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关键词： Adjuvant therapy   Immunotherapy   Kidney cancer   Neoadjuvant therapy  

摘要： Objective The treatment landscape for renal cell carcinoma (RCC) is rapidly evolving. The aim of this review is to summarize the randomized-controlled trials evaluating the role of immunotherapy in neoadjuvant or adjuvant setting. Materials and methods We searched PubMed, Cochrane Central Register of Controlled Trials, and *** for studies including neoadjuvant or adjuvant immunotherapy, and provided a brief overview of the pharmacodynamics of immunotherapy for RCC. Results Several drugs are currently under investigation. In the neoadjuvant setting, four studies are evaluating the role of single-agent immunotherapy, one of dual-agent immunotherapy, and four studies the role of immunotherapy in combination with tyrosine kinase inhibitors or anti-interleukin-1 beta. In the adjuvant setting, two studies are evaluating the role of single-agent immunotherapy and two of dual-agent immunotherapy. Conclusions The approval of immune checkpoint inhibition as a front-line therapeutic strategy for advanced RCC has also ultimately led to the investigation of these agents first in the adjuvant and then in the neoadjuvant setting. Currently, there are nine studies aimed to evaluate the role of immunotherapy in the neoadjuvant setting and four studies in the adjuvant setting.

关键词： deciduous teeth   IgG4   Immunoglobulin   Immunohistochemistry   periapical lesion   permanent teeth  

摘要： Aim To characterize plasma cell subsets in chronic periapical lesions affecting permanent and primary teeth. Methodology Only chronic periapical lesions without root canal treatment were selected. Twenty-one radicular cysts and 7 periapical granulomas affecting permanent teeth and 19 radicular cysts and 4 periapical granulomas affecting primary teeth were assessed for immunoglobulin (Ig) light chain (kappa and lambda), Ig heavy chain (IgG, IgG4, IgA, IgM and IgD) and plasma cell immunohistochemical markers (MUM1/IRF4, EMA and CD138). The data acquired were analysed by Student's t test, Mann-Whitney U, Friedman test followed by Dunn's multiple comparison test and Spearman's rank correlation. Results All cases were polyclonal (having similar kappa/lambda light chain ratios). IgG was most abundant compared to other Ig heavy chains (all, P < 0.001);like Ig light chains, but unlike IgA, there was greater expression of IgG in the primary compared to the permanent dentition, for both radicular cysts (P < 0.001) and periapical granulomas (P = 0.53). Notably, IgG4 expression was greater in the permanent than the primary dentition, for both radicular cyst (P < 0.05) and periapical granuloma (P = 0.65). IgM and IgD expression was scarce and variable, whereas plasma cell populations were detected efficiently through EMA, CD138 and MUM1/IRF4 markers, the latter being more sensitive in both dentitions. Conclusions There were slight variations in the Ig light and heavy chain profiles in chronic periapical lesions when comparing the permanent and primary dentitions. The ability of IgG4+ plasma cell infiltration to modulate inflammatory responses in chronic periapical lesions arising from permanent as opposed to primary teeth should be considered in future studies.

关键词： pure red cell aplasia   HSC transplantation   ABO mismatch  

摘要： Pure red cell aplasia (PRCA) following allogeneic haematopoietic stem cell transplantation (aHSCT) with major ABO incompatibility is responsible for transfusion dependent anaemia, impaired quality of life and iron overload. We conducted a retrospective study, over a 10-year period, which included all consecutive patients who received a major ABO mismatched aHSCT, to assess the impact of specific treatment on PRCA. We did not observe any PRCA in the 57 aHSCT issued from cord blood. Among the remaining 631 patients, cumulative incidence of PRCA was 10 center dot 5% [range 8 center dot 2-13.0]. The median duration of resolved PRCA was 171 days [IQR 116;261]. Pre-transplant high isohaemagglutinins titre was associated with an increased risk of PRCA (P < 10(-4)). PRCA did not affect overall survival (P = 0 center dot 95). Twenty-two patients (33 center dot 3%) received at least one specific treatment. The most commonly used treatments were rituximab (17 patients) and donor lymphocyte infusion (DLI;seven patients). Regarding PRCA resolution, we did not observe a significant difference between treated or untreated subjects (HR = 0 center dot 93, 95% confidence interval (CI) 0 center dot 48- 1 center dot 80;P = 0 center dot 82). Similar results were observed with erythropoietin treatment (22 patients, HR = 0 center dot 86 95% CI: [0 center dot 47-1 center dot 57] P = 0 center dot 62). Our data do not support the use of erythropoietin, rituximab or DLI for the treatment of PRCA.

