The macrophage at the intersection of immunity and metabolism in obesity

Obesity is a worldwide pandemic representing one of the major challenges that societies face around the globe. Identifying the mechanisms involved in its development and propagation will help the development of preventative and therapeutic strategies that may help control its rising rates

Clinical Use and Therapeutic Potential of IVIG/SCIG, Plasma-Derived IgA or IgM, and Other Alternative Immunoglobulin Preparations

Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM

The epigenetic landscape of renal cancer

This is an accepted manuscript of an article published by Nature in Nature Reviews: Nephrology on 28/11/2016, available online: https://doi.org/10.1038/nrneph.2016.168 The accepted version of the publication may differ from the final published version.The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers

The effect of cannabis exposure on pubertal outcomes: a systematic review

E Danielle Sims,1–3 Sama Anvari,1,2,4,* Yung Lee,1,2,4,* Zainab Samaan,5 Laura Banfield,6 Lehana Thabane,1,7–10 M Constantine Samaan1–4,7 1Department of Pediatrics, McMaster University, Hamilton, ON, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, ON, Canada; 3Medical Sciences Graduate Program, McMaster University, Hamilton, ON, Canada; 4Michael G. De Groote School of Medicine, McMaster University, Hamilton, ON, Canada; 5Department of Psychiatry and Neurobehavioral Sciences, McMaster University, Hamilton, ON, Canada; 6Health Sciences Library, McMaster University, Hamilton, ON, Canada; 7Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 8Department of Anesthesia, McMaster University, Hamilton, ON, Canada; 9Centre for Evaluation of Medicines, Hamilton, ON, Canada; 10Biostatistics Unit, St. Joseph’s Healthcare, Hamilton, ON, Canada *These authors contributed equally to this work Purpose: Several countries are legalizing the use of medicinal cannabis and easing restrictions on its recreational use. While adults have been the primary target of these initiatives, expanding access to cannabis will likely lead to increased use by children. While the effects of cannabis on pediatric neuropsychological and mental health outcomes have been broadly studied, there are limited data on the physical health effects of cannabis, including endocrine health. Animal studies have shown that chronic cannabis use leads to delayed sexual maturation; however, its effects on pubertal outcomes in children are not well studied. This systematic review aimed to assess the effect of cannabis use on pubertal timing and tempo in children.Methods: We conducted a systematic review with literature searches in MEDLINE, Embase, Cochrane Database of Systematic Reviews, Central, PsycINFO, CINAHL, Web of Science, and SPORTDiscus from inception to February 2018. A gray literature search was also completed in Clinicaltrials.gov and ProQuest Dissertations and Theses A&I. The primary outcome was pubertal timing, while secondary outcomes included pubertal tempo and final height and weight. We had no restrictions on date or language of publication of papers. Two reviewers independently assessed records for eligibility, with a third reviewer resolving disagreements.Results: Our database and gray literature searches identified 759 records. A total of 29 full-text papers were assessed for eligibility. However, all studies were ultimately excluded as they did not meet the eligibility criteria.Conclusion: Our results highlight a significant gap in existing literature regarding the effects of cannabis use on puberty. Adequately powered longitudinal studies are urgently needed to provide pediatricians and other health care providers with high-quality information on the potential effects of cannabis on the physical health of children.Prospective Registrar of Systematic Reviews Registration: PROSPERO no.: CRD42018089397. Keywords: marijuana, puberty, children, pediatric, tetrahydrocannabinol, cannabi

Evaluating the prevalence of diabetes mellitus subtypes in childhood cancer survivors: a systematic review protocol

Sondra Song Jie Chen,1,2 Ajantha Nadarajah,1,2 Laura Banfield,3 Adam Fleming,1,4 Lehana Thabane,5–8 Carol Portwine,1,4 M Constantine Samaan1–2,51Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 3Health Sciences Library, McMaster University, Hamilton, Ontario, Canada; 4Division of Pediatric Hematology/Oncology, McMaster Children’s Hospital, Hamilton, Ontario, Canada; 5Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; 6Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada; 7Centre for Evaluation of Medicines, St Joseph’s Health Care, Hamilton, Ontario, Canada; 8Biostatistics Unit, St Joseph’s Healthcare, Hamilton, Ontario, CanadaObjectives: The number of children who survive cancer is reaching new record levels, thanks to improved management strategies. However, this population is predisposed to chronic health conditions including cardiovascular disease and type 2 diabetes, yet the full scale of these diagnoses in this population is unclear. This protocol describes the conduct of a systematic review to report on the prevalence of diabetes mellitus (DM) subtypes in childhood cancer survivors.Methods: Searches will be conducted in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. We will also search gray literature in Theses A&I, ProQuest Dissertations, and Web of Science as well as clinicaltrials.gov. Screening search results and data abstraction will be done independently by two reviewers. We will conduct a meta-analysis if two studies have similar designs, populations, methods, and outcome measures reported.Results: The findings of this systematic review will provide insights into the scale of diabetes in childhood cancer survivors to allow the prioritization of subpopulations that need specific interventions to screen, prevent, and treat DM. This will likely lead to improved outcomes in childhood cancer survivors.Keywords: systematic review protocol, childhood cancer, cancer survivorship, diabetes mellitus, type 1 diabetes mellitus, type 2 diabetes mellitu

