Marta Alves

Retinal Neurodegeneration in Diabetic Patients Without Diabetic Retinopathy

PurposenTo compare the thickness of all retinal layers between a nondiabetic group and diabetic patients without diabetic retinopathy (DR).nnnMethodsnCross-sectional study, in which all subjects underwent an ophthalmic examination including optical coherence tomography. After automatic retinal segmentation, each retinal layer thickness (eight separate layers and overall thickness) was calculated in all nine Early Treatment Diabetic Retinopathy Study (ETDRS) areas. The choroidal thickness (CT) also was measured at five locations. Generalized additive regression models were used to analyze the data.nnnResultsnA total of 175 patients were recruited, 50 nondiabetic subjects and 125 diabetic patients without DR, stratified into three groups according to diabetes duration: group I (<5 years, n = 55), group II (5-10 years, n = 39), and group III (>10 years, n = 31). Overall, groups I and III of diabetic patients had a decrease in the photoreceptor layer (PR) thickness, when compared with the nondiabetic subjects in six ETDRS areas (P < 0.0007). Patients with more recent diagnosis (group I) had thinner PR than those with moderate duration (group II). Interestingly, patients with longer known disease (group III) had the thinnest PR values. There were no overall differences in the remaining retinal parameters.nnnConclusionsnRetinal thickness profile is not linear throughout disease duration. Even in the absence of funduscopic disease, PR layer in diabetic patients seems to differ from nondiabetic subjects, thus suggesting that some form of neurodegeneration may take place before clinical signs of vascular problems arise.

Predictive impact on medium-term mortality of hematological parameters in Acute Coronary Syndromes: added value on top of GRACE risk score.

Background: Red Cell Distribution Width (RDW) prognostic value in patients with Acute Coronary Syndrome (ACS) has been well validated whereas that of Platelet Distribution Width (PDW) is less well known. Objectives: Investigate the incremental prognostic value, on top of GRACE risk score, of a new variable resulting from the combination of RDW and PDW. Methods: Consecutive patients with ACS. Complete blood count, with RDW and PDW, was obtained. Primary endpoint was one-year all-cause mortality and Cox regression models were used to measure the influence of RDW and PDW on patients’ survival time. A new combination categorical variable (RDW/PDW) was created with both discretized RDW and PDW and logistic regression models were used. Predictive value and discriminative ability of the model with GRACE risk score alone and of the model with inclusion of RDW/PDW was assessed. Results: We included 787 patients. Hospital and one-year mortality rates were 5.1% and 7.8%, respectively. Both continuous RDW and PDW were independent predictors of death. The best cut-off for RDW was 13.9%, and 14.5% for PDW. Inclusion of RDW/PDW in a model with GRACE risk score improved the AUC from 0.81 (95% CI 0.75–0.86) to 0.84 (95% CI 0.79–0.90) (p=0.024) with an improvement in total NRI (56%) and IDI (0.048). Conclusions: Simple markers such as RDW and PDW can be useful in risk stratification of death after ACS. Combining both markers with GRACE risk score improved the predictive value for all-cause mortality and reduced the estimated risk of those who did not die.

Retina and Choroid of Diabetic Patients Without Observed Retinal Vascular Changes: A Longitudinal Study

