Role of biopsy sampling for diagnosis of early and progressed hepatocellular carcinoma

The current guidelines for the diagnosis of hepatocellular carcinoma (HCC) recommend liver biopsy for hepatic nodules which do not demonstrate the typical features of HCC on imaging. Thus, while not all HCCs are biopsied for histological confirmation, the nodules that pathologists now encounter on biopsy specimens are frequently well-differentiated early HCCs. This paper reviews the pathological features of HCC and its precursor lesions on liver biopsy specimens, with special emphasis on the differential diagnosis between well-differentiated HCCs and high-grade dysplastic nodules, and discusses the different roles of liver biopsy in diagnosis and management of early and progressed HCC. The potential role of liver biopsy for the development of molecular markers to predict prognosis and response to targeted therapy is also discussed.     

Liver abnormalities in connective tissue diseases

The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd–Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.     

Ability of low-dose helical CT to distinguish between benign and malignant noncalcified lung nodules

STUDY OBJECTIVES: Low-dose helical CT scanning identifies early stage lung malignancies and also a large proportion of lung nodules of uncertain diagnostic and prognostic significance (ie, indeterminate nodules). The sensitivity, specificity, and predictive value of these indeterminate nodules detected by CT scanning as part of a lung cancer screening program is largely unknown. We therefore calculated the sensitivity, specificity, and predictive values of CT-detected lung nodules that were followed up at least 18 months. DESIGN: Single-arm screening trial with longitudinal follow-up. SETTING: Rural areas of United States, from 2000 to 2004. PARTICIPANTS: Former and current nuclear weapons workers, >/= 45 years old, including smokers and never-smokers, with variable exposure to occupational lung carcinogens. INTERVENTIONS: A total of 4,401 participants were CT scanned for lung cancer with an initial full chest low-dose CT scan, interval CT scans at 3, 6, and 12 months for indeterminate lung nodules (eg, nodules not immediately suspicious for lung cancer), and a 18-month, full-chest, low-dose incidence CT scan. RESULTS: We achieved follow-up for a minimum of 18 months for > 95% of 807 participants with indeterminate or suspicious lung nodules. Only 3 of 727 indeterminate nodules were identified as being malignant during the subsequent 18 months. The radiologist's designation of a nodule as suspicious had a sensitivity of 84.2% and a specificity of 96.6%. Given a prior probability of lung cancer of 2.4%, positive and negative predictive values were 37.2% and 99.6%. Overall, we detected 33 primary lung cancers, including 19 stage I cancers, 5 stage II cancers, 7 stage III-IV cancers, and 3 limited-stage small cell cancers. CONCLUSIONS: Helical CT scanning detects many indeterminate nodules, but few are malignant. CT scanning has high sensitivity and specificity to detect early lung cancer. The problem of false-positive results in helical CT scanning is limited and can be rationally managed. Current CT follow-up recommendations are supported.     

Solid or partly solid solitary pulmonary nodules: their characterization using contrast wash-in and morphologic features at helical CT

BACKGROUND: Solitary pulmonary nodule (SPN) evaluation based on analyses of combined wash-in (WI) and washout (WO) values obtained by helical dynamic CT (HDCT) scanning is useful for malignant SPN characterization, because this method has higher specificity and accuracy than that based on analyses of WI values only. However, increased specificity results in reduced sensitivity and the missing of malignant SPNs. Thus, the purpose of this study was to seek the most effective method for SPN characterization during HDCT scanning. METHODS: After obtaining unenhanced CT scans, dynamic CT scanning was performed using a helical technique (images were obtained at 30, 60, 90, and 120 s, and at 5 and 15 min after the initiation of IV contrast administration) in 486 patients with a solid or partly solid SPN. Diagnostic efficacies were compared for three approaches involving considerations of WI values (in Housfield units [HU]) only, both WI and WO HU values, and WI HU values and morphologic characteristics. RESULTS: Considering WI values only (> or = 25 HU), sensitivity, specificity, and accuracy for malignancy were 98% (233 of 237 nodules), 46% (114 of 249 nodules), and 71% (347 of 486 nodules), respectively. Using both a WI value of > or = 25 HU and a WO value of 5 to 36 HU, the corresponding values were 89% (212 of 237 nodules), 79% (197 of 249 nodules), and 84% (409 of 486 nodules), respectively; for a WI value of > or = 25 HU and a malignant morphology, the corresponding values were 92% (219 of 237 nodules), 79% (197 of 249 nodules), and 86% (416 of 486 nodules), respectively (these values were significantly different between the WI-only group and the other two groups; p = 0.001). CONCLUSIONS: The efficacy of SPN evaluation based on analyses of WI values plus morphologic features during HDCT scanning appears to be equivalent to that based on analyses of WI plus WO values, thus obviating the need for WO scans, which saves time and reduces radiation exposure of the patient.     

