Thrombolysis for aneurysmal subarachnoid haemorrhage.

Background: Aneurysmal subarachnoid haemorrhage continues to cause a significant burden of morbidity and mortality despite advances in care. Trials investigating local administration of thrombolytics have reported promising results.

Objectives: - To assess the effect of thrombolysis on improving functional outcome and case fatality following aneurysmal subarachnoid haemorrhage - To determine the effect of thrombolysis on the risk of cerebral artery vasospasm, delayed cerebral ischaemia, and hydrocephalus following subarachnoid haemorrhage - To determine the risk of complications of local thrombolysis in aneurysmal subarachnoid haemorrhage SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (last searched 9 March 2023), MEDLINE Ovid (1946 to 9 March 2023), and Embase Ovid (1974 to 9 March 2023).

Understanding Cancer Treatment Decision Making Among Cancer Survivors: Weighing Cancer Recurrence Versus Cardiotoxicity.

Background: Nearly 20% of US cancer survivors develop cardiovascular disease (CVD) from cardiotoxic cancer treatments. Patients and providers may consider alternative treatments to lower cardiotoxicity risk, but these may be less effective at preventing relapse/recurrence, presenting a difficult tradeoff.

Aims: This study explored survivors' cancer treatment decision-making when weighing this tradeoff.

Plasma proteomic biomarkers as mediators or moderators for the association between poor cardiovascular health and white matter microstructural integrity: The UK Biobank study.

Introduction: The plasma proteome's mediating or moderating roles in the association between poor cardiovascular health (CVH) and brain white matter (WM) microstructural integrity are largely unknown.

Methods: Data from 3953 UK Biobank participants were used (40-70 years, 2006-2010), with a neuroimaging visit between 2014 and 2021. Poor CVH was determined using Life's Essential 8 (LE8) and reversing standardized z-scores (LE8 ).

Highly Efficient Compositional and Compound Specific Isotopic Analysis of Volatile Primary Amines and Ammonia in the Murchison Meteorite Using SPME On-Fiber Derivatization: Optimization for Bennu Sample Analyses.

Rationale: Extraterrestrial amines and ammonia are critical ingredients for the formation of astrobiologically important compounds such as amino acids and nucleobases. However, conventional methods for analyzing the composition and isotopic ratios of volatile amines suffer from lengthy derivatization and purification procedures, high sample mass consumption, and chromatographic interferences from derivatization reagents and non-target compounds.

Methods: Here we demonstrate a highly efficient method to analyze the composition and compound specific isotopic ratios of C to C amines as well as ammonia based on solid phase micro-extraction (SPME) on-fiber derivatization.

Internalizing Psychiatric Symptoms in People With Mosaicism for Trisomy 21.

People with mosaicism for trisomy 21 have been shown to exhibit many of the same phenotypic traits present in people with non-mosaic Down syndrome, but with varying symptom severity. However, the behavioral phenotype of people with mosaic Down syndrome (mDS) has not been well characterized. This study aimed to examine the prevalence of self-report and caregiver-report symptoms of depression and anxiety among a sample of 62 participants with mDS aged 12-46 and assess their association with the percentage of trisomy 21 in blood and/or buccal mucosa cells.

digitalMALDI: A Single-Particle-Based Mass Spectrometric Detection System for Biomolecules.

The development of a real-time system for characterizing individual biomolecule-containing aerosol particles presents a transformative opportunity to monitor respiratory conditions, including infections and lung diseases. Existing molecular assay technologies, although effective, rely on costly reagents, are relatively slow, and face challenges in multiplexing, limiting their use for real-time applications. To overcome these challenges, we developed digitalMALDI, a laser-based mass spectrometry system designed for single-particle characterization.

A Retrospective Review of Oral N-Acetylcysteine for Habit-Driven Cutaneous Disorders.

Oral N-acetylcysteine (NAC) has shown efficacy for debilitating habit-driven and neuropsychiatric disorders in small, mostly adult studies. We retrospectively evaluated the therapeutic use and safety of oral NAC in 93 children from the Children's Hospital of Philadelphia. This study supports the use of oral NAC for habit-driven skin, hair, and nail abnormalities in pediatric patients.

