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: Remnant cholesterol (RC), the cholesterol content of triglyceride-rich lipoproteins, is an emerging residual risk factor for atherosclerotic cardiovascular disease. Data on the prognostic significance after an ischemic stroke are limited.

Objectives: To investigate the association between RC and risk for cardiac events following hospitalization for an ischemic stroke.

Methods: Data were collected for 5697 patients (39.5% women) affiliated with Clalit Health Services and hospitalized with an acute ischemic stroke. Adjusted Cox-regression models were used to estimate the association between RC percentiles, calculated using a routine post-discharge lipid profile, and risk for future myocardial infarction (MI) or coronary revascularization.

Results: Mean age was 69 ± 10 years; 78% were treated by lipid-lowering therapies. During median follow-up of 22 months, a MI or coronary revascularization event occurred in 243 patients. After multivariable adjustment including lipid-lowering therapies and non-HDL-C, RC was associated with higher MI or revascularization risk: hazard ratio (95% confidence interval): 1.42 (1.10–1.85), 1.50 (1.11–2.02), 1.62 (1.09–2.40), and 1.93 (1.22–3.06), in those with RC percentiles ≥ 50th (23.3 mg/dl), ≥ 75th (31.8 mg/dl), ≥ 90th (42.1 mg/dl), and ≥ 95th (49.1 mg/dl), compared to < 50th percentile. When RC and non-HDL-C levels were discordant, the level of RC better reflected higher risk for adverse cardiac events.

Conclusions: Elevated RC following acute ischemic stroke is a risk factor for MI or coronary revascularization, independent of lipid-lowering therapies and non-HDL-C and may serve as a residual cardiovascular risk marker and potential treatment target in patients with ischemic stroke.

Background: Functional mitral and tricuspid regurgitation (fMR and fTR, respectively) portend increased morbidity and mortality among heart failure (HF) patients.

Objectives: To characterize acute decompensated valvular HF (VHF) as a novel HF category, defined by presence of either more than moderate fTR or more than moderate fMR with left ventricular ejection fraction (LVEF) ≤ 50%.

Methods: Patients with VHF were prospectively enrolled over a 6-month period and compared to acute decompensated heart failure (ADHF) patients without significant fTR or fMR. We used a standardized diuretic protocol when indicated, and appropriate inpatient guideline-directed medical therapy was initiated.

Results: Among 322 patients admitted with ADHF, 83 (26%) met VHF criteria with mean age 66 ± 13 years, 43 (52%) males, and median LVEF of 30% (20–55). Of 61 patients in whom the diuretic protocol was initiated, 59 (97%) had an adequate response (i.e., > 100 cc/hour for at least 6 hours). VHF patients had longer length of hospitalization (8 [5–13] vs. 5 [3–8] days, P < 0.001), and higher rates of 90–day heart replacement therapy (HRT) or death (hazard ratio 2.52, 95% confidence interval (1.13–5.64); P = 0.024).

Conclusions: Over a quarter of ADHF patients can be newly categorized as VHF patients, distinguished by prolonged hospitalization and worse 90-day mortality / HRT rate. The initial response rate to a standardized diuretic protocol was high.

Background: Initiating oral antidiabetic therapy, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, is generally not recommended during hospitalization. However, guidelines since 2021 have supported their use in heart failure with reduced ejection fraction (HFrEF), and since 2023 in preserved ejection fraction (HFpEF).

Objectives: To assess the safety and outcomes of initiating SGLT2 inhibitors during hospitalization for acute heart failure (HF).

Methods: We conducted a historical cohort study of 307 patients admitted with acute HF between October 2018 and April 2022. Patients were grouped as chronic SGLT2i users, new initiators during hospitalization, or controls who did not receive SGLT2i.

Results: Among the 307 patients, 50.4% had HFrEF, 30.8% HFpEF, and 18.8% HF with mildly reduced ejection fraction. In-hospital mortality was 3.6% (11 patients); 2-year mortality was 37.7% (116 patients). New SGLT2i initiators had the lowest 2-year mortality (22.2%) compared to controls (43.9%) and chronic users (41.8%) (P = 0.008). They also had the lowest 1-year rehospitalization rates (18.3% vs. 35.5% vs. 32.8%; P = 0.025). Multivariable analysis identified older age and co-morbidities as independent predictors of mortality. SGLT2i initiation was associated with reduced rehospitalization. Adverse effects occurred in 15.6% of SGLT2i users, mainly acute kidney injury.

Conclusions: In-hospital SGLT2 inhibitor initiation in patients with HF appears safe and is associated with reduced post-discharge mortality and readmission rates.