The Benefits Conferred by Radial Access for Cardiac Catheterization Are Offset by a Paradoxical Increase in the Rate of Vascular Access Site Complications With Femoral Access: The Campeau Radial Paradox

ObjectivesThe purpose of this study was to assess whether the benefits conferred by radial access (RA) at an individual level are offset by a proportionally greater incidence of vascular access site complications (VASC) at a population level when femoral access (FA) is performed.BackgroundThe recent widespread adoption of RA for cardiac catheterization has been associated with increased rates of VASCs when FA is attempted.MethodsLogistic regression was used to calculate the adjusted VASC rate in a contemporary cohort of consecutive patients (2006 to 2008) where both RA and FA were used, and compared it with the adjusted VASC rate observed in a historical control cohort (1996 to 1998) where only FA was used. We calculated the adjusted attributable risk to estimate the proportion of VASC attributable to the introduction of RA in FA patients of the contemporary cohort.ResultsA total of 17,059 patients were included. At a population level, the VASC rate was higher in the overall contemporary cohort compared with the historical cohort (adjusted rates: 2.91% vs. 1.98%; odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.17 to 1.89; p = 0.001). In the contemporary cohort, RA patients experienced fewer VASC than FA patients (adjusted rates: 1.44% vs. 4.19%; OR: 0.33, 95% CI: 0.23 to 0.48; p < 0.001). We observed a higher VASC rate in FA patients in the contemporary cohort compared with the historical cohort (adjusted rates: 4.19% vs. 1.98%; OR: 2.16, 95% CI: 1.67 to 2.81; p < 0.001). This finding was consistent for both diagnostic and therapeutic catheterizations separately. The proportion of VASCs attributable to RA in the contemporary FA patients was estimated at 52.7%.ConclusionsIn a contemporary population where both RA and FA were used, the safety benefit associated with RA is offset by a paradoxical increase in VASCs among FA patients. The existence of this radial paradox should be taken into consideration, especially among trainees and default radial operators.     

5-Year Outcomes After Transcatheter Aortic Valve Implantation With CoreValve Prosthesis

ObjectivesThe purpose of this analysis was to assess 5-year outcomes of transcatheter aortic valve implantation (TAVI) using the current technology of the self-expanding CoreValve prosthesis (Medtronic Inc., Minneapolis, Minnesota).BackgroundThere is a paucity of evidence on long-term durability of currently available transcatheter heart valves.MethodsStarting in June 2007, all consecutive patients with severe aortic stenosis undergoing TAVI with the third-generation 18-F CoreValve device in 8 Italian centers were prospectively included in the ClinicalService Project. For the purposes of this study, we included only consecutive patients with 5-year follow-up data available (n = 353) treated from June 2007 to August 2009. All outcomes were reported according to VARC (Valve Academic Research Consortium)-1 criteria.ResultsAll-cause mortality rates at 1, 2, 3, 4, and 5 years were 21%, 29%, 38%, 48%, and 55.0%, respectively. Cardiovascular mortality rates at 1, 2, 3, 4, and 5 years were 10%, 14%, 19%, 23%, and 28.0%, respectively. The overall neurological event rate at 5 years was 7.5%, of which more than two-thirds occurred early after the procedure. During follow-up, there were 241 rehospitalizations for cardiovascular reasons in 164 (46%) patients. Among all rehospitalizations, acute heart failure was the most frequently reported (42.7%), followed by requirement of permanent pacemaker implantation (17.4%). On echocardiography, mean transaortic gradients decreased from 55.6 ± 16.8 mm Hg (pre-TAVI) to 12.8 ± 10.9 mm Hg (5-year post-TAVI) (p < 0.001). Late prosthesis failure occurred in 5 cases (1.4%); among these, redo TAVI was successfully carried out in 2 patients (0.6%) presenting with symptomatic prosthesis restenosis. The remaining 3 cases of prosthesis failure did not undergo further invasive interventions. Ten patients (2.8%) showed late mild stenosis with a mean transaortic gradient ranging from 20 to 40 mm Hg. No other cases of structural or nonstructural valvular deterioration were observed. Valve thrombosis or late valve embolization were not reported.ConclusionsTAVI with the currently adopted CoreValve generation was associated with sustained clinical outcomes up to 5-year follow-up, with a low rate (1.4%) of significant prosthetic valve degeneration. The procedure appears to be an adequate and lasting resolution of aortic stenosis in selected high-risk patients.     

