A Neuronavigation System Using a Mobile Augmented Reality Solution.

BACKGROUND: Image-guided surgery has shown great utility in neurosurgery, especially in allowing for more accurate surgical planning and navigation. The current gold standard for image-guided neurosurgery is neuronavigation, which provides millimetric accuracy on such tasks. However, these approaches often require a complicated setup and have high cost, hindering their potential in low- and middle-income countries. The aim of this study was to develop and evaluate the performance of a mobile-based augmented reality neuronavigation solution under different conditions in a preclinical environment. METHODS: The application was developed using the Swift programming language and was tested on a replica of a human scalp under variable lighting, with different numbers of registration points and target point position conditions. For each condition, reference points were input into the application, and the target points were computed for 10 iterations. The mean registration error and target error were used to assess the performance of the application. RESULTS: In the best-case scenario, the proposed solution had a mean target error of 2.6 ± 1.6 mm. CONCLUSIONS: Our approach provides a viable, low-cost, easy-to-use, portable method for locating points on the scalp surface with an accuracy of 2.6 ± 1.6 mm in the best-case scenario.

Cerebral vasoreactivity, a surrogate marker of cerebrovascular disease, is not impaired in subjects with lifetime, untreated, congenital isolated GH deficiency.

OBJECTIVES: Cerebrovascular disease (CeVD) is a major cause of death and disability. The role of the GH/IGF-I axis on CeVD risk is controversial. Patients with GH deficiency (GHD) in the setting of hypopituitarism often exhibit CeVD predisposing factors, like low nitric oxide generation, endothelial dysfunction, increased visceral fat mass, increased levels of LDL cholesterol, and increased intima-media thickness, a surrogate marker of atherosclerosis. However, several confounders such as the primary hypothalamic-pituitary lesion, hormonal replacement therapies, consequences of surgery and radiotherapy, may influence this relationship. Therefore, we decided to assess cerebral vasoreactivity, a surrogate marker of CeVD, in adult subjects with untreated isolated GHD (IGHD) due to the same homozygous null mutation in the GHRH receptor gene. METHODS: A cross-sectional study was carried out in 25 adult IGHD subjects and 25 age- and gender-matched controls. Interview, physical examination, laboratory data, intima-media thickness measurement, and transcranial Doppler were performed. The intracranial hemodynamics (mean flow velocity, pulsatility and resistance indexes) were measured, and the response to the vasodilatory stimulus by breath-holding maneuver (breath-holding index) was calculated. RESULTS: IGHD and control groups were similar in Framingham risk score and intima-media thickness. Similarly, there was no difference in mean flow velocity, pulsatility, resistance, and breath-holding index. CONCLUSIONS: Lifetime, untreated IGHD does not cause impaired cerebral vasoreactivity.

Brazilian adult individuals with untreated isolated GH deficiency do not have accelerated subclinical atherosclerosis.

GH and its principal mediator IGF1 have important effects on metabolic and cardiovascular (CV) status. While acquired GH deficiency (GHD) is often associated with increased CV risk, the consequences of congenital GHD are not known. We have described a large group of patients with isolated GHD (IGHD) due to a homozygous mutation (c.57+1G>A) in the GH releasing hormone receptor gene, and shown that adult GH-naïve individuals have no evidence of clinically evident premature atherosclerosis. To test whether subclinical atherosclerosis is anticipated in untreated IGHD, we performed a cross-sectional study of 25 IGHD and 27 adult controls matched for age and gender. A comprehensive clinical and biochemical panel and coronary artery calcium scores were evaluated by multi-detector tomography. Height, weight, IGF1, homeostasis model assessment of insulin resistance, creatinine and creatininekinase were lower in the IGHD group. Median and interquartile range of calcium scores distribution was similar in the two groups: IGHD 0(0) and control 0(4.9). The vast majority of the calcium scores (20 of 25 IGHD (80%) and 18 of 27 controls (66.6%)) were equal to zero (difference not significant). There was no difference in the calcium scores classification. None of IGHD subjects had minimal calcification, which were present in four controls. Three IGHD and four controls had mild calcification. There were two IGHD individuals with moderate calcification and one control with severe calcification. Our study provides evidence that subjects with congenital isolated lifetime and untreated severe IGHD do not have accelerated subclinical coronary atherosclerosis.

