Scaffold- and graft-based biological augmentation of rotator cuff repair: an updated systematic review and meta-analysis of preclinical and clinical studies for 2010-2022.

BACKGROUND: Despite advancements in the surgical techniques of rotator cuff repair (RCR), there remains a high retear rate. Biological augmentation of repairs with overlaying grafts and scaffolds may enhance healing and strengthen the repair construct. This study aimed to investigate the efficacy and safety of scaffold-based (nonstructural) and overlay graft-based (structural) biological augmentation in RCR (excluding superior capsule reconstruction and bridging techniques) in both preclinical and clinical studies. METHODS: This systematic review was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, as well as guidelines outlined by The Cochrane Collaboration. A search of the PubMed, Embase, and Cochrane Library databases from 2010 until 2022 was conducted to identify studies reporting the clinical, functional, and/or patient-reported outcomes of ≥1 biological augmentation method in either animal models or humans. The methodologic quality of included primary studies was appraised using the Checklist to Evaluate a Report of a Non-pharmacological Trial (CLEAR-NPT) for randomized controlled trials and using the Methodological Index for Non-randomized Studies (MINORS) for nonrandomized studies. RESULTS: A total of 62 studies (Level I-IV evidence) were included, comprising 47 studies reporting outcomes in animal models and 15 clinical studies. Of the 47 animal-model studies, 41 (87.2%) demonstrated biomechanical and histologic enhancement with improved RCR load to failure, stiffness, and strength. Of the 15 clinical studies, 10 (66.7%) illustrated improvement in postoperative clinical, functional, and patient-reported outcomes (eg, retear rate, radiographic thickness and footprint, and patient functional scores). No study reported a significant detriment to repair with augmentation, and all studies endorsed low complication rates. A meta-analysis of pooled retear rates demonstrated significantly lower odds of retear after treatment with biological augmentation of RCR compared with treatment with non-augmented RCR (odds ratio, 0.28; P < .00001), with low heterogeneity (I2 = 0.11). CONCLUSIONS: Graft and scaffold augmentations have shown favorable results in both preclinical and clinical studies. Of the investigated clinical grafts and scaffolds, acellular human dermal allograft and bovine collagen demonstrate the most promising preliminary evidence in the graft and scaffold categories, respectively. With a low risk of bias, meta-analysis revealed that biological augmentation significantly lowered the odds of retear. Although further investigation is warranted, these findings suggest graft and scaffold biological augmentation of RCR to be safe.

Local Intraoperative Marrow-Derived Augmentation for Primary Rotator Cuff Repair: An Updated Systematic Review and Meta-analysis of Studies From 2010 to 2022.

Background: Recurrent tears of the rotator cuff pose a substantial problem despite advances in repair technique. Biologic augmentation via marrow stimulation or vented anchors may strengthen the suture-tendon junction and improve healing rates of native tissue, thereby enhancing outcomes of primary surgical repair. Purpose: To provide a focused systematic review and meta-analysis of local, intraoperative marrow-derived augmentation techniques in clinical primary rotator cuff repair. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of PubMed, Embase, and Cochrane was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 2131 studies from 2010 to 2022, focused on either marrow stimulation or vented anchors, were isolated and classified as either preclinical or clinical. Meta-analysis was performed for comparative marrow stimulation and vented anchor studies. Heterogeneity was tested through calculation of I 2. Results: A total of 13 clinical studies were included in the review. All 9 comparative studies included in the meta-analysis demonstrated high methodologic quality or a low risk of bias. The pooled retear rate across all 9 clinical studies for patients undergoing marrow stimulation was 11%. For the 5 studies in the meta-analysis, the pooled retear rates were 15% for marrow stimulation and 30% for controls. Meta-analysis demonstrated a significant difference in the overall retear rate that favored marrow stimulation (odds ratio [OR], 0.41; 95% CI, 0.25-0.66; P = .0003; I 2 = 0%). Similarly, meta-analysis of the Constant score at final follow-up demonstrated a statistically significant difference between the 2 groups that favored a higher Constant score in the marrow stimulation group (mean difference, 2.84; 95% CI, 1.02-4.66; P = .002; I 2 = 29%). Vented anchors demonstrated improved ossification and bone density at the anchor site, but no difference in outcomes or retear. Pooled retear rates were 22.5% for vented anchors and 27.8% for controls. Conclusion: Current evidence demonstrates that marrow-stimulation techniques may have a positive impact on healing and retear rate, while vented anchors have a muted impact relative to nonvented anchors. Although available evidence is limited and more research is needed, findings to date suggest that marrow stimulation techniques may be an inexpensive, straightforward technique to consider in qualifying patients to prevent rotator cuff retears.

