True Positive Cases Research Articles

Nine years of newborn screening for classical galactosemia in the Netherlands: Effectiveness of screening methods, and identification of patients with previously unreported phenotypes.

Newborn screening (NBS) for classical galactosemia (CG) was introduced in the Netherlands in 2007. Multiple screening methods have been used since, and currently a two-tier system is used, with residual enzyme activity of galactose-1-phosphate-uridyltransferase (GALT) and total galactose concentration in dried blood spots as the primary and secondary markers. As it is essential to monitor effectiveness of NBS programs, we assessed the effectiveness of different screening methods used over time (primary aim), and aimed to identify and investigate patients identified through NBS with previously unreported clinical and biochemical phenotypes (secondary aim). The effectiveness of different screening methods and their cut-off values (COVs), as used from 2007 through 2015, was determined, and the clinical and biochemical data of all identified patients were retrospectively collected. All screening methods and COVs resulted in relatively high false-positive rates and low positive predictive values. Total galactose levels in dried blood spots were far above the COV for NBS in all true positive cases. A total of 31 galactosemia patients were identified, and when corrected for a family with three affected siblings, 14% had a previously unreported phenotype and genotype. These individuals did not demonstrate any symptoms at the time of diagnosis while still being exposed to galactose, had galactose-1-phosphate values below detection limit within months after the start of diet, and had previously unreported genotypes. Optimization of NBS for CG in the Netherlands is warranted because of the high false-positive rate, which may result in significant harm. Furthermore, a surprising 14% of newborns identified with CG by screening had previously unreported clinical and biochemical phenotypes and genotypes. For them, individualized prognostication and treatment are warranted, in order to avoid unnecessary stringent galactose restriction.

Sensitivity and specificity of multispectral imaging in detecting central serous chorioretinopathy

Central serous chorioretinopathy (CSCR) is a common and idiopathic retinal disorder that affects young to middle aged adults. The aim of this study was to describe the characteristics of eyes with CSCR using a light-emitting diode (LED)-based multispectral imaging (MSI) system and to evaluate the diagnostic reliability of MSI compared to fluorescein angiography (FA) in detecting CSCR. A total of 56 eyes among 52 patients with 1 or more retinal pigment epithelium (RPE) abnormality were retrospectively enrolled in the study. The patients underwent complete examination, including optical coherence tomography, FA, indocyanine-green angiography, and MSI. MSI images were retrospectively reviewed by experienced masked graders. Diagnoses that were made based on MSI alone were compared with those that were made using FA. Sensitivity and specificity were calculated, and the morphological features on MSI were summarized. Among 56 eyes in 52 patients, MSI detected 22 of 26 true-positive CSCR cases but missed 4 FA-confirmed lesions. Further, it correctly excluded 30 of 30 non-CSCR lesions. The sensitivity and specificity of MSI were 84.6 and 100%, respectively, for identifying CSCR. Using MSI, RPE leakage was observed in 25 (96.2%) of 26 eyes with CSCR, which was comparable to the performance of FA. Dome-shaped areas of signal, which corresponded to fluid accumulation associated with neurosensory retinal detachment or RPE detachment were observed in 23 (88.5%) of 26 eyes. As a non-invasive technique, MSI permitted the visualization of RPE leakage and neurosensory detachment and allowed good detection of CSCR in this selected clinical population. Lasers Surg. Med. 49:498-505, 2017. © 2016 Wiley Periodicals, Inc.

Diagnostic Accuracy of Magnetic Resonance Cholangio- Pancreatography in Choledocholithiasis

Objectives: To estimate the diagnostic accuracy of MRCP in the detection of bile duct calculi in patients with obstructive jaundice using ERCP as gold standard. Study Design: This is a cross sectional study. The study was conducted at Department of Diagnostic Radiology and Imaging Civil Hospital Karachi, from 01-08-2013 to 31-12-2014. Materials & Methods: This study comprises 249 cases of clinically observed obstructive jaundice which were referred by hospital consultants or by general practitioner to the Radiology Department for Magnetic Resonance Cholangio-Pancreatography (MRCP). Inclusion criteria were Patients of either gender between 26- 70 years of age with obstructive jaundice, raised direct bilirubin levels of 3 mg/dl and above, raised alkaline phosphatase levels and abdominal ultrasound showed suspicion of stone in dilated or non-dilated common bile duct. Previously Diagnosed cases of Choledocholithiasis, patients of chronic liver disease and those for which MRI is contraindicated such as those with surgical clips, braces were excluded from the study. Standard MRI technique carried out for evaluation of bile duct calculi in obstructive jaundice patients. Its features were carefully evaluated in terms of presence and absence of calculus / calculi, dilatation of CBD and pancreatic duct and presence of intrahepatic cholestasis by the consultant radiologist. Data entered and Statistical analyses were carried out by using SPSS version 17. Sensitivity, specificity, diagnostic accuracy positive and negative predictable values were calculated. Mean and frequency distribution for ages and gender was calculated respectively. Results: Mean age of the patients was 45.54 ±11.352 years. Gender distribution shows, 42 patients (17%) were male while remaining 207 patients (83%) were female. True positive cases for stones were 145 (58%) and false positive cases were 80 (32%). Positive predictive value was 91.77%, negative predictive value 87.91% with sensitivity 92.95%, specificity 86.02% and Diagnostic accuracy were found to be 90.36%. Conclusion: It is conclude that Magnetic Resonance Cholangio-Pancreatography (MRCP) is a safe, precise, relatively fast, with no ionizing radiation and non-invasive imaging modality for the assessment of common bile duct stones in patients of obstructive jaundice. The result of this study recommends that MR Imaging showed high Sensitivity and positive predictive values in the detection of bile duct calculi.

