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As the US population continues to grow in racial and ethnic diversity, we also continue to see healthcare disparities across racial lines. Considerable attention has been given to creating a physician workforce that better reflects the population served by healthcare professionals. To address the low numbers of women and underrepresented minorities in procedural based specialties, Nth Dimensions has sought to address and eliminate healthcare disparities through strategic pipeline initiatives. This is a retrospective observational cohort study of 118 medical students from 29 accredited US medical schools, who were awarded a position in the Nth Dimensions Summer Internship program between 2005 and 2012. Overall, 84 NDSI scholars applied and 81 matched into procedure-based specialties; therefore the overall retention rate was 75% and the overall match rate across the eight cohorts was 72.3%. Through intervention-based change, the authors hypothesize that greater numbers in the residency training cohorts can lead to a greater number of physicians with diverse backgrounds and perspectives. Ultimately, this will enhance quality of care for all patients and improve decision making process that influence healthcare systems. Strategic pipeline programs increase successful recruit women and underrepresented minorities to apply and matriculate into procedure based residency programs. This is a retrospective observational cohort study of 118 medical students who completed the Nth Dimensions Summer Internship program between 2005 and 2012. Overall, 84 NDSI scholars applied and 81 matched into procedure-based specialties; therefore the overall retention rate was 75% and the overall match rate across the eight cohorts was 72.3%.

Background Women and minorities remain underrepresented in orthopaedic surgery. In an attempt to increase the diversity of those entering the physician workforce, Nth Dimensions implemented a targeted pipeline curriculum that includes the Orthopaedic Summer Internship Program. The program exposes medical students to the specialty of orthopaedic surgery and equips students to be competitive applicants to orthopaedic surgery residency programs. The effect of this program on women and underrepresented minority applicants to orthopaedic residencies is highlighted in this article. Questions/purposes (1) For women we asked: is completing the Orthopaedic Summer Internship Program associated with higher odds of applying to orthopaedic surgery residency? (2) For underrepresented minorities, is completing the Orthopaedic Summer Internship Program associated with higher odds of applying to orthopaedic residency? Methods Between 2005 and 2012, 118 students completed the Nth Dimensions/American Academy of Orthopaedic Surgeons Orthopaedic Summer Internship Program. The summer internship consisted of an 8-week clinical and research program between the first and second years of medical school and included a series of musculoskeletal lectures, hands-on, practical workshops, presentation of a completed research project, ongoing mentoring, professional development, and counselling through each participant’s subsequent years of medical school. In correlation with available national application data, residency application data were obtained for those Orthopaedic Summer Internship Program participants who applied to the match between 2011 through 2014. For these 4 cohort years, we evaluated whether this program was associated with increased odds of applying to orthopaedic surgery residency compared with national controls. For the same four cohorts, we evaluated whether underrepresented minority students who completed the program had increased odds of applying to an orthopaedic surgery residency compared with national controls. Results Fifty Orthopaedic Summer Internship scholars applied for an orthopaedic residency position. For women, completion of the Orthopaedic Summer Internship was associated with increased odds of applying to orthopaedic surgery residency (after summer internship: nine of 17 [35%]; national controls: 800 of 78,316 [1%]; odds ratio [OR], 51.3; 95% confidence interval [CI], 21.1–122.0; p < 0.001). Similarly, for underrepresented minorities, Orthopaedic Summer Internship completion was also associated with increased odds of orthopaedic applications from 2011 to 2014 (after Orthopaedic Summer Internship: 15 of 48 [31%]; non-Orthopaedic Summer Internship applicants nationally: 782 of 25,676 [3%]; OR, 14.5 [7.3–27.5]; p < 0.001). Conclusions Completion of the Nth Dimensions Orthopaedic Summer Internship Program has a positive impact on increasing the odds of each student participant applying to an orthopaedic surgery residency program. This program may be a key factor in contributing to the pipeline of women and underrepresented minorities into orthopaedic surgery. Level of Evidence Level III, therapeutic study.

