IL-10 in cancer: an essential thermostatic regulator between homeostatic immunity and inflammation - a comprehensive review.

Cytokines are soluble proteins that mediate intercellular signaling regulating immune and inflammatory responses. Cytokine modulation represents a promising cancer immunotherapy approach for immune-mediated tumor regression. However, redundancy in cytokine signaling and cytokines' pleiotropy, narrow therapeutic window, systemic toxicity, short half-life and limited efficacy represent outstanding challenges for cytokine-based cancer immunotherapies. Recently, there has been interest in the paradoxical role of IL-10 in cancer, its controversial prognostic utility and novel strategies to enhance its therapeutic profile. Here, the authors review the literature surrounding the role of IL-10 within the tumor microenvironment, its prognostic correlates to cancer patient outcomes and its pro- and antitumor effects, and they assess the legitimacy of potential therapeutic strategies harnessing IL-10 by outlining the notable preclinical and clinical evidence to date.

The effects of acute hyperglycaemia on sports and exercise performance in type 1 diabetes: A systematic review and meta-analysis.

OBJECTIVES: People with type 1 diabetes (T1D) are advised by health care professionals to target mild hyperglycaemia before and during exercise, to reduce the risk of hypoglycaemia. This review aimed to summarise the available evidence on the effects of acute hyperglycaemia on sports and exercise performance in T1D. DESIGN: Systematic review and meta-analysis. METHODS: Medline, EMBASE, CENTRAL, and Web of Science were searched until 29th May 2023 for studies investigating the effects of acute hyperglycaemia on any sports or exercise performance outcome in T1D. Random-effects meta-analysis was performed using standardised mean differences (SMD) when more than one study reported data for similar outcomes. Certainty of evidence for each outcome was assessed using GRADE. RESULTS: Seven studies were included in the review, comprising data from 119 people with T1D. Meta-analysis provided moderate-certainty evidence that acute hyperglycaemia does not significantly affect aerobic exercise performance (SMD -0.17; 95 % CI -0.59, 0.26; p = 0.44). There is low- or very-low certainty evidence that acute hyperglycaemia has no effect on anaerobic (two outcomes), neuromuscular (seven outcomes) or neurocognitive performance (three outcomes), except impaired isometric knee extension strength. One study provided low-certainty evidence that the performance effects of hyperglycaemia may depend on circulating insulin levels. CONCLUSIONS: Acute hyperglycaemia before or during exercise appears unlikely to affect aerobic performance to an extent that is relevant to most people with T1D, based on limited evidence. Future research in this field should focus on anaerobic, neuromuscular and neurocognitive performance, and examine the relevance of circulating insulin levels.

Clinical Outcomes Following Use of Tranexamic Acid in High Tibial Osteotomy: A Systematic Review.

This study aimed to evaluate the clinical outcomes following administration of tranexamic acid (TXA) in patients undergoing high tibial osteotomy (HTO) through a systematic review of current available evidence. A systematic database search of PubMed, Embase and Cumulative Index of Nursing and Allied Health Literature (CINAHL) was performed from inception up to December 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Inclusion criteria were (i) randomised control trials, cohort studies or case-control studies that had more than 10 patients; (ii) studies reporting outcomes after TXA administration, of any route, before or after HTO, compared to placebo, control and different doses or routes; and (iii) studies reporting blood loss, including haemoglobin (Hb) drop, estimated blood loss, transfusion requirement and complications. Case reports, reviews, abstracts, non-HTO studies, non-human studies and duplicates were excluded. A synthesized comparison of drain output, wound complications, transfusion requirement and pooled analyses of blood loss and Hb drop was performed. Eleven studies involving 974 patients were included. Nine studies had placebo comparison, and two used single-dose TXA versus multiple doses. All studies reported on postoperative hemoglobin and nine on blood loss. In the six TXA versus placebo studies reporting on total blood loss, the TXA group had a pooled, estimated standardised mean difference (SMD) in blood loss of -2.37 (95% confidence interval (CI) -3.67, -1.07; P = 0.0004). For the Hb drop, on postoperative days (PODs) one, two, and five, the SMDs were -0.97 (95% CI -1.19, -0.75; P < 0.00001) for POD1, -0.74 (95% CI -1.03, -0.46; P < 0.00001) for POD2 and -0.87 (95% CI -1.10, -0.64; P < 0.00001) for POD5. TXA administration in HTO significantly reduces perioperative blood loss. This can greatly improve recovery, reduce complications and shorten length of stay. This is especially pertinent given supply shortages of NHS blood resources.

Cytokine-based Cancer Immunotherapy: Challenges and Opportunities for IL-10.

Cancer immunotherapy is an evolving field of research. Cytokines have been conceptualized as an anticancer therapy for longer than most other cancer immunotherapy modalities. Yet, to date, only two cytokines are FDA-approved: IFN-α and IL-2. Despite the initial breakthrough, both agents have been superseded by other, more efficacious agents such as immune checkpoint inhibitors. Several issues persist with cytokine-based cancer therapies; these are broadly categorised into a) high toxicity and b) low efficacy. Despite the only moderate benefits with early cytokine-based cancer therapies, advances in molecular engineering, genomics, and molecular analysis hold promise to optimise and reinstate cytokine-based therapies in future clinical practice. This review considers five important concepts for the successful clinical application of cytokine-based cancer therapies including: (i) improving pharmacokinetics and pharmacodynamics, (ii) improving local administration strategies, (iii) understanding context-dependent interactions in the tumour-microenvironment, (iv) elucidating the role of genetic polymorphisms, and (v) optimising combination therapies. IL-10 has been the focus of attention in recent years and is discussed herein as an example.