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Abstract Background Lower respiratory infections are a leading cause of severe morbidity and mortality among older adults. Despite ubiquitous exposure to common respiratory pathogens throughout life and near universal seropositivity, antibodies fail to effectively protect the elderly. Therefore, we hypothesized that severe respiratory illness in the elderly is due to deficient CD8+ T cell responses. Results Here, we establish an aged mouse model of human metapneumovirus infection (HMPV) wherein aged C57BL/6 mice exhibit worsened weight loss, clinical disease, lung pathology and delayed viral clearance compared to young adult mice. Aged mice generate fewer lung-infiltrating HMPV epitope-specific CD8+ T cells. Those that do expand demonstrate higher expression of PD-1 and other inhibitory receptors and are functionally impaired. Transplant of aged T cells into young mice and vice versa, as well as adoptive transfer of young versus aged CD8+ T cells into Rag1 −/− recipients, recapitulates the HMPV aged phenotype, suggesting a cell-intrinsic age-associated defect. HMPV-specific aged CD8+ T cells exhibit a terminally exhausted TCF1/7− TOX+ EOMES+ phenotype. We confirmed similar terminal exhaustion of aged CD8+ T cells during influenza viral infection. Conclusions This study identifies terminal CD8+ T cell exhaustion as a mechanism of severe disease from respiratory viral infections in the elderly.

Summary: Intestinal colonization by antigenically foreign microbes necessitates expanded peripheral immune tolerance. Here we show commensal microbiota prime expansion of CD4 T cells unified by the Kruppel-like factor 2 (KLF2) transcriptional regulator and an essential role for KLF2+ CD4 cells in averting microbiota-driven intestinal inflammation. CD4 cells with commensal specificity in secondary lymphoid organs and intestinal tissues are enriched for KLF2 expression, and distinct from FOXP3+ regulatory T cells or other differentiation lineages. Mice with conditional KLF2 deficiency in T cells develop spontaneous rectal prolapse and intestinal inflammation, phenotypes overturned by eliminating microbiota or reconstituting with donor KLF2+ cells. Activated KLF2+ cells selectively produce IL-10, and eliminating IL-10 overrides their suppressive function in vitro and protection against intestinal inflammation in vivo. Together with reduced KLF2+ CD4 cell accumulation in Crohn’s disease, a necessity for the KLF2+ subpopulation of T regulatory type 1 (Tr1) cells in sustaining commensal tolerance is demonstrated.

Abstract Human metapneumovirus (HMPV) is a leading cause of acute lower respiratory tract illness in children and adults. Repeated infections are common and can be severe in young, elderly, and immunocompromised persons due to short-lived protective humoral immunity. In turn, few protective T cell epitopes have been identified in humans. Thus, we infected transgenic mice expressing the common human HLA MHC-I allele B*07:02 (HLA-B7) with HMPV and screened a robust library of overlapping and computationally predicted HLA-B7 binding peptides. Six HLA-B7-restricted CD8+ T cell epitopes were identified using ELISPOT screening in the F, M, and N proteins, with M195–203 (M195) eliciting the strongest responses. MHC-tetramer flow cytometric staining confirmed HLA-B7 epitope-specific CD8+ T cells migrated to lungs and spleen of HMPV-immune mice. Immunization with pooled HLA-B7-restricted peptides reduced viral titer and protected mice from virulent infection. Finally, we confirmed that CD8+ T cells from HLA-B7 positive humans also recognize the identified epitopes. These results enable identification of HMPV-specific CD8+ T cells in humans and help to inform future HMPV vaccine design.

