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1.
Thorac Cardiovasc Surg Rep ; 12(1): e60-e62, 2023 Jan.
Article in English | MEDLINE | ID: mdl-37954493

ABSTRACT

Background There are many known complications that occur after surgical revascularization for patients with significant left main coronary artery disease. Case Description This case report highlights the preoperative workup, surgical approach, and postoperative management of a patient who presents with an aortic pseudoaneurysm and dissection 2 years after the index CABG. Conclusion The development of an aortic pseudoaneurysm in combination with an ascending aortic dissection after prior coronary artery bypass grafting (CABG) is a rare compilation of complications that has scarcely been reported in the literature.

2.
Orthop J Sports Med ; 11(10): 23259671231198246, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37840898

ABSTRACT

Background: There is concern for maintaining the integrity of the reflected head of the rectus femoris during arthroscopic hip joint access. Because of the proximity to the indirect head of the rectus femoris (IHRF), capsulotomy technique and capsular closure during routine hip arthroscopy may play a role in postoperative tendinitis. Purpose: To quantify the extent of injury sustained to the IHRF during interportal versus periportal capsulotomy for routine arthroscopic hip joint access. Study Design: Controlled laboratory study. Methods: A cadaveric study was conducted using 20 fresh-frozen cadaveric hips, in which hip joint access through a periportal capsulotomy (n = 10) or interportal capsulotomy (n = 10) was performed. Capsular closure followed by a layered dissection to the capsuloligamentous complex of the hip joint was then performed to localize the IHRF. Suture proximity to the tendon, tendon disruption, and the IHRF footprint was documented to the nearest 0.01 mm using digital calipers. Statistical analysis was performed using unpaired Student t tests. Results: The mean capsulotomy length for the interportal specimens was 19.27 ± 3.25 mm, and the mean medial and lateral capsulotomy length for the periportal specimens was 4.47 ± 1.60 and 4.26 ± 0.89 mm, respectively. There was violation of the tendon in 3 of 10 interportal specimens and 4 of 10 periportal specimens. There was no significant difference in the closest suture measured to the IHRF for specimens with versus without tendon violation, for either interportal or periportal capsulotomy. Conclusion: We found comparable outcomes with regard to violation of the IHRF between interportal and periportal capsulotomy, with no significant difference in suture proximity to the IHRF in specimens with or without tendon violation. There remains no consensus on the ideal method by which to avoid iatrogenic damage to the IHRF. Clinical Relevance: Our findings provide insight that may lead to future advances in surgical care, such that protection of the tendon during routine hip arthroscopy may allow for improved postoperative rehabilitation and strength.

3.
Front Bioeng Biotechnol ; 11: 1244975, 2023.
Article in English | MEDLINE | ID: mdl-37731766

ABSTRACT

Introduction: A massive rotator cuff tear (RCT) leads to glenohumeral joint destabilization and characteristic degenerative changes, termed cuff tear arthropathy (CTA). Understanding the response of articular cartilage to a massive RCT will elucidate opportunities to promote homeostasis following restoration of joint biomechanics with rotator cuff repair. Mechanically activated calcium-permeating channels, in part, modulate the response of distal femoral chondrocytes in the knee against injurious loading and inflammation. The objective of this study was to investigate PIEZO1-mediated mechanotransduction of glenohumeral articular chondrocytes in the altered biomechanical environment following RCT to ultimately identify potential therapeutic targets to attenuate cartilage degeneration after rotator cuff repair. Methods: First, we quantified mechanical susceptibility of chondrocytes in mouse humeral head cartilage ex vivo with treatments of specific chemical agonists targeting PIEZO1 and TRPV4 channels. Second, using a massive RCT mouse model, chondrocytes were assessed for mechano-vulnerability, PIEZO1 expression, and calcium signaling activity 14-week post-injury, an early stage of CTA. Results: In native humeral head chondrocytes, chemical activation of PIEZO1 (Yoda1) significantly increased chondrocyte mechanical susceptibility against impact loads, while TRPV4 activation (GSK101) significantly decreased impact-induced chondrocyte death. A massive RCT caused morphologic and histologic changes to the glenohumeral joint with decreased sphericity and characteristic bone bruising of the posterior superior quadrant of the humeral head. At early CTA, chondrocytes in RCT limbs exhibit a significantly decreased functional expression of PIEZO1 compared with uninjured or sham controls. Discussion: In contrast to the hypothesis, PIEZO1 expression and activity is not increased, but rather downregulated, after massive RCT at the early stage of cuff tear arthropathy. These results may be secondary to the decreased axial loading after glenohumeral joint decoupling in RCT limbs.

