Faculty Bibliography

The purpose of this study was to compare outcomes in patients who sustained isolated lateral column tibial plateau fractures and combined lateral and posterolateral column tibial plateau fractures (AO/OTA 41B3 lateral split-depression fractures). Fractures were classified according to the three-column classification system of tibial plateau fractures. The primary outcome was the difference in Short Musculoskeletal Function Assessment (SMFA) function index at 12 months postoperatively between patients with lateral column plateau fractures and patients with combined lateral and posterolateral column plateau fractures. Seventy-eight patients were included (mean age: 48.8 ± 14.1 years). Thirty-two patients (41.0%) were in the isolated lateral column group (L), and 46 patients (59.0%) were in the lateral column plus posterolateral column group (L + PL). At 1 year following injury and fixation, the L + PL group demonstrated significantly worse SMFA function index than the L group (19.1 ± 17.7 vs. 9.1 ± 12.5, p = 0.005). Similarly, the L + PL group was significantly more bothered by the sequelae of their injury compared to the L group at 1 year based on the SMFA bothersome index (20.7 ± 23.7 vs. 8.6 ± 12.3, p = 0.005). Patients with combined lateral and posterolateral column tibial plateau fractures demonstrate worse outcomes compared to isolated lateral column fractures 1 year after fixation. The study provides level III evidence.

The hippocampal dentate gyrus (DG) segregates input patterns aided by inhibitory circuits. Despite their importance, few studies have recorded identified DG interneurons in behaving animals. Here, we used electrophysiological recordings, bidirectional optogenetic manipulations, and modeling to characterize parvalbumin (PV)- and somatostatin (SST)-expressing interneurons in freely behaving mice. We employed machine learning to classify granule cells (GCs), mossy cells (MCs), and PV and SST interneurons simultaneously and studied their synaptic interactions in shaping spatial information and responses to entorhinal synaptic inputs. We demonstrated a central role for SST interneurons in regulating the impact of entorhinal excitation and for PV interneurons in feedback inhibition. Finally, optogenetic manipulations revealed a paradoxical observation: instead of merely suppressing firing in the surrounding network, DG interneuron stimulation exacerbated "winner-take-all" dynamics, including paradoxical polysynaptic excitation of some excitatory neurons. Such use-dependent modulation of winner-take-all dynamics may support the selection of content-bearing neuronal ensembles during cognitive processes.

Using CDC's Active Bacterial Core surveillance data, we observed increasing incidence of rare group B Streptococcus serotypes VI and VIII, from 0.007 and 0 cases per 100,000 in 2007 to 0.14 and 0.13 in 2023, respectively. These serotypes disproportionally impacted American Indian/Alaska Native, Asian, and Native Hawaiian/Pacific Islander populations.

BackgroundThe cellular mechanisms that promote the maintenance of cognitive abilities in very old people designated as successful agers remain under-investigated. Here, we report an episodic memory performance-based criteria that differentiates superior cognitive function from normative cognitive function in adults aged 80 and older.ObjectiveUsing this new criteria, we demonstrate how neuropathological and neurobiological underpinnings of superior cognitive performance can be investigated.MethodsThe most recent verbal episodic memory WMS-R Logical Memory Delayed Recall (LM-DR) score was derived from 144 participants with no cognitive impairment (NCI) 80 years or older participants from the Rush Religious Orders Study classified with Superior Cognitive Performance (SCP, LM-DR ≥ 14) or Normal Cognitive Performance (NCP, LM-DR 13 ≥ 7). Both groups were compared on neuropathological measures for neuritic plaque (NP), diffuse plaque (DP), and neurofibrillary tangle (NFT) load.ResultsNP (p = 0.44), DP (p = 0.27), and NFT (p = 0.28) burden did not differ between SCP and NCP cases. LM-DR scores did not correlate with NP (r = -0.08, p = 0.32), DP (r = -0.14, p = 0.07), or NFT (r = -0.12, p = 0.13) load. Biochemical analysis revealed significantly higher levels of heat-shock protein HSPB6 in SCP compared to NCP (p < 0.001).ConclusionsHeat shock protein differences were observed between NCP and SCP groups. This suggests that our proposed criteria for SCP can help identify neurobiological mechanisms of successful cognitive aging. Our SCP criteria are also concordant with the SuperAger criteria which supports the generalizability of the SCP criteria to other datasets.

BACKGROUND:Most branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) are indolent, but distinguishing those harboring high-grade dysplasia or invasive cancer remains difficult. This analysis focuses not on incidental small BD-IPMNs but on the subset whose cyst characteristics bring surgery into the decision-making discussion. Surgery prevents malignant progression but carries morbidity; surveillance avoids overtreatment but risks delayed cancer detection. Current guidelines rely on fixed thresholds that may not reflect individual variation. Our study compared immediate surgery and initial surveillance in patients with BD-IPMNs, using a decision-analytic model that incorporates patient-specific risk factors. METHODS:A Markov decision model compared immediate surgery with initial surveillance, incorporating age, comorbidities, and cyst location. Health states reflected progression from low-grade to high-grade dysplasia and invasive cancer, postoperative complications, recurrence, and quality-of-life decrements. Transition probabilities were derived from published studies and American College of Surgeons (ACS)-National Surgical Quality Improvement Program data. The primary outcome was quality-adjusted life-years (QALYs). RESULTS:For a 60-year-old patient with mild comorbidities and a pancreatic head BD-IPMN, immediate surgery provided 16.8 QALYs versus 16.3 with surveillance (incremental gain, 0.5 QALYs). Lifetime cancer probability was lower with surgery (24.5% vs 33.5%), as was cancer-related mortality (9.3% vs 20.3%), though surgery resulted in more resections for low-grade dysplasia (55.0% vs 15.3%). Age, baseline cancer probability, and perioperative mortality were the strongest determinants of the preferred strategy. CONCLUSIONS:Among patients with BD-IPMNs being considered for surgery, immediate resection offers a modest benefit for younger, healthier individuals, whereas surveillance remains appropriate for older or comorbid patients. These findings support individualized, risk-based management rather than universal application of guideline thresholds.

Among the strategies to improve outcomes of rotator cuff repair, proper surgical technique is quintessential. While the ideal goal of a rotator cuff repair is anatomic restoration of the native tendon footprint, this may not always be possible to accomplish without placing significant tension on the medial stump. Recent literature shows the importance of tension modulation in rotator cuff repair, showing better clinical outcomes and healing rates with tension-reducing techniques, compared with full footprint covering repair, with the difference notable in larger and more retracted tears. Simultaneously single- and double-row repairs showed similar outcomes, better results were achieved with rehabilitation that was conservative rather than accelerated, and no difference was shown between tendon remnant preservation and footprint medialization.

Electrical and structural remodeling of the heart can contribute to the development of cardiac arrhythmias. Ex vivo optical mapping has been used to visualize cardiac electrophysiological properties, activation and phase maps to further elucidate the mechanisms of atrial fibrillation and ventricular fibrillation initiation and persistence. Here we show an epicardial three-dimensional panoramic optical mapping tool integrated with micro-computed tomography automatically segmented with a deep learning model relying on a convolutional neural network to provide structural and electrical activation information in a single three-dimensional volume of a mouse heart. This technique allows for the acquisition and analysis of electrical activity of the entire epicardial surface with submillimeter spatial resolution and a temporal resolution of 1 ms. We establish the use of this method in transgenic mouse hearts with spontaneous atrial fibrillation and ventricular fibrillation, and mouse surgical models of myocardial infarction and left ventricular hypertrophy.

Strain imaging, performed with echocardiography and cardiovascular magnetic resonance (CMR), is a noninvasive technique for detecting subclinical myocardial dysfunction across the heart failure spectrum, in various cardiomyopathies, and within the field of cardio-oncology. By quantifying myocardial deformation, strain enhances diagnosis, risk stratification, and treatment monitoring beyond traditional measures such as ejection fraction. While echocardiography remains the most accessible modality, ongoing advances in CMR techniques-including incorporation of artificial intelligence-promise to improve standardization, reproducibility, and clinical integration of strain imaging in the management of heart failure and cardiovascular care.

Advances in targeted therapies, immunotherapy, and early detection have revolutionized lung cancer treatment and extended survival. Nonetheless, lung cancer remains highly fatal. Here, we identify knowledge gaps and propose critical areas of future research, aligning with the mission of the AACR Lung Cancer Task Force. We delineate research priorities, including advancing prevention initiatives, enhancing early detection strategies, developing novel treatments, and refining patient stratification. Addressing disparities and increasing efforts on relatively neglected lung cancer subtypes are also essential. Finally, international collaboration, centralized clinical trial databases, novel clinical trial designs, and artificial intelligence-driven analytics should accelerate precision medicine and aid in elucidating drug resistance mechanisms. Together, these efforts promise to improve patient outcomes.

BACKGROUND:Donation after the circulatory determination of death (DCD) heart transplantation (HT) is becoming more widely adopted across the United States (US) and Europe. OBJECTIVE:This study compared donor and recipient demographics, intraoperative parameters, and outcomes between DCD HT centers in Europe and the US that contributed to the Outcomes after DCD Cardiac Transplantation Database. METHODS:This was a retrospective observational study across 22 HT centers in Belgium, Spain, the United Kingdom (UK), and the US. All patients undergoing DCD HT at participating centers, from the start of each center's DCD program through 01/01/2023, were included with censor date 01/01/2024. The primary outcome was 1-year survival. Secondary outcomes included severe primary graft dysfunction and incidence of acute cellular rejection. RESULTS:Data from 223 patients in Europe and 281 in the US were analyzed. DCD donors in Europe were significantly older (37 years vs 28 years; p < 0.001). Recipients in Europe had inferior 1-year survival (86.6% vs 91.8%; p = 0.043), but 1-month and 3-years survival were similar. 1-year survival in the direct procurement and preservation (DPP) cohort was significantly higher in the US group (91.2% vs 82.6%; p = 0.02). In the thoraco-abdominal normothermic regional perfusion (taNRP) cohort 1-year survival was similar between Europe and the US. Recipients in Europe had higher use of mechanical circulatory assist post-transplant (17.9% vs 11%; p = 0.03). CONCLUSION/CONCLUSIONS:This study further confirms the safety and efficacy of DCD HT across centers in the US and Europe, despite important differences in donor and recipient demographics and clinical outcomes. Continued collection of international data may identify opportunities to improve outcomes.