Vasoactive Agents in Burn Patients - Perspectives on Angiotensin-II.

Severe burn injury poses significant clinical challenges, often necessitating the use of vasoactive agents to maintain perfusion. This narrative review explores the current landscape of vasoactive agents in acute burn shock resuscitation and severe burn-injured patients who develop septic shock, with a particular focus on the potential role of the novel vasoactive agent, synthetic angiotensin-II (AT-II), in these settings. While catecholamines and vasopressin remain cornerstone therapies, adverse effects, variable patient response, and a new understanding of burn injury pathophysiology highlight the potentially evolving role of vasoactive agents in these clinical scenarios.

Improved tracking of corneal immune cell dynamics using confocal microscopy.

confocal microscopy (IVCM) is a widely used technique for imaging the cornea of the eye with a confocal scanning light ophthalmoscope. Cellular resolution and high contrast are achieved without invasive procedures, suiting the study of living humans. However, acquiring useful image data can be challenging due to the incessant motion of the eye, such that images are typically limited by noise and a restricted field of view.

Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency.

Tissue-resident memory T (T) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common T cell fate remains poorly understood. Here, we show that whereas skin T cells strictly require transforming growth factor β (TGF-β) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-β-independent tissue residency program in the liver and synergizing with TGF-β to drive T cells in the small intestine.

Wearable-Enabled Algorithms for the Estimation of Parkinson's Symptoms Evaluated in a Continuous Home Monitoring Setting Using Inertial Sensors.

Motor symptoms such as tremor and bradykinesia can develop concurrently in Parkinson's disease; thus, the ideal home monitoring system should be capable of tracking symptoms continuously despite background noise from daily activities. The goal of this study is to demonstrate the feasibility of detecting symptom episodes in a free-living scenario, providing a higher level of interpretability to aid AI-powered decision-making. Machine learning models trained on wearable sensor data from scripted activities performed by participants in the lab and clinician ratings of the video recordings of these tasks identified tremor, bradykinesia, and dyskinesia in the supervised lab environment with a balanced accuracy of 83%, 75%, and 81%, respectively, when compared to the clinician ratings.

Redefining our vision: an updated guide to the ocular immune system.

Balanced immune responses in the eyes are crucial to preserve vision. The ocular immune system has long been considered distinct, owing to the so-called 'immune privilege' of its component tissues. More recently, intravital imaging and transcriptomic techniques have reshaped scientific understanding of the ocular immune landscape, such as revealing the specialization of immune cell populations in the various tissues of the eye.

Correlation Between Serum and CSF Concentrations of Midazolam and 1-Hydroxy-Midazolam in Critically Ill Neurosurgical Patients.

Background: Midazolam (MZ) is commonly used in critically ill neurosurgical patients. Neuro-penetration of MZ and its metabolite, 1-hydroxy-midazolam (1-OH-MZ), is not well characterized.

Objective: This study evaluated correlations between serum and cerebrospinal fluid (CSF) concentrations of MZ and 1-OH-MZ and assessed implications on patient sedation.

Towards targeting the breast cancer immune microenvironment.

The tumour immune microenvironment is shaped by the crosstalk between cancer cells, immune cells, fibroblasts, endothelial cells and other stromal components. Although the immune tumour microenvironment (TME) serves as a source of therapeutic targets, it is also considered a friend or foe to tumour-directed therapies. This is readily illustrated by the importance of T cells in triple-negative breast cancer (TNBC), culminating in the advent of immune checkpoint therapy in combination with cytotoxic chemotherapy as standard of care for both early and advanced-stage TNBC, as well as recent promising signs of efficacy in a subset of hormone receptor-positive disease.

The Multifaceted Role of Tissue-Resident Memory T Cells.

Regionalized immune surveillance relies on the concerted efforts of diverse memory T cell populations. Of these, tissue-resident memory T (T) cells are strategically positioned in barrier tissues, where they enable efficient frontline defense against infections and cancer. However, the long-term persistence of these cells has been implicated in a variety of immune-mediated pathologies.

Plasmodium infection induces phenotypic, clonal, and spatial diversity among differentiating CD4 T cells.

Naive CD4 T cells must differentiate in order to orchestrate immunity to Plasmodium, yet understanding of their emerging phenotypes, clonality, spatial distributions, and cellular interactions remains incomplete. Here, we observe that splenic polyclonal CD4 T cells differentiate toward T helper 1 (Th1) and T follicular helper (Tfh)-like states and exhibit rarer phenotypes not elicited among T cell receptor (TCR) transgenic counterparts. TCR clones present at higher frequencies exhibit Th1 skewing, suggesting that variation in major histocompatibility complex class II (MHC-II) interaction influences proliferation and Th1 differentiation.

Intravital Imaging of the Human Cornea Reveals the Differential Effects of Season on Innate and Adaptive Immune Cell Morphodynamics.

Purpose: Defining how the in vivo immune status of peripheral tissues is shaped by the external environment has remained a technical challenge. We recently developed Functional in vivo confocal microscopy (Fun-IVCM) for dynamic, longitudinal imaging of corneal immune cells in living humans. This study investigated the effect of seasonal-driven environmental factors on the morphodynamic features of human corneal immune cell subsets.

Protocol for the isolation of the mouse sympathetic splanchnic-celiac-superior mesenteric ganglion complex.

Neurons that originate from pre-vertebral sympathetic ganglia, the splanchnic-celiac-superior mesenteric ganglion complex (SCSMG) in mouse, have important roles in control of organs of the upper abdomen. Here, we present a protocol for the isolation of the mouse sympathetic SCSMG. We describe steps for surgical incision, ganglia isolation, ganglia fine dissection, and whole-mount SCSMG after clearing-enhanced 3D (Ce3D) clearing method and immunohistochemistry.