An Automated Bioinformatics Pipeline Informing Near-Real-Time Public Health Responses to New HIV Diagnoses in a Statewide HIV Epidemic.

Molecular HIV cluster data can guide public health responses towards ending the HIV epidemic. Currently, real-time data integration, analysis, and interpretation are challenging, leading to a delayed public health response. We present a comprehensive methodology for addressing these challenges through data integration, analysis, and reporting. We integrated heterogeneous data sources across systems and developed an open-source, automatic bioinformatics pipeline that provides molecular HIV cluster data to inform public health responses to new statewide HIV-1 diagnoses, overcoming data management, computational, and analytical challenges. We demonstrate implementation of this pipeline in a statewide HIV epidemic and use it to compare the impact of specific phylogenetic and distance-only methods and datasets on molecular HIV cluster analyses. The pipeline was applied to 18 monthly datasets generated between January 2020 and June 2022 in Rhode Island, USA, that provide statewide molecular HIV data to support routine public health case management by a multi-disciplinary team. The resulting cluster analyses and near-real-time reporting guided public health actions in 37 phylogenetically clustered cases out of 57 new HIV-1 diagnoses. Of the 37, only 21 (57%) clustered by distance-only methods. Through a unique academic-public health partnership, an automated open-source pipeline was developed and applied to prospective, routine analysis of statewide molecular HIV data in near-real-time. This collaboration informed public health actions to optimize disruption of HIV transmission.

Evidence for Utilization of Injectable Biologic Augmentation in Primary Rotator Cuff Repair: A Systematic Review of Data From 2010 to 2022.

Background: Biologic healing after rotator cuff repair remains a significant challenge. Injectable biologic augmentation may improve tissue quality at the suture-tendon interface. Purpose: To investigate the effect of injectable biologic supplementation in rotator cuff repair and to assess the quality and adherence to evolving reporting standards. Study Design: Systematic review; Level of evidence, 3. Methods: A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included were 40 studies: 29 preclinical (in vivo animal models) and 11 clinical. Each clinical study was assessed for quality, risk of bias, and adherence to relevant MIBO (Minimum Information for Studies Evaluating Biologics in Orthopaedics) guidelines. The outcomes of interest were reported load to failure, load to gap, gap size, and stiffness in the preclinical studies, and healing rate and any patient-reported outcome measures in the clinical studies. Results: Injectables reported included growth factors (eg, transforming growth factor-beta 3, erythropoietin), bone marrow-derived mesenchymal stem cells and adipose-derived mesenchymal stem cells (ADSCs), and other agents such as platelet-rich plasma (PRP) and hyaluronic acid. The most common findings for preclinical injectables were increased load to failure (16/29 studies; 55.2%) and improved collagen histological quality (11/29 studies; 37.9%). All 11 clinical studies (10 PRP, 1 ADSC) indicated no adverse events, with similar or improved patient-reported outcomes compared with repairs in the control groups. In 1 study utilizing an innovative delivery technique, a concentrated PRP globule with fibrin matrix was shuttled over a suture to maintain concentrated PRP at the repair site and demonstrated a significant decrease in retears (P = .03) at a 31-month follow-up. A matched-cohort study investigating augmentation with ADSCs demonstrated a significantly lower retear rate in the ADSC-augmented group than the control group at a 28-month follow-up (P < .001). On average, the clinical studies adhered to 66% of relevant MIBO reporting guidelines and had a low risk of bias. Conclusion: Approximately 83% of preclinical studies found a positive biomechanical or histological effect, with no studies showing an overall negative effect. Clinically, utilization of innovative delivery techniques may reduce the risk of arthroscopic washout of PRP and improve retear rates. ADSCs were shown to reduce retear rates at a 28-month follow-up.

Not all clusters are equal: dynamics of molecular HIV-1 clusters in a statewide Rhode Island epidemic.

