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This study sought to correlate the SARS-CoV-2 IgG antibody response level to the BNT162b2 (Pfizer BioNTech) mRNA vaccine after the first and second doses with the reported adverse events.This cohort study examined the adverse events profiles of people vaccinated with BNT162b2 in our institute between late 2020 and May 2021. Adverse events, age, and sex were reported using an electronic questionnaire, and their SARS-CoV-2 IgG antibody levels were retrieved from the hospital database.Between 20 December 2020 and 31 May 2021, the adverse events questionnaire was completed by 9700 individuals who received the first vaccine dose and 8321 who received the second dose. After the first and second doses, the average antibody levels were 62.34 AU/mL (mean 4-373) and 188.19 AU/mL (mean 20-392), respectively. All of the adverse events, except local pain, were more common after the second vaccine dose. Multivariate analysis showed that after the first vaccine dose, female sex and younger age (but not IgG titres) were associated with a higher probability of adverse events (OR 2.377, 95% CI, 1.607-3.515, p = 0.000; OR 0.959, 95% CI, 0.944-0.977, p £0.000; OR 1.002, 95% CI, 0.995-1.008, p £0.601; respectively); however, all three parameters were associated with the incidence of adverse events after the second dose (OR 2.332, 95% CI, 1.636-3.322, p = 0.000; OR 0.984, 95% CI, 0.970-0.999, p £0.039; OR 1.004, 95% CI, 1.001-1.007, p £0.022; respectively).Adverse events are significantly more common after the second BNT162b2 vaccine dose than after the first dose. We found an association between sex, age, and SARS-CoV-2 IgG antibody titre with the incidence of adverse events.

Basic science studies suggest that opioids aggravate disease severity and outcomes in acute pancreatitis. We sought to determine the association of opioid use and opioid type with the clinical course and outcome of acute pancreatitis.In this retrospective single-center observational study, we included all adult patients admitted with acute pancreatitis between 2008 and 2021. Patients were classified into 3 groups based on analgesia type: morphine, noonmorphine opioid, and nonopioid.We included 2308 patients. Of the patients, 343 (14.9%) were treated with morphine, 733 (31.8%) were treated with nonmorphine opioids, and 1232 (53.4%) patients were in the nonopioid group. The incidence of 30-day mortality did not differ significantly between study groups: 3.9%, 2.9%, and 4.4% in the nonopioid, nonmorphine-opioid, and morphine groups, respectively ( P = 0.366).In multivariate analysis, the composite end point consisting of 30-day mortality, invasive ventilation, emergent abdominal surgery, and need for vasopressors was significantly more likely to occur in the morphine group than in the nonopioid group (adjusted odds ratio, 1.69; 95% confidence interval, 1.1-2.598; P = 0.01).Mortality among acute pancreatitis patients did not differ significantly between patients receiving morphine, nonmorphine opioids, and nonopioids. However, morphine treatment was associated with higher rates of some serious adverse events.

Current guidelines for the treatment of heart failure with reduced ejection fraction (HFrEF) are based on studies that have excluded or underrepresented older patients.To assess the value of guideline directed medical therapy (GDMT) in HFrEF patients 80 years of age and older.A single-center retrospective study included patients hospitalized with a first and primary diagnosis of acute decompensated heart failure (ADHF) and ejection fraction (EF) of ≤ 40%. Patients 80 years of age and older were stratified into two groups: GDMT, defined as treatment at hospital discharge with at least two drugs of the following groups: beta-blockers, angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or mineralocorticoid antagonists; and a personalized medicine group, which included patients who were treated with up to one of these drug groups. The primary outcomes were 90-day all-cause mortality, 90-day rehospitalization, and 3-years mortality.The study included 1152 patients with HFrEF. 254 (22%) patients who were at least 80 years old. Of the group, 123 were GDMT at discharge. When GDMT group was compared to the personalized medicine group, there were no statistically significant differences in terms 90-day mortality (17% vs. 13%, P = 0.169), 90-day readmission (51 % vs. 45.6%, P = 0.27), or 3-year mortality (64.5% vs. 63.3%, P = 0.915).Adherence to guidelines in the older adult population may not have the same effect as in younger patients who were studied in the randomized clinical trials. Larger prospective studies are needed to further address this issue.

Congestive heart failure (CHF) is often associated with kidney and pulmonary dysfunction. Activation of the renin‐angiotensin‐aldosterone system (RAAS) contributes to avid sodium retention, cardiac hypertrophy and oedema formation, including lung congestion. While the status of the classic components of RAAS such as renin, angiotensin converting enzyme (ACE), angiotensin II (Ang II) and angiotensin II receptor AT‐1 is well studied in CHF, the expression of angiotensin converting enzyme‐2 (ACE2), a key enzyme of angiotensin 1‐7 (Ang 1‐7) generation in the pulmonary, cardiac and renal systems has not been studied thoroughly in this clinical setting. This issue is of a special interest as Ang 1‐7 counterbalance the vasoconstrictory, pro‐inflammatory and pro‐proliferative actions of Ang II. Furthermore, CHF predisposes to COVID‐19 disease severity, while ACE2 also serves as the binding domain of SARS‐CoV‐2 in human host‐cells, and acts in concert with furin, an important enzyme in the synthesis of BNP in CHF, in permeating viral functionality along TMPRSST2. ADAM17 governs ACE2 shedding from cell membranes. Therefore, the present study was designed to investigate the expression of ACE2, furin, TMPRSS2 and ADAM17 in the lung, heart and kidneys of rats with CHF to understand the exaggerated susceptibility of clinical CHF to COVID‐19 disease. Heart failure was induced in male Sprague Dawley rats by the creation of a surgical aorto‐caval fistula. Sham‐operated rats served as controls. One week after surgery, the animals were subdivided into compensated and decompensated CHF according to urinary sodium excretion. Both groups and their controls were sacrificed, and their hearts, lungs and kidneys were harvested for assessment of tissue remodelling and ACE2, furin, TMPRSS2 and ADAM17 immunoreactivity, expression and immunohistochemical staining. ACE2 immunoreactivity and mRNA levels increased in pulmonary, cardiac and renal tissues of compensated, but not in decompensated CHF. Furin immunoreactivity was increased in both compensated and decompensated CHF in the pulmonary, cardiac tissues and renal cortex but not in the medulla. Interestingly, both the expression and abundance of pulmonary, cardiac and renal TMPRSS2 decreased in CHF in correlation with the severity of the disease. Pulmonary, cardiac and renal ADAM17 mRNA levels were also downregulated in decompensated CHF. Circulating furin levels increased in proportion to CHF severity, whereas plasma ACE2 remained unchanged. In summary, ACE2 and furin are overexpressed in the pulmonary, cardiac and renal tissues of compensated and to a lesser extent of decompensated CHF as compared with their sham controls. The increased expression of the ACE2 in heart failure may serve as a compensatory mechanism, counterbalancing the over‐activity of the deleterious isoform, ACE. Downregulated ADAM17 might enhance membranal ACE2 in COVID‐19 disease, whereas the suppression of TMPRSS2 in CHF argues against its involvement in the exaggerated susceptibility of CHF patients to SARS‐CoV2.