The Integration of Physical Therapists and Occupational Therapists into Burn Wound Care Increases Therapist Productivity, Job Satisfaction, and Multidisciplinary Collaboration.

When attempting to deliver specialized rehabilitation therapy interventions, physical therapists (PTs) and occupational therapists (OTs) must account for dynamic and logistical patient factors such as daily wound care, pain, difficulty progressing range of motion with dressings donned, and ongoing surgical interventions. Additionally, they must attain institution-specific productivity standards. Given burn patients often require considerable multidisciplinary interventions, efficiently planning and delivering rehabilitation therapy interventions within productivity expectations may prove difficult.

The transcription factor SpiB regulates the fibroblastic reticular cell network and CD8 T-cell responses in lymph nodes.

Fibroblastic reticular cells (FRCs) construct microanatomical niches that support lymph node (LN) homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here, we investigated the role of the transcription factor SpiB that is expressed in LN FRCs.

Bone and Skin/Subcutaneous Tissue Concentrations of Cefiderocol During Treatment of Extensively Drug-Resistant Pseudomonas aeruginosa.

Pyoderma gangrenosum is a rare dermatologic disorder that disrupts the skin barrier, requiring immunosuppressive therapy. We successfully used cefiderocol for the treatment of an extensively drug-resistant Pseudomonas aeruginosa bacteremia, and presumed osteomyelitis in a patient with severe pyoderma gangrenosum and associated immunosuppressive therapy while being medically optimized for skin grafting. We obtained bone and skin/subcutaneous tissue while the patient was on cefiderocol under an institutional review board-approved biologic waste recovery protocol.

An Appraisal of Pharmacotherapy-Pertinent Literature Published in 2021 and 2022 for Clinicians Caring for Patients With Thermal or Inhalation Injury.

Studies focusing on pharmacotherapy interventions to aid patients after thermal injury are a minor focus in burn injury-centered studies and published across a wide array of journals, which challenges those with limited resources to keep their knowledge current. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Twenty-three geographically dispersed, board-certified pharmacists participated in the review.

Divergent molecular networks program functionally distinct CD8 skin-resident memory T cells.

Skin-resident CD8 T cells include distinct interferon-γ-producing [tissue-resident memory T type 1 (T1)] and interleukin-17 (IL-17)-producing (T17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms to establish tissue residence is unknown. In this work, we show that T1 and T17 cells navigate divergent trajectories to acquire tissue residency in the skin.

A methodology of phenotyping ICU patients from EHR data: high-fidelity, personalized, and interpretable phenotypes estimation.

Objective: Computing phenotypes that provide high-fidelity, time-dependent characterizations and yield personalized interpretations is challenging, especially given the complexity of physiological and healthcare systems and clinical data quality. This paper develops a methodological pipeline to estimate unmeasured physiological parameters and produce high-fidelity, personalized phenotypes anchored to physiological mechanics from electronic health record (EHR).

Methods: A methodological phenotyping pipeline is developed that computes new phenotypes defined with unmeasurable computational biomarkers quantifying specific physiological properties in real time.

Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Introduction: The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting results.

Aim Of Study: The purpose of this systematic review and meta-analysis was to determine if therapeutic hypothermia provides beneficial neurologic outcomes relative to adverse effects.

Material And Methods: MEDLINE and EMBASE databases were searched for randomized controlled trials of post-cardiac arrest patients comparing therapeutic hypothermia (33 degrees Celsius) to normothermia or the standard of care (36 - 38 degrees Celsius).

Redefining the human corneal immune compartment using dynamic intravital imaging.

The healthy human cornea is a uniquely transparent sensory tissue where immune responses are tightly controlled to preserve vision. The cornea contains immune cells that are widely presumed to be intraepithelial dendritic cells (DCs). Corneal immune cells have diverse cellular morphologies and morphological alterations are used as a marker of inflammation and injury.

Augmented Renal Function in Burn Patients: Occurrence and Discordance With Commonly Used Methods to Assess Renal Function.

Augmented renal clearance (ARC) is defined by supraphysiologic renal function and is associated with drug failure due to subtherapeutic drug exposure. Burn patients are cited as being at high risk for ARC, yet rates of ARC have not been well described. This retrospective study described the prevalence and incidence of ARC, and compared 12-hour urine collection values (CrCl-12) vs.

Single-cell protein expression profiling resolves circulating and resident memory T cell diversity across tissues and infection contexts.

Memory CD8 T cells can be broadly divided into circulating (T) and tissue-resident memory T (T) populations. Despite well-defined migratory and transcriptional differences, the phenotypic and functional delineation of T and T cells, particularly across tissues, remains elusive. Here, we utilized an antibody screening platform and machine learning prediction pipeline (InfinityFlow) to profile >200 proteins in T and T cells in solid organs and barrier locations.

Multi-omic and spatial dissection of immunotherapy response groups in non-small cell lung cancer.

The composition and activation status of the cellular milieu contained within the tumour microenvironment (TME) is becoming increasingly recognized as a driving factor for immunotherapy response. Here, we employed multiplex immunohistochemistry (mIHC), and digital spatial profiling (DSP) to capture the targeted immune proteome and transcriptome of tumour and TME compartments from an immune checkpoint inhibitor (ICI)-treated (n = 41) non-small cell lung cancer (NSCLC) patient cohort. We demonstrate by mIHC that the interaction of CD68 macrophages with PD1 , FoxP3 cells is enriched in ICI refractory tumours (p = 0.