Safety and toxicity of Iopofosine I 131 (CLR 131) with external beam radiation therapy in recurrent or metastatic head and neck cancer: results of a phase 1 single-centre, open-label, single-arm, dose escalation and dose expansion study.

Background: Re-irradiation of recurrent head and neck cancer (HNC) is often limited by tumour adherence to critical structures and/or radiation tolerance of critical normal tissues. Iopofosine I 131 (CLR 131) is a targeted small molecular phospholipid ether (PLE) drug conjugate that delivers iodine-131 selectively to tumour cells. We conducted a phase 1, single-centre, open-label study to determine whether CLR 131 given with reduced dose of external beam radiation therapy (EBRT) would be tolerable and feasible.

Subgroup analyses and heterogeneity of treatment effects in randomized trials: a primer for the clinician.

Purpose Of Review: To date, most randomized clinical trials in critical care report neutral overall results. However, research as to whether heterogenous responses underlie these results and give opportunity for personalized care is gaining momentum but has yet to inform clinical practice guidance. Thus, we aim to provide an overview of methodological approaches to estimating heterogeneity of treatment effects in randomized trials and conjecture about future paths to application in patient care.

Early ultrasonic vocalization deficits and related thyroarytenoid muscle pathology in the transgenic TgF344-AD rat model of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurologic disease and the most common cause of dementia. Classic pathology in AD is characterized by inflammation, abnormal presence of tau protein, and aggregation of β-amyloid that disrupt normal neuronal function and lead to cell death. Deficits in communication also occur during disease progression and significantly reduce health, well-being, and quality of life.

Mechanisms behind changes of neurodegeneration biomarkers in plasma induced by sleep deprivation.

Acute sleep deprivation has been shown to affect cerebrospinal fluid and plasma concentrations of biomarkers associated with neurodegeneration, though the mechanistic underpinnings remain unknown. This study compared individuals who, for one night, were either subject to total sleep deprivation or free sleep, (i) examining plasma concentrations of neurodegeneration biomarkers the morning after sleep deprivation or free sleep and (ii) determining how overnight changes in biomarkers plasma concentrations correlate with indices of meningeal lymphatic and glymphatic clearance functions. Plasma concentrations of amyloid-β 40 and 42, phosphorylated tau peptide 181, glial fibrillary acid protein and neurofilament light were measured longitudinally in subjects who from Day 1 to Day 2 either underwent total sleep deprivation ( = 7) or were allowed free sleep ( = 21).

Urologic practice patterns of pediatricians: a survey from a large multisite pediatric care center.

Objective: To evaluate the practice patterns of pediatricians as they relate to common urologic concerns.

Materials And Methods: An anonymous 15-question survey was created and distributed to all pediatricians at our institution, a large multisite care center. This study was deemed exempt by the institutional review board.

Cerebrospinal Fluid Sphingomyelins in Alzheimer's Disease, Neurodegeneration, and Neuroinflammation.

Background: Sphingomyelin (SM) levels have been associated with Alzheimer's disease (AD), but the association direction has been inconsistent and research on cerebrospinal fluid (CSF) SMs has been limited by sample size, breadth of SMs examined, and diversity of biomarkers available.

Objective: Here, we seek to build on our understanding of the role of SM metabolites in AD by studying a broad range of CSF SMs and biomarkers of AD, neurodegeneration, and neuroinflammation.

Methods: Leveraging two longitudinal AD cohorts with metabolome-wide CSF metabolomics data (n = 502), we analyzed the relationship between the levels of 12 CSF SMs, and AD diagnosis and biomarkers of pathology, neurodegeneration, and neuroinflammation using logistic, linear, and linear mixed effects models.

Development of a Pharmacist-Led Opt-Out Cessation Treatment Protocol for Combustible Tobacco Smoking Within Inpatient Settings.

Although people who smoke cigarettes are overrepresented among hospital inpatients, few are connected with smoking cessation treatment during their hospitalization. Training, accountability for medication use, and monitoring of all patients position pharmacists well to deliver cessation interventions to all hospitalized patients who smoke. A large Midwestern University hospital implemented a pharmacist-led smoking cessation intervention.

Stromal Characteristics and Impact on New Therapies for Metastatic Triple-Negative Breast Cancer.

The heterogenous nature of triple-negative breast cancer (TNBC) is an underlying factor in therapy resistance, metastasis, and overall poor patient outcome. The lack of hormone and growth factor receptors lends to the use of chemotherapy as the first-line treatment for TNBC. However, the failure of chemotherapy demonstrates the need to develop novel immunotherapies, antibody-drug conjugates (ADCs), and other tumor- and stromal-targeted therapeutics for TNBC patients.

Impaired Microvascular Response to Muscle Stretching in Chronic Smokers With Type 2 Diabetes.

Objective: Cigarette smoking promotes endothelial dysfunction and is a prominent catalyst for vascular disease. This study employed laser doppler flowmetry (LDF) and spectral analysis to investigate the skin microvascular response to relatively mild stimulus of stretching in diabetic smokers.

Methods: The study population consisted of thirty type 2 diabetic male patients (15 smokers vs.

Feasibility and optimization of ultra-short echo time MRI for improved imaging of IVC-filters at 3.0 T.

Purpose: To determine the feasibility of ultra-short echo time (UTE) MRA for assessment of inferior vena cava (IVC) filters and evaluate the impact of different imaging protocols at 3.0 T, using conventional Cartesian MRA (cMRA) as the reference standard.

Methods: Patients with IVC-filters were recruited for this prospective IRB-approved, HIPAA-compliant study.

Listeria Cerebritis with Tumor Necrosis Factor Inhibition.

Background: is historically a central nervous system pathogen of consideration in the very young, very old, and immune suppressed. Diagnosis of is based on positive bodily fluid culture or PCR testing. Cerebral edema is nonspecific and can be a manifestation of vasculitis, trauma, anoxia, ischemia, infarction, malignancy, or an infectious process.

Outcome-Related Signatures Identified by Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated after Starting Hu14.18-IL2.

Purpose: We analyzed whole transcriptome sequencing in tumors from 23 patients with stage III or IV melanoma from a pilot trial of the anti-GD2 immunocytokine, hu14.18-IL2, to identify predictive immune and/or tumor biomarkers in patients with melanoma at high risk for recurrence.

Experimental Design: Patients were randomly assigned to receive the first of three monthly courses of hu14.

γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity.

γδ T cells in human solid tumors remain poorly defined. Here, we describe molecular and functional analyses of T-cell receptors (TCR) from tumor-infiltrating γδ T lymphocytes (γδ TIL) that were in direct contact with tumor cells in breast cancer lesions from archival material. We observed that the majority of γδ TILs harbored a proinflammatory phenotype and only a minority associated with the expression of IL17.

Phenotype of children with inconclusive cystic fibrosis diagnosis after newborn screening.

Objective: To characterize the phenotypic expression of children with conductance regulator-related metabolic syndrome (CRMS)/cystic fibrosis screen positive inconclusive diagnosis (CFSPID) designation after positive newborn screening, reassign labeling if applicable and better define these children's prognosis.

Methods: A multicenter cohort with CRMS/CFSPID designation was matched with cystic fibrosis (CF)-diagnosed cohort. Cohorts were prospectively compared on baseline characteristics, cumulative data and when they reached 6 to 7 years at endpoint assessment.

Epinephrine-induced electrical storm after aortic surgery.

Electrical storm (ES) is a potentially lethal syndrome defined as three or more sustained episodes of ventricular tachycardia or ventricular fibrillation within 24 h. There are multiple inciting factors for ES, one of which involves excess catecholamine (endogenous and exogenous) effects. Exogenous catecholamines used for hemodynamic support can paradoxically engender or exacerbate an underling arrhythmia leading to ES.

Cardiac arrhythmia from epinephrine overdose in epidural test dose.

Medication shortages are a clinical reality that force changes in practice patterns leading to unintended consequences. Potential solutions to any drug shortage require a thoughtful, multidisciplinary and often creative approach. Here, we report a case of unintentional epinephrine overdose leading to an unstable cardiac arrhythmia and our subsequent development of a visual cue system to prevent future errors.

Molecular detection of human T-lymphotropic virus type 1 infection among oncology patients in Germany: A retrospective view.

Human T-cell lymphotropic virus (HTLV) belongs to a larger group of primate T-cell lymphotropic viruses (PTLVs) within the family Retroviridae. It is estimated that 10 to 20 million people worldwide may be infected with HTLV-1. Although most of them are asymptomatic, around 5% of infected individuals may develop either HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or Adult T-cell Leukaemia/Lymphoma (ATLL).

Integrating Electrochemical Immunosensing and Cell Adhesion Technologies for Cancer Cell Detection and Enumeration.

We have successfully integrated techniques for controlling cell adhesion and performing electrochemical differential pulse voltammetry (DPV) through the use of digitally controlled microfluidics and patterned transparent indium tin oxide electrode arrays to enable rapid and sensitive enumeration of cancer cells in a scalable microscale format. This integrated approach leverages a dual-working electrode (WE) surface to improve the specificity of the detection system. Here, one of the WE surfaces is functionalized with anti-Melanocortin 1 Receptor antibodies specific to melanoma cancer cells, while the other WE acts as a control (i.

Early transplantation into a vesicostomy: a safe approach for managing patients with severe obstructive lesions who are not candidates for bladder augmentation.

Introduction: Management of severe antenatally detected oligohydramnios with and without obstruction is improving with the result that more fetuses are surviving with early renal failure. Significant advances have occurred in all specialties involved in the management of these patients. All these specialties working together have resulted in the survival of more patients born with renal failure.

The enteric nervous system in PD: gateway, bystander victim, or source of solutions.

Apart from the characteristic and progressive motor- and movement-related problems, Parkinson's disease (PD) patients also suffer from several non-motor symptoms, including gastrointestinal dysfunction. The fact that the enteric nervous system (ENS) controls motility and that one of the typical PD hallmarks, α-synuclein-positive deposits, has also been found in the intestinal wall have rendered the ENS and the gut a popular subject of study in the context of PD. The possibility that these deposits could serve as an early biomarker is obviously of tremendous medical benefit but also the idea that the gut may possibly be a gateway via which the disease is initiated and progressively makes its way via the peripheral nerves to the central nervous system has increased the interest in the ENS-PD link.

Simultaneous determination of dynamic cardiac metabolism and function using PET/MRI.

Background: Cardiac metabolic changes in heart disease precede overt contractile dysfunction. However, metabolism and function are not typically assessed together in clinical practice. The purpose of this study was to develop a cardiac positron emission tomography/magnetic resonance (PET/MR) stress test to assess the dynamic relationship between contractile function and metabolism in a preclinical model.