Percutaneous Mitral Valve Repair in Cancer Patients with Heart Failure and Severe Mitral Regurgitation.

BACKGROUND: Cancer patients with heart failure (HF) and severe mitral regurgitation (MR) are often considered to be at risk for surgical mitral valve repair/replacement. Severe MR inducing symptomatic HF may prevent delivery of potentially cardiotoxic chemotherapy and complicate fluid management with other cancer treatments. OBJECTIVES: To evaluate the outcome of percutaneous mitral valve repair (PMVR) in oncology patients with HF and significant MR. METHODS: Our study comprised 145 patients who underwent PMVR, MitraClip, at Hadassah Medical Center between August 2015 and September 2019, including 28 patients who had active or history of cancer. Data from 28 cancer patients were compared to 117 no-cancer patients from the cohort. RESULTS: There was no significant difference in the mean age of cancer patients and no-cancer patients (76 vs. 80 years, P = 0.16); 67% of the patients had secondary (functional) MR. Among cancer patients, 21 had solid tumor and 7 had hematologic malignancies. Nine patients (32%) had active malignancy at the time of PMVR. The mean short-term risk score of the patients was similar in the two groups, as were both 30-day and 1-year mortality rates (7% vs. 4%, P = 0.52) and (29% vs. 16%, P = 0.13), respectively. CONCLUSIONS: PMVR in cancer patients is associated with similar 30-day and 1-year survival rate compared with patients without cancer. PMVR should be considered for cancer patients presenting with HF and severe MR and despite their malignancy. This approach may allow cancer patients to safely receive planned oncological treatment.

[PREVALENCE OF DEMODEX PARASITES IN PATIENTS WITH CHRONIC BLEPHARITIS AND HEALTHY CONTROLS IN ISRAEL].

INTRODUCTION: Previous studies demonstrated the potential pathogenic relationship between infestation of the eyelashes by the parasite Demodex and chronic blepharitis, whereas other studies did not demonstrate such relations and concluded that Demodex is a normal eyelid flora. AIMS: This study examines the prevalence of Demodex in patients with blepharitis compared to a healthy control group in Israel, in order to further explore and establish its pathogenic role in cases of chronic blepharitis. METHODS: A case-control study was conducted including 110 participants: 60 patients with chronic blepharitis attending a tertiary medical center and 50 subjects with no signs of blepharitis. Six to eight eyelashes were epilated from each participant and studied microscopically for the presence of Demodex by a blinded examiner. Fluorescein stain was added to the "clean" samples in order to reduce the false negative results. RESULTS: Demodex were identified on the eyelashes of 44 patients with blepharitis (73.3%) and 20 controls (40%) (p<0.001). After adjusting for age, blepharitis was still a significant risk factor for the presence of Demodex (OR=2.96, CI 95% 1.2-7.3). CONCLUSIONS: This study supports previous studies demonstrating pathogenic relationship between Demodex infestation of the eyelashes to chronic blepharitis. The authors recommend epilating 6-8 lashes of patients with blepharitis for microscopic identification of these parasites. Fluorescein stain may have a limited role in the recognition of Demodex in parasite free samples.

[TO BE A RESIDENT IN THE DEPARTMENT OF MEDICINE].

INTRODUCTION: Sir William Osler is considered to be one of the fathers of modern medicine who pioneered the practice of bedside teaching of clinical medicine for medical students and residents. Osler was well known as a diagnostician and outstanding therapist with a humanized approach and rare didactic capabilities. Medical training at Hadassah is built on the central tenets of Osler's approach, incorporating the tremendous advances in science and medicine. Training for residents in Internal Medicine is designed to develop a broad base of medical and, if possible, scientific knowledge, as well as skills and competencies to deliver a high standard of patient care. In the past 7 years, 28 residents have undergone specialist training in Internal Medicine B. Among them, 71% were Israeli medical school graduates; 36% were women;18% were recent immigrants to Israel; 78% were Jewish. Among Jewish residents, 32% were religiously observant. Besides the usual assignments of the internal medicine ward, the medical staff of Internal Medicine B excelled in diagnosis of hard to diagnose diseases as described in eleven cases. The diagnosis in some of those cases was a result of listening to the patient, education on clinical reasoning and the use advanced diagnostic tools. The basic unit of the residency is the clinical mission with an emphasis on exposure to novel modalities such as the use of bedside ultra sound along with dealing with end-of-life dilemmas, the management of complex situations and development of communication and interpersonal skills needed to work with close relatives and families facing critical times. The medical training in the internal ward is not just the sum of arbitrary care of the hospitalized patients, but a well-structured plan with gradually increasing demands. Over the past 7 years, residents in Internal Medicine B have achieved successful passing grades of 38/38 on the first attempt oral and written board examinations, a record that attests to the quality of the trainees and the training process. Hadassah has a long history of providing state-of-the-art patient care, and training young physicians to maintain this high standard - but the education process necessitates longstanding efforts and continuous striving for excellence.

