Concomitant Treatment of High-Grade Cartilage Lesions Mitigates Risk of Meniscal Allograft Transplant Failure.

PURPOSE: To identify frequently studied significant preoperative risk factors for meniscal allograft transplantation (MAT) failure. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were used to conduct this systematic review. The database analysis was performed in May of 2022 and included PubMed, Embrace, and Cochrane. Studies between January 1, 2000, and January 1, 2021, were reviewed with search terms, including "meniscal," "meniscus," "transplantation," "transplant," and "allograft." Twenty-one full-text manuscripts met inclusion criteria of studies assessing preoperative risk factors for MAT failure defined as either clinical failure (Lysholm <65) or surgical failure (revision, removal, or conversion to knee arthroplasty). RESULTS: In total, 21 studies were included, comprising 47.6% with a Level of Evidence of Level III and 52.4% with Level of Evidence IV. The analysis involved 2,533 patients, and the mean final follow-up ranged from 2.2 to 20.0 years. The presence of high-grade cartilage defects was the only factor found predictive of MAT surgical failure in the majority of studies in which it was analyzed (5/7 studies, 71.4%). Four of the five studies that found high-grade cartilage defects to be a predictor of MAT surgical failure did not treat all cartilage lesions, while the 2 studies that found high-grade cartilage defects an insignificant predictor of MAT surgical failure treated all defects at the time of MAT. For clinical failure, no risk factors were predictive of MAT failure in the majority of studies, although smoking and concomitant ligamentous or realignment procedures were significant in 1 study. CONCLUSION: The presence of untreated high-grade cartilage appears to elevate the risk of surgical MAT failure; however, concomitant treatment of defects may mitigate their detrimental effect. There is no clear risk factor that consistently predicts clinical failure. Age, sex, BMI, knee compartment, time from prior meniscectomy, femorotibial alignment (after correction), concomitant cartilage procedure, and laterality do not routinely impact MAT failure. LEVEL OF EVIDENCE: Level IV, systematic review.

Bone Marrow Lesions on Preoperative Magnetic Resonance Imaging Correlate With Outcomes Following Isolated Osteochondral Allograft Transplantation.

PURPOSE: The purpose of this study was to investigate the role of preoperative bone marrow lesion (BML) size and location on (1) postoperative patient reported outcomes and (2) postoperative failure and time to failure after osteochondral allograft (OCA) transplantation. METHODS: Consecutive patients from 2 senior surgeons who underwent isolated OCA transplantation to the knee from 2009-2018 were identified for the case series. Preoperative magnetic resonance imaging (MRI) was evaluated for BMLs based on 2 classification systems (Welsch et al. and Costa-Paz et al.) by 2 independent graders. BMLs associated with minimum 1-year postoperative outcomes were evaluated, and the effect of BML classification on survivorship was investigated with Kaplan-Meier curves. RESULTS: The 77 patients who underwent isolated OCA transplantation (mean follow-up: 39.46 ± 22.67 months) and had preoperative MRIs were included. Within this cohort, 82% of patients demonstrated a BML. The preoperative Costa-Paz et al. classification was significantly positively correlated with the postoperative Visual Analog Scale, International Knee Documentation Committee and Veterans RAND 12-Item Health Survey raw scores for both graders (P < 0.05). Failure occurred in 5 of 65 (8%) patients at a mean of 22.86 ± 12.04 months postoperatively. The presence of BML alone did not significantly affect survival (P = 0.780). However, for 1 grader, the Welsch et al. classification was associated with increased risk of graft failure (P = 0.031). CONCLUSION: Preoperative subchondral BMLs were present in 82% of patients undergoing OCA transplantation. We found that more severe BMLs based on the Costa-Paz classification, with increasing involvement in the juxta-articular surface, were correlated with higher postoperative patient-reported functional outcomes after OCA. BMLs may be associated with an increase in graft failure, but their role in this remains unclear. LEVEL OF EVIDENCE: IV, Retrospective Case Series.

MR Vessel Wall Imaging for Atherosclerosis and Vasculitis.

Conventional imaging modalities, such as computed tomography angiography, MR angiography, transcranial Doppler ultrasonography, and digital subtraction angiography, are utilized in evaluating intraluminal or intravascular pathology of the intracranial vessels. Limitations of luminal imaging techniques can lead to inaccurate diagnosis, evaluation, and risk stratification, as many cerebrovascular pathologies contain an extrinsic vessel wall component. Furthermore, vessel wall imaging can provide information regarding extent, treatment response, and biopsy targets for vasculitis cases. Overall, while vessel wall imaging can provide robust data regarding intracranial pathologies, further prospective, multicenter studies are required to improve diagnostic application and accuracy.

Outcomes of Patellar Subchondroplasty Surgery: A Case Series.

A select subset of patients can present with anterior knee pain in the setting of normal patellar tracking, no significant cartilage damage, and the presence of a bone marrow lesion (BML) involving the patella on advanced imaging. One novel treatment option for this condition is patellar subchondroplasty, where calcium phosphate is injected into the subchondral bone under fluoroscopic guidance. The purpose of this study is to report preliminary outcomes of patients who have undergone subchondroplasty of the patella. The surgical log of the senior author was retrospectively reviewed to identify patients who had undergone patellar subchondroplasty from January 2014 to June 2019. Indications for surgery included the presence of retropatellar pain refractory to conservative management without significant arthritis with a related focal BML on magnetic resonance imaging. International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score (KOOS), and Veterans Rand 12-item Health Survey (VR-12) were obtained preoperatively, at 6 months and at final follow-up. Eight patients (nine knees) who underwent patellar subchondroplasty with minimum 1-year follow-up participated in the study. On preoperative magnetic resonance imaging, patients had a mean BML that was 2 cm in diameter. Patients had a median Kellgren-Lawrence grade of 2 both preoperatively and at final radiographic follow-up (15.50 ± 20.52 months). No patient underwent subsequent surgery or conversion to arthroplasty. Compared with baseline, VR-12 mental (p = 0.046) and physical (p = 0.003), KOOS joint replacement (p = 0.024), KOOS pain (p = 0.033), and KOOS sports (p = 0.034) scores were significantly increased at final follow-up (24.00 ± 13.55 months). In addition, on a scale of 0 to 100, patient-reported satisfaction was 73.88 ± 33.90. This study introduces patellar subchondroplasty as a surgical treatment for patients with symptomatic BMLs of the patella without significant arthritis after failure of conservative management. Our results demonstrated good outcomes and patient satisfaction. In addition, no patients converted to patellofemoral or total knee arthroplasty. This study suggests that patellar subchondroplasty may be a reasonable treatment option in the correct patient population.

The Minimal Clinically Important Difference, Substantial Clinical Benefit, and Patient-Acceptable Symptomatic State after Medial Patellofemoral Ligament Reconstruction.

Purpose: To define the minimal clinically important difference (MCID), substantial clinical benefit (SCB) and patient-acceptable symptomatic state (PASS) for patient-reported outcome measures (PROMs) after medial patellofemoral ligament reconstruction (MPFLR) and to investigate the role of preoperative, demographic, and intraoperative variables for predicting achievement of these thresholds. Methods: This retrospective cohort study used a prospectively maintained database of patients undergoing primary MPFLR between August 2015 and December 2019. PROMs included the International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS joint replacement (JR), and Kujala. Anchor-based and distribution-based methods were used to calculate the MCID, SCB, and PASS. Regression analyses were performed to identify prognosticators for achievement of clinically significant thresholds. Results: 139 patients met inclusion criteria (mean age: 21.7± 8.2 years). At 6 months, the MCID values were 8.3 (KOOS-Pain) and 8.5/13.5 (Kujala); SCB values were 1.4 (KOOS-Pain) and 43.7 (KOOS-QOL); and PASS values were 64.9 (IKDC), 83.3 (KOOS-Symptom), 76.8 (KOOS-Pain), 91.2 (KOOS-ADL), 47.5 (KOOS-Sport), 40.6 (KOOS-QOL), and 78.1 (KOOS-JR). At 1 year, the MCID values were 4.2 (KOOS-Pain), 7.2 (KOOS-ADL), 12.4 (KOOS-QOL) and 25.2 (KOOS-JR); SCB were 23.6 (IKDC), 4.2 (KOOS-Symptom), 19.7 (KOOS-Pain), 6.5 (KOOS-ADL), 55.0 (KOOS-Sport), 6.3 (KOOS-QOL), and 19.6/25.2 (KOOS-JR); and PASS were 65.5 (IKDC), 80.4 (KOOS-Symptom), 84.7 (KOOS-Pain), 99.3 (KOOS-ADL), 57.5 (KOOS-Sport), 53.1 (KOOS-QOL), and 76.3 (KOOS-JR). In regression analysis, greater age, body mass index, and preoperative PROMs were negative prognosticators for achieving clinically significant thresholds. Conversely, male gender increased the likelihood of achieving PASS for Kujala at 6 months and KOOS-ADL at 1 year. Conclusions: This study established thresholds for the MCID, SCB, and PASS at 6 months and 1 year after MPFLR, providing physicians an evidence-based method to advise patients and assess outcomes with this surgery. Older patients and those with higher preoperative outcome scores are less likely to report improvement and satisfaction with MPFLR, while male patients are more likely to report some satisfaction. Level of Evidence: Level III, retrospective cohort study (diagnosis).