PURPOSEnTo identify changes in choroidal thickness (CT) and all retinal layers of diabetic patients without diabetic retinopathy (DR) after 1 year of follow-up.nnnDESIGNnProspective observational cohort study.nnnMETHODSnOverall, 125 diabetic patients without DR were included. Two visits were scheduled: the first visit (V1) and a second visit after 12xa0months (V2). At both visits, patients received a complete ophthalmologic evaluation that included OCT. Each retinal layer thickness was calculated for 9 ETDRS sectors, and CT was measured at 13 locations. Generalized linear mixed-effects models were used.nnnRESULTSnOf the 125 patients, 103 completed the study, and 9 of the 103 developed DR (8.7%). CT was significantly higher at V2 than at V1, with an average value of 10-17xa0μm at almost half the locations (500, 1000, and 1500xa0μm temporal; 500 and 1000xa0μm nasal; and 1000xa0μm superior to the fovea) (P < .001-.003). The thicknesses of the ganglion cell layer (I3 and N6 sectors), inner plexiform layer (S6 and N6 sectors), inner nuclear layer (T6 and N6 sectors), and outer plexiform layer (S6 sector), as well as the overall retinal thickness (RT) (S3, N3, I3, S6, and T6 sectors), were decreased at V2 (P < .001). Visible retinopathy was negatively associated with overall RT (central, S3, T3, I3, and N3 sectors, Pxa0= .004-.024) and the thickness of the ONL (T6 and I6 sectors, Pxa0= .007 and Pxa0= .009) and photoreceptor layer (N6 sector, Pxa0= .038). The presence of DR decreased the overall RT by 13.04-16.63xa0μm.nnnCONCLUSIONSnDiabetic patients without DR showed a thicker choroid and a thinner retina, particularly in inner layers, after 1 year of follow-up. These structural changes may correspond to the early neurodegenerative phase of DR.

OCT in Alzheimer’s disease: thinning of the RNFL and superior hemiretina

BackgroundPeripapillary retinal nerve fiber layer (pRNFL) and internal macular layer thinning have been demonstrated in Alzheimer’s disease (AD) with optical coherence tomography (OCT) studies. The purpose of this study is to compare the pRNFL thickness and overall retinal thickness (RT) in AD patients with non-AD patients, using spectral domain optical coherence tomography (SD-OCT) and determine the sectors most characteristically affected in AD.MethodsA cross-sectional study was performed to determine the pRNFL and overall macular RT thicknesses in AD and non-AD patients, attending a tertiary hospital center. For pRNFL, the global and six peripapillary quadrants were calculated, and for overall RT values, the nine Early Treatment Diabetic Retinopathy Study (ETDRS) areas were used. A multiple regression analysis was applied to assess the effects of disease, age, gender, spherical equivalent, visual acuity, intraocular pressure, axial length and blood pressure on pRNFL and overall macular RT. ResultsA total of 202 subjects, including 50 eyes of 50 patients with mild AD (mean age 73.10; SD = 5.36 years) and 152 eyes of 152 patients without AD (mean age 71.03; SD = 4.62 years). After Bonferroni correction, the pRNFL was significantly thinner for the AD group globally and in the temporal superior quadrant (10.76 μm and 20.09 μm mean decrease, respectively). The RT thickness was also decreased in superior sectors S3 and S6 (mean thinning of 9.92 μm and 11.65 μm, respectively). Spearman’s correlation coefficient showed a direct association between pRNFL in the temporal superior quadrant and RT in superior S6 and S3 sectors (rS = 0.41; p < 0.001 and rS = 0.28; p < 0.001, respectively).ConclusionsPatients with AD showed a significant thickness reduction in global and temporal superior quadrants in pRNFL and in superior pericentral and peripheral sectors of RT. These findings may reflect a peripapillary and retinal changes characteristic of AD, suggesting the importance of SD-OCT as a potential adjuvant in early diagnosis of AD. Further studies are needed to understand which retinal layers and macular sectors are more useful as potential ocular biomarker over time in AD.

Choroidal thinning: Alzheimer's disease and aging

The purpose of this study was to measure and to compare macular choroidal thickness (CT) between patients with mild Alzheimers disease (AD), patients without AD, and elderly patients.

