Digital Versus Manual PD-L1 Scoring in Advanced NSCLC From the IMpower110 and IMpower150 Trials.

Introduction: Treatment selection in patients with advanced NSCLC is based on programmed death-ligand 1 (PD-L1) expression, which is usually scored manually and is subject to intra- and inter-pathologist variability. A PD-L1 clone-agnostic artificial intelligence (AI) model for AI-based measurement of PD-L1 (AIM-PD-L1) was developed and assessed in advanced NSCLC using clinical samples from two phase 3 trials.

Methods: IMpower110 evaluated atezolizumab versus chemotherapy in PD-L1-positive metastatic, stage IV, squamous or nonsquamous NSCLC.

Unconventional Alternative Shunts in Pediatric Extrahepatic Portal Vein Obstruction - Experience With Satisfactory Outcome.

Background: Major variceal hemorrhages in children of the Indian subcontinent, are caused by extrahepatic portal vein obstruction (EHPVO). Portosystemic shunt surgery (PSS) is the recommended course of action for long-term care in refractory cases, even if endoscopic techniques constitute the initial line of treatment for acute variceal hemorrhage. The most usual surgery, particularly with splenomegaly, is the proximal splenorenal shunt (PSRS).

Analytical and clinical performance validation of HPV-SEQ, a novel NGS-based liquid biopsy platform for detection and quantification of human papilloma virus circulating tumor DNA.

Background: Human papillomavirus (HPV) is the primary causative driver of oropharyngeal squamous cell carcinoma (OPSCC). Accurate detection of HPV-DNA is critical for risk stratification and management of OPSCC. However, assays designed to detect HPV in primary tumors do not allow monitoring of HPV-DNA over time, whereas commercially available droplet digital PCR-based methods for assessment of circulating cell free (cf)HPV-DNA in plasma remain suboptimal, hindering adaptation into clinical practice.

Early Dynamics of Circulating Tumor HPV-DNA with Neoadjuvant Chemotherapy and Response-Adapted De-escalation in Human Papillomavirus-Associated Oropharyngeal Cancer.

Purpose: Human papillomavirus-associated (HPV+) oropharyngeal carcinoma is associated with excellent survival, yet treatment drives substantial toxicity. Improved biomarkers are needed to select patients for de-escalated treatment. Circulating tumor HPV DNA (ctHPV-DNA) represents a promising noninvasive biomarker to gauge treatment response and surveil for disease recurrence.

Neoadjuvant Nivolumab Plus Chemotherapy Followed by Response-Stratified Chemoradiation Therapy in HPV-Negative Head and Neck Cancer: The DEPEND Phase 2 Nonrandomized Clinical Trial.

Importance: Neoadjuvant immunotherapy in human papillomavirus (HPV)-negative locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) appears promising, yet its role in nonsurgical treatment for head and neck cancer remains undefined. Neoadjuvant nivolumab plus chemotherapy followed by response-stratified de-escalated chemoradiation therapy (CRT) in HPV-negative LA stage IVa/b HNSCC may improve treatment efficacy while reducing treatment-related toxic effects.

Objective: To determine the deep response rate and tolerability of neoadjuvant nivolumab plus chemotherapy followed by response-stratified CRT in nonvirally mediated stage IVa/b HNSCC.

Effects of ex vivo machine perfusion on preservation time and donor age in donation after brain death heart transplantation.

With encouraging early experience, ex vivo machine perfusion (MP) systems are increasingly employed in heart transplantation. In this study, utilizing a national registry database, 2 separate analyses were performed to evaluate the effects of MP on graft preservation time (total n = 22,794; n = 308 with MP) and donor age (total n = 22,581; n = 95 with MP) in donation after brain death (DBD) heart transplantation. The cohort was stratified based on total preservation time (<4 and ≥4 hours) and donor age (<45 and ≥45 years).

Analysis of AI foundation model features decodes the histopathologic landscape of HPV-positive head and neck squamous cell carcinomas.

Objectives: Human papillomavirus (HPV) influences the pathobiology of Head and Neck Squamous Cell Carcinomas (HSNCCs). While deep learning shows promise in detecting HPV from hematoxylin and eosin (H&E) stained slides, the histologic features utilized remain unclear. This study leverages artificial intelligence (AI) foundation models to characterize histopathologic features associated with HPV presence and objectively describe patterns of variability in the HPV-positive space.

