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Thoracolumbar Fractures: Historical Systems and Advancements With the AO Spine Classification
No full textStudy Design: Systematic Review. Objective: To describe the historical classifications of thoracolumbar injuries and their evolution into the AO Spine Thoracolumbar Injury Classification System. Methods: A systematic review of MEDLINE, EMBASE and Cochrane Databases was performed in keeping with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Results: 445 articles were crystallized to 14 included studies. Simple categorization systems offered by Bohler or Watson-Jones merely identify fracture morphology. Holdsworth and Denis conveyed a sense of the stability of injuries by noting columns of stability, but still failed to take into consideration important factors such as neurological status or specific integrity of key stabilizing structures. The AO Spine Thoracolumbar Injury Classification System provides 3 hierarchical categories: type A consisting of compression type injuries, type B composed of distraction injuries and the unstable type C comprising displacement injuries. This communicates the severity of the fracture to clinicians and, with the addition of modifiers, can be synthesised into a scoring system to guide management. This classification is based upon biomechanical stability and increasing likelihood of clinicians offering operative rather than non-operative intervention as fracture severity escalates. Conclusions: A combination of evaluating fracture morphology, integrity of the posterior ligamentous complex and neurological status of the patient in the context of individual patient modifiers is integral to guide surgical decision making. The AO Thoracolumbar Injury Classification System accounts for all of the aforementioned and is the derivative and advancement on existing historical systems. Further nuanced development of scoring systems to guide operative or non-operative management is still required
Obesity Does Not Significantly Impact Clinical Outcomes Following Anterior Cervical Discectomy and Fusion
No full textBACKGROUND: With obesity rates rising among patients undergoing anterior cervical discectomy and fusion (ACDF) and more procedures shifting to outpatient settings, this study aimed to evaluate the impact of body mass index (BMI) on complications, sagittal alignment, and patient-reported outcomes (PROs).
METHODS: A prospectively maintained database of 302 patients who underwent ACDF for myelopathy or radiculopathy between 2020 and 2022 at a single academic center was analyzed. Patients were stratified into four BMI categories: normal (18.5-\u3c 25), overweight (25-\u3c 30), obese class I (30-\u3c 35), and obese class II/III (≥35). Collected data included demographics, comorbidities, perioperative variables, radiographic measures (cSVA, Cobb angle, etc.), and PROs (VAS, NDI). Univariate regression compared demographics, alignment, and PROs, while multivariate analyses assessed complications and perioperative factors.
RESULTS: BMI was not independently associated with higher rates of postoperative complications, including adjacent segment disease, subsidence, reoperation, or other adverse events. Patients in the obese class II/III group had a modestly longer hospital stay (1.35 vs. 0.97 days, p = 0.030), likely reflecting greater baseline comorbidity burden. Cervical sagittal alignment parameters were comparable across BMI groups, and patient-reported outcomes, including pain and disability, showed no significant differences at any postoperative time point.
