Strong Negative Predictive Value Research Articles

Plasma protein electrophoresis as a prognostic indicator in Aspergillus species‐infected Gentoo penguins (Pygoscelis papua papua)

Avian aspergillosis presents a significant threat to captive penguin populations. Currently, a lack of objective prognostic factors limits disease staging, objective reassessment throughout treatment, comparative evaluation of treatment regimes, and appropriate timing of euthanasia. The study objective was to investigate absolute and relative plasma protein fractions by agarose gel electrophoresis (EPH) as predictors of survival in Gentoo penguins (Pygoscelis papua papua) under treatment for aspergillosis. One hundred and eighty-three EPH profiles from individual clinical cases were examined retrospectively. Animal survival to 90days post sampling was established from clinical records; birds either survived (n=146) or died within 90days (n=37), and time to death was recorded. Fourteen variables showed statistically significant differences (P<.05) between surviving and dying birds. Receiver operating characteristic curve analysis identified total albumin concentration (albumin+prealbumin) and albumin-to-globulin (A:G) ratio as having strongest discriminatory values (95% CI) at 0.788 (0.710-0.866) and 0.784 (0.696-0.871), respectively. Albumin (concentration and percentage of total protein) displayed moderate discriminatory value but additionally a weak positive correlation with time to death (95% CI); r=.353 (0.033-0.608) and .424 (0.116-0.658), respectively. Optimized test cutoffs for total albumins, albumin (concentration and percentage of total protein), and A:G ratio achieved moderate sensitivity and specificity, strong negative predictive values, but weak positive predictive values due to a low prevalence of death. Selection of appropriate test cutoff values may provide valuable adjunctive prognostic tools for clinical decision-making when the prognosis is difficult to assess clinically.

Surface Topography Classification Trees for Assessing Severity and Monitoring Progression in Adolescent Idiopathic Scoliosis.

A validation study. The aim of this study was to independently validate the diagnostic accuracy of surface topography (ST) classification trees to identify curve severity and progression using a new sample of data in participants with adolescent idiopathic scoliosis (AIS). Radiographs for diagnosing and monitoring AIS involve harmful radiation exposure repeated at successive clinical visits. Classification trees using a novel ST technique have been proposed to determine curve severity and progression noninvasively that could be used to monitor scoliosis. Forty-five adolescents with AIS treated nonoperatively, with ST scans and radiographs at baseline and follow-up (1 year later), were recruited from a scoliosis clinic. The Cobb angle (CA) from radiographs determined curve severity as mild (10° < CA < 25°) or moderate/severe (CA ≥ 25°) and progression as an increase >5°.ST scans were analyzed to calculate the best plane of symmetry and associated deviation color map. Root mean squares and maximum deviation were calculated for each area of asymmetry. ST measurements were analyzed using two published decision trees developed to maximize sensitivity and negative predictive value. Curves were classified as mild or moderate/severe and curve progression was predicted. Accuracy statistics were calculated to evaluate performance. For curve severity, sensitivity and specificity were 95% and 35%, respectively. Negative and positive predictive values were 90% and 53%, respectively, with an accuracy of 61%. For curve progression, sensitivity and specificity were 73% and 44%, respectively. Negative and positive predictive values were 83% and 30%, respectively, with an accuracy of 51%. Assuming that mild and nonprogressive curves would not require an x-ray, the use of ST decision trees could eliminate 31% of x-rays. Decision trees showed strong negative predictive values and sensitivity suggesting it may be possible to safely use ST asymmetry analysis with validated decision trees to reduce x-rays in patients with mild and nonprogressive curves. 2.

SC18.02 Integrating Lung Cancer Biomarkers into Future Screening Programs

SC18.02 Integrating Lung Cancer Biomarkers into Future Screening Programs

Brentuximab Vedotin Monotherapy and Combined with Low Dose Donor Lymphocyte Infusion to Control Minimal Residual Disease and Sustain Clinical Remission in a Child with Relapsed Anaplastic Large Cell Lymphoma

Minimal residual disease (MRD) appears to have a strong negative predictive value for disease recurrence in children with anaplastic large cell lymphoma (ALCL). Brentuximab vedotin (BV) can be a therapeutic option for MRD-positive patients to achieve molecular remission and to decrease risk of subsequent relapse. We here report a 4-year-old child with ALCL progression during relapse treatment who received BV as a bridging therapy before haploidentical hematopoietic stem-cell transplantation, and as a maintenance therapy post-transplant alone or combined with simultaneous low dose donor-lymphocyte infusions. MRD monitoring showed a complete molecular response and reflected both BV efficiency and graft-versus-lymphoma effect.

A Genetic Risk Score for Insulin Resistance Identify Patients with Chronic Myeloid Leukemia, Treated with Nilotinib, Developing Diabetes

BACKGROUD: Nilotinib, a potent 2nd generation tyrosin kinase inhibitor, is efficacious in the treatment of chronic myelogenous leukemia (CML). Impaired glucose metabolism represents one of the most frequently observed adverse events and several clinical trials, reported a high diabetes incidence during treatment with this drug. The mechanism of this side effect is poorly understood, but recently has been hypothesized an increased postreceptorial insulin resistence. Moreover, "in vitro"results indicated that c-ABL is involved in the insulin receptor signaling pathway. A large number of genetic variants associated with Type 2 diabetes (T2D) are implicated in beta-cell function but the role of common genetic variants associated with insulin resistance in the etiology of T2D, remains poorly documented. Scott R. and al. (Diabetes 2014) recently identified 10 multiple single nucleotide polymorphisms (SNPs) associated with insulin resistance and created a genetic risk scores (uGRS) as complementary tool to for insulin resistance.AIM of the study was to identify whether this uGRS could be a valid prognostic tool in identifying patients developing diabetes during Nilotinib therapyPATIENTS AND METHODS:45 patients (19 males) were included in the study. Twenty-four were treated with Nilotinib in first-line and 21 as second line (10 for resistance, 8 intolerance and 3 for other reasons). None of the subjects studied had abnormal blood glucose or took any antidiabetic drug before Nilotinib treatment.We genotyped all patients with the GRS created by Scott R. including those in, or near, the IRS1, GRB14, ARL15, PPARG, PEPD, ANKRD55/MAP3K1, PDGFC, LYPLAL1, RSPO3, and FAM13A1 genes that have primary effects on subcutaneous adipocyte function. Also we added 2 new variants, one for TCF7L2 gene, associated with insulin secretion and another in FTO gene, whose effect on insulin levels is mediated by BMI. The uGRS was calculated, as previously reported, by summing the number of risk alleles across the 12 variants (0 for risk allele absent, 1 for heterozygosity and 2 for homozygosity for risk allele). A cut-off point for uGRS, maximizing predictivity and sensitivity of the score was calculated using Youden's index. Diabetes and impaired fasting Glycaemia were defined using the American Diabetes association (ADA) criteria. Data were reported as median and range,RESULTS:Age at diagnosis was 45(18-82) years, the Sokal was low in 16 (42%), intermediate in 12 (26%) and high in 17 (32%) patients. During treatment and subsequent follow up of 45(7-127) months, 28 patients remained euglycemic, 5 (2 treated in the first line) developed diabetes after 14(1-32) months and 12 (6 treated as first line) developed IFG in 6 (1-12) months. No IFG patients developed an overt diabetes in the subsequent follow-up of 60.3 (33-102) months.We calculated a cut-off point of 12 for uGRS. When the 28 euglycemic patient were compared with 5 patients becoming diabetics after Nilotinib, uGRS showed a sensibility of 100% and a specificity of 46% in predicting diabetes. Consequently, the positive predictive valuewas 25% where the negative predictive values 100%. When the 28 euglycemic patients were compared with the 12 patients developing IFG after Nilotinib, the sensibility and specificity of uGRS was low: 50% and 46% respectively.CONCLUSIONS: A Genetic risk score for insulin resistance showed high specificity and a strong negative predictive values when used to identify CML patients treated with Nilotinib developing an overt diabetes. Further studies in lager populations are needed to confirm this predictivity that can be used in clinical practice to tailor the best anti TKI therapy. DisclosuresNo relevant conflicts of interest to declare.

A Risk Score for Childhood Obesity in an Urban Latino Cohort

To assess whether individual obesity risk factors, present during gestation, and the first 6months of life, can be combined into a simple prognostic model that has the ability to accurately predict childhood obesity at age 5years in a high-risk cohort. A total of 201 Latina women were recruited during pregnancy, and their infants followed longitudinally. Ten risk factors for childhood obesity were included in an initial logistic model; a second reduced model was created via stepwise deletion (confirmed with nonparametric conditional random forest classifier), after which 5 risk factors remained. From each model, an obesity risk equation was derived, and an obesity risk score was generated for each patient. Derived algorithms were assessed using discrimination, calibration, and via predictive statistics. Of the 166 children followed through age 5 years, 56 (32%) met criteria for childhood obesity. Discrimination accuracy for both derivation models was excellent, and after optimism-corrected bootstrapping, both models showed meaningful clinical performance. Both models were adequately calibrated, showed strong sensitivity and negative predictive value at conservatively set obesity risk thresholds, and displayed excellent specificity among those classified as highest risk. Birth weight z-score and change in weight-for-age z-score between birth and 6months were the risk factors with the strongest contribution to the obesity risk score. Obesity risk algorithms are reliable in their prediction of childhood obesity and have the potential to be integrated into the electronic medical record. These models could provide a filter for directing early prevention resources to children with high obesity risk but should be evaluated in a larger external dataset.

Negative predictive value of procalcitonin in medullary thyroid carcinoma.

Calcitonin (CT), the major biochemical marker in medullary thyroid carcinoma (MTC) is prone to in vitro instability and suffers from scarcity of clinical laboratory platforms. Procalcitonin (PCT), the precursor of CT, free of these shortcomings, has been reported as a potential MTC marker. The aim of this study was to assess the negative predictive value (NPV) of PCT as a first-line marker in MTC. 476 serum samples referred to our laboratory for CT measurements were analyzed for PCT. NPVs of PCT were assessed at 3 cut-offs (0.05, 0.10 and 0.15 ng/mL) and the diagnosis of MTC was based on CT levels. PCT and CT levels were correlated (r=0.7554 for CT levels above 10 pg/mL, n=66). Accepting the CT cut-off based on the upper reference limit the NPV of PCT were 98.1% (0.05 ng/mL), 96.3% (0.10 ng/mL) and 95.4% (0.15 ng/mL) respectively. For a CT cut-off of 100 pg/mL the NPVs of PCT were 100% for all PCT thresholds. Serum PCT has a strong NPV and could be a good candidate for a first-line screening test to exclude MTC in patients with suspicious thyroid nodules or suggestive symptoms. Larger prospective studies are necessary to confirm our results.

A comparison of prevaginal and postvaginal manipulation fetal fibronectin

Fetal fibronectin (fFN) is used as a biomarker for preterm delivery. Currently, its use is discouraged if there has been vaginal manipulation in the previous 24 hours. Our objective is to determine if there are differences between fFN results before and after vaginal manipulation in the form of sterile vaginal exam or transvaginal ultrasound. This was a prospective observational cohort study at a single center of women between 22-33 6/7 weeks at risk for preterm delivery due to: (1) a history of preterm delivery, short cervix, or multifetal gestation; or (2) symptoms of preterm labor. We excluded women with vaginal bleeding or infection, placenta previa, ruptured membranes, cervical dilation >3 cm, or any form of vaginal manipulation in the previous 24 hours. Specimen A was collected prior to planned vaginal exam or transvaginal ultrasound and specimen B was collected within 4 hours. The agreement between specimens A and B was assessed using descriptive statistics. Test characteristics of specimens A and B using the outcome of preterm delivery (<37 weeks) were calculated. In all, 310 specimen pairs from 237 women were collected. Specimen A was positive in 37 (12%) instances and negative in 273 (88%) while specimen B was positive in 39 (13%) and negative in 271 (87%). There were discordant results in 26 specimen pairs. Of these, 14 (5%) negative specimen A results subsequently became positive for specimen B, and 12 (32%) positive specimen A results became negative for specimen B. Overall, there was a 92% agreement between specimens A and B (confidence interval, 88-94%). The specificity of specimens A and B for preterm birth was 90% vs 89%, respectively, with a negative predictive value of 87% for both. The false-negative rate was 12.8% for specimen Aand 13.3% for specimen B. There is a moderately high degree of agreement between prevaginal and postvaginal manipulation fFN results. Their test characteristics for evaluating preterm birth are similar with strong specificity and negative predictive values, and their false-negative rates are not clinically different. Consideration should be made to the utilization of postvaginal manipulation fFN when a prevaginal manipulation specimen is not available.

Rapid Detection of the Three Celiac Disease Risk Genotypes HLA-DQ2.2, HLA-DQ2.5, and HLA-DQ8 by Multiplex Ligation-Dependent Probe Amplification.

Genotyping of HLA-DQ2.2, HLA-DQ2.5, and HLA-DQ8 is important in celiac disease (CD). The absence of these three genotypes has a strong negative predictive value. We designed multiplex ligation-dependent probe amplification (MLPA) for the combined detection of HLA-DQ2.2, HLA-DQ2.5, and HLA-DQ8. The MLPA probe mix was validated against a set of 59 samples characterized by conventional techniques. The MLPA assay genotyped all 59 samples correctly when compared to the results obtained by PCR-SSCP/HD or PCR-SSO and PCR-SSP. The MLPA assay provides a reliable single-reaction analysis of the CD risk genotypes HLA-DQ2.2, HLA-DQ2.5, and HLA-DQ8 allowing for stratification or exclusion of disease risk.

Predictive Value of Somatic Mutations for the Development of Malignancy in Thyroid Nodules by Cytopathology

The purpose of our prospective longitudinal study was to evaluate the predictive efficacy of genetic testing for malignancies in fine-needle aspiration biopsy samples that are cytologically benign at the time of biopsy. A total of 779 aspirated cytological samples collected from thyroid nodules of 626 patients were included in a 3-year follow-up study. Consecutive patients with cytologically benign thyroid nodules by the Bethesda System for Reporting Thyroid Cytopathology were enrolled in the study. At enrollment, somatic 1-point nucleotide polymorphisms of BRAF and RAS family genes were tested by melting-point analysis, while RET/PTC and PAX8/PPAR-gamma rearrangements were examined by real-time polymerase chain reaction. The genetic test was considered to be positive if a somatic mutation was found. Malignant cytopathologic diagnoses were confirmed by histopathology. In samples collected from 779 thyroid nodules, there were 39 BRAF, 33 RAS mutations, and 1 RET/PTC rearrangements found at the beginning of the study. No PAX8/PPAR-gamma rearrangement was identified. There were 52 malignant thyroid tumors removed during follow-up, out of which 24 contained a somatic mutation. The specificity of the presence of somatic mutations for malignancies was as high as 93.3%, and sensitivity was 46.2%. The negative predictive value of genetic testing reached 96.0%. Our results show that our set of genetic tests can predict the appearance of malignancy in benign thyroid nodules (at the beginning of follow-up) with high specificity and strong negative predictive value. BRAF = v-raf murine sarcoma viral oncogene homolog B1 FLUS = follicular lesion of undetermined significance FNAB = fine-needle aspiration biopsy FTC = follicular thyroid carcinoma HRAS = homologous to the oncogene from the Harvey rat sarcoma virus KRAS = homologous to the oncogene from the Kirsten rat sarcoma virus NRAS = first isolated from a human neuroblastoma/neuroblastoma RAS = viral oncogene homolog PAX8 = paired box 8 PCR = polymerase chain reaction PPAR-gamma = peroxisome proliferator-activated receptor gamma PTC = papillary thyroid carcinoma RAS = rat sarcoma RET = rearranged during transfection tyrosine-kinase proto-oncogene SM = somatic mutation SNP = single-nucleotide polymorphism.

The Utility of the Candida Score in Patients With Sepsis.

Candida is a leading cause of infection in the intensive care unit. Colonization versus infection remains a challenge. A Candida Score (CS) of 3 or greater has been used to target antifungal therapy in surgical patients at risk of candidemia but has not been well evaluated in medical patients with sepsis. The aim of this study was to assess utility of the CS in detecting candidemia early in patients with sepsis. This was a secondary analysis of patients with sepsis (n = 77) who were followed up for development of new infections. Patients with known fungal infection at admission were excluded. Candida colonization was defined as Candida cultured from any baseline culture, except blood, as a part of routine clinical care. Candidemia was detected in 8 of 77 participants (10.4%; 4 [15.4%] with a CS ≥3 and 4 [7.8%] with a CS <3). Demographic variables (age, race, sex) were similar among those who did and did not develop candidemia. Using the recommended CS of 3 or greater, sensitivity was (4/8) 50%, specificity was (47/69) 68.1%, positive predictive value was (4/26) 15.4%, and negative predictive value was (47/51) 92.2%. Baseline colonization was significantly higher among those who developed candidemia (50% vs 11.6%; P = .02), but no significant differences were observed among CS components or total scores. Despite a relatively poor sensitivity, a reasonable specificity with a strong negative predictive value makes this tool a viable option for screening medically ill patients who may require antifungal agents. The CS should be evaluated in a larger, more inclusive, medical population.

Molecular Remission One Year Following Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia Predicts Relapse-Free and Overall Survival: A Multi-Institutional Landmark Analysis

▪Introduction: Chronic lymphocytic leukemia (CLL) cells typically carry one or more clonally rearranged immunoglobulin (Ig) genes. The specific sequence of an Ig rearrangement, or clonotype, can serve as a marker of minimal residual disease (MRD) in blood or bone marrow samples. The clonoSEQ assay (Adaptive Biotechnologies Corp) employs a next-generation sequencing (NGS) based MRD quantification method that uses consensus primers to amplify and then sequence the entire repertoire of Ig genes in a clinical sample. Each Ig clonotype, including the one marking a patient's CLL, can then be individually quantified with high precision. We previously demonstrated the utility of this NGS approach for predicting relapse-free survival in a single-institution cohort of CLL patients undergoing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT). In this landmark analysis, we now assess the prognostic utility of molecular MRD quantification one year following RIC alloHCT in a multi-institution cohort.Methods: We retrospectively evaluated the outcomes and MRD status of patients surviving without relapse to one year after RIC alloHCT for CLL. Patients were assessable for MRD based on availability of a tumor specimen from which to determine the CLL-associated Ig heavy chain (IgH) clonotypes and a cryopreserved peripheral blood mononuclear cell (PBMC) aliquot obtained one year post-HCT. Forty-six patients underwent conditioning with total lymphoid irradiation and anti-thymocyte globulin (TLI/ATG) and 56 were conditioned with fludarabine and busulfan (Flu/Bu) regimens. Clonal IgH rearrangements were identified by NGS-based IgH profiling in CLL-bearing blood or marrow samples obtained prior to HCT and these clonotypes were quantified in the IgH repertoire of PBMC samples from one year (+/- 90 days) post-HCT.Results: One hundred two patients were assessable for outcomes beyond the one year post-HCT landmark. Amongst 97 patients with a diagnostic sample available, the IgH clonotype calibration rate was 90%. Five archived diagnostic samples yielded insufficient DNA to proceed with clonotype identification. 87/102 (85%) patients had paired tumor and one year PBMC samples suitable for MRD quantification. Patients receiving TLI/ATG or Flu/Bu conditioning had similar clinical characteristics. Median relapse-free survival (RFS) from the one year landmark was 4.7 years with TLI/ATG and 6.8 years with Flu/Bu (p=0.08; Figure 1A), and overall survival was not significantly different (Figure 1B). Acute GVHD (grades 2-4) occurred in 15.6% with TLI/ATG and 37.5% with Flu/Bu. Chronic GVHD occurred in 53% and 77%, respectively, with less extensive grade chronic GVHD using TLI/ATG (39%) compared with Flu/Bu (73%). Amongst patients alive and in remission one year after RIC alloHCT, peripheral blood MRD <10-6 was associated with more favorable outcomes, with just 5.3% relapsing within 7 years post transplant, compared with 59% relapse in those with ≥10-6 MRD (HR 11, 95% CI 4.3-28, p<0.0001; Figure 1C). MRD negativity one year post-HCT was also associated with improved long term overall survival (HR 2.6, 95% CI 1.1-6.4, p=0.03; Figure 1D).Conclusions: In this non-randomized retrospective analysis of outcomes after RIC alloHCT for high-risk CLL, use of TLI/ATG or Flu/Bu conditioning regimens were associated with similar RFS, though a trend toward earlier relapse with TLI/ATG is observed. Flu/Bu was associated with substantially higher rates of acute and chronic GVHD and higher rates of death in remission. Irrespective of conditioning regimen used, molecular MRD quantification at one year post-HCT provides strong positive and negative predictive value for subsequent relapse. Identification of MRD positive patients at risk for relapse may permit the implementation of post-HCT immune modulation or maintenance treatment to reduce relapse risk for those in need, but spare MRD negative patients from the potential for additional toxicity. [Display omitted] DisclosuresLogan:Pharmacyclics: Consultancy; Amgen: Consultancy; Jazz Pharmaceuticals: Consultancy. Herrera:Genentech: Research Funding; Sequenta, Inc.: Research Funding; Pharmacyclics: Research Funding. Rezvani:Pharmacyclics: Research Funding. Kong:Adaptive Biotechnologies Corp: Employment, Equity Ownership. Faham:Adaptive Biotechnologies Corp.: Employment, Other: Stockholder. Miklos:Pharmacyclics: Research Funding.

Diagnosing dementia in multiple system atrophy by applying Movement Disorder Society diagnostic criteria for Parkinson's disease dementia.

Dementia is an exclusion criterion in current consensus diagnostic criteria, while growing evidence suggests the occurrence of cognitive dysfunction and even dementia in multiple system atrophy (MSA) patients. The main goal of this study was to determine if Movement Disorder Society (MDS) Parkinson's disease dementia (PDD) LEVEL-1 criteria are useful in screening for dementia in MSA patients compared to full cognitive testing (LEVEL-2 criteria). In this retrospective study, MDS diagnostic criteria for PDD were applied in 111 MSA patients from three centres. LEVEL-1 evaluation (short screening test) was compared to LEVEL-2 examination (extensive neuropsychological gold standard assessment). Sensitivity, specificity, positive and negative predictive values were calculated for LEVEL-1 compared to LEVEL-2. Two Mini Mental State Examination (MMSE) cut-off scores were evaluated (<26 according to MDS procedures for the diagnosis of PDD and <27 which has proven more sensitive in a recent study proposing a short procedure for PDD screening). According to these criteria, 11.7% of MSA patients were demented on LEVEL-2 examination. LEVEL-1 examination showed strong specificity (96.9%) and negative predictive value (94.1%), while sensitivity (53.8%) and positive predictive (70%) value were moderate compared to LEVEL-2 evaluation. Sensitivity increased to 84.6% when using a MMSE threshold <27 for LEVEL-1. Executive dysfunction was the main prevalent finding (52% of all patients), while impairment of memory (15%), language (14%) and visuospatial functions was less frequent (13%). Our findings suggest that the MDS PDD short screening test may be useful for the diagnosis of MSA dementia.

Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations.

BackgroundSelection of NSCLC patients for targeted therapy is currently based upon the presence of sensitizing mutations in EGFR and EML4/ALK translocations. The heterogeneity of molecular alterations in lung cancer has led to the ongoing discovery of potential biomarkers and targets in order to improve survival.AimThis study aimed to detect alterations in EGFR, KRAS, BRAF, PIK3CA, MET-gene copy number and ALK rearrangements in a large cohort of 956 NSCLC patients of Hellenic origin using highly sensitive techniques and correlations with clinicopathological characteristics.ResultsMutations were detected in EGFR 10.6% (101 out of 956 samples), KRAS 26.5% (191 out of 720 samples), BRAF 2.5% (12 out of 471 samples), PIK3CA 3.8% (7 out of 184 samples), MET gene amplification was detected in 18% (31 out of 170) and ALK rearrangements in 3.7% (4 out of 107 samples). EGFR mutations were detected in exon 19 (61.4% of mutant cases), exon 21 p.Leu858Arg (19.8%), exon 20 (15.8%), exon 18 (2.9%) and were correlated with gender histology, smoking status and TTF1 staining. p.Thr790Met mutant cases (3.9%) displayed concurrent mutations in exons 19 or 21. Negative TTF-1 staining showed strong negative predictive value for the presence of EGFR mutations. KRAS mutations were associated with histology, the most common mutation being p.Gly12Cys (38%).DiscussionIn conclusion, only 89 patients were eligible for EGFR -TKIs and ALK inhibitors therapy, whereas 257 patients showed other alterations, highlighting the necessity for a detailed molecular profiling potentially leading to more efficient individualized therapies for NSCLC patients.

To evaluate the auxiliary diagnostic value of Japanese respiratory society scoring system for the rapid diagnosis of Mycoplasma pneumoniae pneumonia in inpatients with community acquired pneumonia

To evaluate the auxiliary diagnostic value of Japanese respiratory society (JRS) scoring system for the rapid diagnosis of Mycoplasma pneumoniae pneumonia (MP) in inpatients with community acquired pneumonia (CAP). The clinical data of inpatients with CAP between January 2013 and Novermber 2013 were retrospectively analyzed. The gold standard for identification of MP infection was determined by both positive culture and real time polymerase chain reaction (PCR) methods. Blood and sputum culture were used to detect other bacteria and fungi, and real time PCR to detect Chlamydia and Legionella pneumonia and the common respiratory viruses. Diagnostic test results consistency inspection was performed by Kappa test and continuous variable analysis was performed using t test. Data from 139 CAP inpatients were analyzed. An aetiological diagnosis was made for 61 patients (43.9%). Thirty-five cases (25.2%) were diagnosed as MP infection by the gold standard, while 72 cases (52.0%) by the JRS scoring system. The sensitivity of JRS scoring system for the diagnosis of MP infection was 85.7% (30/35), specificity 59.6% (62/104), positive predictive value 41.7% (30/72)and negative predictive value 92.5% (62/67). According to age, for the patients younger than 40 years old, the sensitivity of JRS routine scoring system for the diagnosis of MP infection was 24/24, specificity was 4/29, positive predictive value 24/49 and negative predictive value was 4/4. The JRS scoring system provides an auxiliary value for the identification of MP pneumonia. It has a high sensitivity and a strong negative predictive value. For patients younger than 40 yrs with low grades of JRS swring system. MP infection can be almost excluded from.

Self-administered hearing loss screening using an interactive, tablet play audiometer with ear bud headphones

Background and objectiveThe timely diagnosis and treatment of acquired hearing loss in the pediatric population has significant implications for a child's development. Audiological assessment in children, however, carries both technological and logistical challenges. Typically, specialized methods (such as play audiometry) are required to maintain the child's attention and can be resource intensive. These challenges were previously addressed by a novel, calibrated, interactive play audiometer for Apple® iOS® called “ShoeBOX Audiometry”. This device has potential applications for deployment in environments where traditional clinical audiometry is either unavailable or impractical. The objective of this study was to assess the screening capability of the tablet audiometer in an uncontrolled environment using consumer ear-bud headphones. MethodsConsecutive patients presenting to the Audiology Clinic at the Children's Hospital of Eastern Ontario (ages 4 and older) were recruited. Participants’ hearing was evaluted using the tablet audiometer calibrated to Apple® In-Ear headphones. The warble tone thresholds obtained were compared to gold standard measurements taken with a traditional clinical audiometer inside a soundbooth. Results80 patients were enrolled. The majority of participants were capable of completing an audiologic assessment using the tablet computer. Due to ambient noise levels outside a soundbooth, thresholds obtained at 500Hz were not consistent with traditional audiometry. Excluding 500Hz threholds, the tablet audiometer demonstrated strong negative predictive value (89.7%) as well as strong sensitivity (91.2%) for hearing loss. ConclusionThresholds obtained in an uncontrolled setting are not reflective of diagnostic thresholds due to the uncalibrated nature of the headphones and variability of the setting without a booth. Nevertheless, the tablet audiometer proved to be both a valid and sensitive instrument for unsupervised screening of warble-tone thresholds in children.

Cardiothoracic ratio for prediction of left ventricular dilation: a systematic review and pooled analysis.

Increased cardiothoracic ratio noted on chest radiographs often prompts concern and further evaluation with additional imaging. This study pools available data assessing the utility of cardiothoracic ratio in predicting left ventricular dilation. A systematic review of the literature was conducted to identify studies comparing cardiothoracic ratio by chest x-ray to left ventricular dilation by echocardiography. Electronic databases were used to identify studies which were then assessed for quality and bias, with those with adequate quality and minimal bias ultimately being included in the pooled analysis. The pooled data were used to determine the sensitivity, specificity, positive predictive value and negative predictive value of cardiomegaly in predicting left ventricular dilation. A total of six studies consisting of 466 patients were included in this analysis. Cardiothoracic ratio had 83.3% sensitivity, 45.4% specificity, 43.5% positive predictive value and 82.7% negative predictive value. When a secondary analysis was conducted with a pediatric study excluded, a total of five studies consisting of 371 patients were included. Cardiothoracic ratio had 86.2% sensitivity, 25.2% specificity, 42.5% positive predictive value and 74.0% negative predictive value. Cardiothoracic ratio as determined by chest radiograph is sensitive but not specific for identifying left ventricular dilation. Cardiothoracic ratio also has a strong negative predictive value for identifying left ventricular dilation.

Negative predictive value of drain amylase concentration for development of pancreatic fistula after pancreaticoduodenectomy

BackgroundPost-operative pancreatic fistula (POPF) is the major source of morbidity following pancreaticoduodenectomy. A predictive indicator would be highly advantageous. One potential marker is drain amylase concentration (DAC). However, its predictive value has not been fully established. Methods405 patients undergoing pancreaticoduodenectomy at our centre over a 10 year period were reviewed to determine the value of DAC as a predictive indicator for the development of POPF. ResultsPOPF developed in 58 patients (14%). These patients suffered greater morbidity. Overall 30-day mortality was 1.5%. Male gender (OR: 5.1; p = 0.0082) and age > 70 (OR 2; p = 0.0372) were independent risk factors for POPF, whilst Type 2 diabetes (OR: 0.2321; p = 0.0090) and pancreatic ductal-adenocarcinoma (OR: 0.3721; p = 0.0039) decreased POPF risk. The DACs post-operatively were significantly higher in those developing POPF, but with significant overlap. ROC curves revealed optimal threshold values for differentiating POPF and non-POPF patients. A DAC°<°1400 U/ml on day 1 and <768 U/ml on day 2, although having a poor positive predictive value (32–44%), had a very strong negative predictive value (97–99%). ConclusionOur data suggest that post-operative DAC below the determined optimal threshold values on day 1 and 2 following pancreaticoduodenectomy carries high negative predictive value for POPF development and identifies patients in whom early drain removal, and enhanced recovery may be considered, with simultaneous assessment of operative and clinical factors.

PO-0461 Heart Rate Variability In Full-term Neonates With Hypoxic Ischaemic Encephalopathy

<h3>Background</h3> Hypoxic Ischaemic Encephalopathy (HIE) remains a significant cause of neonatal death and long term disability. Heart rate variability (HRV) may help identify the presence and severity of encephalopathy. Our aim was to analyse HRV features in full-term neonates with HIE and assess its ability to grade severity of HIE and predict neurodevelopmental outcome at 2-years of age. <h3>Methods</h3> This was a retrospective study of healthy full-term neonates and full-term neonates with HIE. All neonates had multichannel EEG and ECG monitoring from as soon as possible after birth. EEGs were graded at 12, 24, and 48 h (mild, moderate, severe) and 1 h epochs of EEG and ECG data were extracted. Features of HRV were calculated from ECG recordings in each epoch. A comparison of HRV features between HIE and healthy groups and within HIE groups (mild/moderate/severe) was performed. The ability of HRV features to predict neurodevelopmental outcome at 2-years of age was also assessed. <h3>Results</h3> 44 neonates with HIE and 17 healthy controls were included. Measures of HRV were significantly negatively correlated with EEG grade of HIE severity. HRV was significantly reduced between mild and moderate HIE groups. EEG grade of HIE measured at 12, 24, and 24 h after birth has a strong positive predictive value and reduced HRV at 24 and 48 h has a strong negative predictive value for 2 year neurodevelopmental outcome. <h3>Conclusion</h3> HRV features significantly correlate with the grade of HIE severity and may be useful for the prediction of long term outcome.

FGF2 as a potential prognostic biomarker for proneural glioma patients

Background. The survival of high-grade glioma patients is poor and the treatment of these patients can cause severe side effects. This fosters the necessity to identify prognostic biomarkers, in order to optimize treatment and diminish unnecessary suffering of patients. The aim of this study was to identify prognostic biomarkers for high-grade glioma patients.Methods. Eleven proteins were selected for analysis due to their suggested importance for survival of patients with other types of cancers and due to a high variation in protein levels between glioma patients (according to the Human Protein Atlas, www.proteinatlas.org). Protein expression patterns of these 11 proteins were analyzed by immunohistochemistry in tumor samples from 97 high-grade glioma patients. The prognostic values of the proteins were analyzed with univariate and multivariate Cox regression analyses for the high-grade glioma patients, including subgroup analyses of histological subtypes and immunohistochemically defined molecular subtypes.Results. The proteins with the most significant (univariate and multivariate p < 0.05) correlations were analyzed further with cross-validated Kaplan-Meier analyses for the possibility of predicting survival based on the protein expression pattern of the corresponding candidate. Random Forest classification with variable subset selection was used to analyze if a protein signature consisting of any combination of the 11 proteins could predict survival for the high-grade glioma patients and the subgroup with glioblastoma patients. The proteins which correlated most significantly (univariate and multivariate p < 0.05) to survival in the Cox regression analyses were Myc for all high-grade gliomas and FGF2, CA9 and CD44 for the subgroup of proneural gliomas, with FGF2 having a strong negative predictive value for survival. No prognostic signature of the proteins could be found.Conclusion. FGF2 is a potential prognostic biomarker for proneural glioma patients, and warrants further investigation.