Time to Achieving Clinically Significant Outcomes After Meniscal Allograft Transplantation.

PURPOSE: To determine the time to achieving minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) for commonly administered patient-reported outcome (PRO) measures and risk factors affecting achievement of clinically significant outcomes in patients undergoing meniscal allograft transplantation (MAT). METHODS: A prospectively maintained MAT registry was retrospectively reviewed from April 2014 to May 2019. Patients who underwent revision MAT or did not complete preoperative PROs or one post operative time point were excluded. Patients who underwent concomitant procedures were included in the analysis. PROs were administered preoperatively and at 6 months, 1 year, and 2 years postoperatively. Previously defined MCID and PASS thresholds were utilized and Kaplan-Meier survival curve analysis with interval censoring was used to calculate the cumulative percentages of MCID and PASS achievement at each follow-up time interval (5-7, 11-13, and 23-25 months). RESULTS: Eighty patients (age: 28.35 ± 9.76, 50% male) who completed preoperative, 6-month (n = 69, 86% compliance), and 1-year (n = 76, 95% compliance) PROs were included. The majority of patients (>50%) achieved MCID and PASS on most included PROs. Workers' compensation status was found to significantly delay achievement of MCID and PASS on all PROs except for PASS on Knee Injury and Osteoarthritis Outcome Score (KOOS) quality of life (QoL). Higher body mass index (BMI) significantly delayed time to achieving MCID on KOOS Pain and activities of daily living (ADL), as well as PASS on KOOS Symptoms and KOOS QoL. CONCLUSION: This study suggests that the majority of patients have clinically significant improvements in pain and function after MAT, with more than 50% of patients experiencing clinically significant improvement within the first postoperative year. Workers' compensation status and high BMI may prolong time to achievement of MCID and PASS after MAT.

Differential Spatio-Temporal Regulation of T-Box Gene Expression by microRNAs during Cardiac Development.

Cardiovascular development is a complex process that starts with the formation of symmetrically located precardiac mesodermal precursors soon after gastrulation and is completed with the formation of a four-chambered heart with distinct inlet and outlet connections. Multiple transcriptional inputs are required to provide adequate regional identity to the forming atrial and ventricular chambers as well as their flanking regions; i.e., inflow tract, atrioventricular canal, and outflow tract. In this context, regional chamber identity is widely governed by regional activation of distinct T-box family members. Over the last decade, novel layers of gene regulatory mechanisms have been discovered with the identification of non-coding RNAs. microRNAs represent the most well-studied subcategory among short non-coding RNAs. In this study, we sought to investigate the functional role of distinct microRNAs that are predicted to target T-box family members. Our data demonstrated a highly dynamic expression of distinct microRNAs and T-box family members during cardiogenesis, revealing a relatively large subset of complementary and similar microRNA-mRNA expression profiles. Over-expression analyses demonstrated that a given microRNA can distinctly regulate the same T-box family member in distinct cardiac regions and within distinct temporal frameworks, supporting the notion of indirect regulatory mechanisms, and dual luciferase assays on Tbx2, Tbx3 and Tbx5 3' UTR further supported this notion. Overall, our data demonstrated a highly dynamic microRNA and T-box family members expression during cardiogenesis and supported the notion that such microRNAs indirectly regulate the T-box family members in a tissue- and time-dependent manner.