ABBV-319: A CD19-targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies.

Glucocorticoids are key components of the current standard-of-care regimens (e.g., R-CHOP, EPOCH-R, Hyper-CVAD) for treatment of B-cell malignancy. However, systemic glucocorticoid treatment is associated with several adverse events. CD19 displays restricted expression in normal B-cells and is up-regulated in B-cell malignancies. ABBV-319 is a CD19-targeting antibody-drug conjugate (ADC) engineered to reduce glucocorticoid-associated toxicities while possessing three distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced Fc-mediated effector function via afucosylation of the antibody backbone. ABBV-319 elicited potent GRM-driven anti-tumor activity against multiple malignant B-cell lines in vitro as well as in cell line-derived xenografts (CDXs) and patient-derived xenografts (PDXs) in vivo. Remarkably, a single-dose of ABBV-319 induced sustained tumor regression and enhanced anti-tumor activity compared to repeat dosing of systemic prednisolone at the maximum tolerated dose (MTD) in mice. The unconjugated CD19 monoclonal antibody (mAb) also displayed anti-proliferative activity on a subset of B-cell lymphoma cell lines through the inhibition of PI3K signaling. Moreover, afucosylation of the CD19 mAb enhanced Fc-mediated antibody-dependent cellular cytotoxicity (ADCC), and this activity was maintained after conjugation with GRM payloads. Notably, ABBV-319 displayed superior efficacy compared to afucosylated CD19 mAb in human CD34+ PBMC-engrafted NSG-tg(Hu-IL15) transgenic mice, demonstrating enhanced anti-tumor activity when multiple MOAs are enabled. ABBV-319 also showed durable anti-tumor activity across multiple B-cell lymphoma PDX models, including non-germinal center B-cell (GCB) DLBCL and relapsed lymphoma post R-CHOP treatment. Collectively, these data support the ongoing evaluation of ABBV-319 in Phase I clinical trial (NCT05512390).

Ventral Hernia Reconstruction with GORE ENFORM Biomaterial.

Introduction: Ventral hernia repair (VHR) is one of the most common surgeries performed in the United States. Degradable mesh is the recommended choice for patients presenting with high-risk co-morbidities or increased risk for infection. GORE® ENFORM BiomaterialTM is a biosynthetic degradable mesh that has recently been approved for use in ventral hernia reconstruction with no reports of its clinical outcomes. Methods: This study was a single surgeon case series. Patients were included in the study if they underwent VHR with GORE® ENFORM BiomaterialTM. The decision to use GORE® ENFORM BiomaterialTM was the senior surgeon's decision based on the patient's center for disease control classification. Patient comorbidities, hernia characteristics, postoperative hernia recurrence, and surgical site occurrences (SSOs) were collected at in-patient follow-up appointments and chart review. Patients were asked to complete preoperative and postoperative patient-reported outcomes (PROs) using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity short form 3a and the hernia-specific quality of life (HerQLes) survey. Results: A total of 15 patients were included in this study. The average length of follow-up was 315 days. Postoperatively, 26.7% of patients had an SSO with 4 surgical site infections. Two patients required an operative washout with mesh removal. One patient experienced hernia recurrence. Eight of the 15 patients completed preoperative and postoperative PROs. Conclusion: This is the first clinical study to report the outcomes of ventral hernia repair using ENFORM mesh. These results show that Enform mesh is an option to consider in complex ventral hernia reconstruction.