4.
Am J Sports Med ; 51(11): 2815-2823, 2023 09.
Article in English | MEDLINE | ID: mdl-37551708

ABSTRACT

BACKGROUND: Socioeconomic disparities correlate with worse outcomes after arthroscopic rotator cuff repair. However, use of a surrogate to describe socioeconomic disadvantage has been a challenge. The Area Deprivation Index (ADI) is a tool that encompasses 17 socioeconomic variables into a single metric based on census location. HYPOTHESIS: Higher ADI would result in a worse minimal clinically important difference (MCID) for the Patient Reported Outcomes Measurement Information System (PROMIS) and have less improvement in range of motion (ROM) following arthroscopic rotator cuff repair (ARCR). STUDY DESIGN: Cohort study; Level of evidence, 3. METHOD: A retrospective review was performed for patients who underwent arthroscopic rotator cuff repair. Patients in the most socioeconomically disadvantaged quartile (ADIHigh) were compared with the least disadvantaged quartile (ADILow) in the ability to reach MCID. Demographic and surgical features were assessed for attainment of MCID. RESULTS: In total 1382 patients were identified who underwent ARCR, of which a total of 306 patients met final inclusion criteria. A higher percentage of patients within the ADIHigh cohort identified as "Black" or "other" race and had government-issued insurance compared with the ADILow cohort (P < .05). The ADIHigh cohort had significantly worse postoperative forward flexion compared with the ADILow cohort (145.0°± 32.5° vs 156.3°± 23.4°; P = .001) despite starting with comparable preoperative ROM (P = .17). Logistic regression showed that ADI was the only variable significant for predicting achievement of MCID for all 3 PROMIS domains, with the ADIHigh cohort having significantly worse odds of achieving MCID Physical Function (odds ratio [OR], 0.31; P = .001), Pain Interference (OR, 0.21; P = .001), and Depression (OR, 0.28; P = .001). Meanwhile, age, sex, body mass index, and smoking history were nonsignificant. Moreover, "other" for race and Medicare insurance were significant for achievement of MCID Depression but not Physical Function or Pain Interference. Finally, ADI was the main feature for predictive logistic regression modeling. CONCLUSION: ADI served as the only significant predictor for achieving MCID for all 3 PROMIS domains after arthroscopic rotator cuff repair. Patients who face high levels of socioeconomic disadvantage have lower rates of achieving MCID. In addition, patients with greater neighborhood disadvantage demonstrated significantly worse improvement in active forward flexion. Further investigation is required to understand the role of ADI on physical therapy compliance and to identify the barriers that prevent equitable postoperative care.


Subject(s)
Rotator Cuff Injuries , Humans , Aged , United States , Rotator Cuff Injuries/surgery , Rotator Cuff/surgery , Cohort Studies , Minimal Clinically Important Difference , Treatment Outcome , Medicare , Arthroscopy , Retrospective Studies , Pain , Range of Motion, Articular , Patient Reported Outcome Measures , Information Systems
5.
Am J Sports Med ; 51(10): 2659-2670, 2023 08.
Article in English | MEDLINE | ID: mdl-37463114