Pregnancy makes women especially vulnerable to infection. The most common cause of bloodstream infection during pregnancy is by a bacterium called Escherichia coli

Background: Osteochondritis dissecans (OCD) of the knee is a focal idiopathic alteration of subchondral bone and/or its precursor with risk for instability and disruption of adjacent cartilage. Treatment options focused on preventing premature osteoarthritis vary depending on multiple patient and lesion characteristics, including lesion mobility., Purpose: To differentiate lesion mobility before arthroscopy using a multivariable model that includes patient demographic characteristics and physical examination findings., Study Design: Cohort study (Diagnosis); Level of evidence, 2., Methods: Demographic, preoperative physical examination, and radiographic data were collected from a multicenter national prospective cohort of patients with OCD of the knee. Inclusion criteria included patients <19 years of age and patients with arthroscopically confirmed mobility status based on the Research on Osteochondritis Dissecans of the Knee arthroscopy classification. Multivariable logistic regression analysis using stepwise model selection was used to determine factors associated with the likelihood of a mobile versus an immobile lesion. A 75% partition of the data was used for model training, and 25% was used as a validation cohort. Quantitative model fit statistics were computed using the holdout data, including sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), along with the corresponding 95% CI., Results: A total of 407 patients in the prospective cohort met inclusion criteria, and 62% were male. The mean ± SD age was 13.7 ± 2.2 years, height 161.8 ± 5.3 cm, and weight 59.2 ± 42.2 kg. Arthroscopic evaluation yielded 235 immobile and 172 mobile lesions. Multivariable analysis determined that the best model to predict lesion mobility included chronologic age ≥14 years ( P < .001), effusion on physical examination ( P < .001), and any loss of range of motion on physical examination ( P = .07), while controlling for male sex ( P = .38) and weight >54.4 kg ( P = .12). In the 25% holdout validation sample (n = 102), a sensitivity of 83%, a specificity of 82%, and an AUC of 0.89 (95% CI, 0.82-0.95) were achieved with these predictive factors., Conclusion: Age, effusion, and loss of motion can predict knee OCD lesion mobility at the time of arthroscopy. Education about lesion mobility can help with surgical planning and patient and family counseling., Competing Interests: One or more of the authors has declared potential conflict of interest or source of funding (see the Appendix, available in the online version of this article). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Mixed reality refers to the integration of virtual reality into the real-world environment. This digital content can be interacted with in real time. The emergence of mixed reality technology has been made possible by the introduction of head-mounted displays, which are being utilized across multiple surgical specialties. In upper extremity surgery, mixed reality has widespread applications in trauma, corrective surgery, arthroplasty, arthroscopy, and oncology. Preoperatively, mixed reality allows for complex 3D planning. Intraoperatively, surgeons can access this 3D data in a sterile environment. While in its infant stages, mixed reality is likely to become a powerful tool for intraoperative guidance and navigation. Mixed reality can change the paradigm of communication, as it allows the sharing of visual data from the surgeon's perspective, enabling remote assistance and participation.

