Accuracy Of Non-invasive Tests Research Articles

Non-Invasive Detection of Anastomotic Leakage Following Esophageal and Pancreatic Surgery by Urinary Analysis

Background: Esophagectomy or pancreaticoduodenectomy is the standard surgical approach for patients with tumors of the esophagus or pancreatic head. Postoperative mortality is strongly correlated with the occurrence of anastomotic leakage (AL). Delay in diagnosis leads to delay in treatment, which ratifies the need for development of novel and accurate non-invasive diagnostic tests for detection of AL. Urinary volatile organic compounds (VOCs) reflect the metabolic status of an individual, which is associated with a systemic immunological response. The aim of this study was to determine the diagnostic accuracy of urinary VOCs to detect AL after esophagectomy or pancreaticoduodenectomy. Methods: In the present study, urinary VOCs of 63 patients after esophagectomy (n = 31) or pancreaticoduodenectomy (n = 32) were analyzed by means of field asymmetric ion mobility spectrometry. AL was defined according to international study groups. Results: AL was observed in 15 patients (24%). Urinary VOCs of patients with AL after pancreaticoduodenectomy could be distinguished from uncomplicated controls, area under the curve 0.85 (95% CI 0.76–0.93), sensitivity 76%, and specificity 77%. However, this was not observed following esophagectomy, area under the curve 0.51 (95% CI 0.37–0.65). Conclusion: In our study population AL following pancreaticoduodenectomy could be discriminated from uncomplicated controls by means of urinary VOC analysis, NTC03203434.

Non-coding RNAs in endometriosis: a narrative review.

Endometriosis is a benign gynaecological disorder, which affects 10% of reproductive-aged women and is characterized by endometrial cells from the lining of the uterus being found outside the uterine cavity. However, the pathophysiological mechanisms causing the development of this heterogeneous disease remain enigmatic, and a lack of effective biomarkers necessitates surgical intervention for diagnosis. There is international recognition that accurate non-invasive diagnostic tests and more effective therapies are urgently needed. Non-coding RNA (ncRNA) molecules, which are important regulators of cellular function, have been implicated in many chronic conditions. In endometriosis, transcriptome profiling of tissue samples and functional in vivo and in vitro studies demonstrate that ncRNAs are key contributors to the disease process. In this review, we outline the biogenesis of various ncRNAs relevant to endometriosis and then summarize the evidence indicating their roles in regulatory pathways that govern disease establishment and progression. Articles from 2000 to 2016 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: ncRNA and reproduction; ncRNA and endometriosis; miRNA and endometriosis; lncRNA and endometriosis; siRNA and endometriosis; endometriosis; endometrial; cervical; ovary; uterus; reproductive tract. All articles were independently screened for eligibility by the authors. This review integrates extensive information from all relevant published studies focusing on microRNAs, long ncRNAs and short inhibitory RNAs in endometriosis. We outline the biological function and synthesis of microRNAs, long ncRNAs and short inhibitory RNAs and provide detailed findings from human research as well as functional studies carried out both in vitro and in vivo, including animal models. Although variability in findings between individual studies exists, collectively, the extant literature justifies the conclusion that dysregulated ncRNAs are a significant element of the endometriosis condition. There is a compelling case that microRNAs, long non-coding RNAs and short inhibitory RNAs have the potential to influence endometriosis development and persistence through modulating inflammation, proliferation, angiogenesis and tissue remodelling. Rapid advances in ncRNA biomarker discovery and therapeutics relevant to endometriosis are emerging. Unravelling the significance of ncRNAs in endometriosis will pave the way for new diagnostic tests and identify new therapeutic targets and treatment approaches that have the potential to improve clinical options for women with this disabling condition.

IgG4-Associated Cholangitis in Patients Resected for Presumed Perihilar Cholangiocarcinoma: a 30-Year Tertiary Care Experience.

