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Matrix production by tissue-engineered bone is enhanced when the growing tissue is subjected to mechanical forces and/or fluid flow in bioreactor culture. Cells deposit collagen and mineral, depending upon the mechanical loading that they receive. However, the molecular mechanisms of flow-induced signal transduction in bone are poorly understood. The hyaluronan (HA) glycocalyx has been proposed as a potential mediator of mechanical forces in bone. Using a parallel-plate flow chamber the effects of removal of HA on flow-induced collagen production and NF-kappaB activation in MLO-A5 osteoid osteocytes were investigated. Short periods of fluid flow significantly increased collagen production and induced translocation of the NF-kappaB subunit p65 to the cell's nuclei in 65 per cent of the cell population. Enzymatic removal of the HA coat and antibody blocking of CD44 (a transmembrane protein that binds to HA) eliminated the fluid-flow-induced increase in collagen production but had no effect on the translocation of p65. HA and CD44 appear to play roles in transducing the flow signals that modulate collagen production over long-term culture but not in the short-term flow-induced activation of NF-kappaB, implying that multiple signalling events are initiated from the commencement of flow. Understanding the mechanotransduction events that enable fluid flow to stimulate bone matrix production will allow the optimization of bioreactor design and flow profiles for bone tissue engineering. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to determine whether amplitude or temporal patterns of oral-nasal balance differentiate speakers with cleft palate who are classified as belonging to the 'almost but not quite' (ABNQ) and 'sometimes but not always' (SBNA) subgroups of marginal velopharyngeal inadequacy. DESIGN: The nasal accelerometric vibrational index (NAVI) was used to measure amplitude and temporal aspects of oral-nasal balance during the productions of oral and nasal syllables, words, and sentences. NAVI measures obtained include mean amplitude, time integral (area under the curve), duration, rise time, and fall time. SETTING: Tertiary care center for patients with cleft palate-craniofacial anomalies. PARTICIPANTS: Seventeen patients with repaired cleft palate who were assigned by perceptual assessment to the ABNQ subgroup and 17 patients who were assigned to the SBNA subgroup. RESULTS: No differences were found between the ABNQ and SBNA subgroups with regard to patterns of nasalization. Further analysis as a function of level of production and phonetic context revealed no differences between the subgroups. CONCLUSIONS: Although clinicians may report perceived differences in the resonance patterns of speakers who fall within the category of marginal velopharyngeal inadequacy, further division into the ABNQ and SBNA subgroups has yet to be validated. [ABSTRACT FROM AUTHOR]

Direct-acting antiviral (DAA) therapy is associated with a significant reduction in hepatocellular carcinoma (HCC) incidence among patients with cirrhosis, but data are conflicting about the risk of recurrence following DAA therapy. DAA-PASS was a prospective, pragmatic, observational study designed to estimate the risk of HCC recurrence associated with DAA therapy exposure during routine clinical care. Eligible patients were DAA treatment naive with Barcelona Clinic Liver Cancer (BCLC) stage A. Patients were followed at regular intervals for up to 24 months. To provide additional data, outcomes were compared to the Italian Liver Cancer Group (ITA.LI.CA) cohort. Of 42 patients enrolled, 24 were treated with DAA therapy. Ten HCC recurrence events were observed during the study, with 5 each in DAA-treated and DAA-untreated patients (cumulative incidences of 23 and 37 per 100 PY, respectively). The overall crude hazard ratio (HR) for HCC recurrence associated with DAA therapy was 0.6 (95% CI, 0.2-2.2). In the ITA.LI.CA cohort, HCC recurrence was observed in 193 patients during 24 months of follow-up, resulting in a cumulative incidence rate of 28 per 100 PY. Although limited by small sample size, this prospective study suggests DAA therapy is not associated with increased HCC recurrence risk among patients with a history of complete response to prior HCC therapy., (© 2025 John Wiley & Sons Ltd.)

Introduction: This study investigates the applicability of the new metabolic dysfunction-associated steatotic liver disease (MASLD) nomenclature to the real-world TARGET-NASH US adult cohort., Methods: The new MASLD/metabolic steatohepatitis nomenclature was applied to patients enrolled with pragmatic diagnoses of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), and NASH cirrhosis and concordance were determined between the definitions., Results: Approximately 99% of TARGET-NASH participants met the new MASLD diagnostic criteria. Approximately 1,484/1,541 (96.3%, kappa 0.974) nonalcoholic fatty liver patients (metabolic dysfunction-associated steatotic liver), 2,195/2,201 (99.7%, kappa 0.998) NASH patients (metabolic steatohepatitis), and 1,999/2,003 (99.8%, kappa 0.999) NASH cirrhosis patients met the new criteria., Discussion: The new MASLD nomenclature is highly concordant with the previous TARGET-NASH pragmatic definitions., (Copyright © 2024 by The American College of Gastroenterology.)