Retrospective study of spine tumor surgery with intraoperative neurophysiological monitoring

Objective To summarize the application features of IONM in spine tumor surgery and evaluate its value. Methods From September 2012 to June 2015, a total of 119 patients who underwent spine tumor surgery with IONM at the Sun Yatsen Memorial Hospital were retrospectively analyzed. IONM includes somatosensory evoked potentials (SEP), transcranial-electrical stimulation motor evoked potentials (TcE-MEP) and spontaneous, triggered electromyography (EMG). There were 64 males and 55 females with an average age of 44.8 years (range 4-80 years). 59 cases were primary tumors (included 28 cases of neurogenic tumors) and 60 were spinal metastasis. We judged the IONM alarm of true, false positive and negative cases based on whether related to surgery and postoperative neurological function. The statistical indexes were calculated and analyzed. Results The operation time was 2-12 h with an average of 4.8 h and the blood loss was 50-7 000 ml with an average of 1 800 ml. All the patients were followed up for average of 12.6 months (range 4-36 months). IONM alarmed in 17 cases (included 11 cases of neurogenic tumors), in which 8 cases were true positive results including 3 cases directly related to revocable operative maneuvers and 5 cases with definitely spinal cord or peripheral nerve injury, 9 cases were false positive results without certain cause or nerve injury, other 102 cases were true negative results and there was no false negative case. The sensitivity was 100.0%, specificity was 91.9%, Youden index was 0.92, false positive rate was 9.1%, false negative rate was 0.0%, positive predictive value was 47.1%, and negative predictive value was 100.0%. Conclusion The application features of IONM in spine tumor surgery were many systematic changes resulted false positive cases and selectively nerve resection related several true positive cases. IONM can effectively monitor the spinal cord and peripheral nerves and predict the postoperative neurological function. It has high application value in spine tumor surgery. Key words: Spinal neoplasms; Evoked potentials, somatosensory; Evoked potentials, motor; Electromyography

Predictive Value of Mutation Analysis in the Diagnostic Approach to Patients with Unexplained Cytopenia

