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: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are established treatments for peritoneal metastasis from colorectal cancer (PM-CRC). The peritoneal carcinomatosis index (PCI) measures disease burden.

Objectives: To evaluate the effect of PCI on short- and long-term outcomes of patients with PM-CRC who underwent CRS-HIPEC.

Methods: We retrospectively analyzed 120 PM-CRC patients who underwent CRS-HIPEC, categorizing them into four PCI groups (PCI ≤ 3, PCI 4–6, PCI 7–11, PCI >11). We evaluated perioperative outcomes and long-term survival.

Results: Higher PCI scores were associated with increased surgical complexity, longer operative times, more organ resections, and higher blood transfusion requirements. Complete cytoreduction was achieved in 100% of the PCI ≤ 3 group, but only in 70.8% of the PCI > 11 group (P = 0.001). Postoperative outcomes showed a trend toward less major morbidity in low PCI patients (16.7% vs. 28%) and significantly shorter hospital stays (10–13 days vs. 19 days, P = 0.006). The 90-day mortality rate was 0% in the PCI ≤ 3 group compared to 11.5% in the PCI > 11 group. Long-term outcomes revealed significantly better disease-free survival (DFS) and overall survival (OS) for the PCI ≤ 3 group (DFS: 22 months vs. 4–6 months; OS: 79.6 months vs. 21–40 months, P < 0.001).

Conclusions: Patients with low PCI scores experience reduced morbidity and improved long-term survival, supporting the use of CRS-HIPEC in this subgroup. Further research is needed to enhance treatment strategies for patients with high PCI scores.

Thromboangiitis obliterans, also known as Buerger’s disease, is a nonatherosclerotic inflammatory disorder that predominantly involves the small- and medium-sized arteries, veins, and nerves. This condition primarily affects the extremities. Manifestations in other anatomical locations are exceptionally rare. It is almost exclusively seen in relatively young smokers, with an incidence rate of 12.6 per 100,000 individuals in the United States [1].

Tobacco smoking is the most significant risk factor for thromboangiitis obliterans. It plays a crucial role in both the initiation and progression of the disease. Patients typically present with ischemic symptoms resulting from occlusion of the small vessels in the extremities, whereas other symptoms are infrequent [1,2].

The diagnosis is mainly clinical, requiring a history of smoking, characteristic physical findings, and vascular abnormalities observed on imaging. Biopsy is seldom necessary for diagnosis, and smoking cessation remains the sole effective intervention to prevent disease progression [1,2].

In this report, we present the clinical course and surgical management of a 57-year-old male patient with a colonic mass that was histopathologically diagnosed as thromboangiitis obliterans.

Background: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular events, especially following acute exacerbation (AECOPD). However, there is insufficient data to identify high-risk subjects.

Objectives: To evaluate the association between neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, and the risk of cardiovascular events following exacerbation.

Methods: This retrospective cohort included patients with COPD who were hospitalized with AECOPD between January 2016 and December 2022. We took the reference NLR before index admission and evaluated the incidence of major adverse cardiovascular events (MACE) or cardiovascular death over the following year. Multivariate analysis and competing risk regression were used to assess hazard ratio (HR) and NLR threshold for increased cardiovascular risk.

Results: In total, 15,224 patients with AECOPD completed one 1-year follow-up session. The majority were male (54%) with a mean age of 69 ± 3 years. The risk for MACE of patients in the highest NLR quartile was higher over the first year following AECOPD; however, the magnitude of effect decreased over time. After adjustment to other confounders that may increase NLR, a value > 3.5 was found with the strongest predictive power

Conclusion: Community NLR can be used to identify patients at increased risk of cardiovascular events following AECOPD, together with other risk factors. Every effort should be made to reduce exacerbation risk, and target intervention to those patients at highest risk.

Background: Interpretation of blood gases is essential for the correct practice of medicine. Normal ranges for arterial blood gases (ABG) have not been extensively studied in the older population. Also, venous blood gases and venous-arterial pCO₂ gradient have not been studied in this population, even though they signify the majority of hospitalized patients.

Objectives: To determine the normal range for ABG and the bias limits of agreement for arterial-venous difference in the elderly population.

Methods: We recruited 130 elderly patients (> 70 years) and obtained blood gas measurements from venous and arterial blood. Patients were divided into four categories: healthy patients, patients with stable chronic pulmonary disease, hospitalized patients with acute respiratory illness, and hospitalized patients without respiratory disease. Samples were analyzed in a point of care analyzer.

Results: Mean PaCO₂ was 36.9 ± 4.2 mmHg for the healthy control group, 37.0 ± 4.8 mmHg in the stable chronic respiratory group, 37.0 ± 5.0 mmHg in the non-respiratory hospitalization group, and 42.3 ± 11.4 mmHg for the respiratory hospitalization group, Kruskall-Wallis, P <0.0025. Mean bias between venous and arterial CO₂ was +10.0 mmHg with 95% limits of agreement between 2.7 mmHg and -22.8 mmHg.

