High-resolution profiling of pathways of escape for SARS-CoV-2 spike-binding antibodies.

Defining long-term protective immunity to SARS-CoV-2 is one of the most pressing questions of our time and will require a detailed understanding of potential ways this virus can evolve to escape immune protection. Immune protection will most likely be mediated by antibodies that bind to the viral entry protein, spike (S). Here, we used Phage-DMS, an approach that comprehensively interrogates the effect of all possible mutations on binding to a protein of interest, to define the profile of antibody escape to the SARS-CoV-2 S protein using coronavirus disease 2019 (COVID-19) convalescent plasma. Antibody binding was common in two regions, the fusion peptide and the linker region upstream of the heptad repeat region 2. However, escape mutations were variable within these immunodominant regions. There was also individual variation in less commonly targeted epitopes. This study provides a granular view of potential antibody escape pathways and suggests there will be individual variation in antibody-mediated virus evolution.

Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex.

Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of the Lassa virus's glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we used pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affected cell entry and antibody neutralization. Our experiments defined functional constraints throughout GPC. We quantified how GPC mutations affected neutralization with a panel of monoclonal antibodies. All antibodies tested were escaped by mutations that existed among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid the design of therapeutics and vaccines.

Many-core algorithms for high-dimensional gradients on phylogenetic trees.

MOTIVATION: Advancements in high-throughput genomic sequencing are delivering genomic pathogen data at an unprecedented rate, positioning statistical phylogenetics as a critical tool to monitor infectious diseases globally. This rapid growth spurs the need for efficient inference techniques, such as Hamiltonian Monte Carlo (HMC) in a Bayesian framework, to estimate parameters of these phylogenetic models where the dimensions of the parameters increase with the number of sequences N. HMC requires repeated calculation of the gradient of the data log-likelihood with respect to (wrt) all branch-length-specific (BLS) parameters that traditionally takes O(N2) operations using the standard pruning algorithm. A recent study proposes an approach to calculate this gradient in O(N), enabling researchers to take advantage of gradient-based samplers such as HMC. The CPU implementation of this approach makes the calculation of the gradient computationally tractable for nucleotide-based models but falls short in performance for larger state-space size models, such as Markov-modulated and codon models. Here, we describe novel massively parallel algorithms to calculate the gradient of the log-likelihood wrt all BLS parameters that take advantage of graphics processing units (GPUs) and result in many fold higher speedups over previous CPU implementations. RESULTS: We benchmark these GPU algorithms on three computing systems using three evolutionary inference examples exploring complete genomes from 997 dengue viruses, 62 carnivore mitochondria and 49 yeasts, and observe a >128-fold speedup over the CPU implementation for codon-based models and >8-fold speedup for nucleotide-based models. As a practical demonstration, we also estimate the timing of the first introduction of West Nile virus into the continental Unites States under a codon model with a relaxed molecular clock from 104 full viral genomes, an inference task previously intractable. AVAILABILITY AND IMPLEMENTATION: We provide an implementation of our GPU algorithms in BEAGLE v4.0.0 (https://github.com/beagle-dev/beagle-lib), an open-source library for statistical phylogenetics that enables parallel calculations on multi-core CPUs and GPUs. We employ a BEAGLE-implementation using the Bayesian phylogenetics framework BEAST (https://github.com/beast-dev/beast-mcmc).

Using viral sequence diversity to estimate time of HIV infection in infants.

Age at HIV acquisition may influence viral pathogenesis in infants, and yet infection timing (i.e. date of infection) is not always known. Adult studies have estimated infection timing using rates of HIV RNA diversification, however, it is unknown whether adult-trained models can provide accurate predictions when used for infants due to possible differences in viral dynamics. While rates of viral diversification have been well defined for adults, there are limited data characterizing these dynamics for infants. Here, we performed Illumina sequencing of gag and pol using longitudinal plasma samples from 22 Kenyan infants with well-characterized infection timing. We used these data to characterize viral diversity changes over time by designing an infant-trained Bayesian hierarchical regression model that predicts time since infection using viral diversity. We show that diversity accumulates with time for most infants (median rate within pol = 0.00079 diversity/month), and diversity accumulates much faster than in adults (compare previously-reported adult rate within pol = 0.00024 diversity/month [1]). We find that the infant rate of viral diversification varies by individual, gene region, and relative timing of infection, but not by set-point viral load or rate of CD4+ T cell decline. We compare the predictive performance of this infant-trained Bayesian hierarchical regression model with simple linear regression models trained using the same infant data, as well as existing adult-trained models [1]. Using an independent dataset from an additional 15 infants with frequent HIV testing to define infection timing, we demonstrate that infant-trained models more accurately estimate time since infection than existing adult-trained models. This work will be useful for timing HIV acquisition for infants with unknown infection timing and for refining our understanding of how viral diversity accumulates in infants, both of which may have broad implications for the future development of infant-specific therapeutic and preventive interventions.

phippery: a software suite for PhIP-Seq data analysis.