Background: There is limited evidence that histologic remission improves outcomes in Crohn's disease (CD). We aimed to characterize a cohort of patients with CD in endoscopic remission and explore factors associated with subsequent loss of remission (LOR)., Methods: In total, 4474 patients were enrolled in TARGET-IBD, a longitudinal, observational cohort study. Patients with a normal steroid-free colonoscopy (index) were defined as "in endoscopic remission" and were followed for LOR, defined as presence of inflammation, erosion, ulceration, or stricturing on a subsequent colonoscopy or commencement of steroids. Histologic activity was dichotomized using standard of care reports for active inflammation. Unadjusted and multivariable-adjusted Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of LOR in relation to independent variables., Results: Of 658 patients with CD with steroid-free endoscopic remission, the majority were female (57%), white (83%), non-Hispanic (93%); 20% had ileal and 20% isolated colonic disease. Inflammatory (B1) disease was the most common phenotype (43%). Of these 658 patients, 257 (39%) had histologic inflammation on index colonoscopy. Histologic inflammation at index colonoscopy was associated with nearly twice the LOR risk (HR 1.96, 95% CI: 1.50-2.57) with median time to relapse of 1.20 years. Biologic use at index was associated with lower LOR risk (monotherapy, HR 0.61, 95% CI: 0.45-0.82; combination therapy, HR 0.43, 95% CI: 0.28-0.66)., Conclusions: Active histologic inflammation despite endoscopic remission, and lack of biologic use were independently associated with risk of subsequent LOR, providing evidence that histologic remission may impart improved outcomes in patients with CD., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Patients with primary biliary cholangitis (PBC) often suffer with pruritus. We describe the impact of pruritus on quality of life and how it is managed in a real-world cohort., Methods: TARGET-PBC is a longitudinal observational cohort of patients with PBC across the USA. Data include information from medical records for three years prior to the date of consent up to 5 years of follow-up. Enrolled patients were asked to complete patient-reported outcome surveys: PBC-40, 5-D itch, and the PROMIS fatigue survey. Kruskal-Wallis tests were used to compare differences in symptoms between groups., Results: A total of 211 patients with completed PRO surveys were included in the current study. PRO respondents were compared with non-respondents in the TARGET-PBC population and were broadly similar. Pruritus was reported in 170 patients (81%), with those reporting clinically significant pruritus (30%) scoring worse across each domain of the PBC-40 and 5-D itch, more frequently having cirrhosis, and having significantly greater levels of fatigue. Patients reporting clinically significant pruritus were more likely to receive treatment, but 33% had never received treatment (no itch = 43.9%, mild itch = 38.3%)., Conclusions: The prevalence of pruritus was high in this population, and those reporting clinically significant pruritus had a higher likelihood of having advanced disease and worse quality of life. However, this study found that pruritus in PBC is under-treated. This may be due in part to ineffectiveness of current treatments, poor tolerance, or the lack of FDA-approved medications for pruritus., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Nonalcoholic steatohepatitis (NASH), advanced fibrosis, and subsequent cirrhosis and hepatocellular carcinoma are becoming the most common etiology for liver failure and liver transplantation; however, they can only be diagnosed at these potentially reversible stages with a liver biopsy, which is associated with various complications and high expenses. Knowing the difference between the more benign isolated steatosis and the more severe NASH and cirrhosis informs the physician regarding the need for more aggressive management., Objective: We intend to explore the feasibility of using machine learning methods for noninvasive diagnosis of NASH and advanced liver fibrosis and compare machine learning methods with existing quantitative risk scores., Methods: We conducted a retrospective analysis of clinical data from a cohort of 492 patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD), NASH, or advanced fibrosis. We systematically compared 5 widely used machine learning algorithms for the prediction of NAFLD, NASH, and fibrosis using 2 variable encoding strategies. Then, we compared the machine learning methods with 3 existing quantitative scores and identified the important features for prediction using the SHapley Additive exPlanations method., Results: The best machine learning method, gradient boosting (GB), achieved the best area under the curve scores of 0.9043, 0.8166, and 0.8360 for NAFLD, NASH, and advanced fibrosis, respectively. GB also outperformed 3 existing risk scores for fibrosis. Among the variables, alanine aminotransferase (ALT), triglyceride (TG), and BMI were the important risk factors for the prediction of NAFLD, whereas aspartate transaminase (AST), ALT, and TG were the important variables for the prediction of NASH, and AST, hyperglycemia (A 1c ), and high-density lipoprotein were the important variables for predicting advanced fibrosis., Conclusions: It is feasible to use machine learning methods for predicting NAFLD, NASH, and advanced fibrosis using routine clinical data, which potentially can be used to better identify patients who still need liver biopsy. Additionally, understanding the relative importance and differences in predictors could lead to improved understanding of the disease process as well as support for identifying novel treatment options., (©Yonghui Wu, Xi Yang, Heather L Morris, Matthew J Gurka, Elizabeth A Shenkman, Kenneth Cusi, Fernando Bril, William T Donahoo. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 06.06.2022.)

