UW Neurological Surgery Recent PubMed Publications

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC ( NCT03214250 ). In 105 patients analyzed for efficacy, the primary endpoint of...

Anemia is a common finding in a human immunodeficiency virus (HIV)-positive patient with a wide range of possible causes and is a significant risk factor for mortality in acquired immunodeficiency syndrome (AIDS). Opportunistic parvovirus infection-causing pure red cell aplasia is one of its uncommon causes. It has been suggested that immunocompromised patients with abnormal antibody production are more susceptible to acquiring a chronic parvovirus infection requiring long-term intravenous...

CONCLUSIONS: This work presents a quantitatively validated whole-brain simulation of CSF flow for a single healthy subject. The computational methodology improves over the state of the art by eliminating non-physiological boundary conditions and unnecessary assumptions about the mechanical properties of brain tissue, providing an essential step towards clinically useful tools for assessing the development of neurodegenerative disorders.

Background: Most people with alcohol use disorder do not receive treatment, and primary care (PC)-based management of alcohol use disorder is a key strategy to close this gap. Understanding PC patients' perspectives on changing drinking and receiving alcohol-related care is important for this goal, particularly among those who decline alcohol-related care. This study examined perspectives on barriers and facilitators to changing drinking and receiving alcohol-related care among Veterans Health...

Voltage-gated Ca^(2+) (Ca(v)) channels play pivotal roles in regulating gene transcription, neuronal excitability, and neurotransmitter release. To meet the spatial and temporal demands of visual signaling, Ca(v) channels exhibit unusual properties in the retina compared to their counterparts in other areas of the nervous system. In this article, we review current concepts regarding the specific subtypes of Ca(v) channels expressed in the retina, their intrinsic properties and forms of...

The creation of patient-derived cancer organoids represents a key advance in preclinical modeling and has recently been applied to a variety of human solid tumor types. However, conventional methods used to assess in vivo tumor tissue treatment response are poorly suited for the evaluation of cancer organoids because they are time-intensive and involve tissue destruction. To address this issue, we established a suite of 3-dimensional patient-derived glioma organoids, treated them with...

CONCLUSION: The TBI-PRO model adequately estimates long-term outcomes in patients with TBI.

Contaminants of emerging concern (CEC) localize in the biome in variable combinations of complex mixtures that are often environmentally persistent, bioaccumulate and biomagnify, prompting a need for extensive monitoring. Many cosmetics include UV filters that are listed as CECs, such as benzophenone derivatives (oxybenzone, OXYB), cinnamates (2-ethylhexyl 4-methoxycinnamate, EMC) and camphor derivatives (4-methylbenzylidene-camphor, 4MBC). Furthermore, in numerous water sources, these UV...

Emerging evidence suggests that repeated blast exposure (RBE) is associated with brain injury in military personnel. United States (U.S.) Special Operations Forces (SOF) personnel experience high rates of blast exposure during training and combat, but the effects of low-level RBE on brain structure and function in SOF have not been comprehensively characterized. Further, the pathophysiological link between RBE-related brain injuries and cognitive, behavioral, and physical symptoms has not been...

Vaccine-induced sterilizing protection from infection by Plasmodium parasites, the pathogens that cause malaria, will be essential in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive means to this goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface...

Staphylococcus hominis is frequently isolated from human skin, and we hypothesize that it may protect the cutaneous barrier from opportunistic pathogens. We determined that S. hominis makes six unique autoinducing peptide (AIP) signals that inhibit the major virulence factor accessory gene regulator (agr) quorum sensing system of Staphylococcus aureus. We solved and confirmed the structures of three novel AIP signals in conditioned medium by mass spectrometry and then validated synthetic AIP...

CONCLUSIONS: Measuring frailty with mFI-5 additive to established bAVM grading systems may improve assessment of individual patient likelihood of postoperative good functional outcome after hemorrhagic bAVM resection.

CONCLUSION: We report potential risk factors for circulatory shock after moderate-severe TBI. Our study suggests that developing circulatory shock after moderate-severe TBI is associated with poor long-term functional outcomes.

Traumatic brain injury (TBI) remains one of the most fatal and debilitating conditions in the world. Current clinical management in severe TBI patients is mainly concerned with reducing secondary insults and optimizing the balance between substrate delivery and consumption. Over the past decades, multimodality monitoring has become more widely available, and clinical management protocols have been published that recommend potential interventions to correct pathophysiological derangements. Even...

CONCLUSION: Despite a robust and novel experimental medicine approach and evidence of target engagement, anticipated SSc-related biologic effects of GSK2330811 were not different from placebo and safety was unfavourable, suggesting OSM inhibition may not be a useful therapeutic strategy in SSc.

We identified six novel de novo human KCNQ5 variants in children with motor/language delay, intellectual disability (ID), and/or epilepsy by whole exome sequencing. These variants, comprising two nonsense and four missense alterations, were functionally characterized by electrophysiology in HEK293/CHO cells, together with four previously reported KCNQ5 missense variants (Lehman A, Thouta S, Mancini GM, Naidu S, van Slegtenhorst M, McWalter K, Person R, Mwenifumbo J, Salvarinova R; CAUSES Study;...

CONCLUSIONS: Experiences of racial/ethnic discrimination are associated with different research-related outcomes across racial/ethnic groups. Efforts to engage diverse populations should prioritize access to (not willingness to participate in) health-related research.

The N-terminus domain (NTD) of the SARS-CoV-2 Omicron variant spike protien strongly induces multiple inflammatory molecules in human peripheral blood mononuclear cells, unaffected by the mutations observed in the NTD. Olverembatinib, a clinical-stage multi-kinase inhibitor, potently inhibits Omicron NTD-mediated cytokine release.

DTI literature on single-center studies contains conflicting results regarding acute effects of mTBI on WM microstructure and their prognostic significance. This larger-scale multicenter DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From TRACK-TBI, a cohort study at eleven US level 1 trauma centers, a total of 391 acute mTBI patients ages 17-60 years were included and studied at two weeks and six months...

CONCLUSION: HR-QOL outcomes are adversely affected when compared to preoperative status and physical health demonstrates significant attrition over time. HR-QOL outcomes are worse off when compared to an age matched general population. In terms of age, advancing age is associated with worse physical component scores but emotional health may fare better than younger patients.