Adolescent Hypertension Is Associated With Stroke in Young Adulthood: A Nationwide Cohort of 1.9 Million Adolescents.

BACKGROUND: Adult hypertension is a well-established risk factor for stroke in young adults (aged <55 years), and the effects are even more deleterious than at an older age. However, data are limited regarding the association between adolescent hypertension and the risk of stroke in young adulthood. METHODS: A nationwide, retrospective cohort study of adolescents (aged 16-19 years) who were medically evaluated before compulsory military service in Israel during 1985 to 2013. For each candidate for service, hypertension was designated after constructed screening, and the diagnosis was confirmed through a comprehensive workup process. The primary outcome was ischemic and hemorrhagic stroke incidence as registered at the national stroke registry. Cox proportional-hazards models were used. We conducted sensitivity analyses by excluding people with a diabetes diagnosis at adolescence or a new diabetes diagnosis during the follow-up period, analysis of adolescents with overweight, and adolescents with baseline unimpaired health status. RESULTS: The final sample included 1 900 384 adolescents (58% men; median age, 17.3 years). In total, 1474 (0.08%) incidences of stroke (1236 [84%] ischemic) were recorded, at a median age of 43 (interquartile range, 38-47) years. Of these, 18 (0.35%) occurred among the 5221 people with a history of adolescent hypertension. The latter population had a hazard ratio of 2.4 (95% CI, 1.5-3.9) for incident stroke after adjustment for body mass index and baseline sociodemographic factors. Further adjustment for diabetes status yielded a hazard ratio of 2.1 (1.3-3.5). We found similar results when the outcome was ischemic stroke with a hazard ratio of 2.0 (1.2-3.5). Sensitivity analyses for overall stroke, and ischemic stroke only, yielded consistent findings. CONCLUSIONS: Adolescent hypertension is associated with an increased risk of stroke, particularly ischemic stroke, in young adulthood.

Predictors and Adverse Outcomes of Acute Kidney Injury in Hospitalized Renal Transplant Recipients.

Data about in-hospital AKI in RTRs is lacking. We conducted a retrospective study of 292 RTRs, with 807 hospital admissions, to reveal predictors and outcomes of AKI during admission. In-hospital AKI developed in 149 patients (51%). AKI in a previous admission was associated with a more than twofold increased risk of AKI in subsequent admissions (OR 2.13, p < 0.001). Other major significant predictors for in-hospital AKI included an infection as the major admission diagnosis (OR 2.93, p = 0.015), a medical history of hypertension (OR 1.91, p = 0.027), minimum systolic blood pressure (OR 0.98, p = 0.002), maximum tacrolimus trough level (OR 1.08, p = 0.005), hemoglobin level (OR 0.9, p = 0.016) and albumin level (OR 0.51, p = 0.025) during admission. Compared to admissions with no AKI, admissions with AKI were associated with longer length of stay (median time of 3.83 vs. 7.01 days, p < 0.001). In-hospital AKI was associated with higher rates of mortality during admission, almost doubled odds for rehospitalization within 90 days from discharge and increased the risk of overall mortality in multivariable mixed effect models. In-hospital AKI is common and is associated with poor short- and long-term outcomes. Strategies to prevent AKI during admission in RTRs should be implemented to reduce re-admission rates and improve patient survival.

BNT162b2 Third Booster Dose Significantly Increases the Humoral Response Assessed by Both RBD IgG and Neutralizing Antibodies in Renal Transplant Recipients.

Background: An impaired humoral response to full dose of BNT162b2 vaccine was observed in renal transplant recipients (RTR). Methods: To reveal predictors for humoral response to third vaccine, patients were stratified to positive (N = 85) and negative (N = 14) response groups based on receptor-binding domain (RBD) IgG ≥1.1 and neutralizing antibodies (NA) ≥ 16 dilution versus RBD IgG <1.1 or NA < 16, respectively. NA were detected using a SARS-CoV-2 pseudo-virus. Results: Response rate increased from 32.3% (32/99) before the third dose to 85.9% (85/99) post-third vaccine with a significant rise in geometric mean titers (GMTs) for RBD IgG and NA [0.79 (95% CI 0.65-0.96) vs. 3.08 (95% CI 2.76-3.45), p < 0.001 and 17.46 (95% CI 12.38-24.62) vs. 362.2 (95% CI 220.7-594.6), p < 0.001 respective. 80.6% (54/67) seroconverted and 96.9% (31/32) remained positive following the vaccine with a significant increase in GMTs for RBD IgG and NA. Age, ESRD secondary to diabetic nephropathy (DN) and renal allograft function were independent predictors for antibody response in RTR. Mycophenolic acid (MPA) use and dose had no impact on humoral response following the third booster. AEs were recorded for 70.1% of RTR population. Systemic AEs were more common in recipients with a positive humoral response as opposed to non-responders (45.2% versus 15.4% respectively, p = 0.04). Conclusion: 85.9% of RTR develop NA to BNT162b2 third vaccine, found effective in both negative and positive responders prior to the vaccine. Antigenic re-exposure overcame the suppressive effect of MPA on antibody response in RTR.

