Faculty Bibliography

Fructose consumption increases the risk of obesity-related metabolic diseases and some cancers, but its role in hepatocellular carcinogenesis (HCC) remains controversial. Animal studies suggest that high fructose promotes HCC, whereas human data fail to support the positive link between fructose intake and elevated risk of liver cancer. Moreover, fructose metabolism is progressively attenuated in HCC with the loss of key fructolytic enzymes, including fructose-1,6-bisphosphate aldolase B (ALDOB). Here, we report that fructose suppresses HCC through fructose 1-phosphate (F1P)-mediated inhibition of mannose phosphate isomerase (MPI) in the context of ALDOB deficiency. Transcriptomic and metabolic flux analyses using human HCC cells and tissues revealed that liver cancer cells retain a significant ability to metabolize fructose despite the downregulation of fructolytic genes, with ALDOB showing the earliest and most pronounced suppression compared with GLUT2 and KHK. Dietary supplementation with 10% fructose suppressed HCC in liver-specific Aldob knockout mice. Further spatial and single-cell transcriptomic analyses of clinical HCC samples revealed the spatiotemporal dynamics of fructolytic gene expression and identified subsets of cancer cells that retain fructose uptake and phosphorylation capacity (SLC2A2⁺/KHK⁺) but lack ALDOB expression. Upon fructose exposure, accumulated F1P binds to and inhibits MPI, reducing protein N-glycosylation and triggering apoptosis due to maladaptive ER stress. We further performed virtual high-throughput screening of FDA-approved and clinical-trial drugs and identified ebselen as a potent MPI inhibitor. Taken together, the results of our study reveal a novel mechanism by which dietary fructose inhibits HCC through the F1P-MPI axis, suggesting a therapeutic strategy targeting metabolic vulnerabilities in cancer.

Pulsatile tinnitus is a specific type of sound caused by vascular anomalies, usually associated with turbulent blood flow, secondary to high-output stenosis or arterial tortuosity. These alterations can produce rhythmic sounds that compromise patients' quality of life. This report describes the case of a 51-year-old woman with pulsating tinnitus in her right ear for 18 months. No significant changes were identified on arterial computed tomography angiography or cranial magnetic resonance angiography due to the non-completion of the joint venous phase. Carotid Doppler ultrasound showed abnormal flow in the right external carotid artery, with a decreased resistance index, suggesting an arteriovenous fistula. Cerebral angiography confirmed the diagnosis, showing communication between external carotid artery branches and intracranial veins. The patient underwent endovascular treatment with embolization, resulting in complete resolution of symptoms and normalization of Doppler parameters at 24-month follow-up.

Articular cartilage lesions of the knee pose a significant clinical challenge due to the limited regenerative capacity of hyaline cartilage and the wide variability in patient presentation and lesion characteristics. Surface-based cartilage restoration techniques have evolved substantially, shifting from isolated marrow stimulation toward biologically enhanced strategies designed to improve repair tissue quality, durability, and clinical outcomes while preserving native joint anatomy. These techniques are primarily indicated for contained chondral defects without substantial subchondral bone compromise and include scaffold-augmented microfracture, particulated cartilage techniques using juvenile or adult allograft tissue, and matrix-associated autologous chondrocyte implantation (ACI). Selection among these options is driven by patient age, activity level, and expectations, as well as lesion-specific factors such as size, anatomic location, containment, and subchondral bone integrity. Single-stage approaches, including micronized cartilage extracellular matrix augmentation and particulated cartilage allografts, offer reduced procedural burden and avoidance of cell expansion, with favorable short- to mid-term outcomes for small to moderate lesions. In contrast, matrix-induced autologous chondrocyte implantation (MACI) is supported by randomized controlled trials and long-term cohort studies demonstrating sustained improvements in patient-reported outcomes (PROs) beyond 10 years, particularly in younger, active patients with larger isolated defects. Despite these advances, variability in imaging findings, complication profiles, and performance in the patellofemoral joint underscores the importance of appropriate patient selection, meticulous surgical technique, and structured postoperative rehabilitation. This review synthesizes current evidence regarding indications, surgical techniques, outcomes, and limitations of contemporary surface-based cartilage restoration options for the knee, providing a practical framework to guide clinical decision-making in joint preservation surgery.

BACKGROUND/UNASSIGNED:Social determinants of health disparities (SDHD), encompassing environmental, health care, social, educational, and economic factors, are known to increase the risk of complications after various orthopaedic procedures. However, their impact on tibial tubercle osteotomy (TTO) outcomes remains undefined. HYPOTHESIS/PURPOSE/UNASSIGNED:This study aimed to compare complication risks and health care utilization within 90 days and 1 year of primary TTO in patients with versus without SDHD. It was hypothesized that SDHD patients would show higher odds of health care utilization and complications. STUDY DESIGN/UNASSIGNED:Cohort study; Level of evidence, 3. METHODS/UNASSIGNED:Adult (>17 years) patients who underwent primary TTO from January 2010 to April 2023 were identified using the PearlDiver M170 database. The exclusion criteria included inactivity within 90 days after TTO or a history of neoplasm or infection within 90 days before the procedure. The overall cohort was divided into SDHD and non-SDHD groups. Patient characteristics-including age, sex, Elixhauser Comorbidity Index, obesity, type 2 diabetes mellitus, tobacco or nicotine use, and substance use disorder-were abstracted. Patients without versus with SDHD were matched (2:1) based on all demographic variables. Moreover, 90-day and 1-year complications were identified and compared using the Pearson chi-square test and multivariable logistic regression, adjusted for demographic variables. RESULTS/UNASSIGNED:< 0.05). CONCLUSION/UNASSIGNED:The present study found that SDHD patients were associated with increased odds of ED visits, readmissions, VTE, and UTI after primary TTO. Additionally, SDHD patients demonstrated higher odds of revision TTO and nonunion. Further research is needed to identify the root causes of these differences, enabling targeted strategies to reduce future outcome inequities associated with SDHD.

Alzheimer disease neuropathologic change (ADNC) is considered to be the most common cause of cognitive decline and dementia worldwide. ADNC level is determined using the density of neuritic plaques in combination with the topographical distribution of β-amyloid (Aβ) plaques and hyperphosphorylated tau (p-tau)-positive neurofibrillary tangles (NFTs). While cognitive decline correlates with the level of ADNC, there remains a great deal of variation in cognitive outcomes between individuals that is unaccounted for by current neuropathologic evaluation metrics. We leveraged quantitative computer-assisted positive pixel assessments to establish the neocortical p-tau burden in the middle frontal and superior temporal gyri of 61 individuals with Braak NFT stage V who had a wide range of cognitive outcomes and trajectories. Frontal and temporal neocortical p-tau burden varied between 0.2% and 53.7%. Both frontal and temporal p-tau burden directly affected cognitive outcome and correlated with function of multiple cognitive domains, including measures of language/semantic memory and attention/working memory. In multivariable analysis, only p-tau burden and microinfarcts significantly impacted cognitive decline, while Aβ, limbic-predominant age-related TDP-43 encephalopathy, Lewy body pathology, and other measures of cerebrovascular disease did not. Additionally, individuals with low mean neocortical p-tau burden (≤ 13%) had significantly better longitudinal cognitive trajectories over the final 15 years of life compared to those with high burden (≥ 23.5%). These results suggest that while all individuals with Braak stage V have some degree of neurofibrillary degeneration in the neocortex, the significant variation in cognitive decline observed between these individuals can be partially understood as a reflection of the variation in quantitatively assessed neocortical p-tau burden, which had a greater impact on progression to dementia than common comorbid neuropathologies associated with dementia risk. This argues for the incorporation of the density of ADNC-related pathology, in addition to its regional location, as an adjunct to future staging systems for Alzheimer disease.

PURPOSE/UNASSIGNED:The objective of this study was to identify temporal trends in intensity modulated radiation therapy (IMRT) use for patients with cervical cancer who received definitive chemoradiation. METHODS AND MATERIALS/UNASSIGNED:Patients diagnosed with stage IB2-IVA cervical cancer between 2004 and 2019 and treated with definitive chemoradiation were identified in the National Cancer Database. The primary outcome of interest was the use of IMRT versus 3-dimensional conformal radiation therapy (3DCRT) over time. Wilcoxon rank-sum tests, chi-square tests, and multivariable logistic regression were used to identify factors associated with the receipt of IMRT. RESULTS/UNASSIGNED:< .01). Clinical factors associated with increased IMRT use were stage III disease compared with stage I (odds ratio [OR], 1.3; CI, 1.0-1.5) and lymph node involvement (OR, 1.4; CI, 1.2-1.6). The demographic factors associated with increased IMRT receipt were treatment in the western US (OR, 1.5; CI, 1.2-1.8) and in the southern US (OR, 1.3; CI, 1.1-1.5) compared with the northeastern US, and living more than 50 miles from the treatment facility (OR, 1.2; CI, 1.0-1.5). Compared with White patients, Black patients (OR, 0.8; CI, 0.6-0.9) and patients receiving care at community hospitals compared with academic medical centers (OR, 0.7; CI, 0.6-0.7) were less likely to receive IMRT. CONCLUSIONS/UNASSIGNED:IMRT utilization for cervical cancer has increased over the last 15 years, especially for patients with advanced-stage disease or lymph node involvement. Understanding shifts in policy, demographic trends, and practice patterns may provide additional insight into the adoption of advanced technologies.

Current CardioMEMS HF System (Abbott) instructions for use recommend against implantation in obese patients (body mass index >35 kg/m²) whose chest circumference exceeds 165 cm, as placement can be technically challenging and remote interrogation can be unreliable. We present a case of successful CardioMEMS implantation in a patient with significant morbid obesity, exceeding previously reported body size limits, with a body mass index of 77.1 kg/m² and chest circumference of 178 cm. Outpatient device interrogation following implantation has been reliable in optimizing diuretic management and preventing readmissions in this patient.

Nationally, there is increased investment in interventions that address diet-related chronic diseases however few studies and interventions are developed to reflect the values and lifestyles of many communities, presenting a barrier to participation. This study aims to better understand the motivators and barriers for the Bangladeshi American community in Brooklyn, New York to participate in diet-related interventions. Formative qualitative interviews were conducted in English and Bangla with Bangladeshi adults (n = 12) to understand current shopping/cooking behaviors, access and usage of food programs, awareness and interest in food programs, and future program preferences. Participants reported three key themes: centrality of community behaviors for program acceptability, creating opportunities to leverage community and social motivations, and addressing logistical concerns during program development. Gardening emerged as a promising program offering to increase access to fresh produce, strengthen community bonds, and foster cross-cultural understanding. Using community feedback, Harvest Share Seedlings, a community-informed home gardening program, was co-developed and implemented with farming and community partners to increase access to fresh produce for the Bangladeshi community. The findings highlight the need to understand and center community-specific considerations when designing and implementing food programs and interventions. Adopting a community-informed approach increases uptake and acceptability from the community, and ensures sustainability in the long run.