Background: Patients hospitalized for coronavirus disease 2019 (COVID-19) may experience complications following hospitalization and require readmission. In this analysis, we estimated the rate and risk factors associated with COVID-19-related readmission and inpatient mortality., Methods: In this retrospective cohort study, we used deidentified chargemaster data from 297 hospitals across 40 US states on patients hospitalized with COVID-19 from 15 February 2020 through 9 June 2020. Demographics, comorbidities, acute conditions, and clinical characteristics of first hospitalization are summarized. Multivariable logistic regression was used to measure risk factor associations with 30-day readmission and in-hospital mortality., Results: Among 29 659 patients, 1070 (3.6%) were readmitted. Readmitted patients were more likely to have diabetes, hypertension, cardiovascular disease (CVD), or chronic kidney disease (CKD) vs those not readmitted (P < .0001) and to present on first admission with acute kidney injury (15.6% vs 9.2%), congestive heart failure (6.4% vs 2.4%), or cardiomyopathy (2.1% vs 0.8%) (P < .0001). Higher odds of readmission were observed in patients aged >60 vs 18-40 years (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.48-2.50) and those admitted in the Northeast vs West (OR, 1.43; 95% CI, 1.14-1.79) or South (OR, 1.28; 95% CI, 1.11-1.49). Comorbidities including diabetes (OR, 1.34; 95% CI, 1.12-1.60), CVD (OR, 1.46; 95% CI, 1.23-1.72), CKD stage 1-5 (OR, 1.51; 95% CI, 1.25-1.81), and CKD stage 5 (OR, 2.27; 95% CI, 1.81-2.86) were associated with higher odds of readmission; 12.3% of readmitted patients died during second hospitalization., Conclusions: Among this large US population of patients hospitalized with COVID-19, readmission was associated with certain comorbidities and acute conditions during first hospitalization. These findings may inform strategies to mitigate risks of readmission due to COVID-19 complications., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Pediatric non-alcoholic fatty liver disease (NAFLD) is a major public health concern. Aminotransferase (ALT) is frequently used for screening and monitoring, but few studies have reported typical patterns of ALT elevation in children. Methods: TARGET-NASH is a real-world longitudinal observational cohort of patients with NAFLD receiving care across the United States. Analyses included children enrolled between 1 August 2016, and 12 October 2020, with at least one ALT measurement after enrollment. Peak ALT was based on the first and last available record and categorized into clinical cut points: <70 IU/L, >70−<250 IU/L, and >250 IU/L. A chi-squared test was used to compare differences in proportions, and a Kruskal−Wallis test was used to compare the medians and distributions of continuous responses. Results: Analyses included 660 children with a median age of 13 years. Of the 660, a total of 187 had undergone a biopsy and were more likely to be Hispanic or Latino (67% vs. 57%, p = 0.02) and to have cirrhosis (10% vs. 1%, p < 0.001). The highest ALT scores ranged from 28 U/L to 929 U/L; however, these scores varied across time. The prevalence of cirrhosis or any liver fibrosis stage was most common among children with a peak ALT > 70 U/L. Conclusions: Large variability was seen in ALT among children, including many values > 250 U/L. Higher levels of ALT were associated with increased prevalence of comorbidities and more advanced stages of NAFLD. These findings support an increased need for therapeutics and disease severity assessment in children with peak ALT > 70 U/L.

Polypropylene (PPL) mesh is widely used in pelvic floor reconstructive surgery for prolapse and stress urinary incontinence. However, some women, particularly those treated using transvaginal PPL mesh placement for prolapse, experience intractable pain and mesh exposure or extrusion. Explanted tissue from patients with complications following transvaginal implantation of mesh is typified by a dense fibrous capsule with an immune cell-rich infiltrate, suggesting that the host immune response has a role in transvaginal PPL mesh complications through the separate contributions of the host (patient), the biological niche within which the material is implanted and biomaterial properties of the mesh. This immune response might be strongly influenced by both the baseline inflammatory status of the patient, surgical technique and experience, and the unique hormonal, immune and microbial tissue niche of the vagina. Mesh porosity, surface area and stiffness also might have an effect on the immune and tissue response to transvaginal mesh placement. Thus, a regulatory pathway is needed for mesh development that recognizes the roles of host and biological factors in driving the immune response to mesh, as well as mandatory mesh registries and the longitudinal surveillance of patients., (© 2021. Springer Nature Limited.)

Real-world evidence includes all health-related information, such as electronic health records, insurance claims, pharmacy records and wearables that are obtained outside of clinical trials. These data can provide critical insights into the natural history of disease and evaluate the safety and effectiveness of treatment regimens used in clinical practice. Real-world data have been applied to varying degrees by global regulatory agencies to inform and expedite many phases of drug development and help refine the use of therapeutic regimens after marketing, especially in populations that are under-represented in registration trials. For the management of hepatocellular carcinoma, early detection provides the best chance for curative therapies, whose success has been evaluated in numerous cohorts. The availability of novel systemic therapies, including kinase inhibitors and immunotherapies, has provided new treatment options and improved survival in patients with advanced stage hepatocellular carcinoma. Real-world longitudinal observational studies can help understand the long-term safety and effectiveness of these agents., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Promoting patient involvement in managing co-occurring physical and mental health conditions is increasingly recognized as critical to improving outcomes and controlling costs in this growing chronically ill population. The main objective of this study was to conduct an economic evaluation of the Wellness Incentives and Navigation (WIN) intervention as part of a longitudinal randomized pragmatic clinical trial for chronically ill Texas Medicaid enrollees with co-occurring physical and mental health conditions., Methods: The WIN intervention used a personal navigator, motivational interviewing, and a flexible wellness expense account to increase patient activation, that is, the patient's knowledge, skills, and confidence in managing their self-care and co-occurring physical and mental health conditions. Regression models were fit to both participant-level quality-adjusted life years (QALYs) and total costs of care (including the intervention) controlling for demographics, health status, poverty, Medicaid managed care plan, intervention group, and baseline health utility and costs. Incremental costs and QALYs were calculated based on the difference in predicted costs and QALYs under intervention versus usual care and were used to calculate the incremental cost-effectiveness ratios (ICERs). Confidence intervals were calculated using Fieller's method, and sensitivity analyses were performed., Results: The mean ICER for the intervention compared with usual care was $12 511 (95% CI $8971-$16 842), with a sizable majority of participants (70%) having ICERs below $40 000. The WIN intervention also produced higher QALY increases for participants who were sicker at baseline compared to those who were healthier at baseline., Conclusion: The WIN intervention shows considerable promise as a cost-effective intervention in this challenging chronically ill population., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