Category: Bunion Introduction/Purpose: Hallux Valgus is a complex deformity with several attendant components that are present to varying degrees in each patient. Historically primary attention has been paid to correction of the coronal plane deformity, but recent investigations suggest a substantial contribution to the deformity from the axial rotational abnormality of the metatarsal. While the effect of this metatarsal pronation has been demonstrated, the relative contribution of this parameter compared to other components has not been considered. This study aims to investigate the rotational aspect of the deformity and its contribution to successful radiographic correction of the deformity. Methods: A retrospective review of 100 consecutive Lapidus bunionectomy procedures was performed. There were 80 of patients and 89 feet. patients <18yrs, revision surgery and combined surgery, other than forefoot procedures were excluded. There were 79 (88%) females and 10 (12) males. The mean age was55. All feet were followed till radiographic healing was complete. Each foot was examined radiographically and pre and post-operative findings were compared. Along with the typical measurements of Hallux valgus parameters in the coronal plane, an additional measurement was included to estimate metatarsal head pronation (MT head shape and sesamoid position). The radiographic outcomes were then compared to determine the independent effect of metartarsal rotation on outcomes (recurrence, time to fusion). Pearson correlation was utilized to determine significant associations with the outcome parameters for recurrence, time to fusion, and failure to correct the hallux valgus angle (HVA). Results: The average HVA correction was 20.08 degrees and 6.86 degrees for IMA. A total of 68 feet had a positive preop round head sign and correction to a normal MT head shape was observed in 47 feet. A significant increase in recurrence was associated with patients that had persistent MT round sign following correction (p=0.001) and in patients with a higher sesamoid position in the preop period p<0.001). The average time to fusion was 9.56 with 47 (52%) feet were healed at 6 weeks postop. A higher (more lateral) sesamoid position and a higher postop HVA were also associated with longer time to fusion or delayed union. Conclusion: Adequate preoperative radiographic assessment is of the utmost importance to assess the various forces that can contribute to hallux valgus deformity. Newer techniques address coronal and sagittal plane deformity. Failure to correct MT head pronation may lead to increased hallux valgus recurrence, despite sagittal correction measured by improvement of the HVA and IMA angles. Factors that impact time to fusion are also associated with a higher risk of HV recurrence. Sesamoid position and metatarsal head pronation should be considered, and correction of these parameters may be necessary to avoid delayed healing and persistent or recurrent HV.

With the large number of total knee arthroplasties being performed and expectations that these numbers will be on the rise over the coming decades, efforts to provide cost-efficient care are of greater interest. The preferred design of knee arthroplasty implants has changed over time, with the original all-polyethylene tibial (APT) design being replaced by metal-backed tibial (MBT) components, as well as more recent considerations of newer APT designs. Modern APT components have been shown to have similar or superior outcomes than MBT components. Despite their limitations, APT components can be used to reduce the economic burden to the provider, medical institution, and health care system as a whole. There is a paucity of evidence-based literature directly comparing the cost associated with APT and MBT components. The purpose of this report is to review the literature to assess the available data regarding direct and indirect costs of both designs so that orthopedic surgeons can account for economic differences in everyday practice. [ Orthopedics . 2016; 39(3):S61–S66.]

Objectives: Lisfranc injuries are increasingly common among athletes. Tarsometatarsal joint injuries often damage the articular cartilage and increase predisposition for post-traumatic arthritis and functional deformity of the midfoot. Injury-related morbidity in athletes has substantial consequences such as decreased performance and earlier retirement from sports. While open reduction and internal fixation (ORIF) has been established as the standard of care for unstable Lisfranc injuries, there is currently no consensus regarding the optimal technique for stabilization. Extra-articular fixation has been described as a reasonable technique for Lisfranc joint stabilization due to avoidance of iatrogenic articular disruption and subsequent morbidity. The purpose of this study was to assess the pre- and post-operative patient-reported outcomes of athletes with Lisfranc injuries following ORIF using an extra-articular dorsal locking plate. Methods: Following Institutional Review Board (IRB) approval, data was collected prospectively using an institution-based patient-reported outcomes registry. The registry was queried for patients who had undergone open treatment for tarsometatarsal dislocation (CPT 28615) between April 2015 and August 2018. Medical records were reviewed for the following criteria: athlete, 15 - 45 years of age, Lisfranc injury, ORIF, extra-articular dorsal locking plate, and completion of both pre- and post-operative outcomes surveys. 10 athletes were identified. The surveys used were as follows: VAPS, PASS, PROMIS-M, PROMIS-P, SF12-M, SF12-P, FAAM-ADL and FAAM-Sports. A comparison of pre- and post-operative outcomes was performed using paired t-tests. Statistical significance was defined as a p-value <0.05. Results: 10 athletes (5 male, 5 female) with an average age of 18.2 years were analyzed. Sports included football, gymnastics, soccer, hockey, and basketball. Competition levels included high school and college. All athletes had scheduled hardware removal between 3 - 5 months (average 4.4 months) after the initial ORIF. The FAAM-ADL scores (Δ42.49, p <0.0174) improved significantly at 6-months follow-up. The improvement of FAAM-ADL scores continued to trend positively for up to 1-year post-operatively; however, there was insufficient data to analyze for significance. There was no statistical significance observed between pre- and post-operative VAPS, PASS, PROMIS-M, PROMIS-P, SF12-M, SF12-P and FAAM-Sports scores at 6-months follow-up. 100% of athletes returned to sport at an average of 6 months. Conclusion: In athletes, extra-articular dorsal plate fixation of the Lisfranc joint demonstrates improvement in post-operative patient reports of function. Broad-statistical significance across all patient-reported measures was likely limited due to the number of participants. Patient-reported outcomes may serve as a guide to assess athlete progress during the post-operative period. Further studies are needed to compare the long-term outcomes of Lisfranc injuries in athletes following various methods of fixation.

