Low Cholesterol Levels in Younger Heart Failure Patients May Predict Unfavorable Outcomes.

Background and Objectives: Hypercholesterolemia is a main risk-factor leading to ischemic heart disease (IHD). However, among patients with heart failure, the use of lipid lowering drugs in the presence of low cholesterol might be dangerous. This 18-year longitudinal study of patients ≤51 years old investigated the relationship between baseline total cholesterol, low-density lipoprotein cholesterol (LDL-c) and triglyceride levels, and survival among patients with severe HF. Materials and Methods: The average NYHA score of 82 patients ≤51 years old with heart failure was 2.61. They were followed for a mean of 11.3 years (15 months-20 years). Total mortality was 22%. Patients were divided into three groups. Group 1 had plasma LDL-c levels ≤ 80 mg/dl, Group 2, 80-115 mg/dl and Group 3 > 115 mg/dl. Results: Patients with the highest baseline total cholesterol, triglyceride and LDL-c levels > 115 mg/dl had a better survival rate (83%) compared to those with LDL-c < 80 mg/dl (50% survival, p = 0.043). The association between higher LDL-c levels and lower mortality was most noticeable among patients with heart failure. Conclusion: Longitudinal follow-up found that low LDL-c levels may indicate poorer prognosis among patient with heart failure who are ≤51 years old, similar to elderly heart failure patients. Cholesterol lowering drugs in younger patients with heart failure may increase mortality.

Apolipoprotein E (APOE) Genotypes in the Israeli population.

BACKGROUND: APOE genotype strongly affects plasma lipid levels and risk for cardiovascular disease and cognitive decline. Studies of apo-e allelic and APOE genotype frequencies among several populations have revealed interesting ethnic variations that might affect cardiovascular morbidity and cognition deterioration. OBJECTIVES: To evaluate apo-e allelic frequency among Israeli newborns based on known variances in apo-e allelic frequencies in different countries. METHODS: We examined 498 consecutive neonates born at Tel Aviv Sourasky Medical Center. Umbilical cord blood was sampled for genotyping and lipids. Birth weights were recorded. Demographics and parental risk factors for atherosclerosis were obtained from the mothers. RESULTS: Most parents were native-born Israelis. Other countries of origin of grandparents were Morocco, Russia, and Iraq. The prevalence of APOE genotypes in Israel is APOE 2/2: 1.4%, APOE 2/3: 8.2%, APOE 3/3: 77.7%, and APOE 4/4: 11.8%. There were no associations of APOE genotype with parental country of origin. However, there was a tendency for APOE 3/4 to be more frequent in newborns of parents of Asian and African origin. Genotype 3/3 was more frequent in newborns whose parents came from Europe and America (78%) compared to those from Asia or Africa (69%). CONCLUSIONS: It is important to determine risk factors such as APOE genotype for evaluation of premature atherosclerosis. Determining genetic and environmental risk factors may facilitate earlier treatment and prevent heart and brain atherosclerosis. APOE genotypes did not appear to affect total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels in newborns.

Monitoring Pleural Effusion in Elderly Patients Using Internal Thoracic Impedance.

BACKGROUND: Internal thoracic impedance (ITI) measurement is a sensitive method for detecting preclinical pulmonary edema and pleural effusion. OBJECTIVES: To investigate the efficacy of this non-invasive method for detecting early pleural effusion among geriatric patients and to monitor increased ITI during its resolution. METHODS: This prospective, controlled study was conducted between July 2012 and August 2015. The study comprised 70 patients aged 65 to 94 years; and 39 of the patients had pleural effusion. ITI was measured continuously with a RS-207 monitor. The predictive value of ITI monitoring was determined based on a total of eight measurements taken at 12-hour intervals over 84 hours. RESULTS: As a result of medical treatment, the median ITI of the study group increased from 31 (interquartile range [IQR] 28-33 ohms) to 41 ohms (IQR 38-41 ohms; P < 0.001) compared to non-significant changes in the control group. Average respiratory rate (per minute) in the study group decreased from 29 (IQR 28-34) to 19 (IQR 18-20). CONCLUSIONS: ITI monitoring is efficient for diagnosis and for ongoing clinical evaluation of the treatment of elderly patients with pleural effusion. Timely treatment may prevent serious complications of effusions avoiding extended hospitalization.