Predictors of response to cardiac resynchronization therapy: A prospective cohort study

INTRODUCTIONnCardiac resynchronization therapy (CRT) has modified the prognosis of chronic heart failure (HF) with left ventricular systolic dysfunction. However, 30% of patients do not have a favorable response. The big question is how to determine predictors of response.nnnAIMSnTo identify baseline characteristics that might influence echocardiographic response to CRT.nnnMETHODS AND RESULTSnWe performed a prospective single-center hospital-based cohort study of consecutive HF patients selected to CRT (NYHA class II-IV, left ventricular ejection fraction (LVEF) <35% and QRS complex ≥120 ms). Responders were defined as those with a ≥5% absolute increase in LVEF at six months. Clinical, electrocardiographic, laboratory, echocardiographic, autonomic, endothelial and cardiopulmonary function parameters were assessed before CRT device implantation. Logistic regression models were used. Seventy-nine patients were included, 54 male (68.4%), age 68.1 years (standard deviation 10.2), 19 with ischemic etiology (24%). At six months, 51 patients (64.6%) were considered responders. Although by univariate analysis baseline tricuspid annular plane systolic excursion (TAPSE) and serum creatinine were significantly different in responders, on multivariate analysis only TAPSE was independently associated with response, with higher values predicting a positive response to CRT (OR=1.13; 95% CI: 1.02-1.26; p=0.020). TAPSE ≥15 mm was strongly associated with response, and TAPSE <15 mm with non-response (p=0.005). Responders had no TAPSE values below 10 mm.nnnCONCLUSIONnFrom a range of clinical and technical baseline characteristics, multivariate analysis only identified TAPSE as an independent predictor of CRT response, with TAPSE <15 mm associated with non-response. This study highlights the importance of right ventricular dysfunction in CRT response. ClinicalTrials.gov identifier: NCT02413151.Introduction nCardiac resynchronization therapy (CRT) has modified the prognosis of chronic heart failure (HF) with left ventricular systolic dysfunction. However, 30% of patients do not have a favorable response. The big question is how to determine predictors of response.

Choroidal Thickness In Diabetic Patients Without Diabetic Retinopathy.

Purpose: To compare choroidal thickness (CT) between diabetic patients without diabetic retinopathy and a nondiabetic group. To explore how CT relates to disease duration, mean arterial pressure, glycemia, glycosylated hemoglobin, intraocular pressure, and ocular pulse amplitude. Methods: Choroidal thickness was assessed using a spectral-domain optical coherence tomography and enhanced depth mode at 13 locations (subfoveal and 3 measurements 500 &mgr;m apart in 4 directions—nasal, temporal, superior, and inferior). Linear regression models were used. Results: One hundred seventy-five patients were recruited (125 diabetic patients without diabetic retinopathy and 50 nondiabetic patients). In diabetic patients, although without statistical significance, CT showed a trend to be thicker in all locations (6.16–24.27 &mgr;m). Choroidal thickness was negatively associated with age (P < 0.001) in both groups, but only in the diabetic group, it was positively associated to ocular pulse amplitude (with a mean increase between 8.5 &mgr;m and 11.6 &mgr;m for each millimeter of mercury increase in ocular pulse amplitude). Diabetic patients CT seems to stabilize after 150 months of diabetes, increase with higher glycemia levels (>160 mg/dL) while showing no fluctuation with glycosylated hemoglobin and mean arterial pressure. Conclusion: There seems to be a thickening of the choroid in diabetic patients without diabetic retinopathy. Moreover, this tissue may be functionally different in diabetes, as the pattern of associations seems to differ between groups.

Evolution of diffusion tensor imaging parameters after acute subarachnoid haemorrhage: a prospective cohort study

