Ocular Pulse Amplitude and Doppler Waveform Analysis in Glaucoma Patients

PURPOSE: To determine the correlation between ocular blood flow velocities and ocular pulse amplitude (OPA) in glaucoma patients using colour Doppler imaging (CDI) waveform analysis. METHOD: A prospective, observer-masked, case-control study was performed. OPA and blood flow variables from central retinal artery and vein (CRA, CRV), nasal and temporal short posterior ciliary arteries (NPCA, TPCA) and ophthalmic artery (OA) were obtained through dynamic contour tonometry and CDI, respectively. Univariate and multiple regression analyses were performed to explore the correlations between OPA and retrobulbar CDI waveform and systemic cardiovascular parameters (blood pressure, blood pressure amplitude, mean ocular perfusion pressure and peripheral pulse). RESULTS: One hundred and ninety-two patients were included [healthy controls: 55; primary open-angle glaucoma (POAG): 74; normal-tension glaucoma (NTG): 63]. OPA was statistically different between groups (Healthy: 3.17 ± 1.2 mmHg; NTG: 2.58 ± 1.2 mmHg; POAG: 2.60 ± 1.1 mmHg; p < 0.01), but not between the glaucoma groups (p = 0.60). Multiple regression models to explain OPA variance were made for each cohort (healthy: p < 0.001, r = 0.605; NTG: p = 0.003, r = 0.372; POAG: p < 0.001, r = 0.412). OPA was independently associated with retrobulbar CDI parameters in the healthy subjects and POAG patients (healthy CRV resistance index: β = 3.37, CI: 0.16-6.59; healthy NPCA mean systolic/diastolic velocity ratio: β = 1.34, CI: 0.52-2.15; POAG TPCA mean systolic velocity: β = 0.14, CI 0.05-0.23). OPA in the NTG group was associated with diastolic blood pressure and pulse rate (β = -0.04, CI: -0.06 to -0.01; β = -0.04, CI: -0.06 to -0.001, respectively). CONCLUSIONS: Vascular-related models provide a better explanation to OPA variance in healthy individuals than in glaucoma patients. The variables that influence OPA seem to be different in healthy, POAG and NTG patients.

Optimal Cut-Off Value for Homeostasis Model Assessment (HOMA) Index of Insulin-Resistance in a Population of Patients Admitted Electively in a Portuguese Cardiology Ward

INTRODUCTION: Insulin resistance is the pathophysiological key to explain metabolic syndrome. Although clearly useful, the Homeostasis Model Assessment index (an insulin resistance measurement) hasn't been systematically applied in clinical practice. One of the main reasons is the discrepancy in cut-off values reported in different populations. We sought to evaluate in a Portuguese population the ideal cut-off for Homeostasis Model Assessment index and assess its relationship with metabolic syndrome. MATERIAL AND METHODS: We selected a cohort of individuals admitted electively in a Cardiology ward with a BMI < 25 Kg/m2 and no abnormalities in glucose metabolism (fasting plasma glucose < 100 mg/dL and no diabetes). The 90th percentile of the Homeostasis Model Assessment index distribution was used to obtain the ideal cut-off for insulin resistance. We also selected a validation cohort of 300 individuals (no exclusion criteria applied). RESULTS: From 7 000 individuals, and after the exclusion criteria, there were left 1 784 individuals. The 90th percentile for Homeostasis Model Assessment index was 2.33. In the validation cohort, applying that cut-off, we have 49.3% of individuals with insulin resistance. However, only 69.9% of the metabolic syndrome patients had insulin resistance according to that cut-off. By ROC curve analysis, the ideal cut-off for metabolic syndrome is 2.41. Homeostasis Model Assessment index correlated with BMI (r = 0.371, p < 0.001) and is an independent predictor of the presence of metabolic syndrome (OR 19.4, 95% CI 6.6 - 57.2, p < 0.001). DISCUSSION: Our study showed that in a Portuguese population of patients admitted electively in a Cardiology ward, 2.33 is the Homeostasis Model Assessment index cut-off for insulin resistance and 2.41 for metabolic syndrome. CONCLUSION: Homeostasis Model Assessment index is directly correlated with BMI and is an independent predictor of metabolic syndrome.

Invasive Assessment of the Coronary Microcirculation Using the Index of Microcirculatory Resistance: Description and Validation of an Animal Model

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-μm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.

