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 (PRISMA) 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 (BMI). Follow-up duration, indication for surgery, and patient reported outcome measures (PROMs) 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 PROMs. 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 (CTA) or massive rotator cuff tear (MRCT). CONCLUSION: This systematic review demonstrated that patients who undergo rTSA for either GHOA, CTA, or MRCT 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 inpatient settings. The outcome measures included LOS, complications, hospital charges, 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 <0.05 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 (ASA score P=0.12, ECI P=0.067). The SDD cohort was younger than the IP group (SDD 67.0 years vs. 73.0 IP years, P<0.001), and the SDD group higher rate of intraoperative tranexamic acid use (P=0.015) and lower estimated blood loss (P=0.009). There were no differences in 90-day overall minor (P=0.20) and major complications (P=1.00), ED utilization (P=0.63), readmission (P=0.25) or reoperation (P =0.51) between the SDD and IP groups. When stratified by age, there were no differences in overall major (P=0.80) and minor (P=0.36) 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<0.001). There were no differences in hospital charges between SDD and IP primary TSA in all 3 age groups (P=0.82). 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. LEVEL OF EVIDENCE: Level III; Retrospective Comparative Study.

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 due to 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 (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 due to dementia, and 7 were lost to follow-up. The final cohort included 11 shoulders and 11 patients with 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 due to deficient bone stock and high risk for complications.

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.

Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer.

Viral mimicry describes the immune response induced by endogenous stimuli such as double-stranded RNA (dsRNA) from endogenous retroelements. Activation of viral mimicry has the potential to kill cancer cells or augment anti-tumor immune responses. Here, we systematically identify mechanisms of viral mimicry adaptation associated with cancer cell dependencies. Among the top hits is the RNA decay protein XRN1 as an essential gene for the survival of a subset of cancer cell lines. XRN1 dependency is mediated by mitochondrial antiviral signaling protein and protein kinase R activation and is associated with higher levels of cytosolic dsRNA, higher levels of a subset of Alus capable of forming dsRNA, and higher interferon-stimulated gene expression, indicating that cells die due to induction of viral mimicry. Furthermore, dsRNA-inducing drugs such as 5-aza-2'-deoxycytidine and palbociclib can generate a synthetic dependency on XRN1 in cells initially resistant to XRN1 knockout. These results indicate that XRN1 is a promising target for future cancer therapeutics.

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.

Androgen blockade primes NLRP3 in macrophages to induce tumor phagocytosis.

Immune-based therapies induce durable remissions in subsets of patients across multiple malignancies. However, there is limited efficacy of immunotherapy in metastatic castrate-resistant prostate cancer (mCRPC), manifested by an enrichment of immunosuppressive (M2) tumor- associated macrophages (TAM) in the tumor immune microenvironment (TME). Therefore, therapeutic strategies to overcome TAM-mediated immunosuppression are critically needed in mCRPC. Here we discovered that NLR family pyrin domain containing 3 (NLRP3), an innate immune sensing protein, is highly expressed in TAM from metastatic PC patients treated with standard-of-care androgen deprivation therapy (ADT). Importantly, ex vivo studies revealed that androgen receptor (AR) blockade in TAM upregulates NLRP3 expression, but not inflammasome activity, and concurrent AR blockade/NLRP3 agonist (NLRP3a) treatment promotes cancer cell phagocytosis by immunosuppressive M2 TAM. In contrast, NLRP3a monotherapy was sufficient to enhance phagocytosis of cancer cells in anti-tumor (M1) TAM, which exhibit high de novo NLRP3 expression. Critically, combinatorial treatment with ADT/NLRP3a in a murine model of advanced PC resulted in significant tumor control, with tumor clearance in 55% of mice via TAM phagocytosis. Collectively, our results demonstrate NLRP3 as an AR-regulated "macrophage phagocytic checkpoint", inducibly expressed in TAM by ADT and activated by NLRP3a treatment, the combination resulting in TAM-mediated phagocytosis and tumor control.

BET Inhibition Sensitizes Immunologically Cold Rb-Deficient Prostate Cancer to Immune Checkpoint Blockade.

Non-T-cell-inflamed immunologically "cold" tumor microenvironments (TME) are associated with poor responsiveness to immune checkpoint blockade (ICB) and can be sculpted by tumor cell genomics. Here, we evaluated how retinoblastoma (Rb) tumor-suppressor loss-of-function (LOF), one of the most frequent alterations in human cancer and associated with lineage plasticity, poor prognosis, and therapeutic outcomes, alters the TME, and whether therapeutic strategies targeting the molecular consequences of Rb loss enhance ICB efficacy. We performed bioinformatics analysis to elucidate the impact of endogenous Rb LOF on the immune TME in human primary and metastatic tumors. Next, we used isogenic murine models of Rb-deficient prostate cancer for in vitro and in vivo mechanistic studies to examine how Rb loss and bromodomain and extraterminal (BET) domain inhibition (BETi) reprograms the immune landscape, and evaluated in vivo therapeutic efficacy of BETi, singly and in combination with ICB and androgen deprivation therapy. Rb loss was enriched in non-T-cell-inflamed tumors, and Rb-deficient murine tumors demonstrated decreased immune infiltration in vivo. The BETi JQ1 increased immune infiltration into the TME through enhanced tumor cell STING/NF-κB activation and type I IFN signaling within tumor cells, resulting in differential macrophage and T-cell-mediated tumor growth inhibition and sensitization of Rb-deficient prostate cancer to ICB. BETi can reprogram the immunologically cold Rb-deficient TME via STING/NF-κB/IFN signaling to sensitize Rb-deficient prostate cancer to ICB. These data provide the mechanistic rationale to test combinations of BETi and ICB in clinical trials of Rb-deficient prostate cancer.