OBJECTIVES: Molecular epidemiology is a powerful tool to characterize HIV epidemics and prioritize public health interventions. Typically, HIV clusters are assumed to have uniform patterns over time. We hypothesized that assessment of cluster evolution would reveal distinct cluster behavior, possibly improving molecular epidemic characterization, towards disrupting HIV transmission. DESIGN: Retrospective cohort. METHODS: Annual phylogenies were inferred by cumulative aggregation of all available HIV-1 pol sequences of individuals with HIV-1 in Rhode Island (RI) between 1990 and 2020, representing a statewide epidemic. Molecular clusters were detected in annual phylogenies by strict and relaxed cluster definition criteria, and the impact of annual newly-diagnosed HIV-1 cases to the structure of individual clusters was examined over time. RESULTS: Of 2153 individuals, 31% (strict criteria) - 47% (relaxed criteria) clustered. Longitudinal tracking of individual clusters identified three cluster types: normal, semi-normal and abnormal. Normal clusters (83-87% of all identified clusters) showed predicted growing/plateauing dynamics, with approximately three-fold higher growth rates in large (15-18%) vs. small (∼5%) clusters. Semi-normal clusters (1-2% of all clusters) temporarily fluctuated in size and composition. Abnormal clusters (11-16% of all clusters) demonstrated collapses and re-arrangements over time. Borderline values of cluster-defining parameters explained dynamics of non-normal clusters. CONCLUSIONS: Comprehensive tracing of molecular HIV clusters over time in a statewide epidemic identified distinct cluster types, likely missed in cross-sectional analyses, demonstrating that not all clusters are equal. This knowledge challenges current perceptions of consistent cluster behavior over time and could improve molecular surveillance of local HIV epidemics to better inform public health strategies.

A novel comorbidity risk score for predicting postoperative 30-day complications in total shoulder arthroplasty and elucidation of potential racial disparities.

Background: Efficient and effective preoperative identification of those patients with elevated risk may allow for more cost-effective interventions, accurate bundled payment adjustments, and overall improved patient care. Few comorbidity indices have provided clinical utility and adequate discriminative ability in the setting of complications after shoulder arthroplasty (SA). Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for anatomic and/or reverse SA procedures between 2010 and 2019. A subset of comorbidities were utilized including end-stage renal disease, history of hypertension, chronic obstructive pulmonary disease, functional status, history of bleeding disorder, and disseminated cancer. Results: A total of 25,927 patients with an average age of 69.2 (standard deviation ±9.5) years were included in the study. Patients with a comorbidity risk score (CRS) at or above 2 were indicated to have at least a 29.6% 30-day postoperative complication rate after undergoing total shoulder arthroplasty, significantly higher than the described average of approximately 15%. The area under receiver operator curve for the novel CRS scoring system was 0.595, indicating fair discriminative ability to predict 30-day postoperative complications after SA. This illustrates a discriminative ability similar to that of the American Society of Anesthesiologists classification (0.584, confidence interval [CI] 0.578-0.589), modified Charlson Comorbidity Index (0.567, CI 0.561-0.573), and modified Frailty Index (0.534, CI 0.529-0.539), each of which are common comorbidity indices used for the National Surgical Quality Improvement Program database. The average CRS for the population was 0.8537 (CI 0.8011-0.8150; P < .05) while that for the Black demographic was 1.08 (CI 1.03-1.13; P < .001). Our results suggest that if the disparity in CRS among races was corrected, the average complication rate would be decreased by 2.0%. Discussion and Conclusion: A higher CRS score resulted in higher rates of 30-day postoperative complications following SA. Black patients had a higher average CRS than all other races illustrating a racial disparity in comorbidity risk. Although the average complication rate of each race would still be unequal, this could mitigate some of the racial disparities observed and decrease the overall 30-day complication rate in SA. With the rise of bundled payments further increasing the need to preoperatively identify patients at high risk for costly complications, the CRS is based on easily identified, relevant comorbidities that may be an advantageous tool to identify patients at increased risk of complications following SA.

Prevalence and Clinical Impact of Incidental Findings on Preoperative 3D Planning Computed Tomography for Total Shoulder Arthroplasty.

