Faculty Bibliography

Primary elbow osteoarthritis is a functionally limiting condition, predominantly affecting middle-aged men engaged in repetitive manual labor, and is characterized by pain, stiffness, and mechanical symptoms. Evaluation involves a detailed history focusing on pain, loss of motion, and mechanical symptoms, followed by clinical examination for range of motion deficits, crepitus, and instability. Radiographic assessment, including standard radiographs and, when indicated, computed tomography imaging, is essential for staging disease severity, identifying osteophytes, capsular contracture, and joint space narrowing. Initial management is nonsurgical, emphasizing activity modification, NSAIDs, physical therapy, and intra-articular corticosteroid injections. When conservative measures fail, surgical options include arthroscopic or open débridement, osteocapsular arthroplasty, and procedures such as the Outerbridge-Kashiwagi technique. Both arthroscopic and open approaches reliably improve pain, range of motion, and functional scores, with low complication rates. However, open procedures may yield greater flexion gains in select cases. Nonarthroplasty options for primary elbow arthritis encompass a spectrum from conservative management to arthroscopic and open surgical débridement, with treatment tailored to disease severity, patient age, and functional demands.

Exposure to World Trade Center (WTC) dust following the September 11, 2001 attacks has been linked to numerous negative health outcomes in First Responders, including cognitive impairment disproportionately impacting First Responders with aging. However, the mechanisms underlying neurocognitive decline remain poorly characterized. This investigation examined the effects of WTC dust exposure on myelin integrity and neuroinflammatory signaling in twelve-week old male spontaneously hypertensive rats. To model Ground Zero exposure in First Responders, WTC dust was intratracheally administered for two consecutive days (2.43 [± 0.78] mg/day).  It was hypothesized that WTC dust exposure would enhance neuroinflammatory signaling and promote an earlier, progressive decline of myelin abundance. Rats were euthanized at 3 and 12 mo post-exposure. Changes in myelin abundance (Black-Gold II), myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), and microglial responses (ionized calcium-binding protein; Iba1) were assessed through immunohistochemical staining, and cytokines were measured in brain homogenates. WTC dust exposure resulted in increased Black-Gold II staining at 3 mo despite no changes in MBP or CNPase. In contrast, microglial activation and IL-1β concentrations were elevated in dust-exposed rats at 12 mo. Collectively, these data suggest WTC dust exposure induces sustained neuroinflammatory signaling and may elicit a compensatory myelin response indicative of early neurodegeneration.

Chromatin-modifying complexes are critical in gene regulation, yet their proposed interactions with RNA remain poorly understood. Counter to prior models of specific recruitment, we find that WDR5, an essential subunit of the MLL1/KMT2A histone methyltransferase complex, binds RNA promiscuously. Using a stringent approach, we demonstrate that WDR5 directly engages a diverse pool of cellular RNAs, dictated primarily by RNA abundance rather than specific motifs. Equilibrium binding assays show that RNA length, rather than sequence, governs high affinity. WDR5 binds to RNA through multiple surfaces, some of which overlap with MLL1 complex subunit interfaces. Strikingly, we find that RNA binding disrupts the MLL1 complex by competitively displacing WDR5 from these critical protein-protein interactions, leading to a marked inhibition of MLL1 catalytic activity. Further experiments in human cell lines suggest that this disassembly mechanism may operate to homeostatically downregulate MLL1 complex activity, thereby integrating transcriptional activity with chromatin state.

INTRODUCTION/BACKGROUND:The purpose of this case series is to investigate outcomes for repair of fractures of the scapular spine and acromial process following reverse total shoulder arthroplasty (RTSA). METHODS:All adult patients who were treated operatively for a stress scapular spine or acromial fracture following a RTSA at a single center between 2013 and 2024 were identified. All patients underwent operative repair with plate and screw fixation with or without adjunctive bone grafting. Data collected included patient demographics, injury characteristics, fracture classification, surgical details, radiographic findings, and clinical outcomes, which were based on chart review of follow-up visits and revision surgeries. RESULTS:Among 2006 RTSA procedures performed during the study period, 18 patients (0.9%) developed a scapular spine or acromial stress fracture, 16 (88.9%) of which required operative fixation. Mean follow-up after fixation was 23 months. The cohort included 11 women (68.8%) and 5 men (31.2%), with a mean age of 71.9 years. All fractures were attributed to an insufficiency mechanism. Bone graft or biologic augmentation was performed in 11 patients (68.8%). Following index fracture fixation, 10 patients (62.5%) developed a postoperative complication or adverse clinical outcome, including nonunion in 6 patients (37.5%), fracture-related infection in 2 patient (12.5%), subsequent secondary acromial stress fracture in 1 patient (6.2%), and glenoid component loosening with humeral component dislocation in 1 patient (6.2%). Nine patients (56.3%) underwent at least one additional surgical procedure, including 8 patients (50.0%) who required an unplanned reoperation; hardware removal was the most common subsequent procedure (7/16, 43.8%). At final follow-up, 5 patients (31.3%) reported chronic pain, 3 patients (18.8%) had persistent nonunion, and 3 patients (18.8%) had hardware failure managed nonoperatively. The number of plates used and implant positioning did not differ significantly between patients who achieved union and those who did not (p = 0.264). CONCLUSION/CONCLUSIONS:Scapular spine and acromial stress fractures following RTSA are uncommon but clinically consequential complications of reverse total shoulder arthroplasty. Standard operative fixation demonstrated a low rate of success after a single intervention, underscoring the need for alternative treatment strategies. LEVEL OF EVIDENCE/METHODS:Level IV.

