Sonorheometry Device Thresholds in Liver Transplantation: An Observational Retrospective Study.

BACKGROUND: Liver transplantation (LT) remains a potentially haemorrhagic procedure whose perioperative bleeding and transfusion could be better monitored using point-of-care devices. Quantra® is a device based on sonorheometry to assess whole blood clot formation. Our aims were to describe Quantra® parameters during LT and to study their correlations with standard laboratory parameters, and to determine Quantra® cut-off values for thrombocytopenia, hypofibrinogenemia and coagulation factors' deficit. METHODS: In 34 patients undergoing LT, blood samples were collected before surgical incision, 15 min after the beginning of the anhepatic phase, and 15 min after arterial revascularization of the graft. RESULTS: Clotting time (CT) was well correlated with prothrombin (PT) ratio and activated partial thromboplastin time (aPTT) ratio. Platelet contribution to clot stiffness (PCS) was correlated with platelets (ρ = 0.82, p < 0.001) and fibrinogen contribution clot stiffness (FCS) with fibrinogen (Fg) (ρ = 0.74, p < 0.001). CT predicted a PT ratio < 30% with an area under the curve (AUC) of 0.93 (95% CI 0.87-0.98; p < 0.001). PCS predicted a platelet count < 50 G/L with an AUC of 0.87 (95% CI 0.76-0.98, p < 0.001). FCS predicted a Fg < 1.0, 1.2 or 1.5 g/L, with an AUC of 0.86 (95% CI 0.77-094, p < 0.001), 0.82 (95% CI 0.74-0.91, p < 0.001) and 0.88 (95% CI 0.82-0.95, p < 0.001), respectively. CONCLUSION: Quantra® provides a rapid assessment of haemostasis during LT.

Pain phenotyping and investigation of outcomes in physical therapy: An exploratory study in patients with low back pain.

Phenotypes have been proposed as a method of characterizing subgroups based on biopsychosocial factors to identify responders to analgesic treatments. This study aimed to, first, confirm phenotypes in patients with low back pain receiving physical therapy based on an a priori set of factors used to derive subgroups in other pain populations. Second, an exploratory analysis examined if phenotypes differentiated pain and disability outcomes at four weeks of physical therapy. Fifty-five participants completed psychological questionnaires and pressure pain threshold (PPT). Somatization, anxiety, and depression domains of the Symptom-Checklist-90-Revised, and PPT, were entered into a hierarchical agglomerative cluster analysis with Ward's method to identify phenotypes. Repeated measures ANOVAs assessed pain ratings and disability by phenotype at four weeks. Three clusters emerged: 1) high emotional distress and pain sensitivity (n = 10), 2) low emotional distress (n = 34), 3) low pain sensitivity (n = 11). As an exploratory study, clusters did not differentiate pain ratings or disability after four weeks of physical therapy (p's>0.05). However, trends were observed as magnitude of change for pain varied by phenotype. This supports the characterization of homogenous subgroups based on a protocol conducted in the clinical setting with varying effect sizes noted by phenotype for short-term changes in pain. As an exploratory study, future studies should aim to repeat this trial in a larger sample of patients.

Status of ambulatory blood pressure monitoring and home blood pressure monitoring for the diagnosis and management of hypertension in the US: an up-to-date review.

The diagnosis and management of hypertension has been based on the measurement of blood pressure (BP) in the office setting. However, data have demonstrated that BP may substantially differ when measured in the office than when measured outside the office setting. Higher out-of-office BP is associated with increased cardiovascular risk independent of office BP. Ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM) are validated approaches for out-of-office BP measurement. In the 2015 and 2021 United States Preventive Services Task Force (USPSTF) reports on screening for hypertension, ABPM was recommended as the reference standard for out-of-office BP monitoring and for confirming an initial diagnosis of hypertension. This recommendation was based on data from more published studies of ABPM vs. HBPM on the predictive value of out-of-office BP independent of office BP. Therefore, HBPM was recommended as an alternative approach when ABPM was not available or well tolerated. The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline recommended ABPM as the preferred initial approach for detecting white-coat hypertension and masked hypertension among adults not taking antihypertensive medication. In contrast, HBPM was recommended as the preferred initial approach for detecting the white-coat effect and masked uncontrolled hypertension among adults taking antihypertensive medication. The current review provides an overview of ABPM and HBPM in the US, including best practices, BP thresholds that should be used for the diagnosis and treatment of hypertension, barriers to widespread use of such monitoring, US guideline recommendations for ABPM and HBPM, and data supporting HBPM over ABPM.

