Netzhautkomplikationen bei Diabetes

In September 2015 a revised version of the guideline “Prevention and therapy of diabetes-induced retinal complications” was released in Germany. It summarizes current recommendations for diagnosis and therapy of diabetic retinopathy with a special focus on practicability in daily routine. Newly included were the use of optical coherence tomography (OCT) for the diagnosis of diabetic macular edema and the evaluation of the therapeutic effect of anti-VEGF drugs (VEGF: vascular endothelial growth factor) or corticosteroids after intravitreal drug delivery. Screening intervals for diabetic retinopathy were extended to every 2 years for all diabetic patients with no retinopathy and limited systemic risk factors. Patients with known risk factors should be screened annually or in case of retinopathy, followed-up as recommended by the ophthalmologist.     

PD-L1 – inhibitors in neuroendocrine neoplasia: Results from a real-life study

Immune check-point inhibitors (ICIs) have changed our view on how to treat cancer. Despite their approval in treatment of many different cancers, efficacy of immune check-point inhibitors (ICI) in neuroendocrine neoplasia is limited and poorly understood. Established treatment options of neuroendocrine tumors (NET) and neuroendocrine carcinomas (NECs) are based on surgery, tumor-targeted medical treatments, Peptide Receptor Radionuclide Therapy (PRRT), and locoregional therapies. However, in many patients these treatments lose efficacy over time, and novel therapies are urgently needed. We report on 8 patients diagnosed with neuroendocrine neoplasms (NEN) that were treated with ICI (pembrolizumab, avelumab, nivolumab plus ipilimumab) as salvage therapy. In this cohort, we observed tumor response with partial remission in 3 patients and stable disease in 1 patient. Four patients showed progressive disease. Of note, responses were observed both in PD-L1 positive and PD-L1 negative patients. Here, we discuss clinical courses of these patients in the context of available literature to highlight limitations and drawbacks currently preventing the use of ICI in routine management of patients with NEN.     

Brief Report: Educational attainment does not influence brain aging

Education has been related to various advantageous lifetime outcomes. Here, using longitudinal structural MRI data (4,422 observations), we tested the influential hypothesis that higher education translates into slower rates of brain aging. Cross-sectionally, education was modestly associated with regional cortical volume. However, despite marked mean atrophy in the cortex and hippocampus, education did not influence rates of change. The results were replicated across two independent samples. Our findings challenge the view that higher education slows brain aging.     

Improving residents’ confidence in using psychosocial skills

OBJECTIVE: To evaluate an intensive training program’s effects on residents’ confidence in their ability in, anticipation of positive outcomes from, and personal commitment to psychosocial behaviors. DESIGN: Controlled randomized study. SETTING: A university- and community-based primary care residency training program. PARTICIPANTS: 26 first-year residents in internal medicine and family practice. INTERVENTION: The residents were randomly assigned to a control group or to one-month intensive training centered on psychosocial skills needed in primary care. MEASUREMENTS: Questionnaires measuring knowledge of psychosocial medicine, and self-confidence in, anticipation of positive outcomes from, and personal commitment to five skill areas: psychological sensitivity, emotional sensitivity, management of somatization, and directive and nondirective facilitation of patient communication. RESULTS: The trained residents expressed higher self-confidence in all five areas of psychosocial skill (p<0.03 for all tests), anticipated more positive outcomes for emotional sensitivity (p=0.05), managing somatization (p=0.03), and nondirectively facilitating patient communication (p=0.02), and were more strongly committed to being emotionally sensitive (p=0.055) and managing somatization (p=0.056), compared with the untrained residents. The trained residents also evidenced more knowledge of psychosocial medicine than did the untrained residents (p<0.001). CONCLUSIONS: Intensive psychosocial training improves residents’ self-confidence in their ability regarding key psychosocial behaviors and increases their knowledge of psychosocial medicine. Training also increases anticipation of positive outcomes from and personal commitment to some, but not all, psychosocial skills. Presented at the annual meeting of the Society of General Internal Medicine, Washington, DC, April 27–29, 1994. Supported by the Fetzer Institute in Kalamazoo, MI.     