INTRODUCTION: 3D planning software for shoulder arthroplasty recently emerged for aiding in intraoperative determination of native glenoid. These protocols often require increased scan resolution, however, raising the question of an increased prevalence and clinical impact of incidental findings (IFs) from preoperative imaging. METHODS: A retrospective review of preoperative shoulder CT reports was conducted for 333 consecutive patients planning anatomic or reverse total shoulder arthroplasties. Patients with thin-sliced CT scans (1.25 mm) were compared with those with standard CT scans (2.5 mm). Poisson regression was performed with baseline characteristics and potentially pathologic IFs (PPIFs). RESULTS: IFs were present in 131 of the 333 scans (39.3%), and 38 of the 333 scans (11.4%) included PPIFs. Only 8 of the 333 scans (2.4%) required workup, with 2 of the 333 (0.6%) leading to new cancer diagnoses. Thin-sliced CT scans detected a higher mean number of IFs (1.12 versus 0.22, P < 0.001) while the mean number of PPIFs remained similar (0.13 versus 0.10, P = 0.43). CONCLUSION: IFs are frequent; however, only 0.6% scans led to new cancer diagnoses. Comparison of thin-sliced with standard CT scans revealed a higher frequency of IFs but similar PPIFs, indicating increased burden of IFs without the benefit of identifying additional malignancies. As demand rises for shoulder arthroplasties, surgeons should consider the potential hidden costs of IFs when using 3D planning programs.

Acute Proximal Hamstring Tears Can be Defined Using an Imaged-Based Classification.

Purpose: To develop a clinically meaningful proximal hamstring tear classification system and to present outcome data for defined subtypes. Methods: Retrospective review was undertaken of patients diagnosed with proximal hamstring tears at a single institution from 2012 to 2019. Images were reviewed by an orthopedic surgeon and musculoskeletal radiologist. Tears were classified as Type 1: partial with subtypes (1A, 1 cm or mild complete tear; 1B, 1-2 cm or full tear with <2 cm retraction), Type 2: complete single-tendon tears with subtypes (2c conjoint tendon only; 2s semimembranosus tendon only); or Type 3: complete tears with >2 cm retraction. Demographics, patient-reported outcome measures including Hip Outcome Score, Activities of Daily Living Subscore (HOS-ADL) and patient satisfaction were evaluated. A poor outcome was defined as HOS-ADL < 80%, and the patient acceptable symptom state (PASS) was defined as HOS-ADL 89.7%. Results: At a mean follow-up of 38.6 (range: 12-94) months for 114 patients, distributions were as follows: 18.4% Type 1A, 19.2% Type 1B, 7.8% Type 2c, 3.5% Type 2s, and 50.9% Type 3. Intra-observer and inter-observer reliability had a mean Kappa of 0.985 (95% CI: .956, 1.01) and .905 (95% CI: .895 .915). 66 patients underwent surgery, with 68.97% of them being Type 3. The mean HOS-ADL and PASS rate were higher for operatively treated patients (95%, 93.4%) than for nonoperatively treated patients (81.86%, 44.7%). There were significantly more patients satisfied in the surgery group in both Type 1 and Type 3 tears (P = .046 and P = .049). Body mass index was a significant predictor of a poor outcome in Type 3 tears (P = .039). History of corticosteroid or PRP injection, smoking, and diabetes were not significant predictors of a poor outcome. Conclusion: We present an MRI-based classification system for proximal hamstring injuries with both excellent intra-observer and inter-observer reliability. Outcome measures were improved in patients who underwent surgery. Level of Evidence: IV, cohort study: diagnostic case series.

A validated algorithm using current literature to judge the appropriateness of anatomic total shoulder arthroplasty utilizing the RAND/UCLA appropriateness method.

