Israel Medical Association Journal

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease leading to end-stage lung disease (ESLD). Single lung transplantation (SLT) is the primary treatment option for IPF; however, the native lung continues to influence post-transplant outcomes.

Objective: To determine whether the native lung continues to deteriorate under post-transplantation immunosuppression treatment by assessing chest computed tomography (CT) and perfusion scans.

Methods: We conducted a single-center retrospective analysis of patients who underwent SLT for IPF between 2016 and 2023. Serial chest CT scans assessed native lung changes. CT signs of fibrosis were scored for severity according to published criteria for defining pulmonary fibrosis disease progression. Lung volumes and perfusion were calculated.

Results: Among 57 patients (mean age 57 years; 33% female), 42% died during follow-up (median survival 95 months). The most common immunosuppressive regimen (54% of patients) included prednisone, calcineurin inhibitor, and mycophenolate mofetil. CT analysis demonstrated that in 41/57 (72%) patients, fibrosis signs continued to deteriorate. There was also a significant correlation decline in native lung volume and perfusion scans over time (P = 0.0003, P < 0.0001, respectively) (r = 0.82, P = 0.03).

Conclusions: Fibrotic progression in the native lung persists after SLT as demonstrated by both chest CT and nuclear perfusion scan, thus highlighting the importance of ongoing monitoring for accuracy and complications assessment, integrating it into routine surveillance, and ensuring it is consistently considered in post-transplant assessments.

Background: Acute myocarditis (AM) is an inflammatory cardiac condition with heterogeneous clinical manifestations that often overlap with other acute cardiac syndromes, making diagnosis challenging.

Objectives: To characterize the prevalence, clinical profile, and outcomes of AM patients with respiratory viral pathogen detection on nasopharyngeal swabs at admission.

Methods: We retrospectively analyzed all patients admitted to the Sheba Medical Center with confirmed AM between January 2005 and December 2020. Diagnosis was based on compatible presentation, elevated cardiac biomarkers, and supportive imaging findings. Nasopharyngeal swab results, when performed, were reviewed for respiratory viral detection.

Results: Among 425 identified AM cases, 146 (34%) underwent swab testing; 11 (8%) tested positive for respiratory viral pathogens, most commonly influenza A (n=5) and adenovirus (n=3). With one exception, all positive cases occurred during winter or early spring (10/77, 13%). Compared with swab-negative patients, swab-positive individuals were older (47 ± 22 vs. 35 ± 14 years, P = 0.03), more frequently female (45% vs. 14%, P = 0.007), and more often presented with dyspnea (55% vs. 25%, P = 0.036) but less commonly with ST-segment elevation (27% vs. 70%, P = 0.003). No differences were observed in inflammatory markers, imaging findings, or hospital stay.

Conclusions: Respiratory viral detection in AM is uncommon and predominantly seasonal. Nasopharyngeal swabbing is a simple, non-invasive tool that may help identify treatable viral pathogens and guide patient management. These data provide a pre-COVID-19 reference for future studies investigating the impact of viral infection on myocardial injury.

Background: Apparent treatment-resistant hypertension (aTRH) is a high-risk phenotype associated with increased cardiovascular and renal morbidity. Renal denervation (RDN) has emerged as a promising intervention for patients with refractory blood pressure (BP) despite maximal medical therapy.

Objectives: To present the first Israeli prospective cohort evaluating RDN outcomes in aTRH patients.

Methods: The Tel Aviv Renal Denervation registry is a single-center, prospective cohort of 19 patients with aTRH who underwent RDN between 2021 and 2024. Baseline data included demographics, co-morbidities, medication burden, ambulatory BP monitoring (ABPM), and renal function. Outcomes were assessed at 3 and 12 months post-procedure, with repeated measures analyses used to evaluate longitudinal trends.

Results: The cohort (median age 62 years, 42% female) exhibited a high burden of co-morbidities including ischemic heart disease (37%), diabetes (26%), and chronic kidney disease (21%). Baseline ABPM showed a median 24-hour systolic BP of 152 mmHg. Following RDN, mean systolic BP decreased to 143 mmHg at 3 months and 138 mmHg at 12 months (P = 0.097), with a significant reduction in nighttime systolic BP (P = 0.033). Pill burden decreased from a median of 7 to 4 pills daily (P = 0.037). The number of antihypertensive drug classes declined from 6 to 4 (P = 0.052). Renal function remained stable throughout follow-up.

