DNA hypomethylating agents increase activation and cytolytic activity of CD8+ T cells.

We demonstrate that DNA hypomethylating agent (HMA) treatment can directly modulate the anti-tumor response and effector function of CD8+ T cells. In vivo HMA treatment promotes CD8+ T cell tumor infiltration and suppresses tumor growth via CD8+ T cell-dependent activity. Ex vivo, HMAs enhance primary human CD8+ T cell activation markers, effector cytokine production, and anti-tumor cytolytic activity. Epigenomic and transcriptomic profiling shows that HMAs vastly regulate T cell activation-related transcriptional networks, culminating with over-activation of NFATc1 short isoforms. Mechanistically, demethylation of an intragenic CpG island immediately downstream to the 3' UTR of the short isoform was associated with antisense transcription and alternative polyadenylation of NFATc1 short isoforms. High-dimensional single-cell mass cytometry analyses reveal a selective effect of HMAs on a subset of human CD8+ T cell subpopulations, increasing both the number and abundance of a granzyme Bhigh, perforinhigh effector subpopulation. Overall, our findings support the use of HMAs as a therapeutic strategy to boost anti-tumor immune response.

Defining patient satisfaction after reverse total shoulder arthroplasty: a systematic review.

BACKGROUND: The prevalence of reverse total shoulder arthroplasty (rTSA) has grown rapidly. As indications for the procedure expand, the proportion of patients who have satisfactory outcomes after rTSA has not been well defined. This systematic literature review explores overall patient satisfaction after rTSA and defines patient satisfaction based on indication for surgery. METHODS: A literature search was performed for studies describing patient satisfaction after rTSA in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Papers were included if they investigated patient satisfaction after rTSA at a minimum of 2-year follow-up. Data were collected on patient demographics, including age, gender, and body mass index. Follow-up duration, indication for surgery, and patient reported outcome measures relating to patient satisfaction were also recorded. RESULTS: There were a total of 5234 patients and 5288 shoulders from the 45 included studies. The overall study population was 61.2% female and the average age was 71.1 years (range 23-99). Satisfaction results were recorded at final follow-up, with average follow-up of 49.1 months (range 24-228). Overall patient satisfaction ranged from 77.7% to 87.8%, depending on patient satisfaction patient reported outcome measures. When stratified by diagnosis, patients with a diagnosis of glenohumeral osteoarthritis (GHOA) rated better satisfaction on all metrics when compared to patients with a diagnosis of cuff tear arthropathy or massive rotator cuff tear. CONCLUSION: This systematic review demonstrated that patients who undergo rTSA for either GHOA, cuff tear arthropathy, or massive rotator cuff tear are generally satisfied with their procedure, with the rate of satisfaction highest in GHOA. Focusing on patient satisfaction may provide the best overall assessment of health care quality in a very understandable and tangible form. Overall satisfaction rate is valuable information for patient education and can be utilized as part of effective surgical counseling.

Same-day discharge vs. inpatient total shoulder arthroplasty: an age stratified comparison of postoperative outcomes and hospital charges.

BACKGROUND: As the number of total shoulder arthroplasty (TSA) procedures increases, there is a growing interest in improving patient outcomes, limiting costs, and optimizing efficiency. One approach has been to transition these surgeries to an outpatient setting. Therefore, the purpose of this study was to conduct an age-stratified analysis comparing the 90-day postoperative outcomes of primary TSA in the same-day discharge (SDD) and inpatient (IP) settings with a specific focus on the super-elderly. METHODS: This retrospective study included all patients who underwent primary anatomic or reverse TSA between January 2018 and December 2021 in ambulatory and IP settings. The outcome measures included length of stay (LOS), complications, hospital charges, emergency department (ED utilization), readmissions, and reoperations within 90 days following TSA. Patients with LOS ≤8 hours were considered as SDD, and those with LOS >8 hours were considered as IP. P < .05 was considered statistically significant. RESULTS: There were 121 and 174 procedures performed in SDD and IP settings, respectively. There were no differences in comorbidity indices between the SDD and IP groups (American Society of Anesthesiologists score P = .12, Elixhauser Comorbidity Index P = .067). The SDD cohort was younger than the IP group (SDD 67.0 years vs. 73.0 IP years, P < .001), and the SDD group higher rate of intraoperative tranexamic acid use (P = .015) and lower estimated blood loss (P = .009). There were no differences in 90-day overall minor (P = .20) and major complications (P = 1.00), ED utilization (P = .63), readmission (P = .25), or reoperation (P = .51) between the SDD and IP groups. When stratified by age, there were no differences in overall major (P = .80) and minor (P = .36) complications among the groups. However, the LOS was directly correlated with increasing age (LOS = 8.4 hours in ≥65 to <75-year cohort vs. LOS = 25.9 hours in ≥80-year cohort; P < .001). There were no differences in hospital charges between SDD and IP primary TSA in all 3 age groups (P = .82). CONCLUSION: SDD TSA has a shorter LOS without increasing postoperative major and minor complications, ED encounters, readmissions, or reoperations. Older age was not associated with an increase in the complication profile or hospital charges even in the SDD setting, although it was associated with increased LOS in the IP group. These results suggest that TSA can be safely performed expeditiously in an outpatient setting.

