Citations

Abstract Purpose: Adolescents with chronic orthostatic intolerance (COI) experience symptoms related to impaired tolerance of upright posture. Postural Orthostatic Tachycardia Syndrome (POTS) is a specific type of COI, marked by an excessive increase in heart rate (≥40 bpm or an absolute HR >120 bpm) when standing. This study compares Functional Disability Inventory (FDI) scores between adolescents with COI with and without excessive postural tachycardia (POTS subtype). Methods: Patients ≤19 years referred to our POTS program (Aug 2024–Mar 2025) with orthostatic symptoms for>3 months were included. Based on active stand HR, patients were categorized as POTS (HR ≥40 bpm) or COI without excessive postural tachycardia (HR <40 bpm). FDI scores were collected. Chi-square tests assessed group differences. A two-sample t-test compared FDI severity. Linear regression evaluated the association between HR change and FDI score. Results: All data were normally distributed, allowing the use of parametric analyses. Of the 92 patients (46 per group), 78% were female. The mean age was 16.0 ± 1.48 years in the COI group and 16.3 ± 1.7 years in the POTS group, with no significant sex differences between groups. The COI group had a higher mean FDI score than the POTS group, but this difference was not statistically significant. The distribution of FDI severity (mild, moderate, severe) was similar between groups. Linear regression showed a non-significant trend of a 1 bpm increase in heart rate associated with a 0.1055-point decrease in FDI score Conclusion: Functional disability was similar between the COI and POTS groups.

The liver stores substantial numbers of neutral lipid organelles termed lipid droplets (LDs) that accumulate within hepatocytes in response to chronic ethanol (EtOH) consumption leading to hepatic steatosis. Mass spectrometry analysis of LDs isolated from EtOH-damaged rat livers revealed a substantial reduction in the valosin-containing protein ATPase (VCP/p97) that acts to remove targeted proteins from cellular membranes for degradation. Experimental disruption of VCP function resulted in an increase in LD content in hepatocytes and mouse livers along with a marked increase in LD-associated hydroxysteroid dehydrogenase (HSD17β13) known to contribute to hepatic steatosis. Surprisingly, treatment of hepatocytes with the proteasome inhibitor MG132 had no effect on HSD17β13 levels, while a disruption of lysosome function and chaperone-mediated autophagy increased cellular HSD17β13 levels substantially. These findings provide new insights into the cellular mechanisms by which the liver regulates its lipid stores and how this is disrupted by chronic EtOH exposure.