Resolution of Cannabinoid Hyperemesis Syndrome with Benzodiazepines: A Case Series.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is under-recognized by clinicians. It is characterized by nausea, severe abdominal pain, and cyclical vomiting in the context of chronic cannabis use. Oral benzodiazepine is a proposed treatment for CHS. It decreases activation of Cannabinoid Type 1 Receptor (CB1) in the frontal cortex, has a sedative and hypnotic effect and reduces the anticipation of nausea and vomiting. These effects on the central nervous system (CNS) might explain its beneficial antiemetic effect for this syndrome. OBJECTIVES: To increase the index of suspicion for CHS, a unique syndrome that requires a unique treatment with benzodiazepines and not antiemetics. METHODS: We describe a series of four patients with documented cannabis use, who were admitted to an internal medicine department of Meir Medical Center due to symptoms consistent with abdominal pain, nausea, and vomiting. They were initially treated with conventional antiemetics and proton pump inhibitors without response. Intensive investigations were conducted to exclude common and sometimes urgent gastrointestinal or CNS syndromes. RESULTS: After excluding urgent gastrointestinal and CNS origins for the vomiting, we suspected CHS. All four patients experienced similar symptoms and failure of conventional treatment with antiemetics and proton pump inhibitors. They experienced relief after administration of benzodiazepines. CONCLUSIONS: A high index of suspicion for CHS allows for rapid, appropriate treatment with benzodiazepines, which in turn may lead to cessation of the debilitating symptoms caused by this syndrome.

[ASSIMILATING POINT-OF-CARE-ULTRASOUND AS PART OF COMPETENCY AND ASSESSMENT- BASED MEDICAL EDUCATION IN INTERNAL MEDICINE: THE WAY FOR A BETTER RESIDENCY].

INTRODUCTION: The Israeli Society of Internal Medicine (ISIM) has joined a journey led by the Scientific Council of the Israeli Medical Association (IMA) to improve the residency of physicians in Israel. The process of transformation from time and place-based residency to an outcome-oriented, competencies and assessment-based residency is a multi-step, complex process. We describe the theoretical basis of the need for transformation, examples of specific competencies (basic, relating to all residencies and unique, specific for internal medicine) and their means of assessment. Furthermore, we present several examples of similar processes being conducted worldwide. We describe the process so far and the future anticipated challenges. We foresee the residency transformation resulting in elevated professional excellence amongst internists in Israel. Also, we anticipate that residents' satisfaction will rise and eventually, patients will receive better diagnostic and treatment outcomes in our wards.

A nurse-guided, basal-prandial insulin treatment protocol for achieving glycaemic control of hospitalized, non-critically ill diabetes patients, is non-inferior to physician-guided therapy: A pivotal, nurse-empowerment study.

Basal-prandial insulin is established for glycaemic control for hospitalized, type 2 diabetes patients. Empowering nurses to guide such protocols could be advantageous.The study aims to comparatively assess the efficacy and safety of glycaemic control by a nurse-guided protocol with physician-guided therapy. It also aims to assess the impact of empowerment on the nurses' sense of competence. This is a prospective, controlled, randomized, single-blinded study. Validated protocol utilizing basal-prandial insulin was used. Glycaemic control was the primary efficacy outcome, whereas hypoglycaemia and laboratory parameters were followed for safety. Assessment of nurses' psychological empowerment was done. One hundred fifty-eight treatment days of 53 patients were included. Patients were randomized to either study group (n = 27) or control group (n = 26). Glycaemia deviation from liberal range (60-300 mg/dL) was 7.4% of days for nurse-guided, basal-prandial insulin treatment protocol (NGP) and 7.84% for physician-guided therapy (PGT), P = 0.901. Rate of glycaemia deviation from the strict range (100-180 mg/dL) was 49.76% for NGP and 47.38% for PGT, P = 0.703. Mean range of daily deviation was similar (77.05 mg/dL for NGP and 76.04 mg/dL for PGT, P = 0.93). There were no significant differences in safety parameters. An empowerment questionnaire showed tendency for increased nurses' sense of competence. Nurse-guided protocol is non-inferior to physician-guided treatment in efficacy and safety parameters. Nurses' sense of competence was positively influenced.

Peripheral Vascular Disease and Carotid Artery Disease Are Associated with Decreased Bile Acid Excretion.

Low bile acid excretion (BAE) is associated with a higher risk of coronary artery disease (CAD) and cerebrovascular disease (stroke). This study investigated BAE in patients with peripheral vascular disease (PVD) and carotid artery disease (CA) and those without these diseases, compared to patients with CAD, stroke, or no evidence of atherosclerosis. Patients with complaints of chest pain-suspected CAD, syncope, stroke/TIA, severe headache, intermittent claudication, or falls were enrolled. All received a 4-day standard diet with 490 mg of cholesterol and internal standard copper thiocyanate. Fecal BAE was measured using gas-liquid chromatography. One hundred and three patients, sixty-eight (66%) men and thirty-five women (34%), mean age range 60.9 ± 8.9 years, were enrolled in this prospective, 22-year follow-up study. Regression analysis showed that advanced age, total BAE, and excretion of the main fractions were the only significant independent factors that predicted prolonged survival (p < 0.001). Twenty-two years' follow-up revealed only 15% of those with BAE <262.4 mg/24 h survived, compared to >60% of participants without atherosclerosis and a mean BAE of 676 mg/24 h. BAE was lower in patients with polyvascular atherosclerosis than in those with involvement of 1-3 vascular beds. Pearson correlations were found between total BAE and various fractions of BA, as well as HDL cholesterol. BAE and short-term survival were decreased among patients with PVD compared to those with CAD or stroke. Low BAE should be considered a valuable and independent risk factor for PVD.