ABSTRACT

BACKGROUND: Previous studies reported inferior patient-reported outcomes (PROs) after arthroscopic rotator cuff repair for patients receiving workers' compensation (WC) relative to patients with commercial insurance. The extent to which alternative insurance reimbursement, including Medicaid and Medicare, influences outcomes after arthroscopic rotator cuff repair remains understudied. HYPOTHESIS: Compared with patients with commercial insurance reimbursement, patients with WC or government-issued reimbursement would report lower pre- and postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) scores, report higher pre- and postoperative PROMIS Depression (D) and Pain Interference (PI) scores, and experience smaller levels of improvement in all PROMIS domains with surgical intervention. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Demographic and surgical data were extracted from the medical record, and PROMIS domains were prospectively collected. Patients were divided into cohorts based on insurance reimbursement status. Differences between insurance-based cohorts for baseline variables, pre- and postoperative PROMIS scores, and change from baseline to final follow-up (delta) for PROMIS scores were evaluated using Kruskal-Wallis or chi-square tests. Mixed-effects linear regression models were performed to assess the influence of insurance while controlling for other variables. Survival analysis was performed to determine time to achieve minimal clinically important difference (MCID) for each PROMIS domain per cohort. RESULTS: 1252 patients underwent arthroscopic rotator cuff repair, met inclusion criteria, and completed PROMIS questionnaires. Statistically significant differences were noted in demographic variables including age (P < .001), sex (P < .001), ethnicity (P < .001), and body mass index (P < .001) between insurance-based cohorts. Unadjusted analysis revealed significantly higher PF scores and lower PI and D scores for the group with commercial insurance relative to those with Medicare, Medicaid, and WC at 6- and 12-month follow-up (P < .01 all comparisons), except for the Medicare versus commercial subcohort analysis for PI at 6 months (P = .28). These differences persisted for the Medicare, Medicaid, and WC groups (P < .03 all comparisons) after adjustment for confounding variables in linear regression. CONCLUSIONS: The baseline characteristics of patients undergoing arthroscopic rotator cuff repair differed based on insurance reimbursement. Patients with commercial insurance reported improved physical function, decreased pain interference, and improved mood (less depression) relative to patients with government-issued and WC insurance, with maximum improvement 6 to 12 months postoperatively. There were few significant differences between insurance groups in change of PROMIS scores from preoperative to postoperative intervals, indicating that differences in the baseline demographic and surgical characteristics of these groups accounted for differences in response to surgery.


Subject(s)
Rotator Cuff Injuries , Treatment Outcome , Information Systems , Patient Reported Outcome Measures , Arthroscopy , Rotator Cuff Injuries/surgery , Humans , Male , Female , Adult , Middle Aged , Aged , Postoperative Complications
6.
J Card Surg ; 37(9): 2900-2902, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35701995

ABSTRACT

High-risk patients that are not candidates for conventional coronary artery bypass grafting surgery can undergo coronary artery revascularization through less invasive procedures. Hybrid approaches have emerged to address coronary artery disease in this subset of patients. This case report highlights the successful application of a multidisciplinary heart team approach for hybrid coronary revascularization in a very high-risk patient with complex coronary anatomy, who would not otherwise be a candidate for conventional modalities of revascularization. The optimal workup, selection criteria based on anatomy, anticoagulation strategies, and timing of intervention of hybrid coronary revascularization are outlined in this case report.


Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Coronary Artery Bypass/methods , Coronary Artery Disease/etiology , Coronary Artery Disease/surgery , Humans , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome
7.
Front Cell Dev Biol ; 10: 885224, 2022.
Article in English | MEDLINE | ID: mdl-35602590

ABSTRACT

Mechanical factors play critical roles in the pathogenesis of joint disorders like osteoarthritis (OA), a prevalent progressive degenerative joint disease that causes debilitating pain. Chondrocytes in the cartilage are responsible for extracellular matrix (ECM) turnover, and mechanical stimuli heavily influence cartilage maintenance, degeneration, and regeneration via mechanotransduction of chondrocytes. Thus, understanding the disease-associated mechanotransduction mechanisms can shed light on developing effective therapeutic strategies for OA through targeting mechanotransducers to halt progressive cartilage degeneration. Mechanosensitive Ca2+-permeating channels are robustly expressed in primary articular chondrocytes and trigger force-dependent cartilage remodeling and injury responses. This review discusses the current understanding of the roles of Piezo1, Piezo2, and TRPV4 mechanosensitive ion channels in cartilage health and disease with a highlight on the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA.

