Faculty Bibliography
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name:Gan
school:SOM
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4873
Callosal Interhemispheric Communication in Mild Traumatic Brain Injury: A Mediation Analysis on WM Microstructure Effects
BACKGROUND AND PURPOSE/OBJECTIVE:Because the corpus callosum connects the left and right hemispheres and a variety of WM bundles across the brain in complex ways, damage to the neighboring WM microstructure may specifically disrupt interhemispheric communication through the corpus callosum following mild traumatic brain injury. Here we use a mediation framework to investigate how callosal interhemispheric communication is affected by WM microstructure in mild traumatic brain injury. MATERIALS AND METHODS/METHODS:Multishell diffusion MR imaging was performed on 23 patients with mild traumatic brain injury within 1 month of injury and 17 healthy controls, deriving 11 diffusion metrics, including DTI, diffusional kurtosis imaging, and compartment-specific standard model parameters. Interhemispheric processing speed was assessed using the interhemispheric speed of processing task (IHSPT) by measuring the latency between word presentation to the 2 hemivisual fields and oral word articulation. Mediation analysis was performed to assess the indirect effect of neighboring WM microstructures on the relationship between the corpus callosum and IHSPT performance. In addition, we conducted a univariate correlation analysis to investigate the direct association between callosal microstructures and IHSPT performance as well as a multivariate regression analysis to jointly evaluate both callosal and neighboring WM microstructures in association with IHSPT scores for each group. RESULTS:Several significant mediators in the relationships between callosal microstructure and IHSPT performance were found in healthy controls. However, patients with mild traumatic brain injury appeared to lose such normal associations when microstructural changes occurred compared with healthy controls. CONCLUSIONS:This study investigates the effects of neighboring WM microstructure on callosal interhemispheric communication in healthy controls and patients with mild traumatic brain injury, highlighting that neighboring noncallosal WM microstructures are involved in callosal interhemispheric communication and information transfer. Further longitudinal studies may provide insight into the temporal dynamics of interhemispheric recovery following mild traumatic brain injury.
PMID: 38637026
ISSN: 1936-959x
CID: 5650822
Retention of Antibiotic Cement Delivery Implants in Orthopedic Infection Associated With United Fractures Does Not Increase Recurrence Risk
OBJECTIVES/OBJECTIVE:To evaluate whether retention of antibiotic cement delivery devices after resolution of orthopaedic infection is associated with recurrence. DESIGN/UNASSIGNED:Retrospective cohort. SETTING/UNASSIGNED:Academic medical center. PATIENT SELECTION CRITERIA/UNASSIGNED:Patients with a fracture definitively treated with internal fixation that went on to unite and develop a confirmed fracture-related infection or osteomyelitis after a remote fracture surgery and had implantation of antibiotic-impregnated cement for infection management. OUTCOME MEASURES AND COMPARISONS/UNASSIGNED:Patients were divided into whom the antibiotic implants were retained (Retained Cohort) and whom the antibiotic implants were removed (Removed Cohort). Outcome measures included clinical infection resolution, infection recurrence, time to resolution of infection signs, symptoms and laboratory values, reoperation and readmission rates, and need for soft tissue coverage (local flap vs. free tissue transfer) because of recurrence. RESULTS:Of 98 patients treated for fracture-related infection in united fractures or osteomyelitis after a remote fracture surgery, 39 (39.8%) underwent implantation of antibiotic-impregnated cement delivery devices: 21 (21.4%) beads, 7 (7.1%) rods, and 11 (11.2%) blocks. Twenty patients (51.3%) comprised the Retained Cohort and 19 patients (48.7%) comprised the Removed Cohort. There were few differences in demographics ([American Society of Anesthesiology Score, P = 0.026] and [diabetes, P = 0.047]), infection location, and pathogenic profiles. The cohorts demonstrated no difference in eventual resolution of infection (100% in the Retained Cohort, 95% in the Removed Cohort, P = 0.487) and experienced similar time to clinical infection resolution, based on signs, symptoms, and laboratory values ( P = 0.360). There was no difference in incidence of subsequent infection recurrence after clinical infection resolution (1 recurrence Retained vs. 2 recurrences Removed, P = 0.605) for those considered "cured." Compared with the Retained Cohort, the Removed Cohort underwent more reoperations (0.40 vs. 1.84 reoperations, P < 0.001) and admissions after implantation ( P < 0.001). CONCLUSIONS:Retention of antibiotic-impregnated cement delivery devices in patients with orthopaedic infection after fractured bones that have healed was not associated with infection recurrence. Additional surgical intervention with the sole purpose of removing antibiotic delivery devices may not be warranted. LEVEL OF EVIDENCE/METHODS:Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
