Citations

Introduction: Diabetes mellitus (DM) is a complication of chronic pancreatitis (CP). Whether pancreatogenic diabetes associated with CP-DM represents a discrete pathophysiologic entity from type 2 DM (T2DM) remains uncertain. Addressing this question is needed for development of specific measures to manage CP-DM. We approached this question from a unique standpoint, hypothesizing that if CP-DM and T2DM are separate disorders, they should be genetically distinct. To test this hypothesis, we sought to determine whether a genetic risk score (GRS) based on validated single nucleotide polymorphisms for T2DM could distinguish between groups with CP-DM and T2DM. Methods: We used 60 T2DM single nucleotide polymorphisms to construct a weighted GRS in 1,613 subjects from the North American Pancreatitis Study 2 and 2,685 subjects from the Multi-Ethnic Study of Atherosclerosis, all of European origin. Results: The mean GRS was identical between 321 subjects with CP-DM and 423 subjects with T2DM (66.53 vs 66.42, P = 0.95), and the GRS of both diabetic groups was significantly higher than that of nondiabetic controls (n = 3,554, P < 0.0001). Exploratory analyses attempting to enrich the CP-DM group for pancreatogenic diabetes, such as eliminating diabetes diagnosed before CP, requiring pancreas-specific comorbidities, or removing those with a family history of diabetes, did not improve the ability of the GRS to distinguish between CP-DM and T2DM. Discussion: Recognizing that we lacked a gold standard to define CP-DM, our study suggests that CP-DM may be a subtype of T2DM, a notion that should be tested in future, large prospective studies.

Significance Statement Targeting plasma cells to reduce the risk of antibody-mediated rejection and decreased allograft survival due to anti-HLA donor-specific antibodies has not been explored in transplantation. After sensitizing eight rhesus macaques with two sequential mismatched skin allografts, the authors desensitized four with daratumumab (anti-CD38 mAb) and plerixafor (anti-CXCR4) before transplant. Compared with controls, the daratumumab-treated animals had significantly reduced donor-specific antibody levels and prolonged renal graft survival; however, this reduction was not maintained. Two patients treated with daratumumab—one with therapy-resistant acute kidney antibody-mediated rejection and a highly sensitized heart transplant candidate—exhibited a significant decrease in class 1 and 2 donor-specific antibodies that led to clinical improvement of antibody-mediated rejection and heart graft access. These findings suggest daratumumab merits investigation as a potential therapeutic strategy, although further research is needed. Background Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production. Methods To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant. Results The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P <0.05) and prolonged renal graft survival (28.0 days versus 5.2 days; P <0.01). However, the reduction in donor-specific antibodies was not maintained because all recipients demonstrated rapid rebound of antibodies, with profound T cell–mediated rejection. In the two clinical patients, a combined heart and kidney transplant recipient with refractory antibody-mediated rejection and a highly sensitized heart transplant candidate, we also observed a significant decrease in class 1 and 2 donor-specific antibodies that led to clinical improvement of antibody-mediated rejection and to heart graft access. Conclusions Targeting CD38 with daratumumab significantly reduced anti-HLA antibodies and anti-HLA donor-specific antibodies in a nonhuman primate model and in two transplant clinical cases before and after transplant. This supports investigation of daratumumab as a potential therapeutic strategy; however, further research is needed regarding its use for both antibody-mediated rejection and desensitization.

Objective The purpose of this systematic review is to determine (1) current reported treatment options for isolated tibial plateau (TP) cartilage lesions, (2) patient reported outcomes following various treatments, and (3) complication rate and survivorship following various treatments. Design A literature search of PubMed, the Cochrane Library, and CINAHL was conducted adhering to PRISMA guidelines. Patients were included if they had TP cartilage lesions treated with surgery. Lesion characteristics, surgical procedure details, patient reported outcomes, complication, and failure rates were collected. Results Thirteen studies yielded 205 knees with TP cartilage lesions treated surgically. Ages ranged from 12 to 77 years. Surgical techniques included 138 treated with osteochondral allograft transplantation (OCA), 37 treated with osteochondral autograft transfer system (OATS), 11 treated with microfracture, 11 treated with an osteochondral scaffold, and 8 treated with autologous chondrocyte implantation (ACI). The patient-reported outcome measures were heterogeneous, but all reported improvements with the notable exception of one study evaluating microfracture. The rate of complications ranged from 0% to 4.6%. Failure rate ranged from 22% to 46% for OCA and 0% to 16% for OATS. No failures were reported for the additional techniques. Conclusions Various surgical techniques have been utilized for the treatment of TP cartilage lesions. Patient-reported outcome measures were heterogeneous, but improvements were reported following all surgical treatments except for microfracture, which resulted in decreased scores at mid-term follow-up. The complication rate was low for all techniques described. However, the failure rate was higher following unicondylar OCA for salvage treatment of posttraumatic deformities.