We used electronic medical record (EMR) data in the National Patient-Centered Clinical Research Network (PCORnet) to characterize "real-world" prescription patterns of Type 2 diabetes (T2D) medications. We identified a retrospective cohort of 613,203 adult patients with T2D from 33 datamarts (median patient number: 12,711) from 2012 through 2017 using a validated computable phenotype. We characterized outpatient T2D prescriptions for each patient in the 90 days before and after cohort entry, as well as demographics, comorbidities, non-T2D prescriptions, and clinical and laboratory variables in the 730 days prior to cohort entry. Approximately half of the individuals in the cohort were females and 20% Black. Hypertension (60.3%) and hyperlipidemia (50.5%) were highly prevalent. Most patients were prescribed either a single T2D drug class (42.2%) or had no evidence of a T2D prescription in the EMR (42.4%). A smaller percentage was prescribed multiple T2D drug types (15.4%). Among patients prescribed a single T2D drug type, metformin was the most common (42.6%), followed by insulin (18.2%) and sulfonylureas (13.9%). Newer classes represented approximately 13% of single T2D drug type prescriptions (dipeptidyl peptidase-4 inhibitors [6.6%], glucagon-like peptide-1 receptor agonists [2.5%], thiazolidinediones [2.0%], and sodium-glucose cotransporter-2 inhibitors [1.6%]). Among patients prescribed multiple T2D drug types, the most common combination was metformin and sulfonylureas (63.5%). Metformin-based regimens were highly prevalent in PCORnet's T2D population, whereas newer agents were prescribed less frequently. PCORnet is a novel source for the potential conduct of observational studies among patients with T2D., (© 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Background: The incidence of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in children and youth is increasing. However, the current approach for identifying pediatric diabetes and separating by type is costly, because it requires substantial manual efforts., Objective: The purpose of this study was to develop a computable phenotype for accurately and efficiently identifying diabetes and separating T1DM from T2DM in pediatric patients., Methods: This retrospective study utilized a data set from the University of Florida Health Integrated Data Repository to identify 300 patients aged 18 or younger with T1DM, T2DM, or that were healthy based on a developed computable phenotype. Three endocrinology residents/fellows manually reviewed medical records of all probable cases to validate diabetes status and type. This refined computable phenotype was then used to identify all cases of T1DM and T2DM in the OneFlorida Clinical Research Consortium., Results: A total of 295 electronic health records were manually reviewed; of these, 128 cases were found to have T1DM, 35 T2DM, and 132 no diagnosis. The positive predictive value was 94.7%, the sensitivity was 96.9%, specificity was 95.8%, and the negative predictive value was 97.6%. Overall, the computable phenotype was found to be an accurate and sensitive method to pinpoint pediatric patients with T1DM., Conclusions: We developed a computable phenotype for identifying T1DM correctly and efficiently. The computable phenotype that was developed will enable researchers to identify a population accurately and cost-effectively. As such, this will vastly improve the ease of identifying patients for future intervention studies., (©Heather Lynne Morris, William Troy Donahoo, Brittany Bruggeman, Chelsea Zimmerman, Paul Hiers, Victor W Zhong, Desmond Schatz. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 04.09.2020.)

Pronounced health disparities exist in type 1 diabetes (T1D) based on socioeconomic status (SES) yet there are a lack of programs designed to promote health equity for vulnerable communities. The All for ONE (Outreach, Networks, and Education) mentoring program was piloted pairing college students and publicly insured teenagers with T1D to assess feasibility as a possible intervention. There were 22 mentors recruited (mean age 20 ± 2 years; 17 [77%] females; mean HbA1c 8.4 ± 1.5%) and matched with mentees based on gender. There were 42 teens randomized to treatment and control groups including 22 teens in the treatment group (age 14 ± 2 years; 17 [77%] females; HbA1c 9.8 ± 2.3%) and 20 teens in the control group (age 14 ± 2 years; 15 [75%] females; HbA1c 8.9 ± 2.0%) followed over 9 months. Outcome measures included HbA1c and the Children's Hope Scale. The intervention included automated text reminders for blood glucose monitoring, text exchanges, social events with education, and clinic visits with mentors/mentees. Mean change in HbA1c for teens was +0.09% in the intervention group, compared with +0.28% in the control group (P = .61); college students had a reduction in HbA1c of -0.22% (P = .38). Treatment group teens had marked improvement in their hope for the future compared to control group teens (P = .04) and were more likely to attend clinic visits (P = .02). This program established feasibility for a model that could be replicated and modified for other types of settings. Additional research is warranted to study the potential long-term benefits of participating in the All for ONE mentoring program., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: PCORnet, the National Patient-Centered Clinical Research Network, represents an innovative system for the conduct of observational and pragmatic studies. We describe the identification and validation of a retrospective cohort of patients with type 2 diabetes (T2DM) from four PCORnet sites., Methods: We adapted existing computable phenotypes (CP) for the identification of patients with T2DM and evaluated their performance across four PCORnet sites (2012-2016). Patients entered the cohort on the earliest date they met one of three CP categories: (CP1) coded T2DM diagnosis (ICD-9/ICD-10) and an antidiabetic prescription, (CP2) diagnosis and glycosylated hemoglobin (HbA1c) ≥6.5%, or (CP3) an antidiabetic prescription and HbA1c ≥6.5%. We required evidence of health care utilization in each of the 2 prior years for each patient, as we also developed an incident T2DM CP to identify the subset of patients without documentation of T2DM in the 365 days before t 0 . Among a systematic sample of patients, we calculated the positive predictive value (PPV) for the T2DM CP and incident-T2DM CP using electronic health record (EHR) review as reference., Results: The CP identified 50 657 patients with T2DM. The PPV of patients randomly selected for validation was 96.2% (n = 1572; CI:95.1-97.0) and was consistently high across sites. The PPV for the incident-T2DM CP was 5.8% (CI:4.5-7.5)., Conclusions: The T2DM CP accurately and efficiently identified patients with T2DM across multiple sites that participate in PCORnet, although the incident T2DM CP requires further study. PCORnet is a valuable data source for future epidemiological and comparative effectiveness research among patients with T2DM., (© 2019 John Wiley & Sons, Ltd.)

