Tissue plasminogen activator resistance is an early predictor of posttraumatic venous thromboembolism: A prospective study from the CLOTT research group

alexandrossfakianakis shared this article with you from Inoreader Tissue plasminogen activator resistance is an early predictor of posttraumatic venous thromboembolism: A prospective study from the CLOTT research group via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Venous thromboembolism (VTE) remains a frequent postinjury complication with well established but nonmodifiable risk factors. We hypothesized that fibrinolysis shutdown (SD) as measured by thromboelastography (TEG) would be an independent risk factor for VTE in trauma patients. METHODS A subgroup of patients enrolled in the CLOTT-2 (Consortium of Leaders in the Study of Traumatic Thromboembolism 2), multicenter prospective cohort study had kaolin TEG and tissue plasminogen activator (tPA)–TEG data at 12 and 24 hours postadmission. Patients underwent a screening duplex venous ultrasound examination during the first week unless clot was already detected on computed tomography. Injury factors associated with early fibrinolysis SD (defined as kaolin TEG Ly30 ≤0.3%) and/or tPA resistance (tPA-R) (defined as kaolin TEG with tPA 75 ng Ly30 4 U of FFP in the first 24 hours, the presence of a major brain injury or pelvic fracture, and the need for major surgery. In contrast, factors significantly associated with early tPA-R included >4 U of red blood cells transfused in the first 24 hours and the presence of a major chest injury or long bone fracture. Deep vein thrombosis was detected in 15 patients and pulmonary clots in 5 (overall VTE rate, 14.2%). Tissue plasminog en activator resistance at 12 hours was found to be an independent risk factor for VTE (hazard ratio, 5.57; 95% confidence interval, 1.39–22.39). CONCLUSION Early development of a hypercoagulable state as defined by tPA-R at 12 hours after admission represents a potentially modifiable risk factor for postinjury VTE. LEVEL OF EVIDENCE Therapeutic/Care Management; Level II. View on Web

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Early expression of IL-10, IL-12, ARG1, and NOS2 genes in peripheral blood mononuclear cells synergistically correlate with patient outcome after burn injury

alexandrossfakianakis shared this article with you from Inoreader Early expression of IL-10, IL-12, ARG1, and NOS2 genes in peripheral blood mononuclear cells synergistically correlate with patient outcome after burn injury via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND No methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, noninvasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients. METHODS This prospective observational study enrolled two patient cohorts within a single burn center into an institutionally approved institutional review board study. Blood draws were performed View on Web

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Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy

alexandrossfakianakis shared this article with you from Inoreader Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Trauma patients with abnormal fibrinolysis have increased morbidity and mortality. Knowledge of mechanisms differentiating fibrinolytic phenotypes is important to optimize treatment. We hypothesized that subjects with abnormal fibrinolysis identified by whole blood viscoelastometry can also be distinguished by plasma thrombin generation, clot structure, fibrin formation, and plasmin generation measurements. METHODS Platelet-poor plasma (PPP) from an observational cross-sectional trauma cohort with fibrinolysis shutdown (% lysis at 30 minutes [LY30] 3%, n = 9) defined by whole blood thromboelastography were studied. Noninjured control subjects provided comparative samples. Thrombin generation, fibrin structure and formation, and plasmin generation were measured by fluorescence, confocal microscopy, turbidity, and a fluorescence-calibrated plasmin assay, respectively, in the absence/presence of tissue factor or tissue plasminogen activator (tPA). RESULTS Whereas spontaneous thrombin generation was not detected in PPP from control subjects, PPP from hyperfibrinolysis or shutdown patients demonstrated spontaneous thrombin generation, and the lag time was shorter in hyperfibrinolysis versus shutdown. Addition of tissue factor masked this difference but revealed increased thrombin generation in hyperfibrinolysis samples. Compared with shutdown, hyperfibrinolysis PPP formed denser fibrin networks. In the absence of tPA, the fibrin formation rate was faster in shutdown than hyperfibrinolysis, but hyperfibrinolysis clots lysed spontaneously; these differences were masked by addition of tPA. Tissue plasminogen activator–stimulated plasmin generation was similar in hyperfibrinolysis and shutdown samples. Differences in LY30, fibrin structure, and lysis correlated with pH. CONCLUSION This exploratory study using PPP-based assays identified differences in thrombin generation, fibrin formation and structure, and lysis in hyperfibrinolysis and shutdown subgroups. These groups did not differ in their ability to promote tPA-triggered plasmin generation. The ability to characterize these activities in PPP facilitates studies to identify mechanisms that promote adverse outcomes in trauma. LEVEL OF EVIDENCE Prognostic/Epidemiological; Level III. View on Web

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Sapovirus infections in an Australian community-based healthy birth cohort during the first 2-years of life