Introduction: La réparation d'une hernie ventrale (RHV) est l'une des opérations les plus fréquentes aux États-Unis. Le treillis dégradable est le choix recommandé pour les patients ayant des affections connexes à haut risque ou qui sont vulnérables aux infections. Le biomatériau GORE® ENFORM est un treillis biosynthétique dégradable qui a récemment été approuvé pour la reconstruction des hernies ventrales et dont les résultats cliniques n'ont fait l'objet d'aucun rapport. Méthodologie : La présente étude était constituée d'une série de cas réalisée par un seul chirurgien. Les patients étaient inclus dans l'étude s'ils avaient subi une RHV à l'aide de biomatériau GORE® ENFORM. Le chirurgien en chef prenait la décision d'utiliser ce biomatériau d'après la classification du contrôle des maladies au centre du patient. Les chercheurs ont colligé les affections connexes du patient, les caractéristiques de la hernie, les récurrences de hernie postopératoire et les occurrences au foyer de l'opération (OFO) lors des rendez-vous de suivi et de l'examen des dossiers. Les patients ont été invités à préciser leurs résultats préopératoires et postopératoires (RPP) au moyen du formulaire court 3a sur l'intensité de la douleur tiré du système d'information des mesures de résultats déclarés par le patient (PROMIS) et du sondage sur la qualité de vie propre à la hernie (HerQLes). Résultats : Au total, 15 patients ont participé à l'étude et ont été suivis pendant une durée moyenne de 315 jours. Après l'opération, 26,7% des patients ont présenté une OFO ainsi que quatre infections au foyer de l'opération. Deux patients ont eu besoin d'un lessivage opératoire et du retrait du treillis. Un patient a subi une récurrence de la hernie. Huit des 15 patients ont rempli les RDP avant et après l'opération. Conclusion : Il s'agit de la première étude clinique à déclarer les résultats cliniques de la réparation d'une hernie ventrale à l'aide du treillis ENFORM. Ces résultats démontrent que le treillis Enform peut être envisagé pour la reconstruction d'une hernie ventrale complexe.

Identifying Barriers Faced by Applicants without a Home Residency Program when Matching into Plastic Surgery.

Background Applying into plastic surgery (PS) is competitive. Lacking a home residency program (HRP) is another barrier. Our goal is to characterize challenges faced by PS applicants without HRPs and identify solutions. Methods Surveys were designed for current integrated PS residents and applicants in the 2022 Match without HRPs. Surveys were distributed electronically. Only U.S. allopathic graduate responses were included. Results Of 182 individuals surveyed, 74 responded (39%, 33 residents, 41 applicants). Sixty-six percent reported feeling disadvantaged due to lack of an HRP. Seventy-six percent of applicants successfully matched. Of these, 48% felt they required academic time off (research year) versus 10% of unmatched applicants. Ninety-seven percent of matched applicants identified a mentor versus 40% of unmatched applicants ( p < 0.05). Matched applicants identified mentors through research (29%) and cold calling/emailing (25%). Matched versus unmatched applicants utilized the following resources: senior students (74 vs. 10%, p < 0.05) and social media (52 vs. 10%, p < 0.05). Among residents, 16 had PS divisions (48%). Thirty-six percent with divisions felt they had opportunities to explore PS, compared with 12% without divisions. Residents without divisions felt disadvantaged in finding research (94 vs. 65%, p < 0.05), delayed in deciding on PS (50 vs. 28%), and obtaining mentors (44 vs. 35%) and letters of recommendation (31 vs. 24%). Conclusion PS residents and applicants without HRPs reported feeling disadvantaged when matching. The data suggest that access to departments or divisions assists in matching. We identified that external outreach and research were successful strategies to obtain mentorship. To increase awareness for unaffiliated applicants, we should increase networking opportunities during local, regional, and national meetings.

p300 is an obligate integrator of combinatorial transcription factor inputs.

Transcription coactivators are proteins or protein complexes that mediate transcription factor (TF) function. However, they lack DNA-binding capacity, prompting the question of how they engage target loci. Three non-exclusive hypotheses have been posited: coactivators are recruited by complexing with TFs, by binding histones through epigenetic reader domains, or by partitioning into condensates through their extensive intrinsically disordered regions. Using p300 as a prototypical coactivator, we systematically mutated its annotated domains and show by single-molecule tracking in live U2OS cells that coactivator-chromatin binding depends entirely on combinatorial binding of multiple TF-interaction domains. Furthermore, we demonstrate that acetyltransferase activity opposes p300-chromatin association and that the N-terminal TF-interaction domains regulate that activity. Single TF-interaction domains are insufficient for chromatin binding and regulation of catalytic activity, implying a principle that we speculate could broadly apply to eukaryotic gene regulation: a TF must act in coordination with other TFs to recruit coactivator activity.

Solitary Fibrous Tumor of Breast and Axilla: Clinicopathological Profile of Five Tumors With Comparison of Risk Stratification Models.