Interpretation of Heart and Lungs Sounds Acquired via Remote, Digital Auscultation Reached Fair-to-Substantial Levels of Consensus among Specialist Physicians.

BACKGROUND: Technological advancement may bridge gaps between long-practiced medical competencies and modern technologies. Such a domain is the application of digital stethoscopes used for physical examination in telemedicine. This study aimed to validate the level of consensus among physicians regarding the interpretation of remote, digital auscultation of heart and lung sounds. METHODS: Seven specialist physicians considered both the technical quality and clinical interpretation of auscultation findings of pre-recorded heart and lung sounds of patients hospitalized in their homes. TytoCareTM system was used as a remote, digital stethoscope. RESULTS: In total, 140 sounds (70 heart and 70 lungs) were presented to seven specialists. The level of agreement was measured using Fleiss' Kappa (FK) variable. Agreement relating to heart sounds reached low-to-moderate consensus: the overall technical quality (FK = 0.199), rhythm regularity (FK = 0.328), presence of murmurs (FK = 0.469), appreciation of sounds as remote (FK = 0.011), and an overall diagnosis as normal or pathologic (FK = 0.304). The interpretation of some of the lung sounds reached a higher consensus: the overall technical quality (FK = 0.169), crepitus (FK = 0.514), wheezing (FK = 0.704), bronchial sounds (FK = 0.034), and an overall diagnosis as normal or pathological (FK = 0.386). Most Fleiss' Kappa values were in the range of "fare consensus", while in the domains of diagnosing lung crepitus and wheezing, the values increased to the "substantial" level. CONCLUSIONS: Bio signals, as recorded auscultations of the heart and lung sounds serving the process of clinical assessment of remotely situated patients, do not achieve a high enough level of agreement between specialized physicians. These findings should serve as a catalyzer for improving the process of telemedicine-attained bio-signals and their clinical interpretation.

Methylphenidate has mild hyperglycemic and hypokalemia effects and increases leukocyte and neutrophil counts.

Various psychotropic drugs may affect the hematological and biochemical profiles of plasma and its metabolism. Carbamazepine, the most well-known psychotropic drug, can cause substantial hyponatremia. Methylphenidate, a piperidine derivative structurally related to amphetamines, acts as a central nervous system stimulant. The current study evaluated whether methylphenidate affects hematological and biochemical parameters of patients diagnosed with attention deficit hyperactivity disorder.Patients undergoing treatment for attention deficit hyperactivity disorder at our Adolescent Psychiatric Clinic were enrolled in the study. Blood samples for complete blood count and common biochemical analyses were collected before patients started methylphenidate and after 3 months of continuous treatment.Participants included 64 patients comprised the study cohort. There were 48 (75%) males and 16 (25%) females, with a median age of 16 years (range 11-31). The total median potassium level decreased by 0.6 mg/dL (P < .0001), while glucose rose by 15 mg/dL (P < .0001), sodium decreased in 0.7meq/L, (P = .006). The white blood count rose by 1350 cells/µL (P < .033) due to neutrophilia, lymphocytosis and eosinophilia. Hemoglobin rose slightly by 0.1 (P = .041). Changes in calcium, phosphorus, protein, albumin, and liver enzyme levels were not significant.The results indicate that methylphenidate may cause hypokalemia and elevated glucose, leukocyte, neutrophil, lymphocyte and eosinophil counts.

Reduced bile acid excretion is an independent risk factor for stroke and mortality: A prospective follow-up study.

BACKGROUND AND AIMS: Hypercholesterolemia is a major risk factor for atherosclerosis, which is a cornerstone of coronary artery disease (CAD), stroke, peripheral vascular disease, aortic aneurysm and renal artery stenosis. This study investigated the association of bile acid excretion (BAE) with stroke incidence and mortality. METHODS: Patients admitted to Internal Medicine due to chest pain and suspected CAD were enrolled and followed from 1/1998 to 12/2018. Patients received a standard in-hospital diet containing 490 mg/day cholesterol and performed a 24-h stool collection. A continuous, non-absorbable marker was used to evaluate the amount of BAE. RESULTS: This retrospective, historical, follow-up study included 68 men and 35 women (mean age 61.9 ± 8.9 years) admitted to the hospital from 1996 to 1998 due to chest pain and suspected cardiac event. Mean BAE at first admission was higher among survivors (>608.8 mg) than non-survivors (281.5 mg/24h; p<0.001). Total cholesterol, LDL cholesterol and triglyceride levels at baseline did not differ significantly. The main fractions of deoxycholic, lithocholic, and cholic acids were significantly different in the two groups. They were also higher in the survivors. Total BAE was higher in stroke-free patients compared to those who developed stroke: 561.6 mg/24h and 231.2 mg/24h-respectively (p<0.001). Patients with BAE <262.4 developed stroke in 75% cases (18/24). None of 25 patients with BAE >622 mg/24h developed stroke. CONCLUSION: This retrospective, historical cohort follow-up study showed an association between lower amounts of total bile acid, deoxycholic acid and lithocholic acid excretion with stroke risk. Low BAE remained a significant risk-factor after adjusting for main potential confounders and may be an independent risk-factor for stroke.

