Citations

ABSTRACTArthrofibrosis is a common complication following total knee arthroplasty caused by pathologic fibroblast activation and excessive collagen deposition around a synovial joint leading to debilitating loss of motion. Treatment options are limited because the pathologic mechanisms remain to be characterized. Dysregulation of the inflammatory cascade may lead to communication between myofibroblasts and immune cells triggering tissue metaplasia, and excessive collagen deposition described clinically as arthrofibrosis. We explored the novel use of celecoxib (selective cyclooxygenase‐2 [COX‐2] inhibitor) to disrupt the downstream effects of the post‐traumatic inflammatory cascade and inhibit scar tissue formation in a validated rabbit model of arthrofibrosis combined with new parameters for quantifying the stiffness of the posterior capsule. Biomechanical and molecular analyses, of contracted rabbit knee posterior capsule tissue after COX‐2 inhibition revealed increased maximal passive extension and down‐regulation of collagen messenger RNA compared with controls. Histopathologic examination suggested a trend of decreased quantities of dense fibrous connective tissue with COX‐2 inhibition. These data may suggest that inhibiting the inflammatory cascade could potentially reduce pathologic myofibroblast activation, thereby reducing scar tissue formation and increasing the range of motion in arthrofibrotic joints. Implementing a multi‐modal pharmacologic approach may simultaneously target numerous cellular components contributing to the complex process of arthrofibrogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2609–2620, 2019

Abstract Background Cardiac troponin (cTn) assays are used for the diagnosis of acute myocardial infarction and frequently require serial measurements. Recollection of unacceptable specimens for hemolysis can delay results and disrupt timing of serial measurements. This study was designed to assess the influence of hemolysis on a high-sensitivity cTnT assay in granular detail at clinically important concentrations. These were used in consultation with the clinical practice to evaluate risk-based thresholds for acceptable amounts of hemolysis. Methods Plasma pools ranging from <10 to >100 ng/L cTnT were spiked with hemolysate to various degrees of hemolysis and measured using the Elecsys Troponin T Gen 5 STAT assay. The impact of accepting expanded hemolysis thresholds was completed using retrospective data of 12225 serial cTnT results and an additional 4651 baseline cTnT results. Results The mean percent change in cTnT was consistent for a given degree of hemolysis regardless of the initial nonhemolyzed cTnT concentration. Tiered hemolysis thresholds were evaluated for low-risk patients (apparent cTnT ≤8 ng/L), intermediate-risk patients (thresholds for 9–37 ng/L, 38–66 ng/L, and 67–99 ng/L cTnT), and high-risk patients (≥100 ng/L cTnT). The influence of tiered hemolysis thresholds was calculated for patients with serial (0 and 2 h) cTnT results, which demonstrated that the majority of 2-h delta interpretations were unchanged. Implementation of tiered thresholds dramatically decreased recollections for hemolyzed cTnT samples. Conclusion Tiered hemolysis cutoffs minimized disruption to patient care for low- and high-risk patients, while maintaining the integrity of serial measurements for those with intermediate cTnT concentrations.

Selection of antihypertensive treatment according to self-defined ethnicity is recommended by some guidelines but might be better guided by individual genotype rather than ethnicity or race. We compared the extent to which variation in blood pressure response across different ethnicities may be explained by genetic factors: genetically defined ancestry and gene variants at loci known to be associated with blood pressure. We analyzed data from 5 trials in which genotyping had been performed (n=4696) and in which treatment responses to β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker, thiazide or thiazide-like diuretic and calcium channel blocker were available. Genetically defined ancestry for proportion of African ancestry was computed using the 1000 genomes population database as a reference. Differences in response to the thiazide diuretic hydrochlorothiazide, the β-blockers atenolol and metoprolol, the angiotensin-converting enzyme inhibitor lisinopril, and the angiotensin receptor blocker candesartan were more closely associated to genetically defined ancestry than self-defined ethnicity in admixed subjects. A relatively small number of gene variants related to loci associated with drug-signaling pathways ( KCNK3, SULT1C3, AMH, PDE3A, PLCE1, PRKAG2 ) with large effect size (−3.5 to +3.5 mm Hg difference in response per allele) and differing allele frequencies in black versus white individuals explained a large proportion of the difference in response to candesartan and hydrochlorothiazide between these groups. These findings suggest that a genomic precision medicine approach can be used to individualize antihypertensive treatment within and across populations without recourse to surrogates of genetic structure such as self-defined ethnicity.

Background: The training process and practice of orthopaedic surgery is demanding and arduous. Accordingly, grit, self-control, and conscientiousness are desirable qualities in orthopaedic surgeons. Some established orthopaedists have expressed concern that the future generation of surgeons may not possess the same level of grit as their predecessors. The purpose of this study was to evaluate levels of grit among attending orthopaedic surgeons, identify predictors of grit in orthopaedic surgeons, and compare grit scores between attending surgeons and orthopaedic residency applicants. We hypothesized that applicants would demonstrate lower grit and self-control scores but greater conscientiousness scores than attending surgeons. Methods: A total of 2,342 attending orthopaedic surgeons and 895 orthopaedic residency applicants from the 2016-2017 National Resident Matching Program (NRMP) were given surveys that quantified their grit, self-control, and conscientiousness. Demographic and career information also was collected. Results: Assessments were completed by 655 (28%) of 2,342 practicing orthopaedic surgeons and 455 (50.8%) of 895 orthopaedic residency applicants. The residency applicants demonstrated higher mean grit scores (4.12 of 5.0) than the attending orthopaedic surgeons (4.03) (p < 0.01). These average scores placed applicants and attending surgeons at the 70th and 65th percentile, respectively, when compared with the general population. There were no differences in self-control (p = 0.68) or conscientiousness (p = 0.93) between the 2 groups. Attending surgeons with more publications had increased grit (p < 0.01), self-control (p = 0.04), and conscientiousness (p = 0.01) scores. Attending surgeons who had been inducted into the Alpha Omega Alpha honor society as medical students demonstrated greater conscientiousness scores than those who were not members (p = 0.04). Conclusions: Orthopaedic residency applicants were at least as gritty, consistent in their interest, persevering in their efforts, and ambitious as currently practicing orthopaedic surgeons. Although these results may be encouraging and diverge from some preconceived perceptions of “millennials,” it is unclear if they will be predictive of career success in the next generation of orthopaedists.