SUMMARY: We present the phippery software suite for analyzing data from phage display methods that use immunoprecipitation and deep sequencing to capture antibody binding to peptides, often referred to as PhIP-Seq. It has three main components that can be used separately or in conjunction: (i) a Nextflow pipeline, phip-flow, to process raw sequencing data into a compact, multidimensional dataset format and allows for end-to-end automation of reproducible workflows. (ii) a Python API, phippery, which provides interfaces for tasks such as count normalization, enrichment calculation, multidimensional scaling, and more, and (iii) a Streamlit application, phip-viz, as an interactive interface for visualizing the data as a heatmap in a flexible manner. AVAILABILITY AND IMPLEMENTATION: All software packages are publicly available under the MIT License. The phip-flow pipeline: https://github.com/matsengrp/phip-flow. The phippery library: https://github.com/matsengrp/phippery. The phip-viz Streamlit application: https://github.com/matsengrp/phip-viz.

Managing rotator cuff tear arthropathy: a role for cuff tear arthropathy hemiarthroplasty as well as reverse total shoulder arthroplasty.

BACKGROUND: Disabling cuff tear arthropathy (CTA) is commonly managed with reverse shoulder arthroplasty (RSA). However, for patients with CTA having preserved active elevation, cuff tear arthropathy hemiarthroplasty (CTAH) may offer a cost-effective alternative that avoids the complications unique to RSA. We sought to determine the characteristics and outcomes of a series of patients with CTA managed with these procedures. MATERIALS AND METHODS: We retrospectively reviewed 103 patients with CTA treated with shoulder arthroplasty, the type of which was determined by the patient's ability to actively elevate the arm. Outcome measures included the change in the Simple Shoulder Test (SST), the percent maximum improvement in SST (%MPI), and the percentage of patients exceeding the minimal clinically important difference for the change in SST and %MPI. Postoperative x-rays were evaluated to assess the positions of the center of rotation and the greater tuberosity for each implant. RESULTS: Forty-four percent of the 103 patients were managed with CTAH while 56% were managed with RSA. Both arthroplasties resulted in clinically significant improvement. Patients having RSA improved from a mean preoperative SST score of 1.7 (interquartile range [IQR], 0.0-3.0) to a postoperative score of 6.3 (IQR, 2.3-10.0) (P < .01). Patients having CTAH improved from a preoperative SST score of 3.1 (IQR, 1.0-4.0) to a postoperative score of 7.6 (IQR, 5.0-10.) (P < .001). These improvements exceeded the minimal clinically important difference. Instability accounted for most of the RSA complications; however, it did not account for any CTAH complications. The postoperative position of the center of rotation and greater tuberosity on anteroposterior radiographs did not correlate with the clinical outcomes for either procedure. CONCLUSION: For 103 patients with CTA, clinically significant improvement was achieved with appropriately indicated CTAH and RSA. In view of the lower cost of the CTAH implant, it may provide a cost-effective alternative to RSA for patients with retained active elevation.

Anatomic total shoulder arthroplasty for posteriorly eccentric and concentric osteoarthritis: a comparison at minimum 5-year follow-up.

BACKGROUND: In patients with glenohumeral osteoarthritis and posteriorly eccentric wear patterns, the early to mid-term results of TSA using conservative glenoid reaming with no attempt at version correction have been favorable at early follow-up. The purpose of this study is to compare the clinical and radiographic outcomes of TSA using this technique for patients with and without eccentric wear patterns at a minimum 5-year follow-up. METHODS: Patients who underwent TSA with minimum 5-year follow-up were identified from an institutional registry. Preoperative and postoperative radiographs were used to determine humeroglenoid alignment (HGA-AP), humeroscapular alignment (HSA-AP), version, Walch classification and glenoid component seating. The outcome measures were the Simple Shoulder Test, glenoid component radiolucencies, and the occurrence of complications or revisions. RESULTS: Two hundred and ten patients were included in the study, of which 98 (47%) had posteriorly decentered humeral heads and 108 (51%) had centered humeral heads. There were 77 shoulders with Walch type A glenoids and 122 with Walch type B glenoids. At a mean 8-year follow-up, the final SST, change in SST and percentage of maximal improvement was not correlated with pre- and postoperative humeral head centering, Walch classification or glenoid version. There were no preoperative predictors of a low final SST. Two patients (1%) underwent open re-operations during the study period. In patients with Walch B1 and B2 glenoids (n=110), there were no differences in outcome measures between patients with postoperative retroversion of more and less than 15o. While 15 of 51 patients (29%) with minimum 5-year radiographs had glenoid radioluciences, these radiographic findings were not associated with inferior clinical outcomes. On multivariable analysis glenoid component radiolucencies were most strongly associated with incomplete component seating (OR 3.3, p = 0.082). CONCLUSION: The results of TSA with conservative glenoid reaming without attempt at version correction are favorable at minimum 5 year, mean 8-year follow-up. There were no differences in clinical and radiographic outcomes between patients with eccentric and concentric wear patterns. Incomplete glenoid component seating was the greatest predictor of glenoid component radiolucency, but these radiolucencies were not associated with inferior clinical outcomes.

