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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Higher levels of cerebrospinal fluid and plasma neurofilament light in human immunodeficiency virus-associated distal sensory polyneuropathy

alexandrossfakianakis shared this article with you from Inoreader Higher levels of cerebrospinal fluid and plasma neurofilament light in human immunodeficiency virus-associated distal sensory polyneuropathy via Clinical Infectious Diseases Advance Access Abstract Background Neurofilament light chain (NFL) concentrations, reflecting axonal damage, are seen in several polyneuropathies, but have not been studied in HIV distal sensory polyneuropathy (DSP). We evaluated NFL in CSF and plasma in relation to DSP in people with HIV (PWH) from two independent cohorts, and in people without HIV (PWoH). Methods Cohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2. Results Cohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% black, 49.6% white, current CD4+ T-cells (median, IQR) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤ 50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1, but also 51 PWoH, t ogether age 58.4 ± 6.68 years, 41.2% female, 18.0% black, Hispanic, non-Hispanic white 52.0%, 6.00% white. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds. Conclusions Both plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP. View on Web

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Acute hepatitis associated with an echovirus 9 infection in a heart transplant recipient

alexandrossfakianakis shared this article with you from Inoreader Acute hepatitis associated with an echovirus 9 infection in a heart transplant recipient via Journal of Medical Virology Abstract We report a case of severe acute hepatitis due to echovirus 9 in a heart transplant patient treated with conventional immunosuppressive therapy. This case supports the importance of testing for enteroviruses in any type of infectious presentation in immunocompromised populations. This article is protected by copyright. All rights reserved. View on Web

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Outcome and associated predictors for non‐surgical management of large cyst‐like periapical lesions: A CBCT‐based prospective cohort study.

alexandrossfakianakis shared this article with you from Inoreader Outcome and associated predictors for non‐surgical management of large cyst‐like periapical lesions: A CBCT‐based prospective cohort study. via International Endodontic Journal Abstract Aim The aim of this cone-beam computed tomography (CBCT) based study was to evaluate the outcome of non-surgical root canal treatment (RCT) performed for the management of large cyst like periapical lesions (LCPL) and to identify the predictive factors affecting healing. Methodology 54 subjects (77 permanent maxillary anterior teeth) with LCPL (>10mm) of endodontic origin were included. A single operator performed standardised multi-visit RCT. Patients were clinically and radiographically examined at 6,12 months and a CBCT scan was taken at 24 months. Two independent blinded evaluators measured the pre and postoperative volume of periapical lesions on CBCT scans using ITK snap software (version 3.8.0-beta-20181028-win64). The outcome was assessed as a percentage change in lesion volume and dichotomized as success (resolved/reduced) or failure (unchanged/enlarged). Ten pre-operative (gender; age; intraoral draining sinus, soft tissue swelling, tooth discoloration, pulp canal obliteration, open apex, root resorption, cortical bone defect and lesion volume) and four intraoperative (apical extent and density of root filling; number of treatment visits and type of root filling) predictive factors were observed. Bivariate and stepwise multivariable linear regres sion analysis was performed to identify independent predictors affecting treatment outcomes. The significance level was set at 5%. Results A recall rate of 88% was achieved. The success rate of RCT was 82.2% (8.9% resolved, 73.3% reduced). Median lesion volume reduction was 75% (IQR 61%-93%). No pre or intra-operative factors were related to treatment failure. However, presence of preoperative cortical bone defect (palatal versus no cortical defect, β= -51.5; 95% CI: -86.9 to -16, p = 0.006) and apical extent of obturation (long versus flush, β= -27.2; 95% CI: -53.8 to -0.6, p = 0.04) were negatively associated with reduction in lesion volume (%). Conclusion LCPL may be successfully managed with RCT. Preoperative cortical bone defect and apical extent of obturation may negatively influence osseous healing. View on Web

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Post‐COVID‐19 vaccination arm pain diagnosed as complex regional pain syndrome: a case report

alexandrossfakianakis shared this article with you from Inoreader Post‐COVID‐19 vaccination arm pain diagnosed as complex regional pain syndrome: a case report via Pain Practice Abstract As the vaccination efforts against the coronavirus disease-2019 (COVID-19) continue, more patients are likely to present with complications related to COVID-19 vaccination. We describe the first reported case of complex regional pain syndrome (CRPS), involving the upper extremities, that occurred after COVID-19 vaccination. The patient presented with acute-onset severe arm pain and swelling following vaccine administration. Based on the clinical, electrodiagnostic, and radionuclide three-phase bone scan findings, the patient was diagnosed with postvaccination CRPS. The COVID-19 vaccine possibly elicited an immune-mediated inflammatory response to the injected antigen in the patient, who was predisposed to CRPS due to inflammatory immunity. The COVID-19 vaccine elicited an immune-mediated inflammatory response to the injected antigen, resulting in CRPS following COVID-19 vaccination. View on Web

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Total calcium, dairy foods and risk of colorectal cancer: a prospective cohort study of younger US women

alexandrossfakianakis shared this article with you from Inoreader Total calcium, dairy foods and risk of colorectal cancer: a prospective cohort study of younger US women via International Journal of Epidemiology - Advance Access Abstract Background Although colorectal cancer (CRC) incidence is declining among adults aged ≥65 years, CRC incidence in younger adults has been rising. The protective role of calcium in colorectal carcinogenesis has been well established, but evidence is lacking on whether the association varies by age at diagnosis. We investigated the association between total calcium intake and risk of overall CRC and CRC before age 55 years. Methods In the Nurses' Health Study II (1991–2015), 94 205 women aged 25–42 years at baseline were included in the analysis. Diet was assessed every 4 years through validated food frequency questionnaires. Multivariable-adjusted hazard ratios (HRs) and 95% CIs for CRC were estimated using the Cox proportional hazards model. Results We documented 349 incident CRC cases during 2 202 604 person-years of follow-up. Higher total calcium intake was associated with a reduced risk of CRC. Compared with those with <750 mg/day of total calcium intake, the HR of CRC was 0.61 (95% CI, 0.38–0.97) for those who consumed ≥1500 mg/day (P for trend = 0.01). The HR per 300 mg/day increase was 0.85 (95% CI, 0.76–0.95). There was a suggestive inverse association between total calcium intake and CRC before age 55 years (HR per 300 mg/day increase, 0.87; 95% CI, 0.75–1.00), suggesting the importance of calcium intake in the younger population. Conclusions In a cohort of younger women, which reflects the birth cohorts, time periods and age ranges paralleling the recent rise in CRC, higher calcium intake was associated with a decreased risk of CRC. View on Web

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