Introduction: Immune checkpoint inhibitors (ICI), increasingly used cancer therapeutics, can cause off-target inflammatory effects called immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis (ICI-induced IA) and polymyalgia rheumatica (ICI-induced PMR). There are no validated classification criteria or outcome measures for these conditions, and adaptation of treatment recommendations from corresponding rheumatic diseases may not be appropriate. We summarized clinical descriptors of ICI-induced IA and ICI-induced PMR and aggregated domains used for these conditions in order to inform the development of a core set of outcome domains.
View Article and Find Full Text PDFThere are more than 700 genes that encode proteins that function in epigenetic regulation and chromatin modification. Germline variants in these genes (typically heterozygous) are associated with rare neurodevelopmental disorders (NDDs) characterized by growth abnormalities and intellectual and developmental delay. Advancements in next-generation sequencing have dramatically increased the detection of pathogenic sequence variants in genes encoding epigenetic machinery associated with NDDs and, concurrently, the number of clinically uninterpretable variants classified as variants of uncertain significance (VUS).
View Article and Find Full Text PDFBackground: Consumer perceptions of legal cannabis products may drive willingness to purchase from the illegal or legal market; however, little is known on this topic. The current study examined perceptions of legal products among Canadian cannabis consumers over a 3-year period following federal legalization of non-medical cannabis in 2018.
Methods: Data were analyzed from Canadian respondents in the International Cannabis Policy Study, a repeat cross-sectional survey conducted in 2019-2021.
J Racial Ethn Health Disparities
December 2023
Theory and research suggest chronic direct and indirect exposures to racism impact health, and stress-responsive inflammation may play a role in these paths. This study examines links between forms of racism-related stress, salivary markers of inflammation during acute psychosocial stress, and perinatal mental and physical health in a racially heterogenous sample. Pregnant people (n = 108, 27% non-white) self-reported personal and vicarious exposure to racism (racial microaggressions, online racism, overt racial/ethnic discrimination) and racial collective self-esteem, as well as affective symptoms and general physical health.
View Article and Find Full Text PDFBackground: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing.
View Article and Find Full Text PDFBackground: Private hospitals in Australia manage 11% of acute and 48% of rehabilitation stroke admissions, yet little is known about implementation of stroke clinical guidelines in this setting. Clinical guidelines recommend that acute stroke patients be co-located in a stroke unit in a geographically defined area, rather than dispersed across the hospital.
Objective: To investigate post-intervention adherence to clinical guidelines for stroke management, and to explore staff barriers and facilitators to guideline implementation.
Background: Data on the association of multimorbidity and functional impairment with cardiovascular (CV) and non-CV outcomes among older myocardial infarction (MI) patients are limited.
Hypothesis: Multimorbidity and functional impairment among older MI patients are associated with CV and non-CV mortality.
Methods: Patients aged ≥65 years, 1-3 years post-MI, and enrolled between June 2013 and Novemeber 2014 from 349 sites in 25 countries in the global TIGRIS registry were categorized by age, number of comorbidities, and presence and degree of functional impairment.
Sexually dimorphic tissues are formed by cells that are regulated by sex hormones. While a number of systemic hormones and transcription factors are known to regulate proliferation and differentiation of osteoblasts and osteoclasts, the mechanisms that determine sexually dimorphic differences in bone regeneration are unclear. To explore how sex hormones regulate bone regeneration, we compared bone fracture repair between adult male and female mice.
View Article and Find Full Text PDFPurpose: Total hip arthroplasty (THA) in patients with small or unusual proximal femoral anatomy is challenging due to sizing issues, control of version, and implant fixation. The Wagner Cone is a monoblock, fluted, tapered stem with successful outcomes for these patients; however, there is limited information on subsidence, a common finding with cementless stems.
Methods: We retrospectively reviewed our cases using the modified Wagner Cone (Zimmer, Warsaw, IN) implanted over a 13-year period (2006-2019) in patients with small or abnormal proximal femoral anatomy.
Aims: High-risk cardiac surgery is commonly complicated by low cardiac output syndrome (LCOS), which is associated with high mortality. There are limited data derived from multi-centre studies with adjudicated endpoints describing factors associated with LCOS and its downstream clinical outcomes.
Methods And Results: The Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial evaluated prophylactic levosimendan vs.
Elevated red blood cell distribution width (RDW) is associated with increased risk for major adverse cardiovascular events (MACE) and death in patients with cardiovascular disease. The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome (ACS) and elevated atherogenic lipoproteins despite optimized statin treatment. This post hoc analysis determined whether RDW independently predicts risk of MACE and death in patients after recent ACS, whether RDW influences MACE reduction with alirocumab, and whether alirocumab treatment affects RDW.
