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OBJECTIVES: The purpose of this study was to assess the educational reliability and quality of videos shared on YouTube regarding medial collateral ligament (MCL) injuries of the knee. METHODS: Using the search keywords "medial collateral ligament" on YouTube, the first 50 videos were evaluated by two independent reviewers. Video characteristics were extracted, and each video was categorized by upload source and content type. Three scoring systems were used to evaluate the videos: the Journal of the American Medical Association (JAMA) Benchmark Score to assess a video's reliability; the Global Quality Score (GQS) to assess educational quality; the novel MCL Specific Score (MCL-SS) to assess MCL-specific content quality. Linear regression analyses were conducted to explore relationships between video characteristics and scores. RESULTS: Collectively, the videos were viewed 5,759,427 times with a mean number of views per video of 115,189 â± â177,861. The mean JAMA score was 1.8, GQS was 2.1, and MCL-SS was 5.6, indicating both poor reliability and quality. Only videos uploaded by physicians showed a statistically significantly higher mean MCL-SS (P â= â0.032) but were still of low quality with a mean MCL-SS of 9.2 â± â5.9. Multivariate linear regression revealed that videos uploaded by physicians were statistically significant predictors of greater MCL-SS (ß â= â4.108; P â= â0.029). Longer video durations were statistically significant predictors of greater GQS (ß â= â0.001; P â= â0.002) and MCL-SS (ß â= â0.007; P â< â0.001). CONCLUSIONS: YouTube videos regarding MCL injuries, despite their popularity, were found to be on average having poor overall reliability and quality as measured by JAMA, GQS and MCL-SS. LEVEL OF EVIDENCE: III. STUDY DESIGN: Cross-sectional Study.
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Purpose: To evaluate the clinical and radiographic outcomes of patients who have undergone bioabsorbable screw fixation for intact, stable grade I and II osteochondritis dissecans (OCD) lesions for which at least 6 months of conservative management has failed. Methods: A retrospective review of prospectively collected data from a single institution was performed to identify patients who underwent internal fixation of stable grade I and II OCD lesions (according to the Guhl classification) between January 2010 and January 2020. Patients were included regardless of the presence of concomitant procedures. The inclusion criteria consisted of (1) primary surgery, (2) failure of at least 6 months of conservative management, (3) the use of a bioabsorbable screw (or screws), and (4) minimum 2-year clinical follow-up. Radiographs were obtained at a minimum of 1 year postoperatively. Patient demographic characteristics, clinical patient-reported outcomes, complications, and failure rates were noted. Results: Twenty-four knees among 23 patients (96% follow-up) were analyzed and followed up for 6.36 ± 3.42 years (range, 2.0-12.7 years). Patients showed statistically significant postoperative improvements in all patient-reported outcomes including the Lysholm score, International Knee Documentation Committee score, and Knee Injury and Osteoarthritis Outcome Score subscales (P < .05). In 3 knees (12%), a reoperation was required due to failure at an average of 3.64 years after the index procedure. No specific complications were attributed to the use of bioabsorbable screws. Patients in whom primary surgical treatment failed did not differ in demographic characteristics, arthroscopic findings, or surgical treatment from those who had successful treatment. Conclusions: Internal fixation of stable grade I and II OCD lesions with bioabsorbable screws produces reliable results with a 12% rate of failure in appropriately indicated patients in whom at least 6 months of conservative management has failed. Clinical outcomes improved significantly during the mid-term follow-up period. Level of Evidence: Level IV, therapeutic case series.
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PURPOSE: To report the mid-term outcomes of patients who underwent revision meniscal allograft transplantation (RMAT) and compare survivorship free from reoperation and failure with a matched cohort of patients who underwent primary meniscal allograft transplantation (PMAT). METHODS: A retrospective review of prospectively collected data identified patients who underwent RMAT and PMAT between 1999 and 2017. A cohort of PMAT patients matched at a ratio of 2:1 with respect to age, body mass index, sex, and concomitant procedures served as the control group. Patient-reported outcome measures (PROMs) at baseline and at a minimum of 5 years postoperatively were collected. PROMs and the achievement of clinically significant outcomes were analyzed within groups. Graft survivorship free from meniscal reoperation and failure (arthroplasty or subsequent RMAT) was compared between cohorts using log-rank testing. RESULTS: During the study period, 22 RMATs were performed in 22 patients. Of these RMAT patients, 16 met the inclusion criteria (73% follow-up rate). The mean age of RMAT patients was 29.7 ± 9.3 years, and the mean follow-up period was 9.9 ± 4.2 years (range, 5.4-16.8 years). There were no differences between the RMAT cohort and the 32 matched PMAT patients with respect to age (P = .292), body mass index (P = .623), sex (P = .537), concomitant procedures (P ≥ .286), or baseline PROMs (P ≥ .066). The patient acceptable symptomatic state was achieved by the RMAT cohort for the subjective International Knee Documentation Committee score (70%), Lysholm score (38%), and Knee Injury and Osteoarthritis Outcome Score subscales (Pain [73%], Symptoms [64%], Sport [45%], Activities of Daily Living [55%], and Quality of Life [36%]). In the RMAT cohort, 5 patients (31%) underwent subsequent reoperation at a mean of 4.7 ± 2.1 years (range, 1.7-6.7 years) and 5 patients met the criteria for failure at a mean of 4.9 ± 2.9 years (range, 1.2-8.4 years). There were no significant differences in survivorship free from reoperation (P = .735) or failure (P = .170) between the RMAT and PMAT cohorts. CONCLUSIONS: At mid-term follow-up, most patients who underwent RMAT achieved the patient acceptable symptomatic state for the subjective International Knee Documentation Committee score and the Knee Injury and Osteoarthritis Outcome Score subscales of Pain, Symptoms, and Activities of Daily Living. Additionally, there were no differences in survival free from meniscal reoperation or failure between the PMAT and RMAT cohorts. LEVEL OF EVIDENCE: Level III, retrospective comparative cohort.