9.
JAMA Surg ; 157(3): 269-274, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35080596

ABSTRACT

IMPORTANCE: Thoracostomy, or chest tube placement, is used in a variety of clinical indications and can be lifesaving in certain circumstances. There have been developments and modifications to thoracostomy tubes, or chest tubes, over time, but they continue to be a staple in the thoracic surgeon's toolbox as well as adjacent specialties in medicine. This review will provide the nonexpert clinician a comprehensive understanding of the types of chest tubes, indications for their effective use, and key management details for ideal patient outcomes. OBSERVATIONS: This review describes the types of chest tubes, indications for use, techniques for placement, common anatomical landmarks that are encountered with placement and management, and an overview of complications that may arise with tube thoracostomy. In addition, the future direction of chest tubes is explored, as well as the management of chest tubes during the COVID-19 pandemic. CONCLUSIONS AND RELEVANCE: Chest tube management is subjective, but the compilation of data can inform best practices and safe application to successfully manage the pleural space and ameliorate acquired pleural space disease.


Subject(s)
COVID-19 , Chest Tubes , Humans , Pandemics , SARS-CoV-2 , Thoracostomy/methods
11.
Orthop J Sports Med ; 9(8): 23259671211022682, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34485580

ABSTRACT

BACKGROUND: Studies have reported favorable clinical outcomes after osteochondral allograft (OCA) transplantation to treat osteochondral defects and have demonstrated that healing of the osseous component may be critical to outcomes. However, there is currently no consensus on the optimal modality to evaluate osseous healing. PURPOSE: To define parameters for OCA healing using computed tomography (CT) and to investigate whether osseous healing identified using CT is correlated with improved pain and function on patient-reported outcomes (PROs) collected closest in time to the postoperative CT scan and at final follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Of 118 patients who underwent OCA transplantation for articular cartilage defects of the knee over the 10-year study period, 60 were included in final analysis based on completion of CT scans at 5.8 ± 1.9 months postoperatively and PROs collected preoperatively and postoperatively. CT parameters, including osseous incorporation, bone density, subchondral bone congruency, and cystic changes, were summarized for each patient relative to the cohort. Parameters were assessed for inter- and intrarater reliability as well as for covariation with patient characteristics and surgical variables. Structural equation modeling was used to assess correlation of CT parameters with change in PROs from preoperatively to those collected closest in time to CT acquisition and at the final follow-up. RESULTS: Bone incorporation was the most reliable CT parameter. The summarized scores for CT scans were normally distributed across the study population. Variance in CT parameters was independent of age, sex, body mass index, prior surgery, number of grafts, lesion size, and location. No significant correlation (P > .12 across all comparisons) was identified for any combination of CT parameter and change in PROs from baseline for outcomes collected either closest to CT acquisition or at the final follow-up (mean, 38.2 ± 19.9 months; range, 11.6-84.9 months). There was a uniformly positive association between change in PROs and host bone density but not graft bone density, independent of patient characteristics and surgical factors. CONCLUSION: CT parameters were independent of clinical or patient variables within the study population, and osseous incorporation was the most reliable CT parameter. Metrics collected from a single postoperative CT scan was not correlated with clinical outcomes at ≥6-month longitudinal follow-up.

12.
J Thorac Cardiovasc Surg ; 162(4): 1035-1045.e5, 2021 10.
Article in English | MEDLINE | ID: mdl-32204911

ABSTRACT

OBJECTIVE: Stroke remains a potentially devastating complication of aortic arch intervention. The value of neurophysiologic intraoperative monitoring (NIOM) in the early identification of stroke is unclear. We evaluated the utility of NIOM for early stroke detection in aortic arch surgery. METHODS: Across 8 years at our institution, 365 patients underwent aortic arch surgery with hypothermic circulatory arrest, and 224 cases utilized NIOM. One patient was excluded for intraoperative death. In the remaining cohort, we reviewed the incidence, timing, and location of strokes, and the incidence and nature of NIOM alerts. RESULTS: Hemiarch was performed in 154 patients and total arch replacement in 69 patients. Stroke occurred in 6.3% of all cases (14 out of 223), 15.9% of total arches (11 out of 69), and 2.0% of hemiarches (3 out of 154). There were 33 NIOM alerts (14.8%), and 9 patients had both alerts and stroke. Of these, NIOM deficits plausibly correlated with imaging findings in 7 cases (78%). Of the 5 stroke patients without NIOM alerts, 2 developed neurologic symptoms 3 days or more postoperatively, and infarcts in 3 patients did not result in sensory or motor deficits. Excluding 2 patients with late stroke, the sensitivity of NIOM for stroke detection was 75%, specificity was 88.5%, positive predictive value was 27.3%, and negative predictive value was 97.4%. CONCLUSIONS: Despite a low positive predictive value requiring a high level of discrimination when interpreting abnormal findings, NIOM has high sensitivity and specificity for the early stroke detection. Furthermore, its high negative predictive valve is reassuring for low risk of stroke in the absence of alerts.


