Active clinical trials for "Sepsis"

The occurrence of sepsis and its relevant multiple organ dysfunction remain a major problem in intensive care units with high morbidity and mortality. The differentiation between non-infectious and infectious etiologies, severity and organ function evaluation, and prognostic assessment are all challenging in routine clinical practice. Many biomarkers have been suggested for these purpose; however sensitivity and specificity even of high-ranking biomarkers still remain insufficient. Recently, metabolic profiling has attracted interest for biomarker discovery. In this study, LC-MS/MS will be perform to identify serum metabolic biomarkers for differentiation of SIRS/sepsis, severity and organ function evaluation, and prognostic assessment among 65 patients. The investigators enrolled 35 patients who were diagnosed with sepsis, 15 patients who were diagnosed with SIRS, and 15 normal patients. Moreover, the sepsis were further divided into sepsis, severe sepsis, and sepsis patients before death. Small metabolites that were present in patient serum samples were measured by LC-MS/MS techniques and analyzed using multivariate statistical methods, such as Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and Orthogonal Partial Least Squares Discriminant Analysis. Based on the multivariate statistical analysis above, the investigators could distinguish sepsis from normal and SIRS; distinguish the difference among sepsis, severe sepsis and death. We hypothesis that some metabolites as identified in this study are promising biomarker candidates in the field of sepsis diagnosis and treatment.

Critically ill children have abnormal utilization of nutrients such as glucose, lipids and protein. Protein synthesis is increased mainly in the form of immune and signaling proteins, while muscle and structural protein synthesis is decreased. The metabolism of sulfur amino acids through the splanchnic area and specifically methionine and cysteine have not been investigated in critically ill septic children, despite that sulfur amino acids have important roles in thiol, antioxidant and epigenetic reactions. Methionine metabolism in sick children will be influenced by its rate of utilization through different pathways. Our study aims to investigate the metabolism of methionine and cysteine when both amino acids are given by the enteral route in critically ill septic children. The investigators are focused on the rates of transmethylation, remethylation and transsulfuration in critically ill septic children, and if the current standard nutrition maintains methionine nutritional balance and functional requirements in critically ill children fed by the enteral route.

Percutaneously Inserted Central Catheters (PICCs) are special tubes that are inserted into blood vessels of premature babies (neonates) to give them nutrition and medications. Sometimes these tubes get infected and they need to be removed. Also, the babies need to be given medications to treat these infections (antibiotics). PICC infections in neonates are a serious problem and we need to find new ways of detecting infections early so that we can treat them promptly to avoid complications. The purpose of this study is to understand what causes tube infections in neonates and to develop a test to detect tube infections early to avoid complications.

Immunosuppression is the leading cause of death in septic patients. Neutrophils are classical components of innate immunology, but recent studies showed that neutrophils might display antigen presenting function and inhibit lymphocyte proliferation by expressing programmed cell death 1 ligand 1 (PD-L1). Whether neutrophils express PD-L1 and its role in immunosuppression during sepsis remain unclear.

BACKGROUND: Early diagnosis and prognostication of acute kidney injury in patients with sepsis is key to further our understanding this disease and in the evaluation of new interventions for this condition. Many urinary biomarkers have been proposed, but no single one seems to consistently provide additional information on top of clinical and routine biochemical parameters. Some authors have proposed to use a panel of urinary biomarkers to increase the accuracy However, this approach has so far not been tested in a large group of patients with sepsis. In addition, newer and more performant analytical techniques have been developed that warrant testing in the clinical field. PATIENTS AND METHODS: At least 150 consecutive patients admitted to a tertiary care intensive care unit (ICU) with sepsis will be included. After bladder catheterisation, urinary samples will be collected at time points 0, 4 hours and 24 hours after admission, and further daily on day 1-5. Samples will be immediately centrifuged and frozen at -80°C until analysis. Samples will be extracted by removing larger proteins (>20kDa) and de-salting step prior to mass spectrometry analysis. Investigators will use capillary electrophoresis-mass spectrometry (CE-MS) to assess urinary peptides predictive of AKI: 20 peptides constituting the AKI marker pattern previously established from a cohort of ICU patients. Simultaneously, samples will be analysed using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS), an alternative platform to CE-MS, which is currently being developed for routine ICU use. A proof of concept of the technique involved has been successfully applied to a set of urine samples from patients diagnosed with diabetes presenting normoalbuminuria (controls) and macroalbuminuria (cases). Clinical, demographic and biochemical data of patients will be collected during the first 5 days. PATIENT OUTCOME in the short term: development of acute kidney injury according to RIFLE criteria death need for renal replacement therapy during ICU stay on the longer term death need for renal replacement therapy estimated glomerular filtration rate as calculated by MDRD at 3 months, 1 year and 2 years. Using cut-offs , Receiver Operating Characteristics curves, negative and positive predictive value will be used to describe diagnostic performance of the biomarker panel alone, or in combination with basic clinical and/or routine biochemical parameters. Univariate and multivariate logistic regression for death will be used to evaluate prognostication value of the biomarker set. In addition, new discriminatory cut-offs of proteomic patterns as determined by more recent proteomic analysis techniques will be determined in a training set (half of the cohort) and validated in the other half of the cohort. Using the MALDI-TOF MS platform, investigators will assess urinary peptides that were predictive of AKI in a training set (ca. 75 patients) with good diagnostic performance of the marker panel (accuracy above 0.8) . Performance of the biomarker panel will be assessed in a blinded test set of ca. 75 patients to evaluate validity of the model in AKI detection.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify inflammation and serves as a critical mediator of inflammatory response in the context of sepsis. Blocking of TREM-1 can protect against sepsis in mice. This study was designed to investigate whether TREM-1 genomic variations were associated with the prognosis of sepsis. We sequenced 30 sepsis patients with TREM-1 gene of four exons by PCR sequencing. When analyzing the results of sequencing, we found two gene polymorphisms located in exon-2 and exon-4, respectively. Compare with the NCBI dbSNP and Hapmap database, one polymorphisms located in exon-2 is non-synonymous variation rs2234237（Ser25Thr）, the other one located in exon-4 is synonymous variation rs2234246. Two common polymorphisms (rs2234237,rs2234246) within the TREM-1 gene were detected in 80 patients with severe sepsis and in 80 healthy control subjects. This study was explored that whether or not polymorphisms detected within the TREM-1 gene may play a major role in the predisposition to prognosis of sepsis in a Chinese Han cohort.