Standup paddleboard surfing (SUP) is a sports activity in which a person stands upright on a surfboard and propels the board using a single paddle. It is an emerging recreational activity that is attracting public attention and gaining popularity because it promotes fitness, strength, and improved balance. In this review, we discuss the outcomes after severe cardiac events in SUP surfers. We report on six fit individuals (five males and one female, age range 41–69 years) who experienced sudden cardiac arrest (n=3) or acute myocardial infarction occurring during SUP. Cardiopulmonary resuscitation was initiated in three patients on presentation due to ventricular fibrillation. In four patients the culprit coronary artery was the left anterior descending artery treated by percutaneous coronary intervention. All patients were discharged alive. A review of the literature showed a paucity of scientific evidence to substantiate the proposed health benefits of SUP surfing. Our cluster of acute cardiac events occurring during this activity calls for heightened public awareness to better understand the physical demand required to practice SUP. There is a need for more data regarding the cardiovascular clinical aspects of this water activity, and the risks it entails.

Background: Acute cholecystitis (ACC) is one of the most common diagnoses encountered in surgical wards. A number of treatment modalities are available, and various guidelines have been developed to help decision making. Many factors influence treatment strategies, including patient age and frailty. Due to the increasing proportion of older patients, consideration into the best treatment modalities for this population are warranted.

Objectives: To determine outcomes of elderly patients with ACC according to different treatment strategies.

Methods: A retrospective analysis of consecutive patients aged ≥ 80 years who were admitted with a diagnosis of ACC between 2015 and 2019 to a single academic center. Patients were divided into three groups according to treatment: percutaneous cholecystostomy tube placement, cholecystectomy, intravenous antibiotic treatment only.

Results: Overall, 466 patients were included in the cohort. The majority (approximately 75%) were treated with antibiotics only, 17% underwent percutaneous cholecystostomy, and 8% underwent laparoscopic cholecystectomy. One-year mortality was 28.1%. The highest mortality rate was 41.6% in the cholecystostomy group (P = 0.002). In multivariable analysis age, functional status, C-reactive protein, and albumin levels were found to be independent risk factors for 1-year mortality (hazard ratio [HR] 1.08, 0.56, 0.98, 0.4, respectively). Cholecystostomy increased risk of one-year mortality compared to cholecystectomy and antibiotics alone (HR 0.61, 0.23, respectively).

Conclusions: The use of cholecystostomy for ACC in older adults is an independent risk factor for 1-year mortality. Its use in older adults should be reserved for carefully selected cases.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease pathway is heavily influenced by different inflammatory cytokines. There is ample evidence of cannabidiol (CBD) immunomodulation effects.

Objectives: To investigate the effect of CBD on patients with SARS-CoV-2 and to measure the impact on inflammatory cytokines.

Methods: A double blind, placebo-controlled study to compare the clinical outcomes and selected serum cytokine levels in patients with SARS-CoV-2 that received sublingual CBD extraction. Seven patients were randomized to the treatment arm and three to the placebo group.

Results: Clinical outcomes were better in the patient group that received sublingual CBD vs. patients receiving placebo treatment. Serum cytokine mean concentration levels showed differences between the two groups but of mixed trends.

Conclusions: Patients presenting with SARS-CoV-2 and receiving CBD sublingually had better outcomes than those receiving a placebo, although these results did not reflect in selected serum cytokines. Further study is needed.

Background: Several studies have shown an association between increased red blood cell distribution width (RDW) and adverse outcomes in various acute diseases. Small studies have suggested that RDW is a useful predictor of acute pancreatitis severity.

Objectives: To determine the association between RDW at admission and early mortality in acute pancreatitis. To assess whether RDW adds to the predictive ability of the Glasgow Imrie Score.

Methods: In this observational study, we included all adult patients admitted with a primary diagnosis of acute pancreatitis between January 2008 and June 2021. Patients were divided into two groups according to RDW: normal RDW (RDW ≤ 14.5%) and elevated RDW (RDW > 14.5%).

Results: Within 30 days of admission, 29/438 patients (6.6%) with increased RDW and 20/1250 patients (1.6%) with normal RDW had died: univariate analysis (odds ratio 4.6, 95% confidence interval 2.45–7.9, P < 0.001), fully adjusted model (odds ratio 3.29, 95% confidence interval 1.75–6.26, P < 0.001). We calculated receiver operating characteristic curve (ROC) for RDW alone, Glasgow Imrie Score alone, and a combination of Glasgow Imrie Score with RDW. We assessed their ability to predict 30-day mortality. Area under the ROC curve (AUC) of RDW alone was 0.671 and Glasgow Imrie Score AUC was 0.682; Glasgow Imrie Score plus RDW had an AUC of 0.769.