Subject(s)
Aorta, Thoracic/surgery , Blood Vessel Prosthesis Implantation , Circulatory Arrest, Deep Hypothermia Induced , Intraoperative Neurophysiological Monitoring/methods , Postoperative Complications , Stroke , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/methods , Circulatory Arrest, Deep Hypothermia Induced/adverse effects , Circulatory Arrest, Deep Hypothermia Induced/methods , Early Diagnosis , Female , Humans , Incidence , Male , Middle Aged , Outcome and Process Assessment, Health Care , Postoperative Complications/diagnosis , Postoperative Complications/mortality , Postoperative Complications/prevention & control , Predictive Value of Tests , Prognosis , Risk Assessment , Sensitivity and Specificity , Stroke/diagnosis , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , United States/epidemiology
15.
Spine Deform ; 8(2): 177-185, 2020 04.
Article in English | MEDLINE | ID: mdl-32026435

ABSTRACT

STUDY DESIGN: Prospective double-blind, randomized controlled trial. OBJECTIVES: The objective of this study was to validate the efficacy of gabapentin as part of a multimodal pain regimen in a double-blind, randomized controlled trial for patients aged 10-19 years with idiopathic scoliosis undergoing posterior spinal fusion. Perioperative pain management represents a challenge for patients undergoing surgical correction of adolescent spinal deformity. Gabapentin has been shown to decrease postoperative pain and opioid use after spine surgery, but it has not yet been investigated as part of a multimodal pain regimen intended to decrease the perioperative use of opioids. METHODS: Fifty patients were randomized to receive gabapentin or placebo pre- and postoperatively in addition to a standardized medication regime including scheduled ketorolac and as-needed acetaminophen, hydromorphone, and oxycodone. Patients were monitored in the pre-, peri-, and postoperative periods for pain levels, medication dosing, side effects, adverse events, hospitalization length of stay, and parent satisfaction. RESULTS: There were statistically significant decreases in early postoperative pain scores and opioid use as well as total postoperative opioid use for the treatment group relative to controls. There were no statistically significant differences in adverse events, medication side effects, or hospitalization length. Parents of patients in both groups were very satisfied with the pain control provided to their children. CONCLUSIONS: This randomized controlled trial demonstrates that pre- and postoperative administration of gabapentin as part of a multimodal pain management protocol significantly decreases both opioid use and visual analog pain scales in the first two postoperative days after posterior spinal fusion for adolescent idiopathic scoliosis. Gabapentin should be considered as a standard medication for perioperative pain control in this patient population. LEVEL OF EVIDENCE: Level I.


Subject(s)
Analgesics/administration & dosage , Gabapentin/administration & dosage , Pain Management/methods , Pain, Postoperative/drug therapy , Scoliosis/surgery , Spinal Fusion/methods , Adolescent , Analgesics, Opioid/administration & dosage , Child , Double-Blind Method , Female , Humans , Male , Pain Measurement , Pain, Postoperative/diagnosis , Patient Satisfaction , Treatment Outcome , Young Adult
16.
J Am Acad Orthop Surg Glob Res Rev ; 4(5): e2000003, 2020 05.
Article in English | MEDLINE | ID: mdl-33970581