Conclusions: In elderly patients, the range of PaCO₂ measurements was similar to the accepted normal range in clinical practice. Venous-arterial PCO₂ gradient had high bias and wide limits of agreement, similar to previously published studies.

Background: Lung transplantation (LT) is a viable option for end-stage chronic obstructive pulmonary disease (COPD) patients when conventional treatments fail. However, sex disparities in mortality outcomes among COPD patients awaiting LT remain understudied. LT waiting lists are generally shorter in Western countries compared to Israel.

Objectives: To evaluate sex-specific differences in mortality and co-morbidities among COPD patients awaiting lung transplantation, to identify key risk factors influencing survival.

Methods: We assessed associations between sex, co-morbidities, exacerbations, and mortality using Cox regression models, adjusting for confounders. Survival curves for lung transplant candidates were stratified by sex using Fine and Gray models.

Results: We identified 385 COPD patients listed for LT at Rabin Medical Center. Females exhibited higher rates of asthma (P = 0.008), anxiety (P = 0.005), and depression (P = 0.002); males were more frequently diagnosed with ischemic heart disease (26.5% vs. 10.83%, P = 0.001) and had a higher lung transplant rate (24.9% vs. 15%, P = 0.029). Multivariate analysis revealed that female sex (hazard ratio [HR] 1.55, 95% confidence interval [95%CI] 1.06–2.29, P = 0.025), older age (HR 1.02, 95%CI 1.002–1.054, P = 0.035), ischemic heart disease (HR 1.69, 95%CI 1.12–2.48, P = 0.011), and depression (HR 1.81, 95%CI 1.15–2.83, P < 0.01) were significantly associated with increased mortality. Females showed higher 1-year mortality rates than males (40.3% vs. 29.8%, P < 0.001).

Conclusions: Female sex is a significant risk factor for increased mortality among COPD patients awaiting LT, likely due to a higher burden of co-morbidities.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to a wide spectrum of clinical severity. The gold standard diagnosis of infection is reverse transcription polymerase chain reaction of nasopharyngeal swabs, which also provides a semiquantitative assessment of viral loads by measuring cycle threshold (CT) values.

Objective: To assess whether CT values at admission can predict mortality and oxygen needs among individuals hospitalized for coronavirus disease 2019 (COVID-19).

Methods: The retrospective study included adults hospitalized for COVID-19 between 1 August 2020 and 30 April 2021 at Barzilai University Medical Center. Patients were categorized according to initial CT values as high (≥ 25) or low (< 25) values. The primary outcome was the association between CT values during admission and overall mortality.

Results: The study group included 636 patients, with a mean age of 67.2 years, 54.4% males. Overall mortality of patients with CT values < 25 was significantly higher (odds ratio for mortality 1.78 vs. patients with CT ≥ 25, P = 0.002). Significantly more patients in the low CT group required oxygen support than in the high CT group, 50% vs. 31.9% (P < 0.001). An inverse association between CT values and mortality rates remained significant in multivariate regression analysis, such that a 1-unit decrease in CT was associated with a 6% increased mortality.

Conclusions: Lower CT values at admission were associated with increased mortality among patients hospitalized for COVID-19. CT values can be used to predict outcomes among such patients.

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends a ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) of less than 70% (FEV1/FVC < 0.7) after bronchodilators as the criteria for obstruction. However, because the FEV1/FVC ratio decreases with age, using a fixed ratio may lead to overdiagnosis of obstruction in the geriatric population. Using the lower limit of normal (LLN) as threshold for obstruction has been suggested.

Objectives: To determine the rate of overdiagnosis using the GOLD criteria compared to LLN in patients aged 60 and older. To find a better threshold with a minimal rate of over- and underdiagnosis.

Methods: The study population included adults aged 60 years and older who performed pulmonary function test (PFT) at Shaare Zedek Medical Center between 2014 and 2019 with results of FEV1/FVC < 0.7.

Results: We included 430 patients aged 60 years and older, 273 males (63.5%) and 157 females (36.5%). Mean age was 72 ± 8 years. Overdiagnosis was found in 35.6% of patients (95% confidence interval 31.1–40.3%) by using the GOLD criteria compared to the LLN. Overdiagnosis was reduced to 6.4% with the 0.65 threshold. The ideal point of the FEV1/FVC ratio where overdiagnosis and underdiagnosis were at their lowest rates was 0.638.

Conclusions: Use of the GOLD criteria for airflow obstruction may be associated with an overdiagnosis of more than 35% in patients older than 60 years. Lowering the FEV1/FVC ratio to < 0.65 might be more accurate in this population.

Background: The association between new-onset atopic dermatitis (AD) and the coronavirus disease 2019 (COVID-19) pandemic was scarcely documented in the literature.

