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关键词： Proteases   Macroautophagy   Disease genetics   Neural ageing   Neurological disorders  

摘要： A Correction to this paper has been published: https://***/10.1038/s41418-021-00783-2

关键词： Early T-stage head and neck cancer   Transoral surgery   Complete resection   Primary control   Predictive factor  

摘要： Background We had previously identified the following risk factors for insufficient control of early T-stage head and neck cancer by transoral surgery (TOS): (1) tumor thickness > 7 mm on enhanced computed tomography (CT), and (2) poor differentiation in pathological examination. We subsequently used a different patient cohort to validate the usefulness of these factors in determining the need for adaptation of TOS. Study setting A prospective observational study Methods Patients who received TOS as a definitive treatment between April 1, 2016 and September 30, 2020 were included. Primary control rates (by single TOS and TOS alone) in relation to the above-mentioned risk factors were calculated. Overall (O), recurrence-free (RF), and disease-free (DF) survival (S) outcomes were evaluated. A combination analysis based on the number of risk factors was also performed. Results Patients with tumor thickness > 7 mm had a 2.88-fold [95% confidence interval (CI) 1.01-8.51] higher risk of incomplete primary resection by single TOS, while patients who showed poor differentiation on pathological assessments had a 13.14-fold (95% CI 3.66-47.14) higher risk of insufficient primary control by TOS alone. The 3 year OS, RFS, and DFS rates were 99%, 83%, and 63%, respectively. Patients with both risk factors had a 93.00-fold (95% CI 4.99-1732.00) higher risk of incomplete primary control by TOS alone. Conclusions Among patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma, primary control by TOS alone may not be achieved in patients with both risk factors, that is, tumor thickness > 7 mm as measured by enhanced CT and poor differentiation on pathological examination.

关键词： total joint arthroplasty   mortality   red cell distribution width   Charlson comorbidity index   outcome  

摘要： Introduction: Mortality after total joint arthroplasty (TJA) has been thoroughly explored. Short and long-term mortality appear to be correlated with patient comorbidities. Red Cell Distribution Width (RDW) is a commonly performed test that reflects the variation in red blood cell size. This study investigated the utility of RDW, when combined with comorbidity indices, in predicting mortality after TJA. Methods: Using a single institutional database, 30,437 primary TJA were identified. Patient demographics (age, gender, body mass index (BMI), pre-operative hemoglobin, RDW, and Charlson Comorbidity Index(CCI)) were queried. The primary outcome was 1-year mortality after TJA. Anemia was defined as hemoglobin <12g/dL for women and <13 g/dL for men. The normal range for RDW is 11.5-14.5%. A preliminary analysis assessed the bivariate association between demographics, preoperative anemia, RDW, CCI, and all-cause mortality within 1-year after TJA. A multivariate regression model was con-ducted to determine independent predictors of 1-year mortality. Finally, ROC curves were used to compare AUC of RDW, CCI and the combination of both in predicting 1-year mortality. Results: The mean RDW was 13.6% +/- 1.2. Eighteen percent of patients had pre-operative anemia. The mean CCI was 0.4 +/- 0.9. RDW, anemia, CCI, and age were significantly associated with a higher incidence of 1-year mortality. RDW, CCI, age, and male sex were found to be independent risk factors for 1-year mortality. RDW (AUC = 0.68) was a better predictor of mortality compared to CCI (AUC = 0.66). The combination of RDW and CCI (AUC = 0.76) predicted 1-year mortality more accurately than CCI or RDW alone. Conclusion: RDW appears to be a useful parameter that, when combined with CCI, can predict the risk for 1-year mortality after TJA. Published by Elsevier Inc.