Subject(s)
Knee Injuries , Osteoarthritis , Humans , Child, Preschool , Child , Adolescent , Reoperation , Menisci, Tibial/transplantation , Retrospective Studies , Follow-Up Studies , Activities of Daily Living , Quality of Life , Knee Joint/surgery , Osteoarthritis/surgery , Allografts , Pain/surgery , Knee Injuries/surgery , Patient Reported Outcome MeasuresABSTRACT
PURPOSE: To report midterm outcomes after primary medial and lateral meniscal allograft transplantation (MAT) with fresh-frozen allografts implanted with the bridge-in-slot technique in the adolescent patient population. METHODS: Adolescent patients less than 18 years old at the time of primary MAT from 1999 to 2016 were retrospectively identified. International Knee Documentation Committee (IKDC) subjective form, Lysholm, and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales scores were collected before surgery and at 1-year, 2-year, and a minimum 5-year follow-up. Thresholds for achieving clinically significant outcomes were calculated, and the proportion of patients achieving minimal clinically important difference (MCID), patient-acceptable symptomatic state (PASS), and substantial clinical benefit (SCB) was determined. Meniscus reoperation (partial, subtotal, or total meniscectomy, repair, or failure) and failure (revision MAT or conversion to arthroplasty) rates were determined. RESULTS: Forty-four (female n = 33; male n = 11) of 62 identified patients met inclusion criteria and were followed for a mean of 9.5 ± 3.8 years (range, 5.0-17.7). Lateral MAT was performed in most patients (n = 35/44 [80%]). Isolated MAT was performed in 27 (61%) patients. Common concomitant procedures included osteochondral allograft transplantation (32%), autologous chondrocyte implantation (18%), and anterior cruciate ligament reconstruction (14%). MCID, PASS, and SCB were achieved by patients at a minimum 5-year follow-up for IKDC (62%; 76%; 31%), Lysholm (62%; 79%; 23%), and KOOS questionnaires (Pain [65%; 81%; 41%], Symptoms [58%; 81%; 47%], Activities of Daily Living [53%; 77%; 35%], Sport [86%; 75%; 50%], and Quality of Life [59%; 81%; 59%]), respectively. Fourteen patients (32%) underwent reoperation at an average of 5.0 ± 4.3 years (range, 0.8-14.0) after MAT. Three (7%) patients met criteria for failure, requiring revision MAT an average of 3.8 ± 1.1 years (range, 2.8-4.9) after transplantation. No patients underwent arthroplasty. Overall survival free from failure at 1, 2, 5, and 10 years was 100%, 100%, 93%, and 93%, respectively. At the time of final follow-up, 80% of patients reported satisfaction with their current physical status. CONCLUSIONS: Primary MAT in adolescent patients resulted in significant and durable functional improvements at mid- to long-term follow-up. At an average of 9.5 years after surgery, meniscal reoperation rate was 32% whereas graft survival free of revision MAT was 93%. Adolescents undergoing MAT demonstrated similar functional outcomes and graft survivability when compared to available adult MAT literature. LEVEL OF EVIDENCE: Level IV, retrospective case series.