Does Adding Hydrogen Peroxide to Chlorhexidine Gluconate Increase the Effectiveness of Skin Preparation in Reducing Cutaneous Cutibacterium Levels? A Randomized Controlled Trial.

INTRODUCTION: Shoulder periprosthetic joint infection (PJI) is most commonly caused by Cutibacterium. Effective removal of these bacteria from the skin is difficult because Cutibacterium live protected in the dermal sebaceous glands beneath the skin surface to which surgical preparation solutions, such as chlorhexidine gluconate (CHG), are applied. There is conflicting evidence on the additional benefit of using hydrogen peroxide (H2O2) as an adjunct to CHG in eliminating Cutibacterium from the skin. A previous study demonstrated that after CHG skin preparation, repopulation of Cutibacterium from sebaceous glands onto the skin surface occurs in 90% of shoulders by 60 minutes after application. The objective of this randomized controlled study was to determine the effectiveness of adding H2O2 to CHG in reducing skin Cutibacterium. METHODS: Eighteen male volunteers (36 shoulders) were recruited for this study. The two shoulders of each volunteer were randomized to receive the control preparation ("CHG-only" - 2% CHG in 70% isopropyl alcohol [ISA] alone) or the study preparation ("H2O2+CHG" - 3% H2O2 followed by 2% CHG in 70% ISA). Skin swabs were taken from each shoulder prior to skin preparation and again at 60 minutes after preparation. Swabs were cultured for Cutibacterium and observed for 14 days. Cutibacterium skin load was reported using a semi-quantitative system based on the number of quadrants growing on the culture plate. RESULTS: Prior to skin preparation, 100% of the CHG-only shoulders and 100% of the H2O2+CHG shoulders had positive skin surface cultures for Cutibacterium. Repopulation of Cutibacterium on the skin at 60 minutes occurred in 78% of CHG-only and 78% of H2O2+CHG shoulders (p=1.00). Reduction of Cutibacterium skin levels occurred in 56% of CHG-only and 61% of H2O2+CHG shoulders (p=0.735). Cutibacterium levels were significantly decreased from before skin preparation to 60 minutes after preparation in both the CHG-only (2.1 ± 0.8 to 1.3 ± 0.9, p=0.003) and the H2O2+CHG groups (2.2 ± 0.7 to 1.4 ± 0.9, p<0.001). Substantial skin surface levels of Cutibacterium were present at 60 minutes after both preparations. CONCLUSIONS: In this randomized controlled study, there was no additional benefit of using hydrogen peroxide as an adjunct to chlorhexidine gluconate skin preparation in the reduction of cutaneous Cutibacterium levels. Neither preparation was able to eliminate repopulation of Cutibacterium on the skin surface from the dermal sebaceous glands.

Anatomic shoulder arthroplasty: the correlation between patient resilience, mental health, and outcome.

