Disentangling the detrimental effects of local from systemic adipose tissue dysfunction on articular cartilage in the knee.

Objective: Obesity increases osteoarthritis (OA) risk due to adipose tissue dysfunction with associated metabolic syndrome and excess weight. Lipodystrophy syndromes exhibit systemic metabolic and inflammatory abnormalities similar to obesity without biomechanical overloading. Here, we used lipodystrophy mouse models to investigate the effects of systemic versus intra-articular adipose tissue dysfunction on the knee.

Rates of paclitaxel hypersensitivity reactions using a modified Markman's infusion protocol as primary prophylaxis.

Purpose: Markman's desensitisation protocol allows successful retreatment of patients who have had significant paclitaxel hypersensitivity reactions. We aimed to reduce the risk and severity of paclitaxel hypersensitivity reactions by introducing this protocol as primary prophylaxis.

Methods: We evaluated all patients with a gynaecological malignancy receiving paclitaxel before (December 2018 to September 2019) and after (October 2019 to July 2020) the implementation of a modified Markman's desensitisation protocol.

Progress in the Treatment of Small Intestine Cancer.

Small intestine cancer is rare, accounting for approximately 3% of all gastrointestinal malignancies. The most common histological subtypes include adenocarcinoma, neuroendocrine tumours (NETs) and gastrointestinal stromal tumours (GISTs). In localised disease, surgery remains the mainstay of treatment and the best approach to improve survival.

Taxonomy of fibroblasts and progenitors in the synovial joint at single-cell resolution.

Objectives: Fibroblasts in synovium include fibroblast-like synoviocytes (FLS) in the lining and + connective-tissue fibroblasts in the sublining. We aimed to investigate their developmental origin and relationship with adult progenitors.

Methods: To discriminate between -lineage cells deriving from the embryonic joint interzone and other -expressing fibroblasts and progenitors, adult mice were used and cartilage injury was induced to activate progenitors.

Targeting the IL-6-Yap-Snail signalling axis in synovial fibroblasts ameliorates inflammatory arthritis.

Objective: We aimed to understand the role of the transcriptional co-factor Yes-associated protein (Yap) in the molecular pathway underpinning the pathogenic transformation of synovial fibroblasts (SF) in rheumatoid arthritis (RA) to become invasive and cause joint destruction.

Methods: Synovium from patients with RA and mice with antigen-induced arthritis (AIA) was analysed by immunostaining and qRT-PCR. SF were targeted using and mice, crossed with fluorescent reporters for cell tracing and mice for conditional ablation.

Decision-making in Orthopaedic Oncology: Does Cognitive Bias Affect a Virtual Patient's Choice Between Limb Salvage and Amputation?

Background: The local treatment of extremity sarcomas usually is predicated on a decision between limb salvage and amputation. The manner in which surgical options are presented in the context of shared decision-making may influence this decision. In a population of "simulated" patients-survey respondents presented with a mock clinical vignette and then asked to choose between treatments-we assessed cognitive bias by deliberate alteration of the subjective presentation of the same objective information.

Stress Urinary Incontinence Surgery in Washington State Before and After Introduction of the Mesh Midurethral Sling.

Objectives: Mesh midurethral slings (MUSs) are safe, effective treatments for female stress urinary incontinence (SUI), but many companies have ceased production because of controversies surrounding transvaginal mesh. To determine if introduction of MUS has increased the complication rate associated with SUI surgery, we compared women undergoing SUI surgery in the MUS era to those who had surgery prior its introduction.

Methods: This was a retrospective cohort study of a statewide hospital discharge database.

Automating Electronic Clinical Data Capture for Quality Improvement and Research: The CERTAIN Validation Project of Real World Evidence.

Background: The availability of high fidelity electronic health record (EHR) data is a hallmark of the learning health care system. Washington State's Surgical Care Outcomes and Assessment Program (SCOAP) is a network of hospitals participating in quality improvement (QI) registries wherein data are manually abstracted from EHRs. To create the Comparative Effectiveness Research and Translation Network (CERTAIN), we semi-automated SCOAP data abstraction using a centralized federated data model, created a central data repository (CDR), and assessed whether these data could be used as real world evidence for QI and research.

