Browsing by Author "Pinho, S."
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- [CR-POSSUM and Surgical Apgar Score as predictive factors for patients' allocation after colorectal surgery]Publication . Pinho, S.; Lagarto, F.; Gomes, B.; Costa, L.; Nunes, C.; Oliveira, C.Background and objectives: Surgical patients frequently require admission in high-dependency units or intensive care units. Resources are scarce and there are no universally accepted admission criteria, so patients' allocation must be optimized. The purpose of this study was to investigate the relationship between postoperative destination of patients submitted to colorectal surgery and the scores ColoRectal Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (CR-POSSUM) and Surgical Apgar Score (SAS) and, secondarily find cut-offs to aid this allocation. Methods: A cross-sectional prospective observational study, including all adult patients undergoing colorectal surgery during a 2 years period. Data collected from the electronic clinical process and anesthesia records. Results: A total of 358 patients were included. Median score for SAS was 8 and CR-POSSUM had a median mortality probability of 4.5%. Immediate admission on high-dependency units/intensive care units occurred in 51 patients and late admission in 18. Scores from ward and high-dependency units/intensive care units patients were statistically different (SAS: 8 vs. 7, p<0.001; CR-POSSUM: 4.4% vs. 15.9%, p<0.001). Both scores were found to be predictors of immediate postoperative destination (p<0.001). Concerning immediate high-dependency units/intensive care units admission, CR-POSSUM showed a strong association (AUC 0.78, p=0.034) with a ≥9.16 cut-off point (sensitivity: 62.5%; specificity: 75.2%), outperforming SAS (AUC 0.67, p=0.048), with a ≤7 cut-off point (sensitivity: 67.3%; specificity: 56.1%). Conclusions: Both CR-POSSUM and SAS were associated with the clinical decision to admit a patient to the high-dependency units/intensive care units immediately after surgery. CR-POSSUM alone showed a better discriminative capacity.
- Glycans as Key Checkpoints of T Cell Activity and FunctionPublication . Pereira, M.; Alves, I.; Vicente, M.; Campar, A.; Silva, M.; Padrão, N.; Pinto, V.; Fernandes, Â.; Dias, A.; Pinho, S.The immune system is highly controlled and fine-tuned by glycosylation, through the addition of a diversity of carbohydrates structures (glycans) to virtually all immune cell receptors. Despite a relative backlog in understanding the importance of glycans in the immune system, due to its inherent complexity, remarkable findings have been highlighting the essential contributions of glycosylation in the regulation of both innate and adaptive immune responses with important implications in the pathogenesis of major diseases such as autoimmunity and cancer. Glycans are implicated in fundamental cellular and molecular processes that regulate both stimulatory and inhibitory immune pathways. Besides being actively involved in pathogen recognition through interaction with glycan-binding proteins (such as C-type lectins), glycans have been also shown to regulate key pathophysiological steps within T cell biology such as T cell development and thymocyte selection; T cell activity and signaling as well as T cell differentiation and proliferation. These effects of glycans in T cells functions highlight their importance as determinants of either self-tolerance or T cell hyper-responsiveness which ultimately might be implicated in the creation of tolerogenic pathways in cancer or loss of immunological tolerance in autoimmunity. This review discusses how specific glycans (with a focus on N-linked glycans) act as regulators of T cell biology and their implications in disease.
- Metabolic control of T cell immune response through glycans in inflammatory bowel diseasePublication . Dias, A.; Correia, A.; Pereira, M.; Almeida, C.; Alves, I.; Pinto, V.; Catarino, T.; Mendes, N.; Leander, M.; Oliva-Teles, M.; Maia, L.; Delerue-Matos, C.; Taniguchi, N.i; Lima, Margarida; Pedroto, I.; Marcos-Pinto, Ricardo; Lago, P.; Reis, C.; Vilanova, M.; Pinho, S.Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5-/-, MGAT5+/-) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.