PURPOSE/UNASSIGNED:This treat-and-resect clinical study evaluated a specialized form of pulsed electric field (PEF) ablation's potential to modulate antitumor immunity in early-stage non-small cell lung cancer (NSCLC). Tertiary lymphoid structures (TLS) are lymphoid aggregates that recruit immune cells into the tumor microenvironment (TME) and serve as immunity-generating neighborhoods. TLS with germinal centers (GC) have strong prognostic value in most cancers and promote tumor control and responsiveness to immune-based therapies, but no commercially available therapeutics induce their formation. The Aliya System is a proprietary electrosurgical technology that delivers microsecond electrical pulses to tissue, achieving tumor clearance while maintaining stromal architecture. PATIENTS AND METHODS/UNASSIGNED:Treatment group patients received ablation immediately after diagnostic biopsy versus a biopsy-only control group. Herein, we report on exploratory endpoints examining immune modulation in blood and tumor samples collected from patients in both groups. RESULTS/UNASSIGNED:Histopathologic assessments revealed the presence of TLS with GC in resected tumors. Tissue cytokine assessments and single-cell RNA sequencing demonstrated upregulation of cytokines capable of recruiting and organizing TLS-associated lymphocytes, including CXCL13, and significant increases in GC-related immune populations, including class-switched memory B and plasma cells in ablated tumors versus preablation biopsies. Ablation group patients had more tumors containing TLS with GC (47%) versus control (24%). Ablation group patients exhibited enhanced systemic immunity, with increased serum high mobility group box 1 and circulating cytotoxic T cells. CONCLUSIONS/UNASSIGNED:This specialized PEF may orchestrate multiple simultaneous changes that promote a more immunologically active TME and represent a new approach for improving immunotherapeutic regimen responses in patients with NSCLC.

BACKGROUND/PURPOSE/UNASSIGNED:The effectiveness of intraoral scanners in accurately recording partially edentulous mandibles is still under scrutiny. This study aimed to assess the accuracy of digital impressions obtained using an intraoral scanner in a partially edentulous mandibular arch. MATERIALS AND METHODS/UNASSIGNED:A partially edentulous typodont model with missing five teeth was digitally scanned using a calibrated desktop scanner to create a reference model. The scan was saved as a standard tessellation language (STL) file and used as the control dataset. The same typodont model was then scanned 20 times using an intraoral scanner (IOS), with each digital impression exported in STL format. All datasets were analyzed using a best-fit registration algorithm in specialized software to compare the IOS scans against the reference model. RESULTS/UNASSIGNED:0.05). CONCLUSION/UNASSIGNED:The findings of this study indicate that the intraoral scanner evaluated is capable of generating digital impressions with clinically acceptable accuracy in partially edentulous mandibular arches.

The American College of Obstetricians and Gynecologists (ACOG) recently revised its guidance regarding the evaluation of postmenopausal bleeding (PMB), recommending combined transvaginal ultrasonography (TV U/S) and endometrial (EM) sampling for most patients undergoing initial assessment. This perspective examines the evidence underlying these recommendations and considers their potential implications for clinical practice. Prior ACOG guidance recognized that, when the endometrium is fully visualized and measures ≤4 mm, TV U/S provides a highly effective means of excluding endometrial cancer (EC) in most women with PMB if the TV U/S is adequate and there is no persistent bleeding. Their revised recommendations place greater emphasis on EM sampling, including in several patient populations previously considered appropriate candidates for ultrasound-based evaluation. This perspective reviews the evidence this new guidance relied upon, as well as limitations of blind EM sampling, including published false-negative rates even in cases of known carcinoma, technical challenges associated with tissue acquisition, and potential procedural complications. Particular attention is given to women receiving menopausal hormone therapy, as well as nulliparous women in whom EM sampling may be technically difficult. My perspective is that former guideline-based approaches remain generally appropriate. The concern about the increasing mortality of EC in the United States is appropriate, as is the concern about racial disparities in the incidence and mortality of EC. However, the new ACOG revision will result in inappropriate, invasive EM sampling in a large number of women. The potential harms, as well as difficulties in obtaining tissue, will be substantial. Any real attempt to reduce the mortality of EC will require a better understanding of patient-specific risk factors, as well as information about less common non-EM type II cancers, especially in Black women, and better patient and practitioner education relative to PMB.