Subject(s)
Anterior Cruciate Ligament Reconstruction , Meniscus , Adult , Humans , Adolescent , Female , Male , Retrospective Studies , Activities of Daily Living , Follow-Up Studies , Quality of Life , Arthroplasty , Menisci, Tibial/surgery , AllograftsABSTRACT
OBJECTIVE: 20-40% of individuals whose seizures are not controlled by anti-seizure medications exhibit manifestations comparable to epileptic seizures (ES), but there are no EEG correlates. These events are called functional or dissociative seizures (FDS). Due to limited access to EEG-monitoring and inconclusive results, we aimed to develop an alternative diagnostic tool that distinguishes ES vs. FDS. We evaluated the temporal evolution of ECG-based measures of autonomic function (heart rate variability, HRV) to determine whether they distinguish ES vs. FDS. METHODS: The prospective study includes patients admitted to the University of Rochester Epilepsy Monitoring Unit. Participants are 18-65 years old, without therapies or co-morbidities associated with altered autonomics. A habitual ES or FDS is recorded during admission. HRV analysis is performed to evaluate the temporal changes in autonomic function during the periictal period (150-minutes each pre-/post-ictal). We determined if autonomic measures distinguish ES vs. FDS. RESULTS: The study includes 53 ES and 46 FDS. Temporal evolution of HR and autonomics significantly differ surrounding ES vs. FDS. The pre-to-post-ictal change (delta) in HR differs surrounding ES vs. FDS, stratified for convulsive and non-convulsive events. Post-ictal HR, total autonomic (SDNN & Total Power), vagal (RMSSD & HF), and baroreflex (LF) function differ for convulsive ES vs. convulsive FDS. HR distinguishes non-convulsive ES vs. non-convulsive FDS with ROC>0.7, sensitivity>70%, but specificity<50%. HR-delta and post-ictal HR, SDNN, RMSSD, LF, HF, and Total Power each distinguish convulsive ES vs. convulsive FDS (ROC, 0.83-0.98). Models with HR-delta and post-ictal HR provide the highest diagnostic accuracy for convulsive ES vs. convulsive FDS: 92% sensitivity, 94% specificity, ROC 0.99). SIGNIFICANCE: HR and HRV measures accurately distinguish convulsive, but not non-convulsive, events (ES vs. FDS). Results establish the framework for future studies to apply this diagnostic tool to more heterogeneous populations, and on out-of-hospital recordings, particularly for populations without access to epilepsy monitoring units.
Subject(s)
Epilepsy , Psychogenic Nonepileptic Seizures , Humans , Adolescent , Young Adult , Adult , Middle Aged , Aged , Heart Rate/physiology , Prospective Studies , Electroencephalography/methods , Epilepsy/diagnosis , Seizures/diagnosisABSTRACT
BACKGROUND: Meniscal allograft transplantation (MAT) has been shown to provide clinical benefits in patients with symptomatic meniscal deficiency in the short term and midterm. There is, however, a paucity of data regarding long-term outcomes after MAT using fresh-frozen allografts and the bridge-in-slot technique. PURPOSE: To report clinical outcomes and revision rates after primary MAT with fresh-frozen allografts and the bridge-in-slot technique in a large case series of patients at a 10-year minimum follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective review of prospectively collected data was performed on patients undergoing primary MAT between 2001 and 2012. Lysholm, International Knee Documentation Committee subjective form, and Knee injury and Osteoarthritis Outcome Score subscales were collected preoperatively and at 1-, 2-, 5-, and minimum 10-year follow-ups. Cox proportional hazards modeling was used to identify variables associated with reoperation and failure, defined as revision MAT or conversion to arthroplasty. Reoperation was defined as a subsequent surgical intervention on the transplanted meniscus, including partial or total meniscectomy, meniscal repair, or failure as defined in the previous sentence. RESULTS: A total of 174 patients undergoing MAT met the inclusion criteria and were followed for a mean of 12.7 ± 2.7 years (range, 10.0-21.0 years). The mean age at surgery was 28.3 ± 10.1 years. The patients were predominantly female (n = 92; 53%), and medial MAT was the most commonly performed procedure (n = 91; 52%). Concomitant procedures were performed in 115 patients (66%), with the most common procedure being osteochondral allograft transplantation (n = 59; 34%). Patients demonstrated statistically significant postoperative improvements at all time points for all patient-reported outcome measures (P≤ .0001). A total of 65 patients (37%) underwent a meniscal reoperation at a mean time of 6.6 ± 5.5 years (range, 0.3-16.7 years) postoperatively. A total of 40 patients (23%) met the criteria for failure at a mean time of 7.3 ± 5.0 years (range, 1.0-17.4 years) after MAT, with 22 of these patients having undergone a previous meniscal reoperation. At the final follow-up, 13 patients (7%) had undergone revision MAT and 27 (15%) had converted to arthroplasty. The MAT survival rates free of meniscal reoperation and failure were 73% and 85% at 10 years and 60% and 72% at 15 years, respectively. At the time of the final follow-up, 86% of patients reported that they were satisfied with their overall postoperative condition. CONCLUSION: Primary MAT demonstrates efficacy and durability with high rates of patient satisfaction at a minimum 10-year follow-up. Patients should be counseled that although reoperation rates may approach 40% at 15 years, rates of overall revision MAT and conversion to arthroplasty remain low at long-term follow-up.