Introduction: Solitary fibrous tumor (SFT) is a fibroblastic tumor with malignant potential that is underpinned by a recurrent inv12(q13q13)-derived NAB2::STAT6 fusion. Breast and axilla are uncommon locations for this entity. Methods: Records of two academic institutions were electronically searched for breast and axillary SFTs. Clinical and pathologic data were reviewed. Literature review for breast or axillary SFTs was performed. Present study and previously reported tumors were stratified using five SFT risk models: original and modified Demicco metastatic risk, Salas local recurrence risk, Salas metastatic risk, and Thompson local recurrence risk. Results: Five patients with breast or axillary SFT were identified. Median age was 49 years, and median follow-up (available for four patients) was 82 months. Three patients showed no evidence of disease, and one developed recurrence. Literature review identified 58 patients with breast or axillary SFT. Median age was 54 years, and median follow-up (available for 35 patients) was 24 months. Thirty-one patients showed no evidence of disease, three developed recurrence, and one developed metastasis. Original and modified Demicco models and Thompson model showed the highest sensitivity; original and modified Demicco models and Salas metastatic risk model demonstrated the highest specificity. Kaplan-Meier models were used to assess recurrence-free probability (RFP). Original and modified Demicco models predicted RFP when stratified by "low risk" and "moderate/intermediate and high risk" tumor, though sample size was small. Conclusions: While many SFTs of breast and axilla remain indolent, a subset may develop recurrence and rarely metastasize. The modified Demicco risk model demonstrated optimal performance characteristics.

Comprehensive Clinical-Pathologic Assessment of Malignant Phyllodes Tumors: Proposing Refined Diagnostic Criteria.

The latest World Health Organization classification of breast tumors recommends diagnosing malignant phyllodes tumors (MPTs) when all 5 morphologic features are present: permeative borders, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses per 10 high-power fields (HPF), and stromal overgrowth. We assessed the performance of this recommendation to capture MPTs and features predictive of distant metastasis in a multi-institutional retrospective study. Of 65 MPTs, most cases had at least focally permeative borders (58, 89%), with marked stromal cellularity in 40 (61.5%), marked atypia in 38 (58.5%), ≥10 mitoses per 10 HPF in 50 (77%), and stromal overgrowth in 56 (86%). Distant metastases were observed in 20 (31%) patients (median follow-up 24.5 mo, 1 to 204). Only 13 of 65 (20%) cases had all 5 morphologic features, while only 7 of 20 (35%) cases with distant metastases had all 5 features. In univariate analysis, only marked stromal atypia ( P =0.004) and cellularity ( P =0.017) were associated with decreased distant metastasis-free survival. In multivariate Cox regression, the combination of stromal overgrowth, marked stromal cellularity, and atypia (C-index 0.721, 95% CI: 0.578, 0.863) was associated with decreased distant metastasis-free survival. The current World Health Organization recommendation will miss a significant number of MPTs with distant metastases. We propose refined diagnostic criteria for MPTs: (1) stromal overgrowth combined with ≥1 feature(s) (marked cellularity, marked atypia, or ≥10 mitoses per 10 HPF), or (2) in the absence of stromal overgrowth, marked cellularity combined with ≥1 feature(s) (permeative borders, marked atypia, or ≥10 mitoses per 10 HPF).

Mendelian randomization analysis revealed potential metabolic causal factors for breast cancer.

Observational studies showed that metabolic phenotypes were associated with the risk of developing breast cancer (BC). However, those results are inconsistent regarding the magnitude of the association, particularly by subtypes of breast cancer. Furthermore, the mechanisms of the association remain unclear. We performed two-sample Mendelian randomization (MR) analyses to evaluate the causal effect of metabolic risk factors on breast cancer in the European population. Assessed individually using MR, body mass index (BMI) (odds ratio [OR] 0.94, 95% Confidence interval [CI] 0.90-0.98, P = 0.007), high-density lipoprotein cholesterol (HDL-C) (OR 1.10, 95% CI 1.07-1.13, P = 6.10 × 10-11) and triglycerides (TG) (OR 0.92, 95% CI 0.90-0.96, P = 1.58 × 10-6) were causally related to breast cancer risk. In multivariable MR, only HDL-C (OR 1.08; 95% CI 1.02-1.14; P = 0.02) retained a robust effect, suggesting that the genetic association between BMI, HDL-C and TG with breast cancer risk in univariable analysis was explained via HDL-C. These findings suggest a possible causal role of HDL-C in breast cancer etiology.

Management of Complex Hand and Wrist Ligament Injuries.

