Novel approaches to treatment of leptomeningeal metastases.

Purpose Of Review: The incidence of leptomeningeal metastases is increasing in the setting of improved survival from systemic cancers. In more recent years, our understanding of leptomeningeal metastasis pathogenesis, how to diagnose and treat has been evolving.

Recent Findings: Diagnosing leptomeningeal metastasis has been challenging due to the limitations of cytology and neuroimaging; However, newer techniques detecting circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) have shown potential advantage with diagnosis, quantification and detection of oncogenic mutations.

Why the Post- Era Requires Protecting Conscientious Provision as We Protect Conscientious Refusal in Health Care.

The US Supreme Court overturned in June 2022, and now each state's legislature will decide if and when its citizens will have legal access to abortion care and if and when its physicians will be criminalized for providing what is considered to be the standard of care by multiple health-related organizations. This extraordinary change in the medico-legal landscape requires reevaluation of health profession codes of ethics related to clinician conscience. This article argues that these codes must now be expanded to address 2 newly critical areas: physician advocacy to make abortion illegal and affirmative protection for "conscientious provision" in hostile environments on par with protection of conscientious refusal.

A phase I/II study of intrathecal trastuzumab in human epidermal growth factor receptor 2-positive (HER2-positive) cancer with leptomeningeal metastases: Safety, efficacy, and cerebrospinal fluid pharmacokinetics.

Background: Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum-tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive leptomeningeal disease (LMD).

Methods: This multicenter study enrolled 34 LMD patients in a combined phase I/II study in treating patients with intrathecal trastuzumab.

Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions.

Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management.

How Should Representation of Subjects With LEP Become More Equitable in Clinical Trials?

Underrepresentation of individuals with limited English proficiency (LEP) who speak Spanish is ongoing in phase 3 biomedical clinical trials and exacerbates health inequity. This article suggests strategies for increasing representation of Spanish speakers in clinical rials by emphasizing the importance of early engagement with Spanish language communities, inclusive participant recruitment, and collaborative trial design and implementation. Although investigators and institutions administering government-funded research must meet federal requirements for language assistance, journal editors, peer reviewers, institutional review board members, academic health centers, and all beneficiaries of the biomedical and behavioral research enterprise in the United States must motivate linguistic inclusion.

Pediatric Burns Unique Characteristics Among Ultra-Orthodox Jewish Minority-Retrospective Study.

Burn injuries are a significant cause of morbidity among children. Ultra-Orthodox Jewish children are at higher risk for burn injuries. The goal of this study was to examine the clinical characteristics of moderate to severe burns in this population in comparison to the general population in Israel.

Time-Variant SRC Kinase Activation Determines Endothelial Permeability Response.

In the current model of endothelial barrier regulation, the tyrosine kinase SRC is purported to induce disassembly of endothelial adherens junctions (AJs) via phosphorylation of VE cadherin, and thereby increase junctional permeability. Here, using a chemical biology approach to temporally control SRC activation, we show that SRC exerts distinct time-variant effects on the endothelial barrier. We discovered that the immediate effect of SRC activation was to transiently enhance endothelial barrier function as the result of accumulation of VE cadherin at AJs and formation of morphologically distinct reticular AJs.

Why We Should Stop Using the Term "Elective Abortion".

In abortion care, the term "elective" is often used as a moral judgment that determines which patients are entitled to care. Secular health care organizations that attempt to avoid controversy by allowing "therapeutic" but not "elective" abortions are using medical terminology to reinforce regressive social norms concerning motherhood and women's sexuality because what distinguishes pregnant women with medical indications for abortion is that they originally wanted to become mothers or, in cases of rape, that they did not consent to sex. Secular health care organizations should stop denying the moral agency of patients and physicians who conclude abortion is morally acceptable and should only use the word when billing codes require it.

Interprofessionalism and the Practice of Health Psychology in Hospital and Community: Walking the Bridge Between Here and There.

Interprofessionalism is a cornerstone for health care reform and is an important dimension for success for the practice of professional psychology in integrated care settings, whether in academic health centers, ambulatory clinics, or in independent practice. This article examines salient skills that have allowed the author to practice in both primary and tertiary health care settings, as well as in academic health centers and independent community practice. The scientist practitioner model of professional psychology has served to guide the author as a "roadmap" for successful collaborative, integrated care in the changing health care environment.

Targeted Recycling of the Lateral Border Recycling Compartment Precedes Adherens Junction Dissociation during Transendothelial Migration.