Clinical and radiographic outcomes of shoulder hemiarthroplasty for patients with glenoid medialization.

BACKGROUND: Glenoid bone loss in shoulder arthroplasty is a difficult problem that is prone to complications because of challenges with achieving glenoid component fixation and stability. The purpose of this study was to evaluate the outcomes of primary shoulder hemiarthroplasty for patients with severe glenoid medialization precluding placement of a glenoid component. METHODS: This was a retrospective case series evaluating patients who underwent shoulder hemiarthroplasty for severe glenoid erosion and medialization between 2010 and 2020. Patients were evaluated via chart review and phone survey to determine if there were any reoperations at final follow-up and to obtain Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and Simple Shoulder Test (SST) scores. Preoperative and postoperative radiographs were evaluated and compared to determine glenoid morphology, version, medialization, acromiohumeral distance, and humeral offset. Final postoperative films were also evaluated for anterosuperior migration and signs of mechanical failure, including loosening or periprosthetic fracture. RESULTS: Overall, there were 28 patients during this period who underwent shoulder hemiarthroplasty for severe glenoid medialization. Eight patients were deceased at the time of the study, 2 were unable to complete surveys because of dementia, and 7 were lost to follow-up. The final cohort included 11 shoulders and 11 patients with a mean age of 71 ± 7.1 years and mean follow-up of 6.7 years (range 1.6-13.0 years). Mean postoperative SANE, ASES, and SST scores were 80.6 ± 17.6, 71.5 ± 29.3, and 7.6 ± 2.0, respectively. There were no reoperations or revision surgeries at final follow-up. Radiographic evaluation demonstrated severe glenoid medialization and decreased lateral humeral offset, which was unchanged postoperatively. There were 2 patients with signs of anterosuperior migration at final radiographic follow-up but no signs of implant failure. CONCLUSION: Shoulder hemiarthroplasty for severe medial glenoid bone loss provides modest clinical outcomes and low rates of reoperation at mid- to long-term follow-up and is an option worth considering in cases where placement of a glenoid component is challenging because of deficient bone stock and high risk for complications.

Shoulder periprosthetic joint infection is associated with increased mortality.

BACKGROUND: Periprosthetic joint infections (PJIs) are a catastrophic complication after shoulder arthroplasty and may be associated with an increased mortality risk, as seen in hip and knee arthroplasty. Shoulder PJI organisms differ from hip and knee infections, as lower-virulence organisms, such as Cutibacterium acnes, are more commonly encountered. This study evaluated the association between shoulder PJI and mortality. METHODS: We retrospectively identified 411 patients who underwent revision shoulder arthroplasty from 2007 to 2020 at a single institution. 2018 International Consensus Meeting on Musculoskeletal Infection criteria were used to categorize each case as definite, probable, possible, or unlikely PJI. Mortality rate was assessed by performing chart reviews and an obituary search. Revision cases were grouped into a septic cohort (definite and probable PJI) and an aseptic cohort (possible and unlikely PJI). Kaplan-Meier analyses were performed to compare survival between septic and aseptic groups. The log-rank test was used to compare cumulative survival distributions and survival rates at 90 days, 6 months, 1 year, 2 years, and 5 years. Demographic information, Charlson Comorbidity Index (CCI), and culture data were collected. PJI organisms were categorized as virulent or nonvirulent per an infectious disease specialist, and predictors of mortality were determined by performing stepwise logistic regression analyses. RESULTS: The overall mortality rate was significantly greater (P < .001) in the septic group (20.5%) than in the aseptic group (6.6%). When evaluating time from revision surgery to death, patients with PJI had significantly greater mortality compared with those undergoing aseptic revision at 2 years (7.7% vs. 2.1%, P = .01) and 5 years (17% vs. 5.1%, P < .001). Body mass index, CCI, race, sex, and age were not significantly different between groups. Groups differed in utilization of 2-staged procedures (65% septic, 9% aseptic, P < .001). Multivariate regression analysis found that the variables most associated with mortality were septic revision, 2-staged procedures, and CCI. In the septic group, patients with C acnes PJI had a significantly lower mortality rate when compared to PJI from any other offending organism (3.1% vs. 48.4%, P = .001). CONCLUSION: Revision shoulder arthroplasty in the setting of PJI not only carries severe functional consequences for patients but is also associated with an increased mortality risk. Furthermore, C acnes infections are associated with a more favorable survival profile than PJI resulting from other organisms. Continued efforts to decrease shoulder arthroplasty infection rates are warranted and may influence long-term survival.

Complications after operative treatment of high-grade acromioclavicular injuries.

BACKGROUND: Treatment of Rockwood type III-V acromioclavicular (AC) joint injuries remains controversial. Numerous reconstruction techniques have been proposed. The purpose of this study was to describe the complication profile in a large cohort of patients who underwent surgical management of AC joint separations using a variety of reconstruction strategies. METHODS: All patients who underwent surgery for AC joint injuries from 2013 to 2019 at a single institution were identified. Chart review was performed to capture patient demographics, radiographic measurements, operative techniques, postoperative complications, and revision surgery. Structural failure was defined as a radiographic loss of reduction of greater than 50% when comparing immediate and final postoperative imaging. Logistic regression analysis was performed to identify risk factors for complications and revision surgery. RESULTS: Of the 279 patients included in the study, 66 (24%) had type III separations, 20 (7%) type IV, and 193 (69%) type V. Fifty-three percent underwent surgery acutely (<6 weeks of injury), and 40% were chronic (>3 months). A total of 252 of the 279 surgeries (90%) were performed open and 27 (10%) were arthroscopically assisted. Allograft was used in 164 of 279 (59%) cases. Specific operative techniques (with or without allograft) included hook plating (1%), modified Weaver Dunn (16%), cortical button fixation (18%), and suture fixation (65%). At mean 28-week follow-up, 108 complications were identified in 97 patients (35%). Complications were identified at mean 20 ± 21 weeks. Sixty-nine structural failures (25%) were identified. Persistent AC joint pain requiring injection, clavicle fracture, adhesive capsulitis, and hardware complications were the other most common complications. Twenty-one patients (8%) underwent unplanned revision surgery at mean 38 ± 28 weeks after the index procedure, with the most common indication for structural failure, hardware complications, or fracture of the clavicle or coracoid. Patients who had surgery after 6 weeks from injury had a significantly greater risk of having a complication (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.34-7.77, P = .009) and a significantly greater risk of having structural failure (OR 2.65, 95% CI 1.38-5.28, P = .004). Patients who had an arthroscopic technique had a greater risk of structural failure (P = .002). Complications, structural failure, and revision surgery were not significantly correlated with use of allograft or specific operative techniques. CONCLUSION: Surgical management of AC joint injuries is associated with a relatively high complication profile. Loss of reduction in the postoperative period is common. However, the revision surgery rate is low. These findings are important for patient preoperative counseling.

Interplay of Aging and Lot-to-Lot Variability on the Physical and Chemical Properties of Excipients: A Case Study of Mono- and Diglycerides.

The present study investigates the chemical composition governing the physical properties of mono- and diglycerides (MDGs) at the microstructural level, as a function of aging and lot-to-lot variability. The physical structure of the MDG plays a vital role in ameliorating the emulsion stability and is widely explored in diverse research horizons related to the pharmaceutical, cosmetic, and food industries. In an effort to understand the mechanism of emulsion stabilization, physical properties were extensively evaluated in selective commercial lots to determine if there is a correlation between the chemical composition of MDG and physical properties. The solid state of the MDG samples with different aging profiles was characterized using X-ray scattering, differential scanning calorimetry, attenuated total reflection-Fourier transform infrared spectroscopy, and NMR relaxometry. Moreover, the kinetic aspect of solid-state transformation was also evaluated via treating MDG samples with a heat-cool cycle. The chemical composition of MDGs was quantified using a quantitative NMR (qNMR) method. Interestingly, the X-ray scattering results demonstrated a change in the MDG polymorphic form and an increase in the %ß content as a function of aging. The increase in the %ß content led to the formation of rigid crystal structures of MDG, as evident from the NMR relaxometry. Chemical quantification of isomeric composition revealed chemical composition change as a potentially critical factor responsible for the altered physical structures of MDG with respect to aging and lot-to-lot variability. The findings correlated the solid-state transformation with the change in the chemical composition of the MDG as a combined effect of aging and lot-to-lot variability. This work serves as a basis to better understand the interdependency of the physicochemical properties of MDG. Furthermore, the present work can also be used as guidance for setting up the specifications of MDG, as per the required polymorphic form for a multitude of applications.