Ligamentous injuries in the hand and wrist are often underdiagnosed and can present with significant functional limitations if there is untimely recognition of injury. Adequate repair or reconstruction is critical in restoring joint stability and mobility. The purpose of this review is to provide an overview of the metacarpophalangeal joint, scapholunate interosseous ligament (SLIL), and non-SLIL carpal ligament anatomy, diagnosis, imaging, treatment consideration and options, as well as surgical techniques encompassing repair, reconstruction, and fusion.

p300 Is an Obligate Integrator of Combinatorial Transcription Factor Inputs.

Transcription coactivators are proteins or protein complexes that mediate transcription factor (TF) function. However, they lack DNA binding capacity, prompting the question of how they engage target loci. Three non-exclusive hypotheses have been posited: coactivators are recruited by complexing with TFs, by binding histones through epigenetic reader domains, or by partitioning into phase-separated compartments through their extensive intrinsically disordered regions (IDRs). Using p300 as a prototypical coactivator, we systematically mutated its annotated domains and show by single-molecule tracking in live cells that coactivator-chromatin binding depends entirely on combinatorial binding of multiple TF-interaction domains. Furthermore, we demonstrate that acetyltransferase activity negatively impacts p300-chromatin association and that the N-terminal TF-interaction domains regulate that activity. Single TF-interaction domains are insufficient for both chromatin binding and regulation of catalytic activity, implying a principle that could broadly inform eukaryotic gene regulation: a TF must act in coordination with other TFs to recruit coactivator activity.

Closed reduction of nasoseptal fractures: key concepts for predictable results.

Nasal complex injuries are the most common facial fracture encountered in the trauma population. Multiple surgical techniques for treatment of these fractures have been described with varying results. The goal of this study was to review the efficacy of closed reduction of nasal and septal fractures using a technique based upon several key concepts. We reviewed the records of patients who had undergone isolated nasal and/or septal fractures with closed reduction at our institution between January 2013 and November 2021. Inclusion criteria consisted of preoperative CT imaging, surgical treatment within fourteen days of initial injury, and follow up of at least one year. All patients were treated under general or deep sedation. The same surgical technique was applied with closed reduction of the septum and nasal bones with internal and external postoperative splints. Of the 232 records initially reviewed, 103 met inclusion criteria. Four patients had undergone revision septorhinoplasty (3.9%). Mean (range) follow up was 2.7 (1-8.2) years. Three patients had undergone revision nasal repair due to persistent airflow obstruction with complete resolution of symptoms after revision. The other patient received multiple revisions at another institution as a result of their dissatisfaction with cosmesis without improvement. Closed reduction of nasal and septal fractures can be a highly successful procedure and yield predictable results, limiting the need for post-traumatic open septorhinoplastic surgery. Five critical concepts of nasal fracture repair can help surgeons achieve predictable functional and cosmetic results: selection, timing, anaesthesia, reduction, and support.

Association Between Hospital Monopoly Status, Patient Socioeconomic Disadvantage, and Total Joint Arthroplasty Price Disclosure.

INTRODUCTION: In recent years, healthcare institutions and regulatory bodies have enacted cost transparency mandates for routine interventions such as total hip arthroplasty and total knee arthroplasty. However, disclosure rates remain low. This study examined the effect of financial characteristics of hospitals and the socioeconomic status of patients on price disclosure. METHODS: Hospitals conducting total hip arthroplasty/total knee arthroplasty, their quality ratings, and procedural volumes were identified using the Leapfrog Hospital Survey and linked to procedure-specific prices. Financial performance and the Area Deprivation Index (ADI) were used to correlate disclosure rates with hospital and patient characteristics. Hospital financial, operational, and patient summary statistics were compared by price-disclosure status using two-sample t -tests for continuous variables and Pearson chi-square test for categorical variables. The association between total joint arthroplasty price disclosure and hospital ADI was further evaluated using modified Poisson regression. RESULTS: A total of 1,425 hospitals certified by the Centers for Medicare & Medicaid Services were identified in the United States. 50.5% (n = 721) of hospitals had no published payer-specific price information. Hospitals in an area of higher socioeconomic disadvantage were more likely to disclose prices of total joint arthroplasty (incidence rate ratio = 0.966, 95% CI: 0.937 to 0.995, P = 0.024). Hospitals that were considered monopolies or were for-profit were less likely to disclose prices (IRR = 1.15, 95% CI: 1.030 to 1.280, P = 0.01; IRR = 1.256, 95% CI: 0.986 to 1.526, P = 0.038, respectively). When accounting for both ADI and monopoly status, hospitals with patients who had a higher ADI were more likely to disclose costs for a total joint arthroplasty, whereas for-profit hospitals or hospitals considered monopolies in their HSA were less likely to disclose prices. DISCUSSION: For nonmonopoly hospitals, a higher ADI correlated with a higher likelihood of price disclosure. However, for monopoly hospitals, there was no significant association between ADI and price disclosure. LEVEL OF EVIDENCE: II.