Arrest of atherosclerosis progression after interruption of GH replacement in adults with congenital isolated GH deficiency.

OBJECTIVE: GH replacement therapy (GHRT) in adult-onset GH deficiency (AOGHD) reduces carotid intima-media thickness (IMT) and increases myocardial mass, with improvement of systolic and diastolic function. These observations have reinforced the use of GHRT on AOGHD. Conversely, we have previously reported that in adults with lifetime congenital and severe isolated GH deficiency (IGHD) due to a mutation in GHRH receptor gene (GHRHR), a 6-month treatment with depot GH increased carotid IMT, caused the development of atherosclerotic plaques, and an increase in left ventricular mass index (LVMI), posterior wall, and septal thickness and ejection fraction. Such effects persisted 12 months after treatment (12-month washout - 12 mo). METHODS: We have studied the cardiovascular status (by echocardiography and carotid ultrasonography) of these subjects 60 months after completion of therapy (60-month washout - 60 mo). RESULTS: Carotid IMT reduced significantly from 12 to 60 mo, returning to baseline (pre-therapy) value. The number of individuals with plaques was similar at 12 and 60 mo, remaining higher than pre-therapy. LVMI, relative posterior wall thickness, and septum thickness did not change between 12 and 60 mo, but absolute posterior wall increased from 12 to 60 mo. Systolic function, evaluated by ejection fraction and shortening fraction, was reduced at 60 mo in comparison with 12 mo returning to baseline levels. The E/A wave ratio (expression of diastolic function) decreased at 60 mo compared with both 12 mo and baseline. CONCLUSIONS: In adults with lifetime congenital IGHD, the increase in carotid IMT elicited by GHRT was transitory and returned to baseline 5 years after therapy discontinuation. Despite this, the number of subjects with plaques remained stable at 60 mo and higher than at baseline.

Suspeita de Apneia Obstrutiva do Sono definida pelo Questionário de Berlim prediz eventos em pacientes com Síndrome Coronariana Aguda / Suspicion of Obstructive Sleep Apnea by Berlin Questionnaire predicts events in patients with Acute Coronary Syndrome / Sospecha de apnea obstructiva del sueño definida por el cuestionario de Berlín predice eventos en pacientes con síndrome coronario agudo

FUNDAMENTO: De um ponto de vista mecanístico, a apneia obstrutiva do sono (SAOS) pode causar distúrbios extras à homeostase cardiovascular na presença de síndrome coronariana aguda (SCA). OBJETIVO: Investigar se um diagnóstico clínico padronizado de SAOS, em pacientes com SCA, prediz o risco de eventos cardiovasculares durante hospitalização. MÉTODOS: Em um estudo de coorte prospectivo, um grupo de 200 pacientes com diagnóstico de SCA estabelecido entre Setembro de 2005 e Novembro de 2007, foram estratificados pelo Questionário de Berlim (QB) para o risco de SAOS (alto ou baixo risco). Foi testado se o subgrupo de alto risco para SAOS apresenta maior tendência à eventos cardiovasculares. O endpoint primário avaliado foi um desfecho composto de morte cardiovascular, eventos cardíacos isquêmicos recorrentes, edema pulmonar agudo e acidente vascular cerebral durante a hospitalização. RESULTADOS: Noventa e quatro (47 por cento) dos pacientes identificados pelo QB apresentavam suspeita de SAOS. Alto risco para SAOS estava associado com uma mortalidade mais elevada, embora sem diferença estatística (4,25 por cento vs 0,94 por cento; p=0,189), mas com uma estatisticamente significante maior incidência de desfecho composto de eventos cardiovasculares (18,08 por cento vs 6,6 por cento; p=0,016). No modelo de regressão logística, os preditores multivariados de desfecho composto de eventos cardiovasculares foram idade (OR = 1,048; IC95 por cento: 1,008 a 1,090; p=0,019), fração de ejeção do VE (OR = 0,954; IC95 por cento: 0,920 a 0,989; p=0,010), e risco mais elevado de SAOS (OR = 3,657; IC95 por cento: 1,216 a 10,996; p=0,021). CONCLUSÃO: O uso de um questionário simples e validado (QB) para identificar pacientes com risco mais elevado de SAOS pode ajudar a prever o desfecho cardiovascular durante a hospitalização. Além disso, nossos dados sugerem que SAOS é muito comum em pacientes com SCA.

