Israel Medical Association Journal

Background: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular events, especially following acute exacerbation (AECOPD). However, there is insufficient data to identify high-risk subjects.

Objectives: To evaluate the association between neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, and the risk of cardiovascular events following exacerbation.

Methods: This retrospective cohort included patients with COPD who were hospitalized with AECOPD between January 2016 and December 2022. We took the reference NLR before index admission and evaluated the incidence of major adverse cardiovascular events (MACE) or cardiovascular death over the following year. Multivariate analysis and competing risk regression were used to assess hazard ratio (HR) and NLR threshold for increased cardiovascular risk.

Results: In total, 15,224 patients with AECOPD completed one 1-year follow-up session. The majority were male (54%) with a mean age of 69 ± 3 years. The risk for MACE of patients in the highest NLR quartile was higher over the first year following AECOPD; however, the magnitude of effect decreased over time. After adjustment to other confounders that may increase NLR, a value > 3.5 was found with the strongest predictive power

Conclusion: Community NLR can be used to identify patients at increased risk of cardiovascular events following AECOPD, together with other risk factors. Every effort should be made to reduce exacerbation risk, and target intervention to those patients at highest risk.

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: 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: 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: 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.

Background: Solid organ transplant (SOT) recipients represent a particularly vulnerable group due to their reliance on immunosuppressive therapies. Previous studies indicated a mortality rate of 20%-30% among SOT recipients with coronavirus disease 2019 (COVID-19). With the advent of the Omicron variant in November 2021, characterized by milder symptoms and lower mortality rates in the general population, safety measures relaxed, potentially impacting vulnerable populations like SOT recipients.

Objectives: To investigate mortality and morbidity among hospitalized SOT recipients with COVID-19 infection during the Omicron wave.

Methods: A retrospective, propensity-matched cohort study conducted at the Rabin Medical Center, Israel, spanned from November 2021 to June 2023. Adult SOT recipients hospitalized with COVID-19 were compared to matched controls.

Results: Among 139 hospitalized SOT recipients and 209 controls, SOT recipients hospitalized with COVID-19 displayed higher in-hospital mortality (19% vs. 11%) and 90-day all-cause mortality (30% vs. 17%). In addition, the 90-day readmission rate was significantly higher among SOT recipients (43% vs. 31%). Multivariable analysis confirmed these trends, with SOT recipients exhibiting increased risk for mortality, readmission, invasive ventilation, and intensive care unit admission.

Conclusions: The heightened vulnerability of hospitalized SOT recipients during the Omicron wave was characterized by higher mortality and readmission rates compared to matched controls. Despite the perceived milder nature of the Omicron variant, SOT recipients remain disproportionately affected. Continued vigilance and targeted interventions are necessary for this population including vaccinations and adherence to preventive measures. Investigating this population’s outcomes through the changing COVID-19 variants is still warranted.

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 coronavirus disease 2019 (COVID-19) pandemic showed the need to evaluate disease severity promptly at the time of hospital admission. 

Objectives: To establish an admission protocol, which included clinical and laboratory findings. 

Methods: We conducted a retrospective study at Wolfson Medical Center, Israel, for a period of 19 months (2020–2021). We established a protocol for patients who were admitted with COVID-19 infection. The protocol parameters included demographic data, co-morbidities, immune status, oxygen level at room air on admission, oxygen demand, lymphopenia, C-reactive protein (CRP) level, lactate dehydrogenase, D-DIMER, creatinine, aspartate transferase, alanine aminotransferase, and ferritin. Based on this protocol, we defined the severity of COVID-19 at the beginning of hospitalization and started treatment without delay. This protocol included ferritin levels as a guide to severity and outcome of patients. A database was established for all the parameters of the patients included in the study. 

Results: The study included 407 patients; 207 males (50.9%), 200 females (49.1%). The age range was 18–101 years. Hyperferritinemia (> 1000 ng/dl) was one of the strongest and most significant predictors for severe disease in these patients (P < 0.001). Lymphopenia, high levels of CRP, alanine aminotransferase, aspartate transferase, lactate dehydrogenase, and creatinine also correlated with severe disease, complications, and death. 

Conclusions: Abnormal ferritin levels were a very significant and clear indicator of the development of severe COVID-19. The addition of ferritin levels to our protocol aided in finding which patients were at increased risk for morbidity and mortality.

Background: Prognostication is complex in patients critically ill with coronavirus disease 2019 (COVID-19).

Objectives: To describe the natural history of ventilated critical COVID-19 patients.