Sex difference and outcome trends following surgical aortic valve replacement from the National Inpatient Sample (NIS) Database.

BACKGROUND: Based on worldwide registries, approximately 50% of patients who underwent aortic valve replacement (AVR) via surgical aortic valve replacement are females. Although AVR procedures have improved greatly in recent years, differences in outcome including mortality between sexes remain. We aimed to investigate the trends in SAVR outcomes in females versus males. METHODS: Using the 2011-2017 National Inpatient Sample (NIS) database, we identified hospitalizations for patients with diagnosis of aortic stenosis during which SAVR was performed. Patients' sociodemographic and clinical characteristics, procedure complications, and mortality were analyzed. Piecewise regression analyses were performed to assess temporal trends in SAVR utilization in females versus males. Multivariable analyses were performed to identify predictors of in-hospital mortality. RESULTS: A total of 392,087 hospitalizations for SAVR across the USA were analyzed. Utilization of SAVR in both sex patients decreased significantly during the years 2011-2017. Males compared to females had significantly higher rates of hyperlipidemia, chronic renal disease, peripheral artery disease, coronary artery disease and tended to be smokers. Differences in mortality rates among sexes were observed for SAVR procedures. Women had higher in-hospital mortality with 3.7% compared to men with 2.5% (OR 1.38 [95% CI 1.33-1.43, P<0.001]). In a multivariable regression model analysis adjusted for potential confounders, women had higher mortality risk with odd ratio (OR 1.38 [95% CI 1.33-1.43], P<0.001). Women had significantly higher rates of vascular complications (5.1% compared to men with 4.6%, P=0.002). CONCLUSIONS: Utilization of SAVR showed a downward trend during the study period. Higher in-hospital mortality was recorded in females compared to males.

The Relationship between Body Mass Index and In-Hospital Mortality in Bacteremic Sepsis.

BACKGROUND: The association between Body Mass Index (BMI) and clinical outcomes following sepsis continues to be debated. We aimed to investigate the relationship between BMI and in-hospital clinical course and mortality in patients hospitalized with bacteremic sepsis using real-world data. METHODS: A sampled cohort of patients hospitalized with bacteremic sepsis between October 2015 and December 2016 was identified in the National Inpatient Sample (NIS) database. In-hospital mortality and length of stay were defined as the relevant outcomes. Patients were divided into 6 BMI (kg/m2) subgroups; (1) underweight ≤ 19, (2) normal-weight 20-25, (3) over-weight 26-30, (4) obese I 31-35, (5) obese II 36-39, and (6) obese stage III ≥ 40. A multivariable logistic regression model was used to find predictors of mortality, and a linear regression model was used to find predictors of an extended length of stay (LOS). RESULTS: An estimated total of 90,760 hospitalizations for bacteremic sepsis across the U.S. were analyzed. The data showed a reverse-J-shaped relationship between BMI and study population outcomes, with the underweight patients (BMI ≤ 19 kg/m2) suffering from higher mortality and longer LOS as did the normal-weight patients (BMI 20-25 kg/m2) when compared to the higher BMI groups. The seemingly protective effect of a higher BMI diminished in the highest BMI group (BMI ≥ 40 kg/m2). In the multivariable regression model, BMI subgroups of ≤19 kg/m2 and ≥40 kg/m2 were found to be independent predictors of mortality. CONCLUSIONS: A reverse-J-shaped relationship between BMI and mortality was documented, confirming the "obesity paradox" in the real-world setting in patients hospitalized for sepsis and bacteremia.

Outcomes of Acute Coronary Syndrome Patients Who Presented with Cardiogenic Shock versus Patients Who Developed Cardiogenic Shock during Hospitalization.