Cemented versus uncemented fixation of second-generation Trabecular Metal glenoid components: minimum 5-year outcomes.

BACKGROUND: Total shoulder arthroplasty (TSA) with second-generation Trabecular Metal™ implants (Zimmer, Warsaw, IN, USA) has shown good short-term outcomes. Differences in outcomes between cemented and uncemented fixation are unknown. This study compared the clinical, radiographic, and patient-rated outcomes of TSA with cemented vs. uncemented TM glenoids at minimum 5-year follow-up. METHODS: Patients who underwent anatomic TSA with second-generation TM glenoid components for primary osteoarthritis were identified for minimum 5-year follow-up. The patients were divided into 2 groups: cemented and uncemented glenoid fixation. Outcome measures included implant survival, patient-rated outcome scores (Patient-Reported Outcomes Measurement Information System [PROMIS] and American Shoulder and Elbow Surgeons scores), shoulder range of motion, and radiographic analysis. Findings were compared between groups. RESULTS: The study included 55 shoulders: 27 in the cemented group (21 with full radiographic follow-up) and 28 in the uncemented group (22 with full radiographic follow-up). Both groups had similar follow-up times (6.6 years in cemented group vs. 6.7 years in uncemented group, P = .60). Moreover, the groups did not differ significantly in sex composition, age at the time of surgery, or preoperative Walch glenoid grade distribution. No patients required revision surgery. The 2 groups had similar preoperative range of motion, but patients in the uncemented group had greater follow-up forward flexion (P = .03), external rotation (P < .01), and lateral elevation (P = .03) than did patients in the cemented group. PROMIS scores were not significantly different between groups. American Shoulder and Elbow Surgeons scores were similar (89.8 in cemented group vs. 94.1 in uncemented group, P = .21). Mid-term radiographs showed a metal debris rate of 24% in the cemented group and 27% in the uncemented group. Although these values were not significantly different (P = .90), the frequency of mild metal debris (grade 1-2), when present, was greater in the uncemented group (grade 2 in 6 shoulders) than in the cemented group (grade 1 in 4 and grade 2 in 1, P = .02). There was a greater presence of mild (grade 1) radiolucent lines in the uncemented group (64%) than in the cemented group (29%, P < .01). No glenoid had evidence of loosening (defined by a change in position or radiolucent lines > 2 mm). The presence of metal debris and radiolucent lines did not have a significant effect on clinical outcomes. CONCLUSION: At minimum 5-year follow-up, TSA patients with TM glenoids demonstrated excellent clinical and patient-reported outcomes with a 100% implant survival rate, regardless of cemented vs. uncemented fixation. However, the uncemented group showed a significantly higher rate of radiolucent lines and a higher frequency of mild metal debris. These radiographic findings did not affect the clinical outcomes, and their implications for long-term outcomes and prosthesis survival is unknown.

Developing a Biorelevant Dissolution Method for an Extrudable Core System (ECS) Osmotic Tablet.

The objective of this work is to develop a biorelevant dissolution method to support the clinical study for In Vitro In Vivo Correlation (IVIVC) of the first commercially approved single-layer extrudable core system (ECS) osmotic tablet - the 11 mg tofacitinib modified-release tablet. The dissolution conditions were selected through analysis of experimental work including several designed experiments (DoE). The Apparatus 2 (paddles) was selected over the Apparatus 1 (baskets) to minimize the dissolution test variability. The paddle speed was kept at 50 rpm to be conservative and because higher paddle speed did not offer statistically significant improvement in dissolution test variability. The buffer of 50 mM potassium phosphate at pH 6.8 was selected over other buffers at lower or acid pH as the in vivo drug release is expected to occur in the small intestinal region, where the pH is approximately neutral. Finally, the statistically designed experiments proved that use of the Japanese basket sinkers was effective in reducing dissolution variability and eliminating the artificial shift in dissolution profile caused by final pink color-coated tablets sticking to the dissolution vessel. Discriminatory power of the method was verified and the method was validated per ICH and FDA guidelines. Since a Level A IVIVC is established from the analysis of the results of both in vivo clinical study and in vitro dissolution testing, the method is proven to be biorelevant. It also serves a suitable quality control dissolution method.

