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: Out-of-hospital cardiac arrest (OHCA) poses a considerable health burden and offers poor prognosis. Information about OHCA in Israel is scarce.

Objectives: To present a pilot registry of prehospital and in-hospital characteristics of patients with OHCA.

Methods: A descriptive study was conducted of consecutive adult patients with OHCA treated in the field by Magen David Adom (MDA) paramedics and treated at the Sheba Medical Center.

Results: The study included 99 patients with OHCA who were brought by MDA to the Sheba Medical Center. The median age was 79 years (IQR 67–89(, 61% were male. In total, 69% of the events occurred at home, 16% at nursing facilities, 10% on streets, and 2% in public buildings. Most events (80%) were witnessed. Bystander-basic life support (BLS) was administered to 28%, 45% received BLS from an emergency medical service first responder. Automated external defibrillation was used in 40% of cases. In our cohort, 51 patients (51%) survived initial treatment in the emergency department (ED) and were hospitalized. Electrocardiography at arrival demonstrated ST-elevation in 22% of cases. Coronary angiography was performed in 19% (n=19) of patients, and 12% (n=12) underwent percutaneous intervention. Eventually, 26 patients (26%) survived to discharge with a Cerebral performance categories were as follows: 13% (n=13) with good cerebral performance, 10% (n=10) with moderate disability, and 3% (n=3) with severe disability or unconscious.

Conclusions: Among those admitted after surviving ED resuscitation, half survived to discharge. Most of those who survived hospitalization and were discharged with good neurological performance were young males.

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: Direct oral anticoagulants (DOACs) have significantly transformed anticoagulant therapy, improving effectiveness, safety, and convenience in managing thromboembolic conditions. However, concerns persist regarding drug-related problems (DRPs) associated with DOACs, necessitating the establishment of multidisciplinary antithrombotic stewardship programs to optimize the selection, dosing, and monitoring of DOACs.

Objectives: To evaluate the incidence and types of DRPs associated with DOACs, the frequency of clinical pharmacist consultations, the acceptance rates of the clinical pharmacist recommendations, and physicians' adherence to appropriate DOACs prescribing practices.

Methods: A retrospective cohort study was conducted over 4 months in the internal medicine departments at Shamir Medical Center (Assaf Harofeh), Israel. The study included patients aged 18 years and older who were prescribed DOACs (apixaban, rivaroxaban, and dabigatran). Data on patient characteristics and clinical outcomes were collected from electronic medical records. A clinical pharmacist reviewed and reassessed the appropriateness of DOAC prescribing.

Results: During the study period, 415 patients receiving DOACs were identified. Among them, 28.4% had inappropriate DOAC prescriptions leading to 128 recommended interventions. The most common DRP was underdosing (29.7%) followed by unjustified antiplatelet use (26.6%). Clinical pharmacists performed 85.9% of the interventions, with a physician acceptance rate of 72.7%. Patients with inappropriate DOAC prescriptions exhibited increased trends in thromboembolic events and in-hospital mortality.

Conclusions: Despite over a decade of clinical experience with DOACs, DRPs remain a significant challenge. Implementing antithrombotic stewardship programs is critical for optimizing DOACs use, reducing DRPs, and enhancing patient safety.

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.

Background: Behcet's syndrome (BS) is a multisystem syndrome that typically manifests as recurrent oral and genital ulcers, as well as other systemic manifestations. Few studies describing the characteristics of BS among Israeli patients have been published.

Objectives: To describe the characteristics of BS patients and to compare Jewish and Arab subpopulations.

Methods: We retrospectively reviewed electronic medical records and extracted demographic, clinical, laboratory, and medication data for each patient. We compared the Jewish and Arabic BS patients.

Results: The cohort included 98 patients. Males constituted 49 (50%); mean age at the time of diagnosis was 29.9 years; 71 (72.4%) were Arab and 27 (27.6%) were Jewish. Oral ulcers were evident in 93 patients (94.9%) and genital ulcers in 54 (55.1%). Involvement of the skin, joints, eyes, gastrointestinal tract, and neurologic and vascular systems were demonstrated among 42 (42.9%), 57 (58.2%), 47 (48.0%), 8 (8.2%), 10 (10.2%), and 15 (15.3%), respectively. HLA B51 was positive in 24 of 37 (64.9%). Pathergy was positive in 8 of 12 (66.7%). Colchicine was used in 82 (83.7%), azathioprine 47 (48%), methotrexate 16 (16.3%), apremilast 10 (10.2%), cyclosporine-A 8 (8.2%), adalimumab 26 (26.5%), infliximab 12 (12.2%), cyclophosphamide 1 (1.0%), tocilizumab 2 (2.0%), and anti-coagulation 6 (6.1%). The Arab and Jewish subpopulations were significantly different regarding male proportion, 40 (56.3%) vs. 9 (33.3%), P = 0.042.

