Israel Medical Association Journal

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: Rising rates of antibiotic resistance pose a major challenge in the treatment of Helicobacter pylori (H. pylori) infection. Current treatment guidelines emphasize the importance of acquiring local resistance data to select an effective empirical regimen.

Objectives: To analyze trends in H. pylori antibiotic resistance over two decades in Israel.

Methods: Data from Clalit Health Services for H. pylori isolates cultured from gastric biopsies between January 2007 and December 2023 were included. Susceptibility to clarithromycin, amoxicillin, metronidazole, tetracycline, and levofloxacin was determined using E-tests. Demographic and clinical variables were retrieved to identify predictors of resistance.

Results: We identified 2521 H. pylori isolates (71.6% females, mean age 44.4 ± 15.8 years). Most individuals were residents of central Israel (84.6%) and of Jewish ethnicity (87.8%). Antibiotic resistance was observed in 71.6% of isolates for clarithromycin, 64.3% for metronidazole, and 19.4% for levofloxacin. Resistance to tetracycline and amoxicillin was minimal (0.2% and 1.2%, respectively). Dual clarithromycin-metronidazole resistance occurred in 50.4%, and triple resistance (clarithromycin-metronidazole-levofloxacin) was found in 12.0%. Between 2007 and 2012, clarithromycin resistance increased 5.3% annually, then tapered (odds ratio [OR] 1.05, 95% confidence interval [95%CI] 3.84–6.85, P < 0.001). Age and prior antibiotic use were predictors of resistance for all antibiotics, with the greatest effect observed for drugs in the same class. Female sex was associated with higher resistance to levofloxacin (OR 1.62, 95%CI, 1.28–2.05, P < 0.001).

Conclusions: Antibiotic resistance to H. pylori is high in our geographical region. Nevertheless, resistance rates have remained steady over recent years.

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: Mycosis fungoides (MF) combined with photosensitive/autoimmune diseases has been reported, yet there are limited data regarding the therapeutic considerations in these patients, specifically phototherapy, a mainstay skin-directed treatment (SDT), being a relative or complete contra-indication.

Objectives: To outline therapeutic considerations for patients with MF who had also been diagnosed with photosensitive/autoimmune diseases.

Methods: We conducted a retrospective analysis of patients with MF who were treated at our center between January 2008 and December 2024with photosensitive/autoimmune diseases, especially collagen vascular diseases (CVD) or autoimmune bullous diseases (AIBD),

Results: Eight patients were diagnosed with MF at a median age of 39 years. Seven had early-stage (4-IA, 3-IB) and one had Sézary syndrome. Six early-stage MF patients were diagnosed with lupus erythematosus (LE, 4) or AIBD (2) and were treated with SDT (topical corticosteroids/chlormethine gel), systemic retinoid or methotrexate. A patient with resistant early-stage MF and discoid LE was treated with electron beam and interferon. One patient who presented with variegate porphyria and localized MF was treated with electron beam. The patient with Sézary syndrome had inclusion body myositis. He was treated with low-dose total skin electron beam, methotrexate, extracorporeal photopheresis, and subsequently with romidepsin. After a median of 8 years, no stage progression of MF was observed. The Sézary syndrome patient achieved down-staging and was at stage IB. There was no aggravation of the co-morbidity in any of the patients.

Conclusions: Effective management of MF and associated photosensitive or autoimmune co-morbidities underscore the need for individualized treatment strategies in patients with these unique dual diagnoses.

Diabetes mellitus (DM) is a serious and growing global health challenge. The number of people diagnosed with diabetes continues to rise, and it is projected that by 2035 more than 592 million individuals worldwide will have diabetes [1]. DM can impact the heart through various mechanisms. Vascular complications are associated with diabetes and include both epicardial coronary artery and small vessel disease. Cardiomyopathy and heart failure may also occur. Insulin resistance causes cardiomyocytes to have a reduced capacity for glucose utilization, leading to increased uptake of free fatty acids. This, in turn, results in triglyceride storage and lipotoxicity, which contribute to impaired cardiac contractility [2].