Subject(s)
Arthroplasty, Replacement, Knee , Meniscus , Humans , Female , Adolescent , Young Adult , Adult , Male , Survivorship , Transplantation, Homologous , AllograftsABSTRACT
BACKGROUND: Long-term outcomes of osteochondral allograft (OCA) transplantation to the humeral head have been sparsely reported in the literature. PURPOSE: To evaluate outcomes and survivorship of OCA transplantation to the humeral head in patients with osteochondral defects at a minimum of 10 years of follow-up. METHODS: A registry of patients who underwent humeral head OCA transplantation between 2004 and 2012 was reviewed. Patients completed pre and postoperative surveys including the American Shoulder and Elbow Surgeons score, Simple Shoulder Test, Short Form 12 (SF-12), and the visual analog scale. Failure was defined by conversion to shoulder arthroplasty. RESULTS: Fifteen of 21 (71%) patients with a minimum of ten year of follow-up (mean: 14.2 ± 2.40) were identified. Mean patient age was 26.1 ± 8.8 years at the time of transplantation and eight (53%) patients were male. Surgery was performed on the dominant shoulder in 11 of the 15 (73%) cases. The use of local anesthetic delivered via an intra-articular pain pump was the most often reported underlying etiology of chondral injury (n = 9; 60%). Eight (53%) patients were treated with an allograft plug, while seven (47%) patients were treated with a mushroom cap allograft. At final follow-up, mean American Shoulder and Elbow Surgeons (49.9 to 81.1; P = .048) and Simple Shoulder Test (43.1 to 83.3; P = .010) significantly improved compared to baseline. Changes in mean SF-12 physical (41.4 to 48.1; P = .354), SF-12 mental (57.5 to 51.8; P = .354), and visual analog scale (4.0 to 2.8; P = .618) did not reach statistical significance. Eight (53%) patients required conversion to shoulder arthroplasty at an average of 4.8 ± 4.7 years (range: 0.6-13.2). Kaplan-Meier graft survival probabilities were 60% at 10 years and 41% at 15 years. CONCLUSION: OCA transplantation to the humeral head can result in acceptable long-term function for patients with osteochondral defects. While patient-reported outcomes metrics were generally improved compared to baseline, OCA graft survival probabilities diminished with time. The findings from this study can be used to counsel future patients with significant glenohumeral cartilage injuries and set expectations about the potential for further surgery.
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PURPOSE: To determine the improvements in patient-reported outcome measures (PROMs) necessary to achieve minimal clinically important difference (MCID), patient-acceptable symptomatic state (PASS), and substantial clinical benefit (SCB) after primary meniscal allograft transplantation (MAT) at a minimum of 5-year follow-up, while identifying variables predictive of achieving clinically significant outcomes (CSOs). METHODS: A retrospective review was performed to identify patients undergoing primary MAT at a single institution from 1999 to 2016. Lysholm, International Knee Documentation Committee (IKDC), and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales were collected before surgery and at a minimum of 5-year follow-up. A distribution-based approach was used to calculate MCID, whereas an anchor-based approach was used to calculate SCB and PASS. Multivariate logistic regression was performed to determine factors associated with CSO achievement. RESULTS: A total of 202 patients undergoing MAT (56% medial, 44% lateral) were included with a mean follow-up of 9.8 ± 4.1 years, age of 29.7 ± 8.5 years, and body mass index (BMI) of 26.5 ± 4.7. Thresholds for achieving MCID, PASS, and SCB, respectively, at a minimum 5-year follow-up for Lysholm (10.3, 74.5, 32.5), IKDC (12.1, 55.6, 29.1), and KOOS subscales questionnaires (Pain [11.0, 70.7, 25.1], Symptoms [11.0, 60.8, 19.6], Activities of Daily Living [10.5, 90.3, 17.9], Sport [16.2, 47.4, 37.5], and Quality of Life [13.6, 40.5, 37.3]) were calculated. Reduced odds of achieving MCID were associated with higher preoperative PROM scores, BMI, patient age, concomitant osteotomy, male sex, and worker's compensation (WC) status. Reduced odds of achieving PASS were associated with lower preoperative PROM scores, higher BMI (particularly ≥30), patient age, and WC status. Reduced odds of achieving SCB were associated with higher preoperative PROM scores and WC status. CONCLUSIONS: This study established the MCID, PASS, and SCB at 5-year minimum follow-up for the Lysholm score, IKDC, and KOOS subscales in patients who underwent MAT. Increased BMI and patient age, male sex, performance of concomitant osteotomy, WC status, and preoperative PROM scores were associated with failure to achieve CSOs after primary MAT at a minimum of 5-year follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic study, retrospective case series.