Pleural tuberculosis in the United States: incidence and drug resistance

BACKGROUND: Pleural tuberculosis (TB) should be considered in any patient with a lymphocytic pleural effusion. The diagnostic approach is under debate. Knowledge of pleural TB epidemiology would be beneficial. To help clarify pleural TB epidemiology, we analyzed US national TB surveillance data for 1993 to 2003. METHODS: We compared pleural TB to pulmonary TB (where each was reported as the major site of TB disease, and no additional sites of disease were reported). Applicable statistical tests were performed; p < 0.05 was considered to be significant. RESULTS: From 1993 through 2003, 7,549 cases of pleural TB and 156,779 cases of pulmonary TB were reported (in 2003: pleural TB, 536 cases; pulmonary TB, 10,551 cases). The annual proportion of pleural TB was relatively stable (median rate, 3.6%; range, 3.3 to 4.0%) compared to that for pulmonary TB, which steadily decreased (average annual decrease, 0.9%; p < 0.01). Pleural TB occurred significantly more often than pulmonary TB among persons >/= 65 years old (30.4% vs 23.3%, respectively; p < 0.01), and it occurred significantly less often among children < 15 years old (1.8% vs 6.1%, respectively; p < 0.01) and persons 45 to 64 years old (22.9% vs 27.9%, respectively; p < 0.01). Pleural TB patients (63.4%) were born slightly more often in the United States than were pulmonary TB patients (60.9%; p < 0.01). Drug-resistance patterns of pleural TB broadly reflected those of pulmonary TB. However, isolates from pleural TB patients were less often resistant to at least isoniazid (6.0% vs 7.8%, respectively; p < 0.01) and to at least one first-line TB drug (9.9% vs 11.9%, respectively; p < 0.01) compared with pulmonary TB patients. CONCLUSIONS: Knowledge of pleural TB demographic, clinical, and drug-resistance patterns may assist clinicians in making diagnostic and therapeutic decisions.     

CMR in Patients With Severe Myocarditis: Diagnostic Value of Quantitative Tissue Markers Including Extracellular Volume Imaging