▪The diagnostic approach to unexplained cytopenia is hampered by the poor specificity of dysplastic changes that may complicate the distinction between myeloid neoplasms (MN) and non-malignant cytopenias. In the last years, several somatic mutations were identified in MN; however, the diagnostic value of mutation analysis needs to be defined. In this study, we performed a mutation screening in a prospective cohort of patients with unexplained cytopenia undergoing a comprehensive diagnostic work-up, with the aim to estimate the predictive value of somatic mutations.This study included two cohorts: a learning cohort that consisted of 683 consecutive patients investigated for unexplained cytopenia at the Policlinico San Matteo & University of Pavia, Italy, between 2003 and 2015; and a validation cohort, including 190 patients referred as second opinion for suspected MDS. A set of 42 genes was analyzed on DNA from peripheral blood granulocytes using Illumina HiSeq (Illumina Inc., CA, USA). The diagnosis of patients in the learning cohort was MN in 409 cases (233 MDS, 86 MDS/MPN, 35 MPN; 55 AML), other cytopenia in 120 cases, whereas in 154 patients a provisional diagnosis of Idiopathic Cytopenia of Undetermined Significance (ICUS) was adopted. After a median follow-up of 22 months (range 3-136), 38 patients in this category developed a MN (ICUS-MN).The most frequently mutated genes were TET2 (171/683, 25%), ASXL1 (15%), SRSF2 (14%), SF3B1 (11%), DNMT3A (10%), RUNX1 (9%). Significantly higher number of mutations per subject and variant allele frequency (VAF) were observed in MN (n=2, range 0-9; VAF=0.39, 0.03-0.57) compared with ICUS (n=0, 0-7; VAF=0.31, 0.03-0.51) or other cytopenia (n=0, 0-2; VAF=0.06, 0.03-0.44) (P<0.001). Fifty-seven of 409 (14%) MN patients did not carry any mutation in the set of analyzed genes. Among these, 6 had MDS del(5q), while 18 received a diagnosis of MDS based on mild dysplasia with normal karyotype, and showed a 5-year probability of progression of 0%, suggesting that a diagnosis of MDS might have been not appropriate despite WHO criteria. When accounting for these cases, an unmutated status had a negative predictive value for MN of 0.83. Conversely, having two or more mutations had a positive predictive value (PPV) for MN of 0.94. We then performed ROC analyses to explore the cut-off value of VAF with the highest predictive value for MN, and found that a VAF equal or higher than 0.10 had a PPV for having or developing MN of 0.92.Next, we calculated the predictive value for diagnosis of MN of the most frequently mutated genes. In multivariable logistic regression, having two or more mutations (OR=4.07, P<0.001) or carrying SF3B1 mutation (OR=3.56, P=0.016) were independent predictors for MDS or other MN. SF3B1 mutation showed a specificity for myelodysplasia of 0.99, suggesting that this lesion may provide presumptive evidence of MDS even in the absence of definitive morphological features. RNA splicing genes (SF3B1, SRSF2, U2AF1) and RUNX1 had the highest predictive value for MN irrespective of co-occurring mutations, PPVs ranging from 0.88 to 0.93. PPVs increased to 0.97-0.99 when accounting for ICUS-MN as true positive cases. Conversely, PPVs of mutations in genes of DNA methylation (TET2, DNMT3A) and chromatin (ASXL1) as isolated lesions ranged from 0.39 to 0.69, while having one or more co-mutated genes significantly increased PPVs to 0.88-0.96.Among patients with a diagnosis of ICUS, 57 of 154 (37%) carried one or more mutations (Clonal Cytopenia of Undetermined Significance, CCUS). Patients with CCUS showed a significantly higher probability of developing MDS compared with those without evidence of clonality (HR=7.48, 10-year cumulative probabilities of progression: 96% vs 15% respectively, P<.001).Finally, the predictive values of mutation analysis were tested in the independent validation cohort of patients referred to our institution for suspected MDS, and were fully confirmed.In conclusion, selected mutated genes or co-mutation patterns may identify patients with high likelihood of having MDS or other MN. The definition of a category of CCUS allows to recognize with high sensitivity patients who do not fulfill diagnostic criteria but are at high risk of developing MDS. Taken together, these data suggest that mutation analysis on peripheral blood cells may significantly improve current diagnostic approach to patients with unexplained cytopenia. DisclosuresOgawa:Sumitomo Dainippon Pharma: Research Funding; Takeda Pharmaceuticals: Consultancy, Research Funding; Kan research institute: Consultancy, Research Funding.

Role of 18F-FDG PET/CT in patients with pyrexia of unknown origin

ObjectivesThis paper is a prospective observational study to assess the role of 18F-FDG PET/CT in evaluation of pyrexia of unknown origin (PUO) in a hospital based population in a tertiary level referral center in an Indian metropolitan city. Materials and methodsMedical records of 25 patients who underwent 18FDG PET/CT as a part of investigative work up of PUO were analyzed. A diagnostic CT scan was performed from the level of clavicle to the pubic symphysis in arterial and venous phases of contrast administration. Equilibrium phase images were obtained from vertex to mid-thigh without breath hold instructions with subsequent PET acquisition from vertex to mid-thigh, and these two sets of images were fused to obtain PET/CT fused images. Two radiologists with considerable PET-CT experience evaluated the contrast enhanced CT and 18-FDG PET-CT images separately and tried to identify the probable cause of fever in the 25 patients. ResultsRecords of 25 patients (13 Females, 12 Males) were evaluated. Abnormal focal FDG uptake was found in 21 patients and contributed to final diagnosis (TP) in 20 patients with 1 false positive results (FP). In the rest of the 4 patients with negative PET/CT final specific diagnosis (FN) was made only in 2 patients (2/4-50%) and in 2 patients no diagnosis was made (TN). The PET/CT had a sensitivity of 90.91%, specificity of 66.67%, positive predictive value (PPV) of 95.24% and negative predictive value (NPV-50%). TP cases included 8 cases of Kochs (2 cases of tubercular lymphadenitis, 1 case of tubercular pleural effusion, 1 case of spinal kochs, 1 case of genitourinary kochs, 1 case of Cutaneous Koch, 1 case of splenic Koch; 1 case of abdominal Koch); 4 cases of focal infections/abscesses, 1 cases of lymphoma, 2 cases of Sarcoidosis, 1 case of Kikuchi Fusimoto, 1 case of aortoarteritis, 1 case of Castleman's disease, 1 case of Rosai Dorfman and 1 case of thyroiditis. FN negative cases included one case of meningitis and one case of giant cell arteritis. One false positive case was due to focal hyper metabolism on PET in the caecum.In comparison, on CECT, probable etiology was suspected in 11 patients, out of which 8 cases were true positive (TP), 3 cases were false positive and 12 were false negative. In 2 patients no diagnosis was made (TN). CECT had a sensitivity of 42.86%, specificity of 50% positive predictive value (PPV) of 84% and negative predictive value (NPV-14.29%). Thus 18F-FDG PET/CT improved the sensitivity (90.91% vs 42.86%), specificity (66.67% vs 50%), Positive predicate value (95.24% vs 84%) and Negative predicate value (50% vs 14.29%) as compared CECT alone. ConclusionsFDG PET/CT is better than CECT in making a specific diagnosis in the evaluation of PUO. It also helps in deciding the best possible site for biopsy.

