Citations

AbstractOsteoblast differentiation is controlled by transcription factor RUNX2 which temporally activates or represses several bone‐related genes, including those encoding extracellular matrix proteins or factors that control cell‐cell, and cell‐matrix interactions. Cell‐cell communication in the many skeletal pericellular micro‐niches is critical for bone development and involves paracrine secretion of growth factors and morphogens. This paracrine signaling is in part regulated by “A Disintegrin And Metalloproteinase” (ADAM) proteins. These cell membrane‐associated metalloproteinases support proteolytic release (“shedding”) of protein ectodomains residing at the cell surface. We analyzed microarray and RNA‐sequencing data for Adam genes and show that Adam17, Adam10, and Adam9 are stimulated during BMP2 mediated induction of osteogenic differentiation and are robustly expressed in human osteoblastic cells. ADAM17, which was initially identified as a tumor necrosis factor alpha (TNFα) converting enzyme also called (TACE), regulates TNFα‐signaling pathway, which inhibits osteoblast differentiation. We demonstrate that Adam17 expression is suppressed by RUNX2 during osteoblast differentiation through the proximal Adam17 promoter region (−0.4 kb) containing two functional RUNX2 binding motifs. Adam17 downregulation during osteoblast differentiation is paralleled by increased RUNX2 expression, cytoplasmic‐nuclear translocation and enhanced binding to the Adam17 proximal promoter. Forced expression of Adam17 reduces Runx2 and Alpl expression, indicating that Adam17 may negatively modulate osteoblast differentiation. These findings suggest a novel regulatory mechanism involving a reciprocal Runx2‐Adam17 negative feedback loop to regulate progression through osteoblast differentiation. Our results suggest that RUNX2 may control paracrine signaling through regulation of ectodomain shedding at the cell surface of osteoblasts by directly suppressing Adam17 expression.

Background: There are limited data comparing the outcomes of all-inside versus inside-out meniscal repair techniques. Purpose: To assess failure rates and clinical outcomes after the surgical repair of bucket-handle meniscal tears utilizing either an all-inside or inside-out technique. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with bucket-handle meniscal tears undergoing all-inside or inside-out repair at a single institution between 2003 and 2013 were analyzed. A total of 28 mensici repaired utilizing second-generation all-inside suturing devices and 42 menisci repaired using an inside-out technique were eligible for inclusion. Rigorous propensity matching was performed on the basis of age, sex, tear laterality, rim width, and concomitant anterior cruciate ligament reconstruction (ACLR), resulting in a total of 40 patients equally distributed between the 2 repair techniques for comparison. Retear-free survival as well as preoperative and postoperative International Knee Documentation Committee (IKDC) and Tegner scores and physical examination findings were subsequently analyzed. Results: Twenty patients who underwent all-inside repair (14 male; mean age, 23.7 ± 6.7 years) were successfully propensity matched to 20 patients who underwent inside-out meniscal repair (15 male; mean age, 22.5 ± 7.6 years), with a mean retear-free follow-up of 4.4 years (range, 2.5-7.4 years). Four (20%) all-inside repairs and 4 (20%) inside-out repairs failed over the course of follow-up ( P > .999), with a mean time to failure of 2.7 years (range, 1.3-4.4 years) and 5.0 years (range, 0.8-7.5 years), respectively ( P = .25). Increasing patient age trended toward a decreased clinical retear rate, independent of the repair technique (hazard ratio, 0.86; P = .056). There were no significant differences in the Tegner scores, IKDC scores, or range of motion between the groups as a whole or when subcategorizing by age, sex, body mass index, tear complexity, rim width, isolated versus concomitant ACLR, or medial- versus lateral-sided repair. There were no complications in the all-inside group, while there was a 10% rate of minor complications in the inside-out group ( P = .49). Conclusion: Overall, satisfactory clinical outcomes are achievable at short-term to midterm follow-up with both inside-out and all-inside repair techniques of bucket-handle meniscal tears in rigorously matched patients with similar meniscal tear patterns.

