Vascular calcification in peritoneal dialysis patients and its association with bone-derived molecules and bone histomorphometry / Calcificación vascular en pacientes en diálisis peritoneal y su asociación con moléculas derivadas de hueso e histomorfometría ósea

Introduction: Data regarding vascular calcification (VC) in contemporary peritoneal dialysis (PD) patients is scarce. Bone–vascular axis has been demonstrated in hemodialysis (HD). However, studies showing the link between bone disease and VC in PD patients are lacking. The role of sclerostin, dickkopf-related protein 1 (DKK-1), receptor activator for nuclear factor kB ligand and osteoprotegerin (OPG) in VC in PD remains to clarify. Materials and methods: Bone biopsy was performed in 47 prevalent PD patients with histomorphometric analysis. Patients were submitted to pelvis and hands X-ray to evaluate VC using the Adragão score (AS). Relevant clinical and biochemical data was collected. Results: Thirteen patients (27.7%) had positive AS (AS≥1). Patients with VC were significantly older (58.9 vs. 50.4 years, p=0.011), had a lower dialysis dose (KT/V 2.0 vs. 2.4, p=0.025) and a higher glycosylated hemoglobin (7.2 vs. 5.4%, p=0.001). There was not any laboratorial parameter of mineral and bone disease used in clinical practice different between patients with or without VC. All diabetic patients had VC but only 8.1% of non-diabetic had VC (p<0.001). Patients with VC showed significantly higher erythrocyte sedimentation rate (ESR) (91.1 vs. 60.0mm/h, p=0.001), sclerostin (2250.0 vs. 1745.8pg/mL, p=0.035), DKK-1 (1451.6 vs. 1042.9pg/mL, p=0.041) and OPG levels (2904.9 vs. 1518.2pg/mL, p=0.002). On multivariate analysis, only ESR remained statistically significant (OR 1.07; 95% CI 1.01–1.14; p=0.022). Bone histomorphometric findings were not different in patients with VC. There was no correlation between bone formation rate and AS (r=−0.039; p=0.796). Conclusion: The presence of VC was not associated with bone turnover and volume evaluated by bone histomorphometry. Inflammation and diabetes seem to play a more relevant role in VC in PD. (AU)

Introducción Los datos sobre calcificación vascular (CV) en pacientes contemporáneos en diálisis peritoneal (DP) son escasos. En pacientes en hemodiálisis, se ha demostrado la existencia de una conexión entre hueso y sistema vascular; sin embargo, faltan estudios que muestren el vínculo entre la enfermedad ósea y la CV en pacientes en DP. Si la esclerostina, la proteína relacionada con Dickkopf 1 (DKK-1), el ligando del receptor activador para el factor nuclear κB (RANKL) y la osteoprotegerina (OPG) tienen un papel en la CV en pacientes en DP aún no está claro. Materiales y métodos Se realizó biopsia ósea en 47 pacientes prevalentes en DP y se analizó mediante histomorfometría. También se tomaron radiografías de pelvis y manos a los pacientes para evaluar la CV mediante el Índice de Adragão (IA). Además, se analizaron datos clínicos y bioquímicos relevantes. Resultados: Trece pacientes (27,7%) tuvieron IA positivo (IA ≥ 1). Los pacientes con CV eran significativamente mayores (58,9 vs 50,4 años, p=0,011) tenían menor dosis de diálisis (KT/V 2,0 vs 2,4, p=0,025) y niveles más elevados de hemoglobina glicosilada (7,2 vs 5,4%, p=0,001). No hubo ningún parámetro de laboratorio de enfermedad mineral y ósea utilizado en la práctica clínica diferente entre pacientes con o sin CV. Todos los pacientes diabéticos mostraron CV, sin embargo, solo el 8,1% de los no diabéticos tenían CV (p <0,001). Además, los pacientes con CV mostraron una velocidad de sedimentación globular más elevada (VSG) (91,1 vs. 60,0mm/h, p=0,001) y mayores concentraciones séricas de esclerostina (2.250,0 vs. 1.745,8 pg/ml, p=0,035), DKK-1 (1451,6 vs 1042,9 pg/ml, p=0,041) y OPG (2.904,9 vs. 1.518,2 pg/ml, p=0,002). En el análisis multivariante, solo la VSG fue estadísticamente significativa (OR 1,07; IC del 95%: 1,01-1,14; p=0,022)... (AU)

Analysis of thermal discomfort associated with synoptic conditions in the city of Pelotas, southernmost region of Brazil.