e18031 Background: HPV+ OPSCC has better outcomes than HPV negative OPSCC but more distant metastatic potential. ICM in HPV+ OPSCC are rare. Data regarding risk factors, clinical presentation and outcomes after ICM diagnosis is limited. This study describes clinical characteristics and outcomes of patients (pts) with HPV+ OPSCC who develop ICM. Methods: Retrospective analysis of pts with HPV+ OPSCC and ICM between 2010 - 2024. Demographic, clinicopathologic, and survival data was collected. Skull base recurrences were excluded. Univariate and multivariate analyses used Cox proportional hazard models; continuous variables binarized by receiver operator curves. Survival assessed via Kaplan-Meier method; reported as median (95% CI). Calculations use BlueSky (v10.3.1). Results: Among 1,999 pts with HPV+ OPSCC, 16 (0.8%) had ICM. Pt characteristics and treatment are summarized in Table 1. Primary tumor sites were base of tongue (56%), tonsil (38%), and unknown (13%). Most pts (n=8, 50%) presented with stage IV disease (6 extracranial metastasis (ECM), 1 ICM only, 1 both). Frontal and parietal lobes were the most frequent ICM sites. Neurological symptoms were present in 10 (62%) pts; ICM was incidentally found in 6 (38%) pts. Median overall survival (mOS) from initial diagnosis was 34 months (21 – not reached) and median time from diagnosis to ICM was 24 months (range 1-112). mOS following ICM detection was 10.9 months (4 -18). On multivariate analysis, only surgical resection (hazard ratio [HR] 0.03, p<0.01) and radiotherapy (HR 0.01, p<0.02) were independently associated with post-ICM survival. With median follow up of 100 months, 14 pts (88%) had died; 2 (12%) were alive. Conclusions: ICM from HPV+ OPSCC are rare but devastating with a mOS <1 year from detection. Most pts were symptomatic, had de novo metastatic disease, and had other sites of metastases. Surgical resection and radiation were associated with improved OS. Multicenter efforts to investigate predictors, multiomic sequencing and identification of pt subsets who may benefit from ICM screening are warranted. Baseline characteristics of Pts with ICM in HPV+ OPSCC. Variable Summary statistics (n=16) Median age (range) 58 (34-71) Male 14 (88%) Smoking history 10 (60%) Clinical stage at diagnosis Stage I: 4 (25%) Stage II: 2 (12.5%) Stage III: 2 (12.5%) Stage IV: 8 (50%) Symptoms at ICM diagnosis Incidental: 6 (38%)Neurological: 10 (62%) Seizure (n=3) Motor/Sensory symptoms (n=3) Altered mental status (n=2) Cognitive symptoms (n=1) Dizziness (n=1) ICM site Frontal lobe: 7 (44%) Parietal lobe: 7 (44%) Occipital lobe: 4 (25%) Temporal lobe: 2 (13%) Cerebellum: 2 (13%) Concurrent ECM Bone: 11 (69%) Lung: 9 (56%) Lymph node: 6 (38%) Liver: 5 (31%) Kidney: 1 (6%) Cranial nerve: 1 (6%) Treatment after ICM Radiotherapy: 15 (94%) Chemotherapy: 10 (63%) Immunotherapy: 9 (56%) Surgery: 8 (50%)

6106 Background: Treatment options for pts with R/M SGC are limited. Responses to chemotherapy (CT) are low with high toxicity and responses to immune checkpoint inhibition (ICI) are <10%. Pemetrexed (PTX) is safe and tolerable with responses reported in pts with R/M SGC. 1 Given enhanced responses with PTX and pembrolizumab (PMB) for lung cancer, we hypothesized that PTX and PMB will have activity for SGC. Herein we present the efficacy results in pts with non-adenoid cystic carcinoma (ACC). Methods: MC200708 is a single arm phase II study of PTX and PMB in pts with R/M SGC (NCT04895735). Pts were treated in 2 cohorts: ACC (cohort A) and non-ACC (cohort B). Key eligibility criteria: ≥18 years, ECOG 0-1, measurable disease. Prior ICI and/or PTX was allowed. Key exclusion criteria: serious comorbidities, autoimmune disease, and brain metastases. Simon’s 2-stage design was used for each cohort. Primary endpoint was overall response rate (ORR). Secondary endpoints: progression free survival (PFS), overall survival (OS), and toxicity. All pts received PTX 500 mg/m2 IV + PMB 200 mg IV q3 weeks until progression or treatment intolerance. Imaging was q3 cycles. Results: 25 pts were enrolled Aug 2021-Feb 2024; 1 cancelled prior to treatment. Of 24 eligible and treated pts, median age was 59.5 years (46-77), 66.7% male, performance status 0 (62.5%) or 1 (37.5%). Histologies were salivary duct carcinoma (SDC, 11), acinic cell carcinoma (8), mucoepidermoid carcinoma (MEC, 3), myoepithelial carcinoma (1), and carcinoma NOS (1). 7 pts had no prior therapies (29.2%). The remaining pts had 1 (33.3%), 2 (29.2%), or ≥ 3 lines of therapy (8.3%). 83.3% of pts had no prior ICI. Median cycles of treatment was 8 (2-34), and duration of response was 12.5 months (4.1-20.6). 9 of 24 pts had a confirmed partial response (PR) for ORR of 37.5% (CI: 18.8-59.4). PRs were seen in 7 pts with SDC (7 of 11, 63.6% PR), 1 with MEC, and 1 with acinic cell. Stable disease (SD) was seen in 5 (20.8%), progressive disease in 8 (33.3%), and 2 didn’t have post-baseline imaging, but were considered non-responders per protocol. Clinical benefit rate was 58.3% (CI: 36.6-77.9). With median follow-up of 12.0 months (2-34.7), median OS is 20.7 months (CI: 17.3-not reached) and median PFS is 6.2 months (CI: 2.1-17.3). 1-year OS and PFS rate is 76.3% (95% CI: 59.9-97.2) and 36.1% (CI: 21.01-62.2), respectively. Common toxicities were grade 1 fatigue and nausea. 6 pts (25.0%) had ≥1 grade 3-4 toxicity possibly related to treatment, mostly hematologic. The 4 pts with grade 3-4 non-heme toxicity had grade 3 fatigue, rash, and heart failure, and 1 grade 4 hypokalemia. Correlative studies investigating biomarkers of response are underway. Conclusions: PTX and PMB has activity in pts with R/M SGC, with promising responses in pts with SDC and median response duration of 1 year. 1 Viscuse et al. Head Neck 2019;41(6):E99-103. Clinical trial information: NCT04895735 .

Abstract Abdominally based free flaps are commonly utilized in the context of breast reconstruction. Historically, postoperative care of these patients involved liberal amounts of intravenous fluid administration; however, overadministration of fluids puts patients at risk of developing flap edema via fluid shifts, electrolyte imbalances, wound dehiscence, and other sequelae. The purpose of this study is to assess fluid administration trends in this cohort at the authors' institution and assess its impact on patient outcomes. A retrospective review was performed on patients who underwent free-flap breast reconstruction. Patient demographics and hospitalization data were collected, and type of abdominal flap and reconstruction timing was noted. Perioperative fluid administration volumes were tracked, and primary outcomes included complication rate and type (e.g., acute blood loss anemia [ABLA], partial/total flap loss, etc.). Multivariable logistic regression was performed to assess the impact of fluid volume on patient outcomes. A total of 115 patients (mean age of 51.3 ± 10.5 years) underwent 188 abdominally based free flaps. Deep inferior epigastric artery perforator flaps were performed most often (n = 91), followed by muscle-sparing transverse rectus abdominis flaps (n = 88). Multivariable logistic regression demonstrated that high perioperative fluid administration (≥9,000 mL) was associated with increased odds of medical complications (odds ratio [OR] = 21.7; confidence interval [CI]: 5.54–84.5; p < 0.001). Patients with high fluid administration volumes experienced an increased (but nonstatistically significant) flap complication rate (OR = 2.96; CI: 0.89–9.88; p = 0.08) and developed ABLA at a higher rate (OR = 15.86; CI: 5.30–46.4; p < 0.001). High-volume resuscitation (≥9,000 mL) was associated with increased odds of ABLA as well as a greater likelihood of medical and flap complications in patients undergoing abdominally based free flaps for breast reconstruction. These data should be used to guide the development of protocols within institutions, which perform free flaps for breast reconstruction.