Distinguishing perihilar cholangiocarcinoma (PHC) from benign forms of sclerosing cholangitis affecting the hilar bile ducts is challenging, since histological confirmation of PHC is difficult to obtain and accurate non-invasive diagnostic tests are not available. IgG4-associated cholangitis (IAC), an imitator of PHC, may present with clinical and radiographical signs of PHC. IAC can be accurately diagnosed with a novel qPCR test. The aim of this study was to investigate the incidence and long-term activity of IAC in patients resected for PHC in a single tertiary center over a period of 30 years. All patients with benign disease who underwent surgery for presumed PHC in our institute between 1984 and 2015 were identified. Benign liver and bile duct specimens were re-evaluated by a pathologist and scored according to international consensus pathology criteria for IgG4-related disease (IgG4-RD). Patients with benign disease still alive were followed-up and a clinical diagnosis of IAC was made using a combination of the HISORt group C (response to steroids) criteria and elevated serum IgG4 levels and/or the novel IgG4/IgG RNA ratio. Also, recurrent symptomatic disease at any time after surgery requiring immunosuppression was assessed. Out of 323 patients who underwent surgery for presumed PHC, 50 patients (15%) had benign disease. In 42% (n = 21/50) of these patients a histological (n = 17) or clinical (n = 4) diagnosis of IAC was established. The remaining patients were diagnosed with unclassified sclerosing inflammation, cystadenoma, or sclerosing hemangioma. Nine out of 12 IAC patients who were followed-up showed episodes of recurrent disease requiring immunosuppressive treatment. Liver and bile duct resections for PHC during three decades disclosed in 15% benign biliary disorders mimicking PHC of which 42% were definitely diagnosed as IAC. IgG4-RD remains active in the majority of patients with IAC years after surgery. Novel diagnostic tests for IAC might reduce misdiagnosis, unnecessary surgery, and life-threatening complications.

Clinical evaluation of the iXip index to reduce prostate re-biopsies

BackgroundProstate biopsy is the gold standard for prostate cancer (PCa) diagnosis, but it's invasive and associated with adverse events. Novel reliable tumor biomarkers and accurate non-invasive tests are required to avoid biopsies. The immune complex PSA-IgM is a new marker for PCa, and it has been included in an algorithm to generate the diagnostic index iXip, which determines the probability of having PCa. In this study we evaluated the ability of iXip to reduce the number of repeat biopsies in patients with a previous negative biopsy and suspicious for PCa. Patients and methods219 patients referred for prostate rebiopsy were included in the study. Each patient underwent a trans-rectal ultrasound-guided prostate biopsy and prostate volume examination. Blood samples were collected before any prostatic manipulation to determine the serological levels of PSA-IgM and PSA. The iXip index was calculated as previously reported using an online calculator. ResultsiXip values in patients with a positive biopsy were significantly higher than the ones observed in negative patients (p-value = 0.001). Based on iXip values, patients were divided in five risk groups: those with iXip < 0.2 had 0% probability of having PCa. High values of the Gleason score (≥7) were observed mostly in patients with iXip 0.3–0.8. ConclusionOur preliminary results show that iXip identifies a sub-group of patients who can safely avoid rebiopsy because they do not have PCa. The index is a promising tool that could reduce the number of unnecessary prostate biopsies and the relative clinical complications and expenses.

Plasma urocortin-1 as a preoperative marker of endometriosis in symptomatic women

Accurate noninvasive diagnostic tests for endometriosis are still missing. This study evaluated the predictive value of the neuropeptide urocortin 1 (Ucn1) to detect pelvic endometriosis in symptomatic women. We enrolled prospectively 97 consecutive women submitted to gynecologic laparoscopy for chronic or acute pelvic pain, infertility or adnexal mass. Preoperative blood samples were assayed for Ucn1 using enzyme immunoassay. Patients with endometriosis had higher plasma Ucn1 levels compared to patients with no lesions (median 59 vs. 34 pg/ml, p < .01, Dunn's test). Elevated plasma Ucn1 levels were found among all endometriosis phenotypes (superficial peritoneal lesions, ovarian endometrioma, and deep infiltrating endometriosis, p < .05 vs. no lesions). Receiver operating characteristics curve analysis identified plasma Ucn1 > 46 pg/mL as the best cutoff point to detect endometriosis vs. no lesions, with 76% sensitivity and 88% specificity (area under the curve [AUC] 0.827, 95% confidence interval [CI] 0.695 − 0.959), but no cutoff could accurately distinguish endometriosis from other pathological conditions (AUC 0.593 [95% CI 0.474 − 0.711]). In women with chronic pelvic pain, infertility, or both symptoms, the probability of endometriosis (positive predictive value) increased consistently with the increase of plasma Ucn1 levels. The present findings suggest that high plasma Ucn1 levels increase the likelihood of endometriosis in symptomatic women.