CONCLUSION: Elevated BMI does not appear to adversely affect surgical outcomes, complication rates, radiographic alignment, or patient-reported outcomes following ACDF. These findings suggest that high BMI should not be viewed as a contraindication to ACDF and that surgical decisions should prioritize overall clinical status rather than weight alone
Resident Mental Health: Creating an Innovative, Sustainable, and Scalable Counseling Program
No full textBackground The ACGME Common Program Requirements emphasize resident well-being and expect GME programs to support resident mental health.1 There are limited specific guidelines on how mental health support should be delivered, resulting in wide variability.1,3 Research on resident-specific mental health services is limited, making best practices difficult to define. Medical students typically receive care through student counseling centers; but this support ends after graduation.3 Residents occupy a dual role as both hospital employees and learners, creating gaps in existing support models, as employee assistance programs are often underutilized by residents. Residents experience higher rates of burnout than age-matched peers in the general population.4 Suicide is the leading cause of resident death; nearly one-third of interns experience a depressive episode.2,5 Stigma and barriers such as time constraints, cost, and waitlists limit help-seeking.4 Early identification and treatment of mental health conditions improve outcomes.4 Residency-specific demands—including long work hours, limited autonomy to take time off, mandatory educational activities, and limited backup—require solutions beyond traditional mental health care.https://jdc.jefferson.edu/phbposters/1007/thumbnail.jp
A General Strategy to Improve the Safety and Efficacy of GPCR-Targeted Drugs
No full textPurpose: G protein-coupled receptors (GPCRs) are integral membrane proteins that constitute the largest family of drug targets. They respond to hormones or drugs and activate downstream signaling pathways via G proteins and β-arrestins, eliciting therapeutic benefits and side effects. For example, β2-adrenergic receptor (β2AR) agonists relax airways in asthma through G protein activation, but cause tolerance, tachyphylaxis, reduced duration of action, and inflammation through activation of β-arrestin signaling. Developing general strategies to bias signaling toward therapeutically relevant pathways could make GPCR-targeted drugs safer and more effective. This project investigates the generality of signaling bias by introducing mutations into the β1-adrenergic receptor (β1AR) that confer sensitivity to the β2AR-selective \u27molecular glue\u27 difluorophenylquinazoline (DFPQ), which inhibits harmful β-arrestin signaling without affecting beneficial G protein activation.
Methods: Chimeric β1AR variants were created with a β2AR-derived mutation (L154V) in transmembrane helix 3 (TM3), a TM4 segment from β2AR, or both, and expressed in HEK293 cells. DFPQ inhibition of isoproterenol-induced β-arrestin-2 recruitment was measured using bioluminescence resonance energy transfer (BRET).
Results: Wild-type β1AR exhibited minimal response to DFPQ. The L154V mutant and TM4 chimera each conferred moderate DFPQ sensitivity, partially inhibiting β-arrestin recruitment. The combination variant greatly enhanced this effect, revealing additive contributions of TM3 and TM4 residues in forming the drug-binding site.
Conclusions: These results demonstrate that TM3/TM4 residues create a transferable allosteric pocket, enabling engineered bias toward G protein signaling in β1AR. Future efforts will assess additional TM3/TM4 variants and design β1AR-selective allosteric drugs that achieve improved cardiovascular outcomes through GPCR signaling bias
Use of Electrocardiograms to Identify Coronary Artery Disease: Cross-Validation of an Artificial Intelligence Model
No full textBACKGROUND: The current gold standard for the diagnosis of coronary artery disease (CAD) is invasive angiography; however, it is an invasive procedure. Therefore, we developed an artificial intelligence model designed to predict significant CAD from a resting digital 12-lead electrocardiogram (ECG).
OBJECTIVES: This retrospective study assessed the model\u27s ability to predict clinically significant CAD in a patient population presenting for coronary angiography.
METHODS: From 2019 to 2021, 16,476 patients had a resting 12-lead digital ECG recorded within 90 days prior to coronary angiography. The artificial intelligence model was developed using 10-fold cross-validation methodology. Clinically significant disease was defined as angiographic diameter stenosis ≥70% in the left anterior descending, left circumflex, or right coronary artery or ≥50% in the left main coronary artery. We then applied the model to an external validation set.
RESULTS: In the cross-validation cohort, the prevalence of clinically significant CAD was 64.5%; the model achieved a positive predictive value of 91.7% (95% CI: 89.9%-93.4%), negative predictive value of 72.8% (95% CI: 69.6%-76.0%), and area under the curve of 91.4% (95% CI: 89.4%-94.4%) in predicting clinically significant CAD. In external validation, the prevalence of clinically significant CAD was 36.0%; the model achieved a positive predictive value of 82.5% (95% CI: 75.9%-89.2%), negative predictive value of 88.1% (95% CI: 84.0%-92.1%), and area under the curve of 92.4% (95% CI: 89.7%-95.1%) in predicting clinically significant CAD.
