A5065918774- Immune Response and Inflammation
- Sepsis Diagnosis and Treatment
- Trauma and Emergency Care Studies
- Immune cells in cancer
- Cardiac Arrest and Resuscitation
- Emergency and Acute Care Studies
- Respiratory Support and Mechanisms
- Immune Cell Function and Interaction
- Intensive Care Unit Cognitive Disorders
- Trauma Management and Diagnosis
- COVID-19 Clinical Research Studies
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Thermal Regulation in Medicine
- Abdominal Trauma and Injuries
- Ubiquitin and proteasome pathways
- Wound Healing and Treatments
- COVID-19 diagnosis using AI
- RNA modifications and cancer
- RNA Research and Splicing
- Cardiac, Anesthesia and Surgical Outcomes
- SARS-CoV-2 detection and testing
- Pressure Ulcer Prevention and Management
- Phagocytosis and Immune Regulation
- Hip and Femur Fractures
- Hospital Admissions and Outcomes
Rhode Island Hospital
2015-2024
Brown University
2015-2024
Providence College
2011-2024
Barts Health NHS Trust
2024
Island Hospital
2019-2023
Lifespan
2018-2023
Society of Surgical Oncology
2016
National Institutes of Health
2011
American Association for the Surgery of Trauma
2011
Rutgers, The State University of New Jersey
2007-2008
Abstract Introduction Following trauma and systemic inflammatory response syndrome (SIRS), the typical is an elevation of total complete blood count (CBC) a reduction lymphocyte count. This leukocytosis typically returns to normal within 48 hours. The persistence following associated with adverse outcomes. Although anergy dysfunction increased risk for infection sepsis, there paucity data regarding impact low in patients. Methods retrospective review prospectively collected from patients...
Background: Normal vital signs are typically associated with improved outcomes in trauma patients. Whether this association is true for geriatric patients unclear. Methods: A Level 1 center retrospective chart review of on presentation (heart rate [HR] and blood pressure) young (aged 17–35 years) 65 years or older) blunt victims from September 2003 to 2008 was preformed. Generalized nonlinear using piecewise regression the linear portion standard logistic models used model risk mortality as...
To test the hypothesis that comparably injured women, especially those in hormonally active age groups, would manifest a better preserved hemodynamic response and tissue perfusion after major trauma than do men.The notion premenopausal women are more resistant men to shock has been shown numerous preclinical models. However, human studies on effects of gender outcome shock-trauma less clear, none examined effect immediate postinjury trauma.Prospective series all patients at Level I center...
Ethnic minorities and low income families tend to be in poorer health have worse outcomes for a spectrum of diseases. Health care provider bias has been reported potentially affect the distribution away from communities, minorities, patients with history substance abuse. Trauma is perceived as disease poor medically underserved. Minorities are overrepresented populations also less likely possess insurance leading potential overlapping effect. Traumatic brain injury (TBI) predominant cause...
Abstract Introduction Sepsis is a deadly inflammatory condition that often leads to an immune suppressed state; however, the events leading this state remain poorly understood. B and T lymphocyte attenuator (BTLA) immune-regulatory receptor shown effectively inhibit CD4+ T-cell function. Therefore, our objectives were determine: 1) if BTLA expression was altered in critically ill patients experimentally induced septic mice, 2) whether augmented associated with poor patient outcomes, 3)...
Abstract BTLA expression contributes to increased septic morbidity, mortality, and decreased innate cell activity in mice, while BTLA+ blood monocyte levels increase ICU patients. A proper inflammatory response is essential for prevention of the systemic inflammation associated with sepsis. an immune-regulatory receptor demonstrated be expressed not only on adaptive immune populations have potent inhibitory effects CD4+ T cells but also (CD11c+ CD11b+ cells) has been shown diminish pathogen...
Abstract Identifying relevant mediators responsible for the pathogenesis during sepsis may lead to finding novel diagnostic and therapeutic targets. Recent studies indicate programmed cell death receptor (PD)-1 plays a significant role in development of immune suppression associated with sepsis. In this study, we determine whether B7-H1, primary ligand PD-1, contributes We report that B7-H1 is upregulated extensively on various cells gene deficiency protects mice from lethality terms...
Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% all hereditary disease alleles classified as mutations mapping to the canonical 5' and 3' splice sites. However, present in exons deeper intronic positions vastly underreported. A recent re-analysis coding exon 10 Lynch Syndrome gene, MLH1, revealed an extremely high rate (77%) lead defective splicing. This finding is confirmed by extending sampling five other MLH1 gene. Further analysis...
Programmed death 1 (PD-1) is an inhibitor protein receptor for the immune system and has been shown to be upregulated in animal models of critical illness as well after trauma burn victims humans. It believed that PD-1 may play a role dysfunction seen surgical illness. However, although prior studies have associated changes expression with altered cell function, it not known if correlation clinical status exists. We therefore aimed describe potential critically ill patients. This...
