Increased circulating cytokine levels in African American women with obesity and elevated HbA1c.

PURPOSE: Obesity has emerged as one of the biggest health crisis and is the leading cause of death and disabilities around the world. BMI trends suggest that majority of the increase in T2D is resulting from the increased prevalence of obesity. In fact, 85.2% of people with T2D are overweight or obese. The highest prevalence for obesity is seen in non-Hispanic, African American women (56.6%). T2D is classified as an inflammatory disease because of elevated, circulating pro-inflammatory cytokines and acute-phase inflammatory proteins. This study was designed to determine how high HbA1c and serum glucose correlate with circulatory cytokine levels in obese, African American women. METHODS: We investigated cytokine/chemokine serum levels using a multiplex assay. Then we used Pairwise Pearson Correlation Test to determine the relationship between clinical metabolic parameters and cytokine/chemokine serum levels. RESULTS: The results indicated that participants with elevated HbA1c exhibited an up regulation of IL-3, IL-4, IL-7, TNF-α, IFN-α2 and CX3CL1 serum levels compared to participants with normal HbA1c. These cytokines were also correlated with several clinical metabolic parameters. CONCLUSIONS: The results suggest that IL-3, IL-4, IL-7, TNF-α, IFN-α2 and CX3CL1 serum levels may contribute to the development and onset of type 2 diabetes.

Clinical Outcomes Following Biologically Enhanced Patch Augmentation Repair as a Salvage Procedure for Revision Massive Rotator Cuff Tears.

PURPOSE: To evaluate the clinical outcomes of patients who underwent biologically enhanced patch augmentation repair for the treatment of revision massive rotator cuff tears. METHODS: Twenty-two patients who underwent arthroscopic and mini-open rotator cuff repair using a patch augmented with platelet-rich plasma and concentrated bone marrow aspirate (cBMA) for revision massive (≥2 tendons) rotator cuff tears from 2009 to 2014, with a minimum 1-year follow-up, were included in the study. In this procedure the medial side of the graft is secured to the rotator cuff tendon remaining medially. American Shoulder and Elbow Surgeons (ASES), Simple Shoulder Test, and postoperative Single Assessment Numerical Evaluation scores were evaluated. To determine the clinical relevance of ASES scores, the minimal clinically important difference, substantial clinical benefit (SCB), and the patient-acceptable symptomatic state (PASS) thresholds were used. Clinical success or failure was defined based on whether the patient reached the SCB threshold. In the laboratory, cellular counting along with the concentration of connective tissue progenitor cells were performed on patch samples from the day of surgery. Scaffolds were processed histologically at days 0, 7,14, and 21 of culture. RESULTS: Patients had significant improvement in the Simple Shoulder Test (2.6 ± 3.0pre vs 5.2 ± 4.2post, P = .01), whereas improvement in pain scores was found to be nonsignificant (5.6 ± 2.5pre vs 4.2 ± 3.4post,P = .11) at final follow-up. Mean ASES improved by Δ14.6 ± 33.4 points; however, this did not reach statistical significance (40.2 ± 21.6pre vs 53.9 ± 31.4post,P = .10). With regards to ASES score, 45% of patients achieved the minimal clinically important difference, 41% the SCB, and 32% reached or exceeded the PASS criteria. At 21 days, there was a significantly greater cell count in scaffolds from patients who had clinical success than those who were failures (P = .02). CONCLUSIONS: Only 41% of patients undergoing biologically enhanced patch augmentation repair reached substantial clinical benefit, whereas 32% reached or exceeded the PASS criteria. LEVEL OF EVIDENCE: Case Series: Level IV.

High Clinical Failure Rate After Latissimus Dorsi Transfer for Revision Massive Rotator Cuff Tears.

PURPOSE: To evaluate the clinical success rate, along with risk factors for failure, in patients undergoing latissimus dorsi transfer for the treatment of massive, irreparable, previously failed rotator cuff tears. METHODS: We performed a retrospective chart review of prospectively collected data from an institutional shoulder outcome registry. All patients who underwent latissimus dorsi transfer for previously failed rotator cuff repair between 2006 and 2013 with a minimum follow-up period of 1 year were included in the study. The indications for inclusion were large (≥2 tendons), retracted, chronic rotator cuff tears with fatty infiltration or atrophy for which prior surgical repair had failed. Preoperative and postoperative American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test scores were collected, along with postoperative Single Assessment Numerical Evaluation scores. Complications and clinical failures (Δ in ASES score <17) were recorded. Patient demographic and tear characteristics were evaluated as potential risk factors for failure. RESULTS: A total of 22 patients (mean age, 53 ± 6 years) were included in the study, with a mean follow-up time of 3.4 ± 1.1 years. Over 63% of patients (n = 14) reported undergoing 2 or more prior failed rotator cuff repairs. Patients undergoing latissimus dorsi transfer showed significant improvements in ASES scores (from 35.2 ± 21.9 preoperatively to 55.8 ± 22.9 postoperatively, P = .001), Simple Shoulder Test scores (from 3.5 ± 3.1 preoperatively to 5.2 ± 3.4 postoperatively, P = .002), and pain scores (from 5.9 ± 2.8 preoperatively to 4.6 ± 4.3 postoperatively, P = .002) at final follow-up. The complication rate after latissimus transfer was 27%. The rate of revision to reverse total shoulder arthroplasty was 13.6% (n = 3) after a mean of 2.7 years, and the clinical failure rate was 41% (n = 9) at final follow-up. An acromiohumeral interval of less than 7 mm (P = .04) and high-grade fatty infiltration (grade 3 or greater, P = .004) were significant preoperative risk factors for clinical failure. CONCLUSIONS: Latissimus dorsi tendon transfer resulted in a clinical failure rate of 41% and complication rate of 27%, with an acromiohumeral interval of less than 7 mm and high-grade fatty infiltration being associated with postoperative failure. LEVEL OF EVIDENCE: Level IV.

Does quality of life influence retear rate following arthroscopic rotator cuff repair?

BACKGROUND: The primary objective was to assess whether a patient's early postoperative quality of life (QOL) correlates with the retear rate following single-tendon double-row rotator cuff repair. METHODS: We performed a secondary analysis of a randomized clinical trial of 58 patients who underwent single-tendon arthroscopic rotator cuff repair of full-thickness tears performed by a single surgeon. Patients were randomized to an early- or delayed-motion protocol. At 6 months, all patients underwent magnetic resonance imaging to assess whether the rotator cuffs were intact or retorn. QOL was assessed preoperatively and at 3 weeks, 6 weeks, 12 weeks, 6 months, and 12 months postoperatively using the Western Ontario Rotator Cuff (WORC) index. RESULTS: After 6 months of rehabilitation, 41 patients (71%) had intact rotator cuff repairs whereas 17 (29%) had full-thickness tears. Patients with torn rotator cuffs at 6 months postoperatively had significantly lower WORC scores at 6 weeks postoperatively (P = .041). Patients with greater improvements in QOL perioperatively (preoperative WORC score minus 6-week postoperative WORC score > 264.5) were more likely to have full-thickness tears by 6 months postoperatively. Compliant patients assigned to the delayed-motion protocol had a failure rate of 11% (2 of 19) compared with 38% (15 of 39) in the noncompliant and early-motion protocol patients (P < .01). Overall, patients who were noncompliant with the shoulder immobilizer were 8.2 times more likely to have a failed repair on magnetic resonance imaging (P = .01). CONCLUSIONS: Patients with better QOL shortly after arthroscopic rotator cuff repair were more likely to have retears by 6 months.

The Scleroderma Hand: Manifestations of Disease and Approach to Management.

Scleroderma is a rare autoimmune connective tissue disorder that often affects the hands. Manifestations in the hands include calcium deposits within the soft tissues that cause pain and may ulcerate through the skin, digital ischemia resulting in chronic wounds and digital gangrene, and joint contracture. Because of the underlying disease, patients with scleroderma have poorly vascularized tissue and a deficient soft tissue envelope, which make surgery particularly challenging. However, when undertaken with care, surgical intervention is often the best option for addressing the disabling hand conditions that so often accompany this disease.

The Relationship Between Tibial Tuberosity-Trochlear Groove Distance and Abnormal Patellar Tracking in Patients With Unilateral Patellar Instability.

PURPOSE: To evaluate the role of tibial tuberosity-trochlear groove (TT-TG) distance in patellofemoral kinematics by retrospectively reviewing the dynamic computed tomography scans of patients with unilateral patellofemoral instability and comparing unstable and contralateral asymptomatic knees. METHODS: We reviewed all dynamic computed tomography scans obtained at one tertiary care hospital from 2008 through 2013 and identified 25 patients with a history of recurrent unilateral patellofemoral instability. During the scans, subjects performed active knee extension against gravity. Both knees were imaged simultaneously. Lateral patellar tilt (LPT) and bisect offset (BO) were measured to assess tracking. TT-TG distance was measured to assess alignment. Measurements were made in full extension, maximum flexion, and approximately 10° increments in between. The significance level was set at P < .05. RESULTS: LPT, BO, and TT-TG distance were highest in extension and decreased with flexion. Measurements were higher in symptomatic than in asymptomatic knees, with significant differences identified for LPT, BO, and TT-TG distance at 5° and 15° and for TT-TG distance at 25° and 35° (P < .05). TT-TG distance was associated with LPT and BO, with r(2) values in symptomatic knees of 0.55 for TT-TG distance and LPT and of 0.45 for TT-TG distance and BO. CONCLUSIONS: In patients with unilateral patellar instability, LPT, BO, and TT-TG distance are higher on the unstable side. An association exists between TT-TG distance and the tracking parameters studied, suggesting that TT-TG distance relates to patellar tracking, and a laterally positioned tibial tuberosity may predispose to instability episodes. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Characterization of patellar maltracking using dynamic kinematic CT imaging in patients with patellar instability.

PURPOSE: Little has been reported on the relationship between patellar maltracking and instability. Patellar maltracking has been subjectively described with the "J sign" but is difficult to assess objectively using traditional imaging. Dynamic kinematic computed tomography (DKCT) allows dynamic assessment of the patellofemoral joint. DKCT was used to visualize and quantify patellar maltracking patterns, and severity of maltracking was correlated with the presence or absence of patellar instability symptoms. METHODS: Seventy-six knees in 38 patients were analysed using DKCT. Maltracking was defined as deviation of the patella from the trajectory of the trochlear groove and was characterized by patellar bisect offset, which was measured at 10° intervals of knee flexion during active flexion and extension. Bisect offset measurements were grouped by number of quadrants of maximum lateral patellar motion, with one, two, and three quadrants corresponding to 75-99, 100-125, and >125 %, respectively. Patellar instability symptoms were correlated with maltracking severity. RESULTS: Two knees were excluded because of poor imaging quality. Fifty of 74 knees had patellar instability, and 13 patients had bilateral symptoms. Of these, four (8 %) had normal tracking patterns; 41 (82 %) had increased lateral translation in extension, which we termed the J-sign pattern; 4 (8 %) had persistent lateralization of the patella throughout range of motion; and 1 had increased lateral translation in flexion. In knees with the J-sign pattern, degree of maltracking was graded by severity: J1 (n = 24), J2 (n = 19), and J3 (n = 15). The sensitivities of J-sign grades in predicting patellar instability symptoms were 50 % (J1), 80 % (J2), and 93 % (J3) (p < 0.01). There were significant differences in sensitivity between knees with no J sign or J1 versus J2 or J3 (p = 0.02). CONCLUSION: DKCT showed several patellar maltracking patterns in patients with patellar instability. A J-sign pattern with more than two quadrants of lateral translation correlated with the presence of patellar instability symptoms. Incorporation of this approach of objectively quantifying maltracking patterns is recommended in the evaluation of patellofemoral instability. LEVEL OF EVIDENCE: IV.