Methods: Due to our legal milieu, active withdrawal of care is not permitted, providing an opportunity to examine the natural history of ventilated critical COVID-19 patients. This retrospective cohort included COVID-19 ICU patients who required mechanical ventilation. Respiratory and laboratory parameters were followed from initiation of mechanical ventilation for 14 days or until extubation, death or tracheostomy.

Results: A total of 112 patients were included in the analysis. Surviving patients were younger than non-survivors (62 years [range 54–69] vs. 66 years [range 62–71], P = 0.01). Survivors had a shorter time to intubation, shorter ventilation duration, and longer hospital stay. Respiratory parameters at intubation were not predictive of mortality. Nevertheless, on ventilation day 10, many of the ventilatory parameters were significantly better in survivors. Regarding laboratory parameters, neutrophil counts were significantly higher in non-survivors on day 1 and C-reactive protein levels were significantly lower in survivors on day 10. Modeling using a generalized estimating equation showed small dynamic differences in ventilatory parameters predictive of survival.

Conclusions: In ventilated COVID-19 patients when there is no active care withdrawal, prognostication may be possible after a week; however, differences between survivors and non-survivors remain small.

Background: Management of patients with reported iodinated contrast media (ICM) allergy is not supported by sufficient data. It is assumed that these patients are at risk for severe reactions, and that premedication provides protection.

Objective: To examine current practice and prognosis in hospitalized patients with ICM allergy.

Methods: In this retrospective study, we analyzed data of 17,356 patients who were hospitalized between 2018 and 2022 and referred for imaging. No-allergy and allergy groups were matched by age, sex, co-morbidities, and indications for imaging. Statistical analysis compared demographic, clinical, and imaging-related parameters.

Results: Our study included records of 501 patients with ICM allergy and 16,855 with no allergy. Patients with allergy were older (70.92 ± 16.25 vs. 59.02 ± 23.74 years, P < 0.001), female preponderance (male proportion 42.5% vs. 54%, P < 0.001), and those with increased cardiovascular and metabolic co-morbidities. The rate of ICM injection was similar among patients with ICM allergy (34%) and no allergy (36%). Most patients with ICM allergy did not receive premedication. Allergic patients demonstrated increased mortality (25.9% vs. 16.5%, P < 0.001); however, this result was not associated with the diagnosis of allergy, anaphylactic reactions, or premedication.

Conclusions: ICM allergy is mostly reported in patients with advanced age and multiple co-morbidities. Mortality was not increased when compared to matched non-allergic individuals. Among patients with reported allergy who were injected with ICM, anaphylaxis was not a cause of death, although fewer than half received premedication. Prospective trials are warranted to revise the clinical approach to ICM allergy.

Background: Diabetic ketoacidosis (DKA) is an acute metabolic, life-threatening complication of diabetes mellitus with a mortality rate that now stand at less than 1%. Although mortality is coupled with the etiology of DKA, literature on the influence of DKA etiology on patient outcome is scarce.

Objectives: To study different triggers for DKA and their effect on outcomes.

Methods: We conducted a retrospective study that include 385 DKA patients from 2004 to 2017. The study compared demographics, clinical presentation, and mortality rates by different precipitating factors.

Results: Patients with DKA due to infections had a higher risk to develop in-hospital mortality after controlling for age and sex (odds ratio 4.40, 95% confidence interval 1.35–14.30), had a higher Charlson Comorbidity Index score, a higher risk of being mechanical ventilated (14% vs. 3%, P < 0.01), and a longer duration of hospitalization (5 days vs. 3 days, P < 0.001).

Conclusions: It is crucial to find the triggers that precipitate DKA and start the treatment as early as possible in addition to the metabolic aspect of the treatment especially when the trigger is an infectious disease.

Background: According to Hamas sources, many Israeli hostages in Gaza were killed by indiscriminate Israeli airstrikes, together with a large number of Palestinian citizens.

Objectives: To verify whether the estimated death rate of Israeli hostages was similar to the estimated death rate of Gaza citizens from these acts of war.

Methods: We used two estimates of hostage death rates, one obtained from Israeli intelligence sources, and one published by a Hamas spokesperson. We used the Palestinian casualty rates published by the Palestinian Ministry of Health. We compared death rates using Fisher's exact test.

Results: By 30 December 2023, the rate of Israeli hostage death was 23/238 (9.7%) according to Israeli intelligence sources, and 60/238 (25.2%) according to Hamas. Both figures are strikingly and significantly higher than the death rate among Palestinians, estimated to be 19,667/2.2 million (0.89%) by 19 December 2023 (P < 0.0001).

