Faculty Bibliography

BACKGROUND/UNASSIGNED:This study compares outcomes and complications of patients with Bado II Monteggia fracture-dislocations that required radial head fixation or replacement based upon approach to the radial head. METHODS/UNASSIGNED:A retrospective review was performed of 159 consecutive patients with proximal ulna fractures and a radial head dislocation or fracture (Monteggia Variant). Injuries were classified by Bado type. Forty-one patients with Bado II Monteggia injuries treated with either a radial head replacement or fixation with complete follow up were included. Demographics, injury information, surgical details, and follow up information including elbow range of motion (ROM) and complications were collected. A trans-osseous posterior (TOP) approach working through the ulna fracture to address the radial head first was used in 19 patients, while 22 patients had their radial head treated via a separate lateral (Kocher) interval after ulnar fixation. Ulnar plate fixation was performed for all patients. Comparisons were made using independent t-tests. RESULTS/UNASSIGNED:Forty-one Monteggia lesions treated through TOP (19, 46 %) or Kocher (22, 64 %) approaches underwent a radial head replacement (33, 80.5 %) or fracture repair (8, 19.5 %) with a mean final follow-up of 15.3 months. At all post-operative visits, groups displayed similar rates of functional elbow ROM. At latest follow-up rates of patient-reported pain, ultimate elbow ROM, time to radiographic healing were equivalent. No significant differences were observed in ulna non-union, joint malalignment, post-operative nerve injury, post-operative infection, heterotopic ossification, incidence of hardware failure, patient-reported pain, and rate of removal of symptomatic hardware. Sub-analysis of radial head replacement versus fixation revealed equivalent percentage of patients with full ROM at each post-operative time point. CONCLUSION/UNASSIGNED:For Bado II Monteggia fracture-dislocations, the surgical approach to the radial head-TOP versus Kocher-does not influence ultimate patient outcomes or complication rates. Radial head replacement and fixation provide comparable results. LEVEL OF EVIDENCE/UNASSIGNED:III.

BACKGROUND:Intestinal ultrasonography (IUS) is increasingly utilised for diagnosing and monitoring IBD. Despite its cost-effectiveness, patient tolerance and suitability for serial bedside assessments, broad adoption has been limited by knowledge gaps in evidence, training and standardisation. AIMS/OBJECTIVE:To summarise key knowledge gaps in the assessment of luminal disease activity, postoperative recurrence, complications, pouch-related disorders and the use of IUS in paediatrics, contrast enhancement, elastography, as well as education, training and future applications involving artificial intelligence. METHODS:We conducted a systematic umbrella review, following PRISMA guidelines, to map the current landscape of high-quality evidence and identify gaps in IUS research relevant to IBD. We searched MEDLINE from inception to February 2025 for systematic reviews, meta-analyses and consensus statements. We extracted data from eligible studies on design, outcomes and identified research gaps. Gaps were categorised by insufficient information, bias, inconsistency or lack of relevant data. RESULTS:Sixty of 507 studies met inclusion criteria. Key gaps included lack of validated and standardised IUS activity indices for Crohn's disease and ulcerative colitis, limited evidence for IUS in post-operative recurrence, paediatric populations and perianal or pouch disease. Data on the use of contrast-enhanced ultrasound and elastography were sparse. Small sample sizes, heterogeneous designs and inadequate follow-up limited most studies. Training, competency assessment and integration of artificial intelligence remain underexplored. CONCLUSIONS:Sizable gaps persist in the evidence base for IUS in IBD. Addressing these gaps through robust, multicentre studies and consensus-driven frameworks is essential to optimise the clinical and research utility of IUS in IBD management.

INTRODUCTION/BACKGROUND:Tibial plateau fractures are some of the most commonly treated injuries around the knee and loss of range of motion has a significant effect on post-operative outcomes, very few studies have demonstrated the impact of flexion contractures. The purpose of this study was to determine the effect that development of a knee flexion contracture has on outcomes following operative repair of tibial plateau fractures. METHODS:Patients operatively treated for tibial plateau fractures (Schatzker II, IV, V, and VI) between 2005-2024 at a multi-center academic urban hospital system were included in this retrospective comparative study. Patients were grouped into 3 cohorts: 1. Full extension (FE), 2. 5-10 degrees of flexion contracture (Mild, ME) and 3. Greater than 10 degrees of flexion (Severe, SE) contracture at 6 months post-operatively. Patients with contracture were matched to patients who regained full extension based on age and Schatzker classification. Statistical analysis was used to evaluate outcomes including patient reported pain levels, Short Musculoskeletal Function Assessment (SMFA) scores, complication rates and reoperation rates. RESULTS:The cohort consisted of 3 groups of 30 patients (14 Schatzker II, 5 Schatzker IV, 3 Schatzker V, and 8 Schatzker VI). The average knee flexion contracture for the mild cohort was 5 degrees and the average knee flexion contracture for the severe cohort was 12.7 degrees. Patients who experienced flexion contracture had poorer SMFA scores at 6 months, and those in the severe cohort had the poorest SMFA scores (112.6) when compared to those with full extension at 6 months (77.7) (p<0.001). Flexion contractures were associated with higher rates of fracture related infection (FRI) (p =0.002). Patients with flexion contracture also had a higher rate of subsequent re-operation, with 36.7% of the ME undergoing re-operation and 40% of SE undergoing re-operation. CONCLUSIONS:Patients who developed a flexion contracture following repair of a tibial plateau fracture experienced worse outcomes, higher rates of complications, increased pain, and poorer function at long term follow up compared to those who achieved full knee extension.