Disturbed Correlation Between Arterial Resistance and Pulsatility in Glaucoma Patients

PURPOSE: (i) To investigate whether pulsatility index (PI) and mean flow velocities (MFV) are altered in glaucoma patients. (ii) To evaluate the significance of PI in retrobulbar autoregulation capacity. METHODS: Patients with primary open-angle glaucoma (POAG; n = 49), normal tension glaucoma (NTG; n = 62) and healthy controls (n = 48) underwent colour Doppler imaging measurements of the retrobulbar vasculature. Kruskal-Wallis test was used to compare variables between the three diagnostic groups. Restricted cubic splines were used to determine nonlinearities between the resistive index (RI) and PI correlations. RESULTS: Mean flow velocities (MFV) were lower in both short posterior ciliary arteries (SCPA) and central retinal arteries (CRA) from the two glaucoma groups (p < 0.04 versus healthy controls). No differences were detected in RI or PI in any arteries of the three diagnostic groups (p > 0.08). In healthy individuals, correlations between RI and PI were linear in all arteries. In both POAG and NTG patients, CRA presented a nonlinear curve with a cutpoint at RI 0.77 (p < 0.001) and 0.61 (p = 0.03), respectively, above which the slope increased nearly five- and tenfold (POAG: 1.96 to 10.06; NTG: -0.46-4.06), respectively. A nonlinear correlation in the ophthalmic artery was only observed in NTG patients, with a cutpoint at RI 0.82 (p < 0.001), above which the slope increased from 3.47 to 14.03. CONCLUSIONS: Glaucoma patients do not present the linear relationships between RI and PI observed in healthy individuals. Their nonlinear relations may be indicative of an altered autoregulation and suggest a possible threshold RI could be determined above which autoregulatory disturbances become more relevant.

N170 Asymmetry as an Index of Inferior Occipital Dysfunction in Patients With Symptomatic Occipital Lobe Epilepsy

Objective: Localizing epileptic foci in posterior brain epilepsy remains a difficult exercise in surgery for epilepsy evaluation. Neither clinical manifestations, neurological, EEG nor neuropsychological evaluations provide strong information about the area of onset, and fast spread of paroxysms often produces mixed features of occipital, temporal and parietal symptoms. We investigated the usefulness of the N170 event-related potential to map epileptic activity in these patients. Methods: A group of seven patients with symptomatic posterior cortex epilepsy were submitted to a high-resolution EEG (78 electrodes), with recordings of interictal spikes and face-evoked N170. Generators of spikes and N170 were localized by source analysis. Range of normal N170 asymmetry was determined in 30 healthy volunteers. Results: In 3 out of 7 patients the N170 inter-hemispheric asymmetry was outside control values. Those were the patients whose spike sources were nearest (within 3 cm) to the fusiform gyrus, while foci further away did not affect the N170 ratio. Conclusions: N170 event-related potential provides useful information about focal cortical dysfunction produced by epileptic foci located in the close neighborhood of the fusiform gyrus, but are unaffected by foci further away. Significance: The N170 evoked by faces can improve the epileptic foci localization in posterior brain epilepsy.

Perinatal Outcome and Change in Body Mass Index in Mothers of Dichorionic Twins: a Longitudinal Cohort Study

We used a prospective cohort to analyze the effect of change in BMI rather than change in weight, in mothers carrying dichorionic twins from a population that did not receive any dietary intervention. A total of 269 mothers (150 nulliparas and 119 multiparas) were evaluated. The average change (%) from the pre-gravid BMI was 7.2+/-6.1, 17.4+/-8.2, and 28.7+/-10.8, at 12-14, 22-25, and 30-34 weeks, respectively, without difference between nulliparas and multiparas. The comparison between maternities below or above the average change from the pregravid BMI failed to demonstrate an advantage (in terms of total twin birthweight and gestational age) of an above average change from the pregravid BMI, even when the lower versus upper quartiles were compared. Our observations reached different conclusions regarding the recommended universal dietary intervention in twin gestations. A cautious approach is advocated towards seemingly harmless excess weight gain, as normal weight women may turn overweight, or even obese, by the end of pregnancy, and be exposed to the untoward effects of obesity on future health and body image.