A Retrospective Analysis of Three Non-Invasive Tests for Initial Diagnosis of &amp;lt;i&amp;gt;Helicobacter pylori&amp;lt;/i&amp;gt; Infection in Children

Proper diagnosis in the pediatric population is required to eradicate Helicobacter pylori (H. pylori) and prevent gastric cancer. Our aim was to assess the performance of non-invasive tests to diagnose H. pylori infection in pediatric patients. A retrospective analysis was performed on 141 pediatric patients requiring endoscopic evaluation and diagnostic tests for H. pylori infection to define the cause of abdominal symptoms. Non-invasive tests included the 13C-urea breath test (UBT), a monoclonal stool antigen test using enzyme-linked immuno-sorbent assay (mSAT), and a serum immunoglobulin G antibody test using antigens derived from Japanese individuals (S-Ab). This study investigated sensitivity, specificity, likelihood ratios for a positive and a negative test (LR+ and LR-), and accuracy of non-invasive tests, in comparison with invasive tests. Eighty two of 141 patients (58%) were recognized as H. pylori positive by invasive methods. When UBT, mSAT or S-Ab were analyzed, all were found to be effective over 94% accurate. Specificity ranged between 86.7% and 95.8%, and sensitivity ranged between 93.8% and 97.1%. When subjects were stratified into three distinct age groups, the best performance was achieved for 1-6 years old with mSAT at 100% for sensitivity, specificity, and accuracy. S-Ab yielded the best results for children 7-12 years old and the UBT test performed best for 13-18 years old. These results demonstrate the utility of UBT, mSAT, and S-Ab non-invasive tests in diagnosing H. pylori but suggest that certain tests may be optimal for children of distinct ages. Three non-invasive tests, UBT, mSAT and S-Ab showed sufficient sensitivity, specificity and accuracy for the initial diagnosis of H. pylori infection among pediatric patients. Non-invasive tests may contribute to achieving minimum invasive diagnosis with combining with a histological test and a culture test in children.

Frequent False-positive Bronchoalveolar Lavage Galactomannan Values in a Real-world Setting

BackgroundInvasive aspergillosis (IA) is the most common invasive mold infection (IMI) and early diagnosis is critical to improving clinical outcomes. Galactomannan (GM) is a major component of the Aspergillus cell wall. BAL GM is one of the mycologic criteria for diagnosis of probable IA, but it is frequently positive in patients with Aspergillus airway colonization, and its specificity has not been well-studied. Our goal was to estimate the specificity of a positive BAL galactomannan value in a contemporary cohort of consecutive patients with BAL GM checked as part of their workup for potential IA.MethodsWe reviewed clinical and microbiologic data of patients who had at least one positive BAL GM (≥0.5), at Brigham and Women’s Hospital from November 2009 to March 2016. We applied EORTC/MSG IMI definitions to classify patients as having possible, probable or proven IMI, excluding BAL GM result as mycologic criterion.ResultsWe studied 134 patients. Median age was 58; 49% were women. 54% had hematologic malignancy (HM), 10% were solid organ (SOT) and 34% hematopoetic stem-cell transplant (HSCT) recipients. 60% received mold-active antifungal treatment. 4 patients (3%) had proven, 60 (45%) probable, 15 (11%) possible, and 55 (41%) no IMI. One had proven mucormycosis, making at least 42% of positive BAL GM results falsely positive (specificity 58%, 95% confidence interval 47–69%). 6-week mortality was 35% overall: 75% for proven, 47% probable, 33% possible, and 20% for no IMI (χ2 for trend P = 0.008). In patients with no IMI, 6-week mortality was comparable in those who did not receive mold-active treatment (13%, 5/38) and those who did (38%, 6/16, Fischer’s P = 0.07).ConclusionIn this study, at least 42% of positive BAL GM values were falsely positive, potentially exposing these patients to unnecessary antifungals. The number of ‘probable’ IMI cases (which, along with proven IMI are typically included in clinical trials of new antifungals) would be falsely increased by 25%, using a positive BAL GM alone to adjudicate IMI status. Accurate noninvasive tests for diagnosis of IMI are urgently needed. Table: % +BAL GM values in patients with no IMI at various cutoff values. BAL GM ≥ 0.5 BAL GM ≥ 0.8 BAL GM ≥ 1.0 Overall 422217 HM 28147 SOT 1005050 HSCT 30117Disclosures All authors: No reported disclosures.

Pathology of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of lesions ranging from steatosis (Non-alcoholic Fatty Liver or NAFL) to a complex pattern with hepatocellular injury and inflammation (non-alcoholic steatohepatitis; NASH) in the absence of alcohol intake. However, it is increasingly clear that intermediate patterns may exist. The histopathological evaluation of liver biopsy samples is central in the diagnosis of NAFLD and NASH in the absence of sufficiently accurate non-invasive tests because a precise definition of each group is a key issue. When at least 5% of hepatocytes display steatosis, patients can be defined as having NAFLD in an appropriate clinical context. When, in addition, lobular inflammation and liver cell clarification/ballooning are present, then the lesion is usually defined as NASH. Evaluation of the stage of fibrosis is even more fundamental than necroinflammation since it is the main prognostic factor of this disease. Semi-quantitative histological scoring systems have been proposed for NAFLD, but they are not useful in clinical practice and each has certain limitations. For comprehensive purposes, we suggest describing histopathological lesions in NAFLD using the SAF (Steatosis, Activity, Fibrosis) score which assesses separately the grade of steatosis (S, from S0 to S3), the grade of activity (A from A0 to A4 by adding grades of ballooning and lobular inflammation, both from 0 to 2) and the stage of fibrosis (F from F0 to F4).

Blood metal ion levels are not a useful test for adverse reactions to metal debris: A systematic review and meta-analysis.

ObjectivesAlarm over the reported high failure rates for metal-on-metal (MoM) hip implants as well as their potential for locally aggressive Adverse Reactions to Metal Debris (ARMDs) has prompted government agencies, internationally, to recommend the monitoring of patients with MoM hip implants. Some have advised that a blood ion level >7 µg/L indicates potential for ARMDs. We report a systematic review and meta-analysis of the performance of metal ion testing for ARMDs.MethodsWe searched MEDLINE and EMBASE to identify articles from which it was possible to reconstruct a 2 × 2 table. Two readers independently reviewed all articles and extracted data using explicit criteria. We computed a summary receiver operating curve using a Bayesian random-effects hierarchical model.ResultsOur literature search returned 575 unique articles; only six met inclusion criteria defined a priori. The discriminative capacity of ion tests was homogeneous across studies but that there was substantial cut-point heterogeneity. Our best estimate of the “true” area under curve (AUC) for metal ion testing is 0.615, with a 95% credible interval of 0.480 to 0.735, thus we can state that the probability that metal ion testing is actually clinically useful with an AUC ≥ 0.75 is 1.7%.ConclusionMetal ion levels are not useful as a screening test for identifying high risk patients because ion testing will either lead to a large burden of false positive patients, or otherwise marginally modify the pre-test probability. With the availability of more accurate non-invasive tests, we did not find any evidence for using blood ion levels to diagnose symptomatic patients.Cite this article: M. Pahuta, J. M. Smolders, J. L. van Susante, J. Peck, P. R. Kim, P. E. Beaule. Blood metal ion levels are not a useful test for adverse reactions to metal debris: a systematic review and meta-analysis. Bone Joint Res 2016;5:379–386. DOI: 10.1302/2046-3758.59.BJR-2016-0027.R1.