The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust.To describe changes in teaching during the first phase of the COVID-19 pandemic.We described the steps implemented at the Technion-Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem.Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs.The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching.

Introduction. A clinical and/or research fellowship abroad has become a prevalent choice among Israeli physicians. However, the influence of fellowship programs on the career path is unclear. We evaluated the role of physicians returning from fellowship in the organizational hierarchy and their professional and academic status. Methods. This was a retrospective, descriptive, cross-sectional study of physicians who completed a survey after accomplishing a fellowship. The survey included questions about the physicians’ attitudes toward the program, programs’ details, and the physicians’ current academic, professional, and administrative status. Information about scientific publications was also collected. Results. Of the 106 physicians receiving the questionnaire, 101 responded. The majority completed a two-year fellowship in North America. Forty percent participated in an integrated program (research and clinical), and 40% participated in clinical programs. Subjectively, the physicians attributed a significant value to the fellowship and positively recommend it. Most of the physicians held managerial positions, academic appointments, and had generated significant research. Discussion. The subjective perspective of all physicians participating in the study was that attending a fellowship program had a positive impact on their careers. Objectively, the accomplishment of a fellowship program empowered the studied physicians to become scholars, senior executives, and opinion leaders in their professional field.

Acute decompensated heart failure (ADHF) is one of the leading causes for hospitalization and mortality. Identifying high risk patients is essential to ensure proper management. Sequential Organ Function Assessment Score (SOFA) is considered an excellent score to predict short-term mortality in sepsis and other life-threatening conditions. To assess the capability of SOFA score in predicting short-term mortality in ADHF. We retrospectively identified patients with first hospitalization with primary diagnosis of ADHF between the years (2008–2018). The SOFA score was calculated for all patients. A total 3232 patients were included in the study. The SOFA score was significantly associated with in-hospital mortality and 30-day mortality. The odds ratios for 1-point increase in the SOFA score were 1.86 (95% CI 1.68–1.96) and 1.627 (95% CI 1.523–1.737) respectively. The SOFA Score demonstrated a good predictive accuracy. The areas under the curve of receiver operating characteristic curves for in-hospital mortality and 30-day mortality were 0.765 (95% CI 0.733–0.798) and 0.706 (95% CI 0.676–0.736) respectively. SOFA score is associated with increased risk of short-term mortality in ADHF. SOFA can be used as a complementary risk score to screen high risk patients who need strict monitoring.

Na+/H+ exchangers (NHEs), encoded by Solute Carrier 9A (SLC9A) genes in human, are ubiquitous integral membrane ion transporters that mediate the electroneutral exchange of H+ with Na+ or K+. NHEs, found in the kidney and intestine, play a major role in the process of fluid reabsorption together via Na+,K+-ATPase pump and Na+ channels. Nevertheless, the expression pattern of NHE in the lung and its role in alveolar fluid homeostasis has not been addressed. Therefore, we aimed to examine the expression of NHE specific isoforms in alveolar epithelium cells (AECs), and assess their role in congestive heart failure.Three NHE isoforms were identified in AEC and A549 cell line, at the level of protein and mRNA; NHE1, NHE2 and mainly NHE8, the latter was shown to be localized in the apical membrane of AEC. Treating A549 cells with angiotensin (Ang) II for 1 and 3 hours displayed a significant reduction in NHE8 protein abundance and to lesser extent at 5 hours; however, there was no effect at 24 hours. Moreover, A549 treated overnight with Ang II downregulated NHE8 protein abundance.CHF rats held for 1 week had increased abundance of NHE8 compared to sham operated rats. However, lower abundance of NHE8 was observed in CHF rats held for 4 weeks.Herein we show, for the first time, the expression of a novel NHE isoform by AEC, namely NHE8. Besides being negatively affected by Ang II, NHE8 protein levels were distinctly affected in CHF rats, which may be related to CHF severity.