Correlation Between Changes in Tibial Tuberosity-Trochlear Groove Distance and Patellar Position During Active Knee Extension on Dynamic Kinematic Computed Tomographic Imaging.

PURPOSE: The purpose of this study was to evaluate changes in tibial tuberosity-trochlear groove (TTTG) distance with knee flexion in patients with patellar instability and correlate it with patellar position. METHODS: Patients with symptomatic patellar instability underwent dynamic kinematic computed tomography (CT) during a cycle of knee extension from flexion. Knee flexion angles and corresponding TTTG distances, bisect offset, and patellar tilt were measured. Of the 51 knees, 37 had data available for interpolation between 5° and 30°. Results were interpolated to standardized intervals between 5° and 30° of knee flexion. Repeated-measures analysis (to identify differences between TTTG measurements at various knee flexion angles) and linear regression models (to assess for correlations between TTTG distance and bisect offset and between TTTG distance and patellar tilt) were used. RESULTS: Fifty-one symptomatic knees in 38 patients were available for analysis. Bisect offset and patellar tilt correlated significantly (P < .001) with TTTG distance over all flexion angles. Interpolated results for comparison resulted in 37 knees in which the mean TTTG distance of 17.2 ± 5.8 mm at 5° decreased to 15.5 ± 5.7, 13.0 ± 5.5, and 11.5 ± 4.9 mm at 10°, 20°, and 30° of knee flexion, respectively. Mean TTTG at 5° was 1.5 times greater than that at 30° (P < .001). At 5°, 70.3% (26 of 37) of knees had a TTTG distance of more than 15 mm; at 30°, only 24.3% (9 of 37) exceeded this threshold. CONCLUSIONS: Knee flexion angle during imaging is a critical factor when measuring TTTG distance to evaluate patellofemoral instability. We found that the mean TTTG distance varied by 5.7 mm between 5° and 30° of flexion in patients with symptomatic instability, although this relationship was not completely linear. Bisect offset and patellar tilt measurements mirrored this pattern, suggesting that TTTG distance influences patellar tracking in these patients. LEVEL OF EVIDENCE: Level IV, prognostic case series.

Imaging characteristics of contralateral asymptomatic patellofemoral joints in patients with unilateral instability.

PURPOSE: To test the hypothesis that in patients with unilateral patellofemoral instability ( PI patellofemoral instability ), the contralateral asymptomatic joints have abnormal morphology and imaging features of osteoarthritis ( OA osteoarthritis ) at four-dimensional ( 4D four-dimensional ) computed tomography (CT). MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant retrospective study. Informed consent was waived. Radiology records were reviewed to identify 25 patients (male-female ratio, 0.56; median age, 20 years; range, 13-43 years) with unilateral PI patellofemoral instability undergoing 4D four-dimensional CT and 25 age- and sex-matched control patients undergoing multidetector CT. Trochlear groove depth ( TGD trochlear groove depth ), tibial tuberosity-trochlear groove ( TT-TG tibial tuberosity-trochlear groove ) distance, and patellar height ratio ( PHR patellar height ratio ) were determined to compare morphology, and bisect offset ( BO bisect offset ) measurements were obtained to compare lateral displacement of the patella between the two groups by using the Wilcoxon rank-sum test. All images were interpreted by trained observers. Tracking patterns of the patellae were determined by obtaining BO bisect offset measurements at various flexion angles with 4D four-dimensional CT. RESULTS: In the contralateral asymptomatic joints, TGD trochlear groove depth (median, 3.0 mm; 95% confidence interval [ CI confidence interval ]: 2.5, 4.6; P < .0001), TT-TG tibial tuberosity-trochlear groove (median, 15 mm; 95% CI confidence interval : 12.7, 18; P = .008), PHR patellar height ratio (median, 1.17; 95% CI confidence interval : 1.09, 1.2; P = .002), and patellar lateral displacement ( BO bisect offset , 85%; 95% CI confidence interval : 76.2%, 98.2%; P < .0001) were different from measurements obtained in the control group: TGD trochlear groove depth median, 5.0 mm (95% CI confidence interval : 2.2, 7.6); TT-TG tibial tuberosity-trochlear groove median, 10.9 mm (95% CI confidence interval : 3.4, 20.7); PHR patellar height ratio median, 0.92 (95% CI confidence interval : 0.67, 1.36); and BO bisect offset median, 63% (95% CI confidence interval : 59%, 68.4%). OA osteoarthritis was detected in 40% of asymmetrical contralateral joints (10 of 25). By using 4D four-dimensional CT data, multiple regression analysis demonstrated that TGD trochlear groove depth (P = .026) and BO bisect offset measurements obtained at 30° of knee flexion (P = .047) had an association with the presence of OA osteoarthritis . CONCLUSION: Abnormal morphology and imaging features of OA osteoarthritis are relatively common in contralateral asymptomatic joints of young patients with unilateral PI patellofemoral instability .