The association between sleep and psychological distress among New York City healthcare workers during the COVID-19 pandemic.

BACKGROUND: Healthcare workers (HCWs) treating patients with COVID-19 report psychological distress. We examined whether disturbed sleep was associated with psychological distress in New York City (NYC) HCWs during the initial peak of the COVID-19 pandemic (April-May 2020). METHODS: HCWs completed a survey screening for acute stress (4-item Primary Care PTSD screen), depressive (Patient Health Questionaire-2), and anxiety (2-item Generalized Anxiety Disorder scale) symptoms. Insomnia symptoms (modified item from the Insomnia Severity Index) and short sleep (SS, sleep duration <6 h/day) were assessed. Poisson regression analyses predicting psychological distress from SS and insomnia symptoms, adjusting for demographics, clinical role/setting, redeployment status, shifts worked, and multiple comparisons were performed. RESULTS: Among 813 HCWs (80.6% female, 59.0% white) mean sleep duration was 5.8 ± 1.2 h/night. Prevalence of SS, insomnia, acute stress, depressive, and anxiety symptoms were 38.8%, 72.8%, 57.9%, 33.8%, and 48.2%, respectively. Insomnia symptoms was associated with acute stress (adjusted prevalence ratio [PR]: 1.51, 95% CI: 1.35, 1.69), depressive (PR: 2.04, 95% CI: 1.78, 2.33), and anxiety (PR: 1.74, 95% CI: 1.55, 1.94) symptoms. SS was also associated with acute stress (PR: 1.17, 95% CI: 1.07, 1.29), depressive (PR: 1.36, 95% CI: 1.233, 1.51), and anxiety (PR: 1.38, 95% CI: 1.26, 1.50) symptoms. LIMITATIONS: Our cross-sectional analysis may preclude the identification of temporal associations and limit causal claims. CONCLUSIONS: In our study, SS and insomnia were associated with psychological distress symptoms in NYC HCWs during the COVID-19 pandemic. Sleep may be a target for interventions to decrease psychological distress among HCWs.

The stress, salt excretion, and nighttime blood pressure (SABRE) study: Rationale and study design.

Background: Abnormal diurnal patterns of blood pressure (BP) on ambulatory BP monitoring (ABPM), defined by reduced BP dipping or elevated nighttime BP, are associated with increased risk for adverse cardiovascular events. Psychological stress is associated with abnormal diurnal patterns of BP. Exposure to an acute stressor (e.g., mental stress task) normally increases urinary sodium excretion. However, some individuals have sodium retention after stress provocation, revealing substantial between-person variability in the degree of stress-induced sodium excretion. Prior research suggests urinary sodium excretion that does not occur during the daytime may shift toward the nighttime, accompanied by an increase in nighttime BP. Associations between psychological stress and the diurnal patterns of sodium excretion and BP are not yet fully understood. Design: The study is conducted in both the laboratory and naturalistic environment with a multi-racial/ethnic sample of 211 healthy adults. In the laboratory, change in urinary sodium excretion in response to mental stress tasks is examined with pre-/post-stress assessments of sodium excretion. Changes in angiotensin-II, catecholamines, BP, heart rate, endothelin-1, and cortisol are also assessed. In the 24-hour naturalistic environment, the diurnal patterns of sodium excretion and systolic BP are assessed as daytime-to-nighttime ratio of sodium excretion and ABPM, respectively. Ecological momentary assessments of perceived stress are also collected. Summary: The SABRE study investigates previously unexplored associations between stress-induced urinary excretion in the laboratory, diurnal patterns of sodium excretion and BP in the naturalistic environment, and ecological stress. It has high potential to advance our understanding of the role of psychological stress in hypertension.

Psychological distress, coping behaviors, and preferences for support among New York healthcare workers during the COVID-19 pandemic.