Conclusions: In this Israeli RDN cohort, patients with aTRH experienced clinically meaningful reductions in BP and medication burden, with preserved renal function and minimal complications. These findings support further expansion of national RDN registries to better guide patient selection and optimize long-term outcomes.

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.

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: Lung transplantation is an advanced medical therapy reserved for patients with end-stage lung disease. Relative to other solid organ transplants, lung transplantation in children is infrequently performed. The most common etiologies for pediatric lung transplantation worldwide are cystic fibrosis, pulmonary hypertension, and children’s interstitial lung disease.

Objectives: To describe our experience in pediatric lung transplants at Israel's largest transplant center.

Methods: We performed a retrospective review of all pediatric lung transplantations conducted in our center since 1997. We recorded demographic characteristics, indication for transplantation, clinical and laboratory parameters, post-transplant complications, and survival rates.

Results: Of 965 lung transplants, 29 (3.0%) were pediatric patients who underwent lung or heart-lung transplants for end-stage lung disease. Age at transplantation ranged from 2 to 18 years, with a median of 14.0 years (IQR 11–15). Primary etiologies for transplantation were cystic fibrosis (44%), pulmonary hypertension (17%), and children’s interstitial lung disease (10%). Survival at 1, 5, 10, and 15 years post-transplant were 90%, 65%, 55%, and 20%, respectively, which is consistent with data reported by pediatric lung transplantation registries. The primary cause of mortality post-transplant was chronic lung allograft dysfunction. Four patients (13.8%) underwent re-transplant. There was no association between survival and transplant indication, nor between survival and type of procedure (lung vs. heart-lung transplant).

Conclusions: The short- and long-term outcomes from our program are consistent with published registry data. These outcomes may reflect the benefits of a centralized pediatric lung transplant program, supported by a multidisciplinary team trained in high-capacity international centers.

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: Hypertensive disorders during pregnancy can lead to significant adverse outcomes. Currently, no established and effective tests have a high predictive value for preeclampsia toxemia (PET) severity and its associated adverse outcomes.

Objectives: To investigate the correlation between the aspartate aminotransferase-to-platelet ratio index (APRI) and the risk of obstetrical and neonatal adverse outcomes in women with PET.

Methods: We conducted a population-based cohort study at a tertiary medical center, which included all women who delivered between the years 2020 and 2022 and were diagnosed with PET. Women with incomplete records, multiple gestations, and fetal malformations were excluded. The median APRI of the cohort was the cut-off point to compare the risk of obstetrical and neonatal complications between low and high APRI scores. A multivariable logistic regression was used to adjust for confounders.

Results: The study included 513 women with PET who met the inclusion criteria. The median APRI score was used as a cut-off value, resulting in 255 women with an APRI score < 0.26 and 258 with a score > 0.26. A higher APRI score was significantly correlated with a small for gestational age (SGA) newborn and preterm delivery before 34 weeks after controlling for parity, previous cesarean delivery (CD), and maternal age (adjusted odds ratio 1.60, 95% confidence interval 1.01–2.55; P = 0.047, adjusted hazard ration 1.75, 95% confidence interval 1.12–3.09, P = 0.047).

Conclusions: In patients with PET, an APRI score > 0.26 was associated with an increased risk for SGA and preterm deliveries.

Background: Despite a significant advance in prevention and treatment of heart failure (HF), patients still struggle with decreased quality of life, high mortality, and recurrent hospitalizations. Several inflammatory cytokines have been widely investigated in the pathogenesis of HF.

Objectives: To investigate the prognostic value of fibrinogen on clinical outcomes of patients admitted with acute HF.

Methods: This retrospective study was based on data of patients hospitalized with acute HF. Demographics, laboratory, and clinical outcomes including length of stay and readmissions were obtained. We compared outcomes of patients with normal (< 430 mg/dl) and high (> 430 mg/dl) fibrinogen levels.

Results: We included 149 patients (mean age 67.6 ± 12.3 years, 73.8% male). In our cohort, 24 (16.1%) had normal fibrinogen (< 430 mg/dl) and 125 (83.9%) had high fibrinogen levels (> 430 mg/dl). Among patients with readmissions for HF, fibrinogen levels were higher (622 ± 136 vs. 470 ± 68, P < 0.001) and were associated with longer hospital stay. Fibrinogen remains an independent risk factor after adjusting to age, diabetes status, and left ventricular ejection fraction.

