Publications by Year: 2026

Colorectal cancer (CRC) is a major global health burden. Although colonoscopy remains the gold standard for screening, less invasive biomarker-based stool and blood tests including FIT, multi-target stool DNA/RNA assays, and blood-based biomarker tests are emerging with promising diagnostic performance. In the post-treatment setting of localized CRC, ctDNA has emerged as a powerful tool, with studies showing it can predict recurrence earlier than imaging or traditional tumor biomarkers. ctDNA testing is used for genomic profiling of CRC to guide therapy decisions. Ongoing research aims to refine ctDNA-based surveillance and integrate it with other biomarkers to transform CRC monitoring and treatment.

OBJECTIVE: Patients on ticagrelor who are undergoing cardiac surgery before completing guideline-recommended washout are at high risk for severe bleeding. This study evaluated whether a novel drug removal device reduces bleeding in patients operated within 2 days from ticagrelor discontinuation.

METHODS: Eligible patients were randomized 1:1 to intraoperative DrugSorb-ATR or sham control. Primary safety end point was adverse events at 30 days. Efficacy was assessed by composite end points comprising bleeding events using Universal Definition of Perioperative Bleeding (UDPB) and 24-hour chest tube drainage (CTD) in the overall and isolated coronary artery bypass grafting (CABG) populations with a hierarchical win ratio (WR) method.

RESULTS: In total, 140 patients were randomized; 132 had surgery and received a study device; and 92% were isolated CABG. Mean age was 65 ± 5 years, and 15% were female. The primary safety end point was met, with similar adverse events reported between groups. The primary efficacy end point was not met in the overall or CABG populations (Win ratio [WR], 1.07; 95% CI, 0.72-1.58; P = .748 and WR, 1.33; 95% CI, 0.86-2.04; P = .202 respectively). The supplementary efficacy end point was met in the CABG population (WR, 1.59; 95% CI, 1.02-2.46, P = .041) with significant reductions also shown in large CTD bleeding events (P = .016) and major bleeding, a composite of severe bleeding events or 24-hour CTD ≥1 L (P = .041). The number needed to treat to prevent a major bleed was 6.

CONCLUSIONS: Intraoperative use of DrugSorb-ATR is safe in patients operated within 2 days of ticagrelor discontinuation. Although the primary end point was not met in the overall population, there were significant reductions in severe bleeding events in the prespecified CABG population.

Visuospatial processing dysfunctions are common in individuals with cerebral visual impairment (CVI) and can have a significant impact on how they perceive and interact with their surrounding environment. To gain further insight into the nature of these deficits, we assessed visual scanning performance in individuals with CVI compared to neurotypically developed controls. In this exploratory story, 16 individuals with CVI (mean age = 19.56 years ± 5.59 SD; mean verbal IQ = 94.85 ± 21.84) and 19 control participants (mean age = 21.37 years ± 5.21 SD; mean verbal IQ = 123.79 ± 12.59) completed the Star Cancellation Test (SCT). Gaze behavior was also recorded using wearable eye tracking (Tobii Pro Glasses 3; 100 Hz sampling rate) during naturalistic and standardized administration of the assessment. Controlling for age and verbal IQ level, we found that while test accuracy was not significantly lower in CVI participants, they took significantly longer to complete the task compared to controls. CVI participants also tended to spend more time verifying their work and had lower cancellation efficiency (a composite performance index incorporating accuracy and completion time). Regarding gaze metrics, CVI subjects had longer total fixation durations and higher fixation counts, as well as greater total saccade amplitudes (scan path length) and saccade counts. However, group differences were not significant when comparing normalized gaze metrics (i.e., average fixation duration and average saccade amplitude). The observed differences in behavioral performance and gaze metrics in CVI are consistent with a profile of less efficient and more effortful visual scanning and search. The use of standardized assessments combined with wearable eye tracking can provide further insight into the nature of visuospatial processing dysfunctions in this population.

Over 20 % of patients with Hodgkin lymphoma (HL) experience disease progression after initial treatment. We evaluated the prognostic utility of circulating tumor DNA (ctDNA) in HL patients. We systematically searched PubMed, Embase, the Cochrane Library, Scopus, and Web of Science up to March 22, 2025. Survival data were extracted from Kaplan-Meier curves and digitized to reconstruct individual patient-level datasets. We applied a hierarchical Bayesian model with weakly informative priors to estimate hazard ratios (HRs), restricted mean survival times (RMSTs), along with their 95 % credible intervals (CrI) up to five years for both progression-free survival (PFS) and overall survival (OS). Ten studies, including 1158 patients, were analyzed. Elevated baseline ctDNA was associated with inferior PFS (HR: 2.74; 95 % CrI: 1.30-5.75) and a 5-year RMST loss of 7.7 (1.2-17.3) months. Prognostic strength increased over time, with interim ctDNA positivity showing an HR of 5.99 (3.46-10.13; ΔRMST: 22.7 months; 12.9-33.2) and end-of-treatment ctDNA positivity showing an HR of 13.4 (3.97-41.87; ΔRMST: 39.2 months; 17.7-49.4). High baseline ctDNA was associated with worse OS (HR: 2.49; 1.07-5.80; ΔRMST: 11.6 months; 0.7-27.8). Similarly, positive ctDNA following treatment predicted worse OS (HR: 4.74; 1.60-14.47; ΔRMST: 16.2 months; 3.0-38.1). To conclude, in HL patients, a higher ctDNA concentration was associated with increased disease progression and mortality, with this association intensifying toward the end-of-treatment. Clinical implementation requires standardization of assay methods, validation of prognostic thresholds, and longitudinal assessment of the independent prognostic value of ctDNA.