OBJECTIVE: The mental health toll of COVID-19 on healthcare workers (HCW) is not yet fully described. We characterized distress, coping, and preferences for support among NYC HCWs during the COVID-19 pandemic. METHODS: This was a cross-sectional web survey of physicians, advanced practice providers, residents/fellows, and nurses, conducted during a peak of inpatient admissions for COVID-19 in NYC (April 9th-April 24th 2020) at a large medical center in NYC (n = 657). RESULTS: Positive screens for psychological symptoms were common; 57% for acute stress, 48% for depressive, and 33% for anxiety symptoms. For each, a higher percent of nurses/advanced practice providers screened positive vs. attending physicians, though housestaff's rates for acute stress and depression did not differ from either. Sixty-one percent of participants reported increased sense of meaning/purpose since the COVID-19 outbreak. Physical activity/exercise was the most common coping behavior (59%), and access to an individual therapist with online self-guided counseling (33%) garnered the most interest. CONCLUSIONS: NYC HCWs, especially nurses and advanced practice providers, are experiencing COVID-19-related psychological distress. Participants reported using empirically-supported coping behaviors, and endorsed indicators of resilience, but they also reported interest in additional wellness resources. Programs developed to mitigate stress among HCWs during the COVID-19 pandemic should integrate HCW preferences.

[Could the publication of new european guidelines change practices in France?] / La publication au JO de nouveaux règlements européens sur les dispositifs médicaux pourrait-elle changer la pratique du diagnostic oncogénétique en France ?

The use of predictive biomarkers in the diagnosis and prediction of the efficacy of targeted therapies for the individualized management of patients is generally based on the use of in vitro medical diagnosis devices that are now covered by the guidelines 90/385/EEC, 93/42/EEC and 98/42/EEC. On 25 May 2017, the European Parliament and Council Regulations 2017/745 and 2017/746 of 5 April 2017, related to medical devices and in vitro medical diagnosis devices, respectively, were published, disrupting years of practices based on European directives. They tend to bring the in vitro diagnosis in Europe closer to the American regulation in order to improve the use of safety diagnosis tests, while the United States have been changing their practices in the face of biomedical, technological and digital evolutions. We will describe the different regulations of diagnostic tests and discuss their applications in the field of oncology.

Several clock genes polymorphisms are meaningful risk factors in the development and severity of cannabis addiction.

Circadian rhythms have been related to psychiatric diseases and regulation of dopaminergic transmission, especially in substance abusers. The relationship between them remained enigmatic and no data on the role of clock genes on cannabis dependence have been documented. We aimed at exploring the role of clock gene genotypes as potential predisposing factor to cannabis addiction, using a high throughput mass spectrometry methodology that enables the large-scale analysis of the known relevant polymorphisms of the clock genes. We have conducted a case-control study on 177 Caucasians categorizing between cannabis-addicted subjects and casual consumers based on structured interviews recorded socio-demographic data, AUDIT, Fagerström test, MINI, and medical examinations. Alcohol, opiates, and stimulants' consumption was as exclusion criteria. We report an association between several Single Nucleotide Polymorphism (SNP)s in main circadian genes SNPs, especially the gene locus HES7/PER1 on chromosome 17 and cannabis consumption as well as the development of neuropsychiatric and social disorders. This SNP's signature that may represent a meaningful risk factor in the development of cannabis dependence and its severity requires to be deeply explored in a prospective study.

Organoselenium Polymer Inhibits Biofilm Formation in Polypropylene Contact Lens Case Material.

OBJECTIVES: Contact lens-acquired bacterial infections are a serious problem. Of the reported cases, inadequate cleaning of the lens case was the most common cause of lens contamination. Organoselenium has been shown to inhibit bacterial attachment to different polymer materials. This study evaluates the ability of an organoselenium monomer, incorporated into the polymer of a polypropylene contact lens case coupon, to block the formation of biofilms in a lens case. METHODS: The bacteria tested were Pseudomonas aeruginosa, Staphylococcus aureus, Stenotrophomonas maltophilia, and Serratia marcescens. For this study, the bacteria were allowed to grow overnight, in trypticase soy broth media, in the presence of the selenium-containing polymer or the same polymer without organoselenium. The material was studied by both colony-forming unit determination and by confocal laser scanning microscopy. RESULTS: The results showed that the organoselenium polymer versus the control polymer resulted in the following effect on biofilm formation: (1) a reduction in P. aeruginosa of 7.3 logs (100%); (2) a reduction in S. aureus of 7.3 logs (100%); (3) a reduction in S. maltophilia of 7.5 logs (100%); and (4) a reduction in S. marcescens reduction of 3.3 logs (99.9%). To test the stability of the organoselenium polypropylene contact lens coupon, the coupon was soaked in PBS for eight weeks at room temperature. It was found that when these soaked coupons were tested against S. aureus, complete inhibition (8.1 logs) was obtained. Because organoselenium cannot leach from the polymer, this would imply that the organoselenium polypropylene contact lens case coupon would be inhibitory toward bacterial biofilm for the life of the case. CONCLUSION: The organoselenium polypropylene contact lens case coupon shows the ability to inhibit biofilm formation. The use of organoselenium copolymer should play an important role in protecting against contact lens case-acquired infection.

Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas.

Analysis of gene expression patterns in normal tissues and their perturbations in tumours can help to identify the functional roles of oncogenes or tumour suppressors and identify potential new therapeutic targets. Here, gene expression correlation networks were derived from 92 normal human lung samples and patient-matched adenocarcinomas. The networks from normal lung show that NKX2-1 is linked to the alveolar type 2 lineage, and identify PEBP4 as a novel marker expressed in alveolar type 2 cells. Differential correlation analysis shows that the NKX2-1 network in tumours includes pathways associated with glutamate metabolism, and identifies Vaccinia-related kinase (VRK1) as a potential drug target in a tumour-specific mitotic network. We show that VRK1 inhibition cooperates with inhibition of poly (ADP-ribose) polymerase signalling to inhibit growth of lung tumour cells. Targeting of genes that are recruited into tumour mitotic networks may provide a wider therapeutic window than that seen by inhibition of known mitotic genes.

The role of stem cells in airway repair: implications for the origins of lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. Recently, advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis. Much of this research has focused on the use of the airway repair model to study response to injury. In this review, we discuss the primary evidence of the role that cancer stem cells play in lung cancer development. The implications of a stem cell origin of lung cancer are reviewed, and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.

Development of a rapid and practical mutation screening assay for human lung adenocarcinoma.

Mortality after initial diagnosis of lung cancer is higher than from any other cancer. Although mutations in several genes, such as EGFR and K-ras, have been associated with clinical outcome, technical complexity, cost and time have rendered routine screening prohibitive for most lung cancer patients prior to treatment. In this study, using both novel and established technologies, we developed a clinically practical assay to survey the status of three frequently mutated genes in lung cancer (EGFR, K-ras and TP53) and two genes (BRAF and ß-catenin) with known hotspot mutations in many other cancers. A single 96-well plate was designed targeting a total of 14 fragments (16 exons) from EGFR, K-ras, TP53, BRAF and ß-catenin. In 96 lung adenocarcinoma patients, the mutation frequencies of three major genes (EGFR, K-ras and TP53) were between 21-24%. Fifty-six out of 96 (58%) patients had a mutation in at least one of the five genes. K-ras mutations positively correlated with smoking pack-years (p=0.035). EGFR mutations were frequent in never-smokers (p=0.0007), Asians (p=0.0204) and non-stage I lung cancer (p=0.016). There was also a trend towards an association between the presence of any mutation and improved recurrence-free survival (p=0.070). We demonstrate that our novel multigene mutation assay technology can rapidly and cost-effectively screen for mutations in lung adenocarcinoma. This screening assay can be used in the clinical setting for the large-scale validation of prognosis and/or predicting therapeutic response so that the majority of lung cancer patients can benefit from leveraging up-to-date knowledge on how mutation profiles may influence treatment options.

A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies.

BACKGROUND: The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. METHODS: A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I-III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). FINDINGS: Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5-80·0) in low-risk, 58·3% (48·9-66·6) in intermediate-risk, and 49·2% (42·2-55·8) in high-risk patients (p(trend)=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0-80·6) in low-risk, 57·4% (48·3-65·5) in intermediate-risk, and 44·6% (40·2-48·9) in high-risk patients (p(trend)<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. INTERPRETATION: Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. FUNDING: UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.