IntroductionFew studies assessed diffusion tensor imaging (DTI) changes in the acute phase of subarachnoid haemorrhage (SAH). We prospectively evaluated DTI parameters in the acute phase of SAH and 8–10xa0days after and analysed whether changes could be related to SAH severity or to the development of delayed cerebral ischemia (DCI).MethodsApparent diffusion coefficient (ADC) and fractional anisotropy (FA) changes over time were assessed in a prospective cohort of patients with acute SAH. Two MRI studies were performed at <72xa0h (MRI-1) and 8–10xa0days (MRI-2). DTI parameters were recorded in 15 ROIs. Linear mixed regression models were used.ResultsForty-two patients were included. Subtle changes in DTI parameters were found between MRI-1 and MRI-2. At the posterior limb of internal capsule (PLIC), a weak evidence of a 0.02 mean increase in FA (pxa0=xa00.064) and a 17.55xa0×xa010−6xa0mm2/s decrease in ADC (pxa0=xa00.052) were found in MRI-2. Both FA and ADC changed over time at the cerebellum (increase of 0.03; pxa0=xa00.017; decrease of 34.73xa0×xa010−6xa0mm2/s; pxa0=xa00.002, respectively). Patients with DCI had lower FA values on MRI-1 and lower ADC on MRI-2, although not reaching statistical significance, compared to non-DCI patients. DTI parameters on MRI-1 were not correlated to clinical admission scales.ConclusionADC and FA values show subtle changes over time in acute SAH at the PLIC and cerebellum although not statistically associated with the severity of SAH or the occurrence of DCI. However, DTI changes occurred mainly in DCI patients, suggesting a possible role of DTI as a marker of DCI.

Fat mass index performs best in monitoring management of obesity in prepubertal children

OBJECTIVEnAn 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.nnnMETHODSnIn a cohort of 60 prepubertal obese children aged 3-9 years included in an outpatient weight management program, BMI, %FM, and FMI were monitored monthly; the last two measurements were assessed using air displacement plethysmography. The outcome measures were the reduction of >5% of each indicator and the time to achieve it.nnnRESULTSnThe rate of detection of the outcome was 33.3% (95% CI: 25.9-41.6) using BMI, significantly lower (p<0.001) than either 63.3% using %FM (95% CI: 50.6-74.8) or 70.0% (95% CI: 57.5-80.1) using FMI. The median time to detect the outcome was 71 days using FMI, shorter than 88 days using %FM, and similar to 70 days using BMI. The agreement between the outcome detected by FMI and by %FM was high (kappa 0.701), but very low between the success detected by BMI and either FMI (kappa 0.231) or %FM (kappa 0.125).nnnCONCLUSIONSnFMI achieved the best combination of ability and swiftness to identify reduction of adiposity during monitoring of weight management in prepubertal obese children.

Symptom clusters and survival in Portuguese patients with advanced cancer

This study aimed to identify clusters of symptoms, to determine the patient characteristics associated with identified, and determine their strength of association with survival in patients with advanced cancer (ACPs). Consecutively eligible ACPs not receiving cancer‐specific treatment, and referred to a Tertiary Palliative Care Clinic, were enrolled in a prospective cohort study. At first consultation, patients rated 9 symptoms through the Edmonton Symptom Assessment System (0–10 scale) and 10 others using a Likert scale (1–5). Principal component analysis was used in an exploratory factor analysis to identify. Of 318 ACPs, 301 met eligibility criteria with a median (range) age of 69 (37–94) years. Three SCs were identified: neuro‐psycho‐metabolic (NPM) (tiredness, lack of appetite, lack of well−being, dyspnea, depression, and anxiety); gastrointestinal (nausea, vomiting, constipation, hiccups, and dry mouth) and sleep impairment (insomnia and sleep disturbance). Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter survival was observed for patients with the NPM cluster (58 vs. 23, P < 0.001), as well as for patients with two or more SCs (45 vs. 21, P = 0.005). In a multivariable model for survival at 30‐days, age (HR: 0.98; 95% CI: 0.97–0.99; P = 0.008), hospitalization at inclusion (HR: 2.27; 95% CI: 1.47–3.51; P < 0.001), poorer performance status (HR: 1.90, 95% CI: 1.24–2.89; P = 0.003), and NPM (HR: 1.64; 95% CI: 1.17–2.31; P = 0.005), were associated with worse survival. Three clinically meaningful SC in patients with advanced cancer were identifiable. The NPM cluster and the presence of two or more SCs, had prognostic value in relation to survival.