Purpose: The aim of this study was to observe the effects of changing humeral tray thickness on the resultant of intraoperative glenohumeral joint loads using a load-sensing system (LSS)., Methods: An rTSA was performed on fresh frozen full-body cadaver shoulders by using an internal proprietary LSS on the humeral side. The glenohumeral loads (Newtons) and the direction of the resultant force applied on the implant were recorded during four standard positions (External rotation, Extension, Abduction, Flexion) and three "complex" positions of Activity Daily Life ("behind back", "overhead reach" and "across chest"). For each position, the thickness was increased from 0 to 6 mm in a continuous fashion using the adjustment feature of the humeral system. Each manoeuvre was repeated three times., Results: All shoulder positions showed a high repeatability of the glenohumeral load magnitude measured with an intra-class correlation coefficient of over 0.9. For each position, we observed a strong but no linear correlation between humeral tray thickness and joint loads. It was a cubical correlation (r s = 0,91) with a short ascending phase, then a plateau phase, and finally a phase with an exponential growth of the loads on the humeral implant. In addition, an increase in trail-poly thickness led to a recentering of force application at the interface of the two glenohumeral implants., Conclusion: This study provides further insight into the effects of humeral implant thickness on rTSA glenohumeral joint loads during different positions of the arm. Data obtained using this type of device could guide surgeons in finding the proper implant balance during rTSA., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Objective:  Although the Accreditation Council for Graduate Medical Education and American Board of Pediatrics (ABP) provide regulations and guidance on fellowship didactic education, each program establishes their own didactic schedules to address these learning needs. Wide variation exists in content, educators, amount of protected educational time, and the format for didactic lectures. This inconsistency can contribute to fellow dissatisfaction, a perceived poor learning experience, and poor attendance. Our objective was to create a Neonatal-Perinatal Medicine (NPM) fellow curriculum based on adult learning theory utilizing fellow input to improve the perceived fellow experience., Study Design:  A needs assessment of current NPM fellows at Cincinnati Children's Hospital was conducted to guide the development of a new curriculum. Fellow perception of educational experience and board preparedness before and after introduction of the new curriculum was collected. Study period was from October 2018 to July 2021., Results:  One hundred percent of the fellows responded to the needs assessment survey. A response rate of 100 and 87.5% were noted on mid-curriculum survey and postcurriculum survey, respectively. Key themes identified and incorporated into the curriculum included schedule structure, content, and delivery mode. A new didactic curriculum implementing a consistent schedule of shorter lectures grouped by organ system targeting ABP core content was created. After curriculum implementation, fellows had higher self-perception of board preparedness, and overall improved satisfaction., Conclusion:  Our positive experience in implementing this curriculum provides a framework for individual programs to implement similar curricula, and could be utilized to aid in development of national NPM curricula., Key Points: · Fellowship didactic education varies significantly resulting in learner dissatisfaction and poor attendance.. · Widespread need to restructure didactic curricula exists.. · Our study provides a framework for future curricula.., Competing Interests: None declared., (Thieme. All rights reserved.)

The challenge of introducing new technologies into established industries is not a problem unique to the biopharmaceutical industry. However, it may be critical to the long-term competitiveness of individual manufacturers and, more importantly, the ability to deliver therapies to patients. This is especially true for new treatment modalities including cell and gene therapies. We review several barriers to technology adoption which have been identified in various public forums including business, regulatory, technology, and people-driven concerns. We also summarize suitable enablers addressing one or more of these barriers along with suggestions for developing synergies or connections between innovation in product discovery and manufacturing or across the supplier, discovery, manufacturing, and regulatory arms of the holistic innovation engine., (© 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Background: The senior author adopted a Triceps Split and Snip approach in 2011. This paper details the results of patients for whom this approach was utilised for open reduction and internal fixation of complex AO type C distal humerus fractures. Methods: A retrospective analysis of a single surgeon's cases was conducted. Range of movement, as well as Mayo Elbow Performance Score (MEPS), and QuickDASH scores were evaluated. Two independent consultants with upper extremity practises evaluated pre- and post-operative radiographs. Results: Seven patients were available for clinical review. The mean age at the time of surgery was 47.7 years (range, 20.3-83.2) and the mean follow-up time was 3.6 years (range, 0.58-8). The average QuickDASH score was 15.85 (range, 0-52.3), average MEPS was 86.88 (range, 60-100) and average total arc of movement (TAM) was 103° (range, 70°-145°). All patients demonstrated 5/5 MRC triceps strength compared to the contralateral side. Conclusions: The Triceps Split and Snip approach for complex distal humerus fractures provided comparable mid-term clinical outcomes when compared to other published data regarding distal humerus fractures. It is versatile and does not compromise the intra-operative option of conversion to a total elbow arthroplasty. Level of Evidence: Level IV (Therapeutic).