Racial and Ethnic Disparities in Antihypertensive Medication Prescribing Patterns and Effectiveness.

Variability in drug effectiveness and provider prescribing patterns have been reported in different racial and ethnic populations. We sought to evaluate antihypertensive drug effectiveness and prescribing patterns among self-identified Hispanic/Latino (Hispanic), Non-Hispanic Black (Black), and Non-Hispanic White (White) populations that enrolled in the NIH All of Us Research Program, a US longitudinal cohort. We employed a self-controlled case study method using electronic health record and survey data from 17,718 White, Hispanic, and Black participants who were diagnosed with essential hypertension and prescribed at least one of 19 commonly used antihypertensive medications. Effectiveness was determined by calculating the reduction in systolic blood pressure measurements after 28 or more days of drug exposure. Starting systolic blood pressure and effectiveness for each medication were compared for self-reported Black, Hispanic, and White participants using adjusted linear regressions. Black and Hispanic participants were started on antihypertensive medications at significantly higher SBP than White participants in 13 and 7 out of 19 medications, respectively. More Black participants were prescribed multiple antihypertensive medications (58.46%) than White (52.35%) or Hispanic (49.9%) participants. First-line HTN medications differed by race and ethnicity. Following the 2017 American College of Cardiology and the American Heart Association High Blood Pressure Guideline release, around 64% of Black participants were prescribed a recommended first-line antihypertensive drug compared with 76% of White and 82% of Hispanic participants. Effect sizes suggested that most antihypertensive drugs were less effective in Hispanic and Black, compared with White, participants, and statistical significance was reached in 6 out of 19 drugs. These results indicate that Black and Hispanic populations may benefit from earlier intervention and screening and highlight the potential benefits of personalizing first-line medications.

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits.

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

Trapezium trabecular morphology in carpometacarpal arthritis.

PURPOSE: In thumb carpometacarpal osteoarthritis, current evidence suggests that degenerative, bony remodeling primarily occurs within the trapezium. Nevertheless, the pathomechanics involved and the most common sites of wear remain controversial. Quantifying structural bone morphology characteristics with high-resolution computed tomography CT (micro-CT) infer regions of load transmission. Using micro-CT, we investigated whether predominant trabecular patterns exist in arthritic versus normal trapeziums. METHODS: We performed micro-CT analysis on 13 normal cadaveric trapeziums and 16 Eaton stage III to IV trapeziums. We computationally divided each specimen into 4 quadrants: volar-ulnar, volar-radial, dorsal-radial, and dorsal-ulnar. Measurements of trabecular bone morphologic parameters included bone volume ratio, connectivity, trabecular number, and trabecular thickness. Using analysis of variance with post hoc Bonferroni/Dunn correction, we compared osteoarthritic and normal specimen quadrant measurements. RESULTS: No significant difference existed in bone volume fraction between the osteoarthritic and normal specimens. Osteoarthritic trapeziums, however, demonstrated significantly higher trabecular number and connectivity than nonosteoarthritic trapeziums. Comparing the volar-ulnar quadrant of osteoarthritis and normal specimens collectively, this quadrant in both consistently possessed significantly higher bone volume fraction, trabecular number, and connectivity than the dorsal-radial and volar-radial quadrants. CONCLUSIONS: The significantly greater trabecular bone volume, thickness, and connectivity in the volar-ulnar quadrant compared with the dorsal-radial and dorsal-ulnar quadrants provides evidence that the greatest compressive loads at the first carpometacarpal joint occur at the volar-ulnar quadrant of the trapezium, representing a consistently affected region of wear in both normal and arthritic states. CLINICAL RELEVANCE: These findings suggest that trapezial trabecular morphology undergoes pathologic alteration. This provides indirect evidence that changes in load transmission occur with thumb carpometacarpal joint arthritis development.

