Factors associated with delayed presentation at the emergency department in patients with acute ischemic stroke.

Background and aims: Pre-hospital delay is a crucial factor that determines the eligibility for intravenous thrombolysis in patients with acute ischemic stroke. We aimed to evaluate the time to presentation at the emergency department (ED) and the factors that affect this time. Patients and methods: We prospectively studied 682 patients who were admitted with acute ischemic stroke (43.3% men, age 79.9 ± 6.6 years). Results: The median time to presentation at the ED was 2.1 h (range 0.15 to 168 h); 68.8% of the patients arrived within 4.5 h and 56.5% arrived within 3 h from the onset of symptoms. Independent predictors of presentation within 4.5 h were the use of emergency medical services (EMS) for transportation to the hospital (OR 2.61, 95% CI 1.38-4.94, p = .003), family history of cardiovascular disease (CVD)(OR 4.0 0,95%CI 1.61-12.23, p = .006) and the absence of history of smoking (OR 2.49, 95% CI 1.13-5.42, p = .021). Independent predictors of presentation within 3 h were the use of EMS for transportation to the hospital (OR 6.24, 95% CI 2.52-16.63, p = .0001), family history of CVD (OR 3.07, 95% CI 1.14-9.43, p = .03), and a moderately severe stroke at admission (OR vs. minor stroke 0.38, 95% CI 0.16-0.87, p = .02). Conclusions: A considerable proportion of patients with acute ischemic stroke arrives at the ED after the 4.5-h threshold for performing intravenous thrombolysis. Non-smokers, patients with a family history of CVD, with moderately severe stroke and those who use the EMS are more likely to arrive on time.

Coxiella Endocarditis as the Cause of Recurrent Fever and Brain Abscess in a Patient with Complex Congenital Heart Disease: A Case Report and Literature Review.

INTRODUCTION: Blood culture-negative infective endocarditis (BCNIE) can present subtly and is associated with a diagnostic delay leading to increased morbidity and mortality. Case Report. We present the case of an 18-year-old male with a history of complex congenital heart disease and 3-year intermittent episodes of fever of unknown origin, who was referred to our hospital for upper and lower extremity focal seizures. Laboratory blood tests were normal, blood cultures were negative, and brain imaging revealed an abscess. Cardiology consultation was requested, and transthoracic echocardiography revealed an intracardiac vegetation. Empiric antibiotic treatment with sultamicillin, gentamycin, and meropenem was initiated. Serology testing was positive for Coxiella burnetii, and the diagnosis of BCNIE was established. The antibiotic course was changed to oral doxycycline for 36 months and led to resolution of IE, with no vegetation detected on TTE after 15 months. CONCLUSION: BCNIE is a life-threatening disease entity that can lead to severe complications, such as valve regurgitation, emboli, and death. Patients with congenital heart disease are particularly vulnerable to IE. Timely diagnosis and antibiotic management are of paramount importance in order to avoid the potentially fatal sequelae.

Impaired antioxidative activity of high-density lipoprotein is associated with more severe acute ischemic stroke.

BACKGROUND/AIMS: High-density lipoprotein (HDL) has important anti-atherogenic functions, including antioxidant effects. However, it is unclear whether the antioxidative activity of HDL is associated with the severity and outcome of acute ischemic stroke. We aimed to evaluate this association. METHODS: We prospectively studied 199 consecutive patients admitted with acute ischemic stroke and followed them up until discharge. We measured HDL antioxidant capacity, HDL-associated paraoxonase-1 (PON1) activity and HDL-associated myeloperoxidase (MPO) levels. Severe stroke was defined as National Institutes of Health Stroke Scale (NIHSS) at admission ≥5. Dependency was defined as modified Rankin scale at discharge between 2 and 5. RESULTS: Patients with severe stroke had lower HDL antioxidant capacity, higher MPO levels and higher MPO/PON1 ratio. Independent risk factors for severe stroke were female gender (RR 2.80, 95% CI 1.37-5.70, p = 0.005), glucose levels (RR 1.01, 95% CI 1.0-1.02, p < 0.01) and HDL antioxidant capacity (RR 1.03, 95% CI 1.01-1.06, p < 0.05). Patients who were dependent at discharge had lower HDL antioxidant capacity, higher MPO levels and higher MPO/PON1 ratio. Independent predictors of dependency at discharge were lack of lipid-lowering treatment (RR 6.86, 95% CI 1.83-25.67, p < 0.005) and NIHSS (RR 1.56, 95% CI 1.29-1.88, p < 0.0001). The HDL antioxidant capacity did not differ between patients who died during hospitalization and those who were discharged. The only independent predictor of in-hospital mortality was NIHSS (RR 1.16, 95% CI 1.06-1.27, p < 0.005). CONCLUSIONS: Impaired antioxidative activity of HDL is associated with more severe acute ischemic stroke and might also predict a worse functional outcome in these patients.