Electrospun filaments are leading to a new generation of medical yarns that have the ability to enhance tissue healing through their biophysical cues. We have recently developed a technology to fabricate continuous electrospun filaments by depositing the submicron fibres onto a thin wire. Here we investigate the influence of pyridine on the fibre deposition. We have added pyridine to polydioxanone solutions at concentrations ranging from 0 to 100 ppm, increasing the conductivity of the solutions almost linearly from 0.04 uS/cm to 7 uS/cm. Following electrospinning, this led to deposition length increasing from 1 cm to 14 cm. The samples containing pyridine easily underwent cold drawing. The strength of drawn filaments increased from 0.8 N to 1.5 N and this corresponded to a decrease in fibre diameter, with values dropping from 2.7 μm to 1 μm. Overall, these findings are useful to increase the reliability of the manufacturing process of continuous electrospun filaments and to vary their biophysical properties required for their application as medical yarns such as surgical sutures., Competing Interests: The authors have declared that no competing interests exist.

Today's sutures are the result of a 4000-year innovation process with regard to their materials and manufacturing techniques, yet little has been done to enhance the therapeutic value of the suture itself. In this review, we explore the historical development, regulatory database and clinical literature of sutures to gain a fuller picture of suture advances to date. First, we examine historical shifts in suture manufacturing companies and review suture regulatory databases to understand the forces driving suture development. Second, we gather the existing clinical evidence of suture efficacy from reviewing the clinical literature and the Food and Drug Administration database in order to identify to what extent sutures have been clinically evaluated and the key clinical areas that would benefit from improved suture materials. Finally, we apply tissue engineering and regenerative medicine design hypotheses to suture materials to identify routes by which bioactive sutures can be designed and passed through regulatory hurdles, to improve surgical outcomes. Our review of the clinical literature revealed that many of the sutures currently in use have been available for decades, yet have never been clinically evaluated. Since suture design and development is industry driven, incremental modifications have allowed for a steady outflow of products while maintaining a safe regulatory position and limiting costs. Until recently, there has been little academic interest in suture development, however the rise of regenerative medicine strategies is shifting the suture paradigm from an inert material, which mechanically approximates tissue, to a bioactive material, which also actively promotes cell-directed repair and a positive healing response. These materials hold significant therapeutic potential, but could be associated with an increased regulatory burden, cost, and clinical evaluation compared with current devices.

Objective: Despite known benefits of patient-perceived collaborative goal setting, we have a limited ability to monitor this process in practice. We developed the Patient Measure of Collaborative Goal Setting (PM-CGS) to evaluate the use of collaborative goal setting from the patient's perspective., Research Design and Methods: A random sample of 400 patients aged 40 years or older, receiving diabetes care from the Virginia Commonwealth University Health System between 8/2012 and 8/2013, were mailed a survey containing potential PM-CGS items (n=44) as well as measures of patient demographics, perceived self-management competence, trust in their physician, and self-management behaviors. Confirmatory factor analysis was used to evaluate construct validity. External validity was evaluated via a structural equation model (SEM) that tested the association of the PM-CGS with self-management behaviors. The direct and two mediated (via trust and self-efficacy) pathways were tested., Results: A total of 259 patients responded to the survey (64% response rate), of which 192 were eligible for inclusion. Results from the factor analysis supported a 37-item measure of patient-perceived CGS spanning five domains: listen and learn; share ideas; caring relationship; measurable objective; and goal achievement support (χ=4366.13, p<0.001; RMSEA=0.08). Results from the SEM supported the external validity of the PM-CGS. The relationship between CGS and self-management was partially mediated by perceived competence (p<0.05). The direct effect between the PM-CGS and self-management was significant (p<0.001)., Conclusions: CGS can be validly measured by the 37-item PM-CGS. Use of the PM-CGS can help illustrate actionable deficits in goal-setting discussions., Competing Interests: Competing interests: None declared.

Background: Patient reports of collaborative goal setting have repeatedly been associated with improved health outcomes, and the American Diabetes Association specifically encourages collaborative goal setting as a component of high quality care. Current limitations in our understanding of what needs to transpire for patients to denote goal setting as "collaborative", remain a barrier to fostering collaborative goal setting in practice., Methods: Four focus groups were conducted among 19 patients with diabetes. A semi-structured focus group guide was used to explore patient perceptions of collaborative goal setting and what needed to happen for goals to be considered collaboratively set. Focus group transcripts were coded using thematic analysis., Results: Collaborative goal setting was described by patients as occurring within the context of a caring relationship where patients and health care providers: (1) listen and learn from each other; (2) share ideas; (3) agree on a measurable objective; and (4) support goal achievement. Patients also articulated clear responsibilities for themselves and clinicians and described collaborative goal setting as a process that occurs over time., Conclusions: Patients perceived collaborative goal setting as a multidimensional process that occurs over time within the context of a caring relationship and encompasses distinct patient and clinician responsibilities., (© The Author(s) 2016.)