Clinical validity and relevance of accidental puncture or laceration as a patient safety indicator for children

PurposeAccidental puncture or laceration (APL) has been endorsed as a patient safety indicator and is being used to compare hospital performance and for reimbursement. We sought to determine the positive predictive value (PPV) of APL as a quality metric in a pediatric population. MethodsWe retrospectively reviewed all cases that met APL administrative criteria over 5years in a quaternary pediatric hospital system. Events were categorized as false positive (FP) or true positive (TP). TP cases were further categorized as “potentially consequential” or “inconsequential”. The PPV of APL was calculated, and a z-test was used to provide 95% confidence intervals. ResultsOf the 238 cases identified, 204 were categorized as TP (86%; 95% CI: 80%–90%). Thirty-four of these events (17%) involved injuries that were considered “inconsequential”. True events that required repair were identified as “potentially consequential” (n=170). Thus, the PPV of APL was 71% (95% CI: 65%–77%). Extenuating factors such as adhesive disease or abnormal anatomy were present in 39% of TP cases. Thirty-four cases (14%) were categorized as FP because no documented injury was found. ConclusionsA large proportion of APL events are either false or clinically irrelevant, thus questioning its usability as a patient safety indicator for children undergoing surgery. Type of studyRetrospective review. Level of evidenceIV.

Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening.

BackgroundNon-invasive prenatal testing (NIPT) identifies fetal aneuploidy by sequencing cell-free DNA in the maternal plasma. Pre-symptomatic maternal malignancies have been incidentally detected during NIPT based on abnormal genomic profiles. This low coverage sequencing approach could have potential for ovarian cancer screening in the non-pregnant population. Our objective was to investigate whether plasma DNA sequencing with a clinical whole genome NIPT platform can detect early- and late-stage high-grade serous ovarian carcinomas (HGSOC).MethodsThis is a case control study of prospectively-collected biobank samples comprising preoperative plasma from 32 women with HGSOC (16 ‘early cancer’ (FIGO I–II) and 16 ‘advanced cancer’ (FIGO III–IV)) and 32 benign controls. Plasma DNA from cases and controls were sequenced using a commercial NIPT platform and chromosome dosage measured.Sequencing data were blindly analyzed with two methods: (1) Subchromosomal changes were called using an open source algorithm WISECONDOR (WIthin-SamplE COpy Number aberration DetectOR). Genomic gains or losses ≥ 15 Mb were prespecified as “screen positive” calls, and mapped to recurrent copy number variations reported in an ovarian cancer genome atlas. (2) Selected whole chromosome gains or losses were reported using the routine NIPT pipeline for fetal aneuploidy.ResultsWe detected 13/32 cancer cases using the subchromosomal analysis (sensitivity 40.6 %, 95 % CI, 23.7–59.4 %), including 6/16 early and 7/16 advanced HGSOC cases. Two of 32 benign controls had subchromosomal gains ≥ 15 Mb (specificity 93.8 %, 95 % CI, 79.2–99.2 %). Twelve of the 13 true positive cancer cases exhibited specific recurrent changes reported in HGSOC tumors. The NIPT pipeline resulted in one “monosomy 18” call from the cancer group, and two “monosomy X” calls in the controls.ConclusionsLow coverage plasma DNA sequencing used for prenatal testing detected 40.6 % of all HGSOC, including 38 % of early stage cases. Our findings demonstrate the potential of a high throughput sequencing platform to screen for early HGSOC in plasma based on characteristic multiple segmental chromosome gains and losses. The performance of this approach may be further improved by refining bioinformatics algorithms and targeting selected cancer copy number variations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0667-6) contains supplementary material, which is available to authorized users.

The role of preoperative graded compression ultrasound in detecting acute appendicitis and influencing the negative appendectomy rate.

The diagnosis of acute appendicitis is mainly clinical and is correct in about 80% of patients, but 20-33% present with atypical findings, which resulted in a negative appendectomy rate of 20-30%. The graded compression ultrasound method in the diagnosis of acute appendicitis was reported with a sensitivity of 89%, and specificity of 95%. In this study, we aim to evaluate the graded compression ultrasonography in the diagnosis of acute appendicitis, its influence on the clinical judgment to operate, and its role in lowering the negative appendectomy rate. 1073 patients treated surgically for acute appendicitis between January 2005 and December 2014 were reviewed. Ultrasound findings, histopathological diagnosis, and positive or negative appendectomy rates were analyzed. 647 (60.3%) patients were males and 426 (39.7%) females. The mean age was 26.5years. Positive ultrasound findings were recorded in 892 (83.13%), while negative findings were recorded in 181 (16.87%). Positive appendectomy was recorded in 983 (91.6%), while negative appendectomy was recorded in 90 (8.4%). The sensitivity was 83%, specificity was 100%, and the rate of negative appendectomy was 8.39%. Graded compression technique of ultrasound is a useful modality, in addition to the clinical judgment of the surgeon and clinical findings, in detecting true positive cases of acute appendicitis, and thus reducing the negative appendectomy rate. Values of 100% specificity, and 8.4% negative appendectomy rate, or better, could be achieved, when an experienced surgeon and a professional radiologist collaborate in the diagnosis of acute appendicitis.

Evaluation of neuroendocrine tumors with 99mTc-EDDA/HYNIC TOC.

This paper is the short review of our preliminary results obtained with 99mTc-EDDA/HYNIC-TOC. The total of 495 patients with different neuroendocrine tumors were investigated during last few years. There have been 334 true positive (TP), 73 true negative (TN), 6 false positive (FP) and 82 false negative findings (FN). Diagnosis was made according to SPECT findings in 122 patients (25%). The mean T/NT ratio for TP cases was significantly higher (p < 0.01) on SPECT (3.12 ± 1.13) than on whole body scan (2.2 ± 0.75). According to our results, overall sensitivity of the method is 80%, specificity 92%, positive predictive value 98%, negative predictive value 47% and accuracy 82%. Fifteen TP patients underwent therapy with 90Y-DOTATATE. Scintigraphy of neuroendocrine tumors with 99mTc-Tektrotyd is a useful method for diagnosis, staging and follow up of the patients suspected to have neuroendocrine tumors. SPECT had important role in diagnosis. It is also helpful in the appropriate choice of the therapy, including the peptide receptor radionuclide therapy. In the absence of 68Ga-labeled peptides and PET/CT, the special emphasize should be given to application of SPECT/CT as well as to the radioguided surgery.

Application of Quantitative Autofluorescence Bronchoscopy Image Analysis Method in Identifying Bronchopulmonary Cancer.

Autofluorescence bronchoscopy shows good sensitivity and poor specificity in detecting dysplasia and cancer of the bronchus. Through quantitative analysis on the target area of autofluorescence bronchoscopy image, determine the optimal identification index and reference value for identifying different types of diseases and explore the value of autofluorescence bronchoscopy in diagnosis of lung cancer. Patients with 1 or more preinvasive bronchial lesions were enrolled and followed up by white-light bronchoscope and autofluorescence bronchoscopy. Color space quantitative image analysis was conducted on the lesion shown in the autofluorescence image using MATLAB image measurement software. A retrospective analysis was conducted on 218 cases with 1208 biopsies. One hundred seventy-three cases were diagnosed as positive, which included 151 true-positive cases and 22 false-positive cases. White-light bronchoscope associated with autofluorescence bronchoscopy was able to differentiate between benign and malignant lesion with a high sensitivity, specificity, positive predictive value, and negative predictive value (92.1%, 59.3%, 87.3%, and 71.1%, respectively). Taking 1.485 as the cutoff value of receiver operating characteristic of red-to-green value to differentiate benign and malignant diseases, the diagnostic sensitivity reached 82.3% and the specificity reached 80.5%. U values could differentiate invasive carcinoma and other groups well. Quantitative image analysis method of autofluorescence bronchoscopy provided effective scientific basis for the diagnosis of lung cancer and precancerous lesions.

Abstract 4958: Immunobiomarkers: novel autoantibody panel comprising oncogenic ERG, C-MYC, AMACR and HERV-K Gag for the detection of prostate cancer