An association between paroxysmal supraventricular tachycardias (PSVT) and elevated cardiac troponin I (cTnI) has been reported in small studies, even in the absence of significant coronary artery or structural heart disease. We sought to explore the prognostic significance of elevated cTnI among patients presenting with PSVT.This is a retrospective single-center observational study conducted between January 2014 and Decemebr 2016. 165 patients (60% men, mean age 55 ± 17 year-old) with an acute episode of regular supraventricular tachyarrhythmia were admitted to the emergency department at Rambam Medical Center. 131 patients had at least one serum cTnI value measured. Of those, 57 had a positive result, defined as serum cTnI of more than 0.028 ng/dL.Multivariate analysis showed that heart rate 150 beats per minute (bpm) on admission (OR = 3.9; 95% CI 1.1.6-9.5; p 0.003) and history of coronary artery disease (CAD) (OR = 3.4; 95% CI 1.2-10.1; p = 0.026) were the only independent predictors of cTnI elevation. After mean follow-up period of 23 ± 7 months, the combined primary outcome of death, coronary intervention (PCI) or myocardial infarction (MI) occurred in 7 patients (12.3%) out of 57 patients with positive cTnI and in zero patients with negative cTn (p = 0.002). Cox proportional hazard model showed that elevated cTnI on admission was an independent predictor of adverse outcomes only in patients with known coronary artery disease (CAD) (HR = 3.3, p = 0.05).Elevated cTnI among patients presenting with PSVT appears to have prognostic significance only in patients with history of CAD. In this patient group elevated cTnI is associated with increased risk of adverse cardiac outcomes. We therefore believe serum cTnI should be measured selectively, such as in patients with symptoms of ischemic chest pain and a high pretest likelihood of having CAD.

Infection with carbapenem-resistant Enterobacteriaceae (CRE) has become an important challenge in health care settings and a growing concern worldwide. Since infection is preceded by colonization, an understanding of the latter may reduce CRE infections. We aimed to characterize the gut microbiota in CRE carriers, assuming that microbiota alterations precede CRE colonization. We evaluated the gut microbiota using 16S rRNA gene sequencing extracted of fecal samples collected from hospitalized CRE carriers and two control groups, hospitalized noncarriers and healthy adults. The microbiota diversity and composition in CRE-colonized patients differed from those of the control group participants. These CRE carriers displayed lower phylogenetic diversity and dysbiotic microbiota, enriched with members of the family Enterobacteriaceae. Concurrent with the enrichment in Enterobacteriaceae, a depletion of anaerobic commensals was observed. Additionally, changes in several predicted metabolic pathways were observed for the CRE carriers. Concomitantly, we found higher prevalence of bacteremia in the CRE carriers. Several clinical factors that might induce changes in the microbiota were examined and found to be insignificant between the groups. The compositional and functional changes in the microbiota of CRE-colonized patients are associated with increased risk for systemic infection. Our study results provide justification for attempts to restore the dysbiotic microbiota with probiotics or fecal transplantation. IMPORTANCE The gut microbiota plays important roles in the host’s normal function and health, including protection against colonization by pathogenic bacteria. Alterations in the gut microbial profile can potentially serve as an early diagnostic tool, as well as a therapeutic strategy against colonization by and carriage of harmful bacteria, including antibiotic-resistant pathogens. Here, we show that the microbiota of hospitalized patients demonstrated specific taxa which differed between carriers of carbapenem-resistant Enterobacteriaceae (CRE) and noncarriers. The difference in the microbiota also dictates alterations in microbiome-specific metabolic capabilities, in association with increased prevalence of systemic infection. Reintroducing specific strains and/or correction of dysbiosis with probiotics or fecal transplantation may potentially lead to colonization by bacterial taxa responsible for protection against or depletion of antibiotic-resistant pathogens.

Aims In the present study, we aimed to determine the relationship between therapeutic decisions during the treatment of acute heart failure (AHF) patients who develop acute kidney injury (AKI) and subsequent renal and clinical outcomes. Methods and results We studied 277 patients with AHF and AKI, defined as an increase of >0.3 mg/dL in serum creatinine. The physician response to AKI was determined through a treatment composite score that captured changes in medical management in response to AKI, including a reduction (≥50%) or discontinuation of selected medication classes [angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACE-Is/ARBs), beta-blockers, and diuretics] and fluids administration. ACE-Is/ARBs, beta-blockers, and diuretics were reduced or discontinued in 103 (55.4%), 84 (38.9%), and 166 (61.5%), respectively. Fluids were administered to 130 (46.9%) patients. Discontinuation rates of ACE-Is/ARBs, beta-blockers, diuretics, and fluids administration were higher in patients with hypotension (systolic blood pressure 1 was associated with greater likelihood of renal function recovery (odds ratio 3.47, 95% confidence interval 2.06-5.83; P 1 (hazard ratio 1.71, 95% confidence interval 1.12-2.61; P = 0.01). After adjustments, the treatment composite score was no longer associated with mortality. Conclusions Discontinuation or dose reduction of diuretics or neurohormonal blockers may improve renal outcome at the price of less efficient decongestion. Our results emphasize the need for randomized clinical trials that address the treatment of AHF patients with AKI.

Objectives. Diabetes mellitus is an endemic disease of the current era. It is important to treat it properly. All antidiabetic medications have side effects and various safety profiles. Case report. Fifty-two years old patient with type II diabetes mellitus, who had spontaneous cutaneous and intra muscular bleeding after starting treatment with Exenatide. The patient’s history did not include any kind of spontaneous bleeding. Investigations did not reveal abnormal platelets count and function or coagulation profile. The use of the Exenatide was discontinued and during one year of follow-up, the patient did not experience an additional occurrence of spontaneous bleeding. Conclusions. To the best of our knowledge, this is the first report of spontaneous bleeding probably caused by Exenatide. The exact pathophysiology, by which the drug can cause spontaneous bleeding, is still not clear and has to be revealed.