ObjectivesThis study evaluated the accuracy of T2, T1, and extracellular volume (ECV) quantification as novel quantitative tissue markers in comparison with standard “Lake-Louise” cardiac magnetic resonance (CMR) criteria to diagnose myocarditis.BackgroundNovel approaches using T2 and T1 mapping may overcome the limitations of signal intensity-based parameters, which would potentially result in a better diagnostic accuracy compared with standard CMR techniques in suspected myocarditis.MethodsCMR was performed in 104 patients with myocarditis and 21 control subjects at 1.5-T. Patients with myocarditis underwent CMR 2 weeks (interquartile range: 1 to 7 weeks) after presentation with new-onset heart failure (n = 66) or acute chest pain (n = 38). T2 and T1 mapping were implemented into a standard protocol including T2-weighted (T2w), early gadolinium enhancement (EGE) CMR, and late gadolinium enhancement (LGE) CMR. T2 quantification was performed using a free-breathing, navigator-gated multiecho sequence. T1 quantification was performed using the modified Look-Locker inversion recovery sequence before and after administration of 0.075 mmol/kg gadobenate dimeglumine. T2, T1, and ECV maps were generated using a plug-in for the OsiriX software (Pixmeo, Bernex, Switzerland) to calculate mean global myocardial T2, T1, and ECV values.ResultsThe diagnostic accuracies of conventional CMR were 70% (95% confidence interval [CI]: 61% to 77%) for T2w CMR, 59% (95% CI: 56% to 73%) for EGE, and 67% (95% CI: 59% to 75%) for LGE. The diagnostic accuracies of mapping techniques were 63% (95% CI: 53% to 73%) for myocardial T2, 69% (95% CI: 60% to 76%) for native myocardial T1, and 76% (95% CI: 68% to 82%) for global myocardial ECV. The diagnostic accuracy of CMR was significantly improved to 90% (95% CI: 84% to 95%) by a stepwise approach, using the presence of LGE and myocardial ECV ≥27% as diagnostic criteria, compared with 79% (95% CI: 71% to 85%; p = 0.0043) for the Lake-Louise criteria.ConclusionsIn patients with clinical evidence for subacute, severe myocarditis, ECV quantification with LGE imaging significantly improved the diagnostic accuracy of CMR compared with standard Lake-Louise criteria.     

Heterogeneity of hepatocellular carcinoma contributes to cancer progression

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease displaying differences in angiogenesis, extracellular matrix proteins, the immune microenvironment and tumor cell populations. Additionally, genetic variations and epigenetic changes of HCC cells could lead to aberrant signaling pathways, induce cancer stem cells and enhance tumor progression. Thus, the heterogeneity in HCC contributes to disease progression and a better understanding of its heterogeneity will greatly aid in the development of strategies for the HCC treatment.     

Diagnostic Accuracy of Myocardial Magnetic Resonance Perfusion to Diagnose Ischemic Stenosis With Fractional Flow Reserve as Reference: Systematic Review and Meta-Analysis

ObjectivesThis paper systematically analyzed the performance of magnetic resonance (MR) perfusion to diagnose coronary artery disease (CAD) with fractional flow reserve (FFR) as the reference standard.BackgroundMyocardial MR perfusion has passed the stage of a research technique and has demonstrated the ability to detect functional or ischemic stenosis of coronary arteries. However, the evidence is limited to single-center studies and small sample sizes.MethodsWe searched PubMed and Embase databases for all published studies that evaluated the accuracy of MR perfusion to diagnose CAD versus FFR. We used an exact binomial rendition of the bivariate mixed-effects regression model with test type as a random-effects covariate to synthesize the available data. Based on Bayes’ theorem, the post-test probability was calculated to guide MR perfusion’s clinical utility.ResultsWe identified 14 studies evaluating 1,073 arteries and 650 patients. The pooled sensitivity and specificity were 0.90 (95% confidence interval [CI]: 0.86 to 0.93) and 0.87 (95% CI: 0.82 to 0.90) at the patient level and 0.89 (95% CI: 0.83 to 0.92) and 0.86 (95% CI: 0.77 to 0.92) at the artery and territory levels, respectively. The area under the summary receiver-operating characteristic at the patient level was 0.95 (95% CI: 0.92 to 0.96) and 0.93 (95% CI: 0.91 to 0.95) at the artery and territory levels, respectively. MR perfusion could increase the post-test probability of CAD >80% in patients with a pre-test probability of >37% and can decrease post-test probability of CAD <20% with a pre-test probability of <72%.ConclusionsWith FFR as the reference standard, the diagnostic ability of MR perfusion to detect ischemic CAD is high.     

