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关键词： Type 2 diabetes   Basal insulin supported oral therapy   Treatment intensification   Patient communication  

摘要： Introduction Despite the development of several recommendations, glycemic control in a large proportion of patients with type 2 diabetes, including those treated with insulin, remains suboptimal. This study is aimed to identify a set of actions to promote the reduction of inappropriate clinical practices in type 2 diabetes failing basal insulin supported oral therapy (BOT). Methods A panel of diabetes specialists was assembled to identify a list of ten corrective actions, "things not to do," for the management of type 2 diabetes: five concerning treatments, procedures and diagnostic tests and five about relationship, communication and information. The Choosing Wisely methodology and approach were the inspiration. Results A total of 73/73 (100%) panelists responded to the survey. Twenty-four actions were proposed. The final list of inappropriate actions deemed most important to improve the management of patients with type 2 diabetes failing BOT were: (1) do not use secretagogues-do not neglect the use of innovative glucose-lowering agents;(2) do not underestimate the risk of lack of hypoglycemia awareness;(3) do not underestimate the benefit of personalization of therapy;(4) do not delay insulin intensification;(5) do not delay modification of the therapeutic regimen. In the area of patient communication, the following actions were identified: (1) do not fail to train in the management of hypoglycemia;(2) do not underestimate whether the patient has understood the modification of therapy;(3) do not prescribe injection therapy without adequately instructing the patient to titrate it;(4) do not ignore the patient's adherence;(5) do not stop listening to the patient and verify learning. Conclusion A set of corrective experience-based actions to enact in a timely manner, which can assist physicians in improving clinical outcomes and patients' needs in terms of communications and interaction, is proposed. The list is intended to promote discussions among diabetes speciali

关键词： interim PET   lymphoma   prognosis   refractory  

摘要： Interim FDG-PET (iPET) in diffuse large B-cell lymphoma (DLBCL) is increasingly practised and used in clinical trials to adapt further therapy. However, the optimum timing and methodology of iPET remains controversial. We retrospectively analysed the iPET results and outcomes of 200 DLBCL patients where FDG-PET was routinely performed at baseline, after 2 cycles (iPET2) and at completion of chemoimmunotherapy. iPET was also performed after 4 cycles (iPET4) where at iPET2, Deauville score (DS) was >= 4. Scans were assessed by blinded expert lymphoma PET physicians for DS, maximum standard uptake value (SUVmax), total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG). Treatment failure was defined as death, progression or refractory disease. 95.5% of patients received R-CHOP. No baseline PET parameter was predicted for EFS or OS independent of the NCCN-IPI. The multivariable analysis at iPET2 showed DS5 (19.5% of cases) predicted treatment failure (HR 6.29, 95% CI 3.01-13.17, P < .001), but DS4 was equivalent to DS1-3. At iPET4, Delta SUVmax < 66% predicted treatment failure (HR 5.49, 95% CI 3.03-9.99, P < .001). By multivariable analysis of all time points, high NCCN-IPI and DS5 at iPET2 were negative predictors of survival. These findings were independent of novel prognostic markers.

关键词： fruits and seeds morphology   identification   PCA   populations variation   Rosa sericea complex  

摘要： In this research, the fruits and seeds' surface morphological features and their taxonomic significance were determined. Additionally, useful traits for delimitation of taxa of Rosa sericea complex were studied. In this research, three taxa of the complex R. sericea, R. omeiensis, and R. sikangensis have been studied. A total of 41 populations and 130 specimens of seeds, and 35 populations and 168 specimens of fruits from 10 different geographical regions of southwest China have been examined. The surface micro-morphological characters of the seeds have been studied through scanning electron microscopy to distinguish important characteristics of the complex taxa. Forty-four different qualitative and quantitative characteristics were observed. Principal component analysis was used to simplify and elucidate the relationship between the studied characters of different population based on the morphology of fruits and seeds' features. Moreover, the numerical taxonomic characters and their variation with elevation have been studied in these species. The most interesting characters observed on the surface of the seeds were stomata, and trichomes, for which density was more at the dorsal and ventral parts, while rarely present on the lateral parts. The fruits and seeds' surface morphology of the studied species was complicated and some variation in the characters, that is, persistent calyx shape, the shape of fruits and seeds, stomata shape, and trichomes size were found significant for delimitation of taxa in the complex. The purpose of this study is to identify the taxa of R. sericea complex based on fruits and seeds' morphological characters, and identification keys.

摘要： Prolonged complete remissions (CRs) are rare in advanced-stage cutaneous T-cell lymphomas (CTCLs). Ifosfamide + etoposide (I+E) have been used to treat lymphomas, combined with platinum-based agents in Hodgkin disease or non-Hodgkin lymphomas including peripheral T-cell lymphomas. Monoclonal antibodies have induced long-term remissions in CTCL but are usually poorly effective in transformed disease Allogeneic haematopoietic stem cell transplantation (alloHSCT) holds a potential for cure but relies on the existence of a pretransplant CR, which may require the use of chemotherapeutic regimens. To our knowledge, to date there are no published data on I+E efficacy and tolerance in advanced refractory CTCL. We performed a retrospective monocentre study on 28 patients with mycosis fungoides (MF, n=15) or Sézary syndrome (SS, n=13) treated with I+E between 2012 and 2019. In this study, I+E showed antitumor activity in these heavily pretreated patients with CTCL, with an ORR of 43%, and no significant difference between the full-dose and reduced-dose regimens in terms of ORR or SAE frequencies, indicating that the reduced regimen may be a suitable option in fragile patients. In conclusion, I+E is a valuable therapeutic option in patients with advanced, refractory CTCL.

关键词： cell synchronization   chondrocytes   articular cartilage   tissue engineering  

摘要： Objective. Although tissue engineering is a promising option for articular cartilage repair, it has been challenging to generate functional cartilaginous tissue. While the synthetic response of chondrocytes can be influenced by various means, most approaches treat chondrocytes as a homogeneous population that would respond similarly. However, isolated cells heterogeneously progress through the cell cycle, which can affect macromolecular biosynthesis. As it is possible to synchronize cells within discrete cell cycle phases, the purpose of this study was to investigate the effects of cell cycle synchronization on the chondrogenic potential of primary articular chondrocytes. Design. Different methods of cell synchronization (serum starvation, thymidine, nocodazole, aphidicolin, and RO-3306) were tested for their ability to synchronize primary articular chondrocytes during the process of cell isolation. Cells (unsynchronized and synchronized) were then encapsulated in alginate gels, cultured for 4 weeks, and analyzed for their structural and biochemical properties. Results. The double-thymidine method yielded the highest level of cell purity, with cells synchronized in S phase. While the cells started to lose synchronization after 24 hours, tissue constructs developed from initially S phase synchronized cells had significantly higher glycosaminoglycan and collagen II amounts than those developed using unsynchronized cells. Conclusions. Initial synchronization led to long-term changes in cartilaginous tissue formation. This effect was postulated to be due to the rapid auto-induction of TGF-beta s by actively dividing S phase cells, thereby stimulating chondrogenesis. Cell synchronization methods may also be applied in conjunction with redifferentiation methods to improve the chondrogenic potential of dedifferentiated or diseased chondrocytes.

关键词： foot-and-mouth disease vaccine   memory T cell   tetramer  

摘要： Foot-and-mouth disease (FMD) is a highly contagious, economically devastating disease of cloven-hooved animals. The development of long-lasting effective FMD vaccines would greatly benefit the global FMD control programme. Deep analysis of adaptive immunity in cattle vaccinated against FMD is technically challenging due to the lack of species-specific tools. In this study, we aimed to identify CD4(+) T-cell epitopes in the FMD virus (FMDV) capsid and to phenotype the CD4(+) T cells that recognize them using bovine major histocompatibility complex (BoLA) class II tetramer. A BoLA class II tetramer based on the DRA/DRB3*020:02 allele and FMDV antigen-stimulated PBMCs from bovine vaccinates were used to successfully identify four epitopes in the FMDV capsid, three of which have not been previously reported;two epitopes were identified in the structural protein VP1, one in VP3 and one in VP4. Specificity of the three novel epitopes was confirmed by proliferation assay. All epitope-expanded T-cell populations produced IFN-gamma in vitro, indicating a long-lasting Th1 cell phenotype after FMD vaccination. VP3-specific CD4(+) T cells exhibited the highest frequency amongst the identified epitopes, comprising >0 center dot 004% of the CD4(+) T-cell population. CD45RO(+)CCR7(+) defined central memory CD4(+) T-cell subpopulations were present in higher frequency in FMDV-specific CD4(+) T-cell populations from FMD-vaccinated cattle ex vivo. This indicates an important role in maintaining cell adaptive immunity after FMD vaccination. Notably, FMDV epitope-loaded tetramers detected the presence of FMDV-specific CD4(+) T cells in bovine PBMC more than four years after vaccination. This work contributes to our understanding of vaccine efficacy.

