A systematic review and Bayesian meta-analysis assessing intelectin-1 in cancer patients and healthy individuals.

Background: Intelectin-1 (ITLN1) is an adipokine with multiple physiological functions, including a role in tumour formation and development. Previous research reported variable ITLN1 levels for cancer patients and healthy individuals. This study aimed to compare ITLN1 concentrations between controls and cancer patients and to determine the adipokine's physiological level. Methods: Five databases were searched in January 2022 for studies that measured the level of ITLN1 in adults that were healthy or diagnosed with any type of cancer. After title, abstract and full-text screening, the methodological quality of the studies was assessed. The extracted data were meta-analysed using the R language and Bayesian statistical techniques. Results: Overall, 15 studies compared circulating ITLN1 levels between healthy individuals (n=3424) and cancer patients (n=1538), but no differences were observed between these studies. ITLN1 was not different between groups in an analysis that evaluated high-quality studies only (n=5). The meta-analysis indicated considerably higher ITLN1 levels in gastrointestinal (i.e., colorectal, pancreatic, gastric) cancer compared to controls, while the other cancer types did not demonstrate differences between groups. The mean ITLN1 level of healthy individuals was 234 ± 21ng/ml (n=136), while the average value in high-quality studies (n=52) was 257 ± 31ng/ml. Conclusion: Different types of cancer showed different circulating ITLN1 patterns. Circulating ITLN1 concentration was higher in gastrointestinal cancer compared to controls, with strong support from the meta-analytical model. Our analysis also determined the mean ITLN1 level in healthy individuals; this is a crucial starting point for understanding how this cytokine associates with diseases. Two-thirds of the studies were of low methodological quality and thus, future work in this field must focus on improved methods. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=303406, identifier CRD42022303406.

Harmony in Chaos: Deciphering the Influence of Ischemic Cardiomyopathy and Non-Cardiac Comorbidities on Holter ECG Parameters in Chronic Heart Failure Patients: A Pilot Study.

Background and Objective: In the landscape of heart failure, non-cardiac comorbidities represent a formidable challenge, imparting adverse prognostic implications. Holter ECG monitoring assumes a supplementary role in delineating myocardial susceptibility and autonomic nervous system dynamics. This study aims to explore the potential correlation between Holter ECG parameters and comorbidities in individuals with ischemic cardiomyopathy experiencing heart failure (HF), with a particular focus on the primary utility of these parameters as prognostic indicators. Materials and Methods: In this prospective inquiry, a cohort of 60 individuals diagnosed with heart failure underwent stratification into subgroups based on the presence of comorbidities, including diabetes, chronic kidney disease, obesity, or hyperuricemia. Upon admission, a thorough evaluation of all participants encompassed echocardiography, laboratory panel analysis, and 24 h Holter monitoring. Results: Significant associations were uncovered between diabetes and unconventional physiological indicators, specifically the Triangular index (p = 0.035) and deceleration capacity (p = 0.002). Pertaining to creatinine clearance, notable correlations surfaced with RMSSD (p = 0.026), PNN50 (p = 0.013), and high-frequency power (p = 0.026). An examination of uric acid levels and distinctive Holter ECG patterns unveiled statistical significance, particularly regarding the deceleration capacity (p = 0.045). Nevertheless, in the evaluation of the Body Mass Index, no statistically significant findings emerged concerning Holter ECG parameters. Conclusions: The identified statistical correlations between non-cardiac comorbidities and patterns elucidated in Holter ECG recordings underscore the heightened diagnostic utility of this investigative modality in the comprehensive evaluation of individuals grappling with HF. Furthermore, we underscore the critical importance of the thorough analysis of Holter ECG recordings, particularly with regard to subtle and emerging parameters that may be overlooked or insufficiently acknowledged.

The Emerging Role of Intelectin-1 in Cancer.

BACKGROUND: Intelectin (ITLN) is an adipokine with two homologs-ITLN1 and ITLN2-that has various physiological functions. Studies analyzing the relationship between ITLN and cancer are focused on ITLN1; the available literature on ITLN2 and cancer is limited. This review aims to evaluate the role of ITLN1 in cancer without imposing any inclusion criteria, to examine pro- and anticancer roles for ITLN1 and to discuss whether the relationship between ITLN and cancer is mediated by obesity. FINDINGS: Overall, ITLN1 level was highly variable in cancer patients but different from healthy individuals. Compared with control groups, patients with gastrointestinal and prostate cancer showed increased concentrations of circulating ITLN1, while patients with gynecological, breast, bladder, and renal cancer had lower ITLN1 levels. Several studies also evaluated tissue and tumor expression of ITLN1. In gastrointestinal cancer, ITLN1 was increased in tumor tissue compared with adjacent healthy tissue and elevated in the visceral adipose tissue of patients compared with controls. Consequently, the high levels of circulating ITLN1 might be determined by the tumor and by the cancer-associated weight loss in gastrointestinal cancer. ITLN1 can activate the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathway. The improper regulation of this pathway may contribute to a series of cellular events that favor tumor development and progression. Obesity has been linked with an increased risk of developing some cancers. Indeed, low circulating ITLN1 levels may be a marker of the metabolic effects of obesity, rather than obesity per se, and might contribute to a deregulation of the PI3K/Akt pathway. CONCLUSIONS: ITLN1 could be associated with cancer formation and progression. Since circulating ITLN1 levels are highly variable and differ between cancer types, the local tumor production of ITLN1 could be more relevant in determining malignant behavior. Future research should aim to identify the source of ITLN1 variability, to understand the differences in ITLN1 between distinct tumor types, and to further explore the signaling pathways through which this adipokine influences cancer biology.

