Meta-Analysis: Evaluating Placebo Rates Across Outcomes in Eosinophilic Oesophagitis Randomised Controlled Trials.

Background: High placebo responses have limited drug development in eosinophilic oesophagitis. The optimal configuration of trial outcomes is uncertain.

Aims: To inform more efficient future trial designs, to characterise clinical, endoscopic and histologic placebo responses in eosinophilic oesophagitis randomised controlled trials (RCTs).

Sustained AWT1 expression by Dupuytren's disease myofibroblasts promotes a proinflammatory milieu.

Palmar fibromatosis, also known as Dupuytren's disease (DD), is a common and heritable fibrosis of the hand. It is characterized by the formation of myofibroblastic nodules that can progress to palmar-digital contractures and permanent loss of dexterity. The presence of inflammatory cell infiltrate within these nodules has been interpreted to suggest a pathogenesis mediated by a proinflammatory microenvironment.

Understanding Inflammation-associated Ophthalmic Pathologies: A Novel 3D Co-culture Model of Monocyte-myofibroblast Immunomodulation.

Purpose: Inflammation is associated with, and may be causal of, a variety of ophthalmic pathologies. These pathologies are currently difficult to model because they involve complex interactions between the innate immune system, stromal cells, and other cells that normally maintain ocular tissue homeostasis. Using transscleral drainage channel fibrosis after glaucoma surgery as an example of inflammation-associated ocular fibrosis, we have assessed a simple but novel 3D cell culture system designed to reveal the immunomodulatory impacts of ocular connective tissue cells on monocytes, a major cellular component of the circulating immune system.

Deciphering the low abundance microbiota of presumed aseptic hip and knee implants.

16S rRNA gene sequencing of DNA extracted from clinically uninfected hip and knee implant samples has revealed polymicrobial populations. However, previous studies assessed 16S rRNA gene sequencing as a technique for the diagnosis of periprosthetic joint infections, leaving the microbiota of presumed aseptic hip and knee implants largely unstudied. These communities of microorganisms might play important roles in aspects of host health, such as aseptic loosening.

Vancomycin is effective in preventing Cutibacterium acnes growth in a mimetic shoulder arthroplasty.

Background: Intra-incisional deposition of vancomycin powder is a strategy to limit Cutibacterium acnes infection after shoulder surgery. Unfortunately, limited research exists examining the effectiveness of vancomycin in a clinically relevant joint infection model. This basic science study investigated the efficacy of vancomycin administration as prophylaxis for C acnes growth in vitro using a mimetic shoulder arthroplasty.

Development of a Three-Dimensional Bioartificial Shoulder Joint Implant Mimetic of Periprosthetic Joint Infection.

Postsurgical infections of the shoulder joint involving are difficult to diagnose and manage. Despite the devastating clinical complications and costly health care burden of joint infections, the scarcity of joint infection models was identified as an unmet need by the 2019 International Consensus on Orthopedic Infections. In this study, we have developed a novel 3D shoulder joint implant mimetic (S-JIM) that includes a surgical metal surface and supports a co-culture of and patient-derived shoulder capsule fibroblasts.

Biomimetic analyses of interactions between macrophages and palmar fascia myofibroblasts derived from Dupuytren's disease reveal distinct inflammatory cytokine responses.

Dupuytren's disease (DD) is a common and heritable fibrosis of the hand. It is characterized by the shortening and thickening of the palmar fascia into myofibroblastic nodules that can progress to palmar-digital contractures and permanent loss of dexterity. Molecular analyses of DD tissues and the presence of inflammatory cell infiltrates suggest a pathogenesis initiated by a proinflammatory fascial milieu that promotes myofibroblast activation and palmar fascia contractures.

Detection and Profiling of Human Coronavirus Immunoglobulins in Critically Ill Coronavirus Disease 2019 Patients.

Objectives: Coronavirus disease 2019 continues to spread worldwide with high levels of morbidity and mortality. We performed anticoronavirus immunoglobulin G profiling of critically ill coronavirus disease 2019 patients to better define their underlying humoral response.

Design: Blood was collected at predetermined ICU days to measure immunoglobulin G with a research multiplex assay against four severe acute respiratory syndrome coronavirus 2 proteins/subunits and against all six additionally known human coronaviruses.

Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation.

Background: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU.

Metabolomics Profiling of Critically Ill Coronavirus Disease 2019 Patients: Identification of Diagnostic and Prognostic Biomarkers.

Objectives: Coronavirus disease 2019 continues to spread rapidly with high mortality. We performed metabolomics profiling of critically ill coronavirus disease 2019 patients to understand better the underlying pathologic processes and pathways, and to identify potential diagnostic/prognostic biomarkers.

Design: Blood was collected at predetermined ICU days to measure the plasma concentrations of 162 metabolites using both direct injection-liquid chromatography-tandem mass spectrometry and proton nuclear magnetic resonance.

Novel Outcome Biomarkers Identified With Targeted Proteomic Analyses of Plasma From Critically Ill Coronavirus Disease 2019 Patients.

Objectives: Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been identified. We performed targeted proteomics on critically ill coronavirus disease 2019 patients to better understand their pathophysiologic mediators and to identify potential outcome markers.

Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation.

Objectives: Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patients to help understand their thrombotic mechanisms.

Inflammation Profiling of Critically Ill Coronavirus Disease 2019 Patients.

Objectives: Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019.

Potential Role of Extracellular ATP Released by Bacteria in Bladder Infection and Contractility.

Urgency urinary incontinence (UUI) and overactive bladder (OAB) can both potentially be influenced by commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various components of the nervous system, eventually resulting in contraction of the detrusor muscle during micturition. This study models host responses to various urogenital bacteria, first by using urothelial bladder cell lines and then with myofibroblast contraction assays.

CCN1 expression by fibroblasts is required for bleomycin-induced skin fibrosis.

The microenvironment contributes to the excessive connective tissue deposition that characterizes fibrosis. Members of the CCN family of matricellular proteins are secreted by fibroblasts into the fibrotic microenvironment; however, the role of endogenous CCN1 in skin fibrosis is unknown. Mice harboring a fibroblast-specific deletion for CCN1 were used to assess if CCN1 contributes to dermal homeostasis, wound healing, and skin fibrosis.

Cutibacterium acnes and the shoulder microbiome.

Background: Advances in DNA sequencing technologies have made it possible to detect microbial genome sequences (microbiomes) within tissues once thought to be sterile. We used this approach to gain insights into the likely sources of Cutibacterium acnes (formerly Propionibacterium acnes) infections within the shoulder.

Methods: Tissue samples were collected from the skin, subcutaneous fat, anterior supraspinatus tendon, middle glenohumeral ligament, and humeral head cartilage of 23 patients (14 male and 9 female patients) during primary arthroplasty surgery.

Cognitive Impairment in Patients with Chronic Neuropathic or Radicular Pain: An Interaction of Pain and Age.

A growing body of empirical research has confirmed an association between chronic pain and cognitive dysfunction. The aim of the present study was to determine whether cognitive function is affected in patients with a diagnosis of chronic neuropathic or radicular pain relative to healthy control participants matched by age, gender, and years of education. We also examined the interaction of pain with age in terms of cognitive performance.

Rapid and Rigorous IL-17A Production by a Distinct Subpopulation of Effector Memory T Lymphocytes Constitutes a Novel Mechanism of Toxic Shock Syndrome Immunopathology.

Toxic shock syndrome (TSS) is caused by staphylococcal and streptococcal superantigens (SAgs) that provoke a swift hyperinflammatory response typified by a cytokine storm. The precipitous decline in the host's clinical status and the lack of targeted therapies for TSS emphasize the need to identify key players of the storm's initial wave. Using a humanized mouse model of TSS and human cells, we herein demonstrate that SAgs elicit in vitro and in vivo IL-17A responses within hours.

Neer Award 2017: A rapid method for detecting Propionibacterium acnes in surgical biopsy specimens from the shoulder.

Background: Propionibacterium (P) acnes infection of the shoulder after arthroplasty is a common and serious complication. Current detection methods for P acnes involve anaerobic cultures that require prolonged incubation periods (typically 7-14 days). We have developed a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) approach that sensitively and specifically identifies P acnes in tissue specimens within a 24-hour period.

Dupuytren's disease susceptibility gene, EPDR1, is involved in myofibroblast contractility.

Background: Dupuytren's Disease is a common disorder of the connective tissue characterized by progressive and irreversible fibroblastic proliferation affecting the palmar fascia. Progressive flexion deformity appears over several months or years and although usually painless, it can result in a serious handicap causing loss of manual dexterity. There is no cure for the disease and the etiology is largely unknown.

Cognitive Coping Style and the Effectiveness of Distraction or Sensation-Focused Instructions in Chronic Pain Patients.

Aim: This study set out to investigate whether cognitive coping strategies that match participants' preferred coping style effectively reduce pain intensity and situational anxiety in a population of people with chronic pain.

Method: Chronic pain patients (N = 43) completed questionnaires on coping style, pain intensity, self-efficacy, and situational/trait anxiety. Participants were classified as Monitors (n = 16) or Blunters (n = 19) based on their Miller Behavioural Style Scale score.

Pretreatment anxiety and pain acceptance are associated with response to trigger point injection therapy for chronic myofascial pain.

Background And Aim: This study examined the psychosocial profile of patients who responded or did not respond to trigger point injection therapy for chronic myofascial pain.

Methods: Seventy one patients with a diagnosis of chronic myofascial pain of the paraspinous muscles completed a pretreatment questionnaire measuring demographic and social factors, and validated scales to assess pain intensity, pain interference (physical and emotional), and defined psychological characteristics (pain catastrophizing, pain acceptance, pain self-efficacy, mood and anxiety). Trigger point injection therapy of the affected areas of myofascial pain was performed and follow-up was conducted by telephone at one week (n = 65) and one month (n = 63) post intervention to assess treatment outcome (pain intensity and pain-related physical interference).