Citations

SummaryThe plasmin substrate, H-D-norleucyl-hexahydrotyrosyl lysine-p-nitroanilide (Spectrozyme-PL), was found to be equiva lent to 6-aminohexanoate as an enhancer of porcine and human plasminogen activation by urokinase and of removal of the 1-77 peptide of plasminogen by plasmin. Activation of plasminogen lacking kringles 1-4, on the other hand, was not influenced by Spectrozyme PL. Although the rate of activation of human plasminogen and the modification of human plasminogen by plasmin are faster by an order of magnitude than that of the activation and modification of porcine plasminogen, both reactions in the human zymogen, the hydrolysis at arg561-val562 and at lys77lys78, are accelerated by Spectrozyme PL. The findings indicate that kinetic interpretation of plasminogen activation in solutions containing substrates, where the substrate has been incorporated to inhibit feedback proteolysis by plasmin, must account for the cofactor activity as well as the inhibitory activity of the substrate.

Background We designed a survey to ascertain the current perspectives of hand surgeons on the evaluation and management of ulnar nerve instability at the elbow. The secondary aim was to assess the concordance of hand surgeons on definitions of the terms “subluxated” and “dislocated” for classification of ulnar nerve instability. Methods A questionnaire, including demographic practice variables, cubital tunnel practice patterns, preoperative imaging and electrodiagnostic evaluation, and a series of standardized intraoperative photographs of ulnar nerve instability at the elbow were developed and distributed to the current American Society for Surgery of the Hand (ASSH) membership. Results A total of 690 (26.8%) members completed the survey; 84.2% of respondents indicated that they evaluate for ulnar nerve instability preoperatively with clinical examination, whereas only 6.1% indicated they routinely obtained dynamic ultrasound. Respondents indicated that the factors most strongly influencing their decision to proceed with anterior transposition of the ulnar nerve were subluxation on physical examination (89.6%), history consistent with ulnar nerve subluxation (85.8%), and muscle atrophy (43.2%). On review of clinical photographs, respondents demonstrated varying degrees of agreement on the terms “subluxated” or “dislocated” and recommendations for ulnar nerve transposition at intermediate degrees of ulnar nerve instability. Conclusion ASSH members routinely evaluate for ulnar nerve instability with history and clinical examination without uniform use of preoperative ultrasound, and nearly half of the time the decision to transpose the ulnar nerve is made intraoperatively. Definitions for the degree of ulnar nerve instability at the elbow are not uniformly agreed upon, and further development of a classification system may be warranted to standardize treatment.

AbstractNursing home (NH) residency is an independent risk factor for venous thromboembolism (VTE), but the VTE burden within the NH population is uncertain. This study estimates VTE incidence and VTE-associated mortality among NH residents. We identified all NH residents in any NH in Olmsted County, Minnesota, United States, 1 October 1998 to 31 December 2005 and all first lifetime VTE among county residents to estimate VTE incidence while resident of local NHs (NHVTE), using Centers for Medicare and Medicaid Services Minimum Data Set and Rochester Epidemiology Project resources. We tested associations between NHVTE and age, sex and time since each NH admission using Poisson modelling. Additionally, we tested incident NHVTE as a potential predictor of survival using Cox proportional hazards, adjusting for age, sex and NH residency. Between 1 October 1998 and 31 December 2005, 3,465 Olmsted County residents with ≥1 admission to a local NH, contributed 4,762 NH stays. Of the 3,465 NH residents, 111 experienced incident NHVTE (2.3% of all eligible stays), for an overall rate of 3,653/100,000 NH person-years (NH-PY). VTE incidence was inversely associated with time since each NH admission, and was highest in the first 7 days after each NH admission (18,764/100,000 NH-PY). The adjusted hazard of death for incident NHVTE was 1.90 (95% confidence interval [CI]: 1.38–2.62). In conclusion, VTE incidence among NH residents was nearly 30-fold higher than published incidence rates for the general Olmsted County population. VTE incidence was highest within 7 days after NH admission, and NHVTE was associated with significantly reduced survival. These data can inform future research and construction of clinical trials regarding short-term prophylaxis.

Objectives Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early‐onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD‐ and schizophrenia (SCZ)‐associated risk variants is associated with an earlier AAO in BD patients. Methods A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn‐Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD‐ and SCZ‐PRSs and AAO were evaluated with regression models. Results BD‐ and SCZ‐PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. Conclusions The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.

Background Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell responses and to promote tolerance has aligned them ideally for a role in vascularized composite allotransplantation (VCA). In this study, we summarize the current evidence for DC therapies for tolerance induction to alleviate the requirement for chronic immunosuppression. Method A comprehensive and structured review of manuscripts published on VCA was performed using the MEDLINE and PubMed databases. All eligible studies published from the year 2000 to 2017 were included in the final results. Result Nineteen original preclinical and clinical studies that employed cell therapy for VCA were included in this review. In vivo DC therapy was found to direct the alloimmune response toward either transplant rejection or tolerance in VCA models. While injection of mature DCs rapidly increases T-cell activity in humans and promotes transplant rejection, the injection of immature DCs acts as an immunosuppressant and inhibits T-cell activity. In addition to immature DCs, mesenchymal stem cells were also found to have a positive effect on allotransplantation of solid organs and bone marrow via cytokine expression which decreases the alloreactive effector lymphocytes and increases CD4+/CD25+/FoxP3 Tregs. Despite the promising findings, the efficacy of cell-based therapies varies greatly across studies, partly due to different methods of cell isolation and purification techniques, source, route and timing of administration, and combination immunosuppressive therapy. Conclusion Additional research is needed to evaluate the efficacy and safety of DC and other cell-based therapeutic measures in human allotransplant recipients. Future direction will focus on the development of novel methods to reduce immunosuppression and develop more individualized management, as well as the clinical application of basic research in the mechanisms of immunologic tolerance.

Background Type 1 diabetes (T1D) care requires multiple daily self-management behaviors (SMBs). Preliminary studies on SMBs rely mainly on self-reported survey and interview data. There is little information on adult T1D SMBs, along with corresponding compensation techniques (CTs), gathered in real-time. Objective The article aims to use a patient-centered approach to design iDECIDE, a smartphone application that gathers daily diabetes SMBs and CTs related to meal and alcohol intake and exercise in real-time, and contrast patients' actual behaviors against those self-reported with the app. Methods Two usability studies were used to improve iDECIDE's functionality. These were followed by a 30-day pilot test of the redesigned app. A survey designed to capture diabetes SMBs and CTs was administered prior to the 30-day pilot test. Survey results were compared against iDECIDE logs. Results Usability studies revealed that participants desired advanced features for self-tracking meals and alcohol intake. Thirteen participants recorded over 1,200 CTs for carbohydrates during the 30-day study. Participants also recorded 76 alcohol and 166 exercise CTs. Comparisons of survey responses and iDECIDE logs showed mean% (standard deviation) concordance of 77% (25) for SMBs related to meals, where concordance of 100% indicates a perfect match. There was low concordance of 35% (35) and 46% (41) for alcohol and exercise events, respectively. Conclusion The high variability found in SMBs and CTs highlights the need for real-time diabetes self-tracking mechanisms to better understand SMBs and CTs. Future work will use the developed app to collect SMBs and CTs and identify patient-specific diabetes adherence barriers that could be addressed with individualized education interventions.