Admission Hydration Status and Ischemic Stroke Outcome-Experience from a National Registry of Hospitalized Stroke Patients.

Reduced intravascular volume upon ischemic stroke (IS) admission has been associated with in-hospital complications, disability, and reduced survival. We aimed to evaluate the association of the urea-to-creatinine ratio (UCR) with disability or death at discharge, length of stay, in-hospital complications, and mortality during the first year. Using a national registry, we identified hospitalized IS patients without renal failure. Disability or death at discharge, length of stay, in-hospital complications, and mortality during the first year were studied by UCR, and associations between UCR levels and each outcome were assessed adjusting for age, sex, stroke severity, comorbidities, use of statins, and use of diuretics. In total, 2212 patients were included. Levels (median (25-75%)) for the main study variables were: urea 5.16 (3.66-6.83) mmol/L; creatinine 80 (64-92) µmol/L; and UCR 65 (58-74). Levels of UCR were significantly higher in patients with disability or death at discharge (p < 0.0001), those with complications during hospitalization (p = 0.03), those with infection during hospitalization (p = 0.0003), and those dead at 1 year (p < 0.0001). Analysis by UCR quartile showed that rates of disability or death at discharge, infections, complications overall, and death at 1 year in patients with UCR in the 4th quartile were significantly higher than in others. Risk-factor-adjusted analysis by UCR quartiles demonstrated an inconsistent independent association between UCR and disability or death after ischemic stroke. A high 1-year mortality rate was observed in IS patients with elevated UCR, yet this finding was not statistically significant after controlling for risk factors. Our study shows inconsistent associations between hydration status and poor functional status at discharge, and no association with length of stay, in-hospital complications (infectious and overall), and 1-year mortality.

Hyperprolactinemia diagnosis in elderly men: a cohort of 28 patients over 65 years.

PURPOSE: To characterize a cohort of elderly men with prolactinomas and their response to treatment. METHODS: We have identified 28 elderly men diagnosed after the age of 65 with prolactinomas at seven different endocrine clinics in Israel. A retrospective electronic chart review identified a control group of 76 younger men with macroprolactinomas treated in one of the centers. RESULTS: Mean age at diagnosis was 71.3 ± 5.6 (range 65-86) years, and current age 76.6 ± 7.5 years. Initial complaints leading to diagnosis included sexual dysfunction in 17 males (61%), headaches in two patients (7%), and visual abnormalities in two (7%). Three men presented with osteoporosis. Ten patients (36%) were diagnosed incidentally following brain imaging for unrelated reasons. Seventeen patients (61%) had macroadenoma, while eleven (39%) presented with a microadenoma or no visible adenoma. Mean prolactin (PRL) at presentation was 1594 (median 382; range 50-18,329) ng/ml. Testosterone was low in 21 men. Patients were treated with cabergoline (max dose, 1.1 ± 0.5 mg/week), except for one given bromocriptine; none required pituitary surgery or radiotherapy. Treatment normalized PRL in 24 patients, and in three men PRL suppressed to <2 ULN. Fifteen men normalized testosterone, three improved without normalization, and in three the normal baseline level increased. After a mean follow-up of 5.3 years, 14/15 patients harboring a macroadenoma showed significant adenoma shrinkage. Most patients reported improvement of low libido/erectile dysfunction. In the control group 60 men (79%) achieved PRL normalization. CONCLUSIONS: Elderly men with prolactinomas are diagnosed incidentally in 36% of cases. Long-term medical therapy is successful, achieving biochemical remission, adenoma shrinkage, and clinical improvement in almost all patients.

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

OBJECTIVE: Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. METHODS: Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. RESULTS: The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. CONCLUSION: IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Pre admission treatment with Beta-blockers in hypertensive patients with acute stroke and 3-month outcome-Data from a national stroke registry.

The impact of beta-blockers (BB) treatment on stroke outcome is unclear. We used data from a prospective national stroke registry to assess the associations between use of BB and poor outcome 3 months after stroke. Using the National Acute Stroke Israeli (NASIS) registry, we identified 1126 patients with ischemic stroke and intracerebral hemorrhage with pre-stroke hypertension treatment, who were followed for 3-months. Functional outcome and mortality at 3-month were compared by use of BB, adjusting for demographics and clinical factors. Pre-stroke use of BB was reported by 615 (54.6%) patients. Users of BB showed higher rates of atrial fibrillation, heart disease, statin use, cancer, and severe stroke. Adjusted odds-ratios (ORs, 95% CI) for BB users compared with non-users 3 months after stroke were 0.86 (0.49-1.52) for mortality and 1.07 (0.76-1.50) for Barthel Index ≤60. In conclusion, treatment with BB is not associated with 3-month poor outcome in hypertensive patients.

Predictors of hypoglycemia in hospitalized patients with diabetes mellitus.

Hypoglycemia is common among hospitalized patients with diabetes mellitus (DM), and is associated with increased morbidity and mortality. Identify pre-admission risk factors associated with in-hospital hypoglycemia. Historical prospectively collected data of adult DM patients hospitalized to medical wards between 2011 and 2013. Hypoglycemia and serious hypoglycemia were defined as at least one blood glucose measurement ≤ 70 and < 54 mg/dl, respectively, during hospitalization. The primary outcome was in-hospital hypoglycemia. The cohort included 5301 patients (mean age 73 ± 13 years, 51% male), including 792 patients (15%) with hypoglycemia, among them 392 patients (7%) with serious hypoglycemia. Patients with hypoglycemia or serious hypoglycemia during hospitalization were older, compared to patients without hypoglycemia and more likely to have chronic renal failure and cerebrovascular disease. Malignancy and female gender were risk factors for hypoglycemia, but not for serious hypoglycemia, while congestive heart failure was associated with increased risk only for serious hypoglycemia. Diabetes mellitus' duration over 10 years was associated with an almost threefold increased risk for hypoglycemia, compared to DM duration less than a year. Insulin treatment and glycated hemoglobin > 9% were also more common in patients with hypoglycemia. Insulin treatment was associated with a fourfold increase in the risk for hypoglycemia among all glycated hemoglobin categories. Our results identified several risk factors for in-hospital hypoglycemia in patients with DM. These findings may lead to appropriate monitoring and early intervention to prevent hypoglycemia and to reduce morbidity and mortality associated with in-hospital hypoglycemia.

IGF-I levels reflect hypopituitarism severity in adults with pituitary dysfunction.

PURPOSE: To evaluate the utility of Insulin-like growth factor I (IGF-I) standard deviation score (SDS) as a surrogate marker of severity of hypopituitarism in adults with pituitary pathology. METHODS: We performed a retrospective data analysis, including 269 consecutive patients with pituitary disease attending a tertiary endocrine clinic in 1990-2015. The medical files were reviewed for the complete pituitary hormone profile, including IGF-I, and clinical data. Age-adjusted assay reference ranges of IGF-I were used to calculate IGF-I SDS for each patient. The main outcome measures were positive and negative predictive values of low and high IGF-I SDS, respectively, for the various pituitary hormone deficiencies. RESULTS: IGF-I SDS correlated negatively with the number of altered pituitary axes (p < 0.001). Gonadotropin was affected in 76.6 % of cases, followed by thyrotropin (58.4 %), corticotropin (49.1 %), and prolactin (22.7 %). Positive and negative predictive values yielded a clear trend for the probability of low/high IGF-I SDS for all affected pituitary axes. Rates of diabetes insipidus correlated with IGF-I SDS values both for the full study population, and specifically for patients with non-functioning pituitary adenomas. CONCLUSIONS: IGF-I SDS can be used to evaluate the somatotroph function, as a valid substitute to absolute IGF-I levels. Moreover, IGF-I SDS predicted the extent of hypopituitarism in adults with pituitary disease, and thus can serve as a marker of hypopituitarism severity.

Trends in admission blood pressure and stroke outcome in patients with acute stroke and transient ischemic attack in a National Acute Stroke registry.

OBJECTIVE: Elevated blood pressure (BP) is common during an acute stroke and is associated with unfavorable outcome. Management of hypertension has improved in recent years. We aimed to evaluate trends in admission BP levels in patients admitted with acute stroke and transient ischemic attack (TIA) over the past decade. METHODS: Data were based on the National Acute Stroke Israeli Registry. The study population comprised 6177 patients, aged at least 18 years admitted for acute stroke (4382 ischemic stroke and 476 intracerebral hemorrhage) or TIA (1227) and had data on BP levels on admission. We studied temporal trends in admission BP and preadmission antihypertensive therapy from 2004 to 2010. RESULTS: Admission SBP (mean ±â€ŠSD) in patients with acute stroke decreased from 161 ±â€Š29 mmHg in 2004 to 153 ±â€Š28 mmHg in 2010 (P < 0.001). Similar trends were observed for patients with TIA. The use of three or more antihypertensive agents before stroke onset increased from 16.9% in 2004 to 20.0% in 2010 (P = 0.02). In patients with acute stroke, higher admission SBP was associated with increased stroke severity (P < 0.001). Rate of disability at discharge or in-hospital death decreased from 71.3% in 2004 to 64.8% in 2010 (P < 0.0001). Admission SBP was associated with disability at discharge or in-hospital death with an adjusted odds ratio (95% confidence interval) of 1.06 (1.04-1.08) per 10 mmHg change in SBP. CONCLUSION: Admission SBP in patients with acute stroke and TIA decreased from 2004 to 2010 and may have contributed to the improved outcome in these patients.

Association of age and admission mean arterial blood pressure in patients with stroke-data from a national stroke registry.

Elevated blood pressure (BP) upon admission is common in patients with ischemic stroke (IS) and intracerebral hemorrhage (ICH). Older patients have a higher prevalence of stroke, but data on admission mean arterial pressure (MAP) patterns in older patients with stroke are scarce. All 6060 patients with IS (72%), ICH (8%) and transient ischemic attack (TIA; 20%) with data on BP and hypertension status on admission in the National Acute Stroke Israeli Registry were included. Admission MAP in the emergency department was studied by age group (<60, 60-74 and ⩾75 years) and stroke type. Linear regression models for admission MAP were produced, including age group, gender, hypertension status and stroke severity as covariates. Interactions between hypertension and age were assessed. Lower MAP (s.d.) was associated with older ages in hypertensive patients (113 (18) mm Hg for age <60 years, 109 (17) for age 60-74 years and 108 (19) for age ⩾75 years, P<0.0001) but not in non-hypertensive IS patients. Among patients with ICH and TIA, a significant negative association of MAP with age was observed for hypertensive patients (P=0.015 and P=0.023, respectively), whereas a significant positive association with age was found in non-hypertensive patients (P=0.023 and P=0.038, respectively). In adjusted regression models, MAP was significantly associated with hypertension in IS, ICH and TIA patients. The interaction between hypertension and age was significantly associated with MAP in IS and ICH patients. In hypertensive patients, the average admission MAP was lower in persons at older ages.

Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism.

CONTEXT: Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. OBJECTIVE: To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. DESIGN: A historical prospective cohort of males with HH. PATIENTS: Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease. RESULTS: Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3%) men pituitary imaging was normal. Microadenoma was found in 8 (10.7%), empty sella and thickened pituitary stalk in one patient (1.3%) each. In other four patients (5.3%) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies. CONCLUSIONS: This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.

Neutral endopeptidase inhibitor versus angiotensin converting enzyme inhibitor in a rat model of the metabolic syndrome.

The antihypertensive treatment in patients with metabolic syndrome is unclear. We therefore used a rat model of the metabolic syndrome and compared the effects of enalapril, an angiotensin-converting-enzyme inhibitor, with candoxatril, a neutral endopeptidase inhibitor that inhibits degradation of atrial natriuretic peptide and, in addition to lowering blood pressure, exerts metabolically beneficial activity. Ten male Sprague Dawley rats were fed regular rat chow for 5 weeks. Fifty male Sprague Dawley rats were fed a high-fructose diet for 3 weeks, followed by addition of enalapril, 10 mg/Kg/d, or candoxatril, 25, 50, or 100 mg/Kg/d, for 2 weeks. Systolic blood pressure, plasma triglyceride level, and insulin level were measured at baseline and after 3 weeks and 5 weeks. Three weeks of a high-fructose diet led to a significant increase in all metabolic parameters. Candoxatril and enalapril lowered systolic blood pressure significantly (candoxatril -10 ± 1 to -22 ± 1 mm Hg and enalapril -27 ± 2 mm Hg). High-dose candoxatril and enalapril significantly decreased plasma triglyceride levels (by 17.8% and 32.8%, respectively), but only high-dose candoxatril decreased plasma insulin levels significantly (by 25.3%). High-dose candoxatril is a metabolically favorable option for lowering blood pressure in a rat model of metabolic syndrome.

Salivary oxidative stress in children during acute asthmatic attack and during remission.

BACKGROUND: Patients with asthma generate an increased amount of reactive oxygen species from peripheral blood cells, which may contribute to its pathogenesis. Saliva analysis is non-invasive and friendly to children. We undertook this study to analyze the salivary oxidative profile and composition in children with asthma during attack and remission, and to compare them with the levels of salivary antioxidants of healthy control children. METHODS: School age (range 6-18 years) children referred to the emergency room for acute asthma were included. Clinical score was assessed, spirometry performed, and saliva samples were collected and analyzed. All measurements were repeated during remission of asthma attack (2-4 weeks after attack). Salivary analysis was performed blindly during asthma attack and the results were compared to those obtained during remission, and to those of the control group. RESULTS: Statistically significant decreases in levels of salivary peroxidase enzyme activity were observed in asthmatic children during attack compared with healthy controls, with partial recovery during remission of attack. Similarly decreased levels of calcium concentrations were observed in asthmatic children, accompanied by increased phosphate levels. CONCLUSIONS: Children with acute asthma attacks exhibit a decrease in the activity of the most important salivary antioxidant enzyme-peroxidase, which is accompanied by other salivary composition alterations. Hence, acute asthma is manifested by salivary changes. This implies systemic oxidative stress in asthma, which may be reflected in salivary analysis.