A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation

alexandrossfakianakis shared this article with you from Inoreader A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation via Annals of Surgery - Most Popular Articles Objective: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). Background: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. In addition, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. Methods: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 years follow up, 32% beyond Milan criteria). The resulting 4 gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. Results: HepatoPredict identifies 99% disease-free patients (>5 year) from a retrospective cohort, including many outside clinical criteria (16%–24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88.5%–94.4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. Conclusions: HepatoPredict outperforms conventional clinical-pathologic selection criteria (Milan, UCSF), providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs. View on Web

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Sirtuin 1 deletion increases inflammation and mortality in sepsis

alexandrossfakianakis shared this article with you from Inoreader Sirtuin 1 deletion increases inflammation and mortality in sepsis via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Sepsis is a hyperinflammatory response to infection that can lead to multiorgan failure and eventually death. Often, the onset of multiorgan failure is heralded by renal dysfunction. Sirtuin 1 (SIRT1) promotes cellular stress resilience by inhibiting inflammation and promoting mitochondrial function. We hypothesize that SIRT1 plays an important role in limiting the inflammatory responses that drive organ failure in sepsis, predominantly via expression in myeloid cells. METHODS We performed cecal ligation and puncture (CLP) on whole body SIRT1 knockout (S1KO) and myeloid cell–specific S1KO (S1KO-LysMCre) mice on a C57BL/6J background. Serum interleukin (IL)-6 was quantified by enzyme-linked immunosorbent assay. Renal mitochondrial complex activity was measured using Oxygraph-2k (Oroboros Instruments, Innsbruck, Austria). Blood urea nitrogen (BUN) was measured from serum. Survival was monitored for up to 5 days. RESULTS Following CLP, S1KO mice had decreased renal mitochondrial complex I–dependent respiratory capacity (241.7 vs. 418.3 mmolO2/mg/min, p = 0.018) and renal mitochondrial complex II–dependent respiratory capacity (932.3 vs. 1,178.4, p = 0.027), as well as reduced rates of fatty acid oxidation (187.3 vs. 250.3, p = 0.022). Sirtuin 1 knockout mice also had increased BUN (48.0 mg/dL vs. 16.0 mg/dL, p = 0.049). Interleukin-6 levels were elevated in S1KO mice (96.5 ng/mL vs. 45.6 ng/mL, p = 0.028) and S1KO-LysMCre mice (35.8 ng/mL vs. 24.5 ng/mL, p = 0.033) compared with controls 12 hours after surgery. Five-day survival in S1KO (33.3% vs. 83.3%, p = 0.025) and S1KO-LysMCre (60% vs. 100%, p = 0.049) mice was decreased compared with controls. CONCLUSION Sirtuin 1 deletion increases systemic inflammation in sepsis. Renal mitochondrial dysfunction, kidney injury, and mortality following CLP were all exacerbated by SIRT1 deletion. Similar effects on inflammation and survival were seen following myeloid cell–specific SIRT1 deletion, indicating that SIRT1 activity in myeloid cells may be a significant contributor for the protective effects of SIRT1 in sepsis. View on Web

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Integrating traffic safety data with area deprivation index: A method to better understand the causes of pediatric pedestrian versus automobile collisions

alexandrossfakianakis shared this article with you from Inoreader Integrating traffic safety data with area deprivation index: A method to better understand the causes of pediatric pedestrian versus automobile collisions via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND The purpose of this study was to identify clinical and traffic factors that influence pediatric pedestrian versus automobile collisions (P-ACs) with an emphasis on health care disparities. METHODS A retrospective review was performed of pediatric (18 years or younger) P-ACs treated at a Level I pediatric trauma center from 2008 to 2018. Demographic, clinical, and traffic scene data were analyzed. Area deprivation index (ADI) was used to measure neighborhood socioeconomic disadvantage (NSD) based on home addresses. Traffic scene data from the California Statewide Integrated Traffic Records System were matched to clinical records. Traffic safety was assessed by the streetlight coverage, the proximity of the collision to home addresses, and sidewalk coverage. Descriptive statistics and univariate analysis for key variables and outcomes were calculated using Kruskal-Wallis, Wilcoxon, χ2, or Fisher's exact tests. Statistical significance was attributed to p values of View on Web

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Transcriptome reveals the dysfunction of pancreatic islets after wound healing in severely burned mice

alexandrossfakianakis shared this article with you from Inoreader Transcriptome reveals the dysfunction of pancreatic islets after wound healing in severely burned mice via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Severely burned patients have a higher risk of diabetes mellitus after healing, but its mechanism remains unclear. Therefore, the purpose of the study was to explore the influence of burns on pancreatic islets of mice after wound healing. METHODS Forty-two male C57BL/6 mice were randomized into a sham group and a burn group and subjected to sham treatment or a third-degree burn model of 30% total body surface area. Fasting blood glucose was detected weekly for 8 weeks after severe burns. Glucose-stimulated insulin secretion was measured 8 weeks post severe burns. Islets of the two groups were isolated and mRNA libraries were sequenced by the Illumina sequencing platform. The expressions of differentially expressed genes (DEGs) related to the cell cycle and the amounts of mitochondrial DNA were detected by quantitative real-time polymerase chain reaction after gene ontology, gene set enrichment analysis, and protein-protein network analysis. Hematoxylin-eosin staining of pancreatic tail tissue and adenosine triphosphate (ATP) assay of islets were performed. RESULTS The levels of fasting blood glucose were significantly higher within 8 weeks post severe burns. Glucose-stimulated insulin secretion was impaired at the eighth week post severe burns. Totally 128 DEGs were selected. Gene ontology and gene set enrichment analysis indicated that the pathways related to the cell cycle, protein processing, and oxidative phosphorylation were downregulated. The expressions of DEGs related to the cell cycle showed a consistent trend with mRNA sequencing data, and most of them were downregulated post severe burns. The cell mass of the burn group was less than that of the sham group. Also, the concentration of ATP and the amount of mitochondrial DNA were lower in the burn group. CONCLUSION In the model of severe-burned mice, disorders in glucose metabolism persist for 8 weeks after burns, which may be related to low islet cell proliferation, downregulation of protein processing, and less ATP production. View on Web

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Reading the signs in penetrating cervical vascular injuries: Analysis of hard/soft signs and initial management from a nationwide vascular trauma database

alexandrossfakianakis shared this article with you from Inoreader Reading the signs in penetrating cervical vascular injuries: Analysis of hard/soft signs and initial management from a nationwide vascular trauma database via Journal of Trauma and Acute Care Surgery - Current Issue BACKGROUND Algorithms for management of penetrating cervical vascular injuries (PCVIs) commonly call for immediate surgery with "hard signs" and imaging before intervention with "soft signs." We sought to analyze the association between initial examination and subsequent evaluation and management approaches. METHODS Analysis of PCVIs from the American Association for the Surgery of Trauma Prospective Observational Vascular Injury Treatment vascular injury registry from 25 US trauma centers was performed. Patients were categorized by initial examination findings of hard signs or soft signs, and subsequent imaging and surgical exploration/repair rates were compared. RESULTS Of 232 PCVI patients, 110 (47%) had hard signs (hemorrhage, expanding hematoma, or ischemia) and 122 (53%) had soft signs. With hard signs, 61 (56%) had immediate operative exploration and 44% underwent computed tomography (CT) imaging. After CT, 20 (18%) required open surgical repair, and 7% had endovascular intervention. Of note, 21 (19%) required no operative intervention. A total of 122 patients (53%) had soft signs on initial examination; 37 (30%) had immediate surgery, and 85 (70%) underwent CT imaging. After CT, 9% had endovascular repair, 7% had open surgery, and 65 (53%) were observed. No difference in mortality was observed for hard signs patients undergoing operative management versus observation alone (23% vs. 17%, p = 0.6). Those with hemorrhage as the primary hard signs most often required surgery (76%), but no interventions were required in 19% of hemorrhage, 20% of ischemia, and 24% of expanding hematoma. CONCLUSION Although hard signs in PCVIs are associated with the need for operative intervention, initial CT imaging can facilitate endovascular options or nonoperative management in a significant subgroup. Hard signs should not be considered an absolute indication for immediate surgical exploration. LEVEL OF EVIDENCE Prognostic/Epidemiological; Level IV. 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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