Diversity among academic orthopedic shoulder and elbow surgery faculty in the United States.

BACKGROUND: The purpose of this study was to perform a cross-sectional analysis of diversity among academic shoulder and elbow surgeons in the United States. METHODS: US shoulder and elbow surgeons who participated in shoulder and elbow fellowship and/or orthopedic surgery resident education as of November 2018 were included. Demographic data (age, gender, race), practice setting, years in practice, academic rank, and leadership roles were collected through publicly available databases and professional profiles. Descriptive statistics were performed and findings were compared between different racial and gender groups. Statistical significance was set at P <.05. RESULTS: A total of 186 orthopedic shoulder and elbow surgeons were identified as participating in shoulder and elbow fellowship and/or orthopedic surgery residency education. Overall, 83.9% were white, 14.5% were Asian, 1.1% were Hispanic, 0.5% were an other race, and 0% were African American. In addition, 94.6% of surgeons were male, whereas 5.4% were female. Further, 64.5% of all surgeons had been in practice for >10 years, and 39.2% worked in an urban setting. Less than half (40.3%) of the surgeons practicing primarily at academic institutions held a professor rank. White surgeons had a significantly greater time in practice vs. nonwhite surgeons (mean 18.8 vs. 12.6 years, P < .01) and were more likely to hold a professor rank (44.0% vs. 21.7%, P = .04). CONCLUSION: Racial and gender diversity among US shoulder and elbow surgeons who participate in fellowship and residency education is lacking. Hispanic, African American, and female surgeons are underrepresented. Efforts should be made to identify the reasons for these deficiencies and address them to further advance the field of orthopedic shoulder and elbow surgery.

What Regions of the Distal Clavicle Have the Greatest Bone Mineral Density and Cortical Thickness? A Cadaveric Study.