PMID: 38206770
ISSN: 1531-2291
CID: 5639712
Zone 2 Fifth Metatarsal Fractures Treated Nonoperatively Have Similar Time to Healing to Those Treated Operatively
OBJECTIVES/OBJECTIVE:To quantify the rate of union and time to clinical and radiographic healing in Zone 2 proximal fifth metatarsal (MT) fractures and compare these outcomes between Zone 2 fractures treated operatively and nonoperatively. DESIGN/UNASSIGNED:Retrospective cohort study. SETTING/UNASSIGNED:Academic Level I Trauma Center. PATIENT SELECTION CRITERIA/UNASSIGNED:Patients with fifth MT fractures who presented between December 2012 and April 2022 and confirmed to have Zone 2 fractures (defined as fractures entering the proximal 4-5 MT articulation on the oblique radiographic view) were included in the study analysis in either the operative or nonoperative cohort. OUTCOME MEASURES AND COMPARISONS/UNASSIGNED:Nonunion, time to clinical healing by, and time to radiographic healing between operative and nonoperative treatment. RESULTS:Among the 499 included patients, 475 patients (95.2%) were initially treated nonoperatively and 24 patients (4.8%) were treated operatively. Both groups were similar in demographics. There was no difference in the proportion of patients with nonunions between groups (6.1% in the nonoperative group vs. 3.8% in the operative group, P = 1.000). In addition, there was no statistically significant difference between groups with respect to the time to clinical healing (9.9 ± 8.3 weeks for the nonoperative group vs. 15.4 ± 15.0 weeks for the operative group, P = 0.117) or the time to radiographic healing (18.7 ± 12 weeks for the nonoperative group vs. 18.5 ± 16.6 weeks for the operative group, P = 0.970). CONCLUSIONS:Zone 2 fifth MT base fractures were successfully treated with nonoperative management. There was no evidence in this study that operative treatment leads to significantly faster clinical or radiographic healing. LEVEL OF EVIDENCE/METHODS:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
PMID: 38206754
ISSN: 1531-2291
CID: 5639702
Approach to High-Risk Multiple Myeloma
Improving the outcome of high-risk myeloma (HRMM) is a key therapeutic aim for the next decade. To achieve this aim, it is necessary to understand in detail the genetic drivers underlying this clinical behavior and to target its biology therapeutically. Advances have already been made, with a focus on consensus guidance and the application of novel immunotherapeutic approaches. Cases of HRMM are likely to have impaired prognosis even with novel strategies. However, if disease eradication and minimal disease states are achieved, then cure may be possible.
PMID: 38195306
ISSN: 1558-1977
CID: 5628622
No difference in clinical and hospital quality outcomes in treatment of reverse obliquity intertrochanteric Hip fractures (AO/OTA 31.A3) based on Cephalomedullary nail length
INTRODUCTION/BACKGROUND:The purpose of this study was to evaluate outcomes following reverse obliquity (RO) intertrochanteric hip fractures based on the use of short cephalomedullary nails (CMNs) compared to long CMNs for fixation. METHODS:An IRB-approved prospectively collected hip fracture registry at an urban academic medical center was queried for all AO/OTA 31A3.1-3 reverse obliquity intertrochanteric (RO) fractures. One hundred and seventy patients with age > 55 years old and minimum 6-month follow-up were identified for analysis. Data was collected for patient demographics, injury details, intraoperative radiographic parameters, perioperative physiologic parameters, hospital quality measures, and outcomes including radiographic time to healing, need for reoperation, nonunion, and mortality. Comparative analyses were conducted between cohorts. Additional multivariable binary logistic and linear regression analyses were performed to evaluate for factors independently associated with short and long nail usage. RESULTS:The mean age of the entire cohort was 80.91±10.09 years: 103 patients had a long CMN implanted, and 67 patients had a short CMN implanted. There were no demographic differences or differences in radiographic time to healing, rates of mortality, readmission, nonunion, and need for reoperation. Univariable analysis revealed that short CMN had lower intraoperative blood loss (111.19±83.97 mL vs 176.72±161.45 mL, p = 0.002), decreased need for transfusion (37% vs. 55 %, p = 0.022), and shorter procedures (118.67±57.87 min vs. 148.95±77.83 min, p = 0.002. Multivariable analysis revealed that short nail usage was associated with decreased intraoperative blood loss, decreased need for transfusion, and shorter operative times. CONCLUSION/CONCLUSIONS:Nail length does not affect healing or hospital quality outcomes in the treatment of RO hip fractures. The use of short CMNs for these fractures did correlate with lower intraoperative blood loss, operative time, and need for blood transfusion, with non-inferior outcomes and similar hospital quality measures when compared to long CMNs.