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BACKGROUND: Although initial studies have demonstrated that concentrated bone marrow aspirate (cBMA) injections promote rotator cuff repair (RCR) healing, there are no randomized prospective studies investigating clinical efficacy. HYPOTHESIS/PURPOSE: To compare outcomes after arthroscopic RCR (aRCR) with and without cBMA augmentation. It was hypothesized that cBMA augmentation would result in statistically significant improvements in clinical outcomes and rotator cuff structural integrity. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients indicated for aRCR of isolated 1- to 3-cm supraspinatus tendon tears were randomized to receive adjunctive cBMA injection or sham incision. Bone marrow was aspirated from the iliac crest, concentrated using a commercially available system, and injected at the aRCR site after repair. Patients were assessed preoperatively and serially until 2 years postoperatively via the following functional indices: American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), Simple Shoulder Test, 12-Item Short Form Health Survey, and Veterans RAND 12-Item Health Survey. Magnetic resonance imaging (MRI) was performed at 1 year to assess rotator cuff structural integrity according to Sugaya classification. Treatment failure was defined as decreased 1- or 2-year ASES or SANE scores as compared with preoperative baseline, the need for revision RCR, or conversion to total shoulder arthroplasty. RESULTS: An overall 91 patients were enrolled (control, n = 45; cBMA, n = 46): 82 (90%) completed 2-year clinical follow-up and 75 (82%) completed 1-year MRI. Functional indices significantly improved in both groups by 6 months and were sustained at 1 and 2 years (all P < .05). The control group showed significantly greater evidence of rotator cuff retear according to Sugaya classification on 1-year MRI (57% vs 18%; P < .001). Treatment failed for 7 patients in each group (control, 16%; cBMA, 15%). CONCLUSION: cBMA-augmented aRCR of isolated supraspinatus tendon tears may result in a structurally superior repair but largely fails to significantly improve treatment failure rates and patient-reported clinical outcomes when compared with aRCR alone. Additional study is warranted to investigate the long-term benefits of improved repair quality on clinical outcomes and repair failure rates. REGISTRATION: NCT02484950 (ClinicalTrials.gov identifier).
Subject(s)
Biological Products , Rotator Cuff Injuries , Humans , Rotator Cuff/surgery , Prospective Studies , Bone Marrow , Rotator Cuff Injuries/surgery , Treatment Outcome , Magnetic Resonance Imaging , Arthroscopy/methodsABSTRACT
PURPOSE: The underlying mechanism for radiation as a potentiator of immune checkpoint inhibition (ICI) is unclear. We developed a novel murine model to investigate the effects of post-irradiation intratumoral heterogeneity (ITH) on response to ICI. EXPERIMENTAL DESIGN: Parental mouse melanoma B16F10 cells were irradiated in vitro (5Gy x 3 fractions), then an a priori determined number of resulting colonies were implanted in C57BL/6J immunocompetent mice creating syngeneic models of unirradiated (parental) and irradiated tumors with low (irradiated-L) and high (irradiated-H) ITH. Mice were treated with placebo, α-PD-L1, α-CTLA-4 or dual ICI. Murine tumors underwent whole exome sequencing (WES). Clinically correlated paired pre- and post-irradiation patient rectal adenocarcinoma samples underwent WES. RESULTS: Irradiated-L tumors showed increased tumor mutational burden (TMB) and a sustained decrease in ITH. Irradiated-L tumors were predicted to express five neoantigens with high variant allele frequency/clonal distribution. Mice with irradiated-L and irradiated-H versus parental B16F10 tumors demonstrated longer overall survival with dual ICI. Only mice with irradiated-L tumors experienced an overall survival benefit with single agent ICI. Clinically correlated rectal adenocarcinoma samples showed similarly increased TMB and decreased ITH following irradiation. CONCLUSIONS: Post-irradiation ITH modulates ICI response in a murine melanoma model. Irradiation may offer a mechanism to widen the therapeutic window of ICI.
Subject(s)
Adenocarcinoma , Melanoma , Animals , Mice , Immune Checkpoint Inhibitors , Mice, Inbred C57BL , CTLA-4 AntigenABSTRACT
â¢: Pathologic meniscal extrusion can compromise meniscal function, leading to increased contact forces in the tibiofemoral compartment and the acceleration of osteoarthritic changes. â¢: Extrusion is typically defined as radial displacement of ≥3 mm outside the tibial border and is best diagnosed via magnetic resonance imaging, although ultrasonography has also demonstrated encouraging diagnostic utility. â¢: Surgical management of meniscal extrusion is based on the underlying etiology, the patient's symptom profile, the preexisting health of the articular surface, and the risk of future chondral injury and osteoarthritis.
Subject(s)
Osteoarthritis , Tibial Meniscus Injuries , Humans , Magnetic Resonance Imaging/methods , Menisci, Tibial/diagnostic imaging , Menisci, Tibial/surgery , Osteoarthritis/pathology , Tibial Meniscus Injuries/diagnostic imaging , Tibial Meniscus Injuries/surgeryABSTRACT
BACKGROUND: Point-of-care treatment options for medium to large symptomatic articular cartilage defects are limited. Minced cartilage implantation is an encouraging single-stage option, providing fresh viable autologous tissue with minimal morbidity and cost. PURPOSE: To determine the histological properties of mechanically minced versus minimally manipulated articular cartilage. STUDY DESIGN: Controlled laboratory study. METHODS: Remnant articular cartilage was collected from fresh femoral condylar allografts. Cartilage samples were divided into 4 groups: cartilage explants with or without fibrin glue and mechanically minced cartilage with or without fibrin glue. Samples were cultured for 42 days. Chondrocyte viability was assessed using live/dead assay. Cellular migration and outgrowth were monitored using bright-field microscopy. Extracellular matrix deposition was assessed via histological staining. Proteoglycan content and synthesis were assessed using dimethylmethylene blue assay and radiolabeled 35S-sulfate, respectively. Type II collagen (COL2A1) gene expression was analyzed via polymerase chain reaction. RESULTS: The mean viability of minced cartilage particles (34% ± 14%) was not significantly reduced compared with baseline (46% ± 13%) on day 0 (P = .90). After culture, no significant difference in the percentage of live cells was appreciated between mechanically minced (58% ± 23%) and explant (73% ± 14%) cartilage in the presence of fibrin glue (P = .52). The addition of fibrin glue did not significantly affect the viability of cartilage samples. The qualitative assessment revealed comparable cellular migration and outgrowth between groups. Proteoglycan synthesis was not significantly different between groups. Histological analysis findings were positive for COL2A1 in all groups, and matrix formation was appreciated in all groups. COL2A1 expression in minced cartilage (1.72 ± 1.88) was significantly higher than in explant cartilage (0.15 ± 0.07) in the presence of fibrin glue (P = .01). CONCLUSION: Mechanically minced articular cartilage remained viable after 42 days of culture in vitro and was comparable with cartilage explants with regard to cellular migration, outgrowth, and extracellular matrix synthesis. CLINICAL RELEVANCE: Mechanically minced articular cartilage is an encouraging intervention for the treatment of symptomatic cartilage defects. Further translational work is warranted to determine the viability of minced cartilage implantation as a single-stage therapeutic intervention in vivo.
Subject(s)
Cartilage, Articular , Cartilage, Articular/metabolism , Chondrocytes/transplantation , Fibrin Tissue Adhesive/pharmacology , Humans , Knee Joint/surgery , Proteoglycans/metabolismABSTRACT
Brachytherapy, which is the placement of radioactive seeds directly into tissue such as the prostate, is an important curative treatment for prostate cancer. By delivering a high dose of radiation from within the prostate gland, brachytherapy is an effective method of killing prostate cancer cells while limiting radiation dose to normal tissue. The main shortcomings of this treatment are: less efficacy against high grade tumor cells, acute urinary retention, and sub-acute urinary frequency and urgency. One strategy to improve brachytherapy is to incorporate therapeutics into brachytherapy. Drugs, such as docetaxel, can improve therapeutic efficacy, and dexamethasone is known to decrease urinary side effects. However, both therapeutics have high systemic side effects. To overcome this challenge, we hypothesized that we can incorporate therapeutics into the inert polymer spacers that are used to correctly space brachytherapy seeds during brachytherapy to enable local drug delivery. To accomplish this, we engineered 3D printed drug-loaded brachytherapy spacers using continuous liquid interface production (CLIP) with different surface patterns to control drug release. These devices have the same physical size as existing spacers, allowing them to easily replace commercial spacers. We examined these drug-loaded spacers using docetaxel and dexamethasone as model drugs in a murine model of prostate cancer. We found that drug-loaded spacers led to higher therapeutic efficacy for brachytherapy, and there was no discernable systemic toxicity from the drug-loaded spacers. STATEMENT OF SIGNIFICANCE: There has been high interest in the application of 3D printing to engineer novel medical devices. However, such efforts have been limited by the lack of technologies that can fabricate devices suitable for real world medical applications. In this study, we demonstrate a unique application for 3D printing to enhance brachytherapy for cancer treatment. We engineered drug-loaded brachytherapy spacers that can be fabricated using Continuous Liquid Interface Production (CLIP) 3D printing, allowing tunable printing of drug-loaded devices, and implanted intraoperatively with brachytherapy seeds. In combined chemotherapy and brachytherapy we are able to achieve greater therapeutic efficacy through local drug delivery and without systemic toxicities. We believe our work will facilitate further investigation in medical applications of 3D printing.