Conclusions: High fibrinogen levels may predict readmissions in patients with HF.

Background: Limited data exist regarding the association between marital status and outcomes among octogenarian and nonagenarian patients with heart failure (HF).

Objectives: To examine the association between marital status and outcomes of octogenarian and nonagenarian patients with HF.

Methods: We conducted a retrospective analysis of 1371 octogenarians and nonagenarians who were hospitalized with HF and enrolled in the multicenter national survey in Israel between March and April 2003. The patients were followed until December 2014. Patients were classified into married (n=562) and unmarried (n=809). The clinical characteristics of the patients by marital status categories were compared by using Student's t-test for continuous variables and the chi-square test for categorical variables. Kaplan–Meier survival analysis was used to present survival estimates according to the different marital status categories and the subsequent 4-year survival probability. Multivariate stepwise Cox proportional hazard regression modeling was used to assess the independent predictors of mortality among the study population.

Results: Married patients were more likely to be male, to smoke, and to have past myocardial infarction and previous revascularization. They tended to have higher rates of peripheral vascular disease and dyslipidemia. Survival analysis showed that 4-year mortality rates were similar between married and unmarried patients. The main consistent independent predictors of 4-year mortality were age, advanced HF (New York Heart association (NYHA) > 2), advanced renal failure, low hemoglobin, high Charlson Comorbidity Index, and low admission systolic blood pressure.

Conclusions: Among the octogenarian and nonagenarian population with HF, being unmarried does not confer an increased risk of mortality. Nevertheless, unmarried patients had a different clinical profile. Higher risk profile, co-morbidities, and advanced age impact mortality among octogenarian and nonagenarian patients.

Background: Locally advanced gastric adenocarcinomas are treated with neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy. Since 2019 the standard of care for perioperative chemotherapy has been FLOT protocol. Concerns regarding the use of FLOT in elderly patients ≥ 65 years of age emerged due to the relatively high toxicity of this protocol.

Objectives: To evaluate the toxicity profile of FLOT and clinical outcome in elderly patients.

Methods: We conducted a retrospective analysis of patients with locally advanced gastric adenocarcinomas treated with FLOT between 2017–2023 at the Sheba Medical Center. The cohort was stratified by age (≥ or < 65 years). The primary outcome was overall survival (OS). Secondary outcomes were treatment-related toxicity. Kaplan-Meier analysis and Cox proportional hazard regression model were used to analyze the effect of exposure variables on OS.

Results: The study cohort included 91 patients. The median age was 60 years (IQR 50–67); 32 patients were included in the ≥ 65 years group, and 59 patients were included in the < 65 years group. Median follow-up was 40 months (IQR 17–58). Patients ≥ 65 years old received fewer cycles of FLOT compared to those < 65 years old (4.5 vs. 7 cycles, respectively, P = 0.03). Despite the difference in treatment intensity and cumulative chemotherapy dose, there was no difference in median OS between patients ≥ 65 years old compared with those < 65 years old (P = 0.68).

Conclusions: Elderly patients with locally advanced gastric adenocarcinomas received fewer cycles of perioperative FLOT without compromising clinical outcomes.

Background: The benefits of corticosteroid administration for suspected premature birth (PTB) are widely accepted. Although a single course of antenatal corticosteroids is generally considered to be safe, there are concerns regarding the safety and benefit of multiple courses. Nevertheless, many women who present with symptoms of PTB do not deliver early.

Objectives: To assess how often we used corticosteroid appropriately in our clinical practice in women who presented with risk of PTB.

Methods: Clinical data were retrospectively collected on patients who were admitted to our clinic between September 2014 and August 2015 due to risk of PTB and who were treated with prenatal corticosteroids.

Results: We identified 305 patients at risk of PTB who were treated with corticosteroids; 42.3% delivered < week 34, 22.5% delivered between weeks 34 and 37, and 35.1% delivered > 37 weeks. In women who delivered after week 37, the more time that elapsed between corticosteroids administration and delivery, the lower the pH and the APGAR scores were. Only 26% of patients delivered 2–14 days after the last steroids course of treatment.

Conclusions: The rate of term deliveries at our center after receiving antenatal corticosteroids due to prior symptoms of preterm labor was 35.1%. The ratio of maternal antenatal corticosteroid administration for potential versus actual PTB at < 37 weeks of gestation was not optimal but acceptable.

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.

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.

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.