P181. Accuracy of non-invasive tests in the initial diagnostic work-up of paediatric inflammatory bowel diseases

P181. Accuracy of non-invasive tests in the initial diagnostic work-up of paediatric inflammatory bowel diseases

Comparison of Serum IgG Antibody Test with Gastric Biopsy for the Detection of Helicobacter Pylori Infection among Egyptian Children.

BACKGROUND:In developing countries, Helicobacter pylori (H. pylori) infection is mainly acquired during childhood and may be a predisposing factor for peptic ulcer or gastric cancer later in life. Noninvasive diagnostic tools are particularly useful in children for screening tests and epidemiological studies. Data on serologic testing of children are lacking. Accurate noninvasive tests for diagnosing Helicobacter pylori infection in children are strongly required.AIM:The aim of this study was to evaluate the performance of a serological test (serum IgG antibody for H. pylori) in Egyptian children with recurrent abdominal pain necessitating endoscopy.SUBJECTS AND METHODS:One hundred children, referred to the endoscopy unit at Mansoura University. Upper endoscopy was done for each with rapid urease test (RUT) and histological examination as the gold standard test for detection of H. pylori infection. Serum samples were collected for detecting IgG for H. pylori infection.RESULTS:The mean age of the subjects included in the study was 7.23 ± 1.94 year. Serological test (IgG to H. pylori) was positive in 60% of all cases. A highly significant association between the standard test and the serological test at a cutoff > 10 U/ml at p = 0.001 were detected for the diagnosis of H. pylori infection. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for the IgG antibody a cutoff > 10 U/ml, were 96.5%, 93%, 13.83, 0.038 respectively.CONCLUSION:Serum IgG antibody to H. pylori infection has a high diagnostic value and can be considered as a suitable and reliable noninvasive test for detection of H. pylori infection.

P1034 ESTIMATED PREVALENCE OF HCV CIRRHOSIS IN THE CHRONIC HEPATITIS COHORT STUDY (CHECS)

Aim: To investigate the accuracy of non-invasive tests for assessing residual cirrhosis in HCV patients after an SVR. Methods: All HCV patients with a pre-treatment histological diagnosis of cirrhosis and available post-SVR liver biopsies had residual liver fibrosis assessed through the following non-invasive methods: APRI, CDS, Fib4, FibroQ, Forns score, Guci Index, King score, Lok Index, PLF. Liver fibrosis staged according to the METAVIR score was the reference standard. The performances of non-invasive tests to diagnose residual cirrhosis were calculated using receiver operating characteristic (ROC) curves analysis. Results: 20 out of 33 patients (61%) included in the study had cirrhosis regression after 61 (48–104) months from an SVR. The overall diagnostic accuracy of all the non invasive serum panels analyzed was suboptimal as indicated by the AUROC values and the operative characteristics of the tests. None of these tests is useful in identifying patients with residual cirrhosis when using both the cut-off indicated by the literature (bold) and the cut off with the best sensitivity and specificity derived from the ROC curves (Table 1).

Aspartate Aminotransferase to Platelet Ratio Index and FibroScan for Predicting Liver Fibrosis with Chronic Hepatitis B

Background: Non-invasive test have been constructed and evaluated mainly for binary diagnoses. The accuracy of non-invasive tests such as aspartate aminotransferase to platelet ratio index (APRI) and transient elastography/FibroScan should be evaluated especially in clinical practice. The aim of the study was to evaluate the accuracy of detailed fibrosis classification available for APRI and FibroScan to liver biopsy in chronic hepatitis B patients. Method: A cross sectional study was conducted in 51 patients with chronic hepatitis B. The patients underwent laboratory test, FibroScan and liver biopsy between April 2011 and July 2013 at Adam Malik Hospital, Medan. Liver biopsy was assessed based on the METAVIR score. Area under receiver operating characteristic curve (AUROC) predictive value was used to evaluate the accuracy of APRI and FibroScan. All data were analyzed using SPSS 20.0. Results : APRI versus METAVIR diagnosed severe fibrosis and cirrhosis with sensitivity 40% and specificity 83.9%, positive predictive value (PPV) 61.5%, negative predictive value (NPV) 68.4%, positive likelihood ratio (LR) 2.48 and negative LR 0.72 with diagnostic accuracy 66.7%. The AUROC value was 0.619 (95% CI = 0.446 – 0.715); kappa = 0.255; p > 0.05. FibroScan versus METAVIR predictive value with sensitivity 75% and specificity 67.6% were PPV 60%, NPV 67.7%, positive LR 2.31 and negative LR 0.36 with diagnostic accuracy 70.6%. The AUROC value was 0.714 (95% CI = 0.567–0.861); kappa 0.409; p < 0.05. Conclusion : FibroScan has better accuracy than APRI for predicting severe fibrosis and cirrhosis in patients with chronic hepatitis B. Keywords : APRI, FibroScan, liver biopsy, chronic hepatitis B

478 TNF -α and IL-8 Predict Cardiac Vasculopathy after Cardiac Transplantation

Purpose: Cardiac allograft vasculopathy (CAV) is a major cause of mortality after heart transplantation. Yearly coronary angiograms are performed post transplantation to screen for CAV. Accurate non-invasive screening tests for CAV might decrease the need for coronary angiograms. Cellular and humoral immune responses have been implicated in the development of CAV; we hypothesized that immune function and cytokine expression could potentially provide information regarding the development of CAV. Methods and Materials: We measured Immuknow, concentration of 12 cytokines and sCD30 in blood collected at the time of routine endomyocardial biopsy and when clinically indicated. CAV was defined as new coronary artery disease (CAD) detected by angiography or a significant worsening (increase in coronary stenosis 50% or more) of previously diagnosed CAD. Results: We collected 162 samples from 56 cardiac transplant recipients. CAV was identified in 4 patients. Significant correlation was observed between CAV and TNFand IL8 (P 0.001). ROC curve was constructed to test the performance of TNFand IL8 in predicting CAV and showed a maximum efficiency for TNFat 38ng/ml (sensitivity 66.67%, specificity 97.74%), and a maximum efficiency for IL8 at 2.2ng/ml (sensitivity 66.67%, specificity 82.71%). No significant correlation between CAV and other immune function parameters was identified. Conclusions: Our data suggest strong correlation between CAV and TNFwhich initiates the proinflammatory response. A significant correlation is also seen with IL-8 which is a potent proinflammatory and chemotactic cytokine. These findings may indicate a major role for these cytokines in the pathogenesis of CAV and should be validated in a larger patient cohort.

A Clinical Prediction Rule and Platelet Count Predict Esophageal Varices in Children

The validation of noninvasive tests to diagnose esophageal varices is a priority in children because repeated endoscopic evaluations are too invasive. We measured the ability of a previously developed noninvasive clinical prediction rule (CPR) to predict the presence of esophageal varices in children. We analyzed data from 108 children, younger than age 18, who received endoscopies at 8 centers, to assess portal hypertension from chronic liver disease or portal vein obstruction. Blood test and abdominal ultrasound scan results were obtained within 4 months of endoscopy. Grading of varices identified by endoscopy was confirmed by independent blinded review. Spleen size, based on data from the ultrasound scan, was expressed as a standard deviation score relative to normal values for age. Of the children studied, 74 had esophageal varices (69%), including 35 with large varices (32%). The best noninvasive predictors of esophageal varices of any size were as follows: platelet:spleen size z-score ratio (area under the receiver operating characteristic curve [AUROC], 0.84; 95% confidence interval [CI] 0.75-0.93), CPR (AUROC, 0.80; 95% CI, 0.70-0.91), and platelet count (AUROC, 0.79; 95% CI, 0.69-0.90). The positive predictive values for the CPR and platelet count were 0.87 and 0.86, the negative predictive values were 0.64 and 0.63, the positive likelihood ratios were 3.06 and 2.76, and the negative likelihood ratios were 0.64 and 0.63, respectively. Based on positive and negative predictive values, the most accurate noninvasive tests were the CPR and platelet counts. Noninvasive tests such as CPR and platelet count can assist in triaging children for endoscopy to identify esophageal varices.

