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Tissue-resident memory T cells (TRM) contained at sites of previous infection provide local protection against reinfection. Whether they form and function in organ transplants where cognate antigen persists is unclear. This is a key question in transplantation as T cells are detected long term in allografts, but it is not known whether they are exhausted or are functional memory T cells. Using a mouse model of kidney transplantation, we showed that antigen-specific and polyclonal effector T cells differentiated in the graft into TRM and subsequently caused allograft rejection. TRM identity was established by surface phenotype, transcriptional profile, and inability to recirculate in parabiosis and retransplantation experiments. Graft TRM proliferated locally, produced interferon-γ upon restimulation, and their in vivo depletion attenuated rejection. The vast majority of antigen-specific and polyclonal TRM lacked phenotypic and transcriptional exhaustion markers. Single-cell analysis of graft T cells early and late after transplantation identified a transcriptional program associated with transition to the tissue-resident state that could serve as a platform for the discovery of therapeutic targets. Thus, recipient effector T cells differentiate into functional graft TRM that maintain rejection locally. Targeting these TRM could improve renal transplant outcomes.A child presented to the emergency department with fever, reduced consciousness, irritability and reduced oral intake. Infective meningitis and encephalitis were within the differential diagnoses. Is a lumbar puncture (LP) indicated and, if so, what is the optimal timing of LP? Will antimicrobial pretreatment affect the cerebrospinal fluid (CSF) results? How can clinicians optimise diagnostic stewardship to benefit individual patients and society at large? Interpretation of rapidly available CSF biochemical tests (protein, glucose and lactate levels) and microscopy can provide a prompt insight into the infective aetiology and inform treatment and further diagnostic testing strategies. Diagnosis of an aetiological pathogen in a patient presenting with central nervous system (CNS) infection has clinical, infection control and public health implications. A plethora of tests are available to enable CSF analysis in patients with possible CNS infection. We aimed to summarise current evidence and guidance to ensure the best possible use of the diagnostics available.
The optimal treatment of patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma remains unknown.
To compare overall survival following treatment with a hysterectomy and adjuvant radiotherapy with or without chemotherapy in this group of patients.
Patients diagnosed between January 2004 and January 2016 with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with hysterectomy and postoperative radiotherapy with or without adjuvant concurrent chemotherapy were identified in the National Cancer Database. Overall survival was assessed with Kaplan-Meier curves. selleck products A Cox model was constructed to evaluate survival after controlling for confounding variables. A logistic regression model was used to reveal predictors of chemotherapy use.
A total of 2173 patients were included. The receipt of chemotherapy was associated with an increased 5-year overall survival from 67.6% to 75.6% (p=0.0313). This association trended toward statistical significance on multivariate analysis (adjusted HR (aHR) 0.80; 95% CI 0.63 to 1.01; p=0.0653). Other factors associated with improved survival were undergoing a lymphadenectomy, absence of lymphovascular space invasion, younger age, smaller tumor size, non-black race, and absence of comorbidities. Patients who underwent brachytherapy, had lymphovascular space invasion, were younger, were diagnosed in the more recent years, and were treated in higher volume centers were more likely to receive adjuvant chemotherapy.
Adjuvant chemotherapy and radiation therapy were associated with an increase in survival in patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma compared with those treated with adjuvant radiotherapy alone.
Adjuvant chemotherapy and radiation therapy were associated with an increase in survival in patients with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma compared with those treated with adjuvant radiotherapy alone.
Community management of atrial fibrillation (AF) often requires the use of electrocardiographic (ECG) investigation. Patients discharged following treatment of AF with fast ventricular response (fast AF) can require numerous ECGs to monitor rate and/or rhythm control. Single-lead ECGs have been proposed as a more convenient and relatively accurate alternative to 12-lead ECGs for rate/rhythm management and also diagnosis of AF. We aimed to examine the feasibility of using the AliveCor single-lead ECG monitor for diagnosis and monitoring of AF in the community setting.
During the course of 6 months, this evaluation of a clinical service improvement pathway used the AliveCor in management of patients requiring (1) follow-up ECGs for AF with previously documented rapid ventricular rate or (2) ECG confirmation of rhythm where AF was suspected. Twelve AliveCor devices provided to the acute community medical team were used to produce 30 s ECG rhythm strips (iECG) that were electronically sent to an overreading physician.
Seventy-four patients (mean age 82 years) were managed on this pathway. (1) The AliveCor was successfully used to monitor the follow-up of 37 patients with fast AF, acquiring a combined total of 113 iECGs (median 1.5 ±3.75 per patient). None of these patients required a subsequent 12-lead ECG and this approach saved an estimate of up to £134.49 per patient. (2) Of 53 patients with abnormal pulses, the system helped identify 8 cases of new onset AF and 19 cases of previously known AF that had reverted from sinus back into AF.
We have demonstrated that the AliveCor system is a feasible, cost-effective, time-efficient and potentially safer alternative to serial 12-lead ECGs for community monitoring and diagnosis of AF.
We have demonstrated that the AliveCor system is a feasible, cost-effective, time-efficient and potentially safer alternative to serial 12-lead ECGs for community monitoring and diagnosis of AF.
Website: https://www.selleckchem.com/products/Sodium-butyrate.html
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