Objectives: Jones’ fractures, 5th metatarsal metaphyseal-diaphyseal junction fractures, are a debilitating injury for the elite athlete, particularly in cutting/pivoting sports. These injuries are usually managed surgically due to the high rate of nonunion and re-fracture. Despite primary screw fixation, delayed union and nonunion are not uncommon. Bone marrow aspirate concentrate (BMAC), an autologous source of hematopoietic and mesenchymal stem cells, has been used to augment healing due to the poor healing potential in the watershed region. We hypothesize that open reduction internal fixation (ORIF) augmented with BMAC will improve patient-reported outcome measures following Jones’ fractures in athletes. Methods: This study was a prospectively collected and maintained review of elite athletes that underwent intramedullary screw fixation augmented with BMAC for Jones’ fractures at an academic medical institution. All patients were evaluated preoperatively and postoperatively to assess differences in patient reported outcomes including VAS, PROMIS, FAAM, SF-12 scores, return to play, and complications. Student’s t test was used in statistical comparison of the preoperative and postoperative outcome scores. P < 0.05 was considered significant. Results: A total of 41 elite athletes were treated with ORIF with BMAC for a Jones fracture with a mean age of 25.59 years (range 19-42). There were 26 (63%) males and 15 females included in the study. Type of athlete ranged across the following sport activities: football, basketball, soccer, volleyball. Of note, patients had significantly improved with lower visual analog score for pain (mean Δ3.56, p= 0.001), higher FAAM scores (mean Δ 43.6, p< 0.001), and PASS scores (increased from 11% to 85%, p< 0.001) at 6 months. Additionally, patients showed improvement in SF12, PROMIS10, and FAAM scores at 12 months, although this was not statistically significant due to insufficient follow up at this time. The average numbers of days lost to competition was 131 days. All patients that have returned to elite competitive sport activity report minimal to no pain. Conclusion: Intramedullary screw fixation of Jones’ fractures with BMAC results in optimal surgical outcomes in the elite athlete. The use of patient reported outcomes continues to be a focus of quality measures and should guide clinical decision making for surgical intervention, return to play, and to assess impact of treatment. A higher powered and long-term study with validated patient-reported outcomes is needed to confirm our observations.

Different biomechanical designs are incorporated into various total knee arthroplasty (TKA) implants. The posterior-stabilized prosthesis design utilizes a polyethylene post and femoral cam in place of the posterior cruciate ligament. This produces a more stable component interface, increased range of motion, and potentially a less technical procedure. This study aimed to assess the short-term (>2 year) outcomes associated with the Vega System posterior-stabilized knee prosthesis (Aesculap Implant Systems, Center Valley, Pennsylvania) based on postoperative radiographs using the Knee Society Roentgenographic Evaluation and Scoring System (KSRESS). Thirty-seven TKA patients who had received the Vega posterior-stabilized knee prosthesis and had postoperative radiographs at each follow-up for a minimum of 2 years were enrolled, retrospectively. Two independent observers evaluated the radiographs using KSRESS. Descriptive statistics were used to analyze the data. The average age and body mass index of patients enrolled was 67 years (range, 51–89 years) and 38.5 kg/m 2 (range, 21.2–54 kg/m 2 ), respectively. Patients had radiographic follow-up for an average of 36 months (range, 24–58 months). Comparison between first and last available postoperative radiographs revealed a stable femoral and tibial interface with no significant change in prosthesis alignment over the follow-up period. Assessment of the short-term survivorship of the Vega posterior-stabilized prosthesis using KSRESS revealed no significant change in alignment after 2 years of follow-up; however, mid- to long-term studies assessing this junction are needed. A future prospective study using KSRESS in combination with clinical follow-up is recommended to allow comparison of the Vega posterior-stabilized to other prostheses. [ Orthopedics . 2016; 39(3):S56–S60.]