Communication Training, Adverse Events, and Quality Measures: 2 Retrospective Database Analyses in Washington State Hospitals.

Objective: Washington State's HealthPact program was launched in 2011 as part of AHRQ's Patient Safety and Medical Liability Reform initiative. HealthPact delivered interdisciplinary communication training to health-care professionals with the goal of enhancing safety. We conducted 2 exploratory, retrospective database analyses to investigate training impact on the frequency of adverse events (AEs) and select quality measures across 3 time frames: pretraining (2009-2011), transition (2012), and posttraining (2013).

Effectiveness of a Medical vs Revascularization Intervention for Intermittent Leg Claudication Based on Patient-Reported Outcomes.

Importance: Intermittent claudication (IC) is the most common presentation of infrainguinal peripheral artery disease. Both medical and revascularization interventions for IC aim to increase walking comfort and distance, but there is inconclusive evidence of the comparative benefit of revascularization given the possible risk of limb loss.

Objective: To compare the effectiveness of a medical (walking program, smoking cessation counseling, and medications) vs revascularization (endovascular or surgical) intervention for IC in the community, focusing on outcomes of greatest importance to patients.

Outpatient Rehabilitation for Medicaid-Insured Children Hospitalized With Traumatic Brain Injury.

Objectives: To describe the prevalence of postdischarge outpatient rehabilitation among Medicaid-insured children hospitalized with a traumatic brain injury (TBI) and to identify factors associated with receipt of services.

Methods: Retrospective cohort of children <21 years, hospitalized for a TBI between 2007 and 2012, from a national Medicaid claims database. Outcome measures were receipt of outpatient rehabilitation (physical, occupational, or speech therapies or physician visits to a rehabilitation provider) 1 and 3 years after discharge.

Hyaluronan expression in primary and secondary brain tumors.

Background: Collectively, primary and secondary brain tumors represent a major public health challenge. Glioblastoma (GBM) is the most common primary brain tumor in adults and is associated with a dismal 5-year survival of only 10%. Breast cancer causes secondary tumors; it occurs in 200,000 patients yearly and 30% of these individuals develop brain metastases which also lead to a very poor prognosis.

Tumor-associated hyaluronan limits efficacy of monoclonal antibody therapy.

Despite tremendous progress in cancer immunotherapy for solid tumors, clinical success of monoclonal antibody (mAb) therapy is often limited by poorly understood mechanisms associated with the tumor microenvironment (TME). Accumulation of hyaluronan (HA), a major component of the TME, occurs in many solid tumor types, and is associated with poor prognosis and treatment resistance in multiple malignancies. In this study, we describe that a physical barrier associated with high levels of HA (HA(high)) in the TME restricts antibody and immune cell access to tumors, suggesting a novel mechanism of in vivo resistance to mAb therapy.

Accumulation of extracellular hyaluronan by hyaluronan synthase 3 promotes tumor growth and modulates the pancreatic cancer microenvironment.

Extensive accumulation of the glycosaminoglycan hyaluronan is found in pancreatic cancer. The role of hyaluronan synthases 2 and 3 (HAS2, 3) was investigated in pancreatic cancer growth and the tumor microenvironment. Overexpression of HAS3 increased hyaluronan synthesis in BxPC-3 pancreatic cancer cells.

Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes.

Objective: To study the association between diabetes status, perioperative hyperglycemia, and adverse events in a statewide surgical cohort.

Background: Perioperative hyperglycemia may increase the risk of adverse events more significantly in patients without diabetes (NDM) than in those with diabetes (DM).

Methods: Using data from the Surgical Care and Outcomes Assessment Program, a cohort study (2010-2012) evaluated diabetes status, perioperative hyperglycemia, and composite adverse events in abdominal, vascular, and spine surgery at 53 hospitals in Washington State.

Enteral contrast in the computed tomography diagnosis of appendicitis: comparative effectiveness in a prospective surgical cohort.