BACKGROUND:Accumulated levels of mutant huntingtin protein (mHTT) and its fragments are considered contributors to the pathogenesis of Huntington's disease (HD). Stimulating autophagy may enhance clearance of mHTT and its aggregates which has been considered as a possible therapeutic strategy. However, the role and competence of the autophagy-lysosomal pathway (ALP) during HD progression in the human disease remains largely unknown. METHODS:Here, we used multiplex confocal and ultrastructural immunocytochemical analyses of ALP functional markers in relation to mHTT aggresome pathology in striatum and the less affected cortex or cerebellum of HD brains staged from Grade HD2 to HD4 by Vonsattel neuropathological criteria compared to controls. RESULTS:Immunolabeling revealed the localization of HTT/mHTT in ALP vesicular compartments labeled by autophagy-related adaptor proteins sequestosome 1 (p62/SQSTM1) and ubiquitin, and cathepsin D (CTSD) as well as HTT-positive inclusions. Although comparatively normal at HD2, neurons at later HD stages exhibited progressive enlargement and clustering of CTSD-immunoreactive autolysosomes/lysosomes and, ultrastructurally, autophagic vacuole/lipofuscin granules accumulated progressively, more prominently in striatum than cortex. These changes were accompanied by rises in levels of HTT/mHTT and p62/SQSTM1, particularly their fragments, in striatum but not in the cortex, and by increases of LAMP1 and LAMP2 RNA and LAMP1 protein. In addition, cargo-loaded autophagosomes and cathepsin-positive autolysosomes were readily observed, implying a lack of significant blockage in autophagosome formation and autophagosome-lysosome fusion. CONCLUSIONS:The findings collectively suggest that upregulated lysosomal biogenesis and preserved proteolysis maintain autophagic clearance in early-stage HD, but the observed progressive HTT build-up and AL accumulation at advanced disease stages may signify a failure in autophagy substrate clearance. These findings support the prospect that ALP stimulation applied at early disease stages, when clearance machinery is fully competent, could lead to therapeutic benefits in HD patients.

Astrocytic Ca²⁺ activity regulates activity-dependent synaptic plasticity, but its role in learning-related synaptic changes in the living brain remains unclear. We found that motor training induced synaptic potentiation on apical dendrites of layer 5 pyramidal neurons, as well as astrocytic Ca²⁺ rises in the mouse motor cortex. Reducing astrocytic Ca²⁺ led to synaptic depotentiation during motor training and subsequent impairment in performance improvement. Notably, synaptic depotentiation occurred on a fraction of dendrites with repetitive dendritic Ca²⁺ activity. On those dendrites, dendritic spines that were active before dendritic Ca²⁺ activity underwent CaMKII-dependent size reduction. In addition, the activation of adenosine receptors prevented repetitive dendritic Ca²⁺ activity and synaptic depotentiation caused by the reduction of astrocytic Ca²⁺, suggesting the involvement of ATP released from astrocytes and adenosine signaling in the processes. Together, these findings reveal the function of astrocytic Ca²⁺ in preventing synaptic depotentiation by limiting repetitive dendritic activity during learning.

INTRODUCTION/BACKGROUND:The purpose of this study was to assess the effect of an acute traumatic meniscus tear that required repair in association with a tibial plateau fracture repair on outcomes. METHODS:Over a 17-year period, 843 patients presented with a tibial plateau fracture and were followed prospectively. 721 patients with Schatzker I-VI fractures were treated operatively via a standardized algorithm. 161 tibial plateau fractures (22.3 %) had an associated meniscus tear that underwent acute repair at the time of bony fixation. These patients were compared to operatively repaired tibial plateau fracture patients with no meniscus injury (NMR). Demographics were collected and outcomes including: radiographic healing, knee range of motion (ROM), and complication rates, were recorded. In addition, re-operation rates were compared and any reoperation for meniscus repair failure identified. All patients had a minimum of 1 year follow up. RESULTS:A total of 524 patients with a mean of 21.4 (range: 12-120) months follow up met inclusion criteria. Patients in the meniscus repair (MR) cohort had poorer knee extension (1.01 degrees, range: 0-30 degrees) compared to the NMR cohort (0.07 degrees, range: 0-10 degrees) (p < 0.001), in addition to poorer knee flexion (123 degrees, range: 0-145 degrees, p = 0.024). Additionally, MR patients reported higher pain scores (mean: 3 and range: 0-8, p = 0.005) at latest follow up. Finally, MR patients had higher rates of infection (8.1 % vs. 3.3 %, p = 0.025) and lateral collapse of the joint (p = 0.032). CONCLUSION/CONCLUSIONS:Patients who had a meniscus repair at the time of tibial plateau fracture repair were found to have poorer knee ROM, more patient reported pain at minimum 12 (mean 24) months post-operation. Additionally, these patients developed more post-operative complications than those patients who did not undergo a meniscus repair.