Aims/hypothesisType 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor prevention efforts to those at the highest risk. The aim of this study was to identify predictive methylation markers for incident type 2 diabetes by combining epigenome-wide association study (EWAS) results from five prospective European cohorts.MethodsWe conducted a meta-analysis of EWASs in blood collected 7–10 years prior to type 2 diabetes diagnosis. DNA methylation was measured with Illumina Infinium Methylation arrays. A total of 1250 cases and 1950 controls from five longitudinal cohorts were included: Doetinchem, ESTHER, KORA1, KORA2 and EPIC-Norfolk. Associations between DNA methylation and incident type 2 diabetes were examined using robust linear regression with adjustment for potential confounders. Inverse-variance fixed-effects meta-analysis of cohort-level individual CpG EWAS estimates was performed using METAL. The methylGSA R package was used for gene set enrichment analysis. Confirmation of genome-wide significant CpG sites was performed in a cohort of Indian Asians (LOLIPOP, UK).ResultsThe meta-analysis identified 76 CpG sites that were differentially methylated in individuals with incident type 2 diabetes compared with control individuals (p values <1.1 × 10−7). Sixty-four out of 76 (84.2%) CpG sites were confirmed by directionally consistent effects and p values <0.05 in an independent cohort of Indian Asians. However, on adjustment for baseline BMI only four CpG sites remained genome-wide significant, and addition of the 76 CpG methylation risk score to a prediction model including established predictors of type 2 diabetes (age, sex, BMI and HbA1c) showed no improvement (AUC 0.757 vs 0.753). Gene set enrichment analysis of the full epigenome-wide results clearly showed enrichment of processes linked to insulin signalling, lipid homeostasis and inflammation.Conclusions/interpretationBy combining results from five European cohorts, and thus significantly increasing study sample size, we identified 76 CpG sites associated with incident type 2 diabetes. Replication of 64 CpGs in an independent cohort of Indian Asians suggests that the association between DNA methylation levels and incident type 2 diabetes is robust and independent of ethnicity. Our data also indicate that BMI partly explains the association between DNA methylation and incident type 2 diabetes. Further studies are required to elucidate the underlying biological mechanisms and to determine potential causal roles of the differentially methylated CpG sites in type 2 diabetes development.

Prostate-cancer biopsy directed at areas of MRI abnormality was compared with standard transrectal ultrasonographic biopsy for diagnostic specificity and sensitivity. MRI-targeted biopsy identified more high-risk cancers and fewer clinically insignificant tumors.

The MDR1 gene encoding the multidrug pump P-glycoprotein is transcriptionally activated in response to diverse extracellular stimuli, including the tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). However, the signal transduction pathway responsible is unknown. Downstream of protein kinase C (PKC), the effects of TPA are often mediated by the Raf-1/MEK/ERK mitogen-activated protein kinase (MAPK) cascade, and Raf-1 has been implicated in MDR1 induction by serum and mitogens. Therefore, we examined the potential role of MAPK activation in TPA-mediated MDR1 induction in human leukemia K562 cells. MDR1 mRNA expression was significantly increased by TPA in the concentration range of 4 - 100 nM, with a maximal response 5 - 10 h after TPA addition. TPA-mediated MDR1 induction was inhibited by several PKC inhibitors including staurosporine, H7 and calphostin C. TPA stimulated the subcellular translocation of PKCalpha from the cytosol to the membrane and nucleus but did not affect other PKC isozymes. TPA also activated the Raf1/MEK/ERK cascade and activated another MAPK member, p38, but not JNK. In order to determine the potential role of MAPKs in MDR1 induction by TPA, specific inhibitors were utilized. The MEK inhibitor PD 098059, as well as the PKC inhibitors, completely blocked TPA-mediated ERK activation. However, under identical conditions, MDR1 induction by TPA was completely unaffected by PD 098059. Furthermore, SB 202190, which effectively inhibited TPA-mediated p38 activation, failed to inhibit TPA-induced MDR1 mRNA expression. These data demonstrate that MDR1 induction by TPA occurs via a PKC-dependent mechanism that operates independently of ERK, p38 or JNK pathways, and thus have important implications for understanding the mechanisms of MDR1 induction by extracellular stimuli.