The purpose of this study is to investigate the relationship between a procalcitonin decrease over 72 hours and outcome in patients who have severe sepsis or septic shock.

The investigators want to identify that whether PD-1/PD-L1 pathway will change in human sepsis, and whether PD-1/PD-L1 pathway play an important role in sepsis induced immunosuppression.

This is a Multicenter, observational, non-interventional registry designed to collect clinical data in Chinese patients who have received CUBICIN treatment under condition of actual usage in clinical practice.

Aims: to explore the value of TREM-1 (triggering receptor expressed on myeloid cells-1) ,PCT(Procalcitonin), as well as CPIS (clinical pulmonary infection score) in the diagnostic and prognostic assessment of VAP (ventilator associated pneumonia); and to make a comparison with WBC (white blood cells) and CRP (C-reactive protein) level as well as SOFA (Sequential Organ Failure Assessment) Score Methods: There were 92 subjects of sepsis, who were either receiving endotracheal intubation or had undergone tracheotomy and were exposed to mechanical ventilation. The subjects were divided into the VAP group (32) and the Non-VAP group (60), the criterion being the contraction of VAP 48 hours after ICU admission. Etiological culture was conducted in BALF (bronchoalveolar lavage fluid). And sTREM-1 density was determined by examining serum sTREM-1, PCT, WBC, CRP and EVC (exhaled ventilator condensate). Meanwhile, the CPIS and SOFA score were worked out. With a 28-day survival as the demarcation line, the VAP group was further divided into the survivors group, who stayed alive for 28 days or more , and the non-survivors group, who died within 28 days. The sTREM-1 and PCT level were denoted as meridians (range interquartile), while the WBC and CRP level as well as the CPIS and SOFA score, means±standard deviations (SD). Results: Averagely, the patients would contract clinically-confirmed VAP 6.9 days after admission, which was mainly traced to Gram-negative bacilli infection. On the very day of diagnosis, compared with the Non-VAP group, the VAP group showed a higher level of serum sTREM-1, PCT, WBC and CRP as well as CPIS and SOFA score（295.6pg/ml vs.143.5pg/ml, P<0.001；4.5ng/ml vs. 1.4ng/ml，P=0.008；16.7×10∧9/L vs.10.9×10∧9/L, P<0.001；11.5mg/dl vs. 7.7mg/dl，P=0.012； 6.0vs. 1.9, P<0.001；10.0vs. 7.5, P=0.017）, AUC (area under the receiver operating characteristic curve）turned out as follows :sTREM-1: 0.73（95% CI 0.61-0.85）;PCT : 0.70（95% CI 0.57-0.83）;WBC: 0.73（95% CI 0.60-0.85）.The CPIS score, which was proved by logistic regression analysis as the sole risky factor to VAP, amounted to 0.96（95% CI 0.91-1.00）. Combined prediction probability containing all the data was calculated in accordance on the relative regression equation. sTREM-1+WBC+CPIS score proved to be most reliable for diagnosis. AUC turned out as 0.98. With 0.277 as the cut-off point, sensitivity measured 0.97, specificity, 0.9 and YDI, 0.87. There were only 5 VAP subjects whose sTREM-1 density could be detected in EVC. The VAP patients were divided into a survivors group (n=15) and a non-survivors group (n=17) with a 28-day survival as the demarcation line. The non-survivors group demonstrated a higher PCT level and higher CPIS & SOFA score than the survivors. （3.0ng/ml vs. 15.3ng/ml，P=0.032；5.4vs. 6.6, P=0.03；8.1vs.11.7 P=0.049). AUC worked out PCT 0.752（95% CI 0.547-0.956）and CPIS 0.764（95% CI 0.575-0.953）. Calculations on the regression equation showed the PCT+CPIS score was most reliable for prognostic assessment. AUC turned out as 0.848. With 0.516 as the demarcation line, sensitivity measured 0.867, specificity, 0.818 and YDI, 0.685. conclusion: WBC + CPIS helps improve VAP diagnosis; PCT+CPIS may be used for VAP prognostic assessment. Taking two items into consideration will be of guiding value in VAP treatment as well as mortality rate reduction. The sTREM-1 level in EVC，however，may be devoid of value for VAP diagnosis.