Alerting on mortality among patients discharged from the emergency department: a machine learning model.

OBJECTIVES: Physicians continuously make tough decisions when discharging patients. Alerting on poor outcomes may help in this decision. This study evaluates a machine learning model for predicting 30-day mortality in emergency department (ED) discharged patients. METHODS: We retrospectively analysed visits of adult patients discharged from a single ED (1/2014-12/2018). Data included demographics, evaluation and treatment in the ED, and discharge diagnosis. The data comprised of both structured and free-text fields. A gradient boosting model was trained to predict mortality within 30 days of release from the ED. The model was trained on data from the years 2014-2017 and validated on data from the year 2018. In order to reduce potential end-of-life bias, a subgroup analysis was performed for non-oncological patients. RESULTS: Overall, 363 635 ED visits of discharged patients were analysed. The 30-day mortality rate was 0.8%. A majority of the mortality cases (65.3%) had a known oncological disease. The model yielded an area under the curve (AUC) of 0.97 (95% CI 0.96 to 0.97) for predicting 30-day mortality. For a sensitivity of 84% (95% CI 0.81 to 0.86), this model had a false positive rate of 1:20. For patients without a known malignancy, the model yielded an AUC of 0.94 (95% CI 0.92 to 0.95). CONCLUSIONS: Although not frequent, patients may die following ED discharge. Machine learning-based tools may help ED physicians identify patients at risk. An optimised decision for hospitalisation or palliative management may improve patient care and system resource allocation.

The Use of Brain Natriuretic Peptide as a Decision-supporting Tool in Hospitalized Patients.

BACKGROUND: Most dyspneic patients in internal medicine departments have co-morbidities that interfere with the clinical diagnosis. The role of brain natriuretic peptide (BNP) levels is well-established in the acute setting but not in hospitalized patients. OBJECTIVES: To evaluate the additive value of BNP tests in patients with dyspnea admitted to medical wards who did not respond to initial treatment. METHODS: We searched the records of patients who were hospitalized in the department of internal medicine D at Sheba Medical Center during 2012 and were tested for BNP in the ward. Data collected included co-morbidity, medical treatments, diagnosis at presentation and discharge, lab results including BNP, re-hospitalization, and mortality at one year following hospitalization. RESULTS: BNP results were found for 169 patients. BNP was taken 1.7 ± 2.7 days after hospitalization. According to BNP levels, dividing the patients into tertiles revealed three equally distributed groups with a distinctive character. The higher tertile was associated with higher rates of cardiac co-morbidities, including heart failure, but not chronic obstructive pulmonary disease. Higher BNP levels were related to one-year re-hospitalization and mortality. In addition, higher BNP levels were associated with higher rates of in-admission diagnosis change. CONCLUSIONS: BNP levels during hospitalization in internal medicine wards are significantly related to cardiac illness, the existence of heart failure, and patient prognosis. Thus, BNP can be a useful tool in managing dyspneic patients in this setting.

The opposing trends of body mass index and blood pressure during 1977-2020; nationwide registry of 2.8 million male and female adolescents.

