Citations

ABSTRACT HLA‐B*15:591 is characterised by a single nucleotide substitution in codon 219 in exon 4.

ABSTRACT The HLA‐DQA1*01:169 allele is characterised by a single nucleotide substitution in codon 175 in exon 3.

Background: Facial nerve injury can result in a spectrum of clinical presentations from complete facial paralysis (CFP) to facial synkinesis. Willingness to pay (WTP) and quality-adjusted life years are established metrics used to assess the societal value of treatments. Objective: To quantify the perceived value of surgery for CFP and synkinesis amongst casual observers, as measured by WTP and quality of life indices. Methods: Casual observers were shown standardized videos of faces with complete paralysis, synkinesis, and nonparalyzed controls (eight videos each). Observers were asked to imagine having each condition and to rate their quality of life and WTP for surgical repair. Results: A total of 557 observers were included (mean age 36.5 years, 59% female). Both complete paralysis and synkinesis were associated with reduced quality-adjusted life year indices (0.9 [95% confidence interval [CI] 0.87–0.93]) for synkinesis; 0.86 (95% CI: 0.83–0.89) for complete paralysis, p = 0.0011). The mean WTP was $22,791 for complete flaccid paralysis and $15,718 for synkinesis repair and increased with income. WTP per quality-adjusted-life year gained was $6,844 for complete paralysis and $6,604 for synkinesis ( p > 0.05). Conclusion: Observers perceived surgical repair of CFP and synkinesis as highly valuable and within common cost-effectiveness thresholds.

AIMS: Evidence-based medicine (EBM) is a necessary attribute required for quality medical practice. Despite being integral in advancing medicine and improving patient outcomes, research and quality improvement (QI) rarely integrate into medical education. We present our curricular course design and reveal students' perceptions of the implementation of this course. In addition, we compared physician assistant (PA) student perceptions from the first two traditional cohorts (4 years undergraduate before entry to PA program) to the accelerated 3+2 pathway cohorts (3 years pre-PA coursework followed by 2 years PA program). METHODS: Faculty developed an EBM course taught through student participation in QI projects and assessed students' perceptions of discovery, collaboration, cognitive ownership, and global sense toward general outcomes through the implementation and analysis of validated survey instruments. RESULTS: All students contributed to QI projects, achieved Quality Academy Bronze certification and Silver assessment and disseminated their work at peer-reviewed conferences. Over 56.4% earned Silver certification, and 36.2% of students had their project published in a journal. Student perception of experiential impact was positive overall, with 83.3% of students minimally responding 'true' to the prompts. All students indicated that after the experience, they possessed a basic understanding of QI approaches. The accelerated students selected 'true' for all other prompts more frequently than the traditional student population. DISCUSSION: This manuscript presents vital educational strategies, highlighting an approach and plan to extrapolate EBM principles beyond PA students and to generalize to other healthcare professionals and students. Through course completion, students met educational objectives and reaped additional benefits that positively impacted their resume building and future job prospects. By honing these skills, students are better prepared to contribute to patient care and advance the field of medicine. The accelerated students perceived greater course benefit likely due to the life-experience differences between the two cohorts, whereby the traditional students matriculated into the program with a breadth of prior knowledge obtained through years of contributions to education and careers.

BACKGROUND: Although the prognostic utility of positron emission tomography (PET) myocardial flow reserve (MFR) is well established, emerging data suggest that reduced subendocardial flows also predict adverse outcomes. However, the incremental value of subendocardial MFR (MFR SE ) beyond transmural MFR (MFR TM ) remains unclear. METHODS: We studied patients in a multicenter PET registry with normal perfusion on stress/rest Rb-82 PET, excluding those with a previous history of coronary artery bypass surgery, heart transplantation, or left ventricular ejection fraction <40%. The optimal MFR SE cutoff for predicting major adverse cardiovascular events (MACEs; death, myocardial infarction [MI], revascularization, or heart failure [HF] hospitalization) was determined using Youden’s index. Patients were stratified into 3 groups: concordant-normal (MFR TM ≥2.0; MFR SE ≥2.1), discordant (low-MFR SE , normal MFR TM ), and abnormal MFR TM . Clinical outcomes were compared by MFR groups. RESULTS: Among 6603 patients (normal N=4103; discordant N=885; abnormal N=1615) the mean age was 66.3±12.4 years, and 54% were women. Compared with the concordant-normal group, patients with discordant low-MFR SE were older and more likely to have hypertension, diabetes, peripheral artery disease, and previous percutaneous coronary intervention. The median MFR TM for normal, discordant, and abnormal groups were 2.86, 2.15, and 1.72, respectively. Over a median follow-up of 4.9 years, 1661 MACE events occurred. Discordant low-MFR SE patients had a higher risk of MACE (hazard ratio [HR], 1.41; 95% CI, 1.22–1.64) and all-cause mortality (HR, 1.36; 95% CI, 1.14–1.61) compared with concordant-normal patients. The discordant group had an intermediate absolute risk of MACE, with an adjusted annualized event rate of 5.79% (95% CI, 5.10–6.49) compared with 3.99% (95% CI, 3.67–4.30; P <0.001) in the concordant-normal group and 8.35% (95% CI, 7.71–9.00; P <0.001) in the abnormal MFR TM group. CONCLUSIONS: Subendocardial MFR reveals clinically meaningful risk heterogeneity among patients with preserved transmural flow reserve, helping refine risk stratification beyond traditional PET metrics.

