Israel Medical Association Journal

Background: Bloodstream infections (BSI) are associated with high morbidity and mortality. Inappropriate empirical antimicrobial therapy leads to poor outcomes.

Objectives: To evaluate the impact of clinical pharmacist intervention on the appropriateness of antibiotic treatment in patients hospitalized with bacteremia.

Methods: A retrospective study was conducted at the Soroka Medical Center in Israel. The intervention was implemented starting in July 2018. We compared 170 patients who received pharmacist intervention (August 2018 to June 2019) to 173 control patients (January 2017 to July 2018). The primary outcome was a composite of appropriate antibiotic choice and dosage.

Results: Pharmacist intervention significantly improved appropriate antibiotic dosing (97.6% vs. 91.3%, P = 0.011) and selection based on pathogen sensitivity (100% vs. 95.4%, P = 0.007). The most significant effect was observed in patients with intermediate renal function (CrCl 30–60 ml/min). Multivariate analysis confirmed pharmacist intervention as a strong predictor of appropriate treatment (odds ratio 5.00, 95% confidence interval 1.64–15.25, P = 0.005). The intervention group had longer hospital stays (median 15 vs. 9 days, P < 0.001) and lower 7-day relapse rates (2.4% vs. 8.7%, P = 0.010).

Conclusions: Clinical pharmacist interventions significantly improved the appropriateness of antibiotic treatment in patients with bacteremia, particularly in those with intermediate renal function. Despite longer hospital stays, the intervention group had lower early relapse rates than the control group. These findings support the integration of clinical pharmacists into antimicrobial stewardship programs.

Background: Vitamin B6 is an essential cofactor in amino acid metabolism. Its deficiency is linked to neuropathy, anemia, and cardiovascular risk. Deficiency is common among hemodialysis patients due to dialytic losses and restrictive diets; however, data related to high-flux (HF) dialysis membranes and Mediterranean dietary patterns are scarce.

Objectives: To assess the prevalence and determinants of deficiency in unsupplemented Israeli hemodialysis patients.

Methods: This retrospective chart review, utilizing a cross-sectional design, was conducted in August 2024. We included 27 chronic hemodialysis patients not receiving vitamin B6 supplementation, representing the available unsupplemented cohort from a unit of approximately 150 patients. Vitamin B6 status was assessed by measuring plasma pyridoxal-5'-phosphate (PLP); deficiency < 20 ng/ml. Clinical and nutritional parameters were evaluated to identify deficiency.

Results: Vitamin B6 deficiency was noted in 63% of patients (median PLP 18 ng/ml, interquartile range 13–23). The cohort was 67% male, median age 74 years. All patients were treated with HF dialyzers. No significant correlations were found between PLP levels and nutritional indices or laboratory markers. A non-significant trend was observed between older age and lower PLP levels (r = -0.35, P = 0.098).

Conclusions: Vitamin B6 deficiency was common among Israeli hemodialysis patients treated with HF dialyzers, despite a presumed Mediterranean diet. It was not associated with nutritional status, suggesting dialysis-related losses, potentially augmented by high-flux membranes, may outweigh intake. Given the high prevalence of deficiency and low cost, routine low-dose vitamin B6 supplementation may be warranted, particularly in older patients.

Immunoglobulin E-mediated cow's milk allergy (IgE-CMA) is the most common food allergy in infancy. Recent evidence suggests that early infant feeding practices, particularly the pattern of cow's milk formula (CMF) exposure during the first days and months of life, may influence the risk of developing IgE-CMA. Studies indicate that transient CMF supplementation followed by prolonged avoidance is associated with an increased risk of IgE-CMA, whereas continued regular CMF consumption after initial exposure may reduce this risk. This review summarizes the current evidence regarding IgE-CMA prevention, discusses the limitations of the available data, presents the recommendations of the Israeli Association of Allergy and Clinical Immunology, and highlights key unanswered questions requiring further research.

Background: Postoperative atrial fibrillation (POAF) is well recognized after cardiac surgery; however, its incidence and clinical course following non-cardiac surgery (NCS) remain unclear.

Objectives: To evaluate the association between POAF after NCS, patient co-morbidities, and type of surgery.

Methods: In this retrospective cohort study, patients who underwent NCS at a private hospital network between 2016 and 2023 were included. Patients with a history of atrial fibrillation (AF) were excluded. Patients who developed POAF within 24-48 hours were compared with those who did not. To address baseline differences, propensity score matching (1:10) and inverse probability weighting combined with Firth’s penalized logistic regression were applied. Odds ratios with 95% confidence intervals were calculated.

Results: POAF developed in 174 patients within 24–48 hours postoperatively, compared with 391,329 controls. Older age, ischemic heart disease, diabetes, and prior stroke were associated with increased odds of POAF, although significance diminished after multivariable adjustment. Weighted regression confirmed these findings with narrower confidence intervals. Higher POAF risk was observed after laparoscopic pancreatectomy, hepatectomy, rectopexy, synovectomy, and gastrectomy. Total knee replacement was the most common procedure among POAF cases, representing 22% of cases and a fourfold increased risk.

