SUMMARY POINTS Ventilator associated pneumonia is the most common healthcare associated infection in intensive care The condition is associated with increased morbidity, mortality, length of stay, ...and costs Lack of a "gold standard" definition leads to both underdiagnosis and overdiagnosis A high clinical suspicion of pneumonia in a ventilated patient should prompt the immediate administration of an appropriate broad spectrum antibiotic(s) Implement evidence based interventions that reduce the incidence of pneumonia in all patients receiving mechanical ventilation
Phenolamides, also known as hydroxycinnamic acid amides or phenylamides, have been reported throughout the plant kingdom, while a few of these amine-conjugated hydroxycinnamic acids are unique in ...foods. The current knowledge of their specific functions in plant development and defense is readily available as is their biosynthesis; however, their functionality in humans is still largely unknown. Of the currently known phenolamides, the most common are avenanthramides, which are unique in oats and similar to the well-known drug Tranilast, which possess anti-inflammatory, antioxidant, anti-itch, and antiatherogenic activities. While recent data have brought to light more information regarding the other known phenolamides, such as hordatines, dimers of agmatine conjugated to hydroxycinnamic acid, and kukoamines, spermine-derived phenolamides, the information is still severely limited, leaving their potential health benefits to speculation. Herein, to highlight the importance of dietary phenolamides to human health, we review and summarize the four major subgroups of phenolamides, including their chemical structures, dietary sources, and reported health benefits. We believe that the studies on phenolamides are still in the infancy stage and additional health benefits of these phenolamides may yet be identified.
Summary Osteoarthritis (OA) is a common chronic joint disorder with a multifactorial etiology including genetic and environmental factors. Metabolic triggered inflammation, induced by nutrient ...overload and metabolic surplus, consists of components such as obesity, pro-inflammatory cytokines and adipokines, abnormal metabolites, acute phase proteins, vitamin D deficiency, and deregulated microRNAs that may play a role in OA pathophysiology. Obesity-related metabolic factors, especially adipokines, contribute to OA development by inducing pro-inflammatory cytokines and degradative enzymes, leading to cartilage matrix impairment and subchondral bone remodeling. Ectopic metabolite deposition and low-grade systemic inflammation can contribute to a toxic internal environment that exacerbates OA. Complement components highly expressed in osteoarthritic joints have also been proposed as causative factors. Vitamin D deficiency has been associated with obesity and is implicated to be associated with cartilage loss in OA. Metabolic microRNAs may explain the inflammatory link between obesity and OA. Therapies targeting metabolic-triggered inflammation and its components are anticipated to have potential for the treatment of OA.
Summary Objective To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, ...and allied healthcare professionals worldwide. Method Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1–10 risk and benefit scores. Results Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). Conclusion These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.
Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular immunotherapy trials offer a means to probe complex tumor-immune interfaces through ...defined T cell/antigen interactions. We treated two patients with metastatic Merkel cell carcinoma with autologous Merkel cell polyomavirus specific CD8+ T cells and immune-checkpoint inhibitors. In both cases, dramatic remissions were associated with dense infiltration of activated CD8+s into the regressing tumors. However, late relapses developed at 22 and 18 months, respectively. Here we report single cell RNA sequencing identified dynamic transcriptional suppression of the specific HLA genes presenting the targeted viral epitope in the resistant tumor as a consequence of intense CD8-mediated immunologic pressure; this is distinguished from genetic HLA-loss by its reversibility with drugs. Transcriptional suppression of Class I loci may underlie resistance to other immunotherapies, including checkpoint inhibitors, and have implications for the design of improved immunotherapy treatments.
Objective:To examine the relationship between longitudinal fluctuations in synovitis with change in pain and cartilage in knee osteoarthritis.Methods:Study subjects were patients 45 years of age and ...older with symptomatic knee osteoarthritis from the Boston Osteoarthritis of the Knee Study. Baseline and follow-up assessments at 15 and 30 months included knee magnetic resonance imaging (MRI), BMI and pain assessment (VAS) over the last week. Synovitis was scored at 3 locations (infrapatellar fat pad, suprapatellar and intercondylar regions) using a semiquantitative scale (0–3) at all 3 time points on MRI. Scores at each site were added to give a summary synovitis score (0–9).Results:We assessed 270 subjects whose mean (SD) age was 66.7 (9.2) years, BMI 31.5 (5.7) kg/m2; 42% were female. There was no correlation of baseline synovitis with baseline pain score (r = 0.09, p = 0.17). The change in summary synovitis score was correlated with the change in pain (r = 0.21, p = 0.0003). An increase of one unit in summary synovitis score resulted in a 3.15-mm increase in VAS pain score (0–100 scale). Effusion change was not associated with pain change. Of the 3 locations for synovitis, changes in the infrapatellar fat pad were most strongly related to pain change. Despite cartilage loss occurring in over 50% of knees, synovitis was not associated with cartilage loss in either tibiofemoral or patellofemoral compartment.Conclusions:Change in synovitis was correlated with change in knee pain, but not loss of cartilage. Treatment of pain in knee osteoarthritis (OA) needs to consider treatment of synovitis.
Synovial abnormalities have been observed at multiple stages of osteoarthritis (OA). Increasing evidence suggests that it may play an important role in the OA pathological process. Many assessment ...systems using magnetic resonance imaging (MRI) and ultrasound have been established to detect synovial inflammation in OA. These have been used to inform the current investigation of OA disease phenotypes and progression and can be utilised in the future for clinical trials developing potential treatments. This narrative review aims to illustrate the importance of synovial tissue in OA and provide an overview of imaging assessments and possible therapies targeting synovial abnormalities.
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