Conclusions: BS is more common among Arabs in northern Israel, but no significant clinical or demographic differences were found except for a higher proportion of male patients among Arabs.

Background: Inflammatory and thrombotic markers play crucial roles in risk stratification for various diseases.

Objectives: To investigate the relative importance of inflammation, measured by C-reactive protein (CRP), and platelet turnover, indicated by immature platelet fraction (IPF), in predicting outcomes for patients with cardiovascular disease, coronavirus disease 2019 (COVID-19), and bacterial infections.

Methods: In this retrospective observational study, we analyzed data from 1473 individuals admitted to the Samson Assuta Ashdod University Hospital between 2018 and 2022. Patients were categorized based on CRP and IPF levels, with a focus on 280 patients in the high CRP/low IPF or high IPF/low CRP tertiles.

Results: The high CRP low IPF group demonstrated significantly higher mortality rates compared to the low CRP high IPF group (13.5% vs. 0.8%, P < 0.001). Logistic regression analysis revealed that the high CRP and low IPF combination was the strongest predictor of mortality (odds ratio 12.951, 95% confidence interval 1.409–119.020, P = 0.024).

Conclusions: The combination of inflammatory (CRP) and thrombotic (IPF) markers provides superior prognostic information compared to individual disease diagnoses in patients with cardiovascular disease, COVID-19, and bacterial infections.

Background: Ectodermal dysplasia-syndactyly syndrome (EDSS) is a rare form of ectodermal dysplasia caused by biallelic mutations in NECTIN4 (PVRL4) gene.

Objectives: To identify new and rare mutations of the NECTIN4 gene in two unrelated families with EDSS.

Methods: Six patients from two unrelated families were diagnosed with EDSS. Next generation sequencing and Sanger sequencing were performed on DNA extracted from peripheral blood from affected and unaffected individuals from the families. We performed a literature search to identify previously reported cases of EDSS.

Results: A homozygous c.680A>G p.His227Arg mutation in NECTIN4 was found in five affected members of both families. One patient was found to be compound heterozygous for the latter mutation and for another novel missense mutation in NECTIN4 (c.79+1G>A). Both mutations affect the extracellular domain of nectin-4. A literature search identified only 13 reported families affected by this rare disorder.

Conclusions: We described two families with six affected members presenting with EDSS caused by two novel NECTIN4 mutations. We also reviewed the current available data on EDSS in the medical literature.

Background: Wilson disease (WD) is an autosomal recessive disease characterized by a defect in hepatocellular copper transport with a wide spectrum of clinical manifestations and reported prevalence.

Objectives: To study the epidemiology and clinical manifestations of WD between two ethnic groups, Jewish and Bedouins, with different marriage patterns, in southern Israel.

Methods: We conducted a retrospective study investigating the clinical course and laboratory characteristics of children diagnosed with WD who were treated at Soroka University Medical Center.

Results: Sixteen patients were diagnosed between 2000 and 2021 (8 males, 50%), 14 were of Bedouins origin. The total cohort prevalence was 1:19,258 while the prevalence of the disease was significantly higher among Bedouins compared to Jews (1:10,828 vs.1:78,270, P-value = 0.004). The median age at diagnosis was 10.2 years, without a significant difference between the groups. The most common presenting symptom was hepatic manifestations: 81.2% had elevated transaminases, 12.5% had jaundice, 25% had neurological symptoms, one had a Kayser-Fleischer ring, and one had psychosis. The mean ceruloplasmin level was 3.0 mg/dl. During follow-up, nine patients normalized transaminases with treatment, while three required liver transplantation. There was no significant difference in the clinical presentation and disease course between the two ethnic groups.

Conclusions: Our cohort showed a high prevalence of WD compared to previous studies, especially among the Bedouin population, which has a high consanguinity rate. The prognosis of WD in our population is similar to other studies and depends mainly on treatment compliance.

Background: Acute bronchiolitis, primarily caused by respiratory syncytial virus (RSV), is the leading cause of hospitalization in young children. Despite international guidelines supporting clinical diagnosis, laboratory evaluations are often conducted with limited validity.

Objectives: To evaluate the association between C-reactive protein (CRP) serum levels on admission and disease severity in children hospitalized due to RSV bronchiolitis.

Methods: This retrospective cohort study included children (0–24 months old) who were hospitalized due to RSV bronchiolitis (2018–2022), CRP levels taken at admission.