Background: Major League Baseball (MLB) recently instituted a combine for their prospective players. Purpose/Hypothesis: The purpose of this study was to report initial epidemiological findings for both physical examination and imaging findings for the MLB Combine. It was hypothesized that most players would have no significant abnormal physical examination findings, but most would have abnormal findings on their shoulder and elbow magnetic resonance imaging (MRI) scans. Study Design: Descriptive epidemiology study. Methods: All players who attended the 2023 MLB Combine were included. History was taken and physical examination was performed by an MLB team physician, and MRI of the shoulder, elbow, cervical spine, and lumbar spine was performed on all players and read by 1 of 2 musculoskeletal radiologists. Physical examination notes and imaging reports were reviewed by the authors and recorded. Data were analyzed separately for pitchers and position players. Results: Overall, 219 players (112 pitchers [51%], 107 position players [49%]) were included. The mean age was 20.4 ± 1.5 years. The majority of players (95%) had no current pain or limitations; 54 players (25%) had a history of previous surgery. For pitchers, 18% underwent previous elbow surgery. With regard to MRI, >80% of pitchers had some abnormality within their ulnar collateral ligament (UCL), the majority of which was UCL scarring/remodeling. 70% of pitchers and 60% of position players had evidence of an olecranon osteophyte. Increased signal within the ulnar nerve was common in pitchers (40%) but rare in position players (4%). For the shoulder, 95% of pitchers and 93% of position players had some rotator cuff abnormality (often tendinosis within the supraspinatus and infraspinatus muscles). Also, 75% of pitchers had MRI evidence of a superior labrum anterior to posterior (SLAP) tear, while 24% of position players demonstrated this. Lumbar spine MRI showed that 47% of position players had a disk protrusion and 46% had a previous pars fracture. Conclusion: Most baseball players who participated in the 2023 MLB Combine had MRI evidence of rotator cuff abnormalities, and many showed evidence of an olecranon osteophyte. Eighteen percent of pitchers had a previous history of elbow surgery. The majority of pitchers had some abnormality within their UCL and evidence of a SLAP tear on MRI scans.

Objective To evaluate the safety and efficacy of MicroPulse Transscleral Laser Therapy (MicroPulse TLT) with the Revised P3 ® Delivery Device. Design Prospective, single-surgeon, interventional study in a tertiary hospital setting. Participants Sixty-two eyes of 40 patients with refractory glaucoma. Methods All subjects received 360-degree MicroPulse TLT treatment (2500 mW, 31.33% duty cycle) over a total of 240 s (8 sweeps; n = 20), 300 s (10 sweeps; n = 22), or 200 s (10 sweeps; n = 20). Participants were followed up for 6 months to assess changes in intraocular pressure (IOP), glaucoma medication burden, and best-corrected visual acuity (BCVA). Surgical success was defined as a reduction of IOP ≥ 30% from baseline and between 6–18 mmHg at last follow-up with no additional anti-glaucoma medications or secondary reinterventions. Results Surgical success was achieved in 72.7% (300 s group), 75.0% (240 s group), and 80.0% (200 s group) of eyes. Mean IOP was significantly reduced ( p < 0.001) by 49.0% (300 s group), 45.66% (240 s group), and 39.8% (200 s group) at 6 months. With all groups combined, the mean number of glaucoma medications was significantly reduced by 17.8% ( p = 0.005), and no significant changes in BCVA were observed at 6 months. Complications were minimal, including four eyes with IOP spikes, one eye with hyphema, and one eye with cystoid macular edema (CME), all of which resolved. Two eyes of the total sample (3.2%) required secondary glaucoma surgery before 6 months. Conclusions Second-generation MicroPulse TLT at fluence values of 154–229 J/cm 2 appears to be a safe and effective option for IOP reduction in refractory glaucoma.

Pick’s disease (PiD) is a rare neurodegenerative disorder defined by dementia, frontotemporal lobe atrophy, and 3-repeat tau inclusions. To elucidate PiD pathobiology, we performed the first bulk transcriptomics study on PiD using short- and long-read sequencing on the parietal cortex of 28 PiD and 15 control samples. We identified several significantly differentially expressed genes, with CCL2 displaying the strongest association with 3-repeat tau pathology and increased burden in PiD compared to those in 4-repeat tau progressive supranuclear palsy (PSP) cases. Investigation of co-expressed genes and pathways suggested the involvement of mRNA processing, mitochondrial function, and immune processes in disease pathobiology. Long-read RNA sequencing on a subset of samples (eight PiD and four control) proposed novel, potentially disease-associated transcripts for AZGP1 , CD44 , HSD11B2 , and WIF1 , predicted to result in truncated proteins. In conclusion, we observed transcriptomic changes in the parietal cortex of patients with PiD that may inform into clinically relevant biomarkers and therapeutic strategies.