Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy.

ADNI Private Partners Scientific Board (PPSB) Diversity, Equity, and Inclusion (DE&I) Working Group: A new collaboration that crosses boundaries for industry, academia, and under-represented patients.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partners Scientific Board (PPSB) Diversity, Equity, and Inclusion Working Group (DE&I WG) was established to work with the ADNI3 Diversity Task Force to provide an industry perspective on increasing the representation of diverse participants in ADNI3 and to build precompetitive cross-industry knowledge in engagement and recruitment of under-represented participants (URPs). In this article, we review and highlight the role and ongoing activities within the ADNI PPSB DE&I WG and provide a cross-industry perspective on areas where precompetitive collaboration can improve the inclusiveness in clinical trials, drawing on examples from ADNI4. HIGHLIGHTS: New collaboration crosses boundaries to allow PPSB DE&I WG members to work together in a preproprietary way.

EXCELLENT Registry: A Prospective, Multicenter, Global Registry of Endovascular Stroke Treatment With the EMBOTRAP Device.

Background: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots.

Methods: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee.

Results: After screening 3799 patients, a total of 997 subjects (mean age, 70.

In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy.

Cancer evolution is a multifaceted process leading to dysregulation of cellular expansion and differentiation through somatic mutations and epigenetic dysfunction. Clonal expansion and evolution is driven by cell-intrinsic and -extrinsic selective pressures, which can be captured with increasing resolution by single-cell and bulk DNA sequencing. Despite the extensive genomic alterations revealed in profiling studies, there remain limited experimental systems to model and perturb evolutionary processes.

Multimodal neuroimaging to characterize symptom-specific networks in movement disorders.

Movement disorders, such as Parkinson's disease, essential tremor, and dystonia, are characterized by their predominant motor symptoms, yet diseases causing abnormal movement also encompass several other symptoms, including non-motor symptoms. Here we review recent advances from studies of brain lesions, neuroimaging, and neuromodulation that provide converging evidence on symptom-specific brain networks in movement disorders. Although movement disorders have traditionally been conceptualized as disorders of the basal ganglia, cumulative data from brain lesions causing parkinsonism, tremor and dystonia have now demonstrated that this view is incomplete.

Overestimation of the Ischemic Core Is Associated With Higher Core Lesion Volume and Degree of Reperfusion After Thrombectomy.

Background CT perfusion (CTP)-derived baseline ischemic core volume (ICV) can overestimate the true extent of infarction, which may result in exclusion of patients with ischemic stroke from endovascular treatment (EVT). Purpose To determine whether ischemic core overestimation is associated with larger ICV and degree of recanalization. Materials and Methods This retrospective multicenter cohort study included patients with acute ischemic stroke triaged at multimodal CT who underwent EVT between January 2015 and January 2022.

Hourglass-Shaped Homo- and Heteronuclear Nonanuclear Lanthanide Clusters: Structures, Magnetism, Photoluminescence, and Theoretical Analysis.

Synthesis of nonameric cationic clusters [Dy(acac)(μ-OH)(μ-OH)]OH·6HO (), [DyTb (acac)(μ-OH)(μ-OH)]OH·2HO (), and [Gd(acac)(μ-OH)(μ-OH)]OH·6HO () (acac = acetylacetonate) is reported. The emission spectrum of shows Dy(III) ion characteristic bands assignable to the F → H ( = 15/2 to 9/2) transitions. Emission due to both Dy(III) and Tb(III) ions is observed for in the visible range, with Tb(III) specific bands appearing due to the D → F ( = 6, 4, and 3) transitions.

Impact of Blood Pressure Targets in Patients With Heart Failure Undergoing Postresuscitation Care: A Subgroup Analysis From a Randomized Controlled Trial.

Background: To assess the effect of targeting higher or lower blood pressure during postresucitation intensive care among comatose patients with out-of-hospital cardiac arrest with a history of heart failure.

Methods: The BOX trial (Blood Pressure and Oxygenation Targets After Out-of-Hospital Cardiac Arrest) was a randomized, controlled, double-blinded, multicenter study comparing titration of vasopressors toward a mean arterial pressure (MAP) of 63 versus 77 mm Hg during postresuscitation intensive care. Patients with a history of heart failure were included in this substudy.