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.

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.

Endogenous retroelements as alarms for disruptions to cellular homeostasis.

Endogenous retroelements are DNA sequences which can duplicate and move to new locations in the genome. Actively moving endogenous retroelements can be disruptive to the host, and their expression is therefore often repressed. Interestingly, drugs that disrupt the repression of endogenous retroelements show promise for treating cancer. Expressed endogenous retroelements can activate innate immune receptors that activate the antiviral response, potentially leading to the death of cancer cells. We discuss disruptions to cellular processes which can lead to activation of the antiviral state from endogenous retroelements, and present the 'fire alarm hypothesis', where we argue that endogenous retroelements act as alarms for disruptions to these cellular processes. Furthermore, we discuss the properties of endogenous retroelements which make them suitable as alarms.

Outcomes of Acute Versus Subacute Scapholunate Ligament Repair.

Purpose: This study investigated the long-term outcomes of direct scapholunate ligament (SLL) repairs with or without dorsal capsulodesis performed within 6 weeks (acute repair) of a SLL tear versus 6 to 12 weeks following injury (subacute repair). Methods: A review of medical records from April 1996 to April 2012 identified 24 patients who underwent SLL repair (12 acute, 12 subacute). Patients returned to the clinic for radiographic examinations of the injured wrist, standardized physical examinations, and validated questionnaires. Results: The mean follow-up times for the acute and subacute groups were 7.2 and 6.2 years, respectively. At the final examination, patients with acute surgery regained more wrist extension (acute = 55°, subacute = 47°). The total wrist flexion-extension arcs, grip strengths, pinch strengths, and patient-rated outcome scores were found to be similar between groups. The final scapholunate gap, scapholunate angle, and the prevalence of arthritis were also found to be similar between the acute and subacute groups. Conclusions: Although SLL repair is more commonly recommended for treatment of acute SLL injuries, there were no significant long-term differences between acute and subacute SLL surgeries (repair ± capsulodesis). Type of study/level of evidence: Prognostic III.

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.

Endogenous Retroelements and the Viral Mimicry Response in Cancer Therapy and Cellular Homeostasis.

Features of the cancer epigenome distinguish cancers from their respective cell of origin and establish therapeutic vulnerabilities that can be exploited through pharmacologic inhibition of DNA- or histone-modifying enzymes. Epigenetic therapies converge with cancer immunotherapies through "viral mimicry," a cellular state of active antiviral response triggered by endogenous nucleic acids often derived from aberrantly transcribed endogenous retrotransposons. This review describes the initial characterization and expansion of viral mimicry-inducing approaches as well as features that "prime" cancers for viral mimicry induction. Increased understanding of viral mimicry in therapeutic contexts suggests potential physiologic roles in cellular homeostasis. SIGNIFICANCE: Recent literature establishes elevated cytosolic double strand RNA (dsRNA) levels as a cancer-specific therapeutic vulnerability that can be elevated by viral mimicry-inducing therapies beyond tolerable thresholds to induce antiviral signaling and increase dependence on dsRNA stress responses mediated by ADAR1. Improved understanding of viral mimicry signaling and tolerance mechanisms reveals synergistic treatment combinations with epigenetic therapies that include inhibition of BCL2, ADAR1, and immune checkpoint blockade. Further characterization of viral mimicry tolerance may identify contexts that maximize efficacy of conventional cancer therapies.

Radiographic and clinical outcomes of second generation Trabecular Metal™ glenoid components in total shoulder arthroplasty.

BACKGROUND: Total shoulder arthroplasty with second generation porous tantalum glenoid implants (Trabecular Metal™) has shown good short-term outcomes, but mid-term outcomes are unknown. This study describes the clinical, radiographic, and patient-rated mid-term outcomes of total shoulder arthroplasty utilizing cemented Trabecular Metal™ glenoid components. METHODS: Patients who underwent anatomic total shoulder arthroplasty with cemented Trabecular Metal™ glenoid components for primary osteoarthritis were identified for minimum five-year follow-up. The primary outcome measure was implant survival; secondary outcome measures included patient-rated outcome scores, shoulder range of motion findings, and radiographic analysis. RESULTS: Twenty-seven patients were enrolled in the study. Twenty-one patients had full radiographic follow-up. Mean follow-up was 6.6 years. There was 100% implant survival. Shoulder range of motion significantly improved and the mean American Shoulder and Elbow Society score was 89.8. There was presence of metal debris radiographically in 24% of patients. Twenty-nine percent of patients had evidence of radiolucency. Fourteen percent of patients had moderate superior subluxation. CONCLUSION: Total shoulder arthroplasty with second generation cemented Trabecular Metal™ glenoid components yielded good outcomes at mean 6.6-year follow-up. Metal debris incidence and clinical outcomes were similar to short-term findings. The presence of metal debris did not significantly affect clinical outcomes. Continued observation of these patients will elucidate longer-term implant survival.