Background: Tissue fibrosis and microvascular rarefaction are hallmarks of progressive renal disease. CD248 is a transmembrane glycoprotein expressed by key effector cells within the stroma of fibrotic kidneys including pericytes, myofibroblasts and stromal fibroblasts. In human disease, increased expression of CD248 by stromal cells predicts progression to end-stage renal failure. We therefore, hypothesized that the genetic deletion of the CD248 gene would protect against fibrosis following kidney injury., Methods: Using the unilateral ureteral obstruction (UUO) model of renal fibrosis, we investigated the effect of genetic deletion of CD248 on post obstructive kidney fibrosis., Results: CD248 null mice were protected from fibrosis and microvascular rarefaction following UUO. Although the precise mechanism is not known, this may to be due to a stabilizing effect of pericytes with less migration and differentiation of pericytes toward a myofibroblast phenotype in CD248-/- mice. CD248-/- fibroblasts also proliferated less and deposited less collagen in vitro., Conclusion: These studies suggest that CD248 stromal cells have a pathogenic role in renal fibrosis and that targeting CD248 is effective at inhibiting both microvascular rarefaction and renal fibrosis through modulation of pericyte and stromal cell function., (© 2015 S. Karger AG, Basel.)

Objective: Little is known about how patient-clinician communication leads to better outcomes. Among patients with diabetes, we describe patient-reported use of collaborative goal setting and evaluate whether perceived competency and physician trust mediate the association between collaborative goal setting and glycemic control., Methods: Data from a patient survey administered in 2008 to a cohort of insured patients aged 18+ years with diabetes who initiated oral mono-therapy between 2000 and 2005 were joined with pharmaceutical claims data for the prior 12 months and laboratory data for the prior and subsequent 12 months (N=1065). A structural equation model (SEM) was used to test mediation models controlling for baseline HbA1c., Results: The hypothesized mediation model was supported. Patient-reported use of more collaborative goal setting was associated with greater perceived self-management competency and increased level of trust in the physician (p<0.05). In turn, both greater perceived competence and increased trust were associated with increased control (p<0.05)., Conclusions: Findings indicate that engaging patients in collaborative goal setting during clinical encounters has potential to foster a trusting patient-clinician relationship as well as enhance patient perceived competence, thereby improving clinical control., Practice Implications: Fostering collaborative goal setting may yield payoffs in improved clinical outcomes among patients with diabetes., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Data of classical inborn errors of metabolism (IEM) of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area., Methods: The laboratory records of plasma amino acids, plasma acylcarnitines and urine organic acids analyses from year 2005 to 2009 inclusive in three regional chemical pathology laboratories providing biochemical and genetic diagnostic services for IEM were retrospectively reviewed., Results: Among the cohort, 43 patients were diagnosed of IEM, including 30 cases (69%) of amino acidemias (predominantly citrin deficiency, hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency and tyrosinemia type I), 5 cases (12%) of organic acidemias (predominantly holocarboxylase synthetase deficiency) and 8 cases (19%) of fatty acid oxidation defects (predominantly carnitine-acylcarnitine translocase deficiency). The incidence of classical IEM in Hong Kong was roughly estimated to be at least 1 case per 4122 lives births, or 0.243 cases per 1000 live births. This incidence is similar to those reported worldwide, including the mainland of China. The estimated incidence of hyperphenylalaninemia was 1 in 29 542 live births., Conclusions: Our data indicate that it is indisputable for the introduction of expanded newborn screening program in Hong Kong. Since Hong Kong is a metropolitan city, a comprehensive expanded newborn screening program and referral system should be available to serve the neonates born in the area.

Antibodies recognizing plasminogen, a key component of the fibrinolytic system, associate with venous thrombotic events in PR3-ANCA vasculitis. Here, we investigated the prevalence and function of anti-plasminogen antibodies in independent UK and Dutch cohorts of patients with ANCA-associated vasculitis (AAV). We screened Ig isolated from patients (AAV-IgG) and healthy controls by ELISA. Eighteen of 74 (24%) UK and 10/38 (26%) Dutch patients with AAV had anti-plasminogen antibodies compared with 0/50 and 1/61 (2%) of controls. We detected anti-plasminogen antibodies in both PR3-ANCA- and MPO-ANCA-positive patients. In addition, we identified anti-tissue plasminogen activator (tPA) antibodies in 13/74 (18%) patients, and these antibodies were more common among patients with anti-plasminogen antibodies (P = 0.011). Eighteen of 74 AAV-IgG (but no control IgG) retarded fibrinolysis in vitro, and this associated with anti-plasminogen and/or anti-tPA antibody positivity. Only 4/18 AAV-IgG retarded fibrinolysis without harboring these antibodies; dual-positive samples retarded fibrinolysis to the greatest extent. Patients with anti-plasminogen antibodies had significantly higher percentages of glomeruli with fibrinoid necrosis (P < 0.05) and cellular crescents (P < 0.001) and had more severely reduced renal function than patients without these antibodies. In conclusion, anti-plasminogen and anti-tPA antibodies occur in AAV and associate with functional inhibition of fibrinolysis in vitro. Seropositivity for anti-plasminogen antibodies correlates with hallmark renal histologic lesions and reduced renal function. Conceivably, therapies that enhance fibrinolysis might benefit a subset of AAV patients.