CONCLUSIONS: This study demonstrated the clinical utility of a deep learning artificial intelligence algorithm to analyze a digital 12-lead ECG to predict the presence of clinically significant CAD as determined by coronary angiography
Perioperative Fluid Management in Pancreaticoduodenectomy in the Era of Goal-Directed Fluid Therapy: A Review of the Literature
No full textBACKGROUND: Pancreaticoduodenectomy (PD) is the only curative option for localized pancreatic head and periampullary malignancies. However, PD is associated with significant perioperative morbidity. Perioperative fluid management has emerged as an important modifiable factor influencing surgical outcomes in PD.
METHODS: In this qualitative review, PubMed/Medline searches were performed between March and August 2025 to review the terms pancreaticoduodenectomy, fluid management, Enhanced Recovery After Surgery, complications, and related terms.
RESULTS: Historically, liberal fluid administration was favored to compensate for third-space losses, but contemporary evidence has linked excessive fluid volumes to complications, such as postoperative pancreatic fistula, anastomotic edema, and increased inflammatory responses. Recent studies, including those utilizing Enhanced Recovery After Surgery (ERAS) protocols, indicate the possible benefit of more restrictive fluid regimens, finding that restrictive fluids are associated with reduced overall complications, lower cardiopulmonary morbidity, and shorter post-operative hospital stays, amongst others. However, overly restrictive strategies may risk hypoperfusion, driving the necessity for a delicate balance between restrictive fluid administration and physiologic demand.
CONCLUSIONS: Goal-directed fluid therapy protocols offer a promising approach to PD fluid management by individualizing fluid delivery, minimizing complications, and improving perfusion metrics, resulting in a more effective restrictive fluid approach. Despite these advancements, heterogeneity in study designs, fluid management definitions, and monitoring tools limits a clear consensus. Future research should prioritize multicenter randomized controlled trials, standardized protocols, and long-term outcome assessments to refine evidence-based, patient-centered fluid management strategies in PD
Intralabyrinthine MRI FLAIR as a Predictive Marker for Hearing Loss in Vestibular Schwannomas in Neurofibromatosis Type 2
No full textBACKGROUND AND OBJECTIVES: The onset of hearing loss due to vestibular schwannomas (VS) is inevitable but does not correlate with the size of the tumor. In patients with Neurofibromatosis Type 2 (NF2) and VS, we previously found an association between pre-contrast fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) signal in the labyrinth and hearing loss. Here, we asked whether FLAIR hyper-intensity could serve as a predictive biomarker for hearing loss in NF2 patients with VS.
METHODS: A prospective longitudinal study (NCT00598351) of NF2 enrolled 168 subjects between 2008 and 2013. This study included 34 patients with small VS (total volume ≤ 500mm
RESULTS: From 34 eligible subjects (mean age 26.8y) with NF2 and small VS, 53 ears met inclusion criteria. Abnormal hearing was recorded in 18 ears at study entry; all 18 ears had FLAIR hyper-intensity. Of the 35 ears with normal hearing, 16 had FLAIR hyper-intensity at study entry, 6 (37.5%) of which developed new hearing loss (median time to hearing loss of 4.45 years). Conversion to FLAIR hyper-intensity occurred in 11 ears, 3 of which proceeded to hearing loss. No hearing loss developed in the eight ears that remained FLAIR negative. FLAIR conversion has high sensitivity (1·00, 95% CI 0·39–1) and negative predictive value (1·00, 95% CI 0·63–1) for new-onset hearing loss. In 4 patients undergoing middle fossa decompression surgery, we found that surgery stabilized hearing but did not reverse FLAIR hyperintensity.
CONCLUSIONS: Our findings suggest that intralabyrinthine FLAIR hyper-intensity is a sensitive, non-invasive biomarker for hearing loss related to VS. Hearing decline followed FLAIR hyper-intensity by approximately 4 years but was absent in ears with normal FLAIR signal.
TRIAL REGISTRATION: Registry: ClinicalTrials.gov, TRN: NCT00060541, Registration date: 4 June 2003.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-026-05422-9