Circulating tumor DNA in head and neck squamous cell carcinoma-current status and future prospects.

Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck. Stagnating survival rates in recent decades, despite advances in the treatment paradigms, surveillance technologies, and multidisciplinary care, leave clinicians with a need for better options for screening, risk-stratifying, and monitoring patients. A growing proportion of patients with HPV-associated SCC have improved outcomes but continue to have a heterogenous response to treatment.

PRMT5 inhibition has a potent anti-tumor activity against adenoid cystic carcinoma of salivary glands.

Background: Adenoid cystic carcinoma (ACC) is a rare glandular malignancy, commonly originating in salivary glands of the head and neck. Given its protracted growth, ACC is usually diagnosed in advanced stage. Treatment of ACC is limited to surgery and/or adjuvant radiotherapy, which often fails to prevent disease recurrence, and no FDA-approved targeted therapies are currently available.

A kinome drug screen identifies multi-TKI synergies and ERBB2 signaling as a therapeutic vulnerability in MYC/TYR subgroup atypical teratoid rhabdoid tumors.

Background: Atypical teratoid rhabdoid tumor (ATRT) is a rare, devastating, and largely incurable pediatric brain tumor. Although recent studies have uncovered 3 molecular subgroups of ATRTs with distinct disease patterns, and signaling features, the therapeutic profiles of ATRT subgroups remain incompletely elucidated.

Methods: We examined the effect of 465 kinase inhibitors on a panel of ATRT subgroup-specific cell lines.

Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer: OPTIMA II Phase 2 Open-Label Nonrandomized Controlled Trial.

Importance: Immune checkpoint inhibitors improve survival in recurrent and/or metastatic head and neck cancer, yet their role in curative human papillomavirus-positive oropharyngeal cancer (HPV+ OPC) remains undefined. Neoadjuvant nivolumab and chemotherapy followed by response-adaptive treatment in HPV+ OPC may increase efficacy while reducing toxicity.

Objective: To determine the deep response rate and tolerability of the addition of neoadjuvant nivolumab to chemotherapy followed by response-adapted locoregional therapy (LRT) in patients with HPV+ OPC.

Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer.

The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated.

Outcomes of Impella 5.0 and 5.5 for cardiogenic shock: A single-center 137 patient experience.

Background: This study evaluated the outcomes of patients with cardiogenic shock (CS) supported with Impella 5.0 or 5.5 and identified risk factors for in-hospital mortality.

Heterotopic ossification in right popliteal fossa causing arterial insufficiency.

Heterotopic ossification (HO) is the abnormal formation of extra-skeletal bone in soft tissue, which can occur after trauma or surgery. HO in joints can cause pain, hinder mobility, and compress surrounding nerves and blood vessels. We present an unusual case of arterial insufficiency caused by HO in the right popliteal fossa.

Cardiogenic shock etiology and exit strategy impact survival in patients with Impella 5.5.

Background: Despite historical differences in cardiogenic shock (CS) outcomes by etiology, outcomes by CS etiology have yet to be described in patients supported by temporary mechanical circulatory support (MCS) with Impella 5.5.

Objectives: This study aims to identify differences in survival and post-support destination for these patients in acute myocardial infarction (AMI) and acute decompensated heart failure (ADHF) CS at a high-volume, tertiary, transplant center.

A comprehensive AI-driven analysis of large-scale omic datasets reveals novel dual-purpose targets for the treatment of cancer and aging.

As aging and tumorigenesis are tightly interconnected biological processes, targeting their common underlying driving pathways may induce dual-purpose anti-aging and anti-cancer effects. Our transcriptomic analyses of 16,740 healthy samples demonstrated tissue-specific age-associated gene expression, with most tumor suppressor genes downregulated during aging. Furthermore, a large-scale pan-cancer analysis of 11 solid tumor types (11,303 cases and 4431 control samples) revealed that many cellular processes, such as protein localization, DNA replication, DNA repair, cell cycle, and RNA metabolism, were upregulated in cancer but downregulated in healthy aging tissues, whereas pathways regulating cellular senescence were upregulated in both aging and cancer.

The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring.

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles.

Race, sex, and socioeconomic disparities affect the clinical stage of patients presenting for treatment of superficial venous disease.

Objective: Superficial venous disease has a U.S. prevalence of nearly 30%, with advanced disease contributing to a significant healthcare burden.