Likelihood Ratio For Positive Test Research Articles

Can MR Spectroscopy Predict Lymph Node Status in Breast cancer

Experimental studies have shown increased concentrations of glycerophosphocholine‐phosphocholine (GPC‐PC), choline, lactate, alanine and uridine diphosphoglucose and higher GPC‐PC/threonine (Thr) in lymph nodes with metastases. As biochemical changes in tumor infiltrated lymph nodes occur earlier than morphological changes and Proton (1H) Magnetic Resonance Spectroscopy MRS) can detect these chemical changes, it can be a potentially useful investigation in evaluation of sentinel lymph node (SLN) in breast cancer for early detection of metastasis. Aim: To evaluate the role of MR Spectroscopy (MRS) in identifying biochemical changes in sentinel lymph node in breast cancer and correlate its findings with histopathology to predict presence of metastasis. Materials &MethodsSLN were obtained from 59 breast cancer patients who underwent SLN biopsy. Each LN was bisected into two equal halves. One half was snap frozen in liquid nitrogen (‐196°C) so that all the enzymatic reactions are arrested and no more metabolic changes occur thereby, keeping the physiological state of the tissues intact. The tissues were then stored at −80°C until perchloric acid extraction was carried out. The other half was subjected to histopathological evaluation (HPE). Conventional HPE of LN was performed using standard Eosin & Hematoxylin staining. MRS: Water‐soluble metabolites from the tissue samples were extracted using PCA extraction procedure as reported in the literature. Proton (1H) MRS of all specimen was performed by an investigator from Department of NMR who was blinded to results of histopathology. Experiments were carried out on a narrow bore spectrometer operating at 700 MHz (Agilent Technologies, Santa Clara, CA, USA) equipped with 5 mm dedicated multinuclear broadband inverse probe at 25°C. Spectrum with water suppression was acquired with a single 60° pulse (Ernst angle). The concentration of of GPC, PC, Thr & Lac were estimated. Statistical Analyses: Levels of concentrations of various metabolites were compared between involved and non‐involved LNs using Wilcoxon rank sum (Mann Whitney) test. Diagnostic test indices were calculated taking histopathology as ‘gold standard’.ResultsMean concentrations of GPC, PC, CHO, Threonine and lactate were significantly increased in involved as compared to non‐involved nodes (Table 1). A cut‐off value of 0.80 for the GPC‐PC/Thr ratio was chosen to obtain a maximum accuracy of 89% for the classification of the lymph nodes based on our previous study. MRS accurately predicted metastasis in 21 of the 24 patients who had lymph node metastasis on histopathology. Out of 35 patients with no lymph node metastasis, MRS correlated accurately with histopathology in 30 of them. Sensitivity, specificity, PPV, NPV and overall accuracy for MRS in detecting LN metastasis were 87.5%; 88%; 80.7%; 90.9% and 86.4% respectively. Likelihood ratio for positive test and negative test for MRS to detect LN metastasis were 6.1 and 0.14 respectively.ConclusionMRS can accurately predict presence of metastasis in SLN in breast cancer. Further studies with a larger sample size are essential before incorporating MR Spectroscopy in routine clinical practice to detect lymph node metastasis in breast cancer.

Self-reported and clinically identified loss of smell and taste among persons tested for COVID-19 in Chennai, southern India, July-August 2020: A cross sectional study

BackgroundEarly detection of symptoms of loss of smell and taste lately added for Coronavirus disease 2019 (COVID-19) has the potential for improving pandemic response. In the Indian context, we compared proportion experiencing new loss of smell or taste among COVID-19 positive and negative individuals in Chennai city, Southern India. MethodsWe did an analytical cross-sectional study among individuals aged 18–80 years undergoing testing at COVID-19 sample collection centres. We ascertained loss of smell and taste using standardised self-reporting and clinical examination procedures. We administered Sino Nasal Outcome (SNOT 22) questionnaire for comprehensive understanding of these symptoms. We compared proportion having symptoms between COVID-19 positive and negative persons. We compared the two assessment methods to compute diagnostic validity indicators. ResultsOf the 277 participants, 169 (61%) were men and mean age of 40.7 years [SD = 13.3]. Fifty eight (21%) had COVID-19 and 12 (36%) of them were asymptomatic. Predominantly reported symptoms were fever (30%), headache (18%) and cough (18%). Self-reported or clinically identified new loss of smell or taste was higher among COVID-19 positive (n = 13; 22%) than negative persons (n = 23; 11%) [p = 0.02]. Sensitivity was higher for self-reported or clinically identified loss of smell (17.2%) than that of loss of taste (6.9%). Negative predictive value for loss of smell or taste, self-reported or clinically identified was 81%. Likelihood ratio of positive test was 2.13. ConclusionLoss of smell or taste are predominantly reported by COVID-19 confirmed individuals. Objective and subjective assessments of smell and taste may be required to identify those requiring COVID-19 testing.

Abstract PS1-38: Role of MR spectroscopy in evaluation of axilla in breast cancer

Abstract The role of surgery for women with breast cancer presenting with clinically negative axilla is being questioned. Trials are underway to evaluate axillary ultrasound (AUS) for non-invasive evaluation of axilla instead of sentinel node biopsy. However, AUS has a sensitivity of 50-59%. Thus, there is a need for non-invasive test to complement AUS. MR Spectoroscopy (MRS) identifies metabolites, viz. glycerophosphocholine (GPC), phosphocholine (PC), threonine (Thr), lactate (Lac), Choline (Cho) etc that are associated with presence of metastasis in axillary lymph nodes (LN) . Biochemical changes in tumor infiltrated LNs occur earlier than morphological changes and MRS can detect these chemical changes, it can be a useful investigation in evaluation of axilla. Aim: To evaluate the role of MR Spectroscopy (MRS) in identifying biochemical changes in axillary lymph nodes in breast cancer and correlate the findings with Histopathology (HP) to predict presence of metastasis.Methods: Axillary lymph nodes were obtained from 59 patients with early breast cancer with clinically negative axilla who underwent surgery. Each LN was bisected into two equal halves. One half of LN was snap frozen in liquid nitrogen (-196°C) and then stored at −80°C until perchloric acid extraction was carried out. Other half of LN was subjected to HP evaluation with standard Eosin and Hematoxylin staining . METHOD OF MR Spectroscopy: Water-soluble metabolites from the tissue samples were extracted using PCA extraction procedure (Seenu et al Magn Reson Imaging 2005 doi: 10.1016/j.mri.2005.10.004). Proton (1H) NMR spectroscopy of specimen was performed. Concentrations of GPC, PC, Thr, Lac, Cho and other metabolites were determined by comparing the integrated intensity of isolated resonances of the compounds of interest with that of the TSP signal, correcting for the number of contributing protons and with the tissue weight . Intensity ratio for metabolites, GPC, PC and Thr (GPC+PC/Thr) was also determined.Statistical Analyses: Levels of concentrations of various metabolites were compared between involved and non-involved lymph nodes using Wilcoxon rank sum test. Diagnostic indices of MRS were assessed in terms of sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios and overall accuracy taking final histopathology as ‘gold standard’ with 95% confidence intervals.Results: Mean concentrations of GPC, PC and Thr were significantly increased in involved as compared to non-involved node (table 1). Cho and Lac were not significantly increased. A cut-off value of 0.80 for the GPC-PC/Thr ratio was chosen to obtain a maximum accuracy of 89% based on previous study. MRS accurately predicted metastasis in 21 of the 24 patients who had LN metastasis on HP. Out of 35 patients with no LN metastasis, MRS correlated accurately with HP in 30 of them. Sensitivity, specificity, PPV, NPV and overall accuracy for MRS in detecting LN metastasis were 87.5%; 88%; 80.7%; 90.9%; and 86.4% respectively. Likelihood ratio for positive test and negative test for MRS to detect LN metastasis were 6.1 and 0.14 respectively.Conclusion: MRS can accurately predict presence of metastasis in axillary lymph nodes in vitro. In vivo studies are essential to corroborate these findings. Mean concentrations of metabolites in axillary lymph nodesInvolvedNon involvedP valueGPC0.5923(SD=0.5726)0.3648(SD=0.6774)0.02PC0.7347(SD=0.9466)0.5286(SD=1.1111)0.03Cho0.6930(SD=0.6756)0.8435(SD=0.5030)0.21Thr2.9656(SD=2.2397)1.1674(SD=1.2274)0.02Lac4.5515(SD=2.3271)3.2907(SD=1.3296)0.31 Citation Format: Srineil Vuthaluru, Anurag Srivastava. Role of MR spectroscopy in evaluation of axilla in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-38.

Brief Screening for Four Mental Illnesses of the Elderly in Community Mental Health Services: the BS4MI-Elderly.

ObjectiveEarly detection and proper management of mental illness can help to prevent severe deterioration. However, with limited financial and human resources of community mental health services, it is not practical to carry out all conventional screening tools simultaneously. In this study, we aimed to develop and validate a brief but comprehensive screening questionnaire for four common mental illnesses of the elderly. MethodsThe brief screening for four mental illnesses of elderly (BS4MI-elderly) is a 14-item binary response questionnaire that covers dementia, depressive disorder, sleep disorder, and hwa-byung. To test validity, we compared conventional scale scores for three groups of participants classified using the BS4MI-elderly. The sensitivity, specificity, predictive value of positive test, likelihood ratio of positive test and internal consistency of the BS4MI-elderly were assessed. Finally, a correlation analysis between the BS4MI-elderly and general mental health scales was conducted. ResultsA total of 254 participants aged over 65 years were recruited. The BS4MI-elderly showed moderate to high sensitivity for the test that distinguishes the normal group from the risk and disorder groups (dementia: 0.61, depressive disorder: 0.88, sleep disorder: 0.85, hwa-byung: 0.94) and high specificity for the test that distinguishes the disorder group from the normal and risk groups (dementia: 0.91, depressive disorder: 0.93, hwa-byung: 0.84, sleep disorder: 0.84). The BS4MI-elderly also exhibited good internal consistency and significant correlations with general mental health scales. ConclusionThe BS4MI-elderly, a brief but comprehensive screening tool, could be a useful instrument for screening the elderly in community mental health services