Chondral Damage After Arthroscopic Repair Techniques for Acute Bony Bankart Lesions: A Biomechanical Study.

BACKGROUND: Bony Bankart lesions can be encountered during treatment of shoulder instability. Current arthroscopic bony Bankart repair techniques involve intra-articular suture placement, but the effect of these repair techniques on the integrity of the humeral head articular surface warrants further investigation. PURPOSE: To quantify the degree of humeral head articular cartilage damage secondary to current arthroscopic bony Bankart repair techniques in a cadaveric model. STUDY DESIGN: Controlled laboratory study. METHODS: Testing was performed in 13 matched pairs of cadaveric glenoids with simulated bony Bankart fractures, with a defect width of 25% of the glenoid diameter. Half of the fractures were repaired with a double-row technique, while the contralateral glenoids were repaired with a single-row technique. Samples were subjected to 20,000 cycles of internal-external rotation across a 90° arc at 2 Hz after a compressive load of 750 N, or 90% body weight (whichever was less) was applied to simulate wear. Cartilage defects on the humeral head were quantified through a custom MATLAB script. Mean cartilage cutout differences were analyzed by the Wilcoxon rank-sum test. RESULTS: Both single- and double-row repairs showed macroscopic damage. The histomorphometric analysis demonstrated that the double-row technique resulted in a significantly (P = .036) more chondral damage (mean, 57,489.1 µm2; SD, 61,262.2 µm2) than the single-row repair (mean, 28,763.5 µm2; SD, 24,4990.2 µm2). CONCLUSION: Both single-row and double-row arthroscopic bony Bankart fixation techniques resulted in damage to the humeral head articular cartilage in the concavity-compression model utilized in this study. The double-row fixation technique resulted in a significantly increased cutout to the humeral head cartilage after simulated wear in this cadaveric model. CLINICAL RELEVANCE: This study provides data demonstrating that placement of intra-articular suture during arthroscopic bony Bankart repair techniques may harm the humeral head cartilage. While the double-row repair of bony Bankart lesions is more stable, it results in increased cartilage damage. These findings suggest that alternative, cartilage-sparing arthroscopic techniques for bony Bankart repair should be investigated.

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.

A Biomechanical, Cadaveric Evaluation of Single- Versus Double-Row Repair Techniques on Stability of Bony Bankart Lesions.

BACKGROUND: Previous studies comparing stability between single- and double-row arthroscopic bony Bankart repair techniques focused only on the measurements of tensile forces on the bony fragment without re-creating a more physiologic testing environment. PURPOSE: To compare dynamic stability and displacement between single- and double-row arthroscopic repair techniques for acute bony Bankart lesions in a concavity-compression cadaveric model simulating physiologic conditions. STUDY DESIGN: Controlled laboratory study. METHODS: Testing was performed on 13 matched pairs of cadaveric glenoids with simulated bony Bankart fractures with a defect width of 25% of the inferior glenoid diameter. Half of the fractures were repaired with a double-row technique, and the contralateral glenoids were repaired with a single-row technique. To determine dynamic biomechanical stability and ultimate step-off of the repairs, a 150-N load and 2000 cycles of internal-external rotation at 1 Hz were applied to specimens to simulate early rehabilitation. Toggle was quantified throughout cycling with a coordinate measuring machine. Three-dimensional spatial measurements were calculated. After cyclic loading, the fracture displacement was measured. RESULTS: The bony Bankart fragment-glenoid initial step-off was found to be significantly greater (P < .001) for the single-row technique (mean, 896 µm; SD, 282 µm) compared with the double-row technique (mean, 436 µm; SD, 313 µm). The motion toggle was found to be significantly greater (P = .017) for the single-row technique (mean, 994 µm; SD, 711 µm) compared with the double-row technique (mean, 408 µm; SD, 384 µm). The ultimate interface displacement was found to be significantly greater (P = .029) for the single-row technique (mean, 1265 µm; SD, 606 µm) compared with the double-row technique (mean, 795 µm; SD, 398 µm). CONCLUSION: Using a concavity-compression glenohumeral cadaveric model, we found that the double-row arthroscopic fixation technique for bony Bankart repair resulted in superior stability and decreased displacement during simulated rehabilitation when compared with the single-row repair technique. CLINICAL RELEVANCE: The findings from this study may help guide surgical decision-making by demonstrating superior biomechanical properties (improved initial step-off, motion toggle, and interface displacement) of the double-row bony Bankart repair technique when compared with single-row fixation. The double-row repair construct demonstrated increased stability of the bony Bankart fragment, which may improve bony Bankart healing.

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.