ABSTRACT

BACKGROUND: Orthopaedic surgery is ever changing and depends on diverse technical and intellectual skill sets. The purpose of the current study was to evaluate the percentage of academic orthopaedic surgeons with additional graduate degrees in the United States. METHODS: Data including advanced degree(s) (eg, PhD, MS, MBA, MPH, JD, and DVM), academic rank, leadership position, subspecialty, years since training completion, and sex were collected from websites for all academic orthopaedic surgery departments in the United States. Univariate analyses were performed to evaluate for differences in demographic data based on the advanced degree status. Data from the National Resident Matching Program (NRMP) were used to characterize graduate degree-holding US senior medical students who ranked orthopaedic surgery first relative to peers without additional advanced degrees and to applicants who ranked other specialties first. RESULTS: Of 4,519 faculty at 175 academic orthopaedic surgery departments in the United States, 7.1% held a graduate degree in addition to a medical doctorate. There was no difference in the percentage of faculty who held departmental leadership positions (P = 0.62) or who were full professors (P = 0.66) based on holding an additional graduate degree. Of 678 US senior applicants who ranked orthopaedic surgery first and successfully matched into the specialty in 2018, 12.5% held an additional graduate degree and 1.3% were MD-PhDs. Orthopaedic surgery had the second lowest percentage of matched medical students with additional advanced degrees, which was significantly lower than the top 10 specialties (range 16.1% to 21.6%; P < 0.05). Orthopaedic surgery recruited 1.6% of all MD-PhD applicants in 2018. DISCUSSION: Few academic orthopaedic surgery faculty and admitted orthopaedic residency candidates have additional graduate school training. The low percentage of orthopaedic faculty and trainees with additional advanced degrees relative to other specialties may represent a missed opportunity to recruit individuals with diverse skills to advance the field of orthopaedic surgery.


Subject(s)
Orthopedic Surgeons , Orthopedics , Students, Medical , Employment , Humans , Leadership , United States
17.
Orthop J Sports Med ; 6(11): 2325967118805441, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30480011

ABSTRACT

BACKGROUND: Osteochondral allograft (OCA) transplantation has become a standard therapy for cartilage restoration in young patients. PURPOSE: To determine the efficacy of fresh OCA transplantation for focal cartilage lesions in patients aged ≥40 years compared with a group of patients aged ≤39 years. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A database was used to identify patients who underwent fresh OCA transplantation in the knee in a single-surgeon practice over a 10-year period and who completed baseline patient-reported outcome (PRO) questionnaires, including the International Knee Documentation Committee (IKDC); Knee injury and Osteoarthritis Outcome Score (KOOS) subscales of Pain, Symptoms, Activities of Daily Living, Quality of Life (QOL), and Sports & Recreation; and Veterans RAND 12-Item Health Survey (VR-12). Patients who completed the same PRO measures at a minimum 12-month follow-up were categorized into 2 groups based on age at surgery and were observed longitudinally. Mixed-model regression was used to predict longitudinal growth curves for each PRO score while controlling for confounding patient and surgical variables. RESULTS: The study group consisted of 38 patients with a mean age of 52.32 years (range, 40-69 years) and mean final follow-up of 44.47 ± 24.32 months. The control group consisted of 42 patients with a mean age of 27.19 years (range, 15-39 years) and mean final follow-up of 33.75 ± 19.53 months. A statistically significant improvement from baseline to final follow-up was seen for the IKDC score and all 5 KOOS subscores in both the study and the control groups (P < .01 in 10 of 12 comparisons and P < .05 for the other 2 comparisons). Maximum improvements were seen in the KOOS QOL and Sports & Recreation subscores for both groups. There was no statistically significant difference between groups in the change from baseline to final follow-up or in differences at any time point in model-based longitudinal projections for any PRO score through 5 years. CONCLUSION: There was a significant improvement of outcomes for both groups, with no statistically significant difference between groups over longitudinal follow-up. The efficacy of fresh OCA transplantation in adults aged ≥40 years with a focal chondral lesion and without osteoarthritis is similar to that of younger adults, and benefits are greatest for the KOOS QOL and Sports & Recreation subscales, which reflect functional outcomes.

18.
Tissue Eng Part A ; 24(3-4): 264-274, 2018 02.
Article in English | MEDLINE | ID: mdl-28474537

ABSTRACT

INTRODUCTION: Biomaterial-based tissue engineering has not successfully reproduced the structural architecture or functional mechanical properties of native articular cartilage. In scaffold-free tissue engineering systems, cells secrete and organize the entire extracellular matrix over time in response to environmental signals such as oxygen level. In this study, we investigated the effect of oxygen on the formation of neocartilage from human-derived chondrogenic cells. MATERIALS AND METHODS: Articular chondrocytes (ACs) and articular cartilage progenitor cells (ACPs) derived from healthy human adults were guided toward cell condensation by centrifugation onto plate inserts that were uncoated or coated with either agarose or fibronectin. Neocartilage discs were cultured at hyperoxic (20%) or physioxic (5%) oxygen levels, and biochemical, biomechanical, and molecular analyses were used to compare the cartilage produced by ACs versus ACPs. RESULTS: Fibronectin-coated inserts proved optimal for growing cartilaginous discs from both cell types. In comparison with culture in hyperoxia, AC neocartilage cultured at physioxia exhibited a significant increase in chondrogenic gene expression, proteoglycan production, and mechanical properties with a concomitant decrease in collagen content. At both oxygen levels, ACP-derived neocartilage produced tissue with significantly enhanced mechanical properties and collagen content relative to AC-derived neocartilage. Both ACs and ACPs produced substantial collagen II and reduced levels of collagens I and X in physioxia relative to hyperoxia. Neocartilage from ACPs exhibited anisotropic organization characteristic of native cartilage with respect to collagen VI of the pericellular matrix when compared with AC-derived neocartilage; however, only ACs produced abundant surface-localized lubricin. DISCUSSION AND CONCLUSIONS: Guiding human-derived cells toward condensation and subsequent culture in physioxia promoted the articular cartilage tissue phenotype for ACs and ACPs. Unlike ACs, ACPs are clonable and highly expandable while retaining chondrogenicity. The ability to generate large tissues utilizing a scaffold-free approach from a single autologous progenitor cell may represent a promising source of neocartilage destined for cartilage repair.


Subject(s)
Cartilage, Articular/cytology , Chondrocytes/cytology , Chondrocytes/physiology , Chondrogenesis/physiology , Cells, Cultured , Collagen Type I/chemistry , Fibronectins/chemistry , Humans , Tissue Engineering/methods , Tissue Scaffolds/chemistry
19.
Orthop J Sports Med ; 5(5): 2325967117707213, 2017 May.
Article in English | MEDLINE | ID: mdl-28589161

ABSTRACT

BACKGROUND: Articular cartilage lacks the ability for intrinsic repair after acute injury, and focal articular cartilage lesions cause significant morbidity worldwide. Arthroscopic debridement (chondroplasty) represents the majority of cartilage procedures of the knee; however, limited data exist regarding outcomes after chondroplasty performed in isolation of concurrent procedures or not as a primary treatment for osteoarthritis (OA). HYPOTHESIS: Arthroscopic mechanical chondroplasty is beneficial for patients with a focal cartilage lesion of the knee in the absence of meniscal pathology or OA. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Potential participants were identified by querying billing data from a 3-year period in a single-surgeon practice, and eligible patients were verified to meet inclusion criteria through electronic medical record review. OA was quantified through Kellgren-Lawrence (KL) scoring. Subjective patient-reported outcome (PRO) scores, including International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), Tegner, Lysholm, and Veterans RAND 12-Item Health Survey (VR-12), were collected preoperatively and at follow-up intervals. International Cartilage Repair Society (ICRS) grade and lesion size were determined at arthroscopy. Linear regression was used to determine the effect of baseline score on final follow-up score. Correlated regression equations were used to assess the relationship of covariates and change in PRO scores. RESULTS: Fifty-three of 86 (62%) eligible participants completed postoperative questionnaires at an average of 31.5 months (range, 11.5-57 months). The mean patient age was 37.3 ± 9.7 years and mean body mass index (BMI) was 27.7 ± 5.6 kg/m2; 33 (62%) participants were women. The mean treated lesion size was 3.3 ± 1.9 cm2, of these, 36 (68%) were ICRS grade 2 or 3, and 42 (79%) patients had a KL score of 0 to -2. On average, the cohort demonstrated significant improvement from baseline for almost all PRO scores. Regression analysis of change in score versus baseline indicated participants with lower preoperative scores gained more benefit from chondroplasty. Correlated regression equations showed KL score >0 and male sex had a consistent positive effect on change in PRO scores, high ICRS grade had a consistent negative effect, and lesion size, age, and obesity had no effect. Eight patients (15%) required further surgical intervention within the follow-up period. CONCLUSION: The clinical efficacy of chondroplasty for repair of focal cartilage defects of the knee has not been studied in isolation from concurrent orthopaedic procedures. Our data show that arthroscopic mechanical chondroplasty is beneficial to patients, and response to surgical intervention is correlated with baseline PRO scores, sex, ICRS grade, and KL score.