Purpose The medical student performance evaluation (MSPE) summarizes a residency applicant’s academic performance. Despite attempts to improve standardized clerkship grading, concerns regarding grade inflation and variability at United States medical schools persist. This study’s aim was to describe current patterns of clerkship grading and applicant performance data provided in the MSPE. Method The authors evaluated Electronic Residency Application Service data submitted to a single institution for the 2016–2017 Match cycle. Clerkship grading characteristics regarding grading tiers, school rank, location, and size were obtained. Data regarding methods for summative comparisons such as key word utilization were also extracted. Descriptive statistics were generated, and generalized linear modeling was performed. Results Data were available for 137/140 (98%) MD-granting U.S. medical schools. Pass/fail grading was most commonly used during the preclinical years (47.4%). A 4-tier system was most common for clerkship grading (31%); however, 19 different grading schemes were identified. A median of 34% of students received the highest clerkship grade (range, 5%–97%). Students attending a top 20 medical school were more likely to receive the highest grade compared with those attending lower-rated schools (40% vs 32%, P < .001). Seventy-three percent of schools ranked students, most commonly using descriptive adjectives. Thirty-two different adjectives were used. Conclusions There is significant institutional variation in clinical grading practices and MSPE data. For core clerkships where most students received the highest grade, the ability to distinguish between applicants diminishes. A standardized approach to reporting clinical performance may allow for better comparison of residency applicants.

Background: Infection following Achilles tendon surgery is a devastating complication and can be difficult to treat and often leads to poor outcomes. A number of treatments have been described, but there is little information concerning outcomes of these treatments. Our purpose was to evaluate the clinical and functional outcomes of patients who have undergone treatment for an infected Achilles tendon after acute and chronic midsubstance repair. Methods: We retrospectively reviewed the medical records of 20 patients who had undergone surgical treatment for an infected Achilles tendon between 2000 and 2016. The mean follow-up time was 21 months (range, 2-68 months). All patients underwent extensive debridement of the tendon with removal of all infected tissue and foreign material. Soft tissue wound coverage was utilized for large wounds that were not amenable to primary or secondary closure. All patients received culture-specific intravenous (IV) antibiotics for 3 to 6 weeks. Postoperatively, the extremity was immobilized in a splint followed by a cast until the wound was healed. The cast was then replaced with a walking boot and the patients were provided a physical therapy program. Functional outcomes were measured using the Foot and Ankle Ability Measure (FAAM) Activity of Daily Living (ADL) scale. Results: All wounds had healed at the time of last follow-up. Three patients (15%) required an unplanned return to the operating room for repeat debridement. All patients were able to walk without the use of a gait aid. Five patients (25%) required continued use of a boot or brace during ambulation. Fourteen patients participated in the FAAM ADL survey. There were 6 patients lost to follow-up. The average FAAM score was 87 (range, 71.4-100). At last follow-up, most patients reported their overall function as “normal” or “nearly normal.” Eradication of infection and satisfactory functional results can be attained after radical debridement, wound closure, and administration of culture-specific IV antibiotics. Level of Evidence: Level IV, retrospective case series.

AbstractBackgroundIL‐10‐producing regulatory B cells (Bregs) are widely ascribed immune regulatory functions. However, Breg subsets in human asthma have not been fully investigated.ObjectiveWe studied Breg subsets in adult allergic asthma patients by assessing two major parameters, frequency and IL‐10 expression. We then investigated factors that affect these two parameters in patients.MethodsPeripheral blood mononuclear cells (PBMCs) of adult allergic asthma patients (N = 26) and non‐asthmatic controls (N = 28) were used to assess the frequency of five subsets of transitional B cells (TBs), three subsets of CD24highCD27+ B cells and B1 cells. In addition to clinical data, IL‐10 expression by individual Breg subsets was assessed by flow cytometry.ResultsAsthma patients had decreases of CD5+ and CD1d+CD5+, but an increase of CD27+ TBs which was significant in patients with moderate asthma (60 < FEV1 < 80). Regardless of asthma severity, there was no significant alteration in the frequencies of 6 other Breg subsets tested. However, we found that oral corticosteroid (OCS) significantly affected the frequency of Bregs in Breg subset‐specific manners. OCS decreased CD5+ and CD1d+CD5+ TBs, but increased CD27+ TBs and CD10+CD24highCD27+ cells. Furthermore, OCS decreased IL‐10 expression by CD27+ TBs, all 3 CD24highCD27+ B cell subsets (CD5+, CD10+ and CD1d+) and B1 cells. OCS‐mediated inhibition of IL‐10 expression was not observed in the other Breg subsets tested.Conclusion & Clinical RelevanceAlterations in the frequency of Bregs and their ability to express IL‐10 are Breg subset‐specific. OCS treatment significantly affects the frequency as well as their ability to express IL‐10 in Breg subset‐specific manners.