In pursuit of a PICS prognostic: An investigation of the agents activating and perpetuating PICS.
追求 PICS 预后:对激活和维持 PICS 的药物进行调查。
基本信息
- 批准号:9123092
- 负责人:
- 金额:$ 3.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-05-16 至 2019-05-15
- 项目状态:已结题
- 来源:
- 关键词:1 year oldAcuteAcute-Phase ReactionAddendumAge-YearsAppearanceBacterial DNABacterial InfectionsBloodBlood CirculationBlunt TraumaCaringCatabolismCause of DeathCessation of lifeChronicClinicalConvalescenceCritical CareCritical IllnessCytochromesDNADevelopmentDiagnosisDiseaseEarly DiagnosisEnzyme-Linked Immunosorbent AssayFloridaFundingGene ExpressionGenetic TranscriptionGenomicsGoalsHMGB1 geneHealthHeat-Shock Proteins 70HospitalizationHospitalsHourImmune systemImmunoassayImmunosuppressionIncidenceInfectionInflammationInflammatoryInflammatory ResponseIntensive Care UnitsInvestigationLeukocytesLipopolysaccharidesMeasuresMedicalMedicineMitochondrial DNAMolecularMultiple Organ FailureNuclearObservational StudyOperative Surgical ProceduresOutcomeOxidasesPathway interactionsPatientsPatternPattern recognition receptorPersonsPhysiciansPlasmaPlayPopulationProceduresProteinsRNARecoveryRecurrenceRefractoryResearchResearch Project GrantsResourcesRhodopsinRoleS100A8 geneSamplingScientistSepsisSeptic ShockSkilled Nursing FacilitiesStimulusSyndromeSystemTNFRSF5 geneTimeTissuesTrainingTraumaTrauma patientTraumatic injuryUnited StatesUniversitiesWound Healingbasecareercollegecostcytokinedesignevidence based guidelineshuman diseaseimprovedindividualized medicineinsightmicrobialmortalitynano-stringnutritionpathogenpatient populationpersonalized medicineprognosticprogramspublic health relevanceresponsetreatment planning
项目摘要
DESCRIPTION (provided by applicant): The proposed surgery training plan is an integrated critical care doctoral dissertation research project, supervised by Dr. Lyle Moldawer within the Sepsis and Critical Illness Research Center (SCIRC) at the University of Florida, College of Medicine. The program is ideally designed to equip the candidate to attain his career goals of becoming a physician-scientist. Traumatic injuries are presently the leading cause of death for persons less than 45 years of age. Severe sepsis has more than doubled since 2000, and sepsis currently represents the 11th leading cause of death, and the leading diagnosed hospitalization expense. Although trauma and sepsis patients are now increasingly surviving their initial and early insults due to improved acute medical care, unfortunately two year survivability for these patients has remained unchanged. For trauma and sepsis patients, the greatest obstacle to convalescence is now a chronic immunological disequilibrium that we have termed persistent inflammation, immunosuppression and catabolism syndrome (PICS), and the declining clinical course is characterized by a persistent acute-phase response with systemic inflammation, continuous protein catabolism (despite optimal nutrition), poor wound healing, immunosuppression, and recurrent infections. The agents activating and perpetuating PICS are unresolved, and currently there is no established paradigm to discriminate between those patients who will improve clinically within 14 days from those who will progress to PICS. Early, if
not immediately after trauma and sepsis onset, pattern recognition receptors (PRRs) that control inflammatory pathways in the innate and adaptive immune system are likely activated by either damage associated molecular patterns [DAMPs: including endogenous mitochondrial DNA and HMGB1] and/or pathogen associated molecular patterns [PAMPs: including bacterial DNA and bacterial lipopolysaccharide] that are released into the circulation during tissue damage and bacterial infection. The objective of this proposal is to develop an early prognostic of trauma and
sepsis clinical trajectory, and to gain insight into the agents activating and perpetuating PICS. The overarching hypothesis is that a time-dependent circulatory load of PAMPs and DAMPs dictates whether trauma and sepsis patients recover or enter PICS. Immediately following trauma and sepsis insult, a small amount of blood (less than 10ml) will be drawn from patients in the intensive care unit. Thereafter, for the duration of ICU stay, blood will be periodically drawn
to determine the interactions between the immune system and the levels of DAMPs and PAMPs. Leukocyte genomic expression and PAMP levels will be measured with NanoString. DAMP levels will be measured by a combination of qPCR, ELISA, and NanoString. As DAMPs and PAMPs are thought to be associated with an increasing number of diseases, the successful completion of these studies may ultimately contribute to a better understanding of many or most human diseases.
描述(由申请人提供):建议的外科培训计划是一个综合重症护理博士论文研究项目,由佛罗里达大学医学院脓毒症和危重疾病研究中心(SCIRC)的Lyle Moldawer博士监督。该计划的理想设计是为了使应聘者能够实现成为一名内科科学家的职业目标。目前,创伤是45岁以下人群死亡的主要原因。自2000年以来,严重脓毒症已经增加了一倍多,目前脓毒症是第11大死亡原因,也是主要的确诊住院费用。虽然创伤和脓毒症患者现在越来越多地从最初和早期的侮辱中幸存下来,但不幸的是,这些患者的两年存活率仍然没有改变。对于创伤和脓毒症患者,目前最大的康复障碍是慢性免疫失衡,我们称之为持续性炎症、免疫抑制和分解代谢综合征(PICS),其下降的临床过程以持续的急性时相反应为特征,伴有全身炎症,持续的蛋白质分解代谢(尽管营养最佳),伤口愈合不良,免疫抑制和反复感染。激活和维持PICS的因素尚未解决,目前还没有确定的范例来区分那些在14天内临床好转的患者和那些将进展到PICS的患者。早,如果
在创伤和脓毒症发作后,控制先天和获得性免疫系统炎症途径的模式识别受体(PRRs)很可能被组织损伤和细菌感染过程中释放到循环中的损伤相关分子模式[DAMPS:包括内源性线粒体DNA和HMGB1]和/或病原体相关分子模式[PAMPs:包括细菌DNA和细菌脂多糖]激活。这项建议的目标是开发创伤的早期预后和
脓毒症的临床轨迹,并深入了解激活和持续PICS的因素。最重要的假设是,依赖时间的PAMP和DAMPS循环负荷决定了创伤和脓毒症患者是康复还是进入PICS。在创伤和败血症伤害后,将立即从重症监护病房的患者中抽出少量血液(少于10毫升)。此后,在ICU逗留期间,将定期抽血
以确定免疫系统与DAMPS和PAMP水平之间的相互作用。白细胞基因组表达和PAMP水平将用纳米线测量。湿气水平将通过qPCR、酶联免疫吸附试验和纳米串相结合进行测量。由于DAMPS和PAMP被认为与越来越多的疾病有关,这些研究的成功完成最终可能有助于更好地了解许多或大多数人类疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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David C Holden其他文献
David C Holden的其他文献
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{{ truncateString('David C Holden', 18)}}的其他基金
In pursuit of a PICS prognostic: An investigation of the agents activating and perpetuating PICS.
追求 PICS 预后:对激活和维持 PICS 的药物进行调查。
- 批准号:
9268439 - 财政年份:2016
- 资助金额:
$ 3.83万 - 项目类别:
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