BACKGROUND: From a mechanistic standpoint, obstructive sleep apnea (OSA) may further disturb cardiovascular homeostasis in the setting of acute coronary syndrome (ACS). OBJECTIVE: We sought to investigate if a standardized clinical diagnosis of OSA, in acute coronary syndrome patients, predicts the risk of cardiovascular events during hospitalization. METHODS: In a prospective cohort study, a group of 200 patients diagnosed with ACS between September 2005 and November 2007 were stratified by the Berlin Questionnaire (BQ) regarding the risk for OSA (high or low risk). We tested if the subgroup of high risk for OSA was prone to a higher frequency of cardiovascular events. The primary endpoint evaluated was a composite outcome of cardiovascular death, recurrent cardiac ischemic events, acute pulmonary edema and stroke during hospitalization. RESULTS: Ninety four (47 percent) patients assessed by the BQ were likely to have OSA. High risk for OSA was associated with a non-significant higher mortality (4.25 percent vs 0.94 percent; p=0.189), but a significant higher incidence of composite cardiovascular events (18.08 percent vs 6.6 percent; p=0.016). In the logistic regression model, multivariate predictors of composite cardiovascular events were age (OR= 1.048; 95 percent CI 1.008 to 1.090; p=0.019), left ventricular ejection fraction (OR= 0.954; 95 percent CI 0.920 to 0.989; p=0.010), and higher risk for OSA (OR= 3.657; 95 percent CI 1.216 to 10.996; p=0.021). CONCLUSION: The use of a simple and validated questionnaire (BQ) to identify patients with higher risk for OSA may help in the prediction of cardiovascular outcome during hospitalization. Moreover, our data suggests that OSA is very common in patients with ACS.

FUNDAMENTO: Desde un punto de vista mecanístico, la apnea obstructiva del sueño (SAOS) puede ocasionar disturbios extras a la homeostasis cardiovascular en la presencia del síndrome coronario aguda (SCA) OBJETIVO: Investigar si un diagnóstico clínico estandarizado de SAOS, en pacientes con SCA, predice el riesgo de eventos cardiovasculares durante la hospitalización. MÉTODOS: En un estudio de cohorte prospectivo, un grupo de 200 pacientes con diagnóstico de SCA elecido entre Septiembre de 2005 y Noviembre de 2007, fueron estratificados por el Cuestionario de Berlín (CB) para el riesgo de SAOS (alto o bajo riesgo). Se probó si el subgrupo de alto riesgo para SAOS presenta mayor tendencia a eventos cardiovasculares. El endpoint primario evaluado fue un desenlace conformado por muerte cardiovascular, eventos cardíacos isquémicos recurrentes, edema pulmonar agudo y accidente vascular cerebral durante la hospitalización. RESULTADOS: Noventa y cuatro (47 por ciento) de los pacientes identificados por el CB presentaban sospecha de SAOS. Alto riesgo para SAOS estaba asociado con una mortalidad más elevada, aunque sin diferencia estadística (4,25 por ciento vs 0,94 por ciento; p=0,189), pero con una estadísticamente significativa mayor incidencia de desenlace conformada por eventos cardiovasculares (18,08 por ciento vs 6,6 por ciento; p=0,016). En el modelo de regresión logística, los predictores multivariados de desenlace conformado por eventos cardiovasculares fueron edad (OR= 1,048; IC95 por ciento: 1,008 a 1,090; p=0,019), fracción de eyección del VI (OR= 0,954; IC95 por ciento: 0,920 a 0,989; p=0,010), y riesgo más elevado de SAOS (OR= 3,657; IC95 por ciento: 1,216 a 10,996; p=0,021). CONCLUSIÓN: El uso de un cuestionario sencillo y validado (CB) para identificar a pacientes con riesgo más elevado de SAOS puede ayudar a prever el desenlace cardiovascular durante la hospitalización. Además de ello, nuestros datos sugieren que SAOS es mucho común en pacientes con SCA.