Abstract INTRODUCTION: Biomarkers for early detection as well as disease stratification are a major area of focus in prostate cancer (CaP) research. Autoantibodies against a large array of tumor associated antigens (TAAs) have been noted in a diverse number of cancers, including CaP. Since autoantibodies represent humoral responses elicited in response to TAAs expressed in tumor cells, it is likely that autoantibodies could serve as diagnostic/prognostic markers for CaP. Hence, the present study addresses the following: i) Are autoantibodies against ERG, an oncogene frequently overexpressed in CaP, present in the sera of patients?; ii) Does a multiplex autoantibody panel containing ERG, AMACR, C-MYC, and HERV-K Gag improve the detection of CaP? METHODS: Sera from 50 CaP patients positive for ERG expression and 50 patients negative for ERG expression, along with 50 healthy control subjects were analyzed. Purified recombinant protein for ERG, AMACR, and C-MYC as well as synthetic peptides corresponding to epitopes in ERG and HERV-K Gag were used in an enzyme-linked immunosorbent assay (ELISA) developed in our laboratory to detect autoantibodies in the sera of CaP patients. In addition, a luciferase immunoprecipitation assay (LIPS), involving a chimeric luciferase-ERG protein, was used as an independent assay to test the presence of anti-ERG autoantibodies. RESULTS: Analysis of patient sera by ELISA revealed significantly higher detection of autoantibodies against ERG (P = 0.0001), AMACR (P &amp;lt; 0.0001), C-MYC (P = 0.0013), and HERV-K Gag (P &amp;lt; 0.0001) proteins in CaP cases compared to healthy controls. The specificity of anti-ERG autoantibodies was supported by a competitive ELISA assay. Further, the LIPS assay was also able to detect anti-ERG autoantibodies in patient sera. In addition, a multiplex panel assay involving ERG, AMACR, and HERV-K Gag greatly improved the detection of true positive CaP cases (AUC = 0.792). CONCLUSIONS: Here we demonstrated that autoantibodies against ERG are present in the sera of prostate cancer patients through ELISA analysis. In addition, utilizing a panel of genes for autoantibody detection, consisting of ERG, AMACR, and HERV-K Gag, showed high specificity for CaP cases. These promising findings suggest the diagnostic potential of autoantibodies and similar autoantibody panels in enhancing CaP diagnosis. Source of Funding: Center for Prostate Disease Research, Uniformed Services University Grant HU0001-10-2-0002, NCI/EDRN Grant ACN12011-001-0, and the National Cancer Institute Grant R01CA162383. Citation Format: Anshu Rastogi, Amina M. Ali, Sreedatta Banerjee, Lakshmi Ravindranath, Gyorgy Petrovics, Shyh-Han Tan, Jennifer Cullen, Yongmei Chen, Denise Young, Isabell A. Sesterhenn, Jacob Kagan, Sudhir Srivastava, David G. McLeod, Shiv Srivastava, Alagarsamy Srinivasan. Immunobiomarkers: novel autoantibody panel comprising oncogenic ERG, C-MYC, AMACR and HERV-K Gag for the detection of prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4958.

Prediction of fragmentation of kidney stones: A statistical approach from NCCT images.

We sought to develop a system to predict the fragmentation of stones using non-contrast computed tomography (NCCT) image analysis of patients with renal stone disease. The features corresponding to first order statistical (FOS) method were extracted from the region of interest in the NCCT scan image of patients undergoing extracorporeal shockwave lithotripsy (ESWL) treatment and the breakability was predicted using neural network. When mean was considered as the feature, the results indicated that the model developed for prediction had sensitivity of 80.7% in true positive (TP) cases. The percent accuracy in identifying correctly the TP and true negative (TN) cases was 90%. TN cases were identified with a specificity of 98.4%. Application of statistical methods and training the neural network system will enable accurate prediction of the fragmentation and outcome of ESWL treatment.

Clinicopathologic Threshold of Acute Colorectal Graft-versus-Host Disease.

-Colon biopsies are often used to determine the presence and severity of acute gastrointestinal graft-versus-host disease following bone marrow transplant. -To establish a threshold consensus within our institution on the number of crypt apoptotic bodies (CAB) indicative of grade 1 acute colorectal graft-versus-host disease, we retrospectively reviewed colon biopsies from posttransplant patients and incorporated clinical and endoscopic findings to validate recently proposed minimum criteria for grade 1 graft-versus-host disease as 7 or more CAB per 10 contiguous crypts. -Eighty-one biopsies performed for suspected graft-versus-host disease from 74 individual patients were initially stratified based on their prior (prestudy) diagnoses: no significant abnormality, grade 1 graft-versus-host disease, and descriptive diagnoses mentioning increased apoptosis. A chart review was performed to assess the clinical and endoscopic impression at the time of biopsy and to determine the subsequent management and outcome. -Twenty-six biopsies with an average of 3 CAB were considered true-negative cases, and 32 biopsies with an average of 9.75 CAB were considered true-positive cases (t = 3.95999, P < .001). True-negative cases had an average density of 1.36 CAB per crypt, and true-positive cases had an average density of 2.97 CAB per crypt (t = 3.950178, P < .001). -A threshold of 7 or more CAB per 10 contiguous crypts promotes appropriate treatment of grade 1 acute graft-versus-host disease after other diagnostic entities are excluded. Although this threshold is 100% specific to grade 1 acute colorectal graft-versus-host disease after other histologic mimics are excluded, this threshold has a low sensitivity (59.4%) as patients with less than 7 CAB per 10 contiguous crypts constitute a heterogeneous group.