Leukocyte transendothelial migration (TEM) requires two major events: local dissociation of adherens junctions manifested as gaps in vascular endothelial (VE)-cadherin staining at the site of TEM and targeted trafficking of the lateral border recycling compartment (LBRC) to the site of TEM. However, the association between LBRC recycling and VE-cadherin gaps remains unknown. We found that when targeting of the LBRC is selectively inhibited using established methods, such as a function blocking anti-platelet endothelial cell adhesion molecule 1 antibody, depolymerizing microtubules, or microinjection of an antibody that inhibits kinesin, VE-cadherin gaps do not form around the blocked leukocyte.

Early administration of oxybutynin improves bladder function and clinical outcomes in newborns with posterior urethral valves.

Purpose: Abnormal bladder function following posterior urethral valve ablation can lead to deleterious effects on renal function and urinary continence. We performed a pilot study to determine if bladder dysfunction could be ameliorated by the early administration of oxybutynin.

Materials And Methods: We enrolled infants who underwent primary posterior urethral valve ablation by the age of 12 months.

Type XVII collagen regulates lamellipod stability, cell motility, and signaling to Rac1 by targeting bullous pemphigoid antigen 1e to alpha6beta4 integrin.

Rac1 activity, polarity, lamellipodial dynamics, and directed motility are defective in keratinocytes exhibiting deficiency in β4 integrin or knockdown of the plakin protein Bullous Pemphigoid Antigen 1e (BPAG1e). The activity of Rac, formation of stable lamellipodia, and directed migration are restored in β4 integrin-deficient cells by inducing expression of a truncated form of β4 integrin, which lacks binding sites for BPAG1e and plectin. In these same cells, BPAG1e, the truncated β4 integrin, and type XVII collagen (Col XVII), a transmembrane BPAG1e-binding protein, but not plectin, colocalize along the substratum-attached surface.

Do current bladder smooth muscle cell isolation procedures result in a homogeneous cell population? Implications for bladder tissue engineering.

Purpose: Conventional techniques used to harvest and culture bladder smooth muscle cells (SMCs) have been thought to yield homogeneous populations of SMCs. In order to delineate the cellular composition of tissue derived bladder cells, this study was conducted to determine whether current culturing techniques result in a uniform population of bladder SMCs that may be utilized for bladder tissue engineering.

Methods: Patient derived bladder muscle was isolated and manually minced followed by enzymatic digestion.

Integrin cross-talk in endothelial cells is regulated by protein kinase A and protein phosphatase 1.

In endothelial cells (ECs) beta1 integrin function-blocking antibodies inhibit alphavbeta3 integrin-mediated adhesion to a recombinant alpha4-laminin fragment (ralpha4LN fragment). beta1 integrin sequestration of talin is not the mechanism by which beta1 integrin modulates alphavbeta3 integrin ligand binding. Rather, treatment of the ECs with beta1 integrin function-blocking antibodies enhances cAMP-dependent protein kinase (PKA) activity and increases beta3 integrin serine phosphorylation.

Alternatively spliced human tissue factor promotes tumor growth and angiogenesis in a pancreatic cancer tumor model.

Introduction: Tissue Factor (TF) expression is observed in many types of cancer, associated with more aggressive disease, and thrombosis. Alternatively-spliced human tissue factor (asHTF) has recently been identified in which exon 5 is deleted. asHTF is soluble due to the substitution of the transmembrane and cytoplasmic domains of exon 6 with a unique COOH-terminal domain.

Non-traditional management of the neurogenic bladder: tissue engineering and neuromodulation.

Patients with spina bifida and a neurogenic bladder have traditionally been managed with clean intermittent catheterization and pharmacotherapy in order to treat abnormal bladder wall dynamics, protect the upper urinary tract from damage, and achieve urinary continence. However, some patients will fail this therapy and require surgical reconstruction in the form of bladder augmentation surgery using reconfigured intestine or stomach to increase the bladder capacity while reducing the internal storage pressure. Despite functional success of bladder augmentation in achieving a low pressure reservoir, there are several associated complications of this operation and patients do not have the ability to volitionally void.

Factors that influence the acceptability of collecting in-home finger stick blood samples in an urban, low-income population.

Objectives: To examine the acceptability of non-medical, community-based interviewers obtaining blood samples during in-home interviews from low-income study participants.

Methods: Two separate focus groups were conducted, one with ten non-medical community-based interviewers and the other with eight research participants from a low-income population. (Both the interviewers and the research participants had previously taken part in a research project over the course of five years.

Effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children.

Objectives: We sought to determine the effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children and to assess whether such changes are associated with morbidity.

Methods: At 6 perioperative time points in 25 patients, plasma levels of atrial natriuretic peptide, brain natriuretic peptide, and guanosine 3', 5'-monophosphate were measured, and the biologic activity of the natriuretic hormone system was quantified. Relationships were sought between changes in brain natriuretic peptide levels, biologic activity, and a number of morbidity indicators.