关键词： Amorphous alloy   Nanoporous materials   Dealloying   Diffusion   Electrochemical reactions  

摘要： The effect of minor addition of Ag and Ni on the dealloying behavior, nanoporous structure, and electrocatalytic property has been investigated using Al45Cu45Ti10 amorphous precursor alloy. The dealloying kinetics is significantly suppressed due to low diffusion rate and enhanced passivation effect by addition of Ag and Ni. Two different types of nanoporous composite structure are fabricated, nanoporous Cu incorporated with Ag particles and bi-metallic nanoporous Cu-Ni. The resulting multi-component nanoporous composites exhibit improved electrocatalytic property for BH4? oxidation. This study offers a strategy for fabricating nanoporous composites to replace precious metal electrocatalysis.

关键词： Epidermal growth factor receptor   Head and neck   Meta-analysis   Primary site   Squamous cell carcinoma  

摘要： Background and purpose: To assess the survival benefits associated with epidermal growth factor receptor (EGFR) inhibitors in head and neck squamous cell carcinoma (HNSCC) according to the primary site. Materials and methods: A systematic review and meta-analysis were conducted for randomized phase III trials comparing treatment with or without EGFR inhibitors in locoregionally advanced, recurrent, or metastatic HNSCC. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Data were pooled using a random-effects model. Results: Seven trials with a total of 3391 patients were included. The addition of EGFR inhibitors improved OS in patients with oral cavity-oropharyngeal carcinoma (hazard ratio [HR] 0.77, 95% confi-dence interval [CI] 0.67-0.87, P < 0.001) but not in patients with hypopharyngeal-laryngeal carcinoma (HR 0.94, 95% CI 0.82-1.08, P = 0.398). A significant interaction was found in favor of oral cavity-oropharyngeal carcinoma (P = 0.029). The addition of EGFR inhibitors increased PFS in both patients with oral cavity-oropharyngeal carcinoma (HR 0.67, 95% CI 0.52-0.85, P = 0.001) and patients with hypopharyngeal-laryngeal carcinoma (HR 0.81, 95% CI 0.69-0.94, P = 0.005). A trend towards significant interaction was found in favor of oral cavity-oropharyngeal carcinoma (P = 0.161). Comparable results were observed in the pre-specified subgroup analyses. Meta-regression analyses suggested that the pri-mary site appeared to be a predictor of survival benefits in HNSCC patients who received treatment with EGFR inhibitors over those who did not. Conclusion: Our meta-analysis suggests that the survival benefits of EGFR inhibitors might depend on pri-mary sites in HNSCC. Further studies are needed to confirm this finding. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 158 (2021) 13-20

关键词： Basal-bolus insulin therapy   Insulin therapy initiation   Japanese people with type 2 diabetes   Premixed insulin therapy   Real-world study  