Intravascular Ultrasound-Derived Minimal Lumen Area Criteria for Functionally Significant Left Main Coronary Artery Stenosis

ObjectivesThis study sought to evaluate the intravascular ultrasound (IVUS) minimal lumen area (MLA) for functionally significant left main coronary artery (LMCA) stenosis using fractional flow reserve (FFR) as the standard.BackgroundThe evaluation of significant LMCA stenosis remains challenging.MethodsWe identified 112 patients with isolated ostial and shaft intermediate LMCA stenosis (angiographic diameter stenosis of 30% to 80%) who underwent IVUS and FFR measurement.ResultsThe FFR was ≤0.80 in 66 LMCA lesions (59%); these exhibited smaller reference vessels, smaller minimal lumen diameter, greater diameter of stenosis, longer lesion length, smaller MLA, larger plaque burden, and more frequent plaque rupture. The independent factors of an FFR of ≤0.80 were plaque rupture (odds ratio [OR]: 4.47; 95% Confidence Interval (CI): 1.35 to 14.8; p = 0.014); body mass index (OR: 1.19; 95% CI: 1.00 to 1.41; p = 0.05), age (OR: 0.95; 95% CI: 0.90 to 1.00; p = 0.031), and IVUS MLA (OR: 0.37; 95% CI: 0.25 to 0.56; p < 0.001). The optimal IVUS MLA cutoff value for an FFR of ≤0.80 was 4.5 mm² (77% sensitivity, 82% specificity, 84% positive predictive value, 75% negative predictive value, area under the curve: 0.83, 95% CI: 0.76 to 0.96; p < 0.001) overall and 4.1 to 4.5 mm² in various subgroups. Adjustment for the body surface area, body mass index, and left ventricular mass did not improve the diagnostic accuracy of the IVUS MLA.ConclusionsIn patients with isolated ostial and shaft intermediate LMCA stenosis, an IVUS-derived MLA of ≤4.5 mm² is a useful index of an FFR of ≤0.80.     

A prognostic tool to predict severe acute pancreatitis in pediatrics

Background/ObjectivesApproximately 15–20% of pediatric patients with acute pancreatitis (AP) develop severe disease. Severity scoring tools were developed for adult patients, but have limitations when applied in children. We aimed to identify early predictors of severe acute pancreatitis (SAP) on hospital admission for early risk stratification of patients.MethodsRetrospective review of AP admissions was conducted. The derivation cohort included cases at Cincinnati Children's Hospital Medical Center (CCHMC) between 2009 and 2013. Clinical data collected during the first 24 h of admission were analyzed and a predictive model was derived through statistical analysis. The performance of the model was evaluated in a validation cohort from 2 more institutions other than CCHMC.ResultsIn the derivation cohort 19% of the 284 admissions were SAP. A generalized linear mixed effect model analysis revealed that lipase, albumin and white blood count (WBC) play a role in the development of SAP (area under the receiver operating curve (AUROC 0.76)). In the validation cohort of 165 AP cases, SAP ranged from 8 to 20% at the three institutions. Performance of the model in this cohort was comparable to the derivation model (AUROC 0.77). There were 369 encounters in the combined derivation and validation pool (AUROC 0.76).ConclusionsThe prognostic severity tool with 3 variables (lipase, albumin, and WBC) obtained within 24 h of admission can be applied to predict SAP in pediatric patients.     

Thrombus Formation Following Transcatheter Aortic Valve Replacement

ObjectivesThis paper reviews the published data and reports 3 cases of thrombosis involving CoreValve (Medtronic, Minneapolis, Minnesota) and 1 involving Edward Sapien (Edwards Lifesciences, Irvine, California) devices. Three of these cases had pathological findings at autopsy.BackgroundOnly a limited number of cases of valve dysfunction with rapid increase of transvalvular aortic gradients or aortic insufficiency post-transcatheter aortic valve replacement (TAVR) have been described. This nonstructural valvular dysfunction has been presumed to be because of early pannus formation or thrombosis.MethodsThrough reviews of the published reports and 4 clinical cases, pathological and clinical findings of early valve thrombosis are examined to elucidate methods for recognition and identifying potential causes and treatments.ResultsThis paper presents 4 cases, 2 of which had increasing gradients post-TAVR. All 3 pathology cases showed presence of a valve thrombosis in at least 2 TAV leaflets on autopsy, but were not visualized by transthoracic echocardiogram or transesophageal echocardiogram. One case was medically treated with oral anti coagulation with normalization of gradients. The consequence of valve thrombosis in all 3 pathology patients either directly or indirectly played a role in their early demise. At least 18 case reports of early valve thrombosis have been published. In 12 of these cases, the early treatment with anticoagulation therapy resolved the thrombus formation and normalized aortic pressures gradients successfully.ConclusionsThese 4 cases elucidate the occurrence of valve thrombosis post-TAVR. Consideration should be given to treatment with dual antiplatelet therapy and oral anticoagulation in patients post-TAVR with increasing mean pressure gradients and maximum aortic valve velocity. Further research should be conducted to create guidelines for antithrombotic therapy following TAVR procedure.     