ABSTRACT Introduction/Aims Patients with cervical spinal cord injury (SCI) prioritize recovery of upper extremity function. Upper extremity reconstruction can restore function in carefully selected individuals. Infralesional cord damage, observed below the neurological level of injury (NLI), may affect postoperative outcomes. We characterized the extent of infralesional lower motor neuron (LMN) injury in patients with traumatic cervical SCI. Methods Each patient underwent electromyography (EMG) of potential donor and recipient muscles based on preoperative clinical evaluation and specific candidacy for nerve and/or tendon transfers. The presence of infralesional pathologic insertional activity (IA), reduced motor unit potential (MUP) recruitment and/or neurogenic MUPs was assessed. The caudal‐most segment with infralesional LMN injury was determined. Inclusion criteria were patients with (1) traumatic cervical SCI; (2) injury ≥ 3 months duration; (3) preoperative planning EMG for nerve and/or tendon transfers. Results Forty‐eight upper extremity EMGs in 25 patients (68% male; mean age 39.5 years at injury) with traumatic cervical SCI were included. The NLI was at C7 or above in each patient, and 64% of SCIs were motor complete. Infralesional EMG abnormalities (median time from injury to EMG 466 days) were found a median of 3.0 (IQR 3.0–4.0) segments below the NLI. Three patients with an NLI as rostral as C1–C2 exhibited LMN injury seven segments below the NLI. Discussion In persons with traumatic cervical SCI, evidence of LMN injury may be observed several segments below the NLI. Defining the true extent of LMN involvement directly informs timing and selection of reconstructive procedures to maximize functional recovery.

Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P &lt; 0.00001) and an earlier age of first exposure to tackle football (P &lt; 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P &lt; 0.04) and rotational force (P &lt; 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

TPS11598 Background: Fibroblast Activation Protein (FAP) is expressed on the surface of cancer-associated fibroblasts and is involved in the formation, maintenance, and spread of tumors. Sarcoma frequently demonstrates high expression of FAP on the tumor cells themselves in contrast to other solid tumors, where it is mainly expressed on CAFs within the tumor stroma. Radioligand therapies utilizing alpha emitting isotopes such as Ac-225 have emerged as promising treatment strategies across multiple targets and indications in oncology. Ac-225 and its daughter radionuclides emit high-energy alpha particles capable of inducing double-stranded DNA breaks, leading to significant cytotoxic effects within cells. Early clinical data for other Ac-225-labeled compounds have shown promising outcomes, particularly in settings where traditional therapies have failed. [Ac-225] RTX-2358 (Ratio Therapeutics Inc, Boston, MA) is a novel FAP-targeted radioligand designed for specific high-affinity binding, resulting in prolonged tumor residence and limited normal tissue uptake. This sustained tumor retention leads to extended delivery of cytotoxic radiation to FAP-expressing tumors. A beta-emitting analog, [Lu-177]RTX-2358, has been administered to more than 25 patients under the German §13.2b compassionate use framework across multiple tumor types. Longitudinal SPECT imaging performed as late as 14 days after administration demonstrated persistent tumor retention with minimal washout. Based on time–activity curve analysis from these data, tumor biological half-time is estimated to be well in excess of 1,000 hours. Renal clearance was observed to be consistent with that reported for established lutetium-177–labeled radioligand therapies. Methods: This study is a seamless Phase 1 / 2 dose escalation study. The Phase 1 portion consists of a 3 x 3 dose escalation design, with patients treated in 3 planned dose escalation cohorts (7.5, 11.25 and 15 MBq) with up to 6, 8-week cycles of [Ac-225]RTX-2358. Backfill of phase 1 cohorts is permitted to facilitate selection of the recommended administered activity level for the subsequent Phase 2 expansion cohort. Dose escalation / de-escalation decisions will be made by a Safety Review Committee. Patients over 18yrs with a history of histologically confirmed relapsed or refractory soft tissue sarcoma (measurable disease per RECIST v1.1) are eligible if they have a positive [Cu-64]LNTH-1363S FAP PET, an ECOG PS 0 to 1, and adequate organ reserve and renal function. Recruitment of the first cohort was completed in December 2025. The ATLAS Study: NCT07156565 Clinical trial information: NCT07156565 .