Citations

Objective Long COVID (LC) refers to the long-term symptoms occurring after SARS-CoV-2 infection and resolution of the initial disease prodrome. While LC is increasingly recognized, knowledge about its biomarkers is still limited. This study examines imaging findings in 18 F-FDG PET-CT scans in 40 patients with LC from an academic LC Clinic, for potential imaging biomarkers. Methods This study included patients aged 18 and older with confirmed positive SARS-CoV-2 PCR test and at least 28 days post-symptom onset. 18 F-FDG PET-CT scans were performed, and brain metabolic activity was compared to a control database to generate Z-scores. Participants were grouped based on their clinical phenotype and Z-scores of different brain regions were analyzed using t-tests. Results The study group was mainly female (70%), with a median age of 53 years, and predominantly non-Hispanic White (90%). Most had pre-existing conditions such as gastrointestinal, cardiovascular, endocrine, and psychiatric disorders. The findings showed significant cerebral hypometabolism in 29 patients with fatigue and post-exertional malaise (PEM), particularly in the left sensorimotor cortex (p=0.0253) and bilateral primary visual cortex (right: p=0.0096, left: p=0.0016), which persisted up to two years after infection. Conclusions In summary, this study identified persistent cerebral hypometabolism in LC patients, especially those with fatigue with PEM, up to two years post-infection. These results suggest that 18 F-FDG PET-CT could be a valuable tool for diagnosing and managing LC. Further research is essential to confirm these findings and improve treatment strategies for patients with LC.

ABSTRACT High dose melphalan (HDM) with autologous stem cell transplant is an established treatment for systemic light chain amyloidosis, but its incremental benefit in the era of effective standard intensity therapy is unknown. We retrospectively analyzed 475 transplant‐eligible patients who completed standard intensity treatment with or without HDM within 12 months at six centers in Europe and the United States between 2010 and 2024 to evaluate outcomes by baseline risk factors, hematologic response, and receipt of HDM. Death was an equally competing risk after the 12‐month landmark chosen to address early non‐proportional hazards and to ensure completion of first‐line therapy. BMPC > 20% was associated with inferior outcomes (HR 1.7), and gain/amp 1q with shorter TTP (HR 2.15), whereas other high‐risk FISH abnormalities were not. In multivariable models, VGPR/CR after standard intensity therapy was associated with longer TTP (HR 0.49/0.29), while gain/amp 1q remained independently associated with shorter TTP (HR 2.18). Receipt of daratumumab and HDM were associated with longer TTP (HR 0.44/0.61). HDM benefited patients who had not achieved CR after standard intensity therapy (mTTP 21.0 vs. 5.7 months without HDM), whereas patients already in CR did not benefit. Higher BMPC at diagnosis was associated with earlier progression in patients not receiving HDM (HR 1.9 for 5%–20% and 4.09 for > 20%), a risk attenuated in the HDM cohort. Gain/amp 1q remained associated with shorter TTP regardless of HDM exposure. These findings support a selective role for HDM, primarily benefiting patients with residual disease after standard intensity therapy or higher BMPC burden at diagnosis.

