Higher executive abilities following a blood transfusion in children and young adults with sickle cell disease

Individuals with sickle cell disease (SCD) experience cognitive deficits; however, it remains unclear whether medical treatments for SCD improve cognition. Given that executive abilities are typically impaired in individuals with SCD, they were the focus of the current study. Our primary hypothesis was that executive abilities would be higher acutely soon after a blood transfusion in children and young adults with SCD. We used tests from the NIH Toolbox to assess executive abilities in 27 participants with SCD receiving chronic transfusion in comparison to 34 participants with SCD receiving hydroxyurea (HU) and 41 non‐SCD demographically matched controls, all of whom were tested at two time points. Participants in the transfusion group completed cognitive testing within 3 days after a transfusion (soon after transfusion) and then within 3 days before their next transfusion (long after transfusion) over an interval of 3‐7 weeks. We found that executive abilities were significantly poorer for the transfusion and HU groups than for the control group. In support of our primary hypothesis, executive abilities for the transfusion group were significantly better soon after a transfusion compared to long after a transfusion, χ²(1) = 17.8, P < .0001. Our results demonstrate that executive abilities were higher acutely following a blood transfusion. These findings have implications for daily functioning, medical decision making, and academic achievement in children and young adults with SCD.     

Early increase of plasma soluble VEGFR-2 is associated with clinical benefit from second-line treatment of paclitaxel and ramucirumab in advanced gastric cancer

Ramucirumab plus paclitaxel is considered the standard of care in the second-line treatment of gastric carcinoma (GC). The aim of this study was to evaluate plasma vascular endothelial growth factor-A (VEGF-A), VEGF-D, and circulating soluble VEGF receptor-2 (sVEGFR-2) as possible markers of resistance or response to ramucirumab administered with paclitaxel in pretreated metastatic GC patients. Plasma samples were collected at different time points (on days 1 and 15 of the first 3 cycles, at best radiologic response and at disease progression). VEGF-A, VEGF-D and sVEGFR-2 were analysed by ELISA. Correlations of biomarker baseline levels or dynamic changes with outcome measures were assessed. Progression-free survival (PFS) was the primary endpoint of the study. Forty-one patients were enrolled. VEGF-A and VEGF-D, but not sVEGFR-2, values significantly increased during treatment compared to baseline (P < 0.001). A positive correlation between VEGF-A and sVEGFR-2 at cycle 2 was found (P=0.045). At univariate analysis, higher baseline levels of VEGF-A were associated with worse OS (P=0.015). Early increase of sVEGFR-2 levels after the first treatment cycle was the only factor associated with longer PFS (6.6 vs. 3.6 months, P=0.049) and OS (18.6 vs. 5.2 months, P=0.008). Significance of sVEGFR-2 early increase was retained at multivariate analysis for OS (HR 0.32; 95% CI 0.12-0.91; P=0.032). The reported results confirmed the prognostic role of baseline VEGF-A and, with the limitations of the limited sample size and the lack of a control arm, suggested that the early increase of sVEGFR-2 after 1 cycle of treatment could be a potential predictive biomarker of benefit from second-line ramucirumab plus paclitaxel in GC.     

In diabetic retinopathy, foveal thickness of 300 μm seems to correlate with functionally significant loss of vision

Purpose To study the relationship between foveal thickness assessed by optical coherence tomography (OCT) and foveal function measured with multi focal electroretinography (mfERG) in patients with non-proliferative diabetic retinopathy, and with no previous laser treatment. Methods Twenty-six eyes from 18 diabetic patients (13 men), aged 59 years, (range 28–79 years), diabetes duration 15 years, (range 2–27 years), with a macular thickness between 200 and 600 μm were evaluated by mfERG, visual acuity (ETDRS score) and OCT. Mean amplitudes and implicit times of the mfERG responses were analyzed within the four innermost (14 degrees) of the six concentric rings. For comparison with the results from the OCT (diameter of measured area = 6 mm) we analyzed the summed response from the first and second ring (central zone), corresponding to the central area of the OCT. The third(zone 2) and fourth (zone 3)of the four innermost of the six concentric rings measured by the mfERG corresponding to the second and third area of OCT. Results An increased macular thickness in the central area of the OCT correlated to reduced amplitudes (r = −0.541; P = 0.004) and prolonged implicit times (r = 0.548; P = 0.004) in the central zone of the mfERG, and inversely correlated with visual acuity, −0.49; P = 0.045. Retinal thickness in the second area was correlated to prolonged implicit times in the second mfERG zone (r = −0.416; P = 0.034). No correlations were found for the third area of the OCT. When macular thickness exceeded 300 μm the decrease of amplitudes and prolonged implicit times, measured by mfERG, seemed to be more pronounced. Conclusion In conclusion increased macular thickness is correlated with reduced amplitudes and prolonged implicit times on the mf ERG and worse visual acuity.