BACKGROUND: Recovery from anatomic shoulder arthroplasty may be enhanced in patients with good mental health and the resilience to participate in the prescribed postoperative rehabilitation program. To test this concept, we utilized validated and reliable scales in determining whether resilience and mental health are associated with the outcome of anatomic arthroplasty. METHODS: Three hundred ninety-nine patients (195 ream and run [RnR] and 204 anatomic total shoulder arthroplasty [aTSA]) were surveyed at a mean follow-up of 6.3 ± 3.3 years. Preoperative variables included age, sex, body mass index, history of prior shoulder surgery, diabetes, visual analog scale for pain, Simple Shoulder Test (SST) scores, and Veteran's RAND 12 Mental Component Score (VR-12 MCS). Outcomes collected included the SST, American Shoulder and Elbow Surgeons (ASES) score, revision rate, and patient satisfaction. Resilience was documented using the Connor-Davidson Resilience Scale 10 (CD-RISC 10) at latest follow-up. Univariable and multivariable regression analyses were used to identify factors significantly associated with follow-up postoperative SST, ASES, and satisfaction. RESULTS: In the univariable analysis, CD-RISC 10 was positively correlated with postoperative SST, ASES, and satisfaction after both RnR and aTSA. The mean CD-RISC 10 scores were higher in the RnR cohort (34.3 ± 4.8 vs. 32.5 ± 6.2 for aTSA, P < .001). Male sex and lower preoperative visual analog scale for pain were correlated with higher ASES after RnR; VR-12 MCS was positively correlated with all outcomes except SST after RnR. In the multivariable linear regression analysis, CD-RISC 10 was independently associated with postoperative SST, ASES and satisfaction scores in aTSA patients. In the RnR cohort, CD-RISC 10 was only correlated with satisfaction. VR-12 MCS was correlated with ASES and satisfaction after RnR. DISCUSSION: In this study of anatomic arthroplasties, increased resilience and better mental health were correlated with better outcomes. RnR patients had higher resilience than aTSA patients. Greater resilience was associated with better outcomes after aTSA. Better mental health was associated with superior outcomes after the ream and run procedure.

2023 Neer Award for Basic Science: Genetics of Cutibacterium acnes in revision shoulder arthroplasty: a large-scale bacterial whole-genome sequencing study.

BACKGROUND: Cutibacterium acnes is the bacterium most commonly responsible for shoulder periprosthetic joint infection (PJI) and is often cultured from samples obtained at the time of revision for failed shoulder arthroplasty. We sought to determine whether these bacteria originate from the patient or from exogenous sources. We also sought to identify which C. acnes genetic traits were associated with the development of shoulder PJI. METHODS: We performed bacterial whole-genome sequencing of C. acnes from a single-institution repository of cultures obtained before or during primary and revision shoulder arthroplasty and correlated the molecular epidemiology and genetic content of strains with clinical features of infection. RESULTS: A total of 341 isolates collected over a 4-year period from 88 patients were sequenced. C. acnes cultured from surgical specimens demonstrated significant similarity to the strains colonizing the skin of the same patient (P < .001). Infrequently, there was evidence of strains shared across unrelated patients, suggesting that exogenous sources of C. acnes culture-positivity were uncommon. Phylotypes IB and II were modestly associated with clinical features of PJI, but all phylotypes appeared inherently capable of causing disease. Chronic shoulder PJI was associated with the absence of common C. acnes genes involved in bacterial quorum-sensing (luxS, tqsA). CONCLUSION: C. acnes strains cultured from deep intraoperative sources during revision shoulder arthroplasty demonstrate strong genetic similarity to the strains colonizing a patient's skin. Some phylotypes of C. acnes commonly colonizing human skin are modestly more virulent than others, but all phylotypes have a capacity for PJI. C. acnes cultured from cases of PJI commonly demonstrated genetic hallmarks associated with adaptation from acute to chronic phases of infection. This is the strongest evidence to date supporting the role of the patient's own, cutaneous C. acnes strains in the pathogenesis of shoulder arthroplasty infection. Our findings support the importance of further research focused on perioperative decolonization and management of endogenous bacteria that are likely to be introduced into the arthroplasty wound at the time of skin incision.

Anatomic Total Shoulder: Predictors of Excellent Outcomes at Five Years after Arthroplasty.

PURPOSE: The objectives of this study were to: report minimum 5-year outcomes in patients undergoing TSA and determine characteristics predictive of patients achieving an excellent functional outcome. METHODS: Pre-operative demographic variables and Simple Shoulder Test (SST) scores were obtained pre-operatively and at a minimum of five years after surgery. A final SST ≥ 10 and percentage of maximal possible improvement (% MPI) of ≥ 66.7% were determined to be the thresholds for excellent outcomes. Univariate and multivariate analysis were performed to identify factors associated with excellent five year clinical outcomes. RESULTS: Of 233 eligible patients, 188 (81%) had adequate follow-up for inclusion in this study. Mean SST scores improved from 3.4 ± 2.4 to 9.7 ± 2.2 (p < 0.001). Male sex was an independent predictor of both SST ≥ 10 (OR 3.46, 95% CI 1.70-7.31; p < 0.001) and %MPI ≥ 66.7 (OR 2.27, 95% CI 1.11-4.81, p = 0.027). Workers' Compensation insurance was predictive of not obtaining SST ≥ 10 (OR 0.12, 95% 0.02-0.60; p = 0.016) or %MPI ≥ 66.7 (OR 0.16, 95% CI 0.03-0.77, p = 0.025). MCID was passed by the vast majority (95%) of patients undergoing TSA and did not necessarily indicate an excellent, satisfactory outcome. CONCLUSION: Male sex and commercial insurance coverage were significantly associated with these excellent outcomes, while Workers' Compensation insurance was associated with failure to achieve this result. Thresholds for excellent outcomes, such as final SST ≥ 10 and %MPI ≥ 66.7, may be useful in identifying the characteristics of patients who benefit most from TSA.