BACKGROUND: There are limited resources to detect and interpret cluster signals in resource-limited hospitals. The aim was to improve the interpretation of pathogen spatiotemporal clustering detected using the SaTScan algorithm - a method that uses space-time scan statistics to detect cluster signals that occur more often than expected.

METHODS: Analysis of electronic data of inpatients with clinical specimens culture positive for seven antimicrobial-resistant pathogens in two tertiary hospitals in Thailand from January to December 2022 was performed. Space-time uniform scan statistics were applied in SaTScan. Four analyses were performed. Analysis 1 did not include antimicrobial susceptibility test (AST) result profiles. Analyses 2, 3, and 4 included AST results of antibiotics that had ≥70%, ≥80%, and ≥90% of available results among the included patients, respectively.

FINDINGS: There were 125,848 microbiology data records collected from a 1188-bed hospital and 54,069 records from a 773-bed hospital in 2022. Multiple cluster signals were detected in both hospitals, including clusters of carbapenem-resistant Gram-negative organisms across different wards over different time periods. The number of cluster signals detected decreased with increasing thresholds used to select antibiotics to be included in the analysis. For instance, Analysis 2 detected 33 clusters, which reduced to 4 clusters in Analysis 4 in the 1188-bed hospital data. Similar patterns were also observed in the 773-bed hospital data. The temporal occurrence of detected cluster signals coincided with the period during which AST results were unavailable in Analyses 2 and 3.

CONCLUSION: The findings suggest that SaTScan is applicable to detect potential cluster signals in resource-limited settings, and the interpretation of detected signals could be supported by graphical presentations of temporal changes in the availability of AST data.

Hemodynamically significant carotid artery stenosis is a common clinical condition that can lead to chronic cerebral hypoperfusion. Despite the well-recognized pivotal role of pial collaterals in maintaining cerebral perfusion during focal arterial occlusions, regulation of microvascular blood flow and oxygenation in the cerebral watershed "pial-collateral territory" during chronic hypoperfusion remains unexplored. To answer this question, we applied 2-photon microscopy and Doppler optical coherence tomography to assess the changes in cerebral blood flow, capillary red-blood-cell (RBC) flux, and intravascular oxygen partial pressure (PO2), seven days after bilateral common-carotid artery stenosis (BCAS). The measurements were performed in the middle-cerebral-artery (MCA) territory and the watershed between the MCA and anterior-cerebral-artery territories in the awake, head-restrained C57BL/6 mice, through a glass-sealed cranial window. The results showed that BCAS induced a significant decrease in microvascular perfusion in the watershed area compared to the MCA territory, with the largest RBC flux reduction observed in the subcortical white matter. The watershed area exhibited a larger drop between arterial and venous PO2 and the calculated oxygen saturation, indicating a significant increase in oxygen extraction fraction following BCAS. Structural analysis of the microvasculature showed significant BCAS-induced dilation of pial collaterals, suggesting a potential compensatory mechanism to improve blood flow in the hypoperfused watershed. However, microvascular morphology did not change in either region, implying an absence of structural remodeling at this early stage. Collectively, these findings point to an oxygen supply-consumption mismatch and heightened vulnerability in the watershed areas, particularly affecting the subcortical white matter, during flow-limiting cervical artery stenosis.

Chronic pain in adolescents commonly disrupts cognitive functioning, sleep, and mental health. Research suggests underdeveloped cognitive skills in adolescents may lead to poor self-management thus reinforcing pain-related disability. This study aims to examine changes across cognition, sleep, and mental health in youth with chronic pain undergoing rehabilitation in addition to identifying associations between improvements across domains of interest. A 4-week observational study was conducted in 42 adolescents (Mage=15.1 years, 76% female) diagnosed with non-cancer chronic pain syndromes and engaged in intensive interdisciplinary pain treatment (IIPT). Questionnaires assessing pain, sleep, and mental health were administered at baseline and discharge. Standardized performance-based assessments (CANTAB®) were employed to measure cognitive domains. Cognitive domains of memory, attention, and executive functioning improved over time (all ps<0.01). Significant reductions in self-reported measures related to pain, sleep disruptions, and mental health symptoms (all ps<0.01) were observed across rehabilitation. Positive associations were identified between improvements in pain, sleep, and mental health measures (all ps<0.05). No significant correlations were identified between improvements in cognition and improvements in other domains. Findings highlight the prospective gains for cognitive outcomes in adolescents with chronic pain undergoing IIPT. Further research is essential to explore mechanisms by which IIPT may directly improve cognitive functioning over the course of treatment.