Expression of the IgE BCR is associated with increased B cell apoptosis, yet in persistent allergy, sustained production of IgE antibodies in the absence of allergen exposure suggests the existence of long-lived IgE plasma cells (PCs). Here we studied the development and localization of IgE PCs in mouse models of allergy. After immunization, IgE PCs underwent maturation in spleen and lymph nodes, acquiring a stable MHCII^loCD93⁺CD98^hiBCR^lo phenotype. Mature IgE PCs had a distinct transcriptional profile adapted to high protein synthesis, glycosylation, and survival and resisted BCR-crosslinking-induced apoptosis. Immunization induced a burst of short-lived IgE PC formation, followed by a reduced differentiation rate over time, compared with IgG1 PCs. Timestamping of PCs revealed long-lived IgE PCs that localize to the spleen, in addition to the bone marrow (BM). Thus, immune challenge can generate both short-lived and long-lived IgE PCs, with long-lived IgE PCs in spleen and BM contributing to allergy persistence.

INTRODUCTION/BACKGROUND:The study aimed to investigate the efficacy of autogenous iliac crest bone graft (ICBG) compared with other graft types in achieving successful fracture nonunion repair. METHODS:An institutional review board-approved retrospective review of prospectively collected data was conducted on a consecutive series of patients surgically treated for fracture nonunions at an academic medical center between September 10, 2004, and August 20, 2023. Patients were analyzed based on which bone graft type-ICBG versus alternative graft types-used during their nonunion repair. Patient demographics, injury characteristics, and surgical history were compared. Outcomes included radiographic healing, time to union, postoperative complications, and revision rate. Cohorts were compared using an independent sample Student t-test for continuous variables and chi-square or Fisher exact tests for categorical variables. One-way analysis of variance with post hoc comparisons assessed differences across treatment strategy groups. RESULTS:Five hundred fifty-six patients were treated surgically for a fracture nonunion using standard internal fixation and a "bone graft" for biologic stimulation. 57.4% of these patients were treated with autogenous ICBG; 42.6% received alternative grafts (iliac crest aspirate, allograft, bone morphogenetic, reamer-irrigation aspirator, and/or demineralized bone matrix, without autogenous cancellous iliac crest). Compared with the alternative cohort, the ICBG cohort showed greater healing success after a single nonunion surgery (95.6% ICBG versus 86.9% alternative, P < 0.001) and faster healing times (4.8 ± 2.4 months versus 7.1 ± 4.9 months, P < 0.001). Complications at the ICBG harvest site included wound infections/hematomas and iliac wing fracture. No notable differences were found in positive cultures at the time of surgery, postoperative fracture-related infection, implant failure, or neurovascular injury. DISCUSSION/CONCLUSIONS:Using autogenous ICBG in the surgical repair of fracture nonunions was associated with higher healing rates compared with alternative graft types, supporting its continued role in enhancing bone healing outcomes, even in the face of infected nonunion.

Fertility in women decreases with age, but the molecular basis for age-related, unexplained infertility remains elusive. Here, we reveal distinct transcriptome changes in oocytes and surrounding cumulus cells from women in their mid-thirties, as evidenced by notably increased transcription of ribosome genes. Additionally, meiosis genes and actin and cohesin components are downregulated in oocytes with age. Lysosomes and proteostasis are also disrupted in cumulus cells. Moreover, DNA hypomethylation and altered heterochromatin deposition at specific genomic loci are linked to increased transcription of ribosome genes. Rapamycin effectively reduces translation and promotes protein homeostasis in cumulus cells. Remarkably, short-term rapamycin allows patients who fail repeated in vitro fertilization cycles with embryo developmental arrest to achieve high-quality blastocysts that yield successful pregnancy and live birth. These data suggest a causal role for elevated transcription of ribosome genes in aging oocytes and cumulus cells and identify rapamycin as a promising treatment for age-related infertility. This study is registered at Chinese Clinical Trial Registry (ChiCTR2300069828).