Community Health Center 340B Program: A Qualitative Study of the Experiences of Patients with Diabetes.

Background: The 340B Drug Pricing Program provides discounted drug prices to safety-net entities which help stretch scarce resources to expand comprehensive services and treat more vulnerable patients. The program has received criticism questioning whether the original intentions are being accomplished. Objective: This qualitative study aimed to understand lived experiences of patients accessing high-cost injectable diabetes medication(s) through a 340B Prescription Cash Discount Program (PCDP) provided at a community health center. Methods: This qualitative study utilized semi-structured individual interviews. We invited patients ≥18 years old with diabetes for >1 year who utilized the 340B PCDP to fill an injectable diabetes medication at least twice between 3/1/2020-3/1/2021 to participate. Trained personnel interviewed ten participants in 11/2021-2/2022 and completed thematic analysis of the transcribed interviews. Results: Themes included 340B feedback, benefits of 340B, consequences of being without 340B, community pharmacy experience, and use of other services. Participants deemed the 340B program as a "lifesaver." Perceived benefits of the program included improved diabetes control and savings that made their prescriptions more affordable. Consequences of being without the program include that medication was too expensive to take as prescribed and rationing/skipping doses. Participants were pleased with the accessibility of the network of contract pharmacies and described benefiting from services supported by 340B savings. Conclusions: Recent criticisms question whether the 340B program accomplishes its original intentions of stretching scarce federal resources to help safety-net entities expand services and treat more patients. This study provides insight into the personal impact of the 340B program on underserved patients with chronic disease accessing high-cost medication(s). Findings highlight crucial strengths of the program from the patient perspective, which policymakers and other stakeholders should consider to provide support for the continuation of these services.

Systematic replication of smoking disease associations using survey responses and EHR data in the All of Us Research Program.

OBJECTIVE: The All of Us Research Program (All of Us) aims to recruit over a million participants to further precision medicine. Essential to the verification of biobanks is a replication of known associations to establish validity. Here, we evaluated how well All of Us data replicated known cigarette smoking associations. MATERIALS AND METHODS: We defined smoking exposure as follows: (1) an EHR Smoking exposure that used International Classification of Disease codes; (2) participant provided information (PPI) Ever Smoking; and, (3) PPI Current Smoking, both from the lifestyle survey. We performed a phenome-wide association study (PheWAS) for each smoking exposure measurement type. For each, we compared the effect sizes derived from the PheWAS to published meta-analyses that studied cigarette smoking from PubMed. We defined two levels of replication of meta-analyses: (1) nominally replicated: which required agreement of direction of effect size, and (2) fully replicated: which required overlap of confidence intervals. RESULTS: PheWASes with EHR Smoking, PPI Ever Smoking, and PPI Current Smoking revealed 736, 492, and 639 phenome-wide significant associations, respectively. We identified 165 meta-analyses representing 99 distinct phenotypes that could be matched to EHR phenotypes. At P < .05, 74 were nominally replicated and 55 were fully replicated. At P < 2.68 × 10-5 (Bonferroni threshold), 58 were nominally replicated and 40 were fully replicated. DISCUSSION: Most phenotypes found in published meta-analyses associated with smoking were nominally replicated in All of Us. Both survey and EHR definitions for smoking produced similar results. CONCLUSION: This study demonstrated the feasibility of studying common exposures using All of Us data.