Background In the developing world, only a small minority of patients have access to radiological services. Over the past decade, technological developments of ultrasound equipment have led to the emergence of point-of-care ultrasonography (POCUS), which is widely used by healthcare professionals of nearly all specialties. We hypothesized that physicians with only basic POCUS training, but with telemedicine support, can use POCUS successfully in rural hospitals in sub-Saharan Africa. Method During a 14-day voluntary clinical work session in a rural hospital in central Uganda, bedside ultrasound scans were performed by use of a pocket-size portable machine by a physician who underwent a five-day training period. All the POCUS studies were reviewed by radiologists and cardiologists abroad with the use of telemedicine. Results During the study period, 30% of patients received a POCUS-augmented physical examination. 16 out of 23 patients (70%) had positive findings; in 20 of them (87%), the management was changed. The technique was successfully used on trauma casualties, patients suffering from shock, patients with cardiorespiratory symptoms, and patients undergoing invasive procedures. Conclusions In a very resource-limited environment, POCUS conducted by basically trained primary care physicians with telemedicine support is a powerful diagnostic tool in a variety of medical conditions.

Congestive heart failure (CHF) often leads to progressive cardiac hypertrophy and salt/water retention as evident by peripheral and lung edema. Although the pathogenesis of CHF remains largely unclarified, it is widely accepted that neurohormonal changes and inflammatory processes are profoundly involved in structural and functional deterioration of vital organs including, heart, kidney and lungs. Corin, a cardiac serine protease, is responsible for converting pro-ANP and pro-BNP to biologically active natriuretic peptides (NPs). Although the involvement of corin in cardiac hypertrophy and heart failure was extensively studied, the alterations in corin and PCSK6, a key enzyme in the conversion of procorin to corin, have not been studied in the pulmonary tissue. Thus, this study aims at examining the status of PCSK6/Corin in the lung of rats with CHF induced by the creation of aorto-caval fistula (ACF) between the abdominal aorta and vena cava in SD rats. Rats with ACF were divided into 2 subgroups based on the pattern of their daily sodium excretion, compensated and decompensated CHF. Placement of ACF led to cardiac hypertrophy, pulmonary congestion, and renal dysfunction, which were more severe in the decompensated subgroup, despite remarkable elevation of circulatory ANP and BNP levels. Corin mRNA and immunoreactive peptide were detected in pulmonary tissue of all experimental groups. However, the expression and abundance of pulmonary corin significantly increased in the decompensated animals, but not in the compensated ones. Noteworthy, the expression of PCSK6 and ANP/BNP in the pulmonary tissue followed a similar pattern as corin. The upregulation of pulmonary Corin/PCSK6 and NPs were accompanied by local activation of cathepsin L and certain cytokines including IL-6. In light of the anti-inflammatory role of NPs, we postulate that the obtained upregulation of pulmonary PCSK6/Corin along NPs in rats with decompensated CHF may represent a counterbalance response to the inflammatory milieu characterizing CHF especially in severe cases.

The purpose of this study was to determine the rate of decline in the diagnostic yield of influenza PCR assay after oseltamivir administration, and to identify risk factors for prolonged shedding. This was a prospective observational study. We included adult inpatients with clinical signs of influenza during the influenza seasons 2015 and 2016, who had positive influenza PCR tests and who were treated with oseltamivir. Clinical follow-up and repeat PCR testing were performed on days 2, 4 and 6 after the first positive test. We defined prolonged shedders as patients who still required hospitalization and had a positive PCR assay on day 4. Risk factors for prolonged shedding were assessed in univariate and multivariate analyses. A total of 215 patients were included in our study. The median age was 64 years and 49.3% were men. The main influenza type was H1N1 (50.1%). Rates of PCR positivity among evaluable patients on days 2, 4 and 6 were 142/215 (66%), 50/78 (64.1%) and 20/30 (66.6%), respectively. Independent risk factors for prolonged shedding (50 patients) included hypoxemia [odds ratio (OR) 2.55, 95% confidence interval (1.3-5.1)] and lower diastolic blood pressure [OR 0.94, 95% CI (0.92-0.97)] on admission. Negative PCR tests taken more than 48 h after initiation of treatment had low diagnostic yield. More severe disease, manifested by hypoxemia and lower blood pressure, is associated with prolonged shedding on oseltamivir treatment.

Infection with Carbapenem-Resistant Enterobacteriaceae (CRE) became an important challenge in health-care settings and a growing concern worldwide. Since infection is preceded by colonization, an understanding of the latter may reduce CRE-infections. We aimed to characterize the gut microbiota after colonization by CRE, assuming that an imbalanced gastrointestinal tract (GIT)-associated microbiota precedes CRE-colonization.We evaluated the GIT-microbiota using 16S rRNA genes sequencing extracted of fecal samples, collected from hospitalized CRE-carriers, and two control groups of hospitalized non-carriers and healthy adults. The microbiota diversity and composition in CRE-colonized patients differed from that of the control groups participants. These CRE-carriers displayed lower phylogenetic diversity and dysbiotic microbiota, enriched with members of the Enterobacteriaceae family. Concurrent with the bloom in Enterobacteriaceae, a depletion of anaerobic commensals was observed. Additionally, changes in several predicted metabolic pathways were observed for the CRE-carriers. Concomitant, we found higher prevalence of bacteremia in the CRE-carriers.Several clinical factors that might induce change in the microbiota were examined and found as insignificant between the groups.CRE-colonized patients have dysbiotic gut microbiota in terms of diversity and community membership, associated with increased risk for systemic infection. Our study results provides justification for attempts to restore the dysbiotic microbiota with probiotics or fecal transplantation.