alexandrossfakianakis shared this article with you from Inoreader Sapovirus infections in an Australian community-based healthy birth cohort during the first 2-years of life via Clinical Infectious Diseases Advance Access Abstract Background Sapovirus is an important cause of acute gastroenteritis (AGE) in young children. However, knowledge gaps remain in community settings. We investigated the epidemiology, disease characteristics and healthcare use associated with sapovirus infections in Australian children during their first 2-years of life. Methods Children in the Brisbane-based Observational Research in Childhood Infectious Diseases birth cohort provided daily gastrointestin al symptoms (vomiting/loose stools), weekly stool swabs, and healthcare data until age 2-years. Swabs were batch-tested for sapovirus using real-time polymerase chain reaction assays. Incidence rates and estimates of associations were calculated. Results Overall, 158 children returned 11,124 swabs. There were 192 sapovirus infection episodes. The incidence rate (IR) in the first 2-years of life was 0.89 episodes per child-year (95% confidence interval [CI] 0.76–1.05), the symptomatic IR was 0.26 episodes per child-year (95%CI 0.17–0.37). Age ≥6-months, the fall season and childcare attendance, increased disease incidence significantly. Fifty-four (30%) of the 180 infections with linked symptom diaries were symptomatic, with 72% recording vomiting and 48% diarrhea. Prior infection reduced risk of further infections (adjusted hazard risk 0.70; 95%CI 0.54–0.81) in the study period. Viral loads were higher and viral shedding duration was longer in symptomatic than asymp tomatic children. Twenty-three (43%) symptomatic episodes required healthcare, including six emergency department presentations and two hospitalizations. Conclusion Sapovirus infections are common in Australian children aged 6–23 months. Efforts to reduce childhood AGE after the global rollout of rotavirus vaccines should include sapovirus where estimates of its incidence in communities will be crucial. View on Web

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Microbial volatiles as diagnostic biomarkers of bacterial lung infection in mechanically ventilated patients

alexandrossfakianakis shared this article with you from Inoreader Microbial volatiles as diagnostic biomarkers of bacterial lung infection in mechanically ventilated patients via Clinical Infectious Diseases Advance Access Abstract Background Early and accurate recognition of respiratory pathogens is crucial to prevent increased risk of mortality in critically ill patients. Microbial-derived volatile organic compounds (mVOCs) in exhaled breath could be used as non-invasive biomarkers of infection to support clinical diagnosis. Methods In this study, we investigated the diagnostic potential of in vitro confirmed mVOCs in the exhaled breath of patients under mechanically ventilation from the BreathDx study. Samples were analysed by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). Results Pathogens from bronchoalveolar lavage (BAL) cultures were identified in 45/89 patients and S. aureus was the most commonly identified pathogen (n = 15). Out of 19 mVOCs detected in the in vitro culture headspace of four common respiratory pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli), 14 were found in exhaled breath samples. Higher concentrations of two mVOCs were found in the exhaled breath of patients infected with S. aureus compared t o those without (3-methylbutanal p < 0.01. AUROC = 0.81-0.87 and 3-methylbutanoic acid p = 0.01. AUROC = 0.79-0.80). In addition, bacteria identified from BAL cultures which are known to metabolise tryptophan (Escherichia coli, Klebsiella oxytoca and Haemophilus influenzae) were grouped and found to produce higher concentrations of indole compared to breath samples with culture-negative (p = 0.034) and other pathogen-positive (p = 0.049) samples. Conclusions This study demonstrates the capability of using mVOCs to detect the presence of specific pathogen groups with potential to support clinical diagnosis. Although not all mVOCs were found in patient samples within this sm all pilot study, further targeted and qualitative investigation is warranted using multi-centre clinical studies. View on Web

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Histological features associated with Human Monkeypox Virus Infection in 2022 outbreak in a non-endemic country

alexandrossfakianakis shared this article with you from Inoreader Histological features associated with Human Monkeypox Virus Infection in 2022 outbreak in a non-endemic country via Clinical Infectious Diseases Advance Access Abstract Skin histology of papule and pustules from 5 MSM patients with Monkeypox infection showed viral intracytoplasmic cytopathic changes, interface dermatitis, marked inflammatory dermic infiltrate including superficial neutrophils and deep lymphocytes perivascular and periadnexal. Histologic description of Monkeypox lesions improves our understanding about clinical presentations and may have some therapeutic implications. View on Web

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New perspectives for prosthetic valve endocarditis - impact of molecular imaging by FISHseq diagnostics

alexandrossfakianakis shared this article with you from Inoreader New perspectives for prosthetic valve endocarditis - impact of molecular imaging by FISHseq diagnostics via Clinical Infectious Diseases Advance Access Abstract BackgroundThe causative microbial etiology of prosthetic valve infective endocarditis (PVE) can be difficult to identify. Our aim was to investigate the benefit of the molecular imaging technique fluorescence in situ hybridization (FISH) combined with 16S rRNA-gene PCR and sequencing (FISHseq) for the analysis of infected prosthetic heart valves. Methods We retrospectively evaluated the diagnostic outcome of 113 prosthetic valves from 105 patients with suspected PVE, treated in the years 2003-2013 in the Department of Cardiac Surgery, Charité University Medicine Berlin. Each prosthetic valve underwent cultural diagnostics and was routinely examined by FISH combined with 16S rRNA-gene PCR and sequencing. We compared classical microbiological culture outcomes (blood and valve cultures) with FISHseq results and evaluated the diagnostic impact of the molecular imaging technique. Results Conventional microbiological diagnostic alone turned out to be insufficient, as 67% of p reoperative blood cultures were non-informative (negative, inconclusive or not obtained) and 67% valve cultures remained negative. FISHseq improved the conventional cultural diagnostic methods in PVE in 30% of the cases and increased diagnostic accuracy. Out of the valve culture-negative PVE cases, FISHseq succeeded to identify the causative pathogen in 35%. Conclusions FISHseq improves PVE diagnostics, complementing the conventional cultural methods. In addition to species identification, FISH provides information about the severity of PVE and state of the pathogens, e.g. stage of biofilm formation, activity and localization on and within the prosthetic material. As a molecular imaging technique, FISHseq enables the unambiguous discrimination of skin flora as contaminant or infectious agent. View on Web

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