Low-grade adenosquamous carcinoma of the breast: a clinical, morphological and immunohistochemical analysis of 25 patients.

AIMS: Due to its rarity and non-specific clinical and pathological features, low-grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple-negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management. METHODS AND RESULTS: Twenty-five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow-up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple-negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow-ups up to 108 months. CONCLUSIONS: LGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis.

Creation of an asynchronous faculty development curriculum on well-written narrative assessments that avoid bias.

BACKGROUND: The COVID-19 pandemic in parallel with concerns about bias in grading resulted in many medical schools adopting pass/fail clinical grading and relying solely on narrative assessments. However, narratives often contain bias and lack specificity. The purpose of this project was to develop asynchronous faculty development to rapidly educate/re-educate > 2000 clinical faculty spread across geographic sites and clinical disciplines on components of a well-written narrative and methods to minimize bias in the assessment of students. METHODS: We describe creation, implementation, and pilot data outcomes for an asynchronous faculty development curriculum created by a committee of volunteer learners and faculty. After reviewing the literature on the presence and impact of bias in clinical rotations and ways to mitigate bias in written narrative assessments, the committee developed a web-based curriculum using multimedia learning theory and principles of adult learning. Just-in-time supplemental materials accompanied the curriculum. The Dean added completion of the module by 90% of clinical faculty to the department chairperson's annual education metric. Module completion was tracked in a learning management system, including time spent in the module and the answer to a single text entry question about intended changes in behavior. Thematic analysis of the text entry question with grounded theory and inductive processing was used to define themes of how faculty anticipate future teaching and assessment as a result of this curricula. OUTCOMES: Between January 1, 2021, and December 1, 2021, 2166 individuals completed the online module; 1820 spent between 5 and 90 min on the module, with a median time of 17 min and an average time of 20.2 min. 15/16 clinical departments achieved completion by 90% or more faculty. Major themes included: changing the wording of future narratives, changing content in future narratives, and focusing on efforts to change how faculty teach and lead teams, including efforts to minimize bias. CONCLUSIONS: We developed a faculty development curriculum on mitigating bias in written narratives with high rates of faculty participation. Inclusion of this module as part of the chair's education performance metric likely impacted participation. Nevertheless, time spent in the module suggests that faculty engaged with the material. Other institutions could easily adapt this curriculum with provided materials.

Biased precursor ingression underlies the center-to-pole pattern of male sex determination in mouse.

During mammalian development, gonadal sex determination results from the commitment of bipotential supporting cells to Sertoli or granulosa cell fates. Typically, this decision is coordinated across the gonad to ensure commitment to a single organ fate. When unified commitment fails in an XY mouse, an ovotestis forms in which supporting cells in the center of the gonad typically develop as Sertoli cells, while supporting cells in the poles develop as granulosa cells. This central bias for Sertoli cell fate was thought to result from the initial expression of the drivers of Sertoli cell fate, SRY and/or SOX9, in the central domain, followed by paracrine expansion to the poles. However, we show here that the earliest cells expressing SRY and SOX9 are widely distributed across the gonad. In addition, Sertoli cell fate does not spread among supporting cells through paracrine relay. Instead, we uncover a center-biased pattern of supporting cell precursor ingression that occurs in both sexes and results in increased supporting cell density in the central domain. Our findings prompt a new model of gonad patterning in which a density-dependent organizing principle dominates Sertoli cell fate stabilization.

Regional anesthesia improves inpatient but not outpatient opioid demand in tibial shaft fracture surgery.