BACKGROUND Privacy restrictions limit access to protected patient-derived health information for research purposes. Consequently, data anonymization is required to allow researchers data access for initial analysis before granting Institutional Review Board approval. A system implemented in our institution enables synthetic data generation that mimics data from real electronic medical records, wherein only fictitious patients are listed. OBJECTIVE This paper studies the validity of results obtained when analyzing synthetic data for medical research. A comprehensive validation process concerning meaningful clinical questions and various types of data was conducted to assess the accuracy and precision of statistical estimates derived from synthetic patient data. METHODS A cross-hospital project was conducted to validate results obtained from synthetic data produced for five contemporary studies on various topics. For each study, results derived from synthetic data were compared to those based on real data. In addition, repeatedly generated synthetic data sets were used to estimate the bias and stability of results obtained from synthetic data. RESULTS This study demonstrated that results derived from synthetic data were predictive of results from real data. When the number of patients was large relative to the number of variables used, highly accurate and strongly consistent results were observed between synthetic and real data. When small populations were accounted for, prediction was of moderate accuracy. CONCLUSIONS The use of synthetic data provides a close estimate to real data results and is thus a powerful tool in shaping research hypotheses and accessing estimated analyses, without risking patient privacy. Synthetic data enables broad access to data, including for out-of-organization researchers, and rapid, safe, and repeatable analysis of data in hospitals or other health organizations where patient privacy is a primary value.

Introduction Symptomatic heart failure is frequent among patients with hypertrophic cardiomyopathy. Once regarded a disease of mostly young adults, recently, hypertrophic cardiomyopathy has been increasingly diagnosed in older patients. There is scarce medical literature specifically dedicated to hypertrophic cardiomyopathy in elderly patients. As a result, their natural history with respect to risk of adverse events such as heart failure, stroke, and sudden cardiac death remains relatively unknown. Purpose We aimed to determine the prognostic and therapeutic implications of heart failure in hypertrophic cardiomyopathy patients older than 65 years old. Methods In this retrospective observational study, we searched our hospital's database for hypertrophic cardiomyopathy patients who were admitted due to acute decompensated heart failure between 1/1/2000 and 31/12/2016. Patients were stratified into two age groups: over 65 years old and under 65 years old (our control group). Our primary outcomes were overall mortality and re-admissions due to acute decompensated heart failure. Results Our cohort included 86 patients. 54 patients were older than 65 years and 32 were younger than 65. There were significantly more women in the over 65 group. In the elderly group, significantly less patients had a history of smoking (26% vs. 47%, p=0.047), whereas more patients had known coronary artery disease (48% vs. 19%, p=0.006). The echocardiographic features of the two groups were similar. The survival rate was not significantly different between the two age groups (10 year survival rate 41% under 65, 37% over 65, p=0.68). There were also no significant differences in the risk of re-admission due to acute decompensated heart failure between the two age groups. Conclusion No differences were seen in overall mortality or in re-admission due to acute decompensated heart failure between older (over 65) and younger (under 65) patients. Hence, it appears prudent to adhere to ESC guidelines for hypertrophic cardiomyopathy management in older hypertrophic cardiomyopathy patients.

Background Recent-onset atrial fibrillation (AF) is a frequent cause for presentation to the emergency department. Recent studies proposed that the addition of biomarker information might improve the prediction of clinical outcomes by enabling identification of patients at high risk. Aim We aimed to examine the role of cardiac troponin I as a predictor of clinical outcome in patients with first episode acute AF. Design Patients, 18 years or older, presenting to our hospital with a primary diagnosis of first episode acute AF were included in this retrospective study. Methods The association between elevated cTnI with mortality or the composite endpoint (mortality, stroke or heart failure) was examined in a univariate Cox regression model. Results Of the 274 study patients, 111 had elevated cTnI levels (41%). Increased cTnI was associated with older age, history of myocardial infarction, higher creatinine levels and higher heart rate (All P

Introduction Prevention of acute decompensated heart failure (ADHF) hospitalizations has both medical and economic implications, yet remains an unmet need. Increases in pulmonary and perhaps upper airway fluid content may be detectable remotely by voice analysis. The Cordio HearO™ system is a mobile application with cloud-based computing, designed to identify distinct speech measures (SM) in standard audio recordings which may be indicative of HF clinical status and provide early warning of impending decompensation. Hypothesis Cordio HearO™ speech analysis can identify clinical worsening of heart failure (HF) patients prior to hospitalization. Methods In this ongoing multicenter, observational study, we recruited 173 New York Heart Association Class II-III, stable stage C chronic heart failure patients. The patients recorded five sentences (2-5 sec each) each day in their native language (English, Hebrew, Arabic or Russian), using Cordio HearO™ operating on standard smartphone devices. Patients have been followed for 3 to 23 months. The current analysis explored the association between different SM parameters and episodes of HF decompensation requiring hospitalization. Results A total of 196,610 recordings, collected over 47,376 patient days of follow up were analyzed during which 13 patients required hospitalization for ADHF. 10 (76.9%) (95% CI: 54.02% - 99.83%) of these episodes were detected by Cordio HearO™ software an average of 12.2 (range 8 to 17 days) days prior to admission. The estimated false-positive event rate per year was 1.47 (95% CI: 1.28 - 1.68). Conclusions Cordio HearO™ novel speech analysis technology may be a useful tool in remote monitoring of HF patients, providing an early warning of impending episodes of decompensation, thus having the potential to reduce ADHF hospitalizations and improve patient quality of life and economic outcomes. Ongoing and future studies will continue to define the role of speech measures in the management of heart failure patients.