Conclusions: In patients with acute pancreatitis, elevated RDW at admission was independently associated with increased 30-day mortality. The addition of RDW to a pancreatitis prognostic tool such as the Glasgow Imrie Score improves its predictive ability.

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].

Letter 1: "Not type 2" by Moti Ravid 

Letter 2: "Hyponatremia, hyperkalemia, and acute kidney injury: clues for the diagnosis of uroperitoneum in patients with new-onset ascites" by Zvi Ackerman and Samuel N. Heyman, 

Letter 3: "Surgery in Mauthausen Concentration Camp" by George M. Weisz

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.

Background: Serum ferritin is a sensitive inflammatory biomarker reflecting cell damage and oxidative stress in inflammatory rheumatic diseases. The use of ferritin for assessment of systemic sclerosis (SSc) activity, severity, and prognosis has not been fully elucidated.

Objectives: To assess the correlation between serum ferritin levels and SSc disease parameters, complications, and outcome.

Methods: Demographic, clinical, and laboratory data, including blood levels of ferritin, were collected from files of patients with SSc who were treated at the Rheumatology Institute at Rambam Health Care Campus from January 2004 to July 2021. The study compared SSc patients with elevated levels of ferritin to those with normal levels.

Results: We extracted data of 241 SSc patients (80% female, 60% with diffuse SSc, mean age 54 ± 15.4 years, mean disease duration 6.8 ± 4.5 years). During follow-up, 39% died. Elevated ferritin levels positively correlated with male sex; short disease duration; lung, heart, and kidney involvement; higher modified Rodnan skin score; anemia; elevated levels of creatinine kinase, C-reactive protein, creatinine, and troponin; reduced pulmonary function tests (forced vital capacity and diffusion capacity of the lung for carbon monoxide); and left ventricular ejection fraction. There were no correlations between ferritin levels and pulmonary hypertension or gastrointestinal involvement. Levels of ferritin negatively correlated with anti-centromere antibodies.

Conclusions: In SSc, ferritin can serve as a marker for ongoing systemic inflammation and prognosis, particularly in patients with lung and heart involvement. Further studies on serial ferritin measurement in the management of SSc patients are warranted.

Hepatitis E Virus (HEV), a single-stranded RNA virus, is the leading cause of viral-induced acute liver failure globally. It is estimated to infect 20 million people annually, resulting in 3.3 million symptomatic cases and 44,000 deaths, worldwide [1]. Transmission is fecal-oral through contaminated food and water, zoonotic spread, or blood transfusions, and usually results in a self-limiting disease. While prevalent in resource-limited countries, cases are sporadic in the developed world [1]. Established risk factors for severe HEV infection include pregnancy, immunocompromised state, and underlying liver disease, while reports of malignancy as a predisposing factor are not well documented [1]. Here we present a case of a patient who, without established risk factors, developed a severe HEV infection leading to multiorgan failure and death.

Background: Pseudomonas aeruginosa (PSA) is an infectious pathogen associated with acute appendicitis; however, it is not consistently addressed by empirical antibiotic therapy, despite potential complications.

Objectives: To investigate the incidence, predictors, and outcomes of PSA-associated acute appendicitis in children.

Methods: We conducted a retrospective analysis involving pediatric patients who underwent acute appendicitis surgery and had positive peritoneal cultures. Clinical, microbiological, and intraoperative data were extracted from medical records.

Results: Among 2523 children with acute appendicitis, 798 (31.6%) underwent peritoneal cultures, revealing 338 positive cases (42.3%), with PSA detected in 77 cases (22.8%). Children with PSA were three times more likely to exhibit high intraoperative grading ≥ 3 (93.4% vs. 76.8%, 95% confidence interval [95%CI] 1.2–8.3, P = 0.023) and nearly four times more likely to have polymicrobial cultures (88.3% vs. 62.1%, 95%CI 1.8–8.0, P < 0.001) than those without PSA in peritoneal cultures. Duration of symptoms did not predict PSA isolation (P = 0.827). Patients with PSA had longer median hospital stays (8 days, interquartile range [IQR] 7–10) than those with other pathogens (7 days, IQR 5–9) (P = 0.004). Antibiotic treatment duration, intensive care unit admission rates, readmission, and mortality were similar between the two groups (P = 0.893, 0.197, 0.760, and 0.761, respectively).

Conclusions: PSA is a common pathogen in children diagnosed with acute appendicitis and positive peritoneal cultures. The likelihood of isolating PSA increases with high-grade intraoperative assessment and in the presence of multiple pathogens in peritoneal cultures, suggests antipseudomonal treatment.