Suspicion of obstructive sleep apnea by Berlin Questionnaire predicts events in patients with acute coronary syndrome.

BACKGROUND: From a mechanistic standpoint, obstructive sleep apnea (OSA) may further disturb cardiovascular homeostasis in the setting of acute coronary syndrome (ACS). OBJECTIVE: We sought to investigate if a standardized clinical diagnosis of OSA, in acute coronary syndrome patients, predicts the risk of cardiovascular events during hospitalization. METHODS: In a prospective cohort study, a group of 200 patients diagnosed with ACS between September 2005 and November 2007 were stratified by the Berlin Questionnaire (BQ) regarding the risk for OSA (high or low risk). We tested if the subgroup of high risk for OSA was prone to a higher frequency of cardiovascular events. The primary endpoint evaluated was a composite outcome of cardiovascular death, recurrent cardiac ischemic events, acute pulmonary edema and stroke during hospitalization. RESULTS: Ninety four (47%) patients assessed by the BQ were likely to have OSA. High risk for OSA was associated with a non-significant higher mortality (4.25% vs 0.94%; p=0.189), but a significant higher incidence of composite cardiovascular events (18.08% vs 6.6%; p=0.016). In the logistic regression model, multivariate predictors of composite cardiovascular events were age (OR= 1.048; 95% CI 1.008 to 1.090; p=0.019), left ventricular ejection fraction (OR= 0.954; 95% CI 0.920 to 0.989; p=0.010), and higher risk for OSA (OR= 3.657; 95% CI 1.216 to 10.996; p=0.021). CONCLUSION: The use of a simple and validated questionnaire (BQ) to identify patients with higher risk for OSA may help in the prediction of cardiovascular outcome during hospitalization. Moreover, our data suggests that OSA is very common in patients with ACS.

Prognostic value of exercise echocardiography in diabetic patients.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death in diabetic patients. Although exercise echocardiography (EE) is established as a useful method for diagnosis and stratification of risk for CAD in the general population, there are few studies on its value as a prognostic tool in diabetic patients. The purpose of this investigation was to evaluate the value of EE in predicting cardiac events in diabetics. METHODS: 193 diabetic patients, 97 males, 59.8 +/- 9.3 yrs (mean +/- SD) were submitted to EE between 2001 and 2006 and followed from 7 to 65 months with median of 29 months by phone calls and personal interviews with patients and their primary physician, and reviewing medical records and death certificates. The end points were cardiac events, defined as non-fatal myocardial infarction, late myocardial revascularization and cardiac death. Sudden death without another explanation was considered cardiac death. Survival free of end points was estimated by the Kaplan-Meier method. RESULTS: Twenty-six cardiac events were registered in 24 individuals during the follow-up. The rates of cardiac events were 20.6 and 7% in patients with positive and negative EE, respectively (p < 0.001). Predictors of cardiac events included sedentary lifestyle, with RR of 2.57 95%CI [1.09 to 6.02] (P = 0.03) and positive EE, with RR 3.63, 95%CI [1.44 to 9.16] (P = 0.01). Patients with positive EE presented higher rates of cardiac events at 12 months (6.8% vs. 2.2%), p = 0.004. CONCLUSION: EE is a useful method to predict cardiac events in diabetic patients with suspected or known CAD.

Chronotropic incompetence and a higher frequency of myocardial ischemia in exercise echocardiography.