Prognostic value of Multidetector Computed Tomography of cirrhosis

Background Liver biopsy is an invasive test used to diagnose chronic liver disease and to assess the degree of hepatic inflammation and fibrosis. In recent years the accuracy of noninvasive tests has increased. The aim of this study was to evaluate whether the hepatic attenuation detected at triphasic MDCT was related to the degree of cirrhosis and allow the prognosis in human patients to be established. Afterwards we have also defined the parenchymal structural alterations and vascular changes detected by CT in an animal model of hepatic cirrhosis.

AST-platelet ratio index, Forns index and FIB-4 in the prediction of significant fibrosis and cirrhosis in patients with chronic hepatitis C

The aim of this study was to evaluate the diagnostic accuracy of aspartate aminotransferase-platelet ratio index, the Forns index and FIB-4 for the assessment of hepatic fibrosis in chronic hepatitis C patients by comparison with liver biopsy. We retrospectively reviewed our computerized data of chronic hepatitis C patients who admitted to the Gastroenterology Clinic between 2004 and 2008. Treatment-naive chronic hepatitis C patients who had undergone liver biopsy and had laboratory test results allowing the calculation of aspartate aminotransferase-platelet ratio index, the Forns index and FIB-4 were included in this study. The degree of fibrosis was scored according to the METAVIR staging system. Significant fibrosis was defined as F2-4 and cirrhosis as F4. Aspartate aminotransferase-platelet ratio index, the Forns index and FIB-4 were calculated based on the original studies. Tests results were compared between groups F0-1 (no or mild fibrosis) versus F2-4 (significant fibrosis) and F03 (no cirrhosis) versus F4 (cirrhosis). One hundred and fifty patients with chronic hepatitis C were included in this study. The areas under the ROC curves of the Forns index, aspartate aminotransferase-platelet ratio index and FIB-4 to predict significant fibrosis were 0.795, 0.774 and 0.764, respectively. The area under the ROC curves of the Forns index, aspartate aminotransferase-platelet ratio index and FIB-4 to predict cirrhosis were 0.879, 0.839 and 0.874, respectively. The Forns index, aspartate aminotransferase-platelet ratio index and FIB-4 were accurate noninvasive blood tests to predict the presence or absence of significant fibrosis and cirrhosis in half of the chronic hepatitis C patients. The Forns index was slightly better than the aspartate aminotransferase-platelet ratio index and FIB-4 in the prediction of significant fibrosis and cirrhosis.

Iron deposition and increased alveolar septal capillary density in nonfibrotic lung tissue are associated with pulmonary hypertension in idiopathic pulmonary fibrosis