Objective: To assess the face validity and the inter-rater reliability of the Vein Assessment Tool (VAT) for classifying veins according to their level of intravenous insertion difficulty., Design: Prospective observational study., Participants: Eight nurses and two radiographers from the Medical Imaging Department and five nurses from the Haematology Day Patient Unit of a large tertiary hospital., Intervention: Assessments of veins in the upper limb were undertaken independently by nurses from two departments of a major tertiary hospital., Main Outcome Measure: Level of inter-rater agreement assessed using intraclass correlation coefficients (ICC)., Results: A total of 125 independent assessments were made by 15 nurses. The mean percentage agreement between raters from Medical Imaging was 84% (SD 10.7; range 60% to 100%) and between raters from Oncology was 92% (SD 17.9; range 60% to 100%). The inter-rater reliability was very high for the ten medical imaging raters 0.83 (95% confidence interval CI = 0.61 - 0.95) and for the Oncology raters 0.93 (95% CI = 0.77-0.99)., Conclusion: The Vein Assessment Tool (VAT) has been validated by a sample of nurses with cannulating experience. Following broader testing it may be useful for research studies or by nurses who wish to objectively describe the condition of a vein for clinical purposes.

The Wiskott-Aldrich syndrome protein (WASP) family activates the Arp2/3 complex leading to the formation of new actin filaments. Here, we study the involvement of Scar1, Scar2, N-WASP, and Arp2/3 complex in dorsal ruffle formation in mouse embryonic fibroblasts (MEFs). Using platelet-derived growth factor to stimulate circular dorsal ruffle assembly in primary E13 and immortalized E9 Scar1(+/+) and Scar1 null MEFs, we establish that Scar1 loss does not impair the formation of dorsal ruffles. Reduction of Scar2 protein levels via small interfering RNA (siRNA) also did not affect dorsal ruffle production. In contrast, wiskostatin, a chemical inhibitor of N-WASP, potently suppressed dorsal ruffle formation in a dose-dependent manner. Furthermore, N-WASP and Arp2 siRNA treatment significantly decreased the formation of dorsal ruffles in MEFs. In addition, the expression of an N-WASP truncation mutant that cannot bind Arp2/3 complex blocked the formation of these structures. Finally, N-WASP(-/-) fibroblast-like cells generated aberrant dorsal ruffles. These ruffles were highly unstable, severely depleted of Arp2/3 complex, and diminished in size. We hypothesize that N-WASP and Arp2/3 complex are part of a multiprotein assembly important for the generation of dorsal ruffles and that Scar1 and Scar2 are dispensable for this process.

Background: The management of simultaneously occurring abdominal aortic aneurysm and intra-abdominal malignancy is controversial. It is unclear whether to treat the aneurysm first or the malignancy, or both simultaneously. If the malignancy is resected first there is a risk of postoperative rupture of the aneurysm. If simultaneous surgery is performed there is a risk of prosthetic graft infection from contamination by gastrointestinal or urinary tract contents., Methods: Relevant papers from 1960 to 1996, identified from Medline and manual searching, were reviewed., Results and Conclusion: The literature supports the conclusion that the lesion of greater priority is that posing the greater threat to the patient; this is usually the aneurysm, especially if it is over 6 cm in diameter. For renal malignancies simultaneous surgery is the treatment of choice, but for bladder cancer the best management is unclear. Large aneurysms should usually be resected in preference to colorectal cancer unless the cancer is locally advanced, perforated or likely to result in early intestinal obstruction. If both lesions are complicated there may be a case for simultaneous treatment.

Sixty-five patients with cleft palate, with or without cleft lip, who received previous pharyngeal flap surgery for chronic velopharyngeal dysfunction in our department, were examined for velopharyngeal status, speech production patterns, and evidence of nasal airway obstruction. Of the 65 subjects, 54 (83.1 percent) showed velopharyngeal function within normal limits, 43 (66.1 percent) showed normal or near-normal speech production, and 58 (89.2 percent) reported snoring sometimes or often. Of the 58 reporting snoring, electrocardiogram (ECG) data for 33 were examined for evidence of right ventricular hypertrophy. Only one (3 percent) of the 33 showed such possible indication. We conclude that by our methods, pharyngeal flap surgery is an effective treatment for velopharyngeal dysfunction. After surgery, patients may report symptoms of nasal airway obstruction during sleep but are not expected to show ECG changes in cardiac function resulting from oxygen deprivation.

With increasing focus on outcome studies, there is continued need for data about whether same-day admission and reduced hospital stay have adverse effects on surgical treatment, including that for cleft lip and palate. In this study, medical records were inspected for all cleft lip and palate patients, aged 1 to 6 years, who had primary palatoplasty or cleft lip/palate revision in this treatment center between 1978 and 1992 (N = 329). Length of stay for 251 (96.5%) of the 260 subjects admitted the day before surgery was from 4 to 7 days; 9 remained in the hospital longer than 8 days. Length of stay for 67 (97.1%) of 69 patients admitted the day of surgery was from 2 to 3 days; 2 were in the hospital for 7 days, and none for 8 or more days. Thirty-seven instances of surgical complications were reported for the 260 patients admitted the day before surgery (14.2%). Twelve complications (17.4%) were recorded for the 69 patients admitted the day of surgery. There was no significant difference in the number of complications between the two groups of patients (Fisher's exact test, p = 0.5682). There was no significant difference in the types of complications observed between the two groups (Fisher's exact test). Surgery was performed at age 1 year for 61 of the 69 patients admitted on the day of surgery (88.4%). The mean age of this group was significantly younger than that of patients operated on earlier than 1989 and admitted on the day before surgery (Wilcoxon's test, p = .0001, Z = 4.48).(ABSTRACT TRUNCATED AT 250 WORDS)

Fifty-eight patients with cleft palate only who had received treatment in the Department of Otolaryngology-Head and Neck Surgery at the University of Iowa were examined for treatment results. Forty-one (70.7 percent) of the 58 patients showed a syndrome or suggestive factors. An unusually high percentage (36 percent) of the 58 patients required secondary surgery for velopharyngeal dysfunction or showed indications for surgery at examination. Some but not all of the relatively low success rate appears related to surgical experience. Speech proficiency, hearing acuity, and dental status were within normal limits or nearly so. The 20 patients with pharyngeal flap surgery were doing well, with minimal indications of functional obstruction.