View Article and Find Full Text PDFCurr Osteoporos Rep
October 2022
Purpose Of Review: This review summarizes recent investigations into the cellular and molecular effects of skeletal aging on the inflammatory response and stem cell function after fracture.
Recent Findings: Proper regulation of the inflammatory phase of fracture healing is essential. Aging is associated with chronic inflammation, which inhibits bone formation and promotes bone resorption.
Study Objective: Develop and evaluate a model that uses health administrative data to categorize cardiovascular (CV) cause of death (COD).
Design: Population-based cohort.
Setting: Ontario, Canada.
Background: Revision of both femoral and tibial components of a total knee arthroplasty (TKA) for aseptic loosening has favorable outcomes. Revision of only one loose component with retention of others has shorter operative time and lower cost; however, implant survivorship and clinical outcomes of these different operations are unclear.
Methods: Between January 2009 and December 2019, a consecutive cohort of revision TKA was reviewed.
Background: An extended trochanteric osteotomy (ETO) is a powerful tool for femoral component revision. There is limited evidence that directly supports its use in the setting of a periprosthetic joint infection (PJI). Cerclage fixation raises the theoretical concern for persistent infection.
View Article and Find Full Text PDFDistortion product otoacoustic emissions (DPOAEs) provide a window into active cochlear processes and have become a popular clinical and research tool. DPOAEs are commonly recorded using stimulus with fixed presentation levels and frequency ratio irrespective of the test frequency. However, this is inconsistent with the changing mechanical properties of the cochlear partition from the base to the apex that lend specific frequency-dependent spatial properties to the cochlear traveling wave.
View Article and Find Full Text PDFWear particles from joint arthroplasties induce chronic inflammation associated with prolonged upregulation of nuclear factor kappa-B (NF-κB) signaling in macrophages and osteoclasts, which leads to osteolysis and implant loosening. Mesenchymal stromal cell (MSC)-based therapy showed great potential for immunomodulation and mitigation of osteolysis , especially in the chronic phase of inflammation. We previously generated genetically modified MSCs that secrete the anti-inflammatory cytokine interleukin 4 (IL-4) in response to NF-κB activation (NFκB-IL-4 MSCs).
View Article and Find Full Text PDFThe number of total joint replacements is increasing, especially in elderly patients, and so too are implant-related complications such as prosthesis loosening. Wear particles from the prosthesis induce a chronic inflammatory reaction and subsequent osteolysis, leading to the need for revision surgery. This study investigated the therapeutic effect of NF-ĸB decoy oligodeoxynucleotides (ODN), mesenchymal stem cells (MSCs), and genetically-modified NF-ĸB sensing interleukin-4 over-secreting MSCs (IL4-MSCs) on chronic inflammation in aged mice.
View Article and Find Full Text PDFLeptospirosis is a bacterial zoonosis caused by pathogenic that are maintained in the kidney lumen of infected animals acting as reservoirs and contaminating the environment via infected urine. The investigation of leptospirosis through a framework has been stimulated by notable genetic diversity of pathogenic combined with a high infection prevalence in certain animal reservoirs. Studies of Madagascar's native mammal fauna have revealed a diversity of with high levels of host-specificity.
View Article and Find Full Text PDFDisorders of the synovial joint, such as osteoarthritis (OA) and rheumatoid arthritis (RA), afflict a substantial proportion of the global population. However, current clinical management has not been focused on fully restoring the native function of joints. Organ-on-chip (OoC), also called a microphysiological system, which typically accommodates multiple human cell-derived tissues/organs under physiological culture conditions, is an emerging platform that potentially overcomes the limitations of current models in developing therapeutics.
View Article and Find Full Text PDFBackground: Ghana has a large and growing burden of injury morbidity and mortality. There is a substantial unmet need for trauma surgery, highlighting a need to understand gaps in care.
Methods: We conducted 8 in-depth interviews with trauma care providers (surgeons, nurses, and specialists) at a large teaching hospital to understand factors that contribute to and reduce delays in the provision of adequate trauma care for severely injured patients.
Background: Total joint arthroplasty (TJA) is one of the most common surgical procedures in the United States; however, racial and ethnic disparities in utilizations and outcomes have been well documented. This systematic review and meta-analysis investigated associations between race/ethnicity and several metrics in total hip arthroplasty (THA) and total knee arthroplasty (TKA).
Methods: In August 2021, PubMed, Scopus, CINAHL, and SPORTDiscus databases were queried.