BackgroundEarly diagnosis of pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) has potential prognostic and therapeutic implications but can be difficult due to the lack of specific clinical manifestations or accurate non-invasive tests. Histopathologic parameters correlating with PH in IPF are also not known. Remodeling of postcapillary pulmonary vessels has been reported in the nonfibrotic areas of explanted lungs from IPF patients. We hypothesized that iron deposition and increased alveolar capillaries, the findings often seen in postcapillary PH, might predict the presence of clinical PH, independent of the severity of fibrosis or ventilatory dysfunction in IPF patients. To test this hypothesis, we examined the association between these histologic parameters and the degree of PH, with consideration of the severity of disease in IPF.MethodsIron deposition and alveolar septal capillary density (ASCD) were evaluated on histologic sections with hematoxylin-eosin, iron, elastin and CD34 stainings. Percentage of predicted forced vital capacity (FVC%) was used for grading pulmonary function status. Fibrosis score assessed on high resolution computed tomography (HRCT) was used for evaluating overall degree of fibrosis in whole lungs. Right ventricular systolic pressure (RVSP) by transthoracic echocardiography was used for the estimation of PH. Univariate and multivariate regression analyses were performed.ResultsA cohort of 154 patients was studied who had the clinicopathological diagnosis of IPF with surgical lung biopsies or explants during the period of 1997 to 2006 at Mayo Clinic Rochester. In univariate analysis, RVSP in our IPF cases was associated with both iron deposition and ASCD (p < 0.001). In multivariate analysis with FVC% and HRCT fibrosis score included, iron deposition (p = 0.02), but not ASCD (p = 0.076), maintained statistically significant association with RVSP. FVC% was associated with RVSP on univariate analysis but not on multivariate analysis, while fibrosis score lacked any association with RVSP by either univariate or multivariate analyses.ConclusionsIron deposition and ASCD in non fibrotic lung tissue showed an association with RVSP, suggesting that these features are possible morphologic predictors of PH in IPF.

Diagnosis and management of endometriosis: The role of the advanced practice nurse in primary care

To discuss the etiology, clinical presentation, diagnosis, and management of endometriosis for the advanced practice nurse (APN) in primary care. Selected research, clinical studies, clinical practice guidelines, and review articles. Commonly encountered by the APN in primary care, endometriosis is a chronic, progressive inflammatory disease characterized by endometrial lesions, cysts, fibrosis, or adhesions in the pelvic cavity, causing chronic pelvic pain and infertility in women of reproductive age. Because of its frequently normal physical examination findings, variable clinical presentations, and nonspecific, overlapping symptoms with other conditions, endometriosis can be difficult to diagnose. As there currently are no accurate noninvasive diagnostic tests specific for endometriosis, it is imperative for the APN to become knowledgeable about the etiology, clinical presentation, diagnosis, and current treatment options of this disease. The APN in primary care plays an essential role in health promotion through disease management and infertility prevention by providing support and much needed information to the patient with endometriosis. APNs can also facilitate quality of care and manage treatments effectively to improve quality of life, reduce pain, and prevent further progression of disease. Practice recommendations include timely diagnosis, pain management, infertility counseling, patient education, and support for quality of life issues.

Diagnosis of Fibrosis and Cirrhosis Using Liver Stiffness Measurement in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Accurate noninvasive tests for liver injury are urgently needed. The aim of this study was to evaluate the accuracy of transient elastography for the diagnosis of fibrosis and cirrhosis in patients with NAFLD and to study factors associated with discordance between transient elastography and histology. Two hundred forty-six consecutive patients from two ethnic groups had successful liver stiffness measurement and satisfactory liver biopsy specimens. The area under the receiver-operating characteristics curve (AUROC) of transient elastography for F3 or higher and F4 disease was 0.93 and 0.95, respectively, and was significantly higher than that of the aspartate aminotransferase-to-alanine aminotransferase ratio, aspartate aminotransferase-to-platelet ratio index, FIB-4, BARD, and NAFLD fibrosis scores (AUROC ranged from 0.62 to 0.81, P < 0.05 for all comparisons). At a cutoff value of 7.9 kPa, the sensitivity, specificity, and positive and negative predictive values for F3 or greater disease were 91%, 75%, 52%, and 97%, respectively. Liver stiffness was not affected by hepatic steatosis, necroinflammation, or body mass index. Discordance of at least two stages between transient elastography and histology was observed in 33 (13.4%) patients. By multivariate analysis, liver biopsy length less than 20 mm and F0-2 disease were associated with discordance. Transient elastography is accurate in most NAFLD patients. Unsatisfactory liver biopsy specimens rather than transient elastography technique account for most cases of discordance. With high negative predictive value and modest positive predictive value, transient elastography is useful as a screening test to exclude advanced fibrosis. Liver biopsy may be considered in NAFLD patients with liver stiffness of at least 7.9 kPa.