Background: Cardiogenic shock (CS) continues to be a severe and fatal complication of acute coronary syndrome (ACS). CS patients have a high mortality rate despite significant progress in primary reperfusion, the management of heart failure and the expansion of mechanical circulatory support strategies. The present study addressed the clinical characteristics, management, and outcomes of ACS patients complicated with CS. Methods: We performed an observational study, using the 2000-2013 Acute Coronary Syndrome Israeli Surveys (ACSIS) database and identified hospitalizations of ACS patients complicated with CS. Patients' demographics and clinical characteristics, complications and outcomes were evaluated. We assessed the outcomes of ACS patients with CS at arrival (on the day of admission) compared with ACS patients who arrived without CS and developed CS during hospitalization. Results: The cohort included 13,434 patients with ACS diagnoses during the study period. Of these, 4.2% were complicated with CS; 224 patients were admitted with both ACS and CS; while 341 ACS patients developed CS only during the hospitalization period. The latter patients had significantly higher rates of MACEs compared with the group of ACS patients who presented with CS at arrival (73% vs. 51%; p < 0.0001). Similarly, the rates of in-hospital mortality (55% vs. 36%; p < 0.0001), 30-day mortality (64% vs. 50%; p = 0.0013) and 1-year mortality (73% vs. 59%; p = 0.0016) were higher in ACS patients who developed CS during hospitalization vs. ACS patients with CS at admission. There was a significant decrease in 1-year mortality trends during the 13 years of this study presented in ACS patients from both groups. Conclusions: Patients who developed CS during hospitalization had higher mortality and MACE rates compared with those who presented with CS at arrival. Further studies should focus on this subgroup of high-risk patients.

Outcomes of patients with acute coronary syndrome according to COVID-19 vaccination status.

BACKGROUND: COVID-19 vaccination has been associated with reduced risk of acute coronary syndrome (ACS); however, several studies have reported cardiovascular complications following vaccination. We aimed to investigate the effect of COVID-19 vaccination status on the treatment and outcome of ACS patients. METHODS: The study was based on the 2021 Acute Coronary Syndrome Israeli Survey. Patients were stratified into two groups according to COVID-19 vaccination status, vaccinated compared to unvaccinated. Patients who had received at least 2 vaccination doses up to 1 week prior to ACS hospitalization were considered vaccinated. The primary endpoint was 1-year all-cause mortality. RESULTS: A total of 1261 patients with ACS were included, of whom 990 (78.5%) were vaccinated. Vaccinated patients were older and less frequently smokers. There were no significant differences in coronary reperfusion rates and treatment with guideline-based medical therapy during hospital stay and at discharge. The primary endpoint of 1-year all-cause mortality occurred in 38 (3.8%) and 14 (5.2%) patients in the vaccinated and unvaccinated groups respectively (P = 0.42). 30-day MACE occurred in 94 (9.5%) in the vaccinated patients compared to 31 (11.5%) in the unvaccinated group (P = 0.39). These results remained similar following adjustment for confounders. CONCLUSION: There was no association between COVID-19 vaccination status and the outcomes of patients with ACS. Our findings provide support for the cardiovascular safety of COVID-19 mRNA vaccines in patients at high cardiovascular risk.

The Impact of CYP2C9*11 Allelic Variant on the Pharmacokinetics of Phenytoin and (S)-Warfarin.

Cytochrome P450 2C9 (CYP2C9) is responsible for the oxidative metabolism of about 15% of commonly used drugs, some of which are characterized by a narrow therapeutic window. CYP2C9 is highly polymorphic, and over 60 alleles have been described. CYP2C9*2 and CYP2C9*3 are the most common polymorphisms among White patients and both are associated with decreased activity. The evidence concerning the functional importance of less frequent variant alleles is scarce. The objective of the current study was to characterize the in vivo activity of CYP2C9 among carriers of CYP2C9*11, one of the "African" alleles and the fourth most common CYP2C9 variant allele among White patients by using two prototype substrates, phenytoin and (S)-warfarin. Single 300-mg phenytoin and 20-mg warfarin doses were given to 150 healthy Ethiopian Jewish participants who were nonsmokers, at least one week apart. (S)-warfarin oral clearance and phenytoin metabolic ratio (PMR) derived from the ratio of 5-(4-hydroxyphenyl)-5-phenylhydantoin in 24-hour urine collection to plasma phenytoin 12 hours (PMR 24/12) or 24 hours (PMR 24/24) post dosing, were used as markers of CYP2C9 activity. PMR 24/12 and PMR 24/24 were reduced by 50% and 62.2%, respectively, among carriers of CYP2C9*1/*11 (n = 13) as compared with carriers of CYP2C9*1/*1 (n = 127) (false discovery rate (FDR) q < 0.001). The respective decrease in (S)-warfarin oral clearance was 52.6% (FDR q < 0.001). In conclusion, the enzyme encoded by CYP2C9*11 is characterized by a more than 50% decrease in the enzymatic activity, resembling the extent of decrease associated with CYP2C9*3 ("no-function allele"). Among patients of African ancestry, CYP2C9*11 genetic analysis should be considered prior to prescribing of narrow therapeutic window drugs such as phenytoin, warfarin, nonsteroidal anti-inflammatory drugs, or siponimod.

Sex difference and outcome trends following transcatheter aortic valve replacement.