Objectives : Assertions regarding afebrile presentation of sepsis frequently lead to superfluous antibiotic treatment. This study aimed to identify the risk factors for afebrile presentation of bacteraemia, focusing on glucocorticoid (GC) treatment and end-stage renal disease (ESRD). Methods : This retrospective cohort study included all patients with bacteraemia caused by common Gram-negative bacteria in one hospital. The exposure variables were GC treatment, administered for at least 48 hours before bacteraemia onset, and ESRD, defined as patients undergoing dialysis. Risk factors were assessed for afebrile presentation, defined as temperature between 36.0–37.7°C for all measurements, 48 hours prior to blood culture collection. Analyses were subgrouped by community-onset and hospital-acquired Gram-negative bacteraemia (GNB). Propensity score (PS)-weighted multivariate analyses were conducted. Results : Of 4179 patients with GNB, 1090 (26.1%) presented without fever before blood culture collection. In community-onset GNB, GC treatment was significantly associated with afebrile presentation, PS-weighted OR 1.42 (95% CI 1.25–1.61), absolute risk increase 7% (95% CI 4.3–9.8%), while ESRD was not. For hospital-acquired GNB, ESRD was significantly associated with afebrile presentation (OR 1.53; 95% CI 1.25–1.86; absolute risk increase 8.5%; 95% CI 4.4–13.1%); GC was not. Other risk factors for afebrile presentation in both subgroups included increasing Charlson comorbidity score, bacteraemia with non-fermenters Pseudomonas aeruginosa or Stenotrophomonas maltophilia (compared with Enterobacteriaceae), and lower albumin levels. Aging was not associated with afebrile presentation of GNB. Conclusion : Although significant associations between GC and ESRD and afebrile presentation of GNB were observed, they were different in community-onset and hospital-acquired GNBs, and absolute risk increases were small.

Aims Heart failure (HF) is one of the leading causes for hospitalization and mortality. After first admission with acute decompensated HF, some patients are in high risk for short‐term and long‐term mortality. These patients should be identified, closely followed up, and treated. It has been observed that blood urea nitrogen (BUN) on admission is a predictive marker for short‐term mortality. Recently, it has been shown that higher BUN levels on discharge are also a bad prognostic predictor. However, the prognostic value of BUN alteration during hospital stay was not investigated; therefore, we aimed to investigate the effect of BUN variation during hospitalization on mortality. Methods and results A retrospective study included patients with first hospitalization with the primary diagnosis of HF. The patients were divided into four groups on the basis of the values of BUN on admission and discharge, respectively: normal‐normal, elevated‐normal, normal‐elevated, and elevated‐elevated. Four thousand seven hundred sixty‐eight patients were included; 2567 were male (53.8%); the mean age was 74.7 ± 12.7 years. The 90 day mortality rate in the normal‐normal group was 7% lower than that in the elevated‐normal (14.6%) and normal‐elevated (19.3%) groups; P value 40 mg/dL, higher BUN levels correlated with higher 90 day mortality rate regardless of creatinine levels, brain natriuretic peptide, or age. Moreover, BUN on admission and on discharge correlated better with mortality than did creatinine and glomerular filtration rate at the same points. Conclusions The BUN both on admission and on discharge is a prognostic predictor in patients with HF; however, patients with elevated levels both on admission and on discharge have the worst prognosis. Moreover, worsening or lack of improvement in BUN during hospitalization is a worse prognostic predictor. To the best of our knowledge, this is the first trial to discuss the BUN change during hospitalization in HF.

Background Community acquired pneumonia (CAP) is a common illness affecting hundreds of millions worldwide. Few studies have investigated the relationship between serum magnesium levels and outcomes of these patients. We aimed to study the association between serum magnesium levels and 30-day mortality among patients with CAP. Methods Retrospective overview of patients hospitalized with CAP between January 1, 2010 and December 31, 2016. Participants were analyzed retrospectively in order to identify the risk factors for a primary endpoint of 30-day mortality. Normal levels of magnesium levels in our laboratory varies between 1.35 and 2.4 mg/dl. Results 3851 patients were included in our cohort. Age > 75 years, blood urea nitrogen (BUN) > 20 mg/dl, hypoalbuminemia, and abnormal levels of magnesium were all associated with increased risk of 30-day mortality. Normal magnesium levels were associated with the lowest mortality rate (14.7%). Notably, within the normal levels, high normal magnesium levels (2–2.4 mg/dl) were correlated with higher mortality rates (30.3%) as compared to levels that ranged between 1.35–2 mg/dl (12.9%). Hypomagnesemia and hypermagnesemia were both associated with excess of 30-day mortality, 18.4 and 50%, respectively. Conclusion Hypomagnesemia and hypermagnesemia on admission were associated with an increased rate of 30-day mortality among adult patients hospitalized with CAP. Interestingly, magnesium levels within the upper normal limits were associated with higher mortality.

Worsening renal function (WRF) and congestion are inextricably related pathophysiologically, suggesting that WRF occurring in conjunction with persistent congestion would be associated with worse clinical outcome. We studied the interdependence between WRF and persistent congestion in 762 patients with acute decompensated heart failure (HF). WRF was defined as ≥0.3 mg/dl increase in serum creatinine above baseline at any time during hospitalization and persistent congestion as ≥1 sign of congestion at discharge. The primary end point was all-cause mortality with mean follow-up of 15 ± 9 months. Readmission for HF was a secondary end point. Persistent congestion was more common in patients with WRF than in patients with stable renal function (51.0% vs 26.6%, p0.0001). Both persistent congestion and persistent WRF were significantly associated with mortality (both p0.0001). There was a strong interaction (p = 0.003) between persistent WRF and congestion, such that the increased risk for mortality occurred predominantly with both WRF and persistent congestion. The adjusted hazard ratio for mortality in patients with persistent congestion as compared with those without was 4.16 (95% confidence interval [CI] 2.20 to 7.86) in patients with WRF and 1.50 (95% CI 1.16 to 1.93) in patients without WRF. In conclusion, persisted congestion is frequently associated with WRF. We have identified a substantial interaction between persistent congestion and WRF such that congestion portends increased mortality particularly when associated with WRF.

Herein, we report a 70-year-old male patient, with recurrent multiple hepatic abscesses, that was admitted to the internal medicine department for treatment of Carbapenem Resistant Escherichia Coli (CRE) bacteremia. The patient was treated with Tigecycline; few days later, he developed qDisseminated Intravascular Coagulation (DIC)q like coagulation study abnormality that seemed to be related to Tigecycline treatment. Upon discontinuing it, the DIC-like condition was resolved. Tigecycline should be considered as a possible etiological factor in patients with DIC-like, and this therapy should be withdrawn immediately in suspected cases.