关键词： diagnosis   low-dose spiral computed tomography   non-small cell lung cancer   tumor-associated autoantibodies  

摘要： Objective The purpose of this study was to analyze the levels of tumor-associated autoantibodies (TAAbs) in lung diseases and determine their diagnostic efficiency in early-stage non-small cell lung cancer (NSCLC). Methods We retrospectively analyzed the levels of 7-TAAbs in 177 newly diagnosed early-stage NSCLC patients, 202 patients with lung benign diseases and 137 healthy cases. The levels of a panel of 7-TAAbs, including p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, GBU4-5, were measured by ELISA. Results The serum levels of p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, and GBU4-5 were not statistically different among NSCLC, benign and healthy groups (p > 0.05). The area under the curve (AUC) of 7-TAAbs was all lower than 0.70. The sensitivity of combined detection was the highest (23.73%), while the specificity was the lowest (88.79%). The positive rates of PGP9.5, SOX2, and combined detection were significantly different among the three groups (p < 0.05). Among them, PGP9.5 and combined detection were significantly different between the NSCLC and benign groups (p < 0.05), PGP9.5, SOX2 and combined detection were significantly different between the NSCLC and healthy groups (p < 0.05). Conclusions The diagnostic efficiency of 7-TAAbs in early-stage NSCLC was not high, so it cannot be used alone as a screening method for NSCLC.

关键词： anti-phospholipid antibody syndrome   autoantibody   B cell   follicular helper T cell   follicular regulatory T cell  

摘要： Primary anti-phospholipid antibody syndrome (pAPS) is a multi-organ autoimmune disease, and autoantibodies are involved in its pathogenesis. Follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) are critical for B cell maturation and antibody production, but their roles in pAPS remain unknown. We enrolled 32 pAPS patients and 23 healthy controls (HCs) and comprehensively analyzed circulating Tfh and Tfr, as well as their subsets, using flow cytometry. Clinical data including autoantibody levels were collected and their correlations with Tfh and Tfr subsets were analyzed. In addition, correlation analyses between B cell functional subsets and Tfh and Tfr were performed. Changes and potential effects of serum cytokines on Tfr and Tfh were further explored. We found the circulating Tfr was significantly decreased while Tfh and Tfh/Tfr ratios were increased in pAPS patients. Tfh2, inducible T cell co-stimulator (ICOS)(+) programmed cell death 1 (PD-1)(+) Tfh and Ki-67(+) Tfh percentages were elevated, while CD45RA(-)forkhead box protein 3 (FoxP3)(hi), Helios(+), T cell immunoglobulin and ITIM (TIGIT)(+) and Ki-67(+) Tfr percentages were decreased in pAPS patients. New memory B cells and plasmablasts were increased and altered B cell subsets and serum autoantibodies were positively correlated with Tfh, Tfh2, ICOS+PD-1(+) Tfh cells and negatively associated with Tfr, CD45RA(-)FoxP3(hi) Tfr and Helios(+) Tfr cells. In addition, pAPS with LA/aCL/beta 2GPI autoantibodies showed lower functional Tfr subsets and higher activated Tfh subsets. Serum interleukin (IL)-4, IL-21, IL-12 and transforming growth factor (TGF)-beta 1 were up-regulated and associated with Tfh and Tfr subset changes. Our study demonstrates that imbalance of circulating Tfr and Tfh, as well as their functional subsets, is associated with abnormal autoantibody levels in pAPS, which may contribute to the pathogenesis of pAPS.

关键词： Cancer surgery   Metastatic disease   Lymph nodes   Immunotherapy  

摘要： Surgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung cancer model, primary subcutaneous tumours were resected with associated dLNs remaining intact, completely resected or partially resected. Median survival after surgery was significantly shorter with complete dLN resection at the time of surgery (49 days (95%CI)) compared to when lymph nodes remained intact (> 88 days;p < 0.05). Survival was partially restored with incomplete lymph node resection and CD8 T cell dependent. Treatment with aCTLA4 whilst effective against the primary tumour was ineffective for metastatic lung disease. Conversely, aPD-1/aCD40 treatment was effective in both the primary and metastatic disease settings and restored the detrimental effects of complete dLN resection on survival. In this pre-clinical lung metastatic disease model that closely reflects the clinical setting, we observe decreased frequency of survival after complete lymphadenectomy, which was ameliorated with partial lymph node removal or with early administration of aPD-1/aCD40 therapy. These findings have direct relevance to surgical lymph node resection and adjuvant immunotherapy in lung cancer, and perhaps other cancer, patients.