This investigation examined the influence of cleft type, type of surgery, age at surgery, and gender on speech proficiency of 204 patients with cleft palate who required only primary palatoplasty. Speech measures were obtained for each subject from at least three annual examinations between the ages of 4 and 16 years. Neither age at surgery nor type of surgery were discriminating factors. The less extensive cleft type, i.e., soft palate only, was associated with greater rates of change in the performance variables than were the other three cleft types. Females showed greater rate changes than males.

The relationship between nasalance scores and perceptual judgments of hypernasality and hyponasality was examined for 74 subjects (51 with cleft palate and 23 noncleft controls). Twenty-nine of the 51 subjects with cleft palate had received pharyngeal flap surgery. Predictive analyses were performed to assess the sensitivity, specificity, and efficiency of the Nasometer as a screening instrument. The overall relationship between perceptual judgments of hypernasality and nasalance scores was good for the nonflap subjects when a nasalance cutoff score of 26 was used. A sensitivity coefficient of 0.87 and a specificity coefficient of 0.93 were obtained. Ninety-one percent of the nasometry-based classifications accurately reflected listener judgments of hypernasality. The correspondence between nasalance scores and clinical judgments of hyponasality was also good for the nonflap subjects when a nasalance cutoff score of 50 was used. Ninety-one percent of these classifications were consistent with the listener judgments. Efficiency of nasometry was poorer for the flap subjects.

Data regarding treatment and outcome for a consecutive series of 73 total laryngectomy patients were collected from clinical records with a follow-up period of 30 to 78 months postoperatively. Notable findings were that 27% were women; 75% reported hoarseness or a voice change as an early symptom; and 22% reported combined heavy use of both cigarettes and alcohol. Of the 73 patients, 38 (52%) died during the follow-up period; 18 of the 38 died within 1 year postoperatively. Thirty-nine (53%) of the 73 had received a surgical tracheoesophageal fistula (TEF) for voice restoration, as either a primary or a secondary procedure. Of the 39, 75% were using the TEF at last examination, with no failures attributed to sphincter spasm. Of the total group, the primary communication modality was reported to be use of a TEF by 44% and use of an electrolarynx by 50%. Limitations of the study and directions for future investigations are discussed.

Bilateral cleft of the lip and palate is by many standards the most complex and severe form of the defect. The complexity and severity of the defect require an unusual degree of cooperation among all specialists and especially between the surgeon and the orthodontist. There are no published findings that we know about in which comprehensive data from a number of disciplines are reported for the same group of bilateral cleft patients. Fifty randomly selected patients with bilateral complete clefts were examined by the Iowa team and two orthodontists from other institutions. The evaluations revealed that a large number of patients over the age of 10 have multiple residual problems requiring further treatment. Only 23 percent of the older patients studied were judged to have had treatment completed by the surgeon, speech pathologist, and orthodontist. It is very difficult to state whether the results obtained by our team can be considered satisfactory because there are no comparable studies that have attempted to evaluate the same parameters in multidisciplinary management.

The necessary information for diagnosis of "cleft palate speech" is available from clinical speech pathology tests and observations for the majority of patients. Test findings about error type and stimulability often give direction to our decisions about speech therapy. Other kinds of tests are useful for confirming these findings or for other purposes. Trial speech therapy is a very useful diagnostic procedure. Problem patients (those who fail to make suitable progress) should be referred without hesitation to a cleft palate team, or to a colleague who is an SLP on that team. Referrals to other specialists should be made appropriately, using careful, clear referral language.

The purposes of this study were to (1) examine the long-term speech status of patients judged to exhibit marginal velopharyngeal competence at 6 years of age and (2) determine whether speech performance data obtained at age 6 could be used to discriminate patients with marginal velopharyngeal competence who eventually demonstrate velopharyngeal incompetence from those who do not. Longitudinal speech performance data were retrieved for 48 subjects and examined descriptively for the total group. Data obtained at the subjects' last evaluation (adolescence) were then used to reassign these subjects into one of three classification groups for estimating velopharyngeal status (competent, marginal, incompetent) on the basis of the clinical ratings of velopharyngeal competence assigned at the time of their last examination in adolescence. Differences in measures of articulation proficiency and hypernasality among the three groups were examined at age 6 using an analysis of variance. A stepwise discriminate analysis was also performed to determine whether the speech data obtained at age 6 could be used to discriminate the three adolescent classification groups. The ANOVA revealed no significant differences among the classification groups in type of articulation errors. Differences in articulation test scores and severity ratings of articulation defectiveness and nasality in connected speech were evident among the groups. The discriminate analysis revealed that the groups could be separated, in part, on the basis of two variables: the severity ratings of articulation defectiveness and nasality.

The purpose of this study was to investigate the effect of production time on the perception of disordered nasalization in children with cleft palate. The subjects with cleft palate included 5 who produced acceptable speech consistently, 5 who produced disordered nasalization consistently, and 10 who were inconsistent in the production of disordered nasalization. We examined a range of production times similar to those for the production of single-word and connected speech tasks. Ten judges used direct magnitude estimation to rate severity of disordered nasalization. An accelerometric ratio technique was used to estimate the extent and timing of nasal acoustic activity. The results showed that reducing the production time did not change perceptible nasalization.