A systematic review examining the relationship between cytokines and cachexia in incurable cancer.

Cancer cachexia is an unmet clinical need that affects more than 50% of patients with cancer. The systemic inflammatory response, which is mediated by a network of cytokines, has an established role in the genesis and maintenance of cancer as well as in cachexia; yet, the specific role of the cytokine milieu in cachexia requires elucidation. This systematic review aims to examine the relationship between cytokines and the cachexia syndrome in patients with incurable cancer. The databases MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO, and Web of Science were searched for studies published between 01/01/2004 and 06/01/2020. Included studies measured cytokines and their relationship with cachexia and related symptoms/signs in adults with incurable cancer. After title screening (n = 5202), the abstracts (n = 1264) and the full-text studies (n = 322) were reviewed independently by two authors. The quality assessment of the selected papers was conducted using the modified Downs and Black checklist. Overall, 1277 patients with incurable cancer and 155 healthy controls were analysed in the 17 eligible studies. The mean age of the patients was 64 ± 15 (mean ± standard deviation). Only 34% of included participants were female. The included studies were assessed as moderate-quality to high-quality evidence (mean quality score: 7.8; range: 5-10). A total of 31 cytokines were examined in this review, of which interleukin-6 (IL-6, 14 studies) and tumour necrosis factor-α (TNF-α, 12 studies) were the most common. The definitions of cachexia and the weight-loss thresholds were highly variable across studies. Although the data could not be meta-analysed due to the high degree of methodological heterogeneity, the findings were discussed in a systematic manner. IL-6, TNF-α, and IL-8 were greater in cachectic patients compared with healthy individuals. Also, IL-6 levels were higher in cachectic participants as opposed to non-cachectic patients. Leptin, interferon-γ, IL-1ß, IL-10, adiponectin, and ghrelin did not demonstrate any significant difference between groups when individuals with cancer cachexia were compared against non-cachectic patients or healthy participants. These findings suggest that a network of cytokines, commonly IL-6, TNF-α, and IL-8, are associated with the development of cachexia. Yet, this relationship is not proven to be causative and future studies should opt for longitudinal designs with consistent methodological approaches, as well as adequate techniques for analysing and reporting the results.

Influence of resistance training load on measures of skeletal muscle hypertrophy and improvements in maximal strength and neuromuscular task performance: A systematic review and meta-analysis.

This systematic review and meta-analysis determined resistance training (RT) load effects on various muscle hypertrophy, strength, and neuromuscular performance task [e.g., countermovement jump (CMJ)] outcomes. Relevent studies comparing higher-load [>60% 1-repetition maximum (RM) or <15-RM] and lower-load (≤60% 1-RM or ≥ 15-RM) RT were identified, with 45 studies (from 4713 total) included in the meta-analysis. Higher- and lower-load RT induced similar muscle hypertrophy at the whole-body (lean/fat-free mass; [ES (95% CI) = 0.05 (-0.20 to 0.29), P = 0.70]), whole-muscle [ES = 0.06 (-0.11 to 0.24), P = 0.47], and muscle fibre [ES = 0.29 (-0.09 to 0.66), P = 0.13] levels. Higher-load RT further improved 1-RM [ES = 0.34 (0.15 to 0.52), P = 0.0003] and isometric [ES = 0.41 (0.07 to 0.76), P = 0.02] strength. The superiority of higher-load RT on 1-RM strength was greater in younger [ES = 0.34 (0.12 to 0.55), P = 0.002] versus older [ES = 0.20 (-0.00 to 0.41), P = 0.05] participants. Higher- and lower-load RT therefore induce similar muscle hypertrophy (at multiple physiological levels), while higher-load RT elicits superior 1-RM and isometric strength. The influence of RT loads on neuromuscular task performance is however unclear.

The Emerging Role of Interleukin 1ß (IL-1ß) in Cancer Cachexia.

Treatment of cancer cachexia remains an unmet need. The host-tumour interface and the resulting sequestration of the pro-inflammatory cytokine Il-1ß is critical in cachexia development. Neuroinflammation mediated via IL-1ß through the hypothalamic pituitary axis results in increased muscle proteolysis and adipose lipolysis, thus creating a prolonged stress-like environment with loss of appetite and increased resting energy expenditure. Recent trials using a monoclonal antibody targeting IL-1ß, canakinumab, have shown a potential role in lung cancer; however, a potential role of targeting IL-1ß to treat cachexia in patients with lung cancer is unclear, yet the underlying pathophysiology provides a sound rationale that this may be a viable therapeutic approach.

Relationship between cytokines and symptoms in people with incurable cancer: A systematic review.

BACKGROUND: Development and spread of cancer is linked to the inflammatory response, in which cytokines serve a key role. The inflammatory response may also form the basis for symptoms of cancer. This systematic review examines the relationship between cytokines and symptoms in incurable cancer. METHODS: MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science and PsycINFO databases were searched for studies from January 2004 to January 2020. RESULTS: Twenty studies were selected (n = 1806 patients, 119 controls). Symptoms studied included depression, fatigue, pain, and loss of appetite. Nine studies examined patients with a specified tumour type, the remainder included patients with a mix of tumour types. Thirty-one cytokines were examined; multiple associations between cytokines and symptoms were described, supporting the hypothesis that cytokines may have a key role in symptom generation. CONCLUSION: Symptoms of incurable cancer are associated with circulating cytokines. Further study is required to characterise these relationships, and to explore their therapeutic potential.