Objectives: To evaluate the incidence of AD in a large nation-wide cohort over 6 years, focusing on changes in incidence following the onset of the COVID-19 pandemic.

Methods: This retrospective cohort study included all members of the largest HMO in Israel (n=4.8 million) from 2017 to 2022. Patients with newly diagnosed AD were identified using the ICD-10 code for AD (L20). Incidence rates were calculated as the number of new diagnoses per 1000 person-years. The pre-COVID period was 1/2017 to 1/2020, and post-COVID 2/2020 to 12/2022. Age-adjusted incidence rates were calculated based on the World Health Organization's standard population.

Results: The overall crude incidence of AD across the study period was 3.38/1000 person-years (PYs). From 2017 to 2022, there was a 36.97% increase in the crude incidence and a 40.44% increase in the age-adjusted incidence, with a mean annual incidence change of +6.5% and +7.1%, respectively. Both crude and adjusted annual incidence increases were significant (P < 0.001, R² = 0.98; P < 0.001, R² = 0.99, respectively). The incidence of AD at the follow-up before the COVID-19 pandemic was 3.07/1000 PYs, and after was 3.71/1000 PYs.

Conclusions: We observed a significant and nearly consistent annual increase in AD incidence from 2017 to 2022, across various sex and age groups. Further research is needed to explore the impact of the COVID-19 pandemic on rising trends in AD incidence.

Background: Ramadan, one of the core tenets of Islam, requires a rigorous fasting regimen from dawn until sunset, during which practitioners abstain from all forms of food and drink. This substantial alteration in daily habits raises pertinent questions regarding its potential implications for cardiovascular health.

Objectives: To analyze the incidence of myocardial infarction (MI) throughout the Ramadan fasting period.

Methods: We retrospectively compared the incidence of MI occurring during Ramadan with that observed during the corresponding non-Ramadan months from 2010 to 2021 using medical records of Muslim patients admitted to the Galilee Medical Center. Ramadan's timing varies from year to year. We used a 3-year comparative framework to ensure seasonal alignment.

Results: During the study period and within a well-defined geographic region, we found that among Muslims, there were 405 MIs: 201 during Ramadan and 204 during non-Ramadan periods, P = 0.282.

Conclusions: The incidence of MI during Ramadan remained stable, indicating that the fasting practice does not significantly heighten the risk of MI.

Background: Antiphospholipid syndrome (APS) is a common form of acquired thrombophilia associated with a high thrombotic risk. Fabry’s disease (FD) is an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (GLA) gene and presents with a wide range of clinical manifestations, including a high rate of thrombosis. Previously reported, 45% of FD patients were found to have antiphospholipid autoantibodies.

Objectives: To determine the prevalence of FD in patients with APS.

Methods: We conducted a prospective study. Data were collected from 41 APS patients at our outpatient clinic at Meir Medical Center in Israel. We utilized chemical and genetic analyses to identify FD among APS patients. Dried blood spot (DBS) was used to assess GLA activity in males, and mutational analysis of the GLA gene was performed by sequencing exons and their flanking regions in women.

Results: Among 41 antiphospholipid patients, one male patient was diagnosed with FD. Gal variants were not detected in any of the tested female patients.

Conclusions: We found a low prevalence (2.4%) of FD in APS patients. Larger studies are needed to evaluate the clinical utility and cost-effectiveness of routine FD screening in this population.

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.

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.

Over the past decade, the introduction of humanized mouse models, especially the transplantation of full-thickness human skin with autologous immune cells onto severe combined immunodeficient (SCID) mice, has transformed pre-clinical dermatology. These composite grafts vascularize and reinnervate within days, retain normal human architecture, evade graft-versus-host disease, and faithfully recapitulate complex cutaneous conditions such as psoriasis, atopic dermatitis, alopecia areata, androgenetic alopecia, vitiligo, pemphigus, and even intrinsic skin aging. Because the grafts respond to murine neuro-endocrine stress pathways yet remain immunologically human, investigators can track how psychological stress, cytokine networks, or targeted drugs shape disease onset, flare, and resolution in a living mini-patient. Unlike conventional murine models, which often capture only a single disease facet and vary by strain, humanized xenografts predict clinical efficacy, metabolism, and toxicity with far greater fidelity, enabling the discovery of pivotal mechanisms (e.g., vascular endothelial growth factor A-driven rejuvenation of aged skin [VEGF-A], voltage-gated potassium channel [Kv1.3], blockade in psoriasis, and alopecia areata) and accelerating the rational design of therapies from Janus kinase (JAK) inhibitors to neurokinin-1 receptor (NK-1R) antagonists. Although access to donor tissue and the need for pathogen-free facilities remain practical hurdles, these models now represent the gold standard for bridging bench and bedside in cutaneous research and for de-risking novel dermatologic and anti-aging interventions before they enter human trials.