BACKGROUND: Patients undergoing operative treatment of tibial shaft fractures have considerable pain largely managed with opioids. Regional anesthesia (RA) has been increasingly used to reduce perioperative opioid use. METHODS: This was a retrospective study of 426 patients that underwent operative treatment of tibial shaft fractures with and without RA. Inpatient opioid consumption and 90-day outpatient opioid demand were measured. RESULTS: RA significantly decreased inpatient opioid consumption for 48 h post-operatively (p = 0.008). Neither inpatient use after 48 h nor outpatient opioid demand differed in patients with RA (p > 0.05). CONCLUSIONS: RA may help with inpatient pain control and reduce opioid use in tibial shaft fracture. LEVEL OF EVIDENCE: Level III, retrospective, therapeutic cohort study.

Consequences and Predictors of Prolonged Tissue Expander Duration in Breast Reconstruction.

BACKGROUND: Tissue expanders (TEs) are temporary devices used in breast reconstruction, which are generally removed within 1 year. There is a paucity of data regarding the potential consequences when TEs have longer indwelling times. Thus, we aim to determine whether prolonged TE implantation length is associated with TE-related complications. METHODS: This is a single-center retrospective review of patients who underwent TE placement for breast reconstruction from 2015 to 2021. Complications were compared between patients who had a TE for >1 year and <1 year. Univariate and multivariate regressions were used to evaluate predictors of TE complications. RESULTS: A total of 582 patients underwent TE placement and 12.2% had the expander for >1 year. Adjuvant chemoradiation, body mass index (BMI), overall stage, and diabetes predicted the duration of TE placement (p ≤ 0.006). Rate of return to the operating room was higher in patients who had TEs in place >1 year (22.5 vs 6.1%, p < 0.001). On multivariate regression, prolonged TE duration predicted an infection requiring antibiotics, readmission, and reoperation (p < 0.001). Reasons for longer indwelling times included need for additional chemoradiation (79.4%), TE infections (12.7%), and requesting a break from surgery (6.3%). CONCLUSION: Indwelling TEs for >1 year are associated with higher rates of infection, readmission, and reoperation even when controlling for adjuvant chemoradiation. Patients with diabetes, a higher BMI, advanced cancer stage, and those requiring adjuvant chemoradiation should be advised they may require a TE for a longer time interval prior to final reconstruction.

Variations in Incidence of Trigger Finger and Response to Corticosteroid Injection after Aromatase Inhibitor Therapy for Breast Cancer.

BACKGROUND: Aromatase inhibitors (AIs), such as letrozole and anastrozole, have been demonstrated to have significant musculoskeletal symptoms in patients. The purpose of this study was to evaluate the effect of specific AI medications on the incidence of trigger finger and independent factors affecting treatment outcomes within this population. METHODS: A retrospective chart review was performed at the authors' institution between the years 2014 and 2018 in patients with the diagnosis of breast cancer. This cohort was then sorted based on receiving medication regimens, trigger finger diagnosis, steroid injections, and need for surgical release of trigger finger. RESULTS: A total of 15,144 patients were included for initial review. The overall rate of trigger finger diagnosis was 2.75% in the entire breast cancer population and 4.5% for patients receiving AI therapy. Patients taking letrozole and anastrozole had an increased odds ratio of 2.0 and 1.7, respectively, for developing trigger finger. Patients who switched between letrozole and anastrozole during treatment had a higher rate of failed steroid injection treatment (45.2% versus 23.5%; P = 0.021). Among patients receiving AI treatment diagnosed with trigger finger, diabetes and hemoglobin A1c level greater than 6.5 were associated with significantly increased rates of failed steroid therapy. CONCLUSIONS: Patients receiving AI therapy have an increased incidence of trigger finger. The outcomes of treatment are equivalent between AI and non-AI trigger finger populations. However, steroid therapy is more likely to fail in patients who require switching of regimens because of significant musculoskeletal symptoms. Poorly controlled diabetes was also an independent factor for compromised steroid treatment of trigger finger. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Pyrocarbon hemiarthroplasty of the shoulder: a systematic review and meta-analysis of clinical results.