Downregulation of EMX2 is associated with clinical outcomes in lung adenocarcinoma patients.

BACKGROUND: The 5-year survival rate for stage I non-small-cell lung cancer (NSCLC) of 50% to 70% indicates that our current staging methods do not adequately predict outcome. Empty spiracles homeobox 2 (EMX2) is a homeo-domain-containing transcription factor that regulates a key developmental pathway known to promote lung tumorigenesis. This study assessed the significance of EMX2 as a prognostic biomarker in lung adenocarcinoma including bronchioloalveolar carcinoma (BAC). PATIENTS AND METHODS: 144 patients with lung adenocarcinoma undergoing surgical resection were studied. Quantitative real-time reverse transcriptase polymerase chain reaction and Immunohistochemistry were used to analyze EMX2 mRNA and protein expression, respectively. Association of EMX2 mRNA expression levels with clinical outcomes was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. RESULTS: EMX2 mRNA expression was significantly downregulated in lung adenocarcinoma compared with matched adjacent normal tissue (P < .001). EMX2 protein expression was similarly found to be downregulated in lung adenocarcinoma. The EMX2-high mRNA expressing group had statistically significant better overall survival (OS) than the EMX2-low mRNA expressing group (P = .005). Subgroup analysis also demonstrated improved survival in stage I patients (P = .01) and patients with BAC (P = .03). Lastly, the EMX2-high mRNA expressing group had statistically significant better recurrence-free survival (RFS) than the EMX2-low mRNA expression group in patients with adenocarcinoma (P < .001). CONCLUSION: EMX2 expression is downregulated in lung adenocarcinoma. Low EMX2 mRNA expression is significantly associated with decreased OS and RFS in patients with lung adenocarcinoma, particularly with stage I disease and BAC.

Association between MTHFR 677C-T polymorphism and alcohol dependence according to Lesch and Babor typology.

Prior studies have associated 677C-T Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with decreased enzymatic activity and modified homocysteine regulation. This study determines and compares MTHFR 677C-T distribution and examines its consequences on homocysteine metabolism and alcohol dependence in alcoholic patients classified according to the Babor and Lesch typologies. MTHFR TT genotype was more prevalent in AD patients with milder alcohol dependence (Babor type A) and with Lesch type 3, associated with depression. MTHFR TT was also associated with hyperhomocysteinemia. Determining MTHFR 677C-T genotype, folate and vitamin B12 levels could assist physicians in identifying type 3 patients and improve addictions management.

Lactate threshold at the same fat-free mass and age is larger in men than women.

The lactate threshold (LT) represents the onset of a metabolic acidosis during graded exercise testing (GXT). It is typically measured as an oxygen uptake (VO(2)) but then ratio scaled by body mass or VO(2) peak to make comparisons among subjects. Theoretical considerations and empirical evidence suggest that this type of ratio scaling is not valid. A method that allows a dependent variable to be compared between groups at that same value of one or more covariates is analysis of covariance (ANCOVA). Our purpose was to compare the LT, estimated non-invasively by gas exchange (LT(GE)), at the same fat-free mass (FFM) and age in 203 sedentary subjects (102 men) aged 20-70 years. Each subject underwent cycle ergometer GXT with LT(GE) measured by the V-slope method. In model development, we discovered an interaction term between sex and age. As dimensional analysis predicts a log-linear relationship between LT(GE) and FFM, two of the model terms were ln LT(GE) and ln FFM. The ANCOVA model was then as follows: dependent variable = ln LT(GE), fixed factor = sex, covariates = ln FFM, age, and sex x age. Sex made a significant contribution to the model (F = 30.7, P < 0.001). At the mean FFM (56.32 kg) and age (44.01 years) of both sexes combined, the LT(GE) was 29% larger in males (1,307 ml min(-1) versus 1,011 ml min(-1)). The model's interaction term resulted in larger differences at younger ages and smaller differences at older ages. We conclude that LT(GE) at the same FFM and age is larger in sedentary men compared to sedentary women.

Protective effect against alcohol dependence of the thermolabile variant of MTHFR.