Subject(s)
Brachytherapy , Prostatic Neoplasms , Animals , Brachytherapy/adverse effects , Brachytherapy/methods , Dexamethasone/pharmacology , Docetaxel/pharmacology , Humans , Male , Mice , Pharmaceutical Preparations , Printing, Three-Dimensional , Prostate/pathology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/radiotherapyABSTRACT
Purpose: To systematically review the literature to determine the injury mechanisms, presentation, and timing of diagnosis for pediatric patients with intratendinous rotator cuff tears and to determine the efficacy of surgical intervention for affected patients. Methods: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus were searched. Studies were included if they involved only pediatric patients, soft-tissue rotator cuff injuries managed surgically, and reported outcomes. Patient characteristics, injury mechanisms, physical examination and imaging findings, time to diagnosis, surgical technique, and treatment outcomes were extracted. Findings were descriptively analyzed with weighted means and proportions. Results: Twenty-one studies comprising 78 patients were included. The age range was 8 to 17 years and 57 were male. The supraspinatus (n = 56) was the most injured tendon. American football was the most reported sport played at the time of injury. Most patients were diagnosed within 6 months of injury via magnetic resonance imaging. Arthroscopic management was undertaken in 68 patients. Forty-six of 51 patients for whom data were available returned to sports at a range of 2.5 to 12 months postoperatively. Repair failure occurred in three patients. Conclusions: The extant literature regarding rotator cuff tears in pediatric patients is limited to reports of low methodological quality. Qualitative synthesis of this low-level literature reveals that rotator cuff tears are mostly reported in male collision sport athletes but may also occur in female athletes and/or throwing athletes. These injuries are often successfully managed via arthroscopic repair, and patients and their families can be reassured that the majority of patients return to sports following surgery. Level of Evidence: Level IV, systematic review of level IV studies.
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Background: Meniscal ramp lesions are injuries of the posterior horn of the medial meniscus at the meniscocapsular junction or the meniscotibial ligament and are frequently associated with concomitant anterior cruciate ligament (ACL) injury. Objective: To review the current literature on meniscal ramp lesion management to better define the indications for and outcomes of repair. Methods: A narrative literature review was performed using PubMed, Embase, and Scopus databases. Studies of all evidence levels (I-V) pertaining to meniscal ramp lesions were reviewed and included. Results: The incidence of ramp lesions has been reported between 16% and 42%. Arthroscopy remains the diagnostic gold standard as magnetic resonance imaging has limited sensitivity. Biomechanically, ramp lesions are known to increase anterior tibial translation and rotational laxity. Clinical investigations regarding optimal management are largely limited to studies of low evidence levels. While case series have demonstrated that repair is safe and efficacious, comparative studies have failed to suggest that repair of stable lesions results in superior outcomes when compared to conservative treatment approaches. However, repair may be warranted in unstable ramp lesion injuries despite the increased risk for revision surgery. Conclusion: While there is evidence to suggest that ramp lesion repair can restore joint kinematics, the current body of clinical literature fails to suggest that outcomes following repair are superior to injuries managed conservatively. The current body of clinical literature is limited, and further robust, long-term study is warranted to better guide injury diagnosis and management protocol.
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Rotator cuff tears are one of the most common causes of shoulder pain and dysfunction seen by orthopaedic surgeons. Although rotator cuff repair (RCR) has been shown to provide optimal outcomes, retear rates average roughly 60% and have been reported to exceed 90%. Retear after RCR is especially prevalent in patients with large, multitendon tears with poor tissue quality. Allograft augmentation of RCR may reinforce anatomically reparable tears, particularly in patients with poor tissue quality. Although various techniques of patch augmented RCR have been described, the procedure remains challenging. This Technical Note describes RCR augmented with acellular dermal allograft using the CuffMend system (Arthrex Inc, Naples, FL), which significantly decreases surgeon demand and helps avoid the pitfalls common with this procedure.
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The ability to return to sport (RTS) after articular cartilage injury is of vital importance to athletes. Discussing the likelihood of returning to sport with patients is necessary, yet patients should be informed of the heterogeneous nature of the variables associated with successful RTS and the methodologic limitations behind current RTS rate estimates. Patient-specific factors affecting RTS are numerous and, in most cases, their isolated effect on RTS rates have yet to be examined and will remain difficult to do so. The purpose of this review is to discuss current RTS rates, explore factors leading to successful RTS, and examine the variability in physical therapy protocols after cartilage procedures, including microfracture, osteochondral allograft transplantation (OCA), autologous chondrocyte implantation (ACI), and meniscal allograft transplantation (MAT). The senior author's postoperative protocols will also be presented, as with a discussion on using RTS as a metric of patient and procedural success. Overall, there is significant variation in reported RTS rates among procedures examined, and providers must continue managing patient expectations when discussing treatment options.