Conclusions: Advanced age and cardiovascular co-morbidities were associated with increased POAF risk after NCS, although attenuated after adjustment. Consistent findings across statistical models support the robustness of the results. Targeted monitoring in high-risk patients may improve postoperative outcomes.

Background: Mass honeybee envenomation (MHE) is a rare occurrence, with possible life-threatening or fatal consequences.

Objectives: To present the first description of multiple simultaneous casualties in a single incident of MHE.

Methods: Nine young men were simultaneously attacked by a large honeybee swarm. All patients were hemodynamically stable on arrival to Sheba Medical Center. One had fiberoptic evidence of laryngeal edema. Eight (89%) of the patients had leukocytosis and laboratory evidence of rhabdomyolysis. Eight patients were hospitalized in an internal medicine ward. The patient who had the most (over 300) stings removed presented with severe rhabdomyolysis and acute renal failure (ARF) and was admitted to the intensive care unit.

Results: Most patients had a benign clinical course and were discharged within 2 days. One patient developed severe rhabdomyolysis and was treated with fluids and urine alkalinization with significant improvement. The clinical course of another patient was complicated by ARF consistent with acute tubular necrosis. His creatinine peaked at 3.04 mg/dl and improved over several days until his discharge.

Conclusions: In our case series, we demonstrated the spectrum of clinical presentations associated with MHE and highlighted the importance of stings load as a prognostic factor, which may dictate early therapeutic intervention.

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.

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.

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.

Background: The prognostic significance of diabetes mellitus (DM) on hospitalization outcomes of patients with acute decompensated heart failure (ADHF) remains inconclusive.

Objectives: To comprehensively assess the clinical outcomes of patients with and without DM hospitalized for ADHF.

Methods: This single center retrospective cohort study included consecutive hospitalized patients with a principal diagnosis of ADHF between 1 January 2010 and 31 December 2019. Patients were categorized into diabetic and non-diabetic groups. The primary outcomes assessed were in-hospital mortality, 1-year overall mortality, and readmission rate within a year of follow-up.

Results: The final analysis involved 787 ADHF patients, with 62% having a pre-existing diagnosis of DM. Despite a higher burden of co-morbidities in diabetic patients, there were no differences in clinical outcomes when compared to non-diabetic counterparts. Specifically, there were no differences in overall hospital mortality (10% vs. 10%, P = 0.675), 1-year mortality (22% vs. 25%, P = 0.389), and re-admissions (51% vs. 56%, P = 0.154). Notably, the 1-year mortality among diabetic patients was not influenced by HbA1c levels documented before or during admission.

Conclusions: The clinical outcomes of patients hospitalized with ADHF did not differ by the presence of diabetes. Instead, our findings emphasize the importance of early heart failure prevention and subsequent hospitalization. Considering the evolving landscape of disease-modifying therapies for heart failure, achieving this goal becomes increasingly feasible.

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: Cardiac implantable electronic devices (CIEDs) are associated with risks of device-related infections (DRI) impacting major adverse outcomes. Staphylococcus aureus (SA) is a leading cause of early pocket infection and bacteremia. While studies in other surgical contexts have suggested that nasal mupirocin treatment and chlorhexidine skin washing may reduce colonization and infection risk, limited data exist for CIED interventions.

Objectives: To assess the impact of SA decolonization on DRI rates.

Methods: We conducted a retrospective, single-center observational study on consecutive patients undergoing CIED interventions (March 2020–March 2022). All patients received pre-procedure antibiotics and chlorhexidine skin washing. Starting in March 2021, additional pre-treatment with mupirocin for SA decolonization was administered. DRI rates within 6 months post-implantation were compared between patients treated according to guidelines (Group 1) and those receiving mupirocin in addition to the recommended guidelines (Group 2).

Results: The study comprised 276 patients (age 77 ± 10 years; 60% male). DRI occurred in five patients (1.8%);80% underwent cardiac resynchronization therapy procedures. In Group 1 (n=177), four patients (2.2%) experienced DRI 11–48 days post-procedure; three with pocket infection (two with negative cultures and one with local Pseudomonas) and one with methicillin-sensitive SA endocarditis necessitating device extraction. In Group 2 (n=99), only one patient (1%) had DRI (Strep. dysgalactiae endocarditis) 135 days post-procedure (P = NS).

Conclusions: The routine decolonization of SA with mupirocin, in addition to guideline-directed protocols, did not significantly affect DRI rates. Larger prospective studies are needed to evaluate the preventive role of routine SA decolonization in CIED procedures.

Background: One-third of patients with acute decompensated heart failure (ADHF) develop worsening kidney function, known as type I cardiorenal syndrome (CRS). CRS is linked to higher mortality rates, prolonged hospital stays, and increased readmissions.

