8 results on '"Hotchkiss, Richard S."'
Search Results
2. The new normal: immunomodulatory agents against sepsis immune suppression.
- Author
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Hutchins, Noelle A., Unsinger, Jacqueline, Hotchkiss, Richard S., and Ayala, Alfred
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IMMUNOLOGICAL adjuvants , *IMMUNOSUPPRESSION , *CRITICALLY ill , *IMMUNOREGULATION , *SEPSIS , *THERAPEUTIC use of cytokines , *PATIENTS , *IMMUNOLOGY - Abstract
Highlights: [•] Sepsis is the leading cause of death in critically ill patients and novel therapies are necessary. [•] Immune suppression is frequently associated with sepsis-related deaths. [•] Therapies or immunomodulatory agents that enhance the immune response should be considered. [•] Cytokines and co-inhibitory receptors represent potential immunomodulatory agents. [ABSTRACT FROM AUTHOR]
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- 2014
- Full Text
- View/download PDF
3. The changing immune system in sepsis Is individualized immuno-modulatory therapy the answer?
- Author
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Boomer, Jonathan S, Green, Jonathan M, and Hotchkiss, Richard S
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SEPSIS , *IMMUNE response , *IMMUNOSUPPRESSION , *APOPTOSIS , *CLINICAL trials , *PATIENTS - Abstract
Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsisinduced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. Currently in clinical trial for sepsis are granulocyte macrophage colony stimulating factor and interferon gamma, immune-therapeutic agents that boost patient immunity. Immuno-adjuvants with promise in clinically-relevant animal models of sepsis include anti-programmed cell death-1 and interleukin-7. The future of immune-therapy in sepsis will necessitate identification of the immunologic phase using clinical and laboratory parameters as well as biomarkers of innate and adaptive immunity. [ABSTRACT FROM AUTHOR]
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- 2014
- Full Text
- View/download PDF
4. Nivolumab plus interferon-γ in the treatment of intractable mucormycosis.
- Author
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Grimaldi, David, Pradier, Olivier, Hotchkiss, Richard S, and Vincent, Jean-Louis
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THERAPEUTIC use of interferons , *MUCORMYCOSIS , *THERAPEUTIC use of monoclonal antibodies , *COMBINATION drug therapy , *PATIENTS , *THERAPEUTICS - Published
- 2017
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5. Widespread Down-Regulation of Cardiac Mitochondrial and Sarcomeric Genes in Patients With Sepsis.
- Author
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Matkovich, Scot J., Al Khiami, Belal, Efimov, Igor R., Evans, Sarah, Vader, Justin, Jain, Ashwin, Brownstein, Bernard H., Hotchkiss, Richard S., and Mann, Douglas L.
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DOWNREGULATION , *MITOCHONDRIAL DNA , *SARCOMERES , *SEPSIS , *MESSENGER RNA , *GENETICS , *PATIENTS - Abstract
Objectives: The mechanism(s) for septic cardiomyopathy in humans is not known. To address this, we measured messenger RNA alterations in hearts from patients who died from systemic sepsis, in comparison to changed messenger RNA expression in nonfailing and failing human hearts.Design: Identification of genes with altered abundance in septic cardiomyopathy, ischemic heart disease, or dilated cardiomyopathy, in comparison to nonfailing hearts.Setting: ICUs at Barnes-Jewish Hospital, St. Louis, MO.Patients: Twenty sepsis patients, 11 ischemic heart disease, nine dilated cardiomyopathy, and 11 nonfailing donors.Interventions: None other than those performed as part of patient care.Measurements and Main Results: Messenger RNA expression levels for 198 mitochondrially localized energy production components, including Krebs cycle and electron transport genes, decreased by 43% ± 5% (mean ± SD). Messenger RNAs for nine genes responsible for sarcomere contraction and excitation-contraction coupling decreased by 43% ± 4% in septic hearts. Surprisingly, the alterations in messenger RNA levels in septic cardiomyopathy were both distinct from and more profound than changes in messenger RNA levels in the hearts of patients with end-stage heart failure.Conclusions: The expression profile of messenger RNAs in the heart of septic patients reveals striking decreases in expression levels of messenger RNAs that encode proteins involved in cardiac energy production and cardiac contractility and is distinct from that observed in patients with heart failure. Although speculative, the global nature of the decreases in messenger RNA expression for genes involved in cardiac energy production and contractility suggests that these changes may represent a short-term adaptive response of the heart in response to acute change in cardiovascular homeostasis. [ABSTRACT FROM AUTHOR]- Published
- 2017
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6. Anti-PD-L1 peptide improves survival in sepsis.
- Author
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Shindo, Yuichiro, McDonough, Jacquelyn S., Chang, Katherine C., Ramachandra, Murali, Sasikumar, Pottayil G., and Hotchkiss, Richard S.
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SEPSIS , *CAUSES of death , *IMMUNOSUPPRESSIVE agents , *NOSOCOMIAL infections , *IMMUNOSUPPRESSION , *PATIENTS - Abstract
Background Sepsis remains a leading cause of death in most intensive care units. Many deaths in sepsis are due to nosocomial infections in patients who have entered the immunosuppressive phase of the disorder. One cause of immunosuppression in sepsis is T-cell exhaustion mediated by programmed cell death-1 (PD-1) interaction with its ligand (PD-L1). Studies demonstrated that blocking the interaction of PD-1 with PD-L1 with knockout mice or inhibitory antibodies reversed T-cell dysfunction and improved sepsis survival. This study assessed the efficacy of a novel short-acting peptide (compound 8) that inhibits PD-1:PD-L1 signaling in a clinically relevant second-hit fungal sepsis model. Methods Mice underwent cecal ligation and puncture to induce peritonitis. Three days later, mice received intravenous injection of Candida albicans . Forty-eight hours after Candida infection, mice were treated with compound 8 or inactive peptide. The effect of Candida infection on expression of coinhibitory molecules, PD-1, and PD-L1 were quantitated by flow cytometry on CD4 + cells, CD8 + cells, natural killer (NK) cells, and natural killer T-cells (NKT). The effect of compound 8 on survival was also examined. Results Four days after fungal infection, PD-1 and PD-L1 expressions were markedly increased on CD4 + , NK, and NKT cells in septic versus sham-operated mice (%PD-1 on CD4 + , 11.9% versus 2.8%; and %PD-L1 on NKT, 14.8% versus 0.5%). Compared with control, compound 8 caused a 2-fold increase in survival from 30% to 60%, P < 0.05. Conclusions Compound 8 significantly improved survival in a clinically relevant immunosuppressive model of sepsis. These results support immunoadjuvant therapy targeting T-cell exhaustion in this lethal disease. [ABSTRACT FROM AUTHOR]
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- 2017
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7. Is this critically ill patient immunocompromised?
- Author
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Pène, Frédéric, Pickkers, Peter, Hotchkiss, Richard, Pène, Frédéric, and Hotchkiss, Richard S
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CRITICALLY ill , *SEPSIS , *IMMUNOSUPPRESSIVE agents , *DRUG side effects , *CANCER patients , *PATIENTS , *CATASTROPHIC illness , *IMMUNOMODULATORS , *CRITICAL care medicine , *INTENSIVE care units , *ADULT respiratory distress syndrome , *IMMUNOCOMPROMISED patients , *THERAPEUTICS - Abstract
The article focuses on the development of sepsis, blood poisoning, to ill patients. Topics mentioned include the importance of patients care management, the effects of immunosuppressive drugs, and the septic patients medical care. Also mentioned are the effectiveness of immunotherapy in cancer patients and the immunoparalysis.
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- 2016
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8. Reactivation of Multiple Viruses in Patients with Sepsis.
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Walton, Andrew H., Muenzer, Jared T., Rasche, David, Boomer, Jonathan S., Sato, Bryan, Brownstein, Bernard H., Pachot, Alexandre, Brooks, Terrence L., Deych, Elena, Shannon, William D., Green, Jonathan M., Storch, Gregory A., and Hotchkiss, Richard S.
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SEPSIS , *IMMUNOSUPPRESSIVE agents , *ANELLOVIRUSES , *VIRAL load , *DEATH rate , *PATIENTS - Abstract
A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality. This study determined if reactivation of herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and correlated with severity. Serial whole blood and plasma samples from 560 critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched patients were analyzed by quantitative-polymerase-chain-reaction for cytomegalovirus (CMV), Epstein-Barr (EBV), herpes-simplex (HSV), human herpes virus-6 (HHV-6), and TTV. Polyomaviruses BK and JC were quantitated in urine. Detectable virus was analyzed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. Patients with protracted sepsis had markedly increased frequency of detectable virus. Cumulative viral DNA detection rates in blood were: CMV (24.2%), EBV (53.2%), HSV (14.1%), HHV-6 (10.4%), and TTV (77.5%). 42.7% of septic patients had presence of two or more viruses. The 50% detection rate for herpesviruses was 5–8 days after sepsis onset. A small subgroup of septic patients had markedly elevated viral loads (>104–106 DNA copies/ml blood) for CMV, EBV, and HSV. Excluding TTV, DNAemia was uncommon in critically-ill non-septic patients and in age-matched healthy controls. Compared to septic patients without DNAemia, septic patients with viremia had increased fungal and opportunistic bacterial infections. Patients with detectable CMV in plasma had higher 90-day mortality compared to CMV-negative patients; p<0.05. Reactivation of latent viruses is common with prolonged sepsis, with frequencies similar to those occurring in transplant patients on immunosuppressive therapy and consistent with development of an immunosuppressive state. Whether reactivated latent viruses contribute to morbidity and mortality in sepsis remains unknown. [ABSTRACT FROM AUTHOR]
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- 2014
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