Coagulation factor XIII serves as protein disulfide isomerase.

Tissue transglutaminase was reported to act as protein disulfide isomerase (PDI). We studied whether plasma transglutaminase - coagulation factor XIII (FXIII) - has PDI activity as well. PDI activity was measured by determining the ability to renature reduced-denatured RNase (rdRNase). We found that FXIII can renature rdRNase, with efficiency comparable to commercial PDI. This PDI activity was inhibited by bacitracin. Like tissue transglutaminase, FXIII-mediated PDI activity is independent of its transglutaminase activity and is located on the A subunit. Surface-associated PDI has been previously shown to catalyse two distinct functions: transnitrosation with subsequent release of intracellular nitric oxide and disulfide bond rearrangement during platelet integrin ligation. Our results imply that FXIII-PDI activity may have a role in platelet function.

Monocytes may be favorable biomarker and predictor of long-term outcome in patients with chronic heart failure: A cohort study.

Although some studies found that an increased monocyte count is a predictive, short-term marker of unfavorable outcomes for patients with acute heart failure (HF), others have reported that monocytosis predicts prolonged survival.The current follow-up study aimed to identify different monocyte count patterns and their prognostic association with HF outcomes.Baseline blood samples for complete blood counts, differential counts, renal function tests, and lipid profiles of 303 chronic HF patients (average NYHA classification 2.8) were prospectively obtained to evaluate whether there is an association between monocyte count and clinical outcomes.Mean follow-up was 11.3 years (range 1 month to 16 years) and 111 (36.6%) patients died during follow-up. Mean monocyte count was 10.6 ±â€Š5.5 and mean left ventricular ejection fraction (LVEF) was 36%. Patients with low monocyte counts (≤6%) had significantly lower survival rates than did those with monocyte counts 6.1% to 14%, or >14% (14.3% vs 70.2% vs. 88%, P < .001). Poorest survival was predicted for patients with NYHA class 3 to 4 and monocyte counts ≤6. Regression analysis showed that monocyte levels, NYHA class, and LVEF values were predictors of mortality, in decreasing importance.The total monocyte count was found to be an important prognostic factor that was inversely associated with predicted long-term mortality among patients with chronic HF. A low total monocyte count was strongly correlated with NYHA class and B-type natriuretic peptide levels, but no correlation was found with LVEF and oxidized low-density lipoproteins. It emerged as an independent risk factor for mortality in patients with chronic HF.

[Probiotics as prophylactic agents against antibiotic-associated diarrhea in hospitalized patients].

BACKGROUND: Antibiotic associated diarrhea is a major cause of morbidity in hospitalized elderly patients. Probiotics may shorten the duration and reduce the recurrence incidence of this problem. The researchers assessed the protective effects of probiotics in hospitalized patients. PATIENTS AND METHODS: Hospitalized patients aged 18 or older, who were scheduled for antibiotic treatment, were randomly assigned to receive either probiotics or placebo in a double-blind placebo controlled study, within 24 hours from the beginning of antibiotic treatment and for three weeks later. Baseline fecal Clostridium difficile toxin levels (A and B) were obtained within 24 hours of treatment. The patients were monitored for diarrhea, antibiotic treatment and duration of stay. The probiotics were also analyzed for sensitivity to antibiotic treatment in vitro. RESULTS: Forty-two patients completed the study; 21 patients were treated with probiotics and 21 with placebo. Diarrhea occurred in 4 patients (9%): one in the placebo group and three in the probiotic group, p=NS. Clostridium toxin samples were negative in 17 (68%) samples and 8 (23%) were positive (+2 to +4). Diarrhea occurred only in patients treated with wide-spectrum antibiotics, (p = 0.04, Chi2). In-vitro culture of the probiotic capsules yielded gram-positive cocci and bacilli, which were susceptible to many of the antibiotics used by the patients in this study. CONCLUSIONS: There was no significant protecting effect of prophylactic probiotics for antibiotic associated diarrhea in hospitalized patients under antibiotic treatment, mainly because of the susceptibility of the probiotic bacteria to the treatment.