Background A recently published, large prospective study showed unexpectedly high prevalence of acute pulmonary embolism (APE) among patients hospitalized for syncope. In such a case, a high incidence of recurrent pulmonary embolism is expected among patients who were discharged without APE workup. Objectives To determine the incidence of symptomatic APE among patients hospitalized for a first episode of syncope and discharged without APE workup or anticoagulation. Methods This retrospective cohort study included patients hospitalized at Rambam Health Care Campus between January 2006 and February 2017 with a primary admission diagnosis of syncope, who were not investigated for APE and were not taking anticoagulants. The patients were followed up for up to three years after discharge. The occurrence of venous thromboembolism (VTE) during the follow-up period was documented. Results The median follow-up duration was 33 months. 1,126 subjects completed a three-year follow-up. During this period, 38 patients (3.38%) developed VTE, 17 (1.51%) of them had APE. The cumulative incidence of VTE and APE was 1.9% (95% CI 1.3%-2.5%) and 0.9% (95% CI 0.4%-1.3%) respectively. Only seven subjects developed APE during the first year of follow-up. The median times from the event of syncope to the development of APE and VTE were 18 and 19 months respectively. Conclusions The cumulative incidence of VTE during a three-year follow-up period after an episode of syncope is low. In the absence of clinical suspicion, a routine diagnostic workup for APE in patients with syncope cannot be recommended.

BackgroundPalliative medicine is a growing field in Israel, and its training program is still in process. The current study aimed to evaluate students’ attitudes regarding a course in palliative care established in a division of oncology.MethodSome 45 medical students in their 5th to 6th years participated in a one-week course on palliative care. At the end of each training week, students were asked to complete a questionnaire, evaluating their attitudes regarding different aspects of the program content, such as its importance and relevance to their training as physicians, as well as the contribution of specific parts of the program to their knowledge regarding palliative care.ResultsThe overall satisfaction of the 45 students was high. The most contributory parts of the course were the multidisciplinary team and the complementary and alternative medicine. Participating in the staff meetings and accompanying physicians in their daily work were scored as the least contributory parts.Significance of resultsThis preliminary study demonstrated students’ overall high satisfaction with the newly established palliative care course and their need for more practical skills. Future studies should investigate and evaluate educational programs in palliative care in order to establish suitable training for medical students.

Antibiotic stewardship programs (ASP) are designed to optimize antibiotic use in hospitals. Antibiotic consumption is one of the measures assessing the effects of ASPs.To evaluate the effect of an ASP on antibiotic consumption in our hospital and compare it to hospitals in Israel and worldwide.Between October 2012 and March 2013 an ASP was implemented in Rambam Hospital. The program included educational activities, publication of local guidelines for empirical antibiotic treatment, structured infectious diseases consultations, pre-authorization antibiotic restrictions and stop orders. We compared antibacterial antibiotic consumption in defined daily doses (DDD)/100 hospital days (HD) between the periods before (1/2010-3/2013) and after (4/2013-9/2014) implementing the ASP. The study was conducted in the medical departments, hematology, the intensive care unit (ICU) and all pediatric wards.Total antibiotic consumption before implementing the ASP was 96±11.2 DDD/100 HD in medical departments, 186.4±42.8 in the ICU and 185.5±59 in hematology; all values were higher than the worldwide-reported averages for these departments. Following the ASP, total antibiotic consumption decreased by 12% (p=0.008) in the medical departments and by 26% (p=0.002) in hematology, mostly due to reductions in non-restricted antibiotics. No significant changes were observed overall in the ICU and in pediatric wards. There was a significant reduction in consumption of vancomycin and carbapenems in all settings, the latter was reduced to nearly half. Amikacin use quadrupled in the medical departments.Implementation of an ASP lead to a reduction in non-restricted and restricted antibiotic consumption, especially carbapenems.

Background Acute exacerbation of COPD (AECOPD) is one of the leading causes for hospitalization and readmission in developed countries. No laboratory indices were consistently found to be associated with readmission risk. Recent evidence attests that red blood cell distribution width (RDW), conveys important information for short and long term prognosis in a variety of medical conditions. Prognostic usefulness of RDW in patients with AECOPD has not been investigated. Objective To evaluate the usefulness of RDW in predicting early adverse outcomes in patients hospitalized due to AECOPD. Methods Patients hospitalized for AECOPD between 2011 and 2013 were revised. Clinical and laboratory parameters were noted. Participants were followed to determine the incidence of readmission due to AECOPD, readmission from any cause and composite end point of readmission or death during 60 days after discharge. Results 539 patients were included in the study. The 60-day overall readmission rate was 26.35%, of that, 41.55% were due to AECOPD. The Presence of heart failure, pH below 7.35 at discharge and abnormal RDW were associated with the composite endpoint. The negative predictive value of normal RDW was 80.12%. Conclusion Increased RDW is an independent negative prognostic factor associated with adverse outcomes after hospitalization due to AECOPD.

Objectives Sepsis is a multifactorial syndrome with increasing incidence of morbidity and mortality. Identification of outcome predictors is therefore essential. Recently, elevated brain natriuretic peptide (BNP) levels have been observed in patients with septic shock. Little information is available concerning BNP levels in patients with critical illness, especially with sepsis. Therefore, this study aims to evaluate the role of BNP as a biomarker for long-term mortality in patients with sepsis. Methods We studied 259 patients with sepsis and absence of heart failure. BNP levels were obtained for all patients. A long-term survival follow-up was done, and survival was evaluated 90 days after admission, and during the subsequent 60 months of follow-up. Results Eighty-two patients died during the 90-day follow-up (31.7%), 53 died in the index hospitalization (20.5%). On multivariate analysis models, elevated values of BNP were a strong predictor of in-hospital mortality, 90-day and 60-month mortality in patients with sepsis. BNP was a better prognostic predictor than the Sepsis-related Organ Failure Assessment (SOFA) score for 90-day mortality, and a better predictor for 60-month mortality in low risk groups. Conclusion In the population of hospitalized patients with sepsis, BNP is a strong independent predictor of short- and long-term mortality.