Is Upper Extremity or Lower Extremity Function More Important for Patient Satisfaction? An Analysis of 24-Month Outcomes from the QOD Cervical Spondylotic Myelopathy Cohort.

Study Design: Retrospective analysis of a prospective, multicenter registry.

Objective: To assess whether upper or lower limb mJOA improvement more strongly associates with patient satisfaction after surgery for cervical spondylotic myelopathy (CSM).

Summary Of Background Data: The modified Japanese Orthopaedic Association (mJOA) is commonly used to assess functional status in patients with CSM.

Outcomes with General Anesthesia Compared to Conscious Sedation for Endovascular Treatment of Medium Vessel Occlusions: Results of an International Multicentric Study.

Background: Optimal anesthetic strategy for the endovascular treatment of stroke is still under debate. Despite scarce data concerning anesthetic management for medium and distal vessel occlusions (MeVOs) some centers empirically support a general anesthesia (GA) strategy in these patients.

Methods: We conducted an international retrospective study of MeVO cases.

Cerebrospinal Fluid cfDNA Sequencing for Classification of Central Nervous System Glioma.

Purpose: Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses.

Experimental Design: We performed targeted next-generation sequencing of CSF cfDNA in a representative cohort of 85 patients presenting at two neurooncological centers with suspicion of primary or recurrent glioma.

Factor XI Inhibition With Heparin Reduces Clot Formation in Simulated Pediatric Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) supplies circulatory support and gas exchange to critically ill patients. Despite the use of systemic anticoagulation, blood exposure to ECMO surfaces causes thromboembolism complications. Inhibition of biomaterial surface-mediated activation of coagulation factor XI (FXI) may prevent device-associated thrombosis.

On-Surface Synthesis and Characterization of a High-Spin Aza-[5]-Triangulene.

Triangulenes are a class of open-shell triangular graphene flakes with total spin increasing with their size. In the last years, on-surface-synthesis strategies have permitted fabricating and engineering triangulenes of various sizes and structures with atomic precision. However, direct proof of the increasing total spin with their size remains elusive.

Increased Metabolic Potential, Efficacy, and Safety of Emerging Treatments in Schizophrenia.

Patients with schizophrenia experience a broad range of detrimental health outcomes resulting from illness severity, heterogeneity of disease, lifestyle behaviors, and adverse effects of antipsychotics. Because of these various factors, patients with schizophrenia have a much higher risk of cardiometabolic abnormalities than people without psychiatric illness. Although exposure to many antipsychotics increases cardiometabolic risk factors, mortality is higher in patients who are not treated versus those who are treated with antipsychotics.

Potential of Urine Biomarkers CHI3L1, NGAL, TIMP-2, IGFBP7, and Combinations as Complementary Diagnostic Tools for Acute Kidney Injury after Pediatric Cardiac Surgery: A Prospective Cohort Study.

Acute kidney injury (AKI) is common after pediatric cardiac surgery (CS). Several urine biomarkers have been validated to detect AKI earlier. The objective of this study was to evaluate urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck as predictors for AKI ≥ 1 in pediatric CS after 48 h and AKI ≥ 2 after 12 h.

Global detection of human variants and isoforms by deep proteome sequencing.

An average shotgun proteomics experiment detects approximately 10,000 human proteins from a single sample. However, individual proteins are typically identified by peptide sequences representing a small fraction of their total amino acids. Hence, an average shotgun experiment fails to distinguish different protein variants and isoforms.

A Focus on Subtle Signs and Motor Behavior to Unveil Awareness in Unresponsive Brain-Impaired Patients: The Importance of Being Clinical.

Brain-injured patients in a state of cognitive motor dissociation (CMD) exhibit a lack of command following using conventional neurobehavioral examination tools but a high level of awareness and language processing when assessed using advanced imaging and electrophysiology techniques. Because of their behavioral unresponsiveness, patients with CMD may seem clinically indistinguishable from those with a true disorder of consciousness that affects awareness on a substantial level (coma, vegetative state/unresponsive wakefulness state, or minimally conscious state minus). Yet, by expanding the range of motor testing across limb, facial, and ocular motricity, we may detect subtle, purposeful movements even in the subset of patients classified as vegetative state/unresponsive wakefulness state.

Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

Objectives: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g.

Methods: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible.