Faculty Bibliography

Therapeutic anticoagulation is essential to prevent and treat venous and arterial thromboembolism. The available agents target coagulation factors involved in thrombus formation but are associated with an increased risk of bleeding. Factor XI plays a minor role in haemostasis but contributes substantially to thrombus expansion, making it an attractive target to mitigate bleeding while maintaining antithrombotic efficacy. Various novel inhibitors, including antisense oligonucleotides, monoclonal antibodies and small molecules, have been developed. Phase II trials in orthopaedic surgery showed dose-dependent reductions in venous thromboembolism without significantly increasing bleeding compared with enoxaparin. In the first phase III trial of a small-molecule inhibitor of activated factor XI in patients with atrial fibrillation, asundexian was associated with a reduction in bleeding but also a higher risk of stroke, compared with apixaban. Factor XI inhibitors appear safe and hold promise for secondary prevention in myocardial infarction and ischaemic stroke, with ongoing phase III trials assessing their broader efficacy and safety. This Review discusses the rationale, pharmacology, evidence and future directions of factor XI inhibitors across various clinical settings.

BACKGROUND/UNASSIGNED:Uniplanar coronal tibiofemoral subluxation (UCTFS) in the setting of multiple ligament knee injury (MLKI) or knee dislocation (KD) has rarely been discussed, and the potential for missed diagnosis may significantly impact long-term outcomes. PURPOSE/UNASSIGNED:To describe the presentation, injury patterns, possible mechanical barriers for reduction, and management for isolated UCTFS after MLKI/KD. STUDY DESIGN/UNASSIGNED:Case series; Level of evidence, 4. METHODS/UNASSIGNED:A retrospective chart review was conducted at 4 institutions to identify patients with KD or MLKI who were evaluated with or developed subsequent UCTFS from January 2001 to January 2024. UCTFS was defined as medial or lateral translation of the tibial plateau in reference to the femoral condyle as seen on coronal imaging (radiograph, computed tomography scan, or magnetic resonance imaging scan), with normal alignment seen on the sagittal imaging. Medical records were reviewed for demographic data, clinical presentation, physical examination, diagnostic imagining, examination under anesthesia, surgical finding, and procedures performed. RESULTS/UNASSIGNED:A total of 15 cases were included. Of these, 12 patients were subluxed laterally and 3 medially. UCTFS was diagnosed at different time points with 10 patients within 1 week, 2 patients between 1 and 6 weeks, and 3 patients after 6 weeks from injury. The most common mechanism of injury was a fall (33%), and the most common pattern of injury was a KD-3L (26.6%). A mechanical blockage to reduction was found in 9 (60%) cases. These included medial soft tissue sleeve incarceration (n = 4), bucket-handle meniscal tears (n = 3), concomitant patellar dislocation (n = 2), and a displaced tibial spine fracture (n = 1). Some patients experienced subluxation due to several sources of mechanical block. Uniplanar external fixation was utilized in 7 patients for management of their initial ligamentous injuries, coronal instability, or a traumatic vascular injury. Hinged external fixation was utilized in 2 patients who presented in a chronic fashion to counter the propensity to subluxation while allowing early motion. CONCLUSION/UNASSIGNED:UCTFS is a rare event that has several potential factors contributing to its cause, and ≥1 of these factors may need to be surgically addressed. Tibiofemoral subluxation can be found at various time points from injury, and awareness and monitoring for its development should be factored into the clinical decision-making. UCTFS is a challenging clinical dilemma that may require multiplanar or hinged external fixation to maintain reduction.

OBJECTIVE:A standardized multifaceted approach to follow-up is crucial for monitoring neurodevelopment in neonates who undergo extracorporeal membrane oxygenation (ECMO). The Pittsburgh Index for Pre-ECMO Risk (PIPER+) score, which predicts the probability of hospital mortality, may help predict adverse neurodevelopmental outcomes. This study sought to assess the neurodevelopment of neonates who were treated with ECMO in our newly developed ECMO program, by analyzing Bayley Scales of Infant Development (BSID) scores obtained at the Neonatal Comprehensive Care Program (NCCP), our neurodevelopmental follow-up clinic, through two years of age. It also aimed to determine whether neurodevelopmental outcomes in our study population were correlated to PIPER+ score, magnetic resonance imaging (MRI), or video electroencephalography (vEEG) findings. STUDY DESIGN/METHODS:We conducted a retrospective chart review of neonatal patients placed on ECMO at our institution between March 2015 and June 2023 who had at least one follow-up visit at the NCCP clinic. The relationships between neurodevelopmental outcomes, quantified by the BSID score, PIPER + score, MRI results, and vEEG abnormalities were analyzed. RESULTS:A total of 18 patients met the inclusion criteria. There was a significant negative correlation (p<0.05) between PIPER+ and BSID scores at 12 months across all developmental domains analyzed. However, this correlation was no longer significant at 24 months. The odds of the combined outcome of mortality or neurodevelopmental impairment at two years of age increased by 17% for each 1% increase in the PIPER+ score. CONCLUSIONS:Higher PIPER+ scores were associated with higher mortality in our population; they also correlated with worse neurodevelopmental outcomes at 12 months, but not at 24 months. It is important and feasible to follow neonates who underwent ECMO using a neurodevelopmental follow-up clinic.

Tessier facial clefts are rare congenital abnormalities and among the most challenging deformities treated by craniofacial surgeons. Despite various surgical interventions, treatment outcomes remain limited, resulting in a higher burden of care and lower quality of life. PreSurgical Infant Orthopedics (PSIO) has shown benefits in cleft care, but its application to Tessier clefts is underreported. This report assesses the long-term surgical outcomes of 3 patients with Tessier clefts who underwent PSIO. The cleft width and premaxilla reduction were observed in all 3 patients.

BACKGROUND/UNASSIGNED:In May 2022, mpox (formerly monkeypox) began spreading globally through LGBTQ+ sexual networks. By August 2022, New York City (NYC) became the global epicenter of the mpox outbreak, with the highest number of cases reported in the United States. Here, we quantify the mpox vaccination effort, focusing on flexible and community-responsive mobile vaccination. METHODS/UNASSIGNED:We describe an on-site mpox vaccination strategy at commercial sex venues, nightlife venues, and pride and health centers, during August 1-November 15, 2022. Data were collected on doses, demographics, and event size to determine and evaluate vaccine uptake. RESULTS/UNASSIGNED:The on-site vaccination strategy resulted in 3358 JYNNEOS doses administered at 363 events at 58 locations, including 22 events at 2 commercial sex venues. Commercial sex venues in New York City closed at the height of the mpox epidemic. We show high uptake of the JYNNEOS vaccine at commercial sex venues, with as many as 60% of attendees of 1 event receiving a JYNNEOS vaccine dose on site. This was possible after New York City health agencies responded to community demand for second doses. Messaging about the importance and availability of vaccination at these parties was community-led. JYNNEOS vaccination via mobile clinics demonstrated less racial and geographic disparity compared with nonmobile vaccinations. We show no increase in mpox cases as commercial sex venues reopened with vaccination on site. CONCLUSIONS/UNASSIGNED:These results demonstrate the success of a community-led rapid response to an emergent mpox outbreak, including at places where people meet for sex.

INTRODUCTION/BACKGROUND:Foundational preacademic skills are crucial for academic success and serve as predictors of socioeconomic status, income and access to healthcare. However, there is a gap in our understanding of neurodevelopmental patterns underlying preacademic skills in children across low-income and middle-income countries (LMICs). It is essential to identify primary global and regional factors that drive children's neurodevelopment in LMICs. This study aims to characterise the typical development of healthy children and factors that influence child development in Bahir Dar, Ethiopia. METHODS AND ANALYSIS/METHODS:The Bahir Dar Child Development Study is a cross-sectional study implemented in two health centres, Shimbit and Abaymado and in Felege Hiwot Comprehensive Specialized Hospital (FHCSH) in Bahir Dar, Amhara, Ethiopia. Healthy children between 6 and 60 months of age will be recruited from the health centres during vaccination visits or via community outreach. Young children aged 6-36 months will complete the Global Scale for Early Development. A battery of paper and tablet-based assessments of neurocognitive outcomes including visual and verbal reasoning, executive functions and school readiness will be completed for children aged 48-60 months. Caregivers will respond to surveys covering sociodemographic information, the child's medical history and nutrition, and psychosocial experiences including parental stress and mental health. During a second visit, participants will undergo a low-field MRI scan using the ultra-low-field point-of-care Hyperfine MRI machine at FHCSH. Analyses will examine relationships between risk and protective factors, brain volumes and neurocognitive/developmental outcomes. ETHICS AND DISSEMINATION/BACKGROUND:The study is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/lRERC/004/2023/Al/05-2024), Mass General Brigham Hospital (2022P002539) and Brown University (STUDY00000474). Findings will be disseminated via local dissemination events, international conferences and publications. TRIAL REGISTERATION NUMBER/BACKGROUND:NCT06648863.

