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-1β, 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.

Introduction Child maltreatment (CM) is associated with mental and physical health disorders in adulthood. Some studies have identified elevated markers of systemic inflammation in adult survivors of CM, and inflammation may mediate the association between CM and later health problems. However, there are methodological inconsistencies in studies of the association between CM and systemic inflammation and findings are conflicting. We performed a systematic review to examine the association of CM with systemic inflammation in adults. Methods A pre-registered systematic review was performed following PRISMA guidelines. Medline, Embase, Scopus and PsychInfo were searched for studies of the association of CM with blood markers of inflammation in adults. Quality was assessed using the Crowe Critical Appraisal Tool. We had intended to perform a meta-analysis, but this was not possible due to variation in study design and reporting. Results Forty-four articles met criteria for inclusion in the review. The most widely reported biomarkers were C-Reactive Protein (CRP) (n = 27), interleukin-6 (IL-6) (n = 24) and Tumour Necrosis Factor-alpha (TNF-a) (n = 17). Three studies were prospective (all relating to CRP) and the remainder were retrospective. 86% of studies were based in high income countries. In the prospective studies, CM was associated with elevated CRP in adulthood. Results of retrospective studies were conflicting. Methodological issues relating to the construct of CM, methods of analysis, and accounting for confounding or mediating variables (particularly Body Mass Index) may contribute to the uncertainty in the field. Conclusions There is some robust evidence from prospective studies that CM is associated with elevated CRP in adulthood. We have identified significant methodological inconsistencies in the literature and have proposed measures that future researchers could employ to improve consistency across studies. Further prospective, longitudinal, research using robust and comparable measures of CM with careful consideration of confounding and mediating variables is required to bring clarity to this field.

Purpose of review Cachexia is defined as ongoing loss of skeletal muscle mass, with or without depletion of adipose tissue and is a common syndrome in cancer patients, affecting 50% of those diagnosed. Cachexia, which cannot be fully reversed and causes significant functional impairment is caused by various mechanisms such as an altered energy balance and disruption of homeostatic control by the central nervous system. This central nervous system deregulation involves hypothalamic pituitary adrenal (HPA) axis stimulation, which can be triggered by IL-1R1 engagement on neuronal processes and endothelium in the microvasculature of the hypothalamus. This review will explore current evidence regarding both the importance of IL-1α in the various components of cancer cachexia and its potential as a therapeutic target. Recent findings IL-1α, which signals through IL-1R1, has been identified as a key agonist in the IL-1 pathway. As such, IL-1α has been explored as a therapeutic target in cancer cachexia, leading to the development of bermekimab, a mAb which neutralizes IL-1α. With a limited array of medication currently available to treat cancer cachexia, bermekimab represents a possible therapy. Summary IL-1α is a key mediator in cachexia development and targeting this may be a viable therapeutic target.

IntroductionChild maltreatment (CM) is associated with mental and physical health disorders in adulthood. Some studies have identified elevated markers of systemic inflammation in adult survivors of CM, and inflammation may mediate the association between CM with later health problems. However, there are methodological inconsistencies in studies of the association between CM and systemic inflammation and findings are conflicting. We performed a systemic review to examine the association of CM with systemic inflammation in adults.MethodsA systematic review was performed following PRISMA . Medline, Embase, Scopus and PsychInfo were searched for studies of the association of CM with blood markers of inflammation in adults. Quality was assessed using the Crowe Critical Appraisal Tool. We had intended to perform a meta-analysis but this was not possible due to variation in study design and reporting.ResultsForty-six articles met criteria for inclusion in the review. The most widely reported biomarkers were C-Reactive Protein (CRP) (n=29), interleukin-6 (n=25) and Tumour Necrosis Factor-alpha (TNF-a). Four studies were prospective (all relating to CRP) and the remainder were retrospective. 85% of studies were based in Western settings. In the prospective studies, CM was associated with elevated CRP in adulthood. Results of retrospective studies were conflicting. Methodological issues relating to the construct of CM, methods of analysis, and accounting for confounding or mediating variables (particularly Body Mass Index) may contribute to the uncertainty in the field.ConclusionsThere is some robust evidence from prospective studies that CM is associated with elevated CRP in adulthood. We have identified significant methodological issues in the literature and have proposed measures that future researchers could employ to improve consistency across studies. Further prospective, longitudinal, research using robust and comparable measures of CM with careful consideration of confounding and mediating variables are required to bring clarity to this field.

Purpose of reviewCancer cachexia is a complex inflammatory syndrome, which presents with a variety of discrete symptoms and signs. This creates a challenge for both clinicians and researchers in recognizing and assessing the syndrome. This review explores the evidence for various measures used in the assessment of cachexia. Recent findingsObjectively, cachexia may be assessed using CT-derived measures of skeletal muscle [skeletal muscle index (SMI) and skeletal muscle density (SMD)]. Evidence suggests that SMD may be of equal or greater value than SMI in assessing cachexia. Inflammatory markers are also used, and include interleukin(IL)-1a; IL-1b; IL-6 and Interferon Gamma (IFNg). Other robust measures include performance status and the modified Glasgow prognostic score (mGPS). These measures, however, are more commonly used in academia. By comparison, clinical assessment is limited to individual measures of patient function, such as hand grip strength (HGS), calf circumference, gait speed, and the 'timed up and go test' (TUG). These have each been linked with components of cachexia but are less well evidenced. Evidence also exists for patientreported quality-of-life measures, based upon the EORTC-QLQ-C30 questionnaire, in assessing cachexia.