BACKGROUND: Osteosynthesis of distal clavicle fractures can be challenging because of comminution, poor bone quality, and deforming forces at the fracture site. A better understanding of regional differences in the bone structure of the distal clavicle is critical to refine fracture fixation strategies, but the variations in BMD and cortical thickness throughout the distal clavicle have not been previously described. PURPOSE: /questions (1) Which distal clavicular regions have the greatest BMD? (2) Which distal clavicular regions have the greatest cortical thickness values? METHODS: Ten distal clavicle specimens were dissected from cadaveric shoulders. Eight specimens were female and two were male, with a mean (range) age of 63 years (59 to 67). The specimens were selected to match known epidemiology, as distal clavicular fractures occur more commonly in older patients with osteoporotic bone, and clavicular fractures in older patients are more common in females than males. The clavicles were then imaged using quantitative micro-CT to create 3-D images. The BMD and cortical thickness were calculated for 10 regions of interest in each specimen. These regions were selected to represent locations where distal clavicular fractures commonly occur and locations of likely bony comminution. Findings were compared between different regions using repeated measures ANOVA with Geiser-Greenhouse correction, followed by Bonferroni method multiple comparison testing. Effect size was also calculated to estimate the magnitude of difference between regions. RESULTS: The four most medial regions of the distal clavicle contained the greatest BMD (anterior intertubercle space 887 ± 31 mgHA/cc, posterior intertubercle space 879 ± 26 mgHA/cc, anterior conoid tubercle 900 ± 21 mgHA/cc, posterior conoid tubercle 896 ± 27 mgHA/cc), while the four most lateral regions contained the least BMD (anterior lateral distal clavicle 804 ± 32 mgHA/cc, posterior lateral distal clavicle 800 ± 38 mgHA/cc, anterior medial distal clavicle 815 ± 27 mgHA/cc, posterior medial distal clavicle 795 ± 26 mgHA/cc). All four most medial regions had greater BMD than the four most lateral regions, with p < 0.001 for all comparisons. For the BMD ANOVA, η was determined to be 0.81, representing a large effect size. The four most medial regions of the distal clavicle also had the greatest cortical thickness (anterior intertubercle space 0.7 ± 0.2 mm, posterior intertubercle space 0.7 ± 0.3 mm, anterior conoid tubercle 0.9 ± 0.2 mm, posterior conoid tubercle 0.7 ± 0.2 mm), while the four most lateral regions had the smallest cortical thickness (anterior lateral distal clavicle 0.2 ± 0.1 mm, posterior lateral distal clavicle 0.2 ± 0.1 mm, anterior medial distal clavicle 0.3 ± 0.1 mm, posterior medial distal clavicle 0.2 ± 0.1 mm). All four most medial regions had greater cortical thickness than the four most lateral regions, with p < 0.001 for all comparisons. For the cortical thickness ANOVA, η was determined to be 0.80, representing a large effect size. No differences in BMDs and cortical thicknesses were found between anterior and posterior regions of interest in any given area. CONCLUSIONS: In the distal clavicle, BMD and cortical thickness are greatest in the conoid tubercle and intertubercle space. When compared with clavicular regions lateral to the trapezoid tubercle, the BMD and cortical thickness of the conoid tubercle and intertubercle space were increased, with a large magnitude of difference. CLINICAL RELEVANCE: Distal clavicular fractures are prone to comminution and modern treatment strategies have centered on the use of locking plate technology and/or suspensory fixation between the coracoid and the clavicle. However, screw pullout or cortical button pull through are known complications of locking plate and suspensory fixation, respectively. Therefore, it seems intuitive that implant placement during internal fixation of distal clavicle fractures should take advantage of the best-available bone. Although osteosynthesis was not directly studied, our study suggests that the best screw purchase in the distal clavicle is available in the areas of the conoid tubercle and intertubercle space, as these areas had the best bone quality. Targeting these areas during implant fixation would likely reduce implant failure and strengthen fixation. Future studies should build on our findings to determine if osteosynthesis of distal clavicular fractures with targeted screw purchase or cortical button placement in the conoid tubercle and intertubercle space increase fixation strength and decreases construct failure. Furthermore, our findings provide consideration for novel distal clavicular locking plate designs with modified screw trajectories or refined surgical techniques with suspensory fixation implants to reliably capture these areas of greatest bone quality.

Reconstruction of the Superior Glenoid Labrum With Biceps Tendon Autograft: A Cadaveric Biomechanical Study.

PURPOSE: To describe 2 superior labral reconstruction techniques using long head of the biceps (LHB) autograft and to investigate the ability of the 2 reconstruction techniques to restore superior restraint to the glenohumeral joint compared with superior labrum-deficient models. METHODS: In this biomechanical study, 10 cadaveric shoulders were cycled on a servohydraulic machine while the force required to cause superior subluxation was recorded. Each specimen was cycled under 4 conditions: intact labrum, SLAP tear, posterior (9- to 12-o'clock position) labral reconstruction using LHB autograft (superior labral reconstruction 1 [SLR1]), and 180° (9- to 3-o'clock position) labral reconstruction using LHB autograft (superior labral reconstruction 2 [SLR2]). RESULTS: The mean peak force required to cause superior subluxation in the intact labrum was 32.75 N versus 19.75 N in the SLAP tear (P = .0120). SLR1 required a mean peak force of 31.23 N versus 44.09 N for SLR2 (P = .0175). SLR1 required 94.96% of the force needed in the intact labrum to cause subluxation, whereas SLR2 required 140.6%. SLR1 and SLR2 required 34.21% higher (P = .0074) and 79.84% higher (P = .0033) forces, respectively, to generate subluxation compared with the SLAP tear state. CONCLUSIONS: Both proposed superior labral reconstruction techniques increased the force needed for humeral head superior migration in the setting of a labral tear. SLR1 (posterior labral reconstruction) closely matched the constraint of an intact labrum, whereas SLR2 (180° labral reconstruction) provided greater superior constraint than an intact labrum. CLINICAL RELEVANCE: The natural history of irreparable rotator cuff tears results in superior glenohumeral escape and eventual arthrosis. The superior glenoid labrum is an important contributor to superior glenohumeral constraint and is often degenerated in this setting. Clinical application of the 2 described superior labral reconstruction techniques may improve glenohumeral superior stability in patients with rotator cuff disease and superior labral deficiency.

Preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores predict postoperative outcome in total shoulder arthroplasty patients.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) has recently been validated in orthopedic patients with upper-extremity disease. The purpose of this study was to describe preoperative and postoperative PROMIS scores in total shoulder arthroplasty (TSA) patients, compare PROMIS physical function (PF) scores with clinical functional measurements, and determine whether preoperative PROMIS scores could predict achievement of the minimal clinically important difference (MCID) postoperatively. METHODS: Preoperative and postoperative (>3 months) PROMIS scores in patients who underwent primary anatomic TSA were reviewed. Preoperative and postoperative shoulder forward flexion and external rotation were also collected. PROMIS PF, pain interference (PI), and depression scores were compared. Accuracy analyses determined whether preoperative PROMIS scores from each domain could predict postoperative achievement of the MCID in the same domain. RESULTS: The study included 62 patients. Significant improvements in PROMIS PF, PI, and depression scores, as well as forward flexion and external rotation, were found postoperatively (P < .001). The multivariate model demonstrated that preoperative PROMIS PF, PI, and depression scores were predictive of postoperative achievement of the MCID (area under the receiver operating characteristic curve, 0.70-0.87). Ninety percent cutoff scores showed that patients with a preoperative PF score lower than 31.7, PI score greater than 66.9, and depression score greater than 55.5 were more likely to achieve the MCID. CONCLUSIONS: In TSA patients, preoperative PROMIS PF, depression, and PI scores demonstrated strong to excellent abilities to predict postoperative achievement of the MCID. PROMIS PF scores were responsive to the functional improvements observed clinically. The reported cutoff scores allow surgeons to identify patients with increased or decreased probabilities of achieving a clinically meaningful improvement after TSA.

Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes.

An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the improved doxorubicin loading (∼40 µg Dox/mg CSP) results in a substantial decrease in MCF-7 cell viability.

Cell-type specific features of circular RNA expression.

Thousands of loci in the human and mouse genomes give rise to circular RNA transcripts; at many of these loci, the predominant RNA isoform is a circle. Using an improved computational approach for circular RNA identification, we found widespread circular RNA expression in Drosophila melanogaster and estimate that in humans, circular RNA may account for 1% as many molecules as poly(A) RNA. Analysis of data from the ENCODE consortium revealed that the repertoire of genes expressing circular RNA, the ratio of circular to linear transcripts for each gene, and even the pattern of splice isoforms of circular RNAs from each gene were cell-type specific. These results suggest that biogenesis of circular RNA is an integral, conserved, and regulated feature of the gene expression program.

Validation of a Skin-Lesion Image-Matching Algorithm Based on Computer Vision Technology.

BACKGROUND: Melanoma incidence is increasing globally, but consistently accurate skin-lesion classification methods remain elusive. We developed a simple software system to classify potentially all types of skin lesions. In the current study, we evaluated the system's ability to identify melanomas with a diameter of 10 mm or larger. MATERIALS AND METHODS: The skin-lesion classification system is composed of a proprietary database of nearly 12,000 diagnosed skin-lesion images and a computer algorithm based on the principles of content-based image retrieval. The algorithm compares characteristics of new skin-lesion images with images in the database to identify the nearest-match diagnosis. RESULTS: Nearly all classification accuracy measures for this new system exceeded 90%, with results for sensitivity of 90.4% (95% confidence interval, 85.6-93.7%), specificity of 91.5% (85.4-95.2%), positive predictive value of 94.5% (90.4-96.9%), negative predictive value of 85.5% (78.7-90.4%), and overall classification accuracy of 90.8% (87.2-93.4%). CONCLUSIONS: The image-matching algorithm performed with high accuracy for the classification of larger melanomas. Furthermore, the system does not require a dermoscope or any other specialized hardware; any close-focusing camera will do. This system has the potential to be an inexpensive and accurate tool for the evaluation of skin lesions in ethnically and geographically diverse populations.

Tunable Conformation-Dependent Engineered Protein·Gold Nanoparticle Nanocomposites.

We demonstrate the fabrication of protein·gold nanoparticle (AuNP) nanocomposites in situ, leading to distinct assemblies dependent upon protein secondary structure. In the presence of pentameric coiled-coil proteins C and Q, which contain histidine tags and have helicities of 54 and 65%, respectively, templation of AuNP results in precipitation of the protein·AuNP composites with AuNPs 6.5 nm in diameter, creating macromolecular assemblies on the micrometer scale. In the absence of the histidine tags, the resulting Cx and Qx proteins, which exhibit lower helicities of 37 and 45%, respectively, stabilize soluble protein·AuNP composites with AuNPs 4.5 nm in diameter for several days without aggregating. By manipulating protein structure via external triggers, such as TFE, we obtain control over the macromolecular conformation and overall physicochemical properties. These hybrid protein·AuNP assemblies can be readily deposited on electrodes, where they can serve as a tunable bionanocomposite kinetic barrier.