BACKGROUND AND OBJECTIVE/OBJECTIVE:The diagnosis of interstitial lung diseases (ILDs) often relies on the integration of various clinical, radiological, and histopathological data. Achieving high diagnostic accuracy in ILDs, particularly for distinguishing usual interstitial pneumonia (UIP), is challenging and requires a multidisciplinary approach. Therefore, this study aimed to develop a multimodal artificial intelligence (AI) algorithm that combines computed tomography (CT) and histopathological images to improve the accuracy and consistency of UIP diagnosis. METHODS:A dataset of CT and pathological images from 324 patients with ILD between 2009 and 2021 was collected. The CT component of the model was trained to identify 28 different radiological features. The pathological counterpart was developed in our previous study. A total of 114 samples were selected and used for testing the multimodal AI model. The performance of the multimodal AI was assessed through comparisons with expert pathologists and general pathologists. RESULTS:The developed multimodal AI demonstrated a substantial improvement in distinguishing UIP from non-UIP, achieving an AUC of 0.92. When applied by general pathologists, the diagnostic agreement rate improved significantly, with a post-model κ score of 0.737 compared to 0.273 pre-model integration. Additionally, the diagnostic consensus rate with expert pulmonary pathologists increased from κ scores of 0.278-0.53 to 0.474-0.602 post-model integration. The model also increased diagnostic confidence among general pathologists. CONCLUSION/CONCLUSIONS:Combining CT and histopathological images, the multimodal AI algorithm enhances pathologists' diagnostic accuracy, consistency, and confidence in identifying UIP, even in cases where specialised expertise is limited.

BACKGROUND:To compare clinical outcomes, return to activities, and rates of revision surgery following arthroscopic glenoid labral repair in patients who were prescribed NSAIDs as part of their postoperative pain management regimen versus those who were not. METHODS:Patients aged 18-55 who underwent primary arthroscopic labral repair at a single academic institution from the years 2016-2020 were retrospectively reviewed. Patients who underwent concomitant rotator cuff repair, remplissage, or did not have minimum 2-year postoperative follow-up were excluded. Patients who were prescribed postoperative NSAIDs were matched 1:1 to those who were not based on age, sex, BMI, and number of suture anchors. Outcomes were assessed using the Visual Analog Scale (VAS) for pain, American Shoulder and Elbow Surgeons Shoulder Score (ASES), Simple Shoulder Test (SST), Single Assessment Numeric Evaluation rating (SANE), and satisfaction. Pre-injury sport and work activity information were recorded. RESULTS:Of 269 eligible patients, 224 patients were included. Patients prescribed NSAIDs postoperatively had similar levels of pain (1.2 vs 1.0, p=0.527) and function (ASES: 90.8 vs 89.9, p=0.824; SST: 91.9 vs 90.6, p=0.646; SANE: 83.8 vs 85.3, p=0.550) compared to those who were not. Rates of revision surgery (2.7% vs 0.9%, p=0.622) and recurrent instability (5.4% vs 8.0%, p=0.594) were similar between NSAID and non-NSAID groups. Rates of return to sport (83.5% vs 77.8%, p=0.318) and return to pre-injury level (59.3% vs 61.6%, p=0.177) were similar between NSAID and non-NSAID groups. Prescription of postoperative NSAIDs was not associated with delayed return to sport (OR:1.47, 95%CI [0.68,3.18], p=0.327) or return to work (OR:0.56, 95%CI [0.14,2.28], p=0.416). CONCLUSIONS:Patients who were prescribed NSAIDs as a part of a postoperative pain management regimen following primary arthroscopic labral repair for glenohumeral instability had similar patient-reported outcomes, revision rates, and rates of return to pre-injury activities compared to those who were not prescribed NSAIDs.

The endoscopic transsphenoidal approach (ETSA) is a commonly used technique that allows for the minimally invasive removal of sellar and parasellar lesions. Augmented reality (AR) applications in ETSA are hypothesized to enhance intraoperative visualization by integrating a 3D-reconstructed model into the operative field. This study describes the workflow and surgical outcomes associated with the Endoscopic Surgical Navigation Advanced Platform (EndoSNAP, Surgical Theater, Cleveland, OH, USA), an AR platform designed for surgical planning and intraoperative navigation in ETSA for sellar and parasellar lesions. We analyzed a cohort of patients who underwent ETSA tumor resection using EndoSNAP. Preoperative MRI and CT scans were reconstructed and merged into a single 360° AR model using the Surgical Rehearsal Platform software. The model was then imported into EndoSNAP, which was integrated with the endoscope and neuronavigation system for real-time intraoperative use. Patient demographics, tumor characteristics, extent of resection (EOR), and endocrinologic and neurologic outcomes were recorded. Eighteen adult patients with newly diagnosed (83%) and recurrent (17%) tumors were included. Pathologies consisted of pituitary adenoma (72%), craniopharyngioma (11%), meningioma (11%), and chordoma (6%). Optic compression was present in 56% of patients, with preoperative visual deficits in 70% of them. Cavernous sinus invasion was observed in 17% of tumors. Preoperative hormonal excess and insufficiency were noted in 56% and 28% of cases, respectively. The mean preoperative tumor volume was 21.4 ± 17 cm³, which decreased to 0.4 ± 0.3 cm³ postoperatively. The mean EOR was 93.6 ± 3.6%. Postoperative complications included CSF leaks requiring surgical repair (17%), seizures related to pre-existing hemispheric trauma (6%), pulmonary embolism (6%), deep venous thrombosis (6%), and sinusitis (6%). These findings suggest that AR-enhanced visualization through EndoSNAP is a feasible and potentially beneficial adjunct in ETSA for sellar and parasellar tumor resection.