Background Ideal cardiovascular health metrics (defined by the American Heart Association Life's Simple 7 [LS7]) are suboptimal among blacks, which results in high risk of cardiovascular disease. We examined the association of multiple stressors with LS7 components among blacks. Methods and Results Using a community‐based cohort of blacks (N=4383), we examined associations of chronic stress, minor stressors, major life events, and a cumulative stress score with LS7 components (smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting plasma glucose) and an LS7 composite score. Multivariable logistic regression assessed the odds of achieving intermediate/ideal levels of cardiovascular health adjusted for demographic, socioeconomic, behavioral, and biomedical factors. The LS7 components with the lowest percentages of intermediate/ideal cardiovascular health levels were diet (39%), body mass index (47%), and physical activity (51%). Higher chronic, minor, and cumulative stress scores were associated with decreased odds (odds ratio [OR]) of achieving intermediate/ideal levels for smoking (OR [95% confidence interval], 0.80 [0.73–0.88], 0.84 [0.75–0.94], and 0.81 [0.74–0.90], respectively). Participants with more major life events had decreased odds of achieving intermediate/ideal levels for smoking (OR, 0.84; 95% confidence interval, 0.76–0.92) and fasting plasma glucose (OR, 0.90; 95% confidence interval, 0.82–0.98). Those with higher scores for minor stressors and major life events were less likely to achieve intermediate or ideal LS7 composite scores (OR [95% confidence interval], 0.89 [0.81–0.97] and 0.91 [0.84–0.98], respectively). Conclusions Blacks with higher levels of multiple stress measures are less likely to achieve intermediate or ideal levels of overall cardiovascular health (LS7 composite score), specific behaviors (smoking), and biological factors (fasting plasma glucose).

OBJECTIVE The overall risk of ischemic stroke from a chronically occluded internal carotid artery (COICA) is around 5%–7% per year despite receiving the best available medical therapy. Here, authors propose a radiographic classification of COICA that can be used as a guide to determine the technical success and safety of endovascular recanalization for symptomatic COICA and to assess the changes in systemic blood pressure following successful revascularization. METHODS The radiographic images of 100 consecutive subjects with COICA were analyzed. A new classification of COICA was proposed based on the morphology, location of occlusion, and presence or absence of reconstitution of the distal ICA. The classification was used to predict successful revascularization in 32 symptomatic COICAs in 31 patients, five of whom were female (5/31 [16.13%]). Patients were included in the study if they had a COICA with ischemic symptoms refractory to medical therapy. Carotid artery occlusion was defined as 100% cross-sectional occlusion of the vessel lumen as documented on CTA or MRA and confirmed by digital subtraction angiography. RESULTS Four types (A–D) of radiographic COICA were identified. Types A and B were more amenable to safe revascularization than types C and D. Recanalization was successful at a rate of 68.75% (22/32 COICAs; type A: 8/8; type B: 8/8; type C: 4/8; type D: 2/8). The perioperative complication rate was 18.75% (6/32; type A: 0/8 [0%]; type B: 1/8 [12.50%]; type C: 3/8 [37.50%], type D: 2/8 [25.00%]). None of these complications led to permanent morbidity or death. Twenty (64.52%) of 31 subjects had improvement in their symptoms at the 2–6 months’ follow-up. A statistically significant decrease in systolic blood pressure (SBP) was noted in 17/21 (80.95%) patients who had successful revascularization, which persisted on follow-up (p = 0.0001). The remaining 10 subjects in whom revascularization failed had no significant changes in SBP (p = 0.73). CONCLUSIONS The pilot study suggested that our proposed classification of COICA may be useful as an adjunctive guide to determine the technical feasibility and safety of revascularization for symptomatic COICA using endovascular techniques. Additionally, successful revascularization may lead to a significant decrease in SBP postprocedure. A Phase 2b trial in larger cohorts to assess the efficacy of endovascular revascularization using our COICA classification is warranted.