Inference of B cell clonal families using heavy/light chain pairing information.

Next generation sequencing of B cell receptor (BCR) repertoires has become a ubiquitous tool for understanding the antibody-mediated immune response: it is now common to have large volumes of sequence data coding for both the heavy and light chain subunits of the BCR. However, until the recent development of high throughput methods of preserving heavy/light chain pairing information, these samples contained no explicit information on which heavy chain sequence pairs with which light chain sequence. One of the first steps in analyzing such BCR repertoire samples is grouping sequences into clonally related families, where each stems from a single rearrangement event. Many methods of accomplishing this have been developed, however, none so far has taken full advantage of the newly-available pairing information. This information can dramatically improve clustering performance, especially for the light chain. The light chain has traditionally been challenging for clonal family inference because of its low diversity and consequent abundance of non-clonal families with indistinguishable naive rearrangements. Here we present a method of incorporating this pairing information into the clustering process in order to arrive at a more accurate partition of the data into clonally related families. We also demonstrate two methods of fixing imperfect pairing information, which may allow for simplified sample preparation and increased sequencing depth. Finally, we describe several other improvements to the partis software package.

Which Components of the Simple Shoulder Test Show Improvement After Scapulothoracic Fusion for Recalcitrant Scapular Winging? Clinical Results at a Minimum of 5 Years of Follow-up.

BACKGROUND: Scapular winging is an uncommon but important cause of shoulder pain and disability. Surgical management can include soft tissue procedures such as split pectoralis major transfer, the Eden-Lange procedure, or a triple tendon transfer. When these procedures do not alleviate symptomatic winging or are inappropriate, scapulothoracic fusion is an alternative, but data on its longer-term effectiveness are sparse. QUESTIONS/PURPOSES: (1) What changes in outcome scores were observed (VAS, Single Assessment Numeric Evaluation [SANE], and Simple Shoulder Test [SST] scores), and what proportion of the patients improved by an amount larger than the minimum clinically important difference (MCID) for the outcome tool in question? (2) Which components of the SST are patients able to perform at a minimum of 5 years? (3) What complications occurred after surgery? METHODS: We performed a retrospective study in a single, large, urban referral medical center of patients who underwent scapulothoracic fusion. Between January 2011 and November 2016, 15 patients underwent scapulothoracic fusion to treat symptomatic scapular winging. Only patients with nondystrophic etiology were included in the analysis (n = 13). Of the 13 remaining patients, one patient was lost to follow-up and another patient died during data collection, leaving 11 patients for the final analysis. Six patients had brachial plexus injuries affecting multiple nerve roots and periscapular muscles, and five had persistent symptoms despite prior tendon transfer. The median age of the patients was 43 years (range 20 to 67 years), and there were six male and five female patients. All patients had a minimum of 5 years of follow-up. There was a median follow-up of 79 months (range 61 to 128 months). The VAS pain score (range 0 to 10, higher scores represent more pain; MCID = 2), SST score (range 0 to 12, higher scores represent less pain and better shoulder function; MCID = 2.3), and SANE score (range 0 to 100, higher scores represent better shoulder function; MCID = 28) were recorded before surgery and at the most recent follow-up. We compared scores from before surgery with those taken at the most recent follow-up and ascertained the proportion of patients whose improvement exceeded the MCID. The number of patients achieving fusion (as confirmed by a CT image), complications, and reoperations was recorded via a record review as well as direct patient query by telephone. RESULTS: The median VAS pain score improved from 7 (range 3 to 10) preoperatively to 3 (range 2 to 5) at the latest follow-up (p < 0.001). The median SANE score improved from 30 (range 0 to 60) preoperatively to 65 (range 40 to 85) at the latest follow-up (p < 0.001). The median SST score improved from 0 (range 0 to 9) to 8 (range 5 to 10) at the latest follow-up (p < 0.001). Ten of 11 patients had improvements exceeding the MCID for VAS, six of 11 had improvements for SANE scores, and nine of 11 had improvements for SST. Preoperative to postoperative improvements in these components of the SST were seen (responses of "yes"): comfort at rest (three of 11 improved to 11 of 11; p < 0.001), sleep comfortably (three of 11 improved to 11 of 11; p < 0.001), place coin on shelf (two of 11 improved to 10 of 11; p < 0.001), lift 1 pound above shoulder (two of 11 improved to eight of 11; p = 0.03), and carry 20 pounds with the arm at side (one of 11 improved to nine of 11; p < 0.001). All 11 patients had successful fusion noted on CT images. There were three complications (progression of glenohumeral arthritis, broken wires, and perioperative chest tube placement) and one reoperation for progression of glenohumeral arthritis with subsequent total shoulder arthroplasty. CONCLUSION: Patients with recalcitrant symptomatic scapular winging often undergo an exhaustive course of clinical examinations, diagnostic tests, physical therapy, and multiple surgical procedures. Those with brachial plexus palsy with involvement of multiple nerves may continue to have symptoms despite nonoperative management and subsequent soft tissue tendon transfers. Scapulothoracic fusion could be considered for patients with persistent pain and decreased function because of recalcitrant scapular winging who are either not candidates for the procedure or have persistent symptoms despite prior soft tissue procedures. LEVEL OF EVIDENCE: Level IV, therapeutic study.

