Is there a practical way of predicting therapeutic success in type 2 diabetes on the basis of psychological features? Development and validation of the Psychological Predictors of Therapeutic success in Diabetes (PPTD) questionnaire

Many psychiatric disorders and symptoms have been associated with impaired metabolic control in type 2 diabetes; several studies focused on non-pathological psychological features. Aims of this observational, longitudinal study are: the assessment of the impact of a wide range of psychological factors on metabolic control in type 2 diabetes; and the development and validation of a simple questionnaire to assess the impact of psychological factors on therapeutic success. To identify psychological factors interfering with attainment of glycemic targets, a prospective 1-year study was performed on a sample of 250 patients with type 2 diabetes. The impact of identified factors on therapeutic outcome was then subsequently verified on a further, independent sample of 200 patients. The first phase of the study allowed the development of a 19-items questionnaire, the Psychological Predictors of Therapeutic success in Diabetes (PPTD) questionnaire. Validation analyses showed that the questionnaire was able to predict therapeutic success. Patients with HbA1c ≤7 % (53 mmol/mol) at follow-up showed higher test scores than those with HbA1c >7 % [31.0 (26.2; 35.0) vs 28.0 (23.0; 32.0); p = 0.016]. The attainment and maintenance of therapeutic goals in patients with type 2 diabetes depend on a wide range of factors. The PPTD is an attempt at condensing the complexity of psychological factors affecting glycemic control in a simple and easy-to-use self-reported questionnaire, which can be used in wide-scale research.     

Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes

Excess cortisol and GH induce insulin resistance, a central feature of type 2 diabetes (T2D). To study whether the insulin sensitizer pioglitazone affects basal cortisol levels and the GH–IGF-I axis in patients with T2D. Forty-eight patients with T2D (men/women = 28:20, age 61 ± 1 years, BMI 31 ± 0.6 kg/m²) were treated for 26 weeks with pioglitazone 30–45 mg daily in addition to their preexisting therapy. Insulin, proinsulin, HbA_1c, IGF-I, IGFBP-1, and basal cortisol were analyzed before and after treatment. Pioglitazone decreased proinsulin/insulin ratio and HbA_1c decreased (HbA_1c from 7.8 ± 0.2 to 6.6 ± 0.2 % in men and from 7.6 ± 0.2 to 6.1 ± 0.2 % in women, p < 0.001 in both). There was a redistribution of fat but no change in waist circumference. IGF-I and adiponectin increased (p ≤ 0.001) in both genders. IGFBP-1 increased but significantly only for the whole group (p = 0.033). Triglycerides decreased significantly in women only (p = 0.015). Before treatment, women had lower basal cortisol (p = 0.045). Basal cortisol increased in women (from 390 ± 26 to 484 ± 32 nmol/L, p = 0.020) but not in men and did not differ between genders at week 26. ΔIGFBP-1 correlated with Δcortisol (r = 0.458; p = 0.049) and Δadiponectin (r = 0.600; p = 0.005) in women only. In addition to the known effect of improving insulin sensitivity, pioglitazone increased IGF-I regardless of gender and in women also increased basal cortisol. Increased IGF-I may contribute to improved insulin sensitivity after treatment. There seems to be gender differences in treatment responses to pioglitazone on lipid metabolism and basal cortisol, perhaps correcting different mechanisms of insulin resistance between genders.     

Increased atherosclerosis in mice with increased vascular biglycan content

Objective

The response to retention hypothesis of atherogenesis proposes that atherosclerosis is initiated via the retention of atherogenic lipoproteins by vascular proteoglycans. Co-localization studies suggest that of all the vascular proteoglycans, biglycan is the one most closely co-localized with LDL. The goal of this study was to determine if over-expression of biglycan in hyperlipidemic mice would increase atherosclerosis development.

Methods

Transgenic mice were developed by expressing biglycan under control of the smooth muscle actin promoter, and were crossed to the LDL receptor deficient (C57BL/6 background) atherosclerotic mouse model. Biglycan transgenic and non-transgenic control mice were fed an atherogenic Western diet for 4–12 weeks.

Results

LDL receptor deficient mice overexpressing biglycan under control of the smooth muscle alpha actin promoter had increased atherosclerosis development that correlated with vascular biglycan content.

Conclusion

Increased vascular biglycan content predisposes to increased lipid retention and increased atherosclerosis development.     

头颈部鳞癌程序性死亡配体-1的共表达基因及 调控网络的生物信息学分析

目的 运用生物信息学的方法绘制头颈部鳞癌（HNSCC）中程序性死亡配体-1（PD-L1）共表达基因关系网络,筛选潜在的PD-L1的协同标志物,寻找可能的PD-L1基因调控肿瘤免疫状态的基因和通路。方法 利用癌症和肿瘤基因图谱（TCGA）中的大样本HNSCC的转录组学数据,在cBioPortal数据平台进行基因集的检索,筛选PD-L1共表达基因,在R语言的clusterProfiler中进行GO-BP和KEGG富集分析,再进行分子关系网络分析,提取重要节点基因（hub基因）,再进行生存分析。结果 筛选出共表达基因117个,共表达基因主要富集在免疫调节和病毒反应过程。网络节度分析得到了10个hub基因,依次为STAT1、IFNG、CXCL10、CCR5、FCGR3A、CXCL9、GBP5、CD86、GZMB、IRF1。生存分析显示：CCR5、CXCL9、GZMB是HNSCC预后相关的重要基因。这些基因均参与了免疫过程,其表达与PD-L1相关（Pearson相关系数为0.30、0.35、0.39,P值均小于0.01）。这些基因高表达在HNSCC中均为保护因素。结论 HNSCC中的PD-L1共表达的主要基因均为免疫相关基因,其中CCR5、CXCL9、GZMB与PD-L1存在共表达关系,与预后相关,其可能与程序性死亡受体-1（PD-1）/PD-L1介导的肿瘤免疫逃避相关,为进一步研究PD-1/PD-L1的作用机制和精准靶向治疗提供了新的参考。     

Refining amyloid complete hematological response: Quantitative serum free light chains superior to ratio

Response assessment in light chain (AL) amyloidosis is based on serum and urine monoclonal protein studies. Newly diagnosed patients (n = 373) who achieved very good partial response or complete response (CR) to first line therapy were assessed for the survival impact of each of the monoclonal protein studies. At end of therapy (EOT), negative serum/urine immunofixation (IFE) was achieved in 61% of patients, 72% achieved normal serum free light chain ratio (sFLCR), and the median involved free light chain (iFLC) and difference between involved to uninvolved light chain (dFLC) were 17 mg/L and 5 mg/L, respectively. Overall, 46% of patients achieved a CR at EOT. At EOT, iFLC ≤20 mg/L and dFLC ≤10 mg/L were additive in survival discrimination to negative serum/urine IFE and were independent predictors of overall survival. In contrast, normalization of sFLCR did not add survival discrimination to serum/urine IFE and was not independent predictor of survival. We propose a new definition for hematological CR to include serum/urine IFE negativity plus iFLC ≤20 mg/L or dFLC ≤10 mg/L, instead of the current definition of serum/urine IFE negativity and normal sFLCR. Complete response using dFLC ≤10 mg/L had the best performance in those with significant renal dysfunction and by light chain isotype, making it the preferred partner to IFE. Validation of these results in a multicenter cohort is warranted.     

Treatment of upper extremity deep vein thrombosis with apixaban and rivaroxaban

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.