A Registry-Based Randomized Trial Comparing Radial and Femoral Approaches in Women Undergoing Percutaneous Coronary Intervention: The SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) Trial

ObjectivesThis study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial.BackgroundWomen are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear.MethodsWomen undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population.ResultsThe trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access.ConclusionsIn this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236)     

B-vitamins intake,DNA-methylation of One Carbon Metabolism and homocysteine pathway genes and myocardial infarction risk: The EPICOR study

Background and aimsSeveral epidemiological studies highlighted the association between folate and B-vitamins low intake and cardiovascular diseases (CVD) risk. Contrasting results were reported on the relationship between folate intake and DNA-methylation. Folate and B-vitamins may modulate DNA-methylation of specific enzymes which are included in the One-Carbon Metabolism (OCM) and in the homocysteine (Hcy) pathways. The aim of the study was to evaluate whether DNA-methylation profiles of OCM and Hcy genes could modulate the myocardial infarction (MI) risk conferred by a low B-vitamins intake.Methods and resultsStudy sample (206 MI cases and 206 matched controls) is a case-control study nested in the prospective EPIC cohort. Methylation levels of 33 candidate genes where extracted by the whole epigenome analysis (Illumina-HumanMethylation450K-BeadChip). We identified three differentially methylated regions in males (TCN2 promoter, CBS 5′UTR, AMT gene-body) and two in females (PON1 gene-body, CBS 5′UTR), each of them characterized by an increased methylation in cases. Functional in silico analysis suggested a decreased expression in cases. A Recursively Partitioned Mixture Model cluster algorithm identified distinct methylation profiles associated to different MI risk: high-risk vs. low-risk methylation profile groups, OR = 3.49, p = 1.87 × 10⁻⁴ and OR = 3.94, p = 0.0317 in males and females respectively (multivariate logistic regression adjusted for classical CVD risk factors). Moreover, a general inverse relationship between B-vitamins intake and DNA-methylation of the candidate genes was observed.ConclusionsOur findings support the hypothesis that DNA-methylation patterns in specific regions of OCM and Hcy pathways genes may modulate the CVD risk conferred by folate and B-vitamins low intake.     

Secretin-stimulated magnetic resonance imaging/magnetic resonance cholangiopancreatography for the detection of chronic pancreatitis: A meta-analysis

ObjectiveTo evaluate the diagnostic accuracy of secretin-stimulated magnetic resonance imaging/magnetic resonance cholangiopancreatography (S-MRI/MRCP) as noninvasive modalities in detecting chronic pancreatitis (CP).MethodsA systematic literature search in the PubMed, EMBASE, Web of Science, Cochrane, and Chinese Biomedical Literature Databases to identify relevant original studies. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (version 2). Study data were independently extracted to calculate sensitivity and specificity, as well as areas under summary receiver operating characteristic curves (AUCs), and to test for heterogeneity and the threshold effect.ResultsThe sample comprised 11 studies including 180 patients with CP and 340 patients without CP. Pooled sensitivity and specificity were 0.72 (95% confidence interval [CI] 0.65–0.78) and 0.87 (95% CI 0.83–0.90), respectively. Pooled positive and negative likelihood ratios were 4.99 (95% CI 2.59–9.61) and 0.32 (95% CI 0.19–0.54), respectively. The diagnostic odds ratio was 23.31 (95% CI 7.50–72.44). The AUC and Q¹ index were 0.8631 and 0.7937, respectively. Publication bias was absent (P = 0.64).ConclusionsS-MRI/MRCP had low sensitivity and moderately high specificity for the detection of CP. Large-scale, quality-controlled, prospective studies are needed to verify the diagnostic accuracy of these modalities.     