Background: Based on worldwide registries, approximately 50% of patients who underwent transcatheter aortic valve replacement (TAVR) are female patients. Although TAVR procedures have improved tremendously in recent years, differences in outcome including mortality between sexes remain. We aimed to investigate the trends in TAVR in the early and new eras of utilization and to assess TAVR outcomes in female patients vs. male patients. Methods: Using the 2011-2017 National Inpatient Sample (NIS) database, we identified hospitalizations for patients with the diagnosis of aortic stenosis during which a TAVR was performed. Patients' sociodemographic and clinical characteristics, procedure complications, and mortality were analyzed. Piecewise regression analyses were performed to assess temporal trends in TAVR utilization in female patients and in male patients. Multivariable analysis was performed to identify predictors of in-hospital mortality. Results: A total of 150,647 hospitalizations for TAVR across the United States were analyzed during 2011-2017. During the study period, a steady upward trend was observed for TAVR procedures in both sexes. From 2011 to 2017, there were significantly more TAVR procedures performed in men [80,477 (53.4%)] than in women [70,170 (46.6%)]. Male patients had significantly higher Deyo-CCI score and comorbidities. Differences in mortality rates among sexes were observed, presenting with higher in-hospital mortality in women than in men, OR 1.26 [95% CI 1.18-1.35], p < 0.001. Conclusion: Utilization of TAVR demonstrated a steady upward trend during 2011-2017, and a similar trend was presented for both sexes. Higher in-hospital mortality was recorded in female patients compared to male patients. Complication rates decreased over the years but without effect on mortality differences between the sex groups.

The Impact of COVID-19 Pandemic on Management and Outcome in Patients with Heart Failure.

BACKGROUND: The COVID-19 pandemic has adversely affected the provision of health care and disease management around the world. COVID-19 carries a high morbidity and mortality rate in elderly and people with comorbidities, including heart failure (HF). The present study addressed the clinical management and outcomes of HF patients during the pandemic. METHODS: We evaluated the clinical management and survival rate of HF patients during the COVID-19 pandemic in Israel (March 2020-April 2021). RESULTS: The cohort included 6748 patients with a diagnosis of HF during the study period. During this period, 843 HF patients (12.5%) were infected with COVID-19, and 194 died from COVID-19, a 23% mortality rate. Patients infected with COVID-19 had a higher percentage of diabetes and obesity. Predictors of mortality included age, male sex, reduced functional capacity, renal dysfunction, and absence of renin-angiotensin system inhibition. During the pandemic, there was a marked decrease in the usage of medical services in the cohort. Cardiovascular hospitalizations, all hospitalization, and emergency room visits were significantly decreased compared to the two years prior to the pandemic, particularly during the lockdowns. There was also an initial decrease in HF clinic visits. Mortality rates were very similar during the pandemic compared to previous years. There was a decline in non-COVID-19 deaths, which were replaced with deaths due to COVID-19. This may result from competing effects and reduced exposure to respiratory infections and other insults due to social distancing. CONCLUSIONS: Mortality rates in HF patients infected with COVID-19 were high. The COVID-19 pandemic resulted in the reduced usage of health services but without increased overall mortality.

Comparison of CYP2C9 Activity in Ethiopian and Non-Ethiopian Jews Using Phenytoin as a Probe.

The pharmacokinetics of CYP2C9 substrates is characterized by substantial interethnic variability. The objective of the study was to compare CYP2C9 activity by using Phenytoin Metabolic Ratio (PMR) between Ethiopian and non-Ethiopian Jews. PMR was derived from the ratio of p-HPPH in 24 h urine collection to plasma phenytoin, 12 h (PMR24/12) or 24 h (PMR24/24) after the administration of 300 mg phenytoin. Analysis of CYP2C9*2, *3, *5, *6, *8, and *11 was carried by direct sequencing. PMR was significantly correlated with CYP2C9 genotype in both groups (p < 0.002). Mean PMR values were similar among Ethiopians and non-Ethiopians despite the fact that the fraction of non-carriers of CYP2C9 variant alleles was significantly different (85 vs. 53%, respectively, p < 0.001). However, among non-carriers of CYP2C9*2, *3, *5, *6, *8, and *11 variant alleles, PMR24/12 and PMR24/24 values were 30 and 34% greater respectively in the non-Ethiopians group (p < 0.001). In conclusion-CYP2C9 activity as measured by PMR is similar in Ethiopian and non-Ethiopian Jews. However, among non-carriers of CYP2C9 variant alleles accounting for 85% of Ethiopian Jews, CYP2C9 activity is decreased by approximately one third as compared with non-Ethiopian Jews. Unique genetic CYP2C9 polymorphisms occurring only in Ethiopians may account for this difference.