Non-Alcoholic Fatty Liver Disease in Patients with HIV Infection

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with HIV infection and appears to be more severe than in HIV-uninfected patients. Both metabolic (e.g., obesity and insulin resistance) and HIV-related factors (e.g., antiretroviral treatment and inflammation) play a role in the pathogenesis of NAFLD in this population. Accordingly, all patients with HIV infection should be evaluated for the presence of NAFLD. Ultrasound is the first-line diagnostic procedure, but non-alcoholic steatohepatitis has to be diagnosed with liver biopsy. However, non-invasive methods, including serological markers and transient elastography, might also be useful in this population. Lifestyle changes represent the cornerstone of treatment. Bariatric surgery, pioglitazone, and vitamin E can be considered in patients with significant fibrosis or at high risk for progression of NAFLD, including those with type 2 diabetes mellitus, metabolic syndrome, elevated transaminases, or pronounced necroinflammation. However, there are no studies that evaluated the safety of efficacy of diet, exercise, or pharmacotherapy in this population. Therefore, research is needed to identify safe and effective pharmacological treatments for NAFLD in patients with HIV infection.

Herpes Zoster and Diabetes Mellitus: A Review.

Accumulating evidence suggests that diabetes mellitus (DM) represents an important risk factor for both herpes zoster and post-herpetic neuralgia. Moreover, post-herpetic neuralgia appears to be more severe and persistent in diabetic patients. On the other hand, a novel vaccine against varicella-zoster virus (VZV) was recently introduced in clinical practice. Given the increased risk and severity of herpes zoster infection in patients with DM, this vaccine might be useful in this population. However, there are limited data regarding the efficacy and safety of vaccination against herpes zoster in the diabetic population. The aim of the present review is to discuss the incidence and consequences of herpes zoster infection in DM and to comment on the role of vaccination against VZV in these patients.

A Comparative Assessment of Cardiovascular Autonomic Reflex Testing and Cardiac 123I-Metaiodobenzylguanidine Imaging in Patients with Type 1 Diabetes Mellitus without Complications or Cardiovascular Risk Factors.

AIM: To compare the cardiovascular autonomic reflex tests (CARTs) with cardiac sympathetic innervation imaging with 123I-metaiodobenzylguanidine (MIBG) in patients with type 1 diabetes mellitus (T1DM). PATIENTS AND METHODS: Forty-nine patients (29 males, mean age 36 ± 10 years, mean T1DM duration 19 ± 6 years) without cardiovascular risk factors were prospectively enrolled. Participants were evaluated for autonomic dysfunction by assessing the mean circular resultant (MCR), Valsalva maneuver (Vals), postural index (PI), and orthostatic hypotension (OH). Within one month from the performance of these tests, patients underwent cardiac MIBG imaging and the ratio of the heart to upper mediastinum count density (H/M) at 4 hours postinjection was calculated (abnormal values, H/M < 1.80). RESULTS: Twenty-nine patients (59%) had abnormal CARTs, and 37 (76%) patients had an H/M_4 < 1.80 (p = 0.456). MCR, PI, Vals, and OH were abnormal in 29 (59%), 8 (16%), 5 (10%), and 11 (22%) patients, respectively. When using H/M_4 < 1.80 as the reference standard, a cutoff point of ≥2 abnormal CARTs had a sensitivity of 100% but a specificity of only 33% for determining CAN. CONCLUSIONS: CARTs are not closely associated with 123I-MIBG measurements, which can detect autonomic dysfunction more efficiently than the former. In comparison to semiquantitative cardiac MIBG assessment, the recommended threshold of ≥2 abnormal CARTs to define cardiovascular autonomic dysfunction is highly sensitive but of limited specificity and is independently determined by the duration of T1DM.

Left ventricular hypertrophy assessed by electrocardiogram is associated with more severe stroke and with higher in-hospital mortality in patients with acute ischemic stroke.