AbstractBackgroundPost‐operative pain management is a critical component of perioperative care. Patients at risk of poorly controlled post‐operative pain may benefit from early measures to optimize pain management. We sought to identify risk factors for post‐operative pain and opioid consumption in patients undergoing liver resection.MethodsThis is a multi‐institutional prospective nested cohort study of patients undergoing open liver resection. Opioid consumption and pain scores were collected following surgery. To estimate the effects of patient factors on opioid consumption (oral morphine equivalents—OME) and on pain scores (NRS‐11), we used generalized linear models and multivariable linear regression model, respectively.ResultsOne hundred and fifty‐three patients who underwent open liver resection between 2013 and 2016 were included in the study. The mean patient age was 62.2 years, and 43.3% were female. Younger patients were significantly more likely to use more opioids in the early post‐operative period (16.7 OME/10 years, p < 0.001). Patient factors that were significantly associated with increased NRS‐11 pain scores also included younger patient age (difference in pain score of 0.3/10 years with cough and 0.2/10 years at rest, p < 0.01 for both) as well as a history of analgesic use (difference in pain score of 0.9 with cough and 0.6 at rest, p < 0.01 and p = 0.07, respectively).ConclusionYounger patients and those with a history of analgesic use are more likely to report higher post‐operative pain and require higher doses of opioids. Early identification of these patients, and measures to better manage their pain, may contribute to optimal perioperative care.

Context: Hockey is a skillful contact sport with an elevated injury risk at higher levels of play. An understanding of injury incidence, type, mechanism, and severity at various levels of competition aids the clinician treating these athletes. The purpose of this clinical review is to discuss the epidemiology of hockey injuries at various levels of participation, including youth, high school, junior, college, and professional. Evidence Acquisition: A literature search was performed by a review of PubMed, Embase, and Cochrane databases and included articles published from 1988 to 2017. Studies were included in this review if determined to be of high quality and containing injury data relevant to the levels of competition. Pertinent data regarding ice hockey injury epidemiology and prevention at various levels of competition were analyzed. Study Design: Clinical review. Level of Evidence: Level 4. Results: Youth, high school, junior, college, and professional hockey players have unique injury patterns. Injuries occur much more often in a game compared with a practice, and injury risk increases with each level of competition. Preventative measures, such as mandatory facial protection and delayed body checking in games until age 13 years, are proven strategies to reduce the risk of facial injury and concussion. Conclusion: An understanding of common injury types and mechanisms according to age and level of play aids the clinician in diagnosis and management. This information can also guide preventative strategies in the areas of education, coaching, rule enforcement, rule modifications, equipment improvement, and sportsmanship.