Results: We included 1874 children (mean age of 6.7 months, 59% males); median CRP level 1.92 mg/dl. Children with elevated CRP (> 1.92 mg/dl) were significantly older (5.1 vs. 3.8 months, P < 0.001) and had higher rates of pneumonia (9.4% vs. 4.3%, P < 0.001), urinary tract infection (UTI), (2.2% vs. 0.2%, P < 0.001), acute otitis media (AOM) (1.7% vs. 0.2%, P < 0.001), admissions to the pediatric intensive care unit (PICU) (7.4% vs. 3.7%, P < 0.001), antibiotic treatment (49.8% vs. 37.2%, P < 0.001), and longer hospitalizations (3.83 vs. 3.31 days, P < 0.001). Multivariable analysis predicted increased risk for UTI, PICU admission, pneumonia, and longer hospitalization (relative risk 11.6, 2.25, 1.98, 1.44, respectively, P < 0.001). CRP thresholds of 3.51, 1.9, and 2.81 mg/dl for PICU admission, UTI, and pneumonia, were calculated using Youden's index with AUC 0.72, 0.62, and 0.61, respectively.

Conclusions: Elevated CRP levels at admission are associated with increased disease severity and higher complication rates in children hospitalized with RSV bronchiolitis.

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure (HF) secondary to left ventricular systolic dysfunction (defined as left ventricular ejection fraction [LVEF]) < 45% toward the end of pregnancy or in the months following delivery, where no other cause of HF is found. Complete understanding of the etiology is lacking, with higher incidence seen in advanced maternal age, multiple gestations, preeclampsia, and anemia [1]. Potential suggested causes include pathological immune response, hormonal abnormalities, stress cytokines, and nutritional deficiencies. Genetic predisposition was demonstrated in some PPCM, most commonly pathogenic loss-of-function truncating variants in Titin gene (TTN) [1]. Other causative genes reported are DMD, LAMP2, DSP, MYH6, SYNM, TPM1, and VCL [1].

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: Heart failure (HF) is an emerging pandemic associated with increased mortality, recurrent hospitalizations, and reduced quality of life. Guideline-directed medical therapy has been shown to improve outcomes, particularly in patients with HF with reduced ejection fraction (HFrEF). The main goal of HF clinics is optimizing medical therapy.

Objectives: To assess the impact of our HF clinic on medical therapy and clinical outcomes.

Methods: We obtained demographic, echocardiographic, and clinical data of patients listed in our HF clinic during a 4-year period. Medical therapy was evaluated based on patient reports and documented data. Recurrent admissions for HF were documented.

Results: A total of 317 patients (74.1% male, median age 66 years, IQR 55–74) were listed in the clinic with a total of 1140 visits. Of these patients, 62.5% had HFrEF, 20.5% presented with mildly reduced ejection fraction, and 17% showed preserved ejection fraction at the time of the first visit. The use of sodium glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists was optimized in 92% and 91% of the patients, respectively. In the subgroup of patients with HFrEF, the use of angiotensin-receptor antagonist/neprilysin inhibitor increased from 22.6% to 87.9% (P < 0.001) and SGLT2 inhibitor use increased from 49.2% to 92% (P < 0.001). During the follow-up period (2.2 years, IQR 1.1–3.1), 203 patients (64%) were readmitted to the hospital for HF at least once. The rate of readmissions decreased over time.

Conclusions: An HF clinic plays an important role in optimizing medical therapy and reducing readmissions.

The issue of genital ulcers (GUs) in Israeli Arab female patients with Behçet's disease (BD is important as GUs are considered a unique feature of BD and stand as diagnostic criterion for the diagnosis in the International Study Group (ISG) criteria [1] and the International Criteria for Behcet Disease (ICBD) [2]. According to the ISG, GUs can be detected by a physician or by the patient [1]. While oral ulcers are easily observable, the identification of more hidden GUs pose a significant challenge.

Background: Intra-articular knee injections (IAKI) are commonly used for diagnostic and therapeutic purposes but may induce anxiety and fear. While existing literature has identified the variance between expected and actual pain levels in various medical procedures, this phenomenon remains unexplored in the context of IAKI.

Objectives: To describe the differences between anticipated and experienced pain recorded during IAKI.

Methods: The study cohort included 50 patients who underwent IAKI by an orthopedic specialist in an outpatient clinic. Patients recruited to the study recorded the anticipated and experienced pain, anxiety index, and factors influencing injection related fear.

Results: The study population (n=50) demonstrated a significant difference between the pain expected before the injection (mean Visual Analogue Scale [VAS] score 6.19) and the actual experienced (mean VAS score 2.07, P-value < 0.001). Significant differences between anticipated and experienced VAS scores were demonstrated for both females and males. There was a significant difference between males and females in terms of estimated VAS score. There was no significant difference between males and females in term of the experienced VAS score. The difference (delta) between expected and experienced pain differed significantly between sexes.

Conclusions: These findings emphasize the importance of educating patients about expected pain levels during IAKI. Presenting this quantified information may reassure patients that the procedure is not as painful as expected, which can potentially increase the compliance.