PWE-048 Small Intestinal Bacterial Overgrowth is Increased in Gastric Bypass, Small Bowel Resection and Short Bowel Syndrome

Introduction Small intestinal bacterial overgrowth (SIBO) testing is confounded by transit time, which can be increased in a number of surgical conditions. This study aims to evaluate whether patients who have undergone a gastric bypass, small bowel resection or who have been diagnosed with short bowel syndrome have a higher prevalence of SIBO than patients who have not, and whether they respond to antibiotic treatment Methods In total, 520 adult patients (360 female, 160 male, mean age 49) who underwent hydrogen and glycocholate-methane breath tests for a suspicion of SIBO between the dates 01/01/2010 and 31/12/2013 were evaluated. Their clinical information including their test results, working diagnosis, management and outcomes of management were recorded. Results 84 patients had undergone a gastric bypass (31), small bowel resection (27) or had been diagnosed with short bowel syndrome (26). 40 of these patients tested positive in both hydrogen and glycocholate-methane breath tests (48.2%). 437 patients with normal anatomy were also tested over the same period, of which 61 tested positive (14.0%). (48.2% vs 14.0%, Chi-square statistic = 50.8911, p = 0). 34 patients who had undergone a gastric bypass, small bowel resection or had been diagnosed with short bowel syndrome who tested positive were treated with antibiotics. 28 (82.4%) benefitted from this. 56 patients who tested positive in the other group were given antibiotics, 41 (73.2%) of whom benefitted from this. Conclusion Patients who had undergone a gastric bypass, small bowel resection or have been diagnosed with short bowel syndrome have a much higher rate of positive SIBO test results compared to patients who have not, and have a similar response rate to antibiotic therapy. This suggests these post-surgical patients have a higher incidence of true SIBO than those with normal anatomy and benefit from antibiotics. This implies these are true positive cases and not false positives due to shortened transit times. Future studies controlling for transit would help clarify these findings further. Disclosure of Interest None Declared

Cycloplegic influence on the accuracy of autorefractometer in myopic and hyperopic children.

To investigate the cycloplegic effect on the accuracy of TOPCON AR RM-8000B autorefractometer in children. This study included 219 children of age 3 to 16 years. Topical 1% cyclopentolate hydrochloride was instilled for attaining cycloplegia. The children with the refractive error of -0.75 Diopter or more were grouped as myopic and more than +1.00 Diopter as hyperopic. Autorefraction was performed in addition to manual refraction. We used the XLSTAT and Medcalc statistics software. Out of 219 children, 149 (68%) were emmetropic, 48 (22%) hyperopic and 22 (10%) myopic (n=70). Males and females constituted 29 (60.42%) and 19 (39.58%) respectively in hyperopic group where as 11 (54.55%) and 9 (45.45%) children were myopic. The means of ages of the children were 10.29 (+/- 2.96) and 13.14 (+/- 2.36) years in hyperopic and myopic groups respectively. Cycloplegic hyperopic and myopic autorefraction revealed mean sphere of +1.45 and -4.06 diopter with correlation coefficient of 0.95 and 0.99 respectively. Non-cycloplegic hyperopic autorefraction showed 74.2% sensitivity and 8.3% specificity at >-1 diopter with area under curve of 0.517 (p LESS THAN 0.0001). Cycloplegic hyperopic autorefraction showed 100% sensitivity and 97.1% specificity at >+1.85 diopter with accuracy of 0.616. Non-cycloplegic myopic autorefraction showed 100% sensitivity and 0.91% specificity at >-0.75 diopter with accuracy of 0.889. Cycloplegic myopic autorefraction showed 100% sensitivity and specificity at >-1.25 diopter with perfect accuracy. Non-cycloplegic hyperopic autorefraction failed to identify true negative cases. Cycloplegic autorefraction identified true positive cases and myopic autorefraction was relatively unaffected by cycloplegia.

Transabdominal sonography comparison with transvaginal sonography

Aims &amp; Objectives: Transvaginal sonography (TVS) comparison with trans-abdominal sonography (TAS) in the diagnosis of pelvic masses Study Design: Retrospective descriptive study conducted at Gynae clinic Jinnah Hospital Lahore with collaboration of radiology department Materials and Methods: Transvaginal Sonogram was compared with transabdominal sonogram in hundred women referred for evaluation of pelvic masses from gynae clinic. All the women were interviewed regarding their age, parity, duration of mass and associated symptoms. Diagnosis was based on the combination of clinical, sonographic (TVS, TAS) and surgical correlation. Both ultrasound modalities were compared for the details about the internal architecture and diagnostic information. Results: Most common age group with pelvic masses was between 26-35yrs. TVS was more sensitive for both uterine and adnexal masses. Sensitivity of TAS was 65% and TVS was 88%. There was a significant difference in diagnosing true positive cases by trans-vaginal approach. (P value &lt; 0.001) Specificity of TAS was 89% and TVS 86% for both uterine and adnexal masses. Image quality was better in 87% of cases with trans-vaginal approach and 5% of cases with trans-abdominal approach and it was equivalent in 8% of cases. There was a significant difference in the image quality between two modalities (P value &lt; 0.001). Regarding anatomical details TAS was better in 12% of cases and TVS was better in 28% of cases and both were equivalent in 60% of cases, Diagnostic information of these two modalities was almost equivalent. TAS was better in 7% of cases and TVS was better in 8% of cases and both were equivalent in 85% of cases Conclusion: The results suggest that TVS has considerable advantage over conventional TAS in evaluation of pelvic masses in women.

The value of a transformation zone component in anal cytology to detect HSIL.

In a cytology-based screening program intended to prevent anal cancer, the anal transformation zone (TZ) should be adequately sampled because it is the site most susceptible to the development of the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). An adequate TZ component is defined as comprising at least 10 rectal columnar or squamous metaplastic cells. In the current study, the authors examined whether the presence of a TZ component in anal cytology correlated with the detection of histological HSIL. In a natural history study of anal human papillomavirus infection in homosexual men, all participants underwent liquid-based cytology and high-resolution anoscopy (HRA) with or without biopsy at each visit. True-negative cytology (negative cytology with non-HSIL biopsy or negative HRA), false-negative cytology (negative cytology with HSIL biopsy), and true-positive cytology (abnormal cytology with HSIL biopsy) were compared with regard to the presence or absence of a TZ component. Of 617 participants, baseline results included 155 true-positive results, 191 true-negative results, and 31 false-negative results. The absence of an adequate TZ component was found to be significantly higher for false-negative (32.3%) than for either true-positive (11.0%; P = .0034) or true-negative (13.1%; P = .0089) results. Significantly more false-negative cases lacked a TZ component compared with either true-positive or true-negative cases. TZ cells may be an important indicator of sample quality for anal cytology because, unlike cervical sampling, the anal canal is not visualized during cytology sampling. Cancer Cytopathol 2016;124:596-601. © 2016 American Cancer Society.

Cost-Effectiveness Analysis of Different Testing Strategies that Use Antibody Levels to Detect Chronic Hepatitis C in Blood Donors.

Aim. We conducted a cost-effectiveness analysis of seven hepatitis C virus (HCV) testing strategies in blood donors. Methods. Three of the seven strategies were based on HCV diagnosis and reporting guidelines in Mexico and four were from previous and current recommendations outlined by the CDC. The strategies that were evaluated determine antibody levels according to the signal-to-cut-off (S/CO) ratio and use reflex Immunoblot (IMB) or HCV RNA tests to confirm true positive (TP) cases of chronic HCV infection. Costs were calculated from the perspective of the Mexican Institute of Social Security (IMSS). A decision tree model was developed to estimate the expected number of true positive cases and costs for the base-case scenarios and for the sensitivity analyses. Results. Base-case findings indicate an extended dominance of the CDC-USA2 and CDC-USA4 options by the IMSS Mexico3 and IMSS-Mexico1 alternatives. The probabilistic sensitivity analyses results suggest that for a willingness-to-pay (WTP) range of $0–9,000 USD the IMSS-Mexico1 strategy is the most cost-effective of all strategies ($5,000 USD per TP). The IMSS-Mexico3, IMSS-Mexico2, and CDC-USA3 strategies are also cost-effective strategies that cost between $7,800 and $8,800 USD per TP case detected. The CDC-USA1 strategy was very expensive and not cost-effective. Conclusions. HCV antibody testing strategies based on the classification of two or three levels of the S/CO are cost-effective procedures to identify patients who require reflex IMB or HCV RNA testing to confirm chronic HCV infection.

Positive predictive values of selected hospital discharge diagnoses to identify infections responsible for hospitalization in the French national hospital database

The identification of infections in electronic health databases is a key issue for pharmacoepidemiology research. The aim of this study was to assess the positive predictive values (PPVs) of hospitalizations for infection in the Système National d'Information Inter-régimes de l'Assurance Maladie, that is the electronic database recording in-and-out hospital data for the entire French population (66 million inhabitants). The source of data was the database of hospitalizations (Programme de Médicalisation des Systèmes d'Informations) of Toulouse University hospital, South of France (2880 beds). Among all hospital stays between September and December 2014, we randomly selected 100 stays with an International Classification of Diseases, 10th revision code of infection as primary diagnosis and 100 as related diagnosis. Medical charts were reviewed to assess the PPV of infection codes, as well as the PPV of correct coding of infection type among the true positive cases. The PPVs of codes of infection as reason for hospitalization were 0.97, 95% confidence interval (CI) [0.93-1.00] for primary diagnosis codes and 0.70, 95% CI [0.61-0.71] for related diagnosis codes. Among the true positive cases, the PPVs of correct coding of the type of infection were, respectively, 0.98, 95% CI [0.95-1.00] and 0.93, 95% CI [0.88-0.98]. Hospitalizations for infection codes have very good PPVs in the Programme de Médicalisation des Systèmes d'Informations. Copyright © 2016 John Wiley & Sons, Ltd.