Evaluation of clinical and inflammatory profile in opioid addiction patients with comorbid pain: results from a multicenter investigation

Brittany B Dennis,1 M Constantine Samaan,2 Monica Bawor,3 James Paul,4 Carolyn Plater,5 Guillaume Pare,1 Andrew Worster,6 Michael Varenbut,5 Jeff Daiter,5 David C Marsh,5,7 Dipika Desai,8 Lehana Thabane,1,9,10 Zainab Samaan1,8,11 1Department of Clinical Epidemiology and Biostatistics, 2Department of Pediatrics, Division of Pediatric Endocrinology, 3McMaster Integrative Neuroscience Discovery and Study Program, 4Department of Anesthesia, McMaster University, Hamilton, 5Ontario Addiction Treatment Centres, Richmond Hill, 6Department of Medicine, Hamilton General Hospital, Hamilton, 7Northern Ontario School of Medicine, Sudbury, 8Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, 9Centre for Evaluation of Medicine, 10System Linked Research Unit, Hamilton, 11Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada Background: Chronic pain is the most commonly reported comorbidity among patients with opioid addiction receiving methadone maintenance treatment (MMT), with an estimated prevalence ranging between 30% and 55%. Evidence suggests that patients with comorbid pain are at high risk for poor treatment response, including continued illicit substance use. Due to the important relationship between the presence of pain and illicit substance abuse within the MMT setting, it is imperative that we target our efforts toward understanding the characteristics of this patient population.Methods: The primary objective of this study was to explore the clinical and inflammatory profile of MMT patients reporting comorbid pain. This multicenter study enrolled patients (n=235) on MMT for the treatment of opioid dependence. Clinical history and blood and urine data were collected. Blood samples were obtained for estimating the serum levels of inflammatory markers (tumor necrosis factor [TNF]-α, interleukin-1 receptor antagonist [IL-1ra], IL-6, IL-8, IL-10, interferon [IFN]-γ and chemokine (C–C motif) ligand 2 [CCL2]). The study objectives were addressed using a descriptive statistical summary and a multivariable logistic regression model constructed in STATA version 12.Results: Among the participants eligible for inclusion (n=235), serum IFN-γ level and substance abuse behavior proved to be important delineating characteristics for the detection of comorbid pain. Analysis of inflammatory profile showed IFN-γ to be significantly elevated among patients reporting comorbid pain (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.17, 3.50; P=0.01). Patients reporting comorbid pain were also found to have an increase in positive opioid urine screens (OR: 1.02; 95% CI: 1.00, 1.03; P=0.01), indicating an increase in illicit opioid consumption.Conclusion: MMT patients with comorbid pain were shown to have elevated IFN-γ and higher rates of continued opioid abuse. The ability to objectively distinguish between patients with comorbid pain may help to both improve the prediction of poor responders to MMT as well as identify treatment approaches such as anti-inflammatory medications as safe alternatives for MMT patients with comorbid pain. Keywords: methadone maintenance treatment, inflammatory markers, TNF-α, IFN-γ, interleukins, CCL2, Brief Pain Inventory, opioid dependenc

The creation of a national coalition to target adolescent idiopathic scoliosis: a meeting report

Milena Cioana,1,2 Devin Peterson,3 Paul Missiuna,3 Ron El-Hawary,4 Timothy Carey,5,6 Murray A Potter,7 Laura Banfield,8 Lehana Thabane,9–12 M Constantine Samaan1,2,9 1Department of Pediatrics, McMaster University, Hamilton, ON, Canada; 2Division of Pediatric Endocrinology, McMaster Children’s Hospital, Hamilton, ON, Canada; 3Division of Orthopedics, Department of Surgery, McMaster University, Hamilton, ON, Canada; 4Orthopedic Surgery Department, IWK Children’s Health Center, Dalhousie University, Halifax, NS, Canada; 5Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada; 6Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; 7Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada; 8Health Sciences Library, McMaster University, Hamilton, ON, Canada; 9Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 10Department of Anesthesia, McMaster University, Hamilton, ON, Canada; 11Centre for Evaluation of Medicines, St Joseph’s Health Care, Hamilton, ON, Canada; 12Biostatistics Unit, St Joseph’s Healthcare-Hamilton, Hamilton, ON, Canada Abstract: In this report, we document the discussions and recommendations of a national conference designed to create a coalition to tackle adolescent idiopathic scoliosis (AIS) held on June 6 and 7, 2017 in Hamilton, ON, Canada. The goal of the establishment of this coalition is to join the efforts of patients, parents, physicians, researchers and other stakeholders to identify stakeholders’ perspectives and to categorize gaps in knowledge and target further AIS research and clinical care priorities. The participants’ main priorities included focus on shared decision making regarding clinical and research priorities between the stakeholders on the clinical, research and policy sides with patients and families. In addition, improvements in the dissemination of information via digital platforms and identification of cost-effective screening strategies that may help early identification and intervention were also recognized as a priority. Commitment was reached to form a national coalition to understand the determinants of this condition and enhance patient outcomes through improved clinical care and research efforts. Keywords: adolescent idiopathic scoliosis, childhood scoliosis, coalition, pediatri