

Objectives: To determine whether PFT caused by animal bites and treated with antibiotics leads to a different outcome than other disease etiologies due to the extensive soft tissue insult and different bacterial flora.

Methods: We conducted a retrospective cohort study of 43 consecutive patients who presented with PFT between 2013 and 2020. The 10 patients who presented with PFT following an animal bite were compared to those who presented with PFT caused by any other etiology.

Results: Patients who were bitten pursued medical attention sooner: 1.9 ± 1.4 days compared with 5.3 ± 4.7 days (P = 0.001). Despite the quicker presentation, patients from the study group received similar antibiotic types and duration as controls. All patients were initially treated with intravenous antibiotics under surveillance of a hand surgeon. One patient (10%) from the study group and four controls (12%) were treated surgically (P = 1). Average follow-up was 17 ± 16 days. At the end of follow-up, one (10%) patient from the study group and three (9%) controls sustained mild range of motion limitation and one (3%) patient from the control group had moderate limitations (P = 0.855).

Conclusions: Intravenous antibiotic treatment, combined with an intensive hand surgeon follow-up, is a viable option for the treatment of PFT caused by animal bites.