LBA10509 Background: The MCED test (Galleri) detects a shared cancer signal from cell-free DNA in blood and predicts a cancer signal origin (CSO) to guide diagnostic (dx) workup. PF2 (NCT05155605) is a large, prospective, multicenter, interventional study of the MCED test’s performance and safety in a diverse US intended-use population. Methods: PF2 enrolled participants aged ≥50y without clinical suspicion of cancer or cancer diagnosis/treatment within 3y of enrollment. Primary objectives were MCED performance and safety in terms of dx testing triggered by a positive (cancer signal detected) MCED test result. Participants with a positive MCED test underwent targeted dx workup guided by the predicted CSO(s). Participant-reported anxiety was assessed with the State Trait Anxiety Inventory. Results: PF2 enrolled 35,878 participants; 32,007 with a 12m cancer assessment were analyzable for performance. Of 287 (0.9%) with a positive MCED test, 173 were diagnosed with cancer within 12m, for a cancer detection rate of 0.5% (95% CI 0.5-0.6%) and positive predictive value of 60.3% (54.5-65.8%). Specificity was 99.6% (99.6-99.7%). 12m episode sensitivity was 69.8% (62.8-76.0%) in a prespecified subgroup of 12 cancers responsible for ⅔ of US cancer deaths, 66.2% (55.1-75.8%) in a subgroup of 6 aggressive cancers with low 5y survival, and 39.3% (34.9-44.0%) across all cancers. Overall CSO prediction accuracy was 91.3% (86.2-94.7%) across all cancers. The MCED test detected 151 new primary and 22 recurrent cancers; additional cancers detected by screening were those with USPSTF A/B (n=31) and C (n=60) recommended screening. Of 151 MCED-detected new primaries, 80 (53.0%) were clinical stage I-II; 107 (70.9%) were stage I-III. Of 80 MCED-detected stage I-II cancers, 71.2% had no USPSTF A/B screening recommendation. Of 35,335 participants analyzable for safety, 213 (0.6%) had invasive procedure(s) to evaluate a positive MCED test result, of which 90% were nonsurgical and 1.8x more likely for participants with vs without cancer diagnosis. Most (87.6%) had a CSO-guided dx evaluation. There were 5 study-related adverse events during the time of dx workup; none were serious. Anxiety temporarily increased for participants with a positive MCED test and cancer diagnosed, and returned to baseline by 12m. Of participants with a positive MCED test, median time from test result to dx resolution was 48d (95% CI 43-56). Few participants (7/63 [11.1%]) had cancer found by dx PET/CT after a targeted dx workup that did not reveal cancer. Conclusion: The MCED test demonstrated robust performance with a favorable safety profile. When MCED testing was added to USPSTF A/B screening, 6.5x more cancers were detected by screening, most at early stages. The diverse, representative PF2 participant population supports the generalizability of these findings to the US intended-use population. Clinical trial information: NCT05155605 .

Abstract Background Preterm premature rupture of membranes (PPROM) and preterm labor (PTL) are adverse obstetrical outcomes that are strongly associated with cervical high-risk human papilloma virus (cHPV) infection at the time of pregnancy. Persistent cHPV may lead to oncogenic changes in the cervico-vaginal tract and can cause inflammation in gestational tissues, but it is unknown how persistent cHPV infection may affect obstetrical outcomes. The aim of this study is to evaluate whether persistent cHPV infection is associated with recurrent PPROM or PTL among patients with a prior spontaneous preterm birth due to PPROM/PTL, and to examine clinical and pathologic characteristics of cHPV infection in this population. Methods We conducted a retrospective cohort study of patients delivering at Mayo Clinic Rochester or Mayo Clinic Health System (5/1/2018–12/31/2023). Eligible patients had ≥ 1 spontaneous preterm birth due to PPROM/PTL and positive cHPV testing. Demographics and pregnancy outcomes from index and subsequent pregnancies were abstracted. Persistent cHPV was defined as > 1 pregnancy with positive cHPV testing. Results Of 191 index pregnancies, 90 (47.1%) and 30 (33.3%) had one and two subsequent pregnancies, respectively. Patients were predominantly White (91.3%), non‑Hispanic (94.2%), non-smokers (72.0%), and 34.8% were unvaccinated for HPV. Approximately one‑third (31%) experienced recurrent PPROM/PTL in the second pregnancy, with recurrence in 40.7% of those with persistent cHPV and 27.4% without (p = 0.69). Excisional procedures occurred before 12.0% of index pregnancies and 20–24% of subsequent pregnancies; recurrence of PTL/PPROM remained high regardless of procedure history. HPV strain data were available for 132 index pregnancies, and types 16 and 18 were more likely to persist into a subsequent pregnancy (p = 0.0043). CIN persistence occurred at similar rates in patients with and without persistent cHPV infection. Placental inflammation rates were high in both patients with persistent and non-persistent cHPV. Conclusion Recurrent PPROM/PTL, CIN persistence, and placental inflammation were common; a finding independent of persistent cHPV infection, excisional procedure history, or HPV vaccination status. These findings suggest that factors other than cHPV persistence may play a larger role in recurrent preterm birth. Larger studies with higher cHPV prevalence and subsequent pregnancies are needed to provide clarity.