What is the optimal management of a loose glenoid component after anatomic total shoulder arthroplasty: a systematic review.

BACKGROUND: Total shoulder arthroplasty (TSA) provides excellent long-term clinical outcomes in the treatment of glenohumeral arthritis. However, symptomatic glenoid polyethylene loosening can be seen at intermediate follow-up and can lead to shoulder pain and dysfunction. The purpose of this study was to perform a systematic review of the available literature to determine the optimal management of symptomatic glenoid loosening with regard to reoperation and patient satisfaction following various approaches to symptomatic glenoid loosening. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies investigating revision arthroplasty for the treatment of glenoid loosening with clinical outcomes were identified. Clinical failure was defined as a repeat procedure after revision arthroplasty. RESULTS: Overall, 14 studies met inclusion criteria that included 483 patients with a mean age of 66.5 ± 3.0 years who underwent revision arthroplasty for symptomatic glenoid loosening. There were 8 studies that discussed conversion to a hemiarthroplasty (HA, 148 patients), 7 studies that discussed glenoid reimplantation in a single setting (1-stage TSA, 157 patients), 2 studies that discussed glenoid reimplantation in a staged setting (2-stage TSA, 18 patients), and 2 studies that discussed conversion to a reverse shoulder arthroplasty (RSA, 164 patients). All patients underwent glenoid component removal. The length of follow-up was significantly shorter in the RSA group (41 months for RSA vs. 56 months for HA vs. 55 months for 1-stage TSA vs. 62 months for 2-stage TSA, P < .001). The reoperation rate at the final follow-up was 19% for the HA cohort, 20% for the 1-stage TSA cohort, 22% for the 2-stage TSA cohort, and 21% for the RSA cohort (P = .971). Patient satisfaction rate at the final follow-up was 62% for the HA cohort, 66% for the 1-stage TSA cohort, 71% for the 2-stage TSA cohort, and 86% for the RSA cohort (P = .045). Positive cultures were noted in 15% of patients with Cutibacterium acnes comprising 72% of positive cultures. CONCLUSIONS: Overall, the optimal management of symptomatic glenoid loosening remains unclear. All 4 types of revision arthroplasty (HA, 1-stage TSA, 2-stage TSA, and RSA) had a similar reoperation rate (20%) at the latest follow-up. Conversion to RSA provided a higher proportion of patients satisfied with the procedure. However, the length of follow-up was significantly shorter than other groups, and therefore longer-term follow-up of this group is needed to determine if results are durable.

Minimum 10-year follow-up of anatomic total shoulder arthroplasty and ream-and-run arthroplasty for primary glenohumeral osteoarthritis.

BACKGROUND: Reports on long term outcomes and failures of shoulder arthroplasty are uncommon. The purpose of this study is to present minimum 10-year outcomes in consecutive patients undergoing ream-and-run and anatomic total shoulder arthroplasty (TSA) for primary glenohumeral arthritis. METHODS: This study analyzed consecutive patients who had undergone a ream-and-run or TSA with minimum 10-year follow-up. Pain scores and Simple Shoulder Test (SST) values were obtained preoperatively and at a minimum of 10 years postoperatively via e-mail or mail-in response. Percentage of maximum possible improvement (%MPI) was also calculated. RESULTS: Of 127 eligible patients, 63 (50%) responded to a 10-year survey. This included 34 patients undergoing ream-and-run arthroplasty and 29 patients undergoing TSA. The ream-and-run patients were significantly younger than the TSA patients (60 ± 7 vs. 68 ± 8, P < .001), predominantly male (97% vs. 41%, P < .001), and had a lower American Society of Anesthesiologists classification (P = .018). In the ream-and-run group, the mean pain score improved from a preoperative value of 6.5 ± 1.9 to 0.9 ± 1.3 (P < .001), and the mean SST score improved from 5.4 ± 2.4 to 10.3 ± 2.1 at 10-year follow-up (P < .001). Twenty-eight (82%) achieved an SST improvement above the minimally clinically important difference (MCID) of 2.6. Four patients (12%) underwent single-stage exchange to another hemiarthroplasty, whereas 1 (3%) required manipulation under anesthesia. In the TSA group, the pain score improved from a preoperative value of 6.6 ± 2.2 to 1.2 ± 2.3 (P < .001), and the SST score improved from 3.8 ± 2.6 to 8.9 ± 2.6 at 10-year follow-up (P < .001). Of the 29 patients who underwent a TSA, 27 (93%) achieved an SST improvement above the MCID of 1.6. No patient in the TSA group required reoperation. CONCLUSION: Although the characteristics of the patients differ between the 2 groups, excellent functional results can be obtained with the ream-and-run arthroplasty and TSA for glenohumeral osteoarthritis.

Factors associated with success of ream-and-run arthroplasty at a minimum of 5 years.

BACKGROUND: Ream-and-run arthroplasty offers improvements in shoulder pain and function for patients with primary glenohumeral arthritis who wish to avoid limitations associated with a polyethylene glenoid component. Longer-term clinical outcome assessments of the ream-and-run procedure are sparse in the literature. This study aimed to present minimum 5-year functional outcomes in a large cohort following ream-and-run arthroplasty to determine factors associated with clinical success and reoperation. METHODS: Patients who underwent ream-and-run surgery with a minimum of 5 years of follow-up were identified through a retrospective review of a prospectively maintained database from a single academic institution. To assess clinical outcomes, the Simple Shoulder Test (SST) was administered and assessed to determine achievement of the minimal clinically important difference, as well as the necessity for open revision surgery. Factors associated with P < .1 on univariate analysis were included in multivariate analysis. RESULTS: Of 228 patients who consented to undergo long-term follow-up, 201 (88%) were included in our analysis (mean follow-up period, 7.6 ± 2.1 years). The average age was 59.4 ± 8.8 years, and 93% of patients were men. The majority of patients had a diagnosis of osteoarthritis (79%) or capsulorrhaphy arthropathy (10%). SST scores improved from a mean of 4.9 ± 2.5 preoperatively to a mean of 10.2 ± 2.6 at latest follow-up. The minimal clinically important difference in the SST score of 2.6 was reached by 165 patients (82%). Male sex (P = .020), nondiabetic status (P = .080), and lower preoperative SST score (P < .001) were included in a multivariate analysis. Male sex (P = .010) and lower preoperative SST score (P < .001) were associated with clinically important improvements in SST scores on multivariate analysis. Open revision surgery was required in 22 patients (11%). Younger age (P < .001), female sex (P = .055), and higher preoperative pain score (P = .023) were included in a multivariate analysis. Only younger age was predictive of open revision surgery (P = .003). CONCLUSIONS: Ream-and-run arthroplasty can provide significant and clinically important improvements in clinical outcomes at minimum 5-year follow-up. Successful clinical outcomes were significantly associated with male sex and lower preoperative SST scores. Reoperation was more common in younger patients.

Revision of total shoulder arthroplasty to hemiarthroplasty: results at mean 5-year follow-up.