Pulmonary Hypertension in Portugal: First Data from a Nationwide Registry

Introduction. Pulmonary arterial hypertension (PAH) is a rare disease that must be managed in specialized centers; therefore, the availability of epidemiological national data is critical. Methods. We conducted a prospective, observational, and multicenter registry with a joint collaboration from five centers from Portugal and included adult incident patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH). Results. Of the 79 patients enrolled in this study, 46 (58.2%) were classified as PAH and 33 patients (41.8%) as CTEPH. PAH patients had a mean age of 43.4 ± 16.4 years. Idiopathic PAH was the most common etiology (37%). At presentation, PAH patients had elevated right atrial pressure (RAP) (7.7 ± 5.9mmHg) and mean pulmonary vascular resistance (11.4 ± 6.5 Wood units), with a low cardiac index (2.7 ± 1.1 L⋅min−1 m−2); no patient was under selective pulmonary vasodilators; however, at follow-up, most patients were on single (50%), double (28%), or triple (9%) combination vasodilator therapy. One-year survival was 93.5%, similar to CTEPH patients (93.9%), that were older (60.0 ± 12.5 years) and had higher RAP (11.0 ± 5.2mmHg,

Predição de Pré-Eclâmpsia no Primeiro Trimestre em Gravidezes de Baixo Risco: Determinação do Cut-Off numa Amostra da População Portuguesa

Objective:We aimed to identify the cut-off for risk of pre-eclampsia (PE) in Portuguese population by applying the first trimester prediction model from Fetal Medicine Foundation (FMF) in a prospective enrolled cohort of low risk pregnant women. Population and methods: A prospective cohort of low risk singleton pregnancies underwent routine first-trimester scree - ning from 2011 through 2013. Maternal characteristics, blood pressure, uterine artery Doppler, levels of pregnancy-associated plasma protein-A (PAPP-A) and free b-human chorionic gonadotropin were evaluated. The prediction of PE in first trimester was calculated through software Astraia, the outcome obtained from medical records and the cutoff value was subse quently calculated. Results:Of the 273 enrolled patients, 7 (2.6%) developed PE. In first trimester women who developed PE presented higher uterine arteries resistance, represented by higher values of lowest and mean uterine pulsatility index, p <0.005. There was no statistical significance among the remaining maternal characteristics, body mass index, blood pressure and PAPP-A. Using the FMF first trimester PE algorithm, an ideal cut-off of 0.045 (1/22) would correctly detect 71% women who developed PE for a 12% false positive rate and a likelihood ratio of 12.98 (area under the curve: 0.69; confidence interval 95%: 0.39-0.99). By applying the reported cutoff to our cohort, we would obtain 71.4% true positives, 88.3% true negatives, 11.4% false positives and 28.6% false negatives. Conclusion: By applying a first trimester PE prediction model to low risk pregnancies derived from a Portuguese population, a significant proportion of patients would have been predicted as high risk. New larger studies are required to confirm the present findings.

Fat Mass Index Performs Best in Monitoring Management of Obesity in Prepubertal Children

An early and accurate recognition of success in treating obesity may increase the compliance of obese children and their families to intervention programs. This observational, prospective study aimed to evaluate the ability and the time to detect a significant reduction of adiposity estimated by body mass index (BMI), percentage of fat mass (%FM), and fat mass index (FMI) during weight management in prepubertal obese children.

Influenza A(H1N1)pdm09 Resistance and Cross-Decreased Susceptibility to Oseltamivir and Zanamivir Antiviral Drugs

Neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are currently the only effective antiviral drugs available worldwide for the management of influenza. The potential development of resistance is continually threatening their use, rationalizing and highlighting the need for a close and sustained evaluation of virus susceptibility. This study aimed to analyze and characterize the phenotypic and genotypic NAIs susceptibility profiles of A(H1N1)pdm09 viruses circulating in Portugal from 2009 to 2010/2011. A total of 144 cases of A(H1N1)pdm09 virus infection from community and hospitalized patients were studied, including three suspected cases of clinical resistance to oseltamivir. Oseltamivir resistance was confirmed for two of the suspected cases. Neuraminidase (NA) H275Y resistant marker was found in viruses from both cases but for one it was only present in 26.2% of virus population, raising questions about the minimal percentage of resistant virus that should be considered relevant. Cross-decreased susceptibility to oseltamivir and zanamivir (2-4 IC50 fold-change) was detected on viruses from two potentially linked community patients from 2009. Both viruses harbored the NA I223V mutation. NA Y155H mutation was found in 18 statistical non-outlier viruses from 2009, having no impact on virus susceptibility. The mutations at NA N369K and V241I may have contributed to the significantly higher baseline IC50 value obtained to oseltamivir for 2010/2011 viruses, compared to viruses from the pandemic period. These results may contribute to a better understanding of the relationship between phenotype and genotype, which is currently challenging, and to the global assessment of A(H1N1)pdm09 virus susceptibility profile and baseline level to NAIs.

Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine Model

BACKGROUND: Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status. OBJECTIVES: To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance. METHODS: Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups. RESULTS: CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted. CONCLUSION: Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.