Associations between blood donors, component modifications, and the alloimmunization of transfusion recipients.

Background: Prior studies have evaluated transfusion recipient variables impacting red blood cell (RBC) alloimmunization, but few focused on potentially modifiable blood donor or blood component variables.

Study Design And Methods: Data from the Recipient Epidemiology and Donor Evaluation Study (REDS)-III, which links donor, component, and patient data in an integrated database, were accessed. For any given RBC unit with sufficient blood donor and component data, we determined if the transfusion recipient experienced a new RBC alloimmunization event ("case") within 16 weeks of the transfusion or not ("control").

Psychosocial Support Needs and Preferences Among Family Caregivers of ICU Patients with Severe Acute Brain Injury: A Qualitative Thematic Analysis.

Background: Family caregivers of patients with severe acute brain injury (SABI) are at risk for clinically significant chronic emotional distress, including depression, anxiety, and posttraumatic stress. Existing psychosocial interventions for caregivers of intensive care unit (ICU) patients are not tailored to the unique needs of caregivers of patients with SABI, do not demonstrate long-term efficacy, and may increase caregiver burden. In this study, we explored the needs and preferences for psychosocial services among SABI caregivers to inform the development and adaptation of interventions to reduce their emotional distress during and after their relative's ICU admission.

Delivering Guideline-Concordant Care for Patients With High-Risk HPV and Normal Cytologic Findings.

Importance: As US health care systems shift to human papillomavirus (HPV)-based cervical cancer screening, more patients are receiving positive high-risk non-16/18 genotype HPV results and negative for intraepithelial lesion or malignancy (NILM) cytological findings. Risk-based management guidelines recommend 2 consecutive negative annual results to return to routine screening.

Objective: To quantify patterns of surveillance testing and associated outcomes for patients after an HPV-positive results and NILM cytologic findings.

Risk Profile and Prognostic Implications of Premature Advanced Coronary Atherosclerotic Disease Among Young to Early Middle-aged Adults: The Coronary Artery Calcium Consortium.

Introduction: Premature advanced subclinical coronary atherosclerosis among young adults is an under-recognized and unique disease phenotype that has not been well characterized.

Methods: We used data from 44,047 participants with no prior CVD history (59.8% male) from the Coronary Artery Calcium (CAC) Consortium.

Distinct molecular and clinical features of specific variants of KRAS codon 12 in pancreatic adenocarcinoma.

PURPOSE Oncogenic mutations in KRAS have been identified in > 85% of pancreatic ductal adenocarcinoma (PDAC) cases. G12D, G12V, and G12R are the most frequent variants. Using large clinical and genomic databases, this study characterizes prognostic and molecular differences between KRAS variants, focusing on KRAS G12D and G12R.

Personalized Dynamic Prediction Model for Biopsy Timing in Patients With Prostate Cancer During Active Surveillance.

Importance: Active surveillance (AS) for patients with prostate cancer (PC) often includes fixed repeat prostate biopsies that do not account for the varying risk of reclassification to significant disease. Given the invasive nature and potential complications of biopsies, a personalized approach is needed to balance the burden of biopsies with the risk of missing disease progression.

Objective: To develop and externally validate a dynamic model that predicts an individual's risk of PC reclassification during AS.

Mpox: What have we learned and how do we better prepare for the future?

The global outbreak of clade IIb mpox in 2022-2023 changed our understanding of the epidemiology and prevention of mpox, simultaneously highlighting inequities in access to vaccines, diagnostics, and therapeutics. With the recent multinational spread of clade Ib mpox, it is important to revisit these lessons to improve future response. In September 2024, an international mpox symposium was held at Johns Hopkins University to discuss what we have learned and how to better prepare for the future.

Progress and Outcomes of Intraoperative Nerve Monitoring During Thyroidectomy.

Importance: Intraoperative nerve monitoring (IONM) is not considered standard of care during thyroidectomy, and guidelines are vague about its use in the absence of strong evidence of superiority over visualization of the recurrent laryngeal nerve (RLN) alone.

Objective: To characterize patterns of IONM use during thyroidectomy in the US and evaluate the association of IONM with postoperative outcomes.

Design, Setting, And Participants: This cohort study used the National Surgical Quality Improvement Program (NSQIP) thyroidectomy data from January 1, 2016, to December 31, 2022.

PSMA+ Extracellular Vesicles are a Biomarker for SABR in Oligorecurrent Prostate Cancer Analysis from the STOMP-like and ORIOLE trial cohorts.

Purpose: Two randomized clinical trials (STOMP and ORIOLE) demonstrated that stereotactic ablative radiotherapy (SABR) can prolong ADT-free survival or progression-free survival (PFS) in patients with metachronous oligometastatic prostate cancer (omCSPC) patients. While most omCSPC patients have a more modest delay in progression, a small subset achieves a durable response following SABR. We investigated the prognostic and predictive value of circulating PSMA-positive extracellular vesicles (PSMA+EV) and prostate specific antigen (PSA) in a biomarker correlative study using blood samples from three independent patient cohorts.

CooccurrenceAffinity: An R package for computing a novel metric of affinity in co-occurrence data that corrects for pervasive errors in traditional indices.

1. Analysis of co-occurrence data with traditional indices has led to many problems such as sensitivity of the indices to prevalence and the same value representing either a strong positive or strong negative association across different datasets. In our recent study (Mainali et al 2022), we revealed the source of the problems that make the traditional indices fundamentally flawed and unreliable-namely that the indices in common use have no target of estimation quantifying degree of association in the non-null case-and we further developed a novel parameter of association, alpha, with complete formulation of the null distribution for estimating the mechanism of affinity.

Loneliness and biomarkers of Alzheimer's disease, axonal damage, and astrogliosis: A coordinated analysis of two longitudinal cohorts.

Objectives: Loneliness is associated with an elevated risk of dementia. There is mixed evidence from imaging studies on whether loneliness is associated with neuropathology in dementia-free adults. This study tests whether loneliness is associated with plasma neurobiomarkers of amyloid (Aβ42/Aβ40), phosphorylated tau 181 (pTau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) and imaging measures of amyloid and tau.

Phase I study of adavosertib with radiation therapy and temozolomide in newly diagnosed glioblastoma and intratumoral drug levels in recurrent glioblastoma.

Purpose: Adavosertib is an oral small molecular inhibitor of Wee1. The Adult Brain Tumor Consortium performed a phase I study of adavosertib, radiation (RT) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) as well as a surgical window of opportunity study in recurrent GBM.

Patients And Methods: The maximum tolerated dose (MTD) of adavosertib was determined in adult patients with newly diagnosed GBM using a standard 3+3 design in 2 separate cohorts: with concurrent RT/TMZ or with adjuvant TMZ.

Community engagement to inform multi-level analyses of the role of neighborhood factors in cancer control behaviors in African Americans.

Background: While community engagement has had a substantial presence in public health research, community input to inform geospatial and health analyses remains underutilized and novel. This manuscript reports on community engagement activities to solicit stakeholder perspectives on the role of neighborhood conditions in health and cancer. We discuss how this community input refined a priori conceptual model to be tested in the larger Families, Friends, and Neighborhoods (FFAN) Study.

Mode of Delivery and Subsequent Motor Function in Children With Myelomeningocele Without In Utero Repair.

Objective: To assess the association between mode of delivery and 2-year motor function in children with prenatal diagnosis of myelomeningocele.

Methods: A multisite retrospective cohort study of children with myelomeningocele across 14 NAFTNet (North American Fetal Therapy Network) centers born between 2007 and 2020 who had a physical examination available at 2 years of life. Exclusion criteria were in utero myelomeningocele repair, postnatal myelomeningocele diagnosis, missing data on fetal presentation at delivery, and contraindications to labor.