BACKGROUND: Elevated blood pressure among adolescents has been shown to be associated with future adverse cardiovascular outcomes and early onset diabetes. Most data regarding systolic and diastolic blood pressure trends are based on surveys of selected populations within 10-20-year periods. The goal of this study was to characterize the secular trend of blood pressure given the rising prevalence of adolescent obesity. METHODS: This nationwide population-based study included 2,785,515 Israeli adolescents (41.6% females, mean age 17.4 years) who were medically evaluated and whose weight, height and blood pressure were measured, prior to mandatory military service between 1977 and 2020. The study period was divided into 5-year intervals. Linear regression models were used to describe the P for trend along the time intervals. Analysis of covariance was used to calculate means of blood pressure adjusted for body mass index. RESULTS: During the study period, the mean body mass index increased by 2.1 and 1.6 kg/m2 in males and females, respectively (P for trend < 0.001 in both sexes). The mean diastolic blood pressure decreased by 3.6 mmHg in males and by 2.9 mmHg in females (P < 0.001 in both sexes). The mean systolic blood pressure increased by 1.6 mmHg in males and decreased by 1.9 mmHg in females. These trends were also consistent when blood pressure values were adjusted to body mass index. CONCLUSION: Despite the increase in body mass index over the last four decades, diastolic blood pressure decreased in both sexes while systolic blood pressure increased slightly in males and decreased in females.

Dissociation Between Long-term Weight Loss Intervention and Blood Pressure: an 18-month Randomized Controlled Trial.

BACKGROUND: Obesity is associated with elevated blood pressure (BP). In patients with obesity and hypertension, weight loss lowers BP, but the long-term effect of weight loss on BP is less clear. OBJECTIVE: We aimed to assess the effect of long-term weight loss intervention on BP in normotensive and hypertensive subjects. DESIGN: Randomized controlled trial. PARTICIPANTS: Two hundred seventy-eight subjects (mean age 47.9 ± 9.3 years, 89% male, 56% hypertensive) with abdominal obesity or elevated serum triglycerides and low high-density lipoprotein cholesterol were recruited. INTERVENTION: Eighteen-month weight loss intervention. MAIN MEASURES: Body weight and BP were measured at baseline, after 6 and 18 months. RESULTS: After 6 months of intervention, in the weight loss phase, body mass index (BMI) decreased by an average of -2.2±1.5 kg/m2 (p<0.001) and both diastolic BP (DBP) and systolic BP (SBP) decreased by -2.1±8.8 mmHg and -2.3±12.9 mmHg, respectively (p<0.01 for both). The change in BMI was similar in normotensive and hypertensive subjects (-2.0±1.6 and -2.3±1.5, p = 0.246). However, DBP and SBP decreased significantly (-5.2±7.1 mmHg and -6.2±12.5 mmHg, respectively, p<0.001 for both) in hypertensive subjects, and increased in normotensive subjects (1.8±9.3 mmHg, p = 0.041 and 2.7±11.7 mmHg, p = 0.017, respectively). After 18 months, in the weight maintenance phase, BMI slightly increased (0.9±1.3 kg/m2, p<0.001) but remained significantly lower than at baseline (p<0.0001). Unlike BMI, DBP and SBP increased significantly in hypertensive subjects (p<0.001) and returned almost to baseline levels. CONCLUSION: Weight-loss intervention reduced BP in hypertensive patients, but this was not maintained in the long run. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01530724.

Normal-range emergency department serum phosphorus levels and all-cause mortality.

PURPOSE OF THE STUDY: Hypophosphataemia and hyperphosphataemia are frequently encountered in hospitalised patients and are associated with significant clinical consequences. However, the prognostic value of normal-range phosphorus levels on all-cause mortality and hospitalisations is not well established. Therefore, we examined the association between normal-range phosphorus levels, all-cause mortality and hospitalisations in patients presenting to the emergency department of a tertiary medical centre in Israel. STUDY DESIGN: A retrospective analysis of patients presenting to the Chaim Sheba Medical Center emergency department between 2012 and 2018. The cohort was divided into quartiles based on emergency department phosphorus levels: 'very-low-normal' (p ≥ 2 mg/dL and p ≤ 2.49 mg/dL), 'low-normal' (p ≥ 2.5 mg/dL and p ≤ 2.99 mg/dL), 'high-normal' (p≥  3 mg/dL and p≤3.49 mg/dL) and 'very-high-normal' (p ≥  3.5 mg/dL and p ≤ 4 mg/dL). We analysed the association between emergency department phosphorus levels, hospitalisation rate and 30-day and 90-day all-cause mortality. RESULTS: Our final analysis included 223 854 patients with normal-range phosphorus levels. Patients with 'very-low-normal' phosphorus levels had the highest mortality rate. Compared with patients with 'high-normal' phosphorus levels, patients with 'very-low-normal' levels had increased 30-day all-cause mortality (OR 1.3, 95% CI 1.1 to 1.4, p<0.001), and increased 90-day all-cause mortality (OR 1.2, 95% CI 1.1 to 1.3, p<0.001). Lower serum phosphorus levels were also associated with a higher hospitalisation rate, both for the internal medicine and general surgery wards (p<0.001). CONCLUSIONS: Lower phosphorus levels, within the normal range, are associated with higher 30-day and 90-day all-cause mortality and hospitalisation rate.

The effect of civil and military flights on coagulation, fibrinolysis and blood flow: insight from a rat model.

BACKGROUND: Air travel thrombosis continues to be a controversial topic. Exposure to hypoxia and hypobaric conditions during air travel is assumed a risk factor. The aim of this study is to explore changes in parameters of coagulation, fibrinolysis and blood flow in a rat model of exposure to hypobaric conditions that imitate commercial and combat flights. METHODS: Sixty Sprague-Dawley male rats, aged 10 weeks, were divided into 5 groups according to the type and duration of exposure to hypobaric conditions. The exposure conditions were 609 m and 7620 m for 2 and 12 h duration. Blood count, thrombin- antithrombin complex, D-dimer, interleukin-1 and interleukin-6 were analyzed. All rats went through flight angiography MRI at day 13-post exposure. RESULTS: No effect of the various exposure conditions was observed on coagulation, fibrinolytic system, IL-1 or IL-6. MRI angiography showed blood flow reduction in lower limb to less than 30% in 50% of the rats. The reduction in blood flow was more pronounced in the left vessel than in the right vessel (p = 0.006, Wilcoxon signed rank test). The extent of occlusion differed across exposure groups in the right, but not the left vessel (p = 0.002, p = 0.150, respectively, Kruskal-Wallis test). However, these differences did not correlate with the exposure conditions. CONCLUSION: In the present rat model, no clear correlation between various hypobaric conditions and activation of coagulation was observed. The reduction in blood flow in the lower limb also occurred in the control group and was not related to the type of exposure.

Emergency Department Triage in the Era of COVID-19: The Sheba Medical Center Experience.

BACKGROUND: Sheba Medical Center, Tel Hashomer, is a tertiary hospital located in the center of Israel. It is the largest hospital in Israel and was the first to face coronavirus disease-2019 (COVID-19) patients in the country at the beginning of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. OBJECTIVES: To describe our experience with the COVID-19 pandemic, focusing on our triage method in the emergency department (ED). Our goal was to keep the main hospitalization buildings clean of infection by separating COVID-19 positive patients from COVID-19 negative patients. METHODS: We divided our ED into two separate sections: a regular non-COVID-19 ED and an advanced biological ED. We created clear protocols of triage for suspected and confirmed COVID-19 patients. We reviewed the data of patients admitted to our ED during the month of March and analyzed the results of our triage method in separating COVID-19 positive from negative patients. RESULTS: During the month of March 2020, 7957 patients were referred to our ED. Among them 2004 were referred to the biological ED and 5953 were referred to the regular ED. Of the 2004 patients referred to the biological ED, 1641 (81.8%) were sampled for SARS-CoV-2 polymerase chain reaction of whom 143 (8.7%) were positive. Only two COVID-19 positive patients unintentionally entered the main clean hospital, making our triage almost full proof. CONCLUSIONS: Our triage method was successful in separating COVID-19 positive from negative patients and maintained the regular hospital clean of COVID-19 allowing treatment continuation of regular non-COVID-19 patients.

Iatrogenic hypertension: a bioinformatic analysis.

It is well known that a myriad of medications and substances can induce side effects that are related to blood pressure (BP) regulation. This study aims to investigate why certain drugs tend to cause iatrogenic hypertension (HTN) and focus on drug targets that are implicated in these conditions.Databases and resources such as SIDER, DrugBank, and Genomatix were utilized in order to bioinformatically investigate HTN-associated drug target-genes for which HTN is a side effect. A tree-like map was created, representing interactions between 198 human genes that relate to the blood pressure system. 72 HTN indicated drugs and 160 HTN-inducing drugs were investigated. HTN-associated genes affected by these drugs were identified. HTN indicated drugs, which target nearly all branches of the interaction tree, were shown to exert an effect on most functional sub-systems of the BP regulatory system; and specifically, for the adrenergic and dopaminergic receptor pathways. High prevalence (25 genes) of shared targets between the HTN indicated and HTN-inducing drug categories was demonstrated. We focus on six drug families which are not indicated for HTN treatment, yet are reported as a major cause for blood pressure side effects. We show the molecular mechanisms that may lead to this iatrogenic effect. Such an analysis may have clinical implications that could allow for the development of tailored medicine with fewer side effects.

The association between fasting plasma glucose and glycated hemoglobin in the prediabetes range and future development of hypertension.

BACKGROUND: Prediabetes is a well-established risk factor for progression to overt diabetes mellitus (DM), which is in turn associated with development of hypertension (HTN) and vice versa. However, the role of prediabetes and HbA1c in particular as an independent risk factor for the development of hypertension is unclear. AIM: In this current study, we aimed to evaluate the association between both fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels in the prediabetes range and development of HTN among a large cohort of normotensive subjects. DESIGN AND METHODS: We investigated 5016 normotensive participants without DM and other cardiovascular risk factors who were annually screened in a tertiary medical center. Subjects were divided into normoglycemic and prediabetic groups. Normoglycemia was defined as HbA1c < 5.7% and FPG < 100 mg/dl. Prediabetes was defined according to the ADA criteria, i.e., 6.5% > HbA1c ≥ 5.7% or impaired fasting glucose (IFG):126 mg/dl > FPG ≥ 100 mg/dl. Subgroup analysis was made by dividing participants into four groups according to FPG and HbA1C levels, i.e., normoglycemia, impaired HbA1c only, IFG only, and both parameters impaired. RESULTS: During a follow-up of 3.7 ± 2.9 years, 318 (6.3%) subjects developed HTN. A cumulative hazard function for the development of hypertension showed a 2.89-fold ([95% CI 2.19-3.83], p < .0001) increased risk for HTN in the prediabetic population. In a multivariable Cox proportional hazard regression model adjusted to common confounding risk factors for HTN, prediabetes was found to be independently associated with a 1.95-fold ([95%, CI 1.43-2.52] p < .0001) increased risk for hypertension. Impaired HbA1C only was not found to be independently associated with HTN, while IFG only showed a 2.13-fold (95%, [CI 1.46-3.11] p < .0001) increased risk for HTN compared to normoglycemic, and a 2.55-fold ([95% CI 1.85-3.51] p < .0001) increased risk for HTN when both parameters impaired. CONCLUSION: Our study demonstrates that FPG in the prediabetes range, albeit not glycated hemoglobin, is independently and significantly associated with future development of HTN. Therefore, our findings further highlight the pivotal predictive role of IFG for HTN development as opposed to the limited independent role of abnormal HbA1c levels.

Renal glucosuria is associated with lower body weight and lower rates of elevated systolic blood pressure: results of a nationwide cross-sectional study of 2.5 million adolescents.

BACKGROUND: Gene coding mutations found in sodium glucose co-transporters (SGLTs) are known to cause renal glucosuria. SGLT2 inhibitors have recently been shown to be effective hypoglycemic agents as well as possessing cardiovascular and renal protective properties. These beneficial effects have to some extent, been attributed to weight loss and reduced blood pressure. The aim of the current study was to evaluate the prevalence of renal glucosuria amongst a large cohort of Israeli adolescents and to investigate whether renal glucosuria is associated with lower body weight and lower blood pressure values. METHODS: Medical and socio-demographic data were collected from the Israeli Defense Force's conscription center's database. A cross-sectional study to evaluate the association between conscripts diagnosed as overweight [BMI percentiles of ≥ 85 and < 95 and obesity (≥ 95 BMI percentile)] and afflicted with renal glucosuria was conducted. In addition, we assessed the association of renal glucosuria with elevated diastolic and systolic blood pressure. Multinomial regression models were used. RESULTS: The final study cohort comprised 2,506,830 conscripts of whom 1108 (0.044%) were diagnosed with renal glucosuria, unrelated to diabetes mellitus, with males twice as affected compared to females. The adjusted odds ratio for overweight and obesity was 0.66 (95% CI 0.50-0.87) and 0.62 (95% CI 0.43-0.88), respectively. Adolescents afflicted with renal glucosuria were also less likely to have an elevated systolic blood pressure of 130-139 mmHg with an adjusted odds ratio of 0.74 (95% CI 0.60-0.90). CONCLUSIONS: Renal glucosuria is associated with lower body weight and obesity as well as with lower rates of elevated systolic blood pressure.

Blood pressure control in type 2 diabetic patients.

Diabetes mellitus (DM) and essential hypertension are common conditions that are frequently present together. Both are considered risk factors for cardiovascular disease and microvascular complications and therefore treatment of both conditions is essential. Many papers were published on blood pressure (BP) targets in diabetic patients, including several works published in the last 2 years. As a result, guidelines differ in their recommendations on BP targets in diabetic patients. The method by which to control hypertension, whether pharmacological or non-pharmacological, is also a matter of debate and has been extensively studied in the literature. In recent years, new medications were introduced for the treatment of DM, some of which also affect BP and the clinician treating hypertensive and diabetic patients should be familiar with these medications and their effect on BP. In this manuscript, we discuss the evidence supporting different BP targets in diabetics and review the various guidelines on this topic. In addition, we discuss the various options available for the treatment of hypertension in diabetics and the recommendations for a specific treatment over the other. Finally we briefly discuss the new diabetic drug classes and their influence on BP.

Effect of tumor necrosis factor-α inhibitors on ambulatory 24-h blood pressure.

Tumor necrosis factor alpha (TNF-α) inhibitors are increasingly being used in inflammatory rheumatic diseases (IRD). The risk of cardiovascular disease is elevated in patients with IRD and TNF-α inhibitors reduce this risk. We assessed whether the beneficial effect of TNF-α inhibitors on cardiovascular risk is mediated by blood pressure reduction. We measured blood pressure levels with 24-h ambulatory blood pressure measurements device in patients with IRD before and 3 months after treatment with TNF-α inhibitors. The study population consisted of 15 subjects (6 men; mean age 45.9 ± 14.1 years). Most patients had either rheumatoid arthritis or psoriatic arthritis and adalimumab was the most common TNF-α inhibitor used. Mean 24-h systolic and diastolic blood pressure levels remained the same after treatment (121 ± 12/66 ± 7 before and 123 ± 11/67 ± 10 mm Hg after; p = 0.88 and 0.66, respectively). The study demonstrates that TNF-α inhibitors have no effect on blood pressure levels.

[SCIENTIFIC PUBLICATIONS: ON HONORS AND GHOSTS].

INTRODUCTION: The ethics committee at the Sackler Faculty of Medicine, Tel Aviv University deals with complaints which are not necessarily related to teaching or to issues in the realm of the Institutional Review Board (Helsinki Commission). Virtually all complaints reaching the committee are based on disputed authorship of scientific publications. Researchers and clinicians are interested in publishing their research in order to share knowledge but also in order to comply with the dictum "Publish or Perish". They are publishing to enhance their reputation, to improve chances for funding and to increase the likelihood for clinical and academic promotion. Yet, lack of appropriate planning and agreements on authorship ahead of time may lead to frictions, misunderstandings and outright belligerence between authors. The issue of authorship is being addressed by scientific journals, academic institutions and committees of editors. All of them have published appropriate guidelines which form the basis for the work of the ethics committee. We deal with "honorary authorship", that is individuals who are listed as authors, although they have not contributed sufficiently to the research in order to merit authorship and we deal with "Ghost Authorship" that is when contributing researchers are not listed, as they should be among authors of a scientific publication. Specific case studies are presented.

Melatonin prevents kidney injury in a high salt diet-induced hypertension model by decreasing oxidative stress.

Melatonin, a potent antioxidant molecule, plays a role in blood pressure regulation. We hypothesized that melatonin may generate a protective effect in a high salt diet (HSD) rodent model mediated by decreasing renal oxidative stress. Dahl salt-sensitive rats were divided into three groups according to diet: normal chow (control); HSD; HSD with melatonin [30/mg/kg/day]) placed in their water (HSD + Mel) over an 8-wk period. Blood pressure was measured by the tail cuff method. Kidney injury was evaluated by 24 H urine protein excretion. Glomerular injury index (GII) (fibrotic glomeruli/100 glomeruli) was evaluated from a Masson's trichrome-stained section. Kidney oxidative stress was determined by superoxide production via dihydroethidium staining. Expression of oxidative stress-related genes was measured by reverse transcriptase-qPCR. Melatonin had no effect on blood pressure increase induced by HSD and attenuated proteinuria induced by HSD (HSD--50.7 ± 12, HSD + Mel--22.3 ± 4.3, controls--6.5 ± 1.0 gram protein/gram creatinine, P < 0.001). HSD-induced glomerular damage was significantly diminished by melatonin (GII in HSD--24 ± 6, HSD + Mel--3.6 ± 0.8, controls--0.8 ± 0.5, P < 0.05). Superoxide production was significantly higher in kidneys of HSD fed rats than the controls (99 ± 9 versus 60 ± 7 relative fluorescent units (RFU)/µm(2), respectively, P < 0.05). Melatonin also decreased superoxide production (74 ± 5 RFU/µm(2), P < 0.05). The expression of kidney inducible nitric oxide synthase and p67(phox) mRNA was significantly higher in HSD than in the controls and HSD + Mel rats. Treatment with melatonin eliminated the deleterious effect of HSD in the kidneys of Dahl salt-sensitive rats. The beneficial effect of melatonin is not mediated by lowering blood pressure but by a direct antioxidative effect.

High-risk type-2 diabetes mellitus patients, without prior ischemic events, have normal blood platelet functionality profiles: a cross-sectional study.

BACKGROUND: Patients with type 2 diabetes mellitus (DM) display a predisposition for vascular disease. Platelets taken from vasculopathic diabetic patients, show enhanced stimuli-induced activation and aggregation responses. Aspirin remains the cornerstone antiplatelet agent for secondary prevention of vascular complications among diabetic patients, yet evidence of its efficacy and safety in primary prevention are conflicting. Our aim was to assess whether high risk diabetic patients, without previous ischemic events, have abnormal platelet functionality profiles. METHODS: The study included 82 diabetic patients and 86 matched non-diabetic patients without prior ischemic events nor treatment with anti-platelet medications. Blood samples were analyzed for platelet markers of activation, turnover and leukocyte-platelet interactions. RESULTS: Our final analysis included 122 males (74 %), with a mean age of 61 years. Mean platelet volume (MPV) was similar between the diabetic patients and controls (9.2 fL for both). Following activation, PAC-1 binding and P-selectin expression were found comparable between the diabetic patients and controls (83 % versus 81 % and 76 % versus 74 %, respectively). Leukocyte-platelet aggregates (LPAs) were similar between the diabetic patients and controls (18 % versus 17 %, respectively). Neutrophil-platelet aggregates (NPAs) and monocyte-platelet aggregates (MPAs) were also found similar in the diabetic patients and controls. Elevated fasting plasma glucose was associated with increased LPAs rates. CONCLUSIONS: High risk type-2 diabetes mellitus patients, without prior ischemic events, have normal blood platelet functionality profiles.

Limited reproducibility of 24-h ambulatory blood pressure monitoring.

Results of 24-h ambulatory blood pressure monitoring (ABPM) including average blood pressure, variability, and nocturnal dipping are considered the gold standard for diagnosis and the best predictor of the future end organ damage in chronic hypertension. Here we report on the reproducibility of ABPM results for these three measures over a period of months. A total of 35 hypertensive patients (43% female, mean age 64 years), underwent two separate ABPM recordings within 14 weeks, with unchanged medical treatment and lifestyle in the interim. The day and night average blood pressure, dipping status of systolic pressure, and the standard deviation of systolic and diastolic blood pressure as a measure of variability were compared between the two recordings. Individual values for average systolic and diastolic pressures showed only a modest correlation between the two measurements (r = 0.56, r = 0.81, p < 0.01). Standard deviations of 24-h pressure were also positively but weakly correlated (r = 0.4, p < 0.001). The occurrence of dipping was reproducible in 71% of the patients. Average blood pressure, pressure variability, and dipping as assessed by ABPM are only moderately reproducible. Clinical decision-making based on single ABPM datasets should be made with caution, and repetition of ABPM seems justified in some cases.

[A rare neurologic syndrome due to a common medical condition].

We describe a patient with hypertension, diabetes mellitus, recurrent strokes, congestive heart failure, chronic atrial fibrillation and renal failure,who was hospitalized twice for chorea. A thorough work-up excluded all common causes for chorea in the elderly. The patient's HbA1c was > 17% and the brain computerized tomography revealed dense lesions in the basal ganglia compatible with Chorea Hyperglycemia Basal Ganglia syndrome. This syndrome includes a combination of chorea, hyperglycemia and dense lesions in the basal ganglia. The hemichorea in this syndrome is provoked by non-ketotic hyperglycemia and improves with insulin treatment. The radiographic picture also improves after there is control of glucose levels and clinical improvement.