BACKGROUND: Exercise echocardiography (EE) is an established method to diagnose coronary artery disease (CAD). Chronotropic incompetence (CI) during the EE may be a marker of myocardial ischemia. The purpose of this investigation was to evaluate the additive value of CI during EE in CAD diagnosis. METHODS: Between 2000 and 2006, 4042 patients (1900 men with a mean age of 56 +/- 11 years) were evaluated by EE. Based on the heart rate (HR) reached during the exercise test, the subjects were divided into two groups: G1 group - 490 patients who failed to achieve 85% of the maximal age-predicted HR, and G2 group - 3552 patients who were able to achieve 85% of the maximal age-predicted HR. Clinical characteristics, left ventricular wall motion abnormalities - wall motion score index (WMSI) - and coronary angiography (CA) were the parameters compared between the two groups. RESULTS: The left ventricular wall motion abnormalities were more frequent in G1 group than in G2 group (54% versus 26%; P < 0.00001). WMSI was higher in G1 group than in G2 group, both at rest (1.06 +/- 0.17 versus 1.02 +/- 0.09; P < 0.0001) and after exercise (1.12 +/- 0.23 versus 1.04 +/- 0.21; P < 0.0001). In G1 group, 82% of the patients with positive EE for myocardial ischemia presented obstructive coronary, compared to 71% (P = 0.03) in G2 group. CONCLUSION: CI is associated with a higher frequency of myocardial ischemia during EE, reinforcing the concept that CI is a marker of the severity of myocardial ischemia.

Congenital growth hormone (GH) deficiency and atherosclerosis: effects of GH replacement in GH-naive adults.

BACKGROUND: GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein. METHODS: We have studied the effects of 6-month GH replacement therapy in 20 adult members of a large Brazilian kindred with lifelong severe and isolated GHD due to a homozygous mutation in GHRH receptor gene (46 +/- 14.5 yr; 122 +/- 7.7 cm; 36.7 +/- 5.4 kg; 10 men). Subjects were studied at baseline, after 6-month bimonthly depot GH injections (Nutropin Depot; Genentech, Inc., South San Francisco, CA) [post GH (pGH)], and after 6- and 12-month washout. RESULTS: Despite modest trough serum IGF-I increase, GH replacement therapy caused a decrease in skinfolds and in waist-hip ratio, with a rebound increase at 12 months. Total and low-density lipoprotein cholesterol were reduced pGH and returned to baseline at 6 months. High-density lipoprotein cholesterol increased pGH, but at 12 months was lower than baseline. A progressive increase in left ventricular mass index, posterior wall, and septum thickness occurred from pGH to 12 months, and of carotid intima-media thickness, from 6 to 12 months. Individuals were 6, 16, and 52 times more likely to have an atherosclerotic carotid plaque at pGH, 6 and 12 months, respectively, when compared with baseline. CONCLUSION: In patients with lifetime isolated GHD, 6-month treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in intima-media thickness and in the number of atherosclerotic carotid plaques.

Heterozygosity for a mutation in the growth hormone-releasing hormone receptor gene does not influence adult stature, but affects body composition.

CONTEXT: Biallelic mutations in the GHRH receptor (GHRHR) gene (GHRHR) are a frequent cause of isolated GH deficiency (IGHD). Although heterozygous carriers of these mutations appear normal, we hypothesized that heterozygosity for a GHRHR mutation might be associated with a subclinical phenotype. METHODS: We studied members of a large Brazilian kindred with IGHD (Itabaianinha cohort) caused by a homozygous null GHRHR mutation. We compared 76 adult subjects (age, 25-75 yr) heterozygous for the mutation (WT/MT) with 77 sex-matched controls from the same population who are homozygous for the wild-type GHRHR allele (WT/WT). RESULTS: We found no difference in adult height and sd score for serum IGF-I between the two groups. Body weight, body mass index, skin folds, waist and hip circumferences, and lean mass were all reduced in WT/MT subjects. Percentage fat mass and waist/hip ratio were similar in the two groups. Fasting insulin and homeostasis model assessment of insulin resistance were lower in WT/MT. The other biochemical parameters [total and fractionated cholesterol, triglycerides, lipoprotein (a), and C-reactive protein] were not different between the two groups. CONCLUSIONS: Heterozygosity for a null GHRHR mutation is not associated with reduction in adult stature or in serum IGF-I but is associated with changes in body composition and possibly an increase in insulin sensitivity. These effects do not seem to be modulated by changes in circulating IGF-I.