PMID: 38447479
ISSN: 1879-0267
CID: 5639792
Serum Metabolomic Markers of Protein-Rich Foods and Incident CKD: Results From the Atherosclerosis Risk in Communities Study
RATIONALE & OBJECTIVE/UNASSIGNED:While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD). STUDY DESIGN/UNASSIGNED:Prospective cohort study. SETTING & PARTICIPANTS/UNASSIGNED:A total of 3,726 participants from the Atherosclerosis Risk in Communities study without CKD at baseline. EXPOSURES/UNASSIGNED:Dietary intake of 6 protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, and poultry), serum metabolites. OUTCOMES/UNASSIGNED:with ≥25% estimated glomerular filtration rate decline relative to visit 1, hospitalization or death related to CKD, or end-stage kidney disease). ANALYTICAL APPROACH/UNASSIGNED:Multivariable linear regression models estimated cross-sectional associations between protein-rich foods and serum metabolites. C statistics assessed the ability of the metabolites to improve the discrimination of highest versus lower 3 quartiles of intake of protein-rich foods beyond covariates (demographics, clinical factors, health behaviors, and the intake of nonprotein food groups). Cox regression models identified prospective associations between protein-related metabolites and incident CKD. RESULTS/UNASSIGNED:). LIMITATIONS/UNASSIGNED:Residual confounding and sample-storage duration. CONCLUSIONS/UNASSIGNED:We identified candidate biomarkers of fish, nuts, red and processed meat, eggs, and poultry. A fish-related metabolite, 1-docosahexaenoylglycerophosphocholine (22:6n3), was associated with a lower risk of CKD.
PMCID:10940775
PMID: 38495599
ISSN: 2590-0595
CID: 5640042
Alignment of brain embeddings and artificial contextual embeddings in natural language points to common geometric patterns
Contextual embeddings, derived from deep language models (DLMs), provide a continuous vectorial representation of language. This embedding space differs fundamentally from the symbolic representations posited by traditional psycholinguistics. We hypothesize that language areas in the human brain, similar to DLMs, rely on a continuous embedding space to represent language. To test this hypothesis, we densely record the neural activity patterns in the inferior frontal gyrus (IFG) of three participants using dense intracranial arrays while they listened to a 30-minute podcast. From these fine-grained spatiotemporal neural recordings, we derive a continuous vectorial representation for each word (i.e., a brain embedding) in each patient. Using stringent zero-shot mapping we demonstrate that brain embeddings in the IFG and the DLM contextual embedding space have common geometric patterns. The common geometric patterns allow us to predict the brain embedding in IFG of a given left-out word based solely on its geometrical relationship to other non-overlapping words in the podcast. Furthermore, we show that contextual embeddings capture the geometry of IFG embeddings better than static word embeddings. The continuous brain embedding space exposes a vector-based neural code for natural language processing in the human brain.
PMCID:10980748
PMID: 38553456
ISSN: 2041-1723
CID: 5645352
Clinical and Radiographic Healing of Nonoperative and Operative Treatment of Jones Fractures
BACKGROUND/UNASSIGNED:Significant heterogeneity in the classification and treatment of zone 3 proximal fifth metatarsal base fractures ("true Jones fractures") exists. This study compared time to clinical and radiographic healing between patients treated operatively and nonoperatively. We hypothesized that patients treated nonoperatively may demonstrate a greater time to clinical healing. METHODS/UNASSIGNED:This was a retrospective cohort study of patients presenting to a large, urban, academic medical center with "Jones" fractures between December 2012 and April 2022. Jones fractures were defined as fifth metatarsal base fractures occurring in the proximal metadiaphyseal region, distal to the articulation of the fourth and fifth metatarsals on the oblique radiographic view. Clinical healing was the time point at which the patient had returned to their baseline ambulatory status with no tenderness to palpation. Radiographic healing was the presence of bridging callus across at least 3 cortices. RESULTS/UNASSIGNED: = .331). Overall healing rate was 96% for the nonoperative group compared with 96.2% for the operative group. CONCLUSION/UNASSIGNED:In this study, nonoperative and operative treatment of true Jones fractures were associated with equivalent clinical and radiographic healing. The rate of delayed union in true Jones fractures was lower than previously described, and there was no difference in delayed union rate between nonoperative and operative management. LEVEL OF EVIDENCE/UNASSIGNED:Level III, retrospective cohort study.
PMID: 38546126
ISSN: 1944-7876
CID: 5645092
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2024.DOI: 10.1093/cid/ciae173
A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered with and without AS03 Adjuvant in Healthy US Adults
INTRODUCTION/BACKGROUND:A surge of human influenza A(H7N9) cases began in 2016 in China due to an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. METHODS:Healthy adults (n=180), ages 19-50 years, were enrolled into this partially-blinded, randomized, multi-center Phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with two different boost intervals (21 versus 120 days) and two dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition (HAI) and neutralizing antibody titers were assessed. RESULTS:Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest HAI GMT (95%CI) observed against the 2017 A(H7N9) strain was 133.4 (83.6, 212.6) among participants who received homologous, adjuvanted 3.75 ug+AS03/2017 doses with delayed boost interval. CONCLUSIONS:Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. (NCT03589807).
PMID: 38537255
ISSN: 1537-6591
CID: 5644952
Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists. 2024.DOI: 10.1177/15266028241231745
The "Woundosome" Concept and Its Impact on Procedural Outcomes in Patients With Chronic Limb-Threatening Ischemia [Editorial]
PMID: 38523459
ISSN: 1545-1550
CID: 5645462