The Influence of Component Design and Positioning on Soft-Tissue Tensioning and Complications in Reverse Total Shoulder Arthroplasty: A Review.

¼ Reverse total shoulder arthroplasty was designed to function in the rotator cuff deficient shoulder by adjusting the glenohumeral center of rotation (COR) to maximize deltoid function.¼ Adjustments in the COR ultimately lead to changes in resting tension of the deltoid and remaining rotator cuff, which can affect implant stability and risk of stress fracture.¼ Soft-tissue balance and complication profiles can be affected by humeral component (version, neck shaft angle, and inlay vs. onlay) and glenoid component (sagittal placement, version, inclination, and lateralization) design and application.¼ A good understanding of the effects on soft-tissue balance and complication profile is critical for surgeons to best provide optimal patient outcomes.

Proximal humerus fractures: Postoperative protocols and factors affecting treatment decisions among shoulder and elbow and orthopedic trauma surgeons.

Background: Proximal humerus fractures (PHFs) can lead to functional decline in geriatric and polytraumatized patients. Treatment of PHFs is an area of much debate and much variability between practitioners. Objectives: We surveyed orthopedic trauma (OT) and shoulder and elbow (SE) surgeons to evaluate differences in postoperative protocols when treating acute PHFs with open reduction internal fixation (ORIF), intramedullary nailing (IMN), or hemi or reverse shoulder arthroplasty (rTSA). Materials and methods: We distributed a web-based survey to three OT and SE associations between August 2018-April 2019. Questions included practice characteristics, standard postoperative protocols for weight-bearing, lifting, and range of motion (ROM) by treatment modality, and factors affecting modality and postoperative protocol decisions. We compared the subspecialties. Results: 239 surgeons [100 (42.2 %) OT, 118 (49.8 %) SE] completed the survey. OT were more likely to allow immediate ROM, lifting, and weight bearing following intramedullary nailing (IMN), open reduction internal fixation with a locking plate (ORIF), or arthroplasty (all p < 0.025), and to allow earlier unrestricted use of the extremity following IMN and arthroplasty (p = 0.001, p = 0.021 respectively). OT were more likely to consider operating on a PHF if there was contralateral upper extremity injury or need of the injured arm for work or activities of daily living (all p < 0.026). The subspecialties did not differ significantly on factors affecting their postoperative protocols. OT preferred IMN and SE surgeons preferred rTSA for allowing immediate unrestricted postoperative weight bearing, ROM, or lifting (all p < 0.001). Conclusion: There are significant differences in postoperative protocols between trauma and SE surgeons when treating PHFs. Postoperative protocols should be further studied to balance surgical outcomes and the risks of functional decline when treating patients with PHFs.

Low acromial insufficiency fracture rate in reverse shoulder arthroplasty with distal clavicle excision.

Background: This study investigated the rate of acromial insufficiency fractures (AIF) in patients undergoing reverse shoulder arthroplasty (RSA) with concomitant distal clavicle excision (DCE). Methods: Patients who underwent primary RSA with DCE by a single surgeon from 2010 to 2021 were identified. Exclusion criteria included revision RSA, RSA for fracture, or cases utilizing an augmented baseplate or bone graft. AIF was defined as a radiographically proven acromion or scapular spine fracture. Pain without an identifiable fracture on imaging was defined as an acromial insufficiency reaction. Patient demographics, implant information, and radiograph measurements were compared between patients with and without acromial pathology. Results: One hundred and seventy-five patients were included. Mean age was 72.8 years, and 67% of patients were female. There were 3/174 acromial insufficiency fractures (1.7%). AIF occurred at a mean of 9.3 months after surgery. Twelve patients had insufficiency reactions (6.9%). Patients with acromial pathology were more likely to be female (p = .003) and have a diagnosis of osteoporosis (p = .047) and inflammatory arthritis (p = .049). There was no significant difference between groups in terms of other factors. Conclusion: The AIF rate in patients who underwent RSA with DCE was 1.7%. These findings suggest that DCE in the setting of RSA may have a protective role against AIF.