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 < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 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.

e22604 Background: Heart, pericardial, and mediastinal tumors are rare neoplasms with potential sex-specific disparities. Despite their clinical significance, long-term temporal trends stratified by sex remain poorly characterized. Methods: We conducted a population-based analysis using data from the Surveillance, Epidemiology, and End Results (SEER) database, evaluating annual case counts from 1975 to 2022, stratified by sex. Temporal trends in total, male, and female cases were assessed using linear regression models. Results: A total of 657 cases were reported over the study period (445 males; 212 females). Total case counts showed a significant upward trend, increasing by 1.25 cases per year (p < 0.001, R² = 0.59). Male cases increased by 0.85 cases/year (p < 0.001), nearly twice the increase observed in females (0.40 cases/year, p < 0.001). Male predominance persisted throughout the study period, with both sexes showing a gradual upward trend, reflecting a consistent sex disparity in these tumors. Conclusions: The occurrence of heart, pericardial, and mediastinal tumors has increased steadily over the past five decades, disproportionately affecting males. These findings highlight persistent sex-based disparities and underscore the need for further sex-specific research to elucidate underlying risk factors and inform targeted surveillance and early detection strategies.

e22593 Background: Pheochromocytoma is a rare neuroendocrine tumor, and population-level data describing long-term temporal trends are limited. Evaluating national patterns over time may improve epidemiologic understanding and clinical awareness. Methods: We performed a retrospective analysis of pheochromocytoma cases recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 through 2022. Annual case counts were examined overall and by race (White, Black, Other, and Unknown). Temporal trends were assessed using Poisson regression, and annual percent change (APC) was calculated to quantify changes over time. Results: A total of 408 pheochromocytoma cases were identified during the study period. Overall case counts increased significantly over time, with Poisson regression demonstrating a consistent upward trend corresponding to an APC of 5.8% per year (p < 0.001). White individuals accounted for the majority of reported cases, while Black and other racial groups had significantly lower case counts compared with the reference population. Visual assessment of decade-level trends suggested a gradual increase from 1975 through approximately 2010, followed by a sharper rise in more recent years. Conclusions: Pheochromocytoma case counts in the United States have increased substantially over the past five decades based on SEER data. These findings suggest evolving epidemiologic patterns in this rare tumor and emphasize the importance of continued surveillance. Observed trends should be interpreted in the context of potential changes in diagnostic practices, imaging utilization, and cancer registry reporting over time.

e19562 Background: Multiple myeloma is a chronic blood cancer in which patients often live for many years, yet the risk of death remains ongoing. While survival has improved over time, population-level studies that combine traditional survival analysis, advanced modeling techniques, and future burden projections are limited. Methods: We performed a population-based retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. Parametric survival modeling was conducted using Weibull regression to better characterize long-term mortality patterns. Machine-learning survival analysis was performed using random survival forests to assess the relative importance of clinical and demographic factors. Annual case counts were analyzed and projected through 2035 using time-series forecasting methods. Results: The study included 8,627 patients with multiple myeloma. Overall survival declined gradually over long-term follow-up, with approximately one-quarter to one-third of patients surviving at extended time points. Female patients experienced better survival than males. Significant survival differences were observed across racial groups, with Asian or Pacific Islander patients demonstrating the most favorable outcomes and American Indian or Alaska Native patients the poorest. In multivariable analyses, age, sex, race, and year of diagnosis were independently associated with survival. Parametric modeling closely mirrored non-parametric survival estimates and supported a time-dependent pattern of mortality. Machine-learning analysis identified year of diagnosis as the strongest predictor of survival, followed by age and race. Forecasting suggested that the burden of multiple myeloma will remain substantial through 2035. Conclusions: Multiple myeloma is associated with long-term survival but persistent mortality risk and ongoing demographic disparities. Combining traditional survival analysis with parametric and machine-learning approaches provides a more complete understanding of outcomes and highlights the sustained future burden of this disease, with important implications for clinical care and healthcare planning.