Diabetes may lead to the production of advanced glycation end (AGE) products, resulting in an accumulation of reactive oxygen species. This accumulation triggers inflammation that can cause myocyte apoptosis and mitochondrial dysfunction. AGE can also contribute to cardiac fibrosis, which increases myocardial stiffness and results in heart failure with preserved ejection fraction (HFpEF) [2].

Background: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings.

Objectives: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine.

Methods: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models.

Results: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038).

Conclusions: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

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: Endocardial leads of permanent pacemakers (PPM) and implantable defibrillators (ICD) across the tricuspid valve (TV) can lead to tricuspid regurgitation (TR) or can worsen existing TR with subsequent severe morbidity and mortality.

Objectives: To evaluate prospectively the efficacy of intraprocedural 2-dimentional-transthoracic echocardiography (2DTTE) in reducing/preventing lead-associated TR.

Methods: We conducted a prospective randomized controlled study comparing echocardiographic results in patients undergoing de-novo PPM/ICD implantation with intraprocedural echo-guided right ventricular (RV) lead placement (Group 1, n=56) versus non-echo guided implantation (Group 2, n=55). Lead position was changed if TR grade was more than baseline in Group 1. Cohort patients underwent 2DTTE at baseline and 3 and/or 6 months after implantation. Excluded were patients with baseline TR > moderate or baseline ≥ moderate RV dysfunction.

Results: The study comprised 111 patients (74.14 ± 11 years of age, 58.6% male, 19% ICD, 42% active leads). In 98 patients there was at least one follow-up echo. Two patients from Group 1 (3.6%) needed intraprocedural RV electrode repositioning. Four patients (3.5%, 2 from each group, all dual chamber PPM, 3 atrial fibrillation, 2 RV pacing > 40%, none with intraprocedural reposition) had TR deterioration during 6 months follow-up. One patient from Group 2 with baseline mild-moderate aortic regurgitation (AR) had worsening TR and AR within 3 months and underwent aortic valve replacement and TV repair.

Conclusions: The rate of mechanically induced lead-associated TR is low; thus, a routine intraprocedural 2DTTE does not have a significant role in reducing/preventing it

Background: Hypomagnesemia (serum magnesium level < 1.7 mg/dl) occurs more frequently in patients with type 2 diabetes mellitus (T2DM).Serum magnesium levels are not routinely tested in hospitalized patients, including in hospitalized patients with T2DM.

Objectives: To evaluate the prevalence of hypomagnesemia among hospitalized T2DM patients treated with proton pump inhibitors (PPIs) and/or diuretics.

Methods: A total of 263 T2DM patients hospitalized in general departments were included in the study and were further divided into four groups: group 1 (patients not treated with PPIs or diuretics), group 2 (patients treated with PPIs), group 3 (patients treated with diuretics), and group 4 (patients treated with both PPIs and diuretics).  Blood and urine samples were taken during the first 24 hours of admission. Electrocardiogram was performed on admission.

Results: Of the 263 T2DM patients, 58 (22.1%) had hypomagnesemia (serum magnesium level < 1.7 mg/dl). Patients in group 2 had the lowest mean serum magnesium level (1.79 mg/dl ± 0.27). Relatively more patients with hypomagnesemia were found in group 2 compared to the other groups, although a statistically significant difference was not observed. Significantly more patients in group 3 and 4 had chronic renal failure. Patients with hypomagnesemia had significantly lower serum calcium levels.

Conclusions: Hospitalized T2DM patients under PPI therapy are at risk for hypomagnesemia and hypocalcemia

Global trends, such as the population aging, the increase of chronic morbidity, soaring costs of healthcare services, and work overload in hospitals raise the need to find innovative solutions for providing quality medical services. One solution adopted by healthcare systems around the world is "home hospitalization," that is, providing an array of necessary health services in the patient's home, instead of in the hospital department. The aim of this focus article is to explore the spread of home hospitalization worldwide and examine the challenges and pathways for its adoption and implementation. Many countries, including the United States, Canada, the United Kingdom, and Australia, operate home-based hospitalization programs. In Israel, the service is in its infancy, but in view of the extreme workload and the high mortality rate from infections in acute care hospitals, home hospitalization has recently gained public interest and political support, which may encourage its further development.

Background: Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor. 

Objectives: To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure. 

Methods: Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability.

Results: Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline. 

Conclusions: These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.