Creating a Metabolic Syndrome Research Resource using the National Health and Nutrition Examination Survey.

Metabolic syndrome (MetS) is multifaceted. Risk factors include visceral adiposity, dyslipidemia, hyperglycemia, hypertension and environmental stimuli. MetS leads to an increased risk of cardiovascular disease, type 2 diabetes and stroke. Comparative studies, however, have identified heterogeneity in the pathology of MetS across groups though the etiology of these differences has yet to be elucidated. The Metabolic Syndrome Research Resource (MetSRR) described in this report is a curated database that provides access to MetS-associated biological and ancillary data and pools current and potential biomarkers of MetS extracted from relevant National Health and Nutrition Examination Survey (NHANES) data from 1999-2016. Each potential biomarker was selected following the review of over 100 peer-reviewed articles. MetSRR includes 28 demographics, survey and known MetS-related variables, including 9 curated categorical variables and 42 potentially novel biomarkers. All measures are captured from over 90 000 individuals. This biocuration effort provides increased access to curated MetS-related data and will serve as a hypothesis-generating tool to aid in novel biomarker discovery. In addition, MetSRR provides the ability to generate and export ethnic group-/race-, sex- and age-specific curated datasets, thus broadening participation in research efforts to identify clinically evaluative MetS biomarkers for disparate populations. Although there are other databases, such as BioM2MetDisease, designed to explore metabolic diseases through analysis of miRNAs and disease phenotypes, MetSRR is the only MetS-specific database designed to explore etiology of MetS across groups, through the biocuration of demographic, biological samples and biometric data. Database URL:  http://www.healthdisparityinformatics.com/MetSRR.

CD 9 and vimentin distinguish clear cell from chromophobe renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) and chromophobe renal cell carcinoma (chRCC) can usually be distinguished by histologic characteristics. Occasionally, diagnosis proves challenging and diagnostic difficulty will likely increase as needle biopsies of renal lesions become more common. METHODS: To identify markers that aid in differentiating ccRCC from chRCC, we used gene expression profiles to identify candidate markers that correlate with histology. 39 antisera and antibodies, including 35 for transcripts identified from gene expression profiling, were evaluated. Promising markers were tested on a tissue microarray (TMA) containing 428 renal neoplasms. Strength of staining of each core on the TMA was formally scored and the distribution of staining across different types of renal neoplasms was analyzed. RESULTS: Based on results from initial immunohistochemical staining of multitissue titer arrays, 23 of the antisera and antibodies were selected for staining of the TMA. For 7 of these markers, strength of staining of each core on the TMA was formally scored. Vimentin (positive in ccRCC) and CD9 (positive in chRCC) best distinguished ccRCC from chRCC. The combination of vimentin negativity and CD9 positivity was found to distinguish chRCC from ccRCC with a sensitivity of 100.0% and a specificity of 95.2%. CONCLUSION: Based on gene expression analysis, we identify CD9 and vimentin as candidate markers for distinguishing between ccRCC and chRCC. In difficult cases and particularly when the amount of diagnostic tissue is limited, vimentin and CD9 staining could serve as a useful adjunct in the differential diagnosis of ccRCC and chRCC.

Serum miR-17 levels are downregulated in obese, African American women with elevated HbA1c.

PURPOSE: Type 2 diabetes is heterogeneous disease characterized by several conditions including hyperglycemia. It is estimated that over 350 million people worldwide are suffering from type 2 diabetes and this number is expected to rise. According to the CDC, African Americans were observed to have a 40% higher incidence of diabetes compared to European Americans. Epigenetic modulating mechanisms such as microRNAs (miRNAs), have recently been established as a massive regulatory machine in metabolic syndrome, obesity and type 2 diabetes. In the present study, we aimed to investigate the serum levels of circulating miRNA 17 (miR-17) of obese, African American women with elevated HbA1c. METHODS: We investigated miR-17 serum levels using qPCR. Then we used Pairwise Pearson Correlation Test to determine the relationship between clinical metabolic parameters and miR-17 serum levels. RESULTS: The results indicated that participants with elevated HbA1c exhibited a down regulation of serum miR-17 levels compared to participants with normal HbA1c. MiR-17 was also correlated with serum calcium in participants with normal HbA1c. CONCLUSIONS: The results suggest that serum miR-17 is involved in the regulation of glucose and calcium homeostasis, which may contribute to the development of type 2 diabetes.