Background: As the number of cartilage restoration procedures is increasing, so is the number of revision procedures. However, there remains limited information on the reasons for failure of primary cartilage restoration procedures. Purpose: To determine the common modes of failure in primary cartilage restoration procedures to improve surgical decision making and patient outcomes. Study Design: Case series; Level of evidence, 4. Methods: Patients who presented for revision after failed cartilage repair surgery were evaluated for factors contributing to failure of the primary procedure. All revision cases performed by a single surgeon at a tertiary center for failed cartilage restoration over a 6-year time frame were identified. In all cases, the medical records, preoperative radiographs, and magnetic resonance imaging scans were reviewed by 2 experienced cartilage surgeons. The cause for failure was categorized as malalignment, meniscal deficiency, graft or biologic failure, or instability. Univariate and descriptive statistics regarding patient demographics, index procedure, lesion location and size, and mechanism of failure were analyzed. Results: A total of 59 cases in 53 patients (32 male, 21 female) met the inclusion criteria. The mean patient age at the time of revision was 27.6 years, and the mean body mass index was 28.4 kg/m 2 . Failed index surgical procedures included 35 microfractures (59%), 12 osteochondral allograft transplantations (20%), 10 osteochondral autograft transfers (17%), 2 nonviable osteochondral allografts (3%), and 2 particulated juvenile chondral allografts (3%). The mean lesion size was 4.4 cm 2 . Reasons for failure included 33 cases with untreated malalignment (56%), 16 with graft failure (27%), 11 with untreated meniscal deficiency (19%), and 3 with untreated instability (5%); 4 cases demonstrated multiple reasons for failure. Conclusion: The most commonly recognized reason for failure was untreated malalignment. While biologic and graft failures will occur, the majority of failures were attributed to untreated background factors such as malalignment, meniscal deficiency, and instability. The stepwise approach of considering and addressing alignment, meniscal volume, and stability remains essential in cartilage restoration surgery.

Abstract This Consensus Document is the first of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the clinical use of intracoronary imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The first document appraises the role of intracoronary imaging to guide percutaneous coronary interventions (PCIs) in clinical practice. Current evidence regarding the impact of intracoronary imaging guidance on cardiovascular outcomes is summarized, and patients or lesions most likely to derive clinical benefit from an imaging-guided intervention are identified. The relevance of the use of IVUS or OCT prior to PCI for optimizing stent sizing (stent length and diameter) and planning the procedural strategy is discussed. Regarding post-implantation imaging, the consensus group recommends key parameters that characterize an optimal PCI result and provides cut-offs to guide corrective measures and optimize the stenting result. Moreover, routine performance of intracoronary imaging in patients with stent failure (restenosis or stent thrombosis) is recommended. Finally, strengths and limitations of IVUS and OCT for guiding PCI and assessing stent failures and areas that warrant further research are critically discussed.

Background: Studies assessing dysplasia’s effect on hip arthroscopy are often limited to the short term and unable to account for demographic factors that may vary between dysplastic and nondysplastic populations. Purpose: To determine the midterm failure rate and patient-reported outcomes of arthroscopic labral repair in the setting of dysplasia and make subsequent failure and outcome comparisons with a rigorously matched nondysplastic control group. Study Design: Cohort study; Level of evidence, 3. Methods: Primary arthroscopic labral repair cases at 2 centers from 2008 to 2011 were reviewed. Patients with lateral center edge angle (LCEA) <25° were matched to nondysplastic controls by age, sex, laterality, body mass index (BMI), Tönnis grade, and capsular repair per a 1:2 matching algorithm. Groups were compared with a visual analog scale (VAS) for pain, modified Harris Hip Score (mHHS), and Hip Outcome Score–Sports Specific Subscale (HOS-SSS) to determine predictors of outcome and failure. Results: Forty-eight patients with dysplasia (mean LCEA, 21.6°; range, 13.0°-24.9°; n = 25 with capsular repair) were matched to 96 controls (mean LCEA, 32.1°; range, 25°-52°; n = 50 with capsular repair) and followed for a mean of 5.7 years (range, 5.0-7.7 years). Patients achieved mean VAS improvements of 3.3 points, mHHS of 19.5, and HOS-SSS of 29.0 points ( P < .01) with no significant differences between the dysplasia and control populations ( P > .05). Five-year failure-free survival was 83.3% for patients with dysplasia and 78.1% for controls ( P = .53). No survival or outcomes difference was observed between patients with dysplasia who did or did not have capsular repair ( P ≥ .45) or when comparing LCEA <20° and LCEA 20° to 25° ( P ≥ .60). BMI ≤30 was associated with increased revision surgery risk ( P < .01). Age >35 years ( P < .05) and Tönnis grade 0 radiographs ( P < .01) predicted failure to reach minimal clinically important differences. Conclusion: With careful selection and modern techniques, patients with dysplasia can benefit significantly and durably from arthroscopic labral repair. The dysplastic cohort had outcomes and failure rates similar to those of rigorously matched controls at midterm follow-up. Subanalyses comparing LCEA <20° and LCEA 20° to 25° are presented for completeness; however, this study was not designed to detect differences in dysplastic subpopulations. BMI ≤30 was associated with increased revision risk. Age >35 years and Tönnis grade 0 radiographs predicted failure to achieve minimal clinically important differences.