BACKGROUND: Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, in particularly in those with marked withdrawal symptoms. The common C677T transition on the methylenetetrahydrofolate reductase (MTHFR) gene influences homocysteinemia. Our objective was to study the prevalence of the MTHFR C677T polymorphism in alcohol-dependent subjects and the influence of this polymorphism on symptoms associated with alcoholism. METHODS: MTHFR C677T polymorphism was determined in 93 control subjects and 242 alcohol-dependent subjects. Serum homocysteine, folate and vitamin B12 levels together with hepatic biological parameters were determined in the control and alcohol-dependent subjects. RESULTS: Hyperhomocysteinemia is frequently observed in alcohol-dependent subjects, particularly in those with marked withdrawal symptoms. Alcohol-dependent subjects showed a significant decrease in MTHFR 677TT prevalence (9%, 21/242) compared to controls (18%, 17/93) (p<0.02). The relative risk estimated as an odds ratio for alcoholism in subjects with the TT genotype is 0.42 (odd ratio 95% confidence interval, 0.21-0.83). Moreover, drinkers with TT genotype presented lower values for markers of alcohol misuse (p<0.05), better liver function tests, a lower frequency of relapses and no marked withdrawal symptoms as assessed by the Lesch typology. CONCLUSION: MTHFR 677TT genotype could play a protective role against alcohol dependence. Moreover, when subjects with MTHFR 677TT genotype become dependent to alcohol, they seem to constitute a subgroup of alcoholic patients with a decreased risk for developing neurotoxic withdrawal symptoms and hepatic toxicity.

Comparison of three methods for detection of the lactate threshold.

The lactate threshold (LT) represents the onset of a metabolic acidosis during graded exercise testing (GXT). It is a valuable measurement in clinical exercise testing and correlates well with endurance performance. Our purpose was to compare three LT detection methods, namely, Inspection (work rate at onset of a systematic increase in blood lactate concentration determined by inspection of blood lactate versus work rate plot), 0.5 mM (work rate which just precedes a rise in blood lactate concentration of >0.5 mM) and log-log (work rate at the intersection of two linear lines in plot of log lactate versus log work rate where the residual sum of squares for both lines added together is minimized). Fourteen subjects underwent cycle ergometer GXT with blood samples obtained at the end of each 3-min work rate increment and analysed for lactate concentration. The mean +/- 95% confidence limits of work rates at LT for the Inspection, 0.5 mM and log-log methods were 104.5 +/- 28.0, 103.2 +/- 28.1 and 105.1 +/- 27.3 W, respectively. Repeated-measures analysis of variance yielded a non-significant F ratio. The Bland-Altman bias +/- 95% limits of agreement for Inspection versus 0.5 mM, Inspection versus log-log and 0.5 mM versus log-log were 1.3 +/- 20.6, -0.6 +/- 12.5 and -1.9 +/- 20.5 W, respectively. The intraclass correlation coefficients for Inspection versus 0.5 mM, Inspection versus log-log and 0.5 mM versus log-log were 0.978, 0.992 and 0.977, respectively. The results of this study suggest that all three methods detect the LT at the same work rate.

New perspectives and strategy research biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Cirrhosis caused by hepatitis B virus, hepatitis C virus or chronic alcohol intake is associated with major risk. Systematic screening for HCC of asymptomatic patients with cirrhosis is needed for earlier detection of small tumors requiring treatment (liver transplantation, surgical resection, percutaneous techniques). The recommended screening strategy among cirrhotic patients is based on regular liver ultrasonography associated with serum alpha-fetoprotein (AFP) assay. As the performance of AFP is not satisfactory, additional tumoral markers are proposed (des-gamma-carboxyprothrombin, glycosylated AFP-L3 fraction). Currently, diagnosis of HCC in cirrhotic patients includes non-invasive tests (imaging after contrast administration, AFP assay); diagnostic biopsy is performed when imaging is limited. After treatment, tumor recurrence is assessed by regular follow-up (AFP assay and imaging). Despite the lack of accurate markers, recent developments in genomic and proteomic approaches will allow the discovery of new biomarkers for primary tumors, as well as for recurrence. This review summarizes the current state of biomarkers for screening, diagnosis and follow-up of HCC, and highlights new perspectives in the field.