Background Privacy restrictions limit access to protected patient-derived health information for research purposes. Consequently, data anonymization is required to allow researchers data access for initial analysis before granting institutional review board approval. A system installed and activated at our institution enables synthetic data generation that mimics data from real electronic medical records, wherein only fictitious patients are listed. Objective This paper aimed to validate the results obtained when analyzing synthetic structured data for medical research. A comprehensive validation process concerning meaningful clinical questions and various types of data was conducted to assess the accuracy and precision of statistical estimates derived from synthetic patient data. Methods A cross-hospital project was conducted to validate results obtained from synthetic data produced for five contemporary studies on various topics. For each study, results derived from synthetic data were compared with those based on real data. In addition, repeatedly generated synthetic datasets were used to estimate the bias and stability of results obtained from synthetic data. Results This study demonstrated that results derived from synthetic data were predictive of results from real data. When the number of patients was large relative to the number of variables used, highly accurate and strongly consistent results were observed between synthetic and real data. For studies based on smaller populations that accounted for confounders and modifiers by multivariate models, predictions were of moderate accuracy, yet clear trends were correctly observed. Conclusions The use of synthetic structured data provides a close estimate to real data results and is thus a powerful tool in shaping research hypotheses and accessing estimated analyses, without risking patient privacy. Synthetic data enable broad access to data (eg, for out-of-organization researchers), and rapid, safe, and repeatable analysis of data in hospitals or other health organizations where patient privacy is a primary value.

Background Procalcitonin and interleukin 6 (IL-6) are well-known predictors of blood culture positivity in patients with sepsis. However, the association of procalcitonin and IL-6 with blood culture positivity was assessed separately in previous studies. This study aims to examine and compare the performance of procalcitonin and IL-6, measured concomitantly, in predicting blood culture positivity in patients with sepsis. Methods Forty adult patients with sepsis were enrolled in the study. Blood cultures were drawn before the institution of antibiotic therapy. The area under the curve (AUC) of the receiver operating characteristic curve was estimated to assess the performance of procalcitonin and IL-6 in predicting blood culture positivity. Results Positive blood cultures were detected in 10 patients (25%). The AUC of procalcitonin and IL-6 was 0.85 and 0.61, respectively. The combined performance of procalcitonin and IL-6 was similar to that of procalcitonin alone, AUC of 0.85. On univariate analysis, only procalcitonin and IL-6 were associated with blood culture positivity. Multivariate logistic regression analysis showed that only procalcitonin was associated with blood culture positivity (odds ratio, 12.15 [1.29-114.0] for levels above the median compared with levels below the median). Using procalcitonin cut points of 1.35 and 2.14 (nanogram per milliliter) enabled 100% and 90% identification of positive blood cultures and reduced the need of blood cultures by 47.5% and 57.5%, respectively. Conclusions Compared with IL-6, procalcitonin better predicts blood culture positivity in patients with sepsis. Using a predefined procalcitonin cut points will predict most positive blood cultures and reduce the need of blood cultures in almost half of patients with sepsis.

Background Brain natriuretic peptide (BNP) is well established in detecting acute decompensation of heart failure (ADHF). The role of BNP at discharge in predicting mortality is less established. Accumulating evidence suggests that inflammatory cytokines play an important role in the development of heart failure. We aimed to examine the contribution of BNP, interleukin 6, and procalcitonin to mortality in ADHF. Methods A cohort of 33 patients with ADHF was identified between March 2009 and June 2010 at Rambam Health Care Campus, Haifa, Israel. The cohort was followed up for all-cause mortality during 6months after hospital discharge. Cox proportional hazard model was used to assess the association between BNP, interleukin-6 and procalcitonin and all-cause mortality. Results As compared to BNP at admission, BNP at discharge was more predictive for all-cause mortality. The area under the curve for BNP at admission and discharge was 0.810 ( P =.004) and 0.864 ( P =.001) respectively. Eleven patients (33.3%) patients who died during the follow-up period had higher BNP levels, median 2031.4 (IQR, 1173.4-2707.2), than those who survived; median 692.5 (IQR, 309.9-1159.9), ( P = .001). On multivariate analysis, BNP remained an independent predictor for 6month all-cause mortality HR 9.58 (95% CI, 2.0-45.89) for levels above the median compared to lower levels, ( P =.005). Albumin, procalcitonin and interleukin 6 were not associated with all-cause mortality. Conclusions BNP at discharge is an independent predictor for all-cause mortality in patients with ADHF. Compared with BNP at admission, BNP at discharge has slightly higher predictive accuracy with regard to 6-month all-cause mortality.

Aims The acute (type 1) cardio-renal syndrome (CRS) refers to an acute worsening of heart function leading to worsening renal function (WRF), and frequently complicates acute decompensated heart failure (ADHF) and acute myocardial infarction (AMI). The aim of this study was to investigate whether hyponatraemia, a surrogate marker of congestion and haemodilution and of neurohormonal activation, could identify patients at risk for WRF. Methods and results We studied the association between hyponatraemia (sodium 0.3 mg/dL in creatinine above baseline) in two separate cohorts: patients with ADHF (n = 525) and patients with AMI (n = 2576). Hyponatraemia on admission was present in 156 patients (19.7%) with ADHF and 461 patients (17.7%) with AMI. Hyponatraemia was more frequent in patients who subsequently developed WRF as compared with patients who did not, in both the ADHF (34.6% vs. 22.2%, P = 0.0003) and AMI (29.7% vs. 21.8%, P