Here, we evaluated the influence of outdoor environmental conditions (synoptic weather conditions) on human thermal discomfort in the five macro-regions of Pelotas city, located in the southernmost region of Brazil. To do this, meteorological sensors (HOBO MX2301A) were installed outside the residences to measure the air temperature, dew point temperature, and relative humidity between 18 January and 20 August 2019. Two well-established simplified biometeorological indices were examined seasonally: (i) humidex for the summer months and (ii) effective temperature as a function of wind for the autumn and winter months. Our findings showed seasonal differences related to human thermal discomfort and outdoor environmental conditions. The thermal discomfort was highest in the afternoons during the summer months and at night during the winter months. The seasonal variation in human thermal discomfort was highly associated with the meteorological conditions. In summer, the presence of the South Atlantic Subtropical Anticyclone (SASA) contributed to heat stress. The SASA combined with the continent's low humidity contributed to the perceived sensation of thermal discomfort. In the winter, thermal discomfort was associated with the decrease in air humidity caused by high atmospheric pressure systems, which led to a decrease in both air temperature and air moisture content. Our findings suggest that a better understanding of the complex interplay between outdoor environmental factors and human thermal comfort is needed in order to mitigate the negative effects of thermal discomfort.

A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study.

INTRODUCTION: Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality. METHODS: Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death. RESULTS: During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models. CONCLUSION: The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.

Vascular calcification in peritoneal dialysis patients and its association with bone-derived molecules and bone histomorphometry.

INTRODUCTION: Data regarding vascular calcification (VC) in contemporary peritoneal dialysis (PD) patients is scarce. Bone-vascular axis has been demonstrated in hemodialysis (HD). However, studies showing the link between bone disease and VC in PD patients are lacking. The role of sclerostin, dickkopf-related protein 1 (DKK-1), receptor activator for nuclear factor kB ligand and osteoprotegerin (OPG) in VC in PD remains to clarify. MATERIALS AND METHODS: Bone biopsy was performed in 47 prevalent PD patients with histomorphometric analysis. Patients were submitted to pelvis and hands X-ray to evaluate VC using the Adragão score (AS). Relevant clinical and biochemical data was collected. RESULTS: Thirteen patients (27.7%) had positive AS (AS≥1). Patients with VC were significantly older (58.9 vs. 50.4 years, p=0.011), had a lower dialysis dose (KT/V 2.0 vs. 2.4, p=0.025) and a higher glycosylated hemoglobin (7.2 vs. 5.4%, p=0.001). There was not any laboratorial parameter of mineral and bone disease used in clinical practice different between patients with or without VC. All diabetic patients had VC but only 8.1% of non-diabetic had VC (p<0.001). Patients with VC showed significantly higher erythrocyte sedimentation rate (ESR) (91.1 vs. 60.0mm/h, p=0.001), sclerostin (2250.0 vs. 1745.8pg/mL, p=0.035), DKK-1 (1451.6 vs. 1042.9pg/mL, p=0.041) and OPG levels (2904.9 vs. 1518.2pg/mL, p=0.002). On multivariate analysis, only ESR remained statistically significant (OR 1.07; 95% CI 1.01-1.14; p=0.022). Bone histomorphometric findings were not different in patients with VC. There was no correlation between bone formation rate and AS (r=-0.039; p=0.796). CONCLUSION: The presence of VC was not associated with bone turnover and volume evaluated by bone histomorphometry. Inflammation and diabetes seem to play a more relevant role in VC in PD.

Effects of Aspirin on Kidney Biopsy Bleeding Complications: A Systematic Review and Meta-Analysis (PROSPERO 2021 CRD42021261005).

Postprocedural bleeding is the main complication of percutaneous kidney biopsy (PKB). Therefore, aspirin is routinely withheld in patients undergoing PKB to reduce the bleeding risk. The authors aimed to examine the association between aspirin use and bleeding during PKB. This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The article search was performed on MEDLINE and Scopus using queries specific to each database. Article inclusion was limited to primary studies. The meta-analysis compared the risk of major bleeding events between the aspirin-exposed versus nonexposed group. Pooled effect estimate was examined using random effects presented as odds ratio with 95% confidence intervals. Heterogeneity was assessed through Cochrane I 2 test statistics. Sensitivity and subgroup analyses were also performed according to kidney type. Ten studies were included in the review and four studies were included in the meta-analysis, reviewing a total of 34,067 PKBs. Definitions for significant aspirin exposure were inconsistent between studies, limiting comparisons. Studies with broader definitions for aspirin exposure mostly showed no correlation between aspirin use and postbiopsy bleeding. Studies with strict definitions for aspirin exposure found an increased risk of hemorrhagic events in the aspirin-exposed group. No significant differences were found between the aspirin-exposed and comparison groups regarding major bleeding events (odds ratio 1.72; 95% confidence interval 0.50 to 5.89, I 2 =84%). High-quality evidence on the effect of aspirin on the bleeding risk is limited. Our meta-analysis did not show a significantly increased risk of major bleeding complications in aspirin-exposed patients. Further studies are needed to define a more comprehensive approach for clinical practice.

Twenty years of real-world data to estimate chronic kidney disease prevalence and staging in an unselected population.

Chronic kidney disease (CKD) represents a global public health burden, but its true prevalence is not fully characterized in the majority of countries. We studied the CKD prevalence in adult users of the primary, secondary and tertiary healthcare units of an integrated health region in northern Portugal (n = 136 993; representing ∼90% of the region's adult population). Of these, 45 983 (33.6%) had at least two estimated glomerular filtration rate (eGFR) assessments and 30 534 (22.2%) had at least two urinary albumin:creatinine ratio (UACR) assessments separated by at least 3 months. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines as a persistent decrease in eGFR (<60 ml/min/1.73 m2) and/or an increase in UACR (≥30 mg/g). The estimated overall prevalence of CKD was 9.8% and was higher in females (5.5%) than males (4.2%). From these, it was possible to stratify 4.7% according to KDIGO guidelines. The prevalence of CKD was higher in older patients (especially in patients >70 years old) and in patients with comorbidities. This is the first real-world-based study to characterize CKD prevalence in a large, unselected Portuguese population. It probably provides the nearest estimate of the true CKD prevalence and may help healthcare providers to guide CKD-related policies and strategies focused on prevention and on the improvement of cardiovascular disease and other outcomes.

Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease.

BACKGROUND: High levels of FGF23 associate with adverse events in CKD. The urinary fractional excretion of phosphate (FePi) might modify this association, although data are limited in moderate and advanced CKD. We investigated the association of combined FePi and serum FGF23 with incident heart failure, cardiovascular events and mortality in patients with CKD stages 2-4. METHODS: Patients from the Chronic Renal Insufficiency Cohort were divided into four groups according to the median of FePi and FGF23: low-FePi/low-FGF23, reference group; high-FePi/low-FGF23; low-FePi/high-FGF23; high-FePi/high-FGF23. Primary outcomes were: the composite of cardiovascular death or hospitalization for heart failure; cardiovascular death; hospitalization for heart failure; and death from any cause. Survival analysis and adjusted regression analyses were performed. RESULTS: We analyzed 3684 patients with a mean age of 58 ± 11 years of whom 45% were male. Mean eGFR was 44 ± 15 ml/min/1.73 m2. The median time of follow-up was 12 (IQR 7-13) years. The risk of the composite of cardiovascular death or hospitalization for heart failure was increased in the low-FePi/high-FGF23 group (HR 1.35; 95%CI 1.09-1.67) and in the high-FePi/high-FGF23 group (HR 1.50; 95%CI 1.20-1.86), compared to the low-FePi/low-FGF23 group. Cardiovascular death and hospitalization for heart failure were also increased in both groups with high FGF23. Death from any cause was increased in the low-FePi/high-FGF23 group (HR 1.56 (95%CI 1.30-1.89) and in the high-FePi/high-FGF23 (HR 1.57 (95%CI 1.29-1.90)). CONCLUSIONS: High FGF23 was associated with heart failure and cardiovascular death in patients with low FePi and high FePi with moderate to advanced CKD. This contrasts with reports in mild CKD.

C3 Glomerulonephritis Presenting With Nephritic and Nephrotic Syndromes: Spontaneous Remission After Six Months on Dialysis.

C3 glomerulopathy is a rare and complex renal disease driven by complement dysregulation, with variable presentation and pathophysiology. We report the case of a middle-aged male patient presenting with nephritic and nephrotic syndromes and low serum C3, whose biopsy established the diagnosis of C3 glomerulonephritis. He was found to be homozygous for the complement factor H-related protein (CFHR)3-CFHR1 deletion, which has been associated with the development of anti-factor H autoantibodies. However, the lack of consistent and accessible nephritic factor assays prevented full clarification of the mechanisms involved in the disease. Interestingly, despite not receiving treatment due to suspicion of malignancy and perceived poor renal prognosis, there was spontaneous recovery after six months on hemodialysis. This case reflects the enduring challenges in establishing the diagnosis and prognosis of C3 glomerulonephritis.

Relaxin-2, pathophysiological insights and outcomes in heart failure with preserved ejection fraction: Findings from the NETDiamond cohort.

AIMS: The role of relaxin-2 as a circulating marker in heart failure (HF) with preserved ejection fraction (HFpEF) is poorly understood. We aimed to characterize relaxin-2 circulating levels in a population of chronic HFpEF patients and their association with long-term prognosis. METHODS: Relaxin-2 serum levels were measured in 85 chronic HFpEF patients from a prospective cohort study (NETDiamond). Clinical, imaging, and analytical data were compared across relaxin-2 tertiles. The primary outcome was a composite of cardiovascular death, HF hospitalisation, acute HF episode or diuretic intensification and the secondary outcome a composite of cardiovascular death and total HF hospitalisations. Cox regression and negative binomial models were used to assess the relation between relaxin-2 and the outcomes. RESULTS: Relaxin-2 levels were positively associated with left atrial volume, left ventricular mass and peripheral oedema, and negatively associated with ischemic heart disease and statin use. Higher relaxin-2 levels were associated with an increased risk of primary outcome, even after adjustment for age, B-type natriuretic peptide (BNP) and glomerular filtration rate (eGFR) (adjusted HR = 2.80, 95%CI 1.4-7.3, p = 0.034 for tertile 3). They were also associated with the occurrence of the secondary outcome (Incidence Rate Ratio = 5.28, 95%CI 1.2-23.2, p = 0.027), but this significance was lost when simultaneously adjusted for BNP and eGFR. CONCLUSION: In chronic HFpEF patients, higher relaxin-2 circulating levels were associated with left chambers remodelling, congestion, and adverse prognosis. These findings support a potential role for relaxin-2 as a pathophysiological agent and as a circulating biomarker in HFpEF.

Absorbed dose rate for marine biota due to the oil spilled using ICRP reference animal and Monte Carlo simulation.

The current study aimed to obtain dose conversion coefficients for marine animals due to an oil spill accident using two variables: crude oil activity concentration and organism depth. Thorium series presented a dose contribution twice that uranium series for similar conditions. Bi-214 and Tl-208 stood out for delivering a higher dose rate for uranium and thorium series, respectively. Results obtained can be used to assess the maximum exposure time for emergency oil control, removal, and mitigation in an oil spill accident.

Evaluation of Renal Osteodystrophy and Serum Bone-Related Biomarkers in a Peritoneal Dialysis Population.