The Manufacturing Readiness Levels (MRLs) developed by the Department of Defense are well-established tools for describing the maturity of new technologies resulting from government-sponsored Research and Development programs, from the concept phase to commercial deployment. While MRLs are generally applicable to a wide range of industries and technologies, there is significant value in offering an industry-specific view on how the basic principles may be applied to biomanufacturing. This paper describes Biomanufacturing Readiness Levels (BRLs) developed by the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), a public/private partnership that is part of the Manufacturing USA network. NIIMBL brings together private, federal, nonprofit, and academic stakeholders to accelerate the deployment of innovative technologies for biopharmaceutical production and to educate and train a world-leading biomanufacturing workforce. We anticipate that these BRLs will lay the groundwork for a shared vocabulary for assessment of technology maturity and readiness for commercial biomanufacturing that effectively meets the needs of this critical, specialized, and highly regulated industry., (© 2022 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Readiness level (RL) frameworks such as technology readiness levels and manufacturing readiness levels describe the status of a technology/manufacturing process on its journey from initial conception to commercial deployment. More importantly, they provide a roadmap to guide technology development and scale-up from a ''totality of system'' approach. Commercialization risks associated with too narrowly focused R&D efforts are mitigated. RLs are defined abstractly so that they can apply to diverse industries and technology sectors. However, differences between technology sectors make necessary the definition of sector specific RL frameworks. Here, we describe bioindustrial manufacturing readiness levels (BioMRLs), a classification system specific to bioindustrial manufacturing. BioMRLs will give program managers, investors, scientists, and engineers a shared vocabulary for prioritizing goals and assessing risks in the development and commercialization of a bioindustrial manufacturing process., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society of Industrial Microbiology and Biotechnology.)

An ambitious 10-year collaborative program is described to invent, design, demonstrate, and support commercialization of integrated biopharmaceutical manufacturing technology intended to transform the industry. Our goal is to enable improved control, robustness, and security of supply, dramatically reduced capital and operating cost, flexibility to supply an extremely diverse and changing portfolio of products in the face of uncertainty and changing demand, and faster product development and supply chain velocity, with sustainable raw materials, components, and energy use. The program is organized into workstreams focused on end-to-end control strategy, equipment flexibility, next generation technology, sustainability, and a physical test bed to evaluate and demonstrate the technologies that are developed. The elements of the program are synergistic. For example, process intensification results in cost reduction as well as increased sustainability. Improved robustness leads to less inventory, which improves costs and supply chain velocity. Flexibility allows more products to be consolidated into fewer factories, reduces the need for new facilities, simplifies the acquisition of additional capacity if needed, and reduces changeover time, which improves cost and velocity. The program incorporates both drug substance and drug product manufacturing, but this paper will focus on the drug substance elements of the program., (© 2021 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Background: The use of an eccentric glenosphere (EG) has been proposed as a way to prevent scapular notching in reverse shoulder arthroplasty (RSA). The purpose of this study was to investigate whether the use of an EG decreases scapular notching compared with matched standard concentric glenosphere (CG) controls., Methods: A retrospective analysis was performed. This study included 49 RSAs with an EG and 49 paired RSAs with a CG with a minimum 60 months of both clinical and radiographic follow-up. Clinical and radiologic outcomes of the EG and CG groups were compared at inclusion and at the last follow-up using the paired Student t test for quantitative data and the χ 2 test for qualitative data. Scapular notching was graded according to the Sirveaux classification. Statistical significance was set at P < .05., Results: Notching was observed 2.7 times (95% confidence interval, 1.0-6.8 times) more often in the CG group (P = .037). The difference in notching severity between the groups was not statistically relevant; however, there was a trend toward more severe notching in the CG group (P = .059). Compared with a CG, an EG did not increase the percentage of radiolucent lines around the screws (3% vs. 1.5%, P = .62), around the post (3% vs. 1.5%, P = .62), or below the baseplate (15% vs. 7.5%, P = .18)., Conclusion: EGs are associated with less notching than CGs. This finding confirms that RSA with an EG is an effective procedure without specific complications at a minimum follow-up of 5 years., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Reverse shoulder arthroplasty is gaining popularity owing to its proven longevity and good outcome scores. Scapular notching remains a concern. This study aimed to assess the safety of larger polyethylene glenospheres with increased eccentricity in comparison with the more conventional metal bearings. The secondary effects on scapular notching, clinical outcomes, range of movement, and complications were also analyzed., Methods: We conducted a 10-year retrospective review of 145 SMR reverse shoulder arthroplasties (LimaCorporate, Udine, Italy) in 132 patients with radiographs at a minimum of 2 years postoperatively. The primary outcome measure was the survivorship of the larger polyethylene glenospheres. Secondary outcomes were the presence and size of notching, subjective satisfaction score, American Shoulder and Elbow Surgeons score, Oxford Shoulder Score, range of motion, and shoulder-related complications., Results: No failures of the polyethylene glenospheres were noted in the 10-year period. At a minimum of 2 years' follow-up, notching was noted in 16 (25%) of the metal glenospheres vs. 9 (11.1%) of the polyethylene glenospheres ( P  = .028). The mean Oxford Shoulder Score was lower for the metal glenospheres ( P  = .005). Range of motion, complications, and overall satisfaction were similar in both groups., Conclusion: The inverted bearing configuration demonstrated no failures at a minimum of 2 years' follow-up. A larger study is required to determine whether the decreased incidence and size of early notching are related to the bearing size or material., (© 2020 The Authors.)

Background: We sought to independently validate published data that volar cortical integrity (VCI) is an independent predictor of maintenance of closed reduction in a series of non-surgically treated distal radius fractures, while simultaneously investigating previously reported predictors of instability. Our null hypothesis was that volar cortical integrity would not affect maintenance of reduction. Methods: Four hundred thirty-three adult distal radius fractures were screened from our Orthopedic database with 112 meeting inclusion criteria. Two groups were determined on the basis of maintenance of reduction (MOR) or loss of reduction (LOR) at 5-6 weeks post-reduction. Bivariate analysis was applied to previously published instability factors along with VCI. A forward stepwise logistic regression was then used to identify instability factors that, as a group, are most predictive of outcome. Results: Results of 112 patients were collected. Reduction was maintained in 62 patients (55.35%) at 5-6 weeks Biivariate analysis showed a statistically significant difference in volar cortical integrity between the 2 groups (80.6% MOR vs 59.2% LOR). Forward stepwise logistic regression analysis of subgroups revealed that post-reduction radial height and VCI were together statistically significant in the model. The presence of VCI, post-reduction radial height greater than or equal to ulnar neutral at the time of initial reduction resulted in a 67.8% successful MOR. Conclusions: We were able to confirm the importance of volar cortical integrity as a predictor of successful maintenance of reduction in non-surgically managed distal radius fractures. When combined with post-reduction radial height greater than or equal to ulnar neutral at the time of initial reduction, it showed a 67.8% MOR with non-operative management in our data-set.

Background: An eccentric glenosphere (EG) has been proposed as a way of preventing scapular notching after reverse shoulder arthroplasty (RSA). Our aim was to report the midterm clinical and radiographic results of EG after RSA. A number of the patients described here were included in a previous study with short-term follow-up. The current retrospective study gave us the opportunity to follow many of these patients for a longer period of time., Methods: A retrospective analysis of prospectively collected data was conducted. Statistical significance was set at P < .001. Forty-nine RSAs with an EG and at least 60 months of follow-up were included. Range of motion (ROM), Constant scores (CSs), and Subjective Shoulder Value (SSV) were assessed. Scapular notching was graded according to the Sirveaux classification., Results: At the last follow-up, the mean improvement in active elevation (ROM) was 46° and the mean CS increased by nearly 31 points (both groups P < .001). The final SSV was 70%. Twenty-one patients (43%) had scapular notching, but in two-thirds of patients it was low-grade., Conclusion: The use of an EG provided excellent clinical outcomes that persisted with midterm follow-up. The rate of notching was lower than in other studies with EGs, but further studies are required to confirm this. An EG was safe and there were no issues with baseplate loosening or failure., (Copyright © 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Night time numbness is a key characteristic of CTS and relief of night time symptoms is one of the outcomes most important to patients. This study tested the null hypothesis that there is no difference between sleep quality and night symptoms before and after carpal tunnel release (CTR). Methods: Forty-four, English-speaking adult patients requesting open CTR for electrodiagnostically confirmed carpal tunnel syndrome completed questionnaires before and after surgery. Average age was 59, 24 patients were men and 20 were women. Patient with a primary or secondary sleep disorder were excluded. Before surgery, patients completed the Pittsburg Sleep Quality index (PSQI). At an average of 3 months after surgery, participants completed PSQI questionnaires. Onset of sleep quality improvement was specifically addressed. Differences between preoperative and postoperative sleep quality were evaluated using the paired t-test. Spearman correlations were used to assess the relationship between continuous variables. Results: Of the 44 patients, 32 (72%) were classified as poor sleepers (PSQI > 5.5) prior to surgery. At 3 months follow up, there was a significant improvement PSQI global scores (7.8 ± 5.1 vs 4 ± 3.5, p < 0.001) as well as subdivisions. Daytime dysfunction (0.2 ± 0.4, p < 0.001) and medication use (1.0 ± 1.2 vs 0.9 ± 1.2, p < 0.045) secondary to sleep disturbance and was improved as well. In all patients, onset of improvement was within 24 hours of surgery. Conclusions: CTR is associated with improvement in sleep quality at 3 months follow-up. CTR improves daytime dysfunction related to the sleep disturbance. The onset of sleep improvement is 24 hours after surgery in most cases.

Background: Asymptomatic, incidental extensor carpi ulnaris (ECU) tendon abnormalities are frequently noted on imaging studies of the wrist. The aim of this investigation was to determine if variations in gross tendon anatomy existed that could possibly account for these findings on MRI and ultrasound (US) imaging. Methods: The upper extremities of eleven (6 male and 5 female) formalin preserved cadavers were dissected and examined under loupe magnification with attention to the dorsal-ulnar wrist and hand and the ECU tendon. The tendons were inspected for anatomic variations, degenerative changes, and any other pathologies. The presence of intra-tendinous splits arising within the ECU tendon was noted and measured. The distances of the splits from the distal tendon insertion and the edge of the extensor retinaculum were recorded. Statistical correlations between age and the tendon splits were considered using R-squared to assess a linear regression. Results: 17 ECU tendons were dissected and examined, and 5 ECU tendons were excluded due to poor preservation of that upper extremity; all five were right sided upper extremities. Eleven of the 17 specimens demonstrated at least one split in the distal tendon: Seven had 1 split, 1 had 2 splits, and 3 had 3 splits. The mean length of the tendon split was 3.52 cm. The mean distance of the distal edge of the split to the tendon insertion site was 2.4 cm. A linear regression was calculated and showed no correlation between age and number of tendon splits. Conclusions: 64% of specimens showed a longitudinal split in the distal ECU tendon. The location of these frequent splits corresponds to imaging abnormalities on MRI and US in prior studies.

Radial head arthroplasty was introduced in 1941 and the literature supports satisfactory overall midterm patient outcomes and acceptable complication profiles with several models. There are several previously described mechanisms by which radial head complications typically occur. We present the case of a rarely described mechanism of radial head implant failure: elbow synovitis and pain from partial dissociation and metallosis in an adjustably aligned, modular, monopolar, mixed metal, press-fit radial head arthroplasty., (Copyright © 2019 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Increased understanding of developmental disorders of the brain has shown that genetic mutations, environmental toxins and biological insults typically act during developmental windows of susceptibility. Identifying these vulnerable periods is a necessary and vital step for safeguarding women and their fetuses against disease causing agents during pregnancy and for developing timely interventions and treatments for neurodevelopmental disorders. We analyzed developmental time-course gene expression data derived from human pluripotent stem cells, with disease association, pathway, and protein interaction databases to identify windows of disease susceptibility during development and the time periods for productive interventions. The results are displayed as interactive Susceptibility Windows Ontological Transcriptome (SWOT) Clocks illustrating disease susceptibility over developmental time. Using this method, we determine the likely windows of susceptibility for multiple neurological disorders using known disease associated genes and genes derived from RNA-sequencing studies including autism spectrum disorder, schizophrenia, and Zika virus induced microcephaly. SWOT clocks provide a valuable tool for integrating data from multiple databases in a developmental context with data generated from next-generation sequencing to help identify windows of susceptibility.

Background: Scapular fractures after reverse shoulder arthroplasty (RSA) are an increasingly reported complication. Information is missing regarding midterm to long-term follow-up consequences. The aim of this study was to determine the rate of scapular fracture (acromial base and spine) after Grammont-style RSA and to report functional and radiographic results of patients with a minimum 5-year follow-up., Materials and Methods: We retrospectively reviewed 1953 Grammont-style RSAs in 1745 patients in a multicenter study. Of these, 953 patients (1035 RSAs) had minimum 5-year follow-up for functional and radiographic assessment (anteroposterior and scapular Y views., Results: Twenty-six patients (1.3%) had sustained a scapular fracture; of these, 19 (10 acromial base and 9 spine fractures) had minimum 5-year follow-up and were reviewed at a mean follow-up of 97 months. Three patients (15.8%) were diagnosed at the last follow-up after an undiagnosed fracture. There were 3 traumatic cases (15.8%) and 13 (68.4%) without antecedent trauma. These 16 patients underwent nonoperative treatment. The fracture was healed in 8 (4 acromion and 4 spine). The average active forward elevation was 109° (range, 50°-170°), and the Constant score was 47.0 points (range, 8-81 points)., Conclusions: Scapular fractures after Grammont-style RSAs are rare (1.3%) but remain a concern. These fractures occur mainly in the early postoperative 6 months. Immobilization with an abduction splint frequently resulted in nonunion or malunion. Final functional outcomes are poor regardless of acromial or spine fracture compared with primary RSA without fracture., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: All-soft tissue suture anchors provide advantages of decreased removal of bone and decreased glenoid volume occupied compared with traditional tap or screw-in suture anchors. Previous published data have led to biomechanical concerns with the use of first-generation all-soft suture anchors., Purpose/hypothesis: The purpose of this study was to evaluate the load to 2-mm displacement and ultimate load to failure of a second-generation all-soft suture anchor, compared with a first-generation anchor and a traditional PEEK (polyether ether ketone) anchor. The null hypothesis was that the newer second-generation anchor will demonstrate no difference in loads to 2-mm displacement after cycling compared with first-generation all-soft suture anchors., Study Design: Controlled laboratory study., Methods: Twenty human cadaveric glenoids were utilized to create 97 total suture anchor sites, and 1 of 3 anchors were randomized and placed into each site: (1) first-generation all-soft suture anchor (Juggerknot; Biomet), (2) second-generation all-soft suture anchor (Suturefix; Smith & Nephew), and (3) a control PEEK anchor (Bioraptor; Smith & Nephew). After initial cyclic loading, load to 2 mm of displacement and ultimate load to failure were measured for each anchor., Results: After cyclic loading, the load to 2-mm displacement was significantly less in first-generation anchors compared with controls ( P < .01). However, the load to 2-mm displacement was significantly greater in second-generation anchors compared with controls ( P < .01). There was no difference in ultimate load to failure between the first- and second-generation all-soft suture anchors ( P > .05)., Conclusion: The newer generation all-soft suture anchors with a theoretically more rigid construct and deployment configuration demonstrate biomechanical characteristics (specifically, with load to 2-mm displacement after cyclic loading) that are improved over first-generation all-soft suture anchors and similar to a traditional solid tap-in anchor. The configuration of these newer generation all-soft suture anchors appears to mitigate the biomechanical concerns of decreased load to failure with first-generation all-soft tissue suture anchors., Clinical Relevance: The theoretical advantages of all-soft anchors may be particularly valuable in revision surgery or in cases where multiple anchors are being placed into a small anatomic area., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Smith & Nephew and Biomet donated the anchors used in this study. A.D. was a previous consultant for Smith & Nephew, Biomet, and Arthrex.

Although the rupture of extensor tendons after distal radius fractures is well described, acute flexor tendon ruptures are much less common. We report a case of acute rupture of the flexor pollicis longus and flexor carpi radialis tendons with acute carpal tunnel syndrome after a Gustilo-Anderson type II open distal radius fracture. We reviewed the literature to identify risk factors for tendon rupture and the development of carpal tunnel syndrome.

Background: Successful arthroscopic repair of symptomatic superior labral tears in young athletes has been well documented. Superior labral repair in patients older than 40 years is controversial, with concerns for residual postoperative pain, stiffness, and higher rates of revision surgery., Purpose: To analyze the published data on the surgical treatment of superior labral injuries in patients aged ≥40 years, including those with concomitant injuries to the rotator cuff., Study Design: Systematic review., Methods: A systematic review of the literature was performed using the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The MEDLINE database via PubMed and the Cochrane Database of Systematic Reviews were searched for articles related to superior labrum anterior-posterior (SLAP) tears. Studies were included if they met the following criteria: the study contained at least 1 group of patients who had undergone arthroscopic repair of a type II or IV SLAP lesion with a minimum 2-year follow-up, objective and/or functional scoring systems were used to evaluate postoperative outcomes, and the mean patient age was ≥40 years for at least 1 treatment arm or subgroup analysis. Studies were excluded if the article was a review or if the article included data for SLAP type I, III, or V to X tears or Bankart lesions., Results: While several authors reported equivalent outcomes of SLAP repair in patients both older than 40 years and younger than 40 years, others demonstrated significantly higher failure rates in the older cohort. Decreased patient satisfaction and increasing complications, including postoperative stiffness and reoperations, occur at higher rates as the patient age increases. The literature demonstrates that biceps tenotomy and tenodesis are reliable alternatives to SLAP repair and that biceps tenotomy is a viable revision procedure for failed SLAP repair. With concomitant rotator cuff tears, the evidence favors debridement or biceps tenotomy over SLAP repair., Conclusion: While studies show that good outcomes can be obtained with SLAP repair in an older cohort of patients, age older than 40 years and workers' compensation status are independent risk factors for increased surgical complications. The cumulative evidence supports labral debridement or biceps tenotomy over labral repair when an associated rotator cuff injury is present., (© 2014 The Author(s).)

The capacity to achieve sufficient concentrations of Ag-specific Ab of the appropriate isotypes is a critical component of immunity that requires efficient differentiation and interactions of Ag-specific B and Th cells along with dendritic cells. Numerous bacterial toxins catalyze mono(ADP-ribosyl)ation of mammalian proteins to influence cell physiology and adaptive immunity. However, little is known about biological functions of intracellular mammalian mono(ADP-ribosyl)transferases, such as any ability to regulate Ab responses. poly-(ADP-ribose) polymerase 14 (PARP14), an intracellular protein highly expressed in lymphoid cells, binds to STAT6 and encodes a catalytic domain with mammalian mono(ADP-ribosyl)transferase activity. In this article, we show that recall IgA as well as the STAT6-dependent IgE Ab responses are impaired in PARP14-deficient mice. Whereas PARP14 regulation of IgE involved a B cell-intrinsic process, the predominant impact on IgA was B cell extrinsic. Of note, PARP14 deficiency reduced the levels of Th17 cells and CD103⁺ DCs, which are implicated in IgA regulation. PARP14 enhanced the expression of RORα, Runx1, and Smad3 after T cell activation, and, importantly, its catalytic activity of PARP14 promoted Th17 differentiation. Collectively, the findings show that PARP14 influences the class distribution, affinity repertoire, and recall capacity of Ab responses in mice, as well as provide direct evidence of the requirement for protein mono-ADP-ribosylation in Th cell differentiation.

We have designed and synthesized a series of HIV protease inhibitors (PIs) with enamino-oxindole substituents optimized to interact with the S2' subsite of the HIV protease binding pocket. Several of these inhibitors have sub-nanomolar K(i) and antiviral IC(50) in the low nM range against WT HIV and against a panel of multi-drug resistant (MDR) strains., (Copyright © 2012 Elsevier Ltd. All rights reserved.)