BACKGROUND: Hemiarthroplasty is often considered in the setting of preserved glenoid cartilage given the high risk of revision associated with total shoulder arthroplasty. Pyrocarbon (PyC) has been used as an implant material that theoretically allows for formation of a neo-membrane that would act like cartilage to reduce glenoid wear. The purpose of this study was to evaluate the clinical outcomes, radiographic outcomes, revision rates, and complication rates in the existing literature on shoulder hemiarthroplasty using PyC. METHODS: The MEDLINE, Embase, and Scopus databases were searched for articles relating to shoulder hemiarthroplasty using the terms "pyrocarbon" or "pyrolytic carbon." Abstracts and articles were screened against predefined inclusion and exclusion criteria, with a minimum of 24 months' follow-up required. Data on patient demographic characteristics, clinical outcome scores, complications, revision rates, and radiographic findings were recorded. Where appropriate, meta-analysis was performed. RESULTS: Twelve studies were selected for final inclusion, with a total of 536 patients. Among the studies reporting preoperative and postoperative range of motion (ROM), an overall improvement in ROM was observed. The mean Constant score was 70.9 points postoperatively, with a mean improvement of 36.2 points (n = 359, 9 studies). Radiographically, 22.8% of patients (n = 536, 8 studies) had evidence of glenoid erosion, 10.4% had changes in implant positioning, and 9.9% had tuberosity thinning. In addition, 1.5% of patients had radiographic subacromial space reduction, whereas 0.7% had an increase in tuberosity thickness. Across all studies, there was an 8.6% complication rate, with the most common cause being glenoid erosion (2.6%, n = 14). There was an overall 7.7% revision rate (n = 41), with 63% of revisions (n = 26) undergoing conversion to reverse or total shoulder arthroplasty. CONCLUSION: PyC hemiarthroplasty shows overall improvements in ROM and patient-reported outcomes for patients. However, there remains concern for glenoid erosion on radiographic evaluation at minimum 2-year follow-up. Although preliminary studies have shown encouraging results, this systematic review emphasizes the need for longer-term follow-up studies with further radiographic evaluation of the severity of glenoid erosion and the association with functional outcomes and failure risk.

Predicting Final Implant Volume in Two-stage Prepectoral Breast Reconstruction.

Two-stage implant-based breast reconstruction remains the most commonly performed reconstructive modality following mastectomy. Although prior studies have explored the relationship between tissue expander (TE) features and permanent implant (PI) size in subpectoral reconstruction, no such study exists in prepectoral reconstruction. This study aims to identify pertinent TE characteristics and evaluate their correlations with PI size for prepectoral implant-based reconstruction. Methods: This study analyzed patients who underwent two-stage prepectoral tissue expansion for breast reconstruction followed by implant placement. Patient demographics and oncologic characteristics were recorded. TE and PI features were evaluated. Significant predictors for PI volume were identified using linear and multivariate regression analyses. Results: We identified 177 patients and 296 breast reconstructions that met inclusion criteria. All reconstructions were performed in the prepectoral plane with the majority using acellular dermal matrix (93.8%) and primarily silicone implants (94.3%). Mean TE size was 485.4 cm3 with mean initial fill of 245.8 cm3 and mean final fill of 454.4 cm3. Mean PI size was 502.9 cm3 with a differential fill volume (PI-TE) of 11.7 cm3. Multivariate analysis identified significant features for PI size prediction, including TE size (R2 = 0.60; P < 0.0001) and TE final fill volume (R2 = 0.57; P < 0.0001). The prediction expression for TE final fill and TE size was calculated as 26.6 + 0.38*(TE final fill) + 0.61*(TE size). Conclusions: TE size and final expansion volume were significant variables for implant size prediction. With prepectoral implant placement gaining popularity, the predictive formula may help optimize preoperative planning and decision-making in prepectoral reconstructions.

Integrating Mental and Social Health in Orthopaedic Practice: The Time Is Now.

Tremendous advances have been made in understanding the intimate relationships between physical, emotional, and social health. There is now a substantial body of evidence demonstrating that mental health and social health may have as much influence on patients' symptom intensity and level of capability-the key metrics of success in orthopaedic care-as pathophysiology. But as a specialty the focus remains mostly on biomedical management (which focuses on structural damage and technical solutions), rather than taking a biopsychosocial approach, which involves screening, measurement, and decision making that prioritizes mental and social health concerns. Failure to do so means orthopaedic surgeons fall short in delivering whole-person care. It is important to highlight the biopsychosocial model of health and healthcare; describe the evidence for mental and social health in orthopaedic practice; outline strategies to identify, measure, and manage psychological and social concerns; and provide frameworks to implement comprehensive models of orthopaedic care that promise to benefit patients, populations, and health systems.