BACKGROUND: Although there is a trend to manage failed anatomic total shoulder arthroplasties (aTSA) with revision to a reverse total shoulder arthroplasty, such revisions can be complicated by difficulties in baseplate fixation, instability, and acromial stress fractures. Some cases of failed aTSA may be safely revised to a hemiarthroplasty (HA). The objectives of this study were to report patient-reported outcomes after conversion from aTSA to HA and assess patient and shoulder characteristics associated with a successful outcome. METHODS: Patients who underwent revision from aTSA to HA between 2009 and 2018 were contacted. Patient demographics, surgical history, intraoperative findings, and microbiology results were collected. Patient-reported outcomes were collected with minimum 2-year follow-up. Preoperative radiographic characteristics were reviewed for component positioning and component loosening. Patients with a clinically significant improvement exceeding the minimal clinically important difference (MCID) of the Simple Shoulder Test (SST) were compared with those patients who did not improve past the MCID. RESULTS: Twenty-nine patients underwent conversion from aTSA to HA with a mean follow-up of 4.5 ± 1.8 years. Intraoperative glenoid or humeral component loosening was found in all 29 patients. Pain improved in 25 of 30 patients (87%), and mean pain scores improved from 6.2 ± 2.3 to 3.1 ± 2.4 (P < .001). SST scores improved from 4.1 ± 3.1 to 7.3 ± 3.2 (P < .001), and 18 of 29 patients (62%) had improvement above the SST MCID threshold of 2.4. The mean American Shoulder and Elbow Surgeons score at the latest follow-up was 64 ± 19, and the Single Assessment Numeric Evaluation score was 65 ± 23. Twenty-two of 29 (76%) patients were satisfied with the procedure. Four patients (14%) required conversion to total shoulder arthroplasty-2 to anatomic and 2 to reverse. An additional 3 patients (10%) had a revision HA performed. No significant differences in patient or shoulder characteristics were found in those patients who improved greater than the MCID of the SST compared patients who improved less than the MCID of the SST. Fifty-nine percent of patients had ≥2 positive cultures with the same bacteria, and 82% of these were with Cutibacterium. Seven of 8 patients (88%) with a loose humeral component had ≥2 positive cultures with the same bacteria. DISCUSSION: Component loosening is a common failure mode after aTSA. Revision to HA can improve pain and patient-reported outcomes in most patients.

Predictors of success following single-stage revision shoulder arthroplasty: results at a mean of five year follow-up in one hundred and twelve patients.

PURPOSE: The objective was to determine factors associated with a successful outcome at a minimum of two years after revision of a failed shoulder arthroplasty. METHODS: We conducted a retrospective study of revision shoulder arthroplasties performed over a ten year period and collected patient-reported outcome data and re-revision data. A successful outcome was defined by improvement greater than the minimal clinically important difference (MCID) for the Simple Shoulder Test (SST). RESULTS: One hundred twelve patients with average follow-up of five years were included. Improvement of VAS pain scores (6.6 ± 2.3 to 2.9 ± 2.6) and SST scores (2.7 ± 2.6 to 6.6 ± 3.3) were significant (p < 0.001). Males were more likely to have a successful outcome than females (p = 0.01). CONCLUSION: Two-thirds of patients experienced clinically significant improvement at a minimum of two years after revision shoulder arthroplasty. Male sex was the strongest independent predictor of a successful outcome.

Dynamics of Cutibacterium repopulation onto the skin surface of the shoulder after chlorhexidine application.

PURPOSE: The objective of this study was to characterize the temporal dynamics of Cutibacterium repopulation of the skin surface after application of chlorhexidine to the shoulder. METHODS: Ten shoulders in five male subjects were used. A skin swab was taken prior to (0 minutes) and then at three, 30, 60, 120, and 240 minutes after skin preparation with 2% chlorhexidine gluconate and 70% isopropyl alcohol. Semi-quantitative bacterial load was measured for each timepoint. RESULTS: From zero minutes (pre-treatment) to three minutes, chlorhexidine-isopropyl alcohol reduced the skin bacterial load in eight out of ten shoulders. Of these eight shoulders, four (50%) had growth by 30 minutes, seven (88%) had growth by 60 minutes, and all eight (100%) had growth by 240 minutes. Compared to the three minutes after chlorhexidine application, bacterial load had significantly increased by 60 minutes but were still significantly lower than the pre-prep bacterial load (0 minutes). CONCLUSION: Following standard surgical skin preparation with chlorhexidine-isopropyl alcohol, the surface of the shoulder is repopulated with Cutibacterium within one hour, presumably from reservoirs in sebaceous glands not penetrated by topical antiseptic agents. Since these dermal glands are transected by skin incision for shoulder arthroplasty, this study suggests that they may be sources of wound contamination during surgery in spite of skin preparation with chlorhexidine.

Lack of Evidence for a Substantial Rate of Templated Mutagenesis in B Cell Diversification.

BCR sequences diversify through mutations introduced by purpose-built cellular machinery. A recent paper has concluded that a "templated mutagenesis" process is a major contributor to somatic hypermutation and therefore Ig diversification in mice and humans. In this proposed process, mutations in the Ig locus are introduced by copying short segments from other Ig genes. If true, this would overturn decades of research on B cell diversification and would require a complete rewrite of computational methods to analyze B cell data for these species. In this paper, we re-evaluate the templated mutagenesis hypothesis. By applying the original inferential method using potential donor templates absent from B cell genomes, we obtain estimates of the methods' false positive rates. We find false positive rates of templated mutagenesis in murine and human Ig loci that are similar to or even higher than the original rate inferences, and by considering the bases used in substitution, we find evidence that if templated mutagenesis occurs, it is at a low rate. We also show that the statistically significant results in the original paper can easily result from a slight misspecification of the null model.