Objective: Our goal was to perform a comparative effectiveness study of intravenous (IV)-only versus IV + enteral contrast in computed tomographic (CT) scans performed for patients undergoing appendectomy across a diverse group of hospitals.

Background: Small randomized trials from tertiary centers suggest that enteral contrast does not improve diagnostic performance of CT for suspected appendicitis, but generalizability has not been demonstrated. Eliminating enteral contrast may improve efficiency, patient comfort, and safety.

Peripheral venous and arterial blood gas analysis in adults: are they comparable? A systematic review and meta-analysis.

Peripheral venous blood gas (PVBG) analysis is increasingly being used as a substitute for arterial blood sampling; however, comparability has not been clearly established. To determine if the pH, PCO2 and PO2 obtained from PVBG analysis is comparable with arterial blood gas (ABG) analysis. A search was conducted of electronic databases as well as hand-searching of journals and reference lists through December 2012 to identify studies comparing PVBG with ABG analysis in adult subjects.

Evaluating the association of preoperative functional status and postoperative functional decline in older patients undergoing major surgery.

This prospective cohort study sought to identify predictors of functional decline in patients aged 65 years or older who underwent major, nonemergent abdominal or thoracic surgery in our tertiary hospital from 2006 to 2008. We used the Stanford Health Assessment Questionnaire-Disability Index (HAQ-DI) to evaluate functional decline; a 0.1 or greater increase was used to indicate a clinically significant decline.

Adoption of laparoscopy for elective colorectal resection: a report from the Surgical Care and Outcomes Assessment Program.

Background: The purpose of this study was to evaluate the adoption of laparoscopic colon surgery and assess its impact in the community at large.

Study Design: The Surgical Care and Outcomes Assessment Program (SCOAP) is a quality improvement benchmarking initiative in the Northwest using medical record-based data. We evaluated the use of laparoscopy and a composite of adverse events (ie, death or clinical reintervention) for patients undergoing elective colorectal surgery at 48 hospitals from the 4th quarter of 2005 through 4th quarter of 2010.

Routine leak testing in colorectal surgery in the Surgical Care and Outcomes Assessment Program.

Objective: To evaluate the effect of routine anastomotic leak testing (performed to screen for leaks) vs selective testing (performed to evaluate for a suspected leak in a higher-risk or technically difficult anastomosis) on outcomes in colorectal surgery because the value of provocative testing of colorectal anastomoses as a quality improvement metric has yet to be determined.

Design: Observational, prospectively designed cohort study.

Setting: Data from Washington state's Surgical Care and Outcomes Assessment Program (SCOAP).

Neoadjuvant chemotherapy in the Medicare cohort with advanced ovarian cancer.

Objective: The value of neoadjuvant chemotherapy (NAC) for the treatment of advanced ovarian cancer has yet to be determined. While NAC may facilitate and simplify complete cytoreduction and reduce the risk of surgery, the delay of surgery related to NAC needs to be balanced against any potential benefit.

Methods: Surveillance, Epidemiology and End-Results (SEER) data linked to Medicare claims were used to identify 6844 women with treated stage III/IV epithelial ovarian cancer (1995-2005).

Diagnostic imaging and biopsy use among elderly medicare beneficiaries with hepatocellular carcinoma.

Purpose: Diagnostic imaging is effective for evaluating patients suspected of having hepatocellular carcinoma (HCC). Although the diagnosis can be established with imaging alone, diagnostic biopsy may be useful for patients with tumors measuring 1 to 2 cm. To date, biopsy and imaging use among patients with HCC has not been evaluated in the general community.

Perioperative pharmacologic prophylaxis for venous thromboembolism in colorectal surgery.

Background: To determine the effectiveness of pharmacologic prophylaxis in preventing clinically relevant venous thromboembolic (VTE) events and deaths after surgery. The Surgical Care Improvement Project recommends that VTE pharmacologic prophylaxis be given within 24 hours of the operation. The bulk of evidence supporting this recommendation uses radiographic end points.