Recurrent Shoulder Instability: Do Morbidity and Treatment Differ Based on Insurance?

BACKGROUND: Patients with public insurance often face barriers to obtaining prompt orthopaedic care. For patients with recurrent traumatic anterior shoulder instability, delayed care may be associated with increasing bone loss and subsequently more extensive surgical procedures. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate whether differences exist in patients undergoing treatment for shoulder instability between those with Medicaid versus non-Medicaid insurance. We hypothesized that at the time of surgery, Medicaid patients would have experienced greater delays in care, would have a more extensive history of instability, would have more bone loss, and would require more extensive surgical procedures than other patients. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients were identified who underwent surgical stabilization for traumatic anterior shoulder instability between January 1, 2011, and December 1, 2015, at a single sports medicine practice. Clinic, billing, and operative records were reviewed for each patient to determine age, sex, insurance type, total number of instability episodes, time from first instability episode to surgery, intraoperative findings, and procedure performed. Glenoid bone loss was quantified by use of preoperative imaging studies. RESULTS: During this time period, 206 patients (55 Medicaid, 131 private insurance, 11 Tricare, 9 workers' compensation) underwent surgical stabilization for traumatic anterior shoulder instability. Average wait time from initial injury to surgery was 1640 days (95% CI, 1155-2125 days) for Medicaid patients compared with 1237 days (95% CI, 834-1639 days) for others (P = .005). Medicaid patients were more likely to have sustained 5 or more instability events at the time of surgery (OR, 3.3; 95% CI, 1.64-6.69; P = .001), had a higher risk of having 15% or more glenoid bone loss on preoperative imaging (OR, 3.5; 95% CI, 1.3-10.0; P = .01), and had a higher risk of requiring Latarjet or other open stabilization procedures as opposed to an arthroscopic repair (OR, 3.0; 95% CI, 1.5-6.2; P = .002) when compared with other patients. CONCLUSION: Among patients undergoing surgery for traumatic anterior shoulder instability, patients with Medicaid had significantly more delayed care. Correspondingly, they reported a more extensive history of instability, were more likely to have severe bone loss, and required more invasive stabilization procedures.

Postoperative Pain After Surgical Treatment of Ankle Fractures: A Prospective Study.

BACKGROUND: Postoperative pain after fixation of ankle fractures has a substantial effect on surgical outcome and patient satisfaction. Patients requiring large amounts of narcotics are at higher risk of long-term use of pain medications. Few prospective studies investigate patient pain experience in the management of ankle fractures. METHODS: We prospectively evaluated the pain experience in 63 patients undergoing open reduction and internal fixation of ankle. The Short-Form McGill Pain Questionnaire was administered preoperatively and postoperatively (PP) at 3 days (3dPP) and 6 weeks (6wPP). Anticipated postoperative pain (APP) was recorded. RESULTS: No significant differences were found between PP, APP, and 3dPP; however, 6wPP was markedly lower. Significant correlations were found between PP and APP and between preoperative and postoperative Short-Form McGill Pain Questionnaire scores. PP and APP were independent predictors of 3dPP; however, only APP was predictive of 6wPP. Sex, age, and inpatient versus outpatient status were not notable factors. No statistically significant differences were found in pain scores between fracture types. CONCLUSIONS: Both preoperative pain severity and anticipated postoperative pain are predictive of postoperative pain levels. Orthopaedic surgeons should place a greater focus on the postoperative management of patient pain and expectations after surgical procedures.