BACKGROUND AND AIMS: Left ventricular hypertrophy (LVH), assessed by electrocardiogram (ECG), is associated with increased risk for stroke. However, few studies that evaluated whether ECG-detected LVH predicts ischemic stroke severity and outcome. We aimed to evaluate these associations. METHODS: We prospectively studied 922 patients consecutively admitted with acute ischemic stroke (age 79.6 ±â€¯6.9 years). Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS≥5. LVH was evaluated with the Sokolow-Lyon index and the Cornell voltage-duration product criteria in an ECG obtained at admission. The outcome was assessed with dependency at discharge (modified Rankin scale 2-5) and in-hospital mortality. RESULTS: Independent predictors of severe stroke were age (relative risk (RR) per year 1.07, 95% confidence interval (CI) 1.03-1.11, p<0.001), female gender (RR 0.36, 95% CI 0.17-0.76, p<0.01), atrial fibrillation (RR 2.07, 95% CI 1.30-3.29, p<0.005), chronic kidney disease (RR 2.38, 95% CI 1.04-5.44, p<0.05), heart rate (RR per 1/min 1.02, 95% CI 1.01-1.04, p<0.005), glucose levels (RR 1.012, 95% CI 1.006-1.018, p<0.001), high-density lipoprotein cholesterol levels (RR 0.976, 95% CI 0.960-0.993, p<0.005) and LVH defined according to the Cornell voltage-duration product criteria (RR 2.08, 95% CI 1.12-3.86, p<0.05). Independent predictors of dependency at discharge were age (RR per year 1.08, 95% CI 1.03-1.13, p<0.001), past smoking (RR versus no smoking 0.42, 95% 0.19-0.89, p<0.05), history of ischemic stroke (RR 2.13, 95% CI 1.23-3.71, p<0.01) and NIHSS at admission (RR 1.48, 95% CI 1.35-1.63, p<0.001). Independent predictors of in-hospital mortality were glucose levels (RR 1.014, 95% CI 1.003-1.025, p<0.05), NIHSS at admission (RR 1.29, 95% CI 1.19-1.41, p<0.001) and LVH according to the Cornell voltage-duration product criteria (RR 4.95, 95% CI 1.09-22.37, p<0.05). CONCLUSIONS: LVH according to the Cornell voltage-duration product criteria appears to be associated with more severe stroke and with higher in-hospital mortality in patients with acute ischemic stroke.

Treatment with Mannitol is Associated with Increased Risk for In-Hospital Mortality in Patients with Acute Ischemic Stroke and Cerebral Edema.

BACKGROUND: Current guidelines state that osmotic therapy is reasonable in patients with clinical deterioration from cerebral infarction-related cerebral edema. However, there are limited data on the safety and efficacy of this therapy. We aimed to evaluate the effect of mannitol on the outcome of ischemic stroke-related cerebral edema. METHODS AND RESULTS: We prospectively studied 922 consecutive patients admitted with acute ischemic stroke. Patients who showed space-occupying brain edema with tissue shifts compressing the midline structures received mannitol. The outcome was assessed with dependency rates at discharge (modified Rankin Scale grade 2-5) and in-hospital mortality. Rates of dependency were higher in patients treated with mannitol (n = 86) than in those who were not (97.7 and 58.5%, respectively; p < 0.001). Independent predictors of dependency were age, history of ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) score at admission. Rates of mortality were higher in patients treated with mannitol than in those who were not (46.5 and 5.6%, respectively; p < 0.001). Independent predictors of in-hospital mortality were diastolic blood pressure [relative risk (RR) 1.05, 95% confidence interval (CI) 1.02-1.08, p < 0.001], NIHSS score at admission (RR 1.19, 95% CI 1.14-1.23, p < 0.001) and treatment with mannitol (RR 3.45, 95% CI 1.55-7.69, p < 0.005). CONCLUSIONS: Administration of mannitol to patients with ischemic stroke-related cerebral edema does not appear to affect the functional outcome and might increase mortality, independently of stroke severity.

Characteristics and management of 1093 patients with clinical diagnosis of familial hypercholesterolemia in Greece: Data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).

BACKGROUND AND AIMS: Although familial hypercholesterolemia (FH) is one of the most common genetic disorders, it remains largely underdiagnosed and undertreated. The Hellenic Atherosclerosis Society has established the Hellenic Familial Hypercholesterolemia (HELLAS-FH) Registry, part of the Familial Hypercholesterolemia Studies Collaboration (FHSC), to evaluate the characteristics and management of patients with FH in Greece. METHODS: Patients with diagnosed FH were recruited by a network of sites throughout Greece. The prevalence of cardiovascular disease (CVD) risk factors, as well as management of FH, was recorded. RESULTS: This interim analysis included 1093 patients (556 male; 950 adults). The median age of FH diagnosis was 42.2 years (interquartile range 27.2-53.0). A family history of CVD was present in 47.8%, while 21.1% of patients had a personal history of CVD. At diagnosis, low-density lipoprotein cholesterol (LDL-C) was 241 ±â€¯76 mg/dL in adults and 229 ±â€¯57 mg/dL in children. Overall, 63.1% of the patients were receiving hypolipidemic drug treatment, mainly statins, at inclusion in the registry. Mean LDL-C of patients receiving drug treatment was 154 ±â€¯76 mg/dL in adults and 136 ±â€¯47 mg/dL in children. The majority of treated patients (87.9%) did not achieve LDL-C targets. CONCLUSIONS: FH in Greece is characterized by a significant delay in diagnosis and a high prevalence of both family and personal history of established CVD. The vast majority of FH patients do not achieve LDL-C targets. Improved awareness and management of FH are definitely needed.

Effects of obesity on the outcome of pneumonia.

INTRODUCTION: Obesity is an important risk factor for both community-acquired pneumonia (CAP) and healthcare-associated pneumonia. In striking contrast, emerging data suggest that obesity is associated with more favorable outcome of pneumonia, a protective effect coined 'the obesity paradox'. Areas covered: The aim of the present review is to summarize the existing evidence on the outcome of pneumonia in obese patients and to discuss the mechanisms underpinning the association between obesity and pneumonia outcome. Several observational studies showed that obesity is associated with better outcome of CAP. In contrast, obesity represents a risk factor for adverse outcome in patients infected with pandemic influenza. Very limited data exist on the association between obesity and the outcome of healthcare-associated pneumonia. The pathophysiological mechanisms contributing to these paradoxical findings are unclear. Expert commentary: It is possible that residual confounding might partly explain the better outcome of pneumonia in obese patients. On the other hand, obesity might indeed offer a survival advantage in patients with acute diseases, including pneumonia. Clearly, larger and well-designed studies are needed to clarify the pathogenetic links between obesity and pneumonia outcome, which might represent novel therapeutic targets in the management of infectious diseases.

Obesity in patients with HIV infection: epidemiology, consequences and treatment options.

INTRODUCTION: Even though wasting used to characterize patients with HIV infection prior to the antiretroviral therapy (ART) era, obesity is becoming increasingly prevalent in this population. Areas covered: In the present review, we discuss the epidemiology, consequences and treatment options for obesity in patients with HIV infection. Expert commentary: Obesity exerts a multitude of detrimental cardiometabolic effects and appears to contribute to the increasing cardiovascular mortality of this population. However, there are very limited data on the optimal management of obesity in patients with HIV infection. Given the potential for interactions between antiobesity agents and ART that might compromise viral control, lifestyle changes should represent the cornerstone for the prevention and management of obesity in HIV infection.

Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and includes simple steatosis and nonalcoholic steatohepatitis (NASH). Since NASH progresses to cirrhosis more frequently and increases liver-related and cardiovascular disease risk substantially more than simple steatosis, there is a great need to differentiate the two entities. Liver biopsy is the gold standard for the diagnosis of NAFLD but its disadvantages, including the risk of complications and sampling bias, stress the need for developing alternative diagnostic methods. Accordingly, several non-invasive markers have been evaluated for the diagnosis of simple steatosis and NASH, including both serological indices and imaging methods. The present review summarizes the current knowledge on the role of these markers in the diagnosis of NAFLD. Current data suggest that ultrasound and the fibrosis-4 score are probably the most appealing methods for detecting steatosis and for distinguishing NASH from simple steatosis, respectively, because of their low cost and relatively high accuracy. However, currently available methods, both serologic and imaging, cannot obviate the need for liver biopsy for diagnosing NASH due to their substantial false positive and false negative rates. Therefore, the current role of these methods is probably limited in patients who are unwilling or have contraindications for undergoing biopsy.

Elevated diastolic but not systolic blood pressure increases mortality risk in hypertensive but not normotensive patients with acute ischemic stroke.

BACKGROUND: The relationship between blood pressure (BP) at admission for acute ischemic stroke and outcome is controversial. We aimed to assess whether only systolic BP (SBP), only diastolic BP (DBP), both or neither predict outcome and whether these associations differ between patients with and without a history of hypertension. METHODS: We prospectively studied all patients who were admitted with acute ischemic stroke (n = 415; 39.5% males, age 78.8 ± 6.6 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). The outcome was evaluated with dependency at discharge (modified Rankin scale between 2 and 5) and in-hospital mortality. RESULTS: In the total study population, independent predictors of dependency at discharge were age, history of prior ischemic stroke, and NIHSS score at admission. Independent predictors of in-hospital mortality were DBP at admission and NIHSS score at admission. In patients with a history of hypertension (n = 343), independent predictors of dependency at discharge were age and NIHSS score at admission whereas independent predictors of in-hospital mortality were DBP at admission and NIHSS score at admission. In patients without a history of hypertension (n = 72), the only independent predictor of dependency at discharge and in-hospital mortality was the NIHSS score at admission. CONCLUSIONS: Higher DBP at admission predict in-hospital mortality in patients with acute ischemic stroke whereas SBP in the acute phase is not associated with short-term outcome. The relationship between DBP at admission and outcome appears to be more prominent in hypertensive patients.