To determine the contribution of programmed death receptor (PD)-1 in morbidity and mortality associated with development indirect-acute lung injury. The immune cell interaction(s) leading to injury are not completely understood. In this respect, we have recently shown that murine surface coinhibitory receptor, PD-1, has a role septic morbidity/mortality is mediated part through effects on innate arm. However, it know if PD-1 how may be at cellular level. -/- mice were used model (hemorrhagic...
Deficiency of the co-inhibitory receptor, Programmed cell death receptor (PD)-1, provides a survival benefit in our murine shock/sepsis model for development indirect acute respiratory distress syndrome (iARDS). Further, clinical significance, patients that develop ARDS express increased PD-1 on their blood leukocytes. While expression and its regulatory role have been associated with mainly T-cell responses, contribution primary ligand, PD-L1, broadly expressed non-immune cells such as lung...
Alternative splicing (AS) and nonsense-mediated mRNA decay (NMD) are highly conserved cellular mechanisms that modulate gene expression. Here we introduce NMD pipeline computes how events premature termination codons to transcripts via frameshift, then predicts the rate of PTC-dependent NMD. We utilize whole blood, deep RNA-sequencing data from critically ill patients study expression in sepsis. Statistical significance was determined as adjusted p value < 0.05 |log2foldchange| > 2 for...
Abnormalities of carbohydrate metabolism and insulin sensitivity have been reported in estrogen deficiency. Estrogen replacement appears to result an improvement these parameters, although progestagens may antagonize effects. We examined the effects transdermal estradiol oral norethisterone on using hyperinsulinemic euglycemic clamp method by performing a randomized, double blind, placebo-controlled study 22 healthy women after surgically induced menopause. After baseline measurements,...
BACKGROUND Lack of health care insurance has been correlated with increased mortality after trauma. Medical comorbidities significantly affect trauma outcomes. Access to and thereby being diagnosed a pretrauma comorbidity is highly dependent on status. The objective this study was determine whether rates or undiagnosed preexisting contribute disparities in observed between insured uninsured patients. METHODS Review patients admitted Level I center during 5-year period. Data extracted from...
Abstract Pulmonary arterial hypertension (PAH) is characterized by endothelial cell (EC) dysfunction. There are no data from living patients to inform whether differential gene expression of pulmonary artery ECs (PAECs) can discern disease subtypes, progression and pathogenesis. We aimed further validate our previously described method propagate right heart catheter (RHC) balloon tips perform additional PAEC phenotyping. performed bulk RNA sequencing PAECs RHC balloons. Using unsupervised...
Studies imply that intestinal barrier dysfunction is a key contributor to morbid events associated with sepsis. Recently, the co-inhibitory molecule programmed death-ligand1 (PD-L1) has been shown be involved in regulation of immune tolerance and/or inflammation. Our previous studies showed PD-L1 gene deficiency reduced sepsis-induced injury morphologically. However, it not known how expression impacts during Here we tested hypothesis expressed on epithelial cells (IECs) role dysfunction. To...
Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. Blood bronchial alveolar lavage fluid (BAL) from humans (n = 10–13) with ARDS controls 5–10) as well murine model 5–6) 6–7) were studied. was induced mice by hemorrhagic shock (day 1) followed poly-microbial sepsis 2). Samples then collected...
Background: In October 2008, Medicare and Medicaid stopped paying for care associated with catheter-related urinary tract infections (UTIs). Although most clinicians agree UTIs are detrimental, there little data to support this belief. Methods: This is a retrospective review of trauma registry from Level I center between 2003 2008. Two proportional hazards regressions were used analyses. The first predicted acquisition UTI as function indwelling catheter use, adjusting age, diabetes, gender,...
We have demonstrated hemorrhagic shock "priming" for the development of indirect acute respiratory distress syndrome (iARDS) in mice following subsequent septic challenge, and show pathology characteristic patients with iARDS, including increased lung microvascular permeability arterial PO2/FI02 reduced to levels comparable mild/moderate ARDS during 48 h hemorrhage. Loss endothelial cell (EC) barrier function is a major component iARDS. EC growth factors, Angiopoietin (Ang)-1 2, maintain...
Critically ill patients with sepsis and acute respiratory distress syndrome have severely altered physiology immune system modifications. RNA splicing is a basic molecular mechanism influenced by physiologic alterations. Immune checkpoint inhibitors, such as B T Lymphocyte Attenuator (BTLA) previously been shown to influence outcomes in critical illness. We hypothesize illness results alternative of the protein, BTLA, resulting soluble form biologic clinical significance. Samples were...