BACKGROUND: Currently, appropriateness criteria evaluating when to perform total shoulder arthroplasty (TSA) is lacking. In the absence of society guidelines and limited quality evidence, the RAND/University California in Los Angeles (UCLA) method provides a suitable alternative to evaluate appropriateness and assist in clinical decision making. Given the rise in utilization, appropriateness criteria for TSA have the potential to be an extremely powerful tool for improving quality of care and controlling costs. Thus, the goal of this study was to test explicit criteria to assess the appropriateness of TSA decision making using the RAND/UCLA appropriateness method. METHODS: A review of recent scientific literature to gather available evidence about the use, effectiveness, efficiency, and the risks involved in surgical intervention was performed by a shoulder/elbow fellowship trained physician. Based on pertinent variables including age, rotator cuff status, previous surgical management, mobility, symptomatology, and imaging classifications, 186 clinical scenarios were created. Appropriateness criteria for TSA were developed using a modified Delphi method with a panel consisting of American Shoulder and Elbow Surgeons (ASES) members. A second panel of ASES members rated the same scenarios, with reliability testing performed to compare groups. RESULTS: Panel members reached agreement in 40 (64%) indications. TSA was appropriate in 15 (24%) of indications. For patients with severe symptomatology, TSA was often appropriate for patients aged <75 years and inconclusive or inappropriate for patients aged >75 years. Among patients aged <65 years, TSA varied between appropriate and inconclusive, often dependent on Walch classification. For patients with moderate symptomatology, TSA was inappropriate or inconclusive for patients aged <65 or >75 years. When compared to the second panel's results, moderate agreement was obtained with a weighted kappa statistic of 0.56. CONCLUSIONS: Using the RAND/UCLA method, ASES members created an appropriateness decision tree for pertinent patient variables. This presents the data in a manner that streamlines the clinical decision-making process and allows for rapid and more reliable determination of appropriateness for practitioners. The decision tree is based on a combination of clinical experience from high-volume ASES-member surgeons and a comprehensive review of current evidence. This tool can be used as part of a broader set of factors, including individual patient characteristics, prior studies, and expert opinion, to inform clinical decision making, improve quality of care, and control costs.

Investigating a Potential Limit to Access to Care: Preoperative Cutoff Values for Body Mass Index for Shoulder Arthroplasty.

INTRODUCTION: The primary purpose of this study was to determine the number of patients who would be denied a complication-free total shoulder arthroplasty (TSA) based on implementation of body mass index (BMI) eligibility cutoffs. METHODS: The National Surgical Quality Improvement Program database was queried to identify all patients who underwent primary TSA. Patient demographics and 30-day postoperative complications were compared according to BMI stratification using the Pearson chi-square test and binary logistic regression analysis adjusted for age and modified Charlson comorbidity index. A BMI eligibility criterion of ≥40 kg/m2 was used to calculate the positive predictive value (PPV) to assess the number of complication-free TSAs that would be denied to avoid a complication in a single patient. RESULTS: A total of 23,284 patients who underwent TSA met inclusion criteria. The overall complication rate was 7.2%. Using a BMI cutoff of ≥40 kg/m2 would yield a PPV of 7% for all Major Complications. This means that 14 complication-free procedures would be denied to avoid a Major Complication. In addition, BMI ≥40 kg/m2 served as an independent risk factor for acute renal failure, pulmonary embolism, ventilator use >48 hours, and readmission. The PPV for these clinically significant complications using BMI ≥40 kg/m2 as a cutoff was 4.9%. This translates into 20 patients being denied a complication-free procedure to avoid a single clinically significant medical complication. If this policy was enforced on the 2,426 patients who exceeded BMI ≥40 kg/m2 in this study, nearly 2,307 patients would be denied the potential benefit of surgery to prevent 119 complications. CONCLUSION: The use of eligibility criteria for primary TSA or RSA based solely on BMI threshold values presents a potential limitation in access to care to these patients who otherwise would have a complication-free procedure. LEVEL OF EVIDENCE: Level III, prognostic, retrospective cohort study.

Surgical Technique for Superior Capsule Reconstruction With 6-mm Acellular Dermal Allograft and Knotless Glenoid Anchors.

Superior capsule reconstruction (SCR) creates a humeral head depressor in the setting of a massive, irreparable rotator cuff tear. Recently, a 6-mm-thick acellular dermal allograft (ACD) has been shown to be noninferior to the standard fascia lata autograft in recreating native shoulder biomechanics. This paper outlines a reproducible means by which to perform an arthroscopic SCR using a 6-mm ACD. A standard diagnostic arthroscopy first assesses the integrity of the subscapularis and infraspinatus tendons. The glenoid anchors are then placed. Accessory anterior and posterolateral portals are made as well as a lateral portal by which to shuttle the graft. Suture management is paramount. Ideally allograft preparation occurs on the back table simultaneously to maintain efficiency. Suture passage through premade holes in the graft, and when the sutures have passed through and been tensioned, the graft is shuttled into place and tied down with medial and lateral row anchors in SpeedBridge fashion. The thickness of ACD has been shown to influence the ability of the reconstructed superior capsule to perform its role as a humeral head depressor. This technique describes the use of a 6-mm-thick ACD to perform an arthroscopic SCR that minimizes both donor-site morbidity and operative time.