These data suggest a potential interplay between SCH and inflammatory activity in atherosclerotic plaque progression toward instability. Moreover, LTR might contribute to plaque stabilization by inhibiting the innate immunity-dependent plaque rupture in patients with SCH.

Background: Most recurrences of early-stage colorectal cancer (CRC) detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent CRC and improve cancer-related outcomes. Methods: Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III CRC was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time-point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. Results: 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% (CI 42.4-80.6) and 48% (CI 28.7-68.1) for COLVERA and CEA (≥5ng/mL), respectively (p=0.046), while specificity was 91.5% (CI 87.7-94.4) and 96.3% (CI 93.4-98.1), respectively (p=0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. Conclusion: COLVERA was more sensitive but less specific than CEA in detecting recurrent CRC. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of CRC recurrence translates into clinical benefit. Impact: This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III CRC Association for Cancer Research.

Background: The classic phenotype of CLN2 disease (neuronal ceroid lipofuscinosis type 2) typically manifests between ages 2 and 4 years with a predictable clinical course marked by epilepsy, language developmental delay, and rapid psychomotor decline. Atypical phenotypes exhibit variable time of onset, symptomatology, and/or progression. Intracerebroventricular-administered cerliponase alfa (rhTPP1 enzyme) has been shown to stabilize motor and language function loss in patients with classic CLN2 disease, but its impact on individuals with atypical phenotypes has not been described. Methods: A chart review was conducted of 14 patients (8 male, 6 female) with atypical CLN2 phenotypes who received cerliponase alfa. Pre- and posttreatment CLN2 Clinical Rating Scale Motor and Language (ML) domain scores were compared. Results: Median age at first presenting symptom was 5.9 years. First reported symptoms were language abnormalities (6 [43%] patients), seizures (4 [29%]), ataxia/language abnormalities (3 [21%]), and ataxia alone (1 [7%]). Median age at diagnosis was 10.8 years. ML score declined before treatment in 13 (93%) patients. Median age at treatment initiation was 11.7 years; treatment duration ranged from 11 to 58 months. From treatment start, ML score remained stable in 11 patients (treatment duration 11-43 months), improved 1 point in 1 patient after 13 months, and declined 1 point in 2 patients after 15 and 58 months, respectively. There were 13 device-related infections in 8 patients (57%) and 10 hypersensitivity reactions in 6 (43%). Conclusions: Cerliponase alfa is well tolerated and has the potential to stabilize motor and language function in patients with atypical phenotypes of CLN2 disease.

Pegvaliase is approved to reduce phenylalanine (Phe) levels for people with phenylketonuria (PKU). PRISM-1 (NCT01819727) and PRISM-2 (NCT01889862) data were analyzed to evaluate the relationship between Phe and inattention in adult participants with PKU. In the modified-intent-to-treat population (N = 156), baseline mean (SE) plasma Phe was 1263 (29) μmol/L and the Attention Deficit Hyperactivity Disorder Rating Scale-IV Inattentive (IA) symptoms score was 9.8 (0.5). Mean (SE) IA scores fell 9.0 (1.1) in Quartile 1 (Phe reduction between 1166 and 2229 μmol/L) versus 4.3 (0.7) in Quartile 4 (Phe reduction of 139 μmol/L to increase of 934 μmol/L), p = 0.004. Least squares mean (SE) change from baseline IA score was À7.9 (0.7) for participants with final Phe ≤ 360 μmol/L and À4.5 (0.7) for final Phe > 360 μmol/L, p < 0.001. In the inattention subgroup, IA scores fell 13.3 (1.5) in Quartile 1 (Phe reduction between 1288 and 2229 μmol/L) versus 6.2 (1.3) in Quartile 4 (Phe reduction of 247 to increase of 934 μmol/L), p = 0.009. Inattention symptoms improved among those whose Phe levels decreased, particularly those with high baseline IA scores. IA improvements were larger among participants with the greatest plasma Phe reductions, supporting this value as a therapeutic goal.