Effect of losartan in aging-related endothelial impairment

Aging is associated with progressive deterioration in endothelial function. We hypothesized that losartan may represent a useful therapeutic strategy to ameliorate endothelial function in aged subjects. Eighteen healthy older subjects (mean age 75 +/- 3 years) were prospectively randomized in a double-blind, crossover fashion to receive either losartan 50 mg/day or placebo for 6 weeks. Subjects were switched to the opposite arm after a 2- week washout period. Flow-mediated dilation (FMD) in the brachial artery and plasma levels of vascular cell adhesion molecule-1, intercellular adhesion molecule (ICAM), moncocyte chemoattractant 1 protein, and E-selectin were measured in both arms at the beginning and end of the 6-week period. Losartan resulted in a 6-mm Hg decrease in systolic blood pressure (from 130 +/- 12 to 124 +/- 13 mm Hg), which was no different from placebo (132 +/- 12 to 127 +/- 13 mm Hg). FMD increased from 3.1 +/- 0.6% to 3.9 +/- 0.6% after losartan, and decreased from 3.3 +/- 0.3% to 2.4 +/- 0.6% after placebo (p = NS for both). In contrast, losartan reduced circulating concentrations of vascular cell adhesion molecule 1 (750 +/- 73 to 572 +/- 39), ICAM (405 +/- 26 to 196 +/- 10), and moncocyte chemoattractant 1 protein (560 +/- 56 to 423 +/- 35) (p <0.01 for all by analysis of variance), but not E-selectin. On univariate analyses, the strongest predictor of baseline endothelial function and change in FMD with losartan was low-density lipoprotein. There was a negative correlation between baseline endothelial function and change in FMD in response to losartan (r(2) = -0.75, p = 0.0003). Baseline ICAM levels alone significantly correlated with low-density lipoprotein cholesterol (r(2) = 0.54, p = 0.02) and weakly correlated with total cholesterol (r(2) = 0.47, p = 0.05). Thus, administration of losartan for a duration of 6 weeks has favorable effects on inflammatory markers in healthy older subjects, but does not alter peripheral conduit endothelial function.     

Characterization of clone-specific rearrangement T-cell receptor gamma- chain genes in lymphomas and leukemias by the polymerase chain reaction and DNA sequencing

The structures of rearranged gamma-chain T-cell antigen receptor (TCR) genes were analyzed in 5 cases of T-cell acute lymphoblastic leukemia (T-ALL), in 15 cases of peripheral T-cell non-Hodgkin's lymphoma (T- NHL), in 1 case with large granular CD8 lymphocytosis, 1 case with CD8 lymphocytosis after autologous bone marrow transplantation for Hodgkin's disease, and in 2 cases with nonneoplastic diseases. Rearranged V-J TCR gamma-gene segments were amplified by the polymerase chain reaction (PCR). Because most of the biopsy tissue or bone marrow samples contained significant amounts of admixed nonmalignant T-cells, direct DNA sequencing of the PCR products yielded mixed sequence data because of coamplification of clonal together with polyclonal TCR gamma V-N-J junctions. Reliable data could only be obtained by cloning the V gamma-J gamma PCR products and sequencing several (4 to 10) randomly chosen clones. In the polyclonal samples, all PCR-derived clones differed in their specific V-N-J junctions, as expected. In the two T- cell lines and in most of the T-cell malignancies, monoclonal PCR products could be identified by the demonstration of clonally restricted V-N-J junctions. In most cases, this information yielded the desired clone-specific sequence and showed a background population of polyclonal TCR gamma cells in each specimen, except for those that were obtained from the T-ALL samples, the cell lines, or the NHL samples with high tumor cell fraction. The results obtained by PCR-directed sequencing were confirmed by temperature-gradient gel electrophoresis (TGGE) that showed distinct DNA bands only with the PCR products containing predominant (ie, monoclonal) TCR gamma V-N-J junctions. By combined sequence and TGGE analysis, it was found that PCR/TGGE is able to distinguish between monoclonal and polyclonal TCR gamma-PCR products. This finding prompted us to complete the analysis of the TCR gamma locus in the samples by PCR/TGGE using primer mixes which covered all possible V gamma and J gamma recombinations. Monoclonality was shown with all mixes by PCR/TGGE in 21 of 24 (87%) of the lymphoproliferations. In summary, the present study shows that the combination of amplifying TCR gamma V-N-J junctions by PCR with the identification of clonal PCR products by TGGE and DNA sequencing is a reliable method for the characterization of clonal TCR gamma sequences.