Clinically available KRAS inhibitors mainly target G12C, which is rare in PDAC and often acquires resistance. Oncogenic KRAS inactivates RB1 via CDK4/6, while RB1 mutation is rare. Thus, CDK4/6 inhibition offers an indirect strategy to counter KRAS-driven malignancy without direct KRAS targeting.

Virtually all pancreatic ductal adenocarcinomas (PDACs) are initiated by activating mutations in the oncogene KRAS, which occur in multiple distinct allelic forms. Although considerable efforts have led to the development of inhibitors targeting specific mutant KRAS proteins, the only agents currently approved for clinical use selectively target the KRASG12C variant. However, KRASG12C mutations are exceedingly rare in pancreatic cancer.

Furthermore, in patients with KRASG12C-mutant pancreatic cancer, treatment with KRASG12C inhibitors has shown only modest clinical benefit, comparable to that of conventional chemotherapeutic regimens, and even in cases with an initial objective response, acquired resistance almost invariably emerges within a limited time frame.

This study aimed to evaluate test-retest reliability and agreement of remote assessments and the interrater reliability of video-recorded functional assessments in myotonic dystrophy type 1. Read more.

Background and Objectives.

UTICalc demonstrated strong diagnostic performance for UTI in febrile children aged 2 to 24 months, supporting its use as an evidence-based adjunct in emergency department patient assessment.

This multicenter diagnostic study prospectively provides the final stage of external validation for UTICalc in young febrile children. We found strong discrimination for the model, which was improved when incorporating dipstick data. This study supports integration into clinical care as a tool for diagnostic stewardship in pediatric care.

Decision curve analysis supported the utility of both UTICalc models across relevant thresholds. However, clinician judgment demonstrated higher sensitivity in the high-volume tertiary centers where this study was conducted, reflecting pediatric emergency medicine practitioner expertise. Because most children presenting for acute care are evaluated outside tertiary centers,²⁷ possibly with limited pediatric expertise and uncertain follow-up, using a 5% risk threshold—despite reducing testing—may not be ideal due to reduced sensitivity. UTICalc may serve as a useful adjunct for clinicians with less pediatric experience or in cases of diagnostic uncertainty, with lower risk thresholds (eg, 2%) potentially more appropriate for patients with persistent symptoms or anticipated barriers to follow-up.

The observed UTI prevalence of 4% in our cohort is consistent with previously reported risk estimates in this population, which ranges from 3% to 11%.^2,28,29 Model performance in our study was comparable with the original derivation and validation study published in 2018, which reported an AUROC of 0.80 in the clinical model and 0.97 in the clinical and dipstick model. Low PPV in our sample is reflective of low disease prevalence.

HHV-6 was identified as a rare cause of fulminant acute hemorrhagic leukoencephalitis in an immunocompetent adult.

This case report describes the presentation of human herpesvirus 6 and acute hemorrhagic leucoencephalitis in a patient without remarkable medical history or immunocompromise.