Objectives: To explore the impact of real-time monitoring of urinary output (UO) trends on personalized pharmacologic management, fluid balance, and clinical outcomes of patients with ADHF admitted to a cardiac intensive care unit.

Methods: Our study comprised 35 patients who were hospitalized with ADHF and continuously monitored for UO (UO_elec). Standard diuretic and fluid protocols were implemented after 2 hours of oliguria, and patient outcomes were compared to a historical matched control (HMC) group. Patients were assessed for daily and cumulative fluid balance (over 72 hours) as well as for the occurrence of acute kidney injury (AKI).

Results: Significantly more patients in the UO_elec group demonstrated negative fluid balance daily and cumulatively over time in the intensive care unit compared to the HMC group: 91% vs. 20%, respectively (P < 0.0001 for 72-hour cumulative fluid balance). The incidence of AKI was significantly lower in the UO_elec monitoring cohort compared to the HMC: 23% vs. 57%, respectively (P = 0.003). Moreover, higher AKI resolution, and lower peak serum creatinine levels were demonstrated in the UO_elec group vs. the HMC group.

Conclusions: Implementing real-time monitoring of UO in ADHF patients allowed for early response to oliguria and goal-directed adjustment to treatment. This finding ultimately led to reduced congestion and contributed to early resolution of AKI.

Cardiac amyloidosis is a form of restrictive cardiomyopathy resulting from the accumulation of misfolded protein aggregates in the myocardial extracellular space. Cardiac amyloidosis stems primarily from the misfolding of monoclonal immunoglobulin light chains (AL) originating from abnormal clonal plasma cell proliferation or transthyretin amyloidosis (ATTR).

Diagnosis of amyloidosis demands a high index of suspicion and requires histological confirmation of pathognomonic green birefringence under polarized light when an infiltrated tissue specimen is stained with Congo-red staining [1,2].

Pleural involvement of systemic amyloidosis has rarely been reported and is considered a serious complication [3]. Pleural amyloidosis is diagnosed with the identification of amyloid deposits in pleural biopsy specimens. However, pleural biopsies are rarely performed for this indication.

We describe the case of a patient with AL cardiac amyloidosis presenting as intractable pleural effusion and diagnosed via pleural biopsy.

Background: Cloacal malformation represents the rarest and most complex congenital anorectal malformation in females and is characterized by the convergence of urinary, gynecological, and intestinal systems within a single common channel. Three-dimensional computed tomography reconstruction (3D CT cloacagram) has emerged as a valuable method for anatomical assessment and preoperative planning.

Objectives: To evaluate our experience with 3D CT cloacagram and assess its results.

Methods: This retrospective case series included all patients with cloacal malformation who underwent preoperative 3D CT cloacagram at a single institution during 2019–2023. Collected data included patient characteristics, timing of the 3D CT cloacagram, results of the 3D CT cloacagram, comparison with endoscopic results, surgical procedures, and postoperative outcome.

Results: Six patients with cloacal malformation were included in this study, including two with posterior cloaca. The median common channel length on 3D CT cloacagram was 24.5 mm (range 9–48 mm) and the median urethral length was 15.5 mm (range 13-24 mm). The surgical approach involved a combined abdominoperineal approach in three patients and posterior sagittal anorectal vaginal urethral plasty in one patient. Two patients were awaiting surgical reconstruction at the time of publication.

Conclusions: Our implementation of 3D cloacagram has facilitated precise measurements of both the urethra and common channel lengths, two key factors in formulating surgical strategies for cloacal reconstruction. Moreover, this technique has markedly improved our capacity for surgical planning contributing to colorectal, gynecological, and urological perspectives.

Background: Galactin-3 has been found to be involved in oocyte maturation, folliculogenesis, implantation, and placentation. The expression of Galactin-3 in the endometrium of women who have successfully undergone in vitro fertilization (IVF) has been suggested as a potential biomarker for predicting successful embryo implantation.

Objectives: To evaluate the expression of Galactin-3 in the sera and follicular fluid of women during IVF cycles.

Methods: This prospective research included 21 women undergoing IVF treatments. Blood samples were taken at four points: day 2 before starting stimulation, trigger day, day of oocyte retrieval, and day of the β-human chorionic gonadotropin level test. In addition, follicular fluid samples were taken on the day of oocyte retrieval. Galactin-3 protein levels were measured in serum and follicular fluid using enzyme-linked immunosorbent assay.

Results: Galactin-3 levels on the stimulation day were positively correlated to estradiol levels on the day of the trigger (0.59, P = 0.02). Among women who achieved pregnancy compared to those who did not, Galectin-3 serum levels were higher on the day of the trigger (17.93 ± 4.35 ng/ml vs. 11.01 ± 3.73 ng/ml, P = 0.015).

Conclusions: These findings may imply a potential role of Galectin-3 on the success of IVF treatments, underscoring the potential importance of inflammatory processes in fertility.