20.
Am J Sports Med ; 45(4): 875-883, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28068480

ABSTRACT

BACKGROUND: Autologous cartilage tissue implants, including the NeoCart implant, are intended to repair focal articular cartilage lesions. Short-term results from United States Food and Drug Administration (FDA) phase I and phase II clinical trials indicated that the NeoCart implant was safe when surgically applied as a cell-based therapy and efficacious compared with microfracture. HYPOTHESIS: Quantitative magnetic resonance imaging (MRI) analysis would reveal NeoCart tissue maturation through to 60-month follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with symptomatic full-thickness cartilage lesions of the distal femoral condyle were treated with NeoCart in FDA clinical trials. Safety and efficacy were evaluated prospectively by MRI and clinical patient-reported outcomes (PROs) through to 60-month follow-up. Qualitative MRI metrics were quantified according to modified MOCART (magnetic resonance observation of cartilage repair tissue) criteria, with an independent evaluation of repair tissue signal intensity. Subjective PROs and objective range of motion (ROM) were obtained at baseline and through to 60 months. RESULTS: Twenty-nine patients treated with NeoCart were observed over a mean of 52.0 ± 15.5 months (median, 60 months). MOCART analyses indicated significant improvement ( P < .001) in cartilage quality from 3 to 24 months, with stabilization from 24 to 60 months. Signal intensity of the repair tissue evolved from hyperintense at early follow-up to isointense after 6 months and to hypointense after 24 months. The temporal progression toward hypointense T2 signals at later time points observed here indicated a further reorganization of the repair tissue toward a dense tissue that was less similar to the surrounding native tissue. However, 80% of patients showed evidence of subchondral bone changes on MRI at all time points; 4 patients (14%) showed no improvement of MRI criteria. Compared with baseline values, significant improvement ( P < .001) was seen in PROs (mean [±SD] baseline to mean [±SD] final follow-up), including the International Knee Documentation Committee score (47.9 ± 17.4 to 75.5 ± 22.1), physical component summary of the Short Form-36 (40.5 ± 7.2 to 51.4 ± 8.1), and all 5 domains of the Knee injury and Osteoarthritis Outcome Score (Pain: 64.8 ± 12.1 to 86.1 ± 17.3; Activities of Daily Living: 75.5 ± 14.8 to 91.6 ± 13.8; Quality of Life: 28.6 ± 15.5 to 69.4 ± 28.0; Symptoms: 65.8 ± 13.8 to 86.6 ± 13.4; Sports and Recreation: 41.4 ± 24.3 to 72.4 ± 28.8). Significant ( P < .0001) decreases from baseline scores for the visual analog scale for pain (34.6 ± 22.5) were seen by 6 months and sustained at final follow-up (14.3 ± 18.4). ROM significantly ( P < .0001) improved from baseline (131.5° ± 7.9°) to final follow-up (140.7° ± 6.3°). CONCLUSION: Longitudinal MRI analysis demonstrated that NeoCart-based repair tissue is durable and evolves over time. For a majority of patients, this progression trended from an initial hyperintense signal to a hypointense signal at later follow-ups. Changes in radiographic measures over time corresponded with improvement in clinical measures, with maximum benefits experienced at 24-month follow-up. Similarly, clinical efficacy for the total cohort, determined by clinical outcome scores, reached a maximum at 24 months without decline to 60 months. Results from safety and exploratory clinical trials indicate that NeoCart is a safe and effective treatment for articular cartilage lesions through to 5-year follow-up. Registration: NCT00548119 ( ClinicalTrials.gov identifier).


Subject(s)
Cartilage, Articular/injuries , Cartilage/transplantation , Knee Injuries/diagnostic imaging , Knee Injuries/surgery , Magnetic Resonance Imaging , Activities of Daily Living , Adult , Cartilage, Articular/diagnostic imaging , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement , Prospective Studies , Quality of Life , Range of Motion, Articular , Transplantation, Autologous , Treatment Outcome , Visual Analog Scale , Wound Healing , Young Adult
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