关键词： basal insulins   insulin analogues   insulin treatment   long-acting basal insulin   professional CGM   type 2  

摘要： Aims To compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes. Materials and Methods We conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin-treated adults with type 2 diabetes and >= 1 hypoglycaemia risk factor. There were two treatment periods, each with 16-week titration and 2-week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once-weekly titration (target: 3.9-5.0 mmol/L) was based on pre-breakfast self-measured blood glucose. The primary endpoint was percentage of TIR (3.910.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9-7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels. Results At baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74;P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR;<3.9 mmol/L) compared with glargine U100 (ETD -0.88% [95% CI: -1.34, -0.42] or 12.7 min/night;post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed. Conclusions Degludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin-treated people with type 2 diabetes.

关键词： adult T-cell lymphoma   adult T-cell leukemia   angioimmunoblastic T-cell lymphoma   CD30(+) lymphoproliferative disorders   cutaneous T-cell lymphoma   cytotoxic primary cutaneous anaplastic large cell lymphoma   extranodal NK   T-cell lymphoma   nasal type   lymphomatoid papulosis   mycosis fungoides   peripheral T-cell lymphoma   not otherwise specified   primary cutaneous acral CD8(+ )T-cell lymphoma   primary cutaneous CD4(+) small   medium T-cell lymphoproliferative disorder   primary cutaneous CD8(+) aggressive epidermotropic cytotoxic T-cell lymphoma   primary cutaneous gamma-delta T-cell lymphoma   Sezary syndrome   subcutaneous panniculitis-like T-cell lymphoma   T-cell lymphoma  

摘要： Primary cutaneous T-cell lymphomas (CTCLs) are defined as lymphomas with a T-cell phenotype that present in the skin without evidence of systemic or extracutaneous disease at initial presentation. CTCLs other than mycosis fungoides and S = ezary syndrome (SS) account for approximately one third of CTCLs and encompass a heterogenous group of non-Hodgkin lymphomas, ranging from indolent lymphoproliferative disorders to aggressive malignancies with a poor prognosis. The spectrum of CTCLs continues to broaden as new provisional entities are classified. Given the morphologic and histologic overlap among CTCLs and other diagnoses, a thorough clinical history, physical evaluation, and clinicopathologic correlation are essential in the work up and diagnosis of these rare entities. This article will summarize the epidemiologic, clinical, pathologic, and diagnostic features of CTCLs other than mycosis fungoides and SS. ( J Am Acad Dermatol 2021;85:1073-90.)

关键词： adult T-cell leukemia   adult T-cell lymphoma   angioimmunoblastic T-cell lymphoma   brentuximab   CD30(+) lymphoproliferative disorders   cutaneous T-cell lymphoma   cytotoxic T-cell lymphoma   extranodalNK/T-cell lymphoma   immunomodulators   mycosis fungoides   nasal type   non-MF/SS   peripheral T-cell lymphoma   not otherwise specified   phototherapy   primary cutaneous acral CD8(+) T-cell lymphoma   primary cutaneous CD4(+) small/medium T-cell lymphoproliferative disorder   primary cutaneousCD8(+) aggressive epidermotropic cytotoxic T-cell lymphoma   primary cutaneous gamma-delta T-cell lymphoma   prognosis   Sezary syndrome   skin-directed treatment   staging   subcutaneous panniculitis-like T-cell lymphoma   systemic treatment   targeted therapies   topical corticosteroids  

摘要： Primary cutaneous T-cell lymphomas (CTCLs) other than mycosis fungoides (MF) and Sezary syndrome (SS) encompass a heterogenous group of non-Hodgkin lymphomas with variable clinical courses, prognoses, and management approaches. Given the morphologic and histologic overlap among the CTCL subtypes and other T-cell lymphomas with cutaneous manifestations, thorough evaluation with clinicopathologic correlation and exclusion of systemic involvement are essential prior to initiating therapy. Staging and treatment recommendations vary, depending on the subtype, clinical behavior, and treatment response. Generally, for subtypes in which staging is recommended, Ann Arbor or tumor, node, metastasis staging specific to CTCL other than MF or SS are used. Formany subtypes, there is no standard treatment to date. Available recommended treatments range widely, from no active or minimal intervention with skin-directed therapy to aggressive systemic therapies that include multi-agent chemotherapy with consideration for hematopoietic stem cell transplant. Emerging targeted therapies, such as brentuximab, a chimeric antibody targeting CD30, show promise in altering the disease course of non-MF/SS CTCLs.