Background: Anterior cruciate ligament (ACL) injury is one of the most frequent orthopaedic injuries and reasons for time loss in sports and carries significant implications, including posttraumatic osteoarthritis (OA). Instability associated with ACL injury has been linked to the development of secondary meniscal tears (defined as tears that develop after the initial ACL injury). To date, no study has examined secondary meniscal tears after ACL injury and their effect on OA and arthroplasty risk. Purpose: To describe the rates and natural history of secondary meniscal tears after ACL injury and to determine the effect of meniscal tear treatment on the development of OA and conversion to total knee arthroplasty (TKA). Study Design: Cohort study; Level of evidence, 3. Methods: A geographic database of >500,000 patients was reviewed to identify patients with primary ACL injuries between January 1, 1990, and December 31, 2005. Information was collected with regard to ACL injury treatment, rates/characteristics of the secondary meniscal tears, and outcomes, including development of OA and conversion to TKA. Kaplan-Meier and adjusted multivariate survival analyses were performed to test for the effect of meniscal treatment on survivorship free of OA and TKA. Results: Of 1398 primary ACL injuries, the overall rate of secondary meniscal tears was 16%. Significantly lower rates of secondary meniscal tears were noted among patients undergoing acute ACL reconstruction within 6 months (7%) as compared with patients with delayed ACL reconstruction (33%, P < .01) and nonoperative ACL management (19%, P < .01). Of the 235 secondary meniscal tears identified (196 patients), 11.5% underwent repair, 73% partial meniscectomy, and 16% were treated nonoperatively. Tears were most often medial in location (77%) and complex in morphology (56% of medial tears, 54% of lateral tears). At the time of final follow-up, no patient undergoing repair of a secondary meniscal tear (0%) underwent TKA, as opposed to 10.9% undergoing meniscectomy and 6.1% receiving nonoperative treatment ( P = .28). Conclusion: Secondary meniscal tears after ACL injury are most common among patients undergoing delayed surgical or nonoperative treatment of their primary ACL injuries. Secondary tears often present as complex tears of the medial meniscus and result in high rates of partial meniscectomy.

Objectives The purpose of this study was to describe an arthroscopic surgical approach to identify and expose the popliteus tendon (PT), posterior fibular head, Fibular collateral ligament (FCL), popliteal fibular ligament (PFL), biceps femoris tendon, and the peroneal nerve. Methods 10 fresh human cadaveric knees were examined arthroscopically using standard anterior and posterior portals. The use of a transeptal approach with both posteromedial and posterolateral portals was required using a standard 30 degrees arthroscope. Optimal portal placement and specific technique and sequence for appropriate visualization of the PLC structures were tested and documented. Results In all specimens, all the PLC structures that we attempted to identify were successfully visualized. These included the PT, posterior fibular head, the FCL, the PFL, biceps femoris tendon, peroneal nerve, PT and FCL femoral attachments. Conclusion This study demonstrated that the identification and exposure of the PLC structures using an all arthroscopic approach can be successfully performed with precise portal placement. This technique may serve as a basis for arthroscopic treatment of PLC injuries.

e18132 Background: Older adults (65+ years) make up > 50% of cancer patients in the US,1 yet, older patient enrollment onto trials remains < 30%.2 This study’s aim was to determine the association between trial level variables and accrual rates of adults 65+ to better design trials that can more improve enrollment of these patients. Methods: We analyzed enrollment percentages of patients age 65+ in non-age specific Alliance trials with > 50 patients, that completed accrual between 1995- 2015. Enrollment percentage by 65+ for each study was compared to cancer incidence percentage by 65+ according to the Surveillance, Epidemiology, and End Results (SEER) Program for the same time periods. Enrollment Disparity Difference (EDD)3, defined as the difference between SEER incidence percentage of patients 65+ and the trial percentage enrollment of 65+ was calculated for each trial ( SEER % – trial %). Univariate analyses (UVA) were performed using simple linear regression to determine trial variables associated with larger EDDs (higher disparity). Variables that had an F-test p-value < 0.20 were included in a multivariable fixed-effects linear model for multivariate analysis (MVA). Results: Median age of 66,708 patients across 237 trials with 10 cancer types was 60 years. Average % of 65+ in trials was lower than average SEER comparison % 65+ per trial (37.6% vs. 57.8%). The median trial EDD, was 16.7%. On UVA, cancer type was significantly associated with higher EDD (see Table). Use of fewer modalities (1, 2, vs 3+) was associated with lower estimated EDDs (1 = -11 [+/-3.6], 2 = -8.9 [+/-3.9], F-test p = .012). On MVA, non-genitourinary (GU) cancer type, number of treatment modalities, and the phase (II or III compared to observational/other) were all significantly associated with higher EDD. Conclusions: Older adults were under-represented in this large sample of trials. This information can be used as a platform to better design disease-specific trials to improve older patient accrual, particularly in disease areas which are under-performing. Support: U10CA180821, U10CA180882, UG1CA189823: https://acknowledgments.alliancefound.org . References: 1. Smith BD et al. J Clin Oncol 27:2758-65, 2009; 2. Hurria A, et al. J Geriatr Oncol 1:40-44, 2010; 3. Pang HH, et al. J Clin Oncol, 2016.[Table: see text]