Specific increase in serum core-fucosylated haptoglobin in patients with chronic pancreatitis

Background/ObjectivesPancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignancies, and its diagnosis in early stages is the most important prognostic factor. Chronic pancreatitis (CP), a common background of PDAC occurrence, is morphologically defined as progressive pancreatic fibrosis and inflammation accompanied by pancreatic exocrine cell atrophy. We recently found that inflammation and fibrosis are independent characteristic histological changes in noncancerous lesions in PDAC patients despite the absence of a past history of clinical CP. Subclinical CP is an important background for PDAC occurrence. Therefore, there is an urgent need to develop a noninvasive and reliable biomarker for CP diagnosis.MethodsFifty-nine healthy volunteers (HV), 159 patients with CP, and 83 patients with PDAC were enrolled in this study. We measured serum total fucosylated haptoglobin (Fuc-Hpt) and core-Fuc-Hpt levels using lectin-antibody enzyme-linked immunosorbent assay kits that we developed. In these kits, total Fuc-Hpt and core-Fuc-Hpt were measured using Aleuria aurantia lectin and Pholiota squarrosa lectin, respectively.ResultsSerum Fuc-Hpt levels were significantly increased in CP patients compared to HV (P < 0.0001) and were further increased in PDAC patients (P < 0.0001). Interestingly, serum core-Fuc-Hpt levels were significantly higher in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Multivariate analyses demonstrated that total serum core-Fuc-Hpt was an independent determinant for CP diagnosis, but Fuc-Hpt was not.ConclusionsA dramatic change in oligosaccharides was observed in serum haptoglobin between CP and PDAC. Serum core-Fuc-Hpt may be a novel and useful biomarker for CP diagnosis.     

Diagnostic value of interferon-gamma in tuberculous pleurisy: a metaanalysis

BACKGROUND: Conventional tests are not always helpful in making a diagnosis of tuberculous pleurisy. Many studies have investigated the usefulness of interferon (IFN)-gamma measurements in pleural fluid for the early diagnosis of tuberculous pleurisy. We conducted a metaanalysis to determine the accuracy of IFN-gamma measurements in the diagnosis of tuberculous pleurisy. METHODS: After a systematic review of English-language studies, sensitivity, specificity, and other measures of accuracy of IFN-gamma concentrations in the diagnosis of pleural effusion were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. RESULTS: Twenty-two studies met our inclusion criteria. The summary estimates for IFN-gamma in the diagnosis of tuberculous pleurisy in the studies included were as follows: sensitivity, 0.89 (95% confidence interval [CI], 0.87 to 0.91); specificity, 0.97 (95% CI, 0.96 to 0.98); positive likelihood ratio, 23.45 (95% CI, 17.31 to 31.78); negative likelihood ratio, 0.11 (95% CI, 0.07 to 0.16); and diagnostic odds ratio, 272.7 (95% CI, 147.5 to 504.2). CONCLUSIONS: IFN-gamma determination is a sensitive and specific test for the diagnosis of tuberculous pleurisy. The measurement of IFN-gamma levels in pleural effusions is thus likely to be a useful tool for diagnosing tuberculous pleurisy. The results of IFN-gamma assays should be interpreted in parallel with clinical findings and the results of conventional tests.     

Noninvasive Imaging of Cardiovascular Injury Related to the Treatment of Cancer

The introduction of multiple treatments for cancer, including chemotherapeutic agents and radiation therapy, has significantly reduced cancer-related morbidity and mortality. However, these therapies can promote a variety of toxicities, among the most severe being the ones involving the cardiovascular system. Currently, for many surviving cancer patients, cardiovascular (CV) events represent the primary cause of morbidity and mortality. Recent data suggest that CV injury occurs early during cancer treatment, creating a substrate for subsequent cardiovascular events. Researchers have investigated the utility of noninvasive imaging strategies to detect the presence of CV injury during and after completion of cancer treatment because it starts early during cancer therapy, often preceding the development of chemotherapy or cancer therapeutics related cardiac dysfunction. In this State-of-the-Art Paper, we review the utility of current clinical and investigative CV noninvasive modalities for the identification and characterization of cancer treatment-related CV toxicity.