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关键词： diabetes   closed-loop   insulin control   basal needs   artificial pancreas  

摘要： Technology advances have made possible improvements such as Continuous Glucose Monitors, giving the patient a glucose reading every few minutes, or insulin pumps, allowing more personalized therapies. With the increasing number of available closed-loop systems, new challenges appear regarding algorithms and functionalities. Several of the analysed systems in this paper try to adapt to changes in some patients' conditions and, in several of these systems, other variables such as basal needs are considered fixed from day to day to simplify the control problem. Therefore, these systems require a correct adjustment of the basal needs profile which becomes crucial to obtain good results. In this paper a novel approach tries to dynamically determine the insulin basal needs of the patient and use this information within a closed-loop algorithm, allowing the system to dynamically adjust in situations of illness, exercise, high-fat-content meals or even partially blocked infusion sites and avoiding the need for setting a basal profile that approximately matches the basal needs of the patient. The insulin sensitivity factor and the glycemic target are also dynamically modified according to the situation of the patient. Basal insulin needs are dynamically determined through linear regression via the decomposition of previously dosed insulin and its effect on the patient's glycemia. Using the obtained value as basal insulin needs and other mechanisms such as basal needs modification through its trend, ISF and glycemic targets modification and low-glucose-suspend threshold, the safety of the algorithm is improved. The dynamic basal insulin needs determination was successfully included in a closed-loop control algorithm and was simulated on 30 virtual patients (10 adults, 10 adolescent and 10 children) using an open-source python implementation of the FDA-approved (Food and Drug Administration) UVa (University of Virginia)/Padova Simulator. Simulations showed that the proposed sy

关键词： drug utilization   epidemiology   insulin   insulin analogues   type 2 diabetes  

摘要： Aims Aim of this study is to describe changes in the utilization of basal insulins (glargine, detemir, degludec, neutral protamine Hagedorn [NPH]) among individuals with type 2 diabetes between 2003 and 2018 in the United Kingdom (UK). Materials and Methods Using the UK Clinical Practice Research Datalink (CPRD) Aurum, we created three study cohorts of individuals with type 2 diabetes: (1) all users of antidiabetic drugs (n = 686,170);(2) initiators of antidiabetic drugs (n = 382,247);and (3) initiators of basal insulins (n = 85,369). Trends in prescription rates were determined using Poisson regression overall and stratified by sex, cardiovascular disease history, and obesity. Crude and adjusted Cox proportional hazards models were used to obtain hazard ratios (HRs) and confidence intervals (CI) comparing rates of treatment change between classes of basal insulins, with an intention-to-treat exposure definition. Results During the study period, prescription rates of insulin analogues increased in the all-user cohort from 118.3 (95% CI: 116.4, 120.2) prescriptions per 1000 person-years in 2003 to 579.4 (95% CI: 576.9, 582.0) in 2018. Prescription rates of NPH decreased from 770.5 (95% CI: 765.0, 775.3) in 2003 to 457.7 (95% CI: 455.5, 460.0) in 2018. Compared to initiators of NPH, initiators of detemir were more likely to change treatment (adjusted HR: 1.31, 95% CI: 1.25, 1.37) while glargine initiators were less likely to change treatment (adjusted HR: 0.85, 95% CI: 0.82, 0.88). Conclusions Basal insulin prescription evolved between 2003 and 2018. Our study provides insight into the evolving use of basal insulin among individuals with type 2 diabetes in the UK.

关键词： Surgery   Gastroenterology  

关键词： Diabetes classification   Graph convolutional network   Data processing   LSTM   Attention mechanism  

摘要： The classification of type 1 and type 2 diabetes is currently performed based on biochemical indicators and clinical experience. However, considering the unsatisfactory efficiency and accuracy of the experience-based diabetes type classification, we aim to propose a data-driven diabetes classification model through exploiting features contained in flash glucose monitoring (FGM) data. In particular, we propose a novel data reorganization and topologization method to reasonably extract the features of glycemic variability influence. Furthermore, a graph convolutional network is adopted to learn the inter-day influence feature and a Long Short-Term Memory network to characterize intra-day glycemic variability, which enables simultaneous characterization of slow and fast dynamics in FGM data. Finally, to visualize the effectiveness of our model, a t-distributed stochastic neighbor embedding method is implemented. The effectiveness of the proposed model is evaluated through a crossvalidation approach using a dataset containing FGM records of 113 diabetic subjects. Compared with classical machine learning algorithms and neural networks, the proposed model achieved the highest specificity value (0.9943) in diabetes type classification, F-Measure (0.8824) and Matthews correlation coefficient score (0.8250). The obtained results indicate the feasibility of achieving diabetes classification by learning the patterns hidden in continuous glucose monitoring data.

关键词： Sinonasal   Lymphoma   Squamous cell carcinoma   Magnetic resonance imaging   Radiomics  

摘要： Purpose To develop and validate an MRI-based radiomics model in differentiation between sinonasal primary lymphomas and squamous cell carcinomas (SCCs). Materials and methods One-hundred-and-fifty-four patients were enrolled (74 individuals with SCCs and 80 with lymphomas). After feature analysis and feature selection with variance threshold and least absolute shrinkage and selection operator (LASSO) methods, an MRI-based radiomics model with the support vector machine (SVM) classifier was constructed in differentiation between lymphomas and SCCs. Areas under the receiver operating characteristic curves (AUCs) of the MRI-based radiomics model were compared with those of radiologists using Delong test. Results Five features (T1 original shape Compactness2, T1 wavelet-HHH first-order Total Energy, T2 wavelet-HLH GLCM Informational Measure of Correlation1, T1 wavelet-LHL GLCM Inverse Variance and T1 square GLRLM Long Run Low Gray Level Emphasis) were finally selected in the radiomics model. The AUC values in differentiation between lymphomas and SCCs were 0.94 for the training dataset and 0.85 for the validation dataset, respectively. For all the patient datasets, the AUC values of radiomics model, readers 1, 2 and 3 were 0.92, 0.76, 0.77 and 0.80, respectively. For the validation datasets, no significant difference was found between the AUCs of the radiomics model and those of the three radiologist (P = 0.459, 0.469, 0.738 for radiologist 1, 2 and 3, respectively). Conclusion An MRI-based radiomics model can help to differentiate sinonasal lymphomas from SCCs with high accuracy.

关键词： beta‐   cell function   induction   intensive insulin therapy   intermittent insulin   maintenance   preservation  

摘要： Aim To test the hypothesis that the addition of periodic courses of short-term intensive insulin therapy (IIT) could enhance the effect of metformin (MET) maintenance therapy on preservation of beta-cell function following induction IIT. Methods In this multicentre, randomized controlled trial, 108 adults with type 2 diabetes (median 1.3 years' duration;HbA1c 6.6% +/- 0.6%) were randomized to 3 weeks of induction IIT (glargine, lispro) followed by MET maintenance, either with or without periodic 2-week courses of IIT every 3 months for 2 years. Beta-cell function was assessed by the Insulin Secretion Sensitivity Index-2 (ISSI-2) at an oral glucose tolerance test every 3 months. Results In both arms, induction IIT increased ISSI-2, improved whole-body insulin sensitivity and reduced hepatic insulin resistance (all P <= .0004). The primary outcome of baseline-adjusted ISSI-2 at 2 years was not improved by the addition of intermittent IIT (MET + IIT) and was slightly higher in the MET arm (baseline-adjusted difference -35 [95% CI: -66, -3]), with three additional beta-cell measures showing no significant differences. Baseline-adjusted HbA1c at 2 years did not differ between MET and MET + IIT (6.3% +/- 0.1% vs. 6.4% +/- 0.1%, P = .46), with 32.6% of participants in each arm maintaining HbA1c of 6.0% or less at 2 years. Conclusion Although initial induction IIT induces metabolic improvement, subsequent repeat courses of IIT every 3 months do not further enhance the effect of MET maintenance therapy on beta-cell function.

关键词： cutaneous neoplasm   dermatology   dermatopathology   immunohistochemistry   PEComa  

摘要： Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms with characteristic epithelioid or spindled cytomorphology that typically grow around blood vessels. These tumors are phenotypically and immunohistochemically distinct, expressing markers of both melanocytic and smooth muscle differentiation. Herein, we describe a case of histopathologically malignant cutaneous PEComa without metastatic spread, with review of the pertinent literature. Telescoping punch biopsy demonstrated an epithelioid neoplasm with marked atypia, hypercellularity, and increased mitotic activity. Immunohistochemical stains for HMB-45, NK1-C3, PGP9.5, MiTF, CD10, and CD68 were positive within tumor cells. In addition, there was diffuse expression of caldesmon and focal cytoplasmic staining for smooth muscle actin on the excision specimen. The patient underwent treatment with surgical excision with adjuvant radiation and surveillance computed tomography (CT). The patient remains free of recurrence or metastatic disease after 10 months of follow-up. To our knowledge, this is only the third reported case of a malignant cutaneous PEComa reported in the literature to date.

关键词： Intravascular large B-cell lymphoma   Intravascular lymphoma   Peritubular capillary   Renal lymphoma  

摘要： We report on a 70-year-old woman with intravascular large B-cell lymphoma, in whom the renal lesion was localized in the peritubular capillaries. The patient complained of fatigue, general malaise, and unsteadiness when walking. Laboratory tests showed anemia, increased C-reactive protein, and mild renal failure, with a serum creatinine level of 1.31 mg/dL and no remarkable proteinuria or hematuria. Renal biopsy showed intravascular large B-cell lymphoma. The large atypical cells were mainly accumulated within the peritubular capillaries and no large atypical cells were found in the glomeruli. Skin and bone marrow biopsies confirmed intravascular large B-cell lymphoma. Brain magnetic resonance imaging showed multiple small infarctions in the cerebral white matter. The patient was treated with dexamethasone, methotrexate, and cytarabine followed by CHOP (combined cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-CHOP (CHOP with the recombinant anti-CD20 antibody rituximab), and her renal function improved soon after the start of chemotherapy.

关键词： GATA3   Cutaneous lymphoma   Mycosis fungoides   Anaplastic large cell lymphoma   Primary cutaneous CD30-positive T cell lymphoproliferative disorders   T helper cell  

摘要： Mycosis fungoides with large cell transformation (MFLCT) can be difficult to distinguish from primary cutaneous CD30+ T cell lymphoproliferative disorders (PC CD30+ LPD), especially primary cutaneous anaplastic large cell lymphoma (PC-ALCL). This diagnostic distinction is critical for appropriate patient management. GATA3 has been proposed to be useful in the discrimination between these two entities. We identified 25 cases of MFLCT and 24 cases of PC CD30+ LPDs (including lymphomatoid papulosis (n=14), PC-ALCL (n=6), and CD30+ LPD, not otherwise specified (n=4)) diagnosed at our institution from 2002 to 2019. Sections from archived specimens were stained to evaluate for GATA3 expression by immunohistochemistry and compared among cutaneous CD30+ T cell LPDs. The majority of the MFLCT cohort had strong, diffuse expression of GATA3 ranging from 0 to 100% of dermal T cells (mean 53.20%) with 15/25 cases (60%) showing GATA3 expression greater than 50%, while the PC CD30+ LPD group showed variable, moderate GATA3 labeling ranging from 0 to 60% of dermal T cells (mean 23.26%), with 5/6 cases (83%) showing GATA3 expression less than 40% (p =0.003). The calculated sensitivity and specificity were 56% and 74%, while positive and negative predictive values were 70% and 61%, respectively. Based on the percent staining of positive cells, using 50% as a cutoff value for expression, GATA3 might be a useful immunohistochemical marker to discriminate MFLCT from PC CD30+ LPDs, including PC-ALCL.

关键词： cardiomyocytes   NLRP3 inflammasome   noncoding RNA   vascular endothelial cells   ventricular remodeling  

摘要： Inflammasomes are a group of multiprotein signaling complexes located in the cytoplasm. Several inflammasomes have been identified, including NLRP1, NLRP2, NLRP3, AIM2, and NLRC4. Among them, NLRP3 was investigated in most detail, and it was reported that it can be activated by many different stimuli. Increased NLRP3 protein expression and inflammasome assembly lead to caspase-1 mediated maturation and release of IL-1 beta, which triggers inflammation and pyroptosis. The activation of the NLRP3 inflammasome has been widely reported in studies of tumors and neurological diseases, but relatively few studies on the cardiovascular system. Ventricular remodeling (VR) is an important factor contributing to heart failure (HF) after myocardial infarction (MI). Consequently, delaying VR is of great significance for improving heart function. Studies have shown that the NLRP3 inflammasome plays an essential role in the process of VR. Here, we reviewed the latest studies on the activation pathway of the NLRP3 inflammasome, focusing on the effects of the NLRP3 inflammasome in primary cells during VR, and finally discuss future research directions in this field.