Conclusions: Israeli airstrikes as the cause of death of Israeli hostages are implausible unless they were specifically exposed to these strikes more than Palestinian citizens.

Background: At the beginning of 2020, the coronavirus disease 2019 (COVID-19) pandemic presented a new burden on healthcare systems.

Objectives: To evaluate the impact of the COVID-19 pandemic on the outcome of non-COVID patients in Israel.

Methods: We conducted a retrospective observational cohort study at a tertiary medical center in Israel. From December 2018 until June 2022, 6796 patients were hospitalized in the internal medicine wards. Patients were grouped based on their admission date: admitted during COVID waves (waves group), admitted between waves (interim group), and admitted during the same months in the previous year (former-year group).

Results: Mortality during hospitalization and 30-day mortality were higher in the waves group compared to the interim and former-year groups (41.4% vs. 30.5% and 24%, 19.4% vs. 17.9% and 12.9%, P < 0.001). In addition, 1-year mortality was higher in the interim group than in the waves and former-year group (39.1 % vs. 32.5% and 33.4%, P = 0.002). There were significant differences in the readmissions, both at 1 year and total number. The waves group had higher rates of mechanical ventilation and noradrenaline administration during hospitalization. Moreover, the waves group exhibited higher troponin levels, lower hemoglobin levels, and more abnormalities in liver and kidney function.

Conclusions: Hospitalized non-COVID patients experienced worse outcomes during the peaks of the pandemic compared to the nadirs and the preceding year, perhaps due to the limited availability of resources. These results underscore the importance of preparing for large-scale threats and implementing effective resource allocation policies.

Background: Influenza and coronavirus disease 2019 (COVID-19) are respiratory diseases with similar modes of transmission. In December 2021, influenza re-emerged after it had been undetected since March 2020 and the Omicron variant replaced the Delta variant. Data directly comparing the two diseases are scarce.

Objectives: To compare the outcomes of patients with both the Omicron variant and influenza during 2021–2022.

Methods: We performed a retrospective study conducted in Beilinson hospital, Israel, from December 2021 to January 2022. We included all hospitalized patients with either laboratory-confirmed COVID-19 or influenza. The primary outcome was 30-day mortality.

Results: We identified 167 patients diagnosed with Omicron and 221 diagnosed with Influenza A. The median age was 71 years for Omicron and 65 years for influenza. Patients with Omicron had a significantly higher Charlson Comorbidity Index score (4 vs. 3, P < 0.001). Patients with Omicron developed more respiratory failure that needed mechanical ventilation (7% vs. 2%, P = 0.05) and vasopressors (14% vs. 2%, P < 0.001) than patients with influenza. In a multivariate model, 30-day mortality was lower in patients diagnosed with influenza than in patients diagnosed with Omicron (19/221 [9%] vs. 44/167 [26%], hazard ratio 0.45, 95% confidence interval 0.25–0.81).

Conclusions: Patients diagnosed with Omicron had higher mortality than patients diagnosed with seasonal influenza. This finding could be due to differences in co-morbidities, the virus pathogenicity, and host responses to infection.

Background: Among the most frequent complications following transcatheter aortic valve replacement (TAVR) is hemostasis imbalance that presents either as thromboembolic or bleeding. Deviations in platelet count (PC) and mean platelet volume (MPV) are markers of hemostasis imbalance.

Objectives: To determine the predictive value of pre- and post-procedural PC and MPV fL 1-year all-cause mortality in patients who underwent TAVR.

Methods: In this population-based study, we included 236 TAVR patients treated at the Tzafon Medical Center between 1 June 2015 and 31 August 2018. Routine blood samples for serum PC levels and MPV fL were taken just before the TAVR and 24-hour post-TAVR. We used backward regression models to evaluate the predictive value of PC and MPV in all-cause mortality in TAVR patients.

Results: In this study cohort, MPV levels 24-hour post-TAVR that were greater than the cohort median of 9 fL (interquartile range 8.5–9.8) were the strongest predictor of 1-year mortality (hazard ratio 1.343, 95% confidence interval 1.059–1.703, P-value 0.015). A statistically significant relationship was seen in the unadjusted regression model as well as after the adjustment for clinical variables.

Conclusions: Serum MPV levels fL 24-hour post-procedure were found to be meaningful markers in predicting 1-year all-cause mortality in patients after TAVR.