ABSTRACT
Surgery is an important treatment for cancer; however, local recurrence following macroscopically-complete resection is common and a significant cause of morbidity and mortality. Systemic chemotherapy is often employed as an adjuvant therapy to prevent recurrence of residual disease, but has limited efficacy due to poor penetration and dose-limiting off-target toxicities. Selective delivery of chemotherapeutics to the surgical bed may eliminate residual tumor cells while avoiding systemic toxicity. While this is challenging for traditional drug delivery technologies, we utilized advances in 3D printing and drug delivery science to engineer a drug-loaded arrowhead array device (AAD) to overcome these challenges. We demonstrated that such a device can be designed, fabricated, and implanted intraoperatively and provide extended release of chemotherapeutics directly to the resection area. Using paclitaxel and cisplatin as model drugs and murine models of cancer, we showed AADs significantly decreased local recurrence post-surgery and improved survival. We further demonstrated the potential for fabricating personalized AADs for intraoperative application in the clinical setting.
Subject(s)
Drug Delivery Systems , Neoplasms , Animals , Mice , Neoplasms/drug therapy , Paclitaxel , Pharmaceutical Preparations , Printing, Three-DimensionalABSTRACT
Focal cartilage defects of the knee are painful and difficult to treat, especially in younger patients1. Seen in up to 60% of patients who undergo knee arthroscopy2, chondral lesions are most common on the patella and medial femoral condyle3. Although the majority of lesions are asymptomatic, a variety of treatment options exist for those that are symptomatic; however, no clear gold-standard treatment has been established. In recent years, osteochondral allograft transplantation has been increasingly utilized because of its versatility and encouraging outcomes4-7. The procedure entails replacing damaged cartilage with a graft of subchondral bone and cartilage from a deceased donor. Indications for this procedure include a symptomatic, full-thickness osteochondral defect typically ≥2 cm2 in size in someone who has failed conservative management. Relative indications include patient age of <40 years and a unipolar defect8,9. Description: Osteochondral allograft transplantation requires meticulous planning, beginning with preoperative radiographs to evaluate the patient's alignment, estimate the lesion size, and aid in matching of a donor femoral condyle. The procedure begins with the patient supine and the knee flexed. A standard arthrotomy incision is performed on the operative side. Once exposure is obtained, a bore is utilized to remove host tissue from the lesion typically to a depth of 5 to 8 mm. Measurements are taken and the donor condyle is appropriately sized to match. A coring reamer is utilized to create the plug from donor tissue, which is trimmed to the corresponding depth. After marrow elements are removed via pulse lavage, the allograft plug is placed within the femoral condyle lesion through minimal force. Alternatives: Nonoperative treatment involves a reduction in high-impact activities and physical therapy. Surgical alternatives include chondroplasty, microfracture, and osteochondral autograft transplantation; however, these options are typically performed for smaller lesions (<2 cm). For larger lesions (≥2 cm), matrix-induced autologous chondrocyte implantation (MACI) can be utilized, but requires 2 surgical procedures. Rationale: Osteochondral allograft transplantation is selected against other procedures for various reasons related to patient goals, preferences, and expectations. Typically, this procedure is favored over microfracture or autograft transplantation when the patient has a large lesion. Allograft transplantation might be favored over MACI because of patient preference for a single surgical procedure instead of 2. Expected Outcomes: To our knowledge, there are currently no Level-I or II trials comparing osteochondral allograft transplantation against other treatments for cartilage defects. There are, however, many systematic reviews of case studies and cohorts that report on outcomes. A 2016 review of 291 patients showed significantly improved patient-reported outcomes at a mean follow-up of 12.3 years5,9. The mean survival of grafts was 94% at 5 years and 84% at 10 years5. Overall, data on long-term survival are lacking because interest in and use of this procedure have only increased over the past few decades10. Finally, the rate of return to sport is promising, with the systematic review by Campbell et al. showing rates as high as 88% with an average time to return to sport of 9.6 months11. Postoperatively, patients can expect to immediately begin passive range of motion. Progression of heel-touch weight-bearing begins at 6 weeks, and patients may return to sport-specific activity after 8 months, as tolerated. Important Tips: Ensure that the allograft is of adequate quality and is size-matched prior to performing the surgical procedure.The cannulated cylinder should be perpendicular to both the host lesion and graft tissue in order to ensure symmetric estimations of size.Save subchondral bone shavings when preparing the host lesion. These can be utilized to take up space if your graft depth is not sufficient to fill the host defect.Utilize saline solution irrigation judiciously when reaming out the host tissue and graft plug. Acronyms & Abbreviations: AAROM = active-assisted range of motionACI = autologous chondrocyte implantationAP = anteroposteriorBMI = body mass indexCPM = continuous passive range of motionGlut/glutes = gluteal musclesHTO = high tibial osteotomyICRS = International Cartilage Repair SocietyLFC = lateral femoral condyleLTP = lateral tibial plateauMACI = matrix-induced autologous chondrocyte implantationMFC = medial femoral condyleMobs = mobilizationMRI = magnetic resonance imagingNSAIDs = non-steroidal anti-inflammatory drugsOAT = osteochondral allograft transplantationPROM = passive range of motionQuad = quadriceps musclesROM = range of motionSLR = straight leg raise.