The spectrum of renal osteodystrophy (ROD) in peritoneal dialysis (PD) patients remains to be clarified. Ideal intact parathormone (iPTH) levels range is still not defined. The role of sclerostin, dickkopf-related protein 1, osteoprotegerin, and receptor activator for nuclear factor κB ligand for the diagnosis of ROD needs to be elucidated. In this cross-sectional study, tetracycline double-labeled bone biopsy was performed in 49 patients with histomorphometric analysis according Kidney Disease Improving Global Outcomes (KDIGO) guidelines. All patients were treated with biocompatible PD solutions, with calcium concentration of 1.25 mmol/L. Adynamic bone was the most frequent diagnosed pattern (42.9%) followed by hyperparathyroid-related bone disease (28.6%). Twenty-two percent of patients had normal bone. In patients with iPTH within the KDIGO recommended range for dialysis patients, adynamic bone was found in 59% of cases. Median (range) iPTH in patients with adynamic bone was 312 (60-631) pg/mL. Median (range) levels of sclerostin varied from 1511.64 (458.84-6387.70) pg/mL in patients with hyperparathyroid bone disease to 2433.1 (1049.59-11354.52) pg/mL in patients with adynamic bone. Sclerostin/iPTH ratio was the best marker of low turnover disease but iPTH performed best in the diagnosis of high turnover disease. Calcium mass transfer was positive in patients with low bone volume. Adynamic bone is the most frequent ROD pattern in contemporary PD. Our results suggest the need to review the iPTH target range for this population. The sclerostin/iPTH ratio showed improved performance compared to iPTH for the diagnosis of low turnover bone. © 2022 American Society for Bone and Mineral Research (ASBMR).

Comparison between oil spill images and look-alikes: an evaluation of SAR-derived observations of the 2019 oil spill incident along Brazilian waters.

Three SAR-derived observations of dark surface patches along the Northeastern Brazilian coastline by the end of 2019 were misreported in the Brazilian media as oil spill-related. Unfortunately, these observations were misled by false positives or look-alikes. Therefore, this paper aims to technically evaluate these look-alike classes by analyzing image attributes found to be helpful to the identification of ocean targets, including oil spills, rain cells, biofilms, and low wind conditions. We use image augmentation to extend our dataset size and create the probability density function curves. The processing includes image segmentation, optimal attribute extraction, and classification with random forest classifiers. Our results contrast with the open-source oil spill detection system and patch classifier methodology called "RIOSS." Analysis of the feature probability density functions based on optimal attributes is promising since we could capture most of the false positive targets in the three SAR-reported images in 2019. The only exception was the biofilm slick observed on October 28th, where the RIOSS mistakenly classified this organic patch as a low wind region with oil spots. This pitfall is acceptable at this project stage since we had only five biogenic film samples to train the algorithm.

Foveal and Extrafoveal Effects of Half-Dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy: A Cohort Study.

PURPOSE: To compare the efficacy and safety of foveal and extrafoveal half-dose photodynamic therapy (HD-PDT) for chronic Central Serous Chorioretinopathy (cCSC). METHODS: This retrospective, cohort study included cCSC eyes submitted to HD-PDT on foveal (F) or extrafoveal (E) areas. Patients were evaluated at baseline and 12 weeks after treatment for best corrected visual acuity (BCVA) and the following spectral-domain optical coherence tomography (SD-OCT) subfoveal parameters: central macular thickness (CMT), outer nuclear layer, external limiting membrane, ellipsoid zone, interdigitation zone, choroidal thickness and subretinal fluid (SRF). RESULTS: F group comprised 33 eyes (47.1%) and E group comprised 37 eyes (52.9%). Both groups showed an improvement of BCVA after HD-PDT with no significant differences in final BCVA (p = .41). CMT and SRF showed a significant improvement after HD-PDT in both groups, but the rate of disruption of the external retinal layers remained stable. During follow-up, SD-OCT parameters and the rate of anatomical success showed no significant differences regarding the treatment location. No major sequelae were noticed. CONCLUSION: Foveal and extrafoveal applications of HD-PDT for cCSC showed comparable efficacy and safety.

Association between serum phosphorus and mortality in NHANES 2003-2006: the effect of gender and renal function.

BACKGROUND: The impact of high serum phosphorus in the general population is still debated. Studies are heterogeneous, most lack an adjustment for parathyroid hormone, vitamin D and phosphorus intake and the effect might differ by gender and renal function. We investigated the association between serum phosphorus and mortality in American adults. METHODS: We prospectively analyzed 5698 non-pregnant and non-CKD adults from the National Health and Nutrition Examination Survey (NHANES) 2003-2006. Serum phosphorus and potential confounders including parathyroid hormone, 25(OH)vitamin D and phosphorus intake were evaluated. All-cause, cardiovascular- and cancer-related deaths were recorded through December 31st, 2015. Sex-specific terciles of serum phosphorus were used to fit adjusted Cox proportional hazard models for mortality. Analysis was stratified by gender and renal function. RESULTS: A total of 590 deaths were recorded over a median follow-up of 81 months. Women showed higher serum phosphorus than men. The adjusted hazard ratio (HR) for all-cause mortality was 1.35 (95% CI 1.08-1.58) (p = 0.033) for the third tercile (versus second tercile). This increased risk was present in participants with estimated glomerular filtration rate (eGFR) below 90 ml/min/1.73 m2 but not above, although interaction was not significant (p = 0.12). Interaction by gender, phosphorus intake, PTH and fasting time was also not detected. For cardiovascular and cancer mortality, the adjusted HR was 0.81 (95% CI 0.33-2.00) (p = NS) and 1.45 (95% CI 0.77-2.72) (p = NS), respectively. CONCLUSIONS: We demonstrated that the highest tercile of serum phosphorus is associated with increased all-cause mortality, irrespective of PTH, 25(OH)vitamin D or phosphorus intake. This association may differ by gender and renal function, but larger studies testing for effect modification are needed.

Efficacy and Safety of Intravitreal Aflibercept Treat and Extend for Polypoidal Choroidal Vasculopathy in the ATLANTIC Study: A Randomized Clinical Trial.

IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. METHODS: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). RESULTS: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. TRIAL REGISTRATION: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.

The Role of Vascular Lesions in Diabetes Across a Spectrum of Clinical Kidney Disease.

INTRODUCTION: The clinical-histologic correlation in diabetic nephropathy is not completely known. METHODS: We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR). RESULTS: Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% <60 ml/min per 1.73 m2). About 170 glomeruli per patient were analyzed, and all samples included vascular tissue. Six subjects (7%) were classified in diabetic nephropathy class I, 61 (68%) in class II-a, 13 (14%) in class II-b, 9 (10%) class III, and 1 (1%) in class IV. Eighty percent to 90% of those with normoalbuminuria or microalbuminuria were classified in class II-a or II-b and <10% in class III; 52% of those with proteinuria were in class II-a, 15% in class II-b, and 19% in class III. Nodular sclerosis (57%) and mesangial expansion (15%) were more frequent in cases with proteinuria than in normoalbuminuria (28% and 8%; P = 0.028 and 0.017). About 20% to 30% of all cases, regardless the level of albuminuria or proteinuria or the histologic class had tubular atrophy, interstitial fibrosis, or inflammation in >10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III. CONCLUSIONS: Weak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes.

From Kidney to Brain: An Uncommon Severe Relapse of Myeloperoxidase Anti-Neutrophil Cytoplasmic Antibody (MPO-ANCA) Vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases that affect medium and small blood vessels, with uncommon, variable central nervous system (CNS) involvement. It poses diagnosis challenges due to the limited accuracy of conventional imaging and vast differential diagnosis. We describe the case of a 76-year-old man with a previously diagnosed myeloperoxidase (MPO)-positive AAV with exclusive renal involvement. The patient presented to our emergency department (ED) with sudden-onset weakness of the right side of the body, difficulty speaking, fever, and a history of progressive cognitive impairment in the previous three months (loss of memory, time and space disorientation, acalculia). Brain imaging showed multiple acute and subacute ischemic lesions, suggesting CNS vasculitic involvement. The patient was treated with methylprednisolone pulses, followed by rituximab, with motor and cognitive improvement. Timely diagnosis and adequate treatment of AAV as a cause for new-onset neurological symptoms are crucial to improve outcomes. Otherwise, a higher risk of relapse remains, and extensive neurological deficits may become permanent. Evidence regarding the best treatment options in these patients is scarce and case reports provide further data on this topic.

Depression after stroke.

Stroke treatment has dramatically improved in recent decades. However, although new treatments have reduced its mortality and the severity of its physical and cognitive sequelae, many people still have incapacitating disabilities following a stroke. Depression is the most common psychiatric disorder following stroke; it is important to recognise and treat as it limits motor and cognitive rehabilitation. Antidepressant medication is an effective treatment and can improve adherence to clinically recommended physical and cognitive tasks, thereby enhancing functional remodelling of neuronal pathways and improving rehabilitation outcomes.