摘要： Objective: Mast cell (MC) activation (MCA) defines the mechanism by which certain patients have symptoms owing to the effect of a wide range of mediators released from MCs upon their activation, when triggered by dif-ferent stimuli. When these symptoms are severe and recurrent, the diagnosis of MCA syndrome (MCAS) might be considered. Here, we review the relevant aspects related to the pathogenesis of MCAS, with special emphasis on the prevalence and diagnostic relevance of KIT mutations. Data Sources: PubMed was searched between 1980 and 2021 using the following terms: mast cell activation syndromes, mast cell activation, anaphylaxis, KIT mutations, KIT D816V, indolent systemic mastocytosis, bone marrow mastocytosis, cutaneous mastocytosis, IgE anaphylaxis, and idiopathic anaphylaxis. Study Selections: Only articles published in English were selected based on their relevance to MCAS or severe and recurrent anaphylaxis. Results: MCAS can be classified as clonal MCAS and nonclonal MCAS depending on the presence vs absence of an underlying KIT mutation (mostly KIT D816V), respectively. In contrast to clonal MCAS in which MCA is associated with a primary MC disorder (ie, primary MCAS) such as mastocytosis or monoclonal MCAS, nonclonal MCAS can be secondary to known or unidentified triggers (ie, secondary and idiopathic MCAS, respectively). Conclusion: The clinical heterogeneity and complexity of the molecular assays needed for the study of patients with MCAS might lead to misdiagnosis, particularly when patients are evaluated at nonspecialized centers. Thus, referral of patients having clinical manifestations suggestive of MCAS to reference centers on mastocytosis and MC diseases is strongly recommended. (c) 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

关键词： prognostic factor   radiotherapy   rituximab   survival   Waldeyer&apos   s ring DLBCL  

摘要： This study aimed to identify the prognostic factors in patients with Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL), comparing the efficacy of radiotherapy (RT) for the WR-DLBCL patients in the pre-rituximab and rituximab eras. We conducted a retrospective analysis of 134 patients diagnosed with WR-DLBCL. Univariate and multivariate analyses were performed to identify the prognostic factors for WR-DLBCL. Then, we divided these patients into the rituximab plus chemotherapy group (R-chemotherapy) (n = 88) and chemotherapy group (n = 46), and the Kaplan-Meier and Cox regression model analyses were applied to investigate the treatment value of RT in both the groups. Multivariate analysis revealed international prognostic index (IPI) >= 3 and chemotherapy without rituximab as significant risk factors for the progression-free survival (PFS, IPI >= 3: p = 0.001;chemotherapy without rituximab: p = 0.002) and overall survival (OS, IPI >= 3, p < 0.001;chemotherapy without rituximab, p = 0.024). Rituximab combined with chemotherapy significantly improved PFS (p = 0.002) and OS (p = 0.006) in these patients. RT did not significantly contribute to the survival in the overall cohort analysis, whereas in the subgroup analysis, RT significantly improved the PFS (p = 0.025) and OS (p = 0.029) for the patients in the chemotherapy group, but not in the R-chemotherapy group. In conclusion, the WR-DLBCL patients could benefit from RT in the pre-rituximab era, whereas the addition of rituximab to chemotherapy significantly improved the survival of WR-DLBCL patients, and the clinical benefit of RT was reduced.

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