摘要： Introduction Basal-bolus (BB) and premixed insulin regimens may lower fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), but are complex to use and associated with weight gain and hypoglycaemia. Although randomized controlled trials and prospective observational studies in insulin-naive Japanese patients with type 2 diabetes (T2D) inadequately controlled with oral antidiabetic drugs (OADs) initiating these regimens have been conducted, real-world data are lacking. This study describes the characteristics of patients initiating these regimens in routine clinical practice and identifies the course and outcomes of therapy in the year following initiation. Methods Adults with T2D initiating BB or premixed regimens following OAD therapies held in a Japanese electronic medical record database were identified (2010-2019). Subcohorts were determined by treatment changes during <= 12 months of follow-up (no change, intensified, switched, discontinued). Outcomes included change in glycated haemoglobin levels (HbA1c), probability of first reaching HbA1c < 7% (stratified by baseline OAD number, HbA1c and age), and hypoglycaemia incidence. Results The main cohorts comprised 1315 BB and 1195 premixed therapy initiators. Most individuals (67.9%) initiated BB as inpatients;50.8% switched at a mean of 47.6 days. Mean HbA1c lowering was - 2.5% for BB and - 1.4% for premixed regimens (no change cohorts). Overall, a greater proportion achieved HbA1c < 7% if they were (at baseline) taking fewer OADs, in a lower HbA1c category, and aged >= 65 years. Hypoglycaemia incidence (< 70 mg/dl) was higher with BB than premixed regimens and lower in patients aged < 65 years. Conclusion Greater HbA1c reductions, but a higher incidence of hypoglycaemia, were reported with BB versus premixed regimens, while both cohorts demonstrated clinically meaningful reductions in HbA1c during follow-up. After initiation, most premixed regimens remained unchanged, whereas switches from BB to less

关键词： Hemi-parasite   scale-like leaves   Subgenus Frisea   systematics   Thesiaceae  

摘要： Thesium L. is in need of revision and has been identified as a high priority for taxonomic research in South Africa. As part of an ongoing effort to revise the genus, a group of nine morphologically similar taxa from Sub -genus Frisea is revised, including three taxa classified by the IUCN as data deficient due to taxonomic prob-lems and one species new to science (T. atratum *** & *** Roux). Species of the group, referred to here as the T. scirpioides complex, share the following characters: (1) inconspicuous unarmed herbs or suffru-tices, (2) scale-like leaves, (3) indeterminate spike-like inflorescences, (4) post-staminal hairs attaching the anthers to the perianth and (5) twisted placental columns. A comprehensive taxonomic revision of the T. scir-pioides complex is presented, including an identification key, updated nomenclature and typifications, descriptions, diagnostic characters, distribution maps and conservation notes. Seven species are recognised and two varieties newly synonymised. (c) 2020 SAAB. Published by Elsevier B.V. All rights reserved.

关键词： DPP‐   IV inhibitor   insulin   meta‐   analysis   T2DM  

摘要： Background To evaluate the efficacy and safety of dipeptidyl peptidase IV (DPP-IV) inhibitors when added to insulin therapy in patients with type 2 diabetes mellitus (T2DM). Methods PubMed, EMBASE, the Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) exploring the efficacy or safety of DPP-IV inhibitors in T2DM patients. The quality of the included RCTs was assessed with the Cochrane risk-of-bias tool. For outcomes, odds ratios or weighted mean differences (WMDs) with 95% CIs were calculated using both random- and fixed-effects models. Results A total of 16 studies were included in the meta-analysis with 5418 participants. Glycosylated hemoglobin (HbA1c) was significantly decreased in the DPP-IV inhibitors with insulin (DPP-IVi/INS) group compared with the insulin-alone (with or without placebo) group (WMD = -0.62%;95% CI: -0.74, -0.49;P < .05). Consistent with this finding, the fasting blood glucose (FBG)-lowering effect (WMD = -0.61 mmol/L;95% CI: -0.77, -0.45;P < .05) and 2-hour postprandial glucose (2hPPG)-lowering efficacy (WMD = -2.39 mmol/L;95% CI: -2.81, -1.97;P < .05) in the DPP-IVi/INS group were also significantly better than in the insulin-alone group. Regarding safety indicators, compared with the insulin-alone group, DPP-IVi/INS treatments had no association with the risk of adverse effects, including hypoglycemia, adverse events (AEs), and serious adverse events (SAEs). Conclusions Compared with insulin treatment alone, treatment with DPP-IVi/INS improved HbA1c, FBG, and 2hPPG without increasing the risk of hypoglycemia, AEs, or SAEs.