Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial.

Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study.

Patient-specific reference model estimation for orthognathic surgical planning.

Purpose: Accurate estimation of reference bony shape models is fundamental for orthognathic surgical planning. Existing methods to derive this model are of two types: one determines the reference model by estimating the deformation field to correct the patient's deformed jaw, often introducing distortions in the predicted reference model; The other derives the reference model using a linear combination of their landmarks/vertices but overlooks the intricate nonlinear relationship between the subjects, compromising the model's precision and quality.

Methods: We have created a self-supervised learning framework to estimate the reference model.

An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202.

Background: Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period.

Knees with isolated lateral compartment osteoarthritis show a substantial variability in functional knee phenotypes with demographic-specific variations: Phenotypic analysis of 305 knees.

Background: The primary aim of this study was to assess and describe the phenotypic variation in the coronal plane of knees affected by isolated lateral compartment osteoarthritis (OA). The secondary aim was to investigate the potential gender-specific and age-related differences in functional knee phenotypes among knees with isolated lateral compartment OA.

Methods: A comprehensive classification system was used to categorize 305 knees with isolated lateral compartment OA based on their mechanical hip-knee-ankle angle (HKA), femoral mechanical angle (FMA), and tibial mechanical angle (TMA).

Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma.

Purpose: In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here.

Longitudinal Evaluation of DCE-MRI as an Early Indicator of Progression after Standard Therapy in Glioblastoma.

Distinguishing treatment-induced imaging changes from progressive disease has important implications for avoiding inappropriate discontinuation of a treatment. Our goal in this study is to evaluate the utility of dynamic contrast-enhanced (DCE) perfusion MRI as a biomarker for the early detection of progression. We hypothesize that DCE-MRI may have the potential as an early predictor for the progression of disease in GBM patients when compared to the current standard of conventional MRI.

Predicting optimal patient-specific postoperative facial landmarks for patients with craniomaxillofacial deformities.

Orthognathic surgery primarily corrects skeletal anomalies and malocclusion to enhance facial aesthetics, aiming for an improved facial appearance. However, this traditional skeletal-driven approach may result in undesirable residual asymmetry. To address this issue, a soft tissue-driven planning methodology has been proposed.

Gilteritinib with or without venetoclax for relapsed/refractory FLT3-mutated acute myeloid leukaemia.

Patients with FLT3-mutated acute myeloid leukaemia (AML) that relapse or are refractory (R/R) to intensive induction have poor outcomes. Gilteritinib has recently become standard-of-care for patients with R/R FLT3-mutated AML. We investigated whether adding venetoclax to gilteritinib (gilt-ven) improves outcomes as compared with gilteritinib monotherapy.

Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement.

Importance: Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient.

Objective: To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement.

Design, Setting, And Participants: This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US.

Epigenetic targeting of PGBD5-dependent DNA damage in SMARCB1-deficient sarcomas.

Despite the potential of targeted epigenetic therapies, most cancers do not respond to current epigenetic drugs. The Polycomb repressive complex EZH2 inhibitor tazemetostat was recently approved for the treatment of -deficient epithelioid sarcomas, based on the functional antagonism between PRC2 and loss of SMARCB1. Through the analysis of tazemetostat-treated patient tumors, we recently defined key principles of their response and resistance to EZH2 epigenetic therapy.

PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma.

Introduction: Intratumoral administration of pexa-vec (pexastimogene devacirepvec), an oncolytic and immunotherapeutic vaccinia virus, given to patients with hepatocellular carcinoma (HCC), is associated with both local and distant tumor responses. We hypothesized subsequent treatment with sorafenib could demonstrate superior efficacy.

Methods: This random phase III open-label study evaluated the sequential treatment with pexa-vec followed by sorafenib compared to sorafenib in patients with advanced HCC and no prior systemic treatment.

Robotic-arm-assisted lateral unicompartmental knee arthroplasty leads to high implant survival and patient satisfaction at mean 10-year follow-up.

Background: There is a lack of literature reporting on long-term outcomes following robotic-arm-assisted lateral unicompartmental knee arthroplasty (UKA). This study assessed the long-term survivorship, patient-reported satisfaction and pain scores following robotic-arm-assisted lateral UKA for lateral compartment osteoarthritis (OA).

Methods: A single surgeon's database was reviewed to identify all patients who underwent robotic-arm-assisted lateral UKA with a cemented, fixed-bearing prosthesis prior to May 2015.

A spike virosome vaccine induces pan-sarbecovirus antibody responses in mice.

Zoonotic events by sarbecoviruses have sparked an epidemic (severe acute respiratory syndrome coronavirus [SARS-CoV]) and a pandemic (SARS-CoV-2) in the past two decades. The continued risk of spillovers from animals to humans is an ongoing threat to global health and a pan-sarbecovirus vaccine would be an important contribution to pandemic preparedness. Here, we describe multivalent virosome-based vaccines that present stabilized spike proteins from four sarbecovirus strains, one from each clade.

Informing evidence-based medicine for opioid use disorder using pharmacoeconomic studies.

Introduction: The health and economic consequences of inadequately treated opioid use disorder (OUD) are substantial. Healthcare systems in the United States (US) and other countries are facing a growing healthcare crisis due to opioids. Although effective medications for OUD exist, relying solely on clinical information is insufficient for addressing the opioid crisis.

Toward a Unified Theory of Why Young People Develop Cancer.

Epidemiologic and genetic studies have now defined specific patterns of incidence and distinct molecular features of cancers in young versus aging people. Here, I review a general framework for the causes of cancer in children and young adults by relating somatic genetic mosaicism and developmental tissue mutagenesis. This framework suggests how aging-associated cancers such as carcinomas, glioblastomas, and myelodysplastic leukemias are causally distinct from cancers that predominantly affect children and young adults, including lymphoblastic and myeloid leukemias, sarcomas, neuroblastomas, medulloblastomas, and other developmental cancers.

Does stereotactic thrombolysis with alteplase for intracerebral haemorrhage alter intraventricular haematoma volume? A secondary analysis of the MISTIE-III trial.

Background: Stereotactic thrombolysis reduces intracerebral haemorrhage (ICH) volume in patients with spontaneous ICH. Whether intrahaematomal alteplase administration is associated with a change in intraventricular haemorrhage volume (deltaIVH) and functional outcomes is unknown.

Methods: Post hoc secondary analysis of the Minimally Invasive Surgery plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III (MISTIE-III) trial in patients with IVH on the stability CT scan.

Sex Differences in Adult Incarceration After Pediatric Traumatic Brain Injury.

Pediatric traumatic brain injury (pTBI) is a major risk factor associated with adulthood incarceration. Most research into the link between pTBI and adulthood incarceration has focused on incarcerated males, who comprise the vast majority of incarcerated adults, particularly in industrialized nations. In this review, we sought to identify sex-related differences in the incidence and pathophysiology of pTBI and subsequent risk of adulthood incarceration.

Improving Image Segmentation with Contextual and Structural Similarity.

Deep learning models for medical image segmentation are usually trained with voxel-wise losses, e.g., cross-entropy loss, focusing on unary supervision without considering inter-voxel relationships.

Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines.

Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers.