St. Vincent's Hospital (Irish: Ospidéal Ollscoile Naomh Uinseann) is a teaching hospital located at Elm Park, south of the city of Dublin, Ireland. It is at the junction of Merrion Road and Nutley Lane opposite the Merrion Centre and adjacent to Elm Park Golf Club. It is managed by Ireland East Hospital Group.
Inflammatory arthritis (IA) is a group of autoimmune diseases characterised by joint inflammation and progressive damage, thus impairing the patient’s quality of life. The JAK/STAT pathway inhibitor Tofacitinib has been successfully introduced into the clinic to treat patients with IA, however its direct effect on T cell responses is widely unknown. This study aims to assess the effect of Tofacitinib on T cell activation, polyfunctionality, proliferation and metabolism. The effect of Tofacitinib on T cells from peripheral blood, synovial fluid and synovial tissue was evaluated with multidimensional flow cytometric analysis. T cell proliferation was assessed by flow cytometry and T cell metabolism was examined by qPCR and Seahorse XF analyser. To investigate the effect of Tofacitinib on T cell polarisation, naïve T cells were differentiated into Th1, Th2 and Th17 with specific cytokine cocktails. Soluble mediators were evaluated by MSD multiplex analysis. Tofacitinib significantly inhibited T helper cell activation as evidenced by a marked reduction in the frequency of PD-1/CD69/CD25-positive cells (p < 0.01). Reduced activation was consistent with impairment of pathogenic polyfunctionality of peripheral blood and synovial tissue-derived T cells. The impact of Tofacitinib on T cell plasticity was further substantiated by reduced T cell polarisation towards Th1 (p < 0.05), Th2 (p < 0.05), Th17 (p < 0.05) and a reduction in genes associated with T cell functions. The attenuation of pathogenic T cell responses is linked to metabolic adaptation, with Tofacitinib leading to a switch in metabolic capacity, mainly ascribed to the CD4−CD8+ T cell compartment. Tofacitinib strongly alters T cell responses and potentially limits T cell pathogenicity by decreasing their activation, polyfunctionality, differentiation, and metabolic potential in both the circulation and the joints of patients with inflammatory arthritis.
Screen-detected colorectal cancers (CRCs) represent an increasing proportion of diagnoses as population screening is expanded. They are associated with improved prognosis compared to non-screening cases even when adjusted for stage. We aimed to evaluate the histopathological features and impact on survival of faecal immunochemical test (FIT)–based screen-detected CRCs with comparison to a cohort of non-screening cases. We analysed a database of screen-detected CRCs (n = 191) in our institution since screening began in 2012 with comparison to a cohort of non-screening cases (2019–2020, n = 358). Histopathological reports were reviewed for prognostic factors such as lymphovascular invasion (LVI), perineural invasion (PNI) and tumour budding. The patient record was reviewed for survival analysis. Screen-detected CRCs were associated with an earlier stage of diagnosis (p = 0.002) and had lower rates of serosal involvement (T4) (20
To critically appraise and evaluate the safety and efficacy of intraoperative tranexamic acid (TXA) administration during transurethral resection of the prostate (TURP). A systematic search of online databases was conducted to identify randomised-controlled trials (RCTs) which compared surgical outcomes and complication rates in patients undergoing TURP for benign prostatic hyperplasia (BPH) who were treated with TXA (intervention) as compared to placebo/none (control). The efficacy of intraoperative TXA was evaluated through outcomes related to blood loss, rate of blood transfusion and operative time. The safety of TXA was evaluated through pooled analysis of both deep venous thrombosis and pulmonary emboli. Nine RCTs met the inclusion criteria for this meta-analysis in which a total of 661 patients underwent TURP for BPH (331 TXA: 330 Control). There was significantly less intraoperative bleeding in the TXA group (MD –40.23 mL [95
The concept of a therapeutic window of opportunity, defined as the period from symptom onset during which treatment initiation yields the most favorable patient outcomes, is applied in routine clinical practice across a range of inflammatory conditions. It has become an increasingly important area of interest in hidradenitis suppurativa (HS), a disease in which recurrent inflammation and accumulating damage can lead to irreversible destruction of skin architecture. Biologic therapies, aiming to suppress the inflammatory burden and prevent disease progression, are currently only permitted in moderate to severe HS. However, as there is no consensus definition of moderate disease, physicians may face uncertainty about when to consider or switch biologic therapy. To identify the boundaries of the window of opportunity within HS, global HS experts have developed frameworks for defining moderate HS and disease progression. It is proposed that prompt medical treatment should be administered to patients with moderate HS, defined as patients with inadequate control of HS symptoms on conventional therapies, or one inflamed skin tunnel (draining/non-draining), or four or more inflammatory lesions (including inflammatory nodules and abscesses) involving two or more anatomic areas. Furthermore, the proposed definition for disease progression is the development of one or more new tunnel(s) and/or the extension of existing tunnels, or development of one or more persistent HS lesions in an anatomical region not previously affected, or any increase in the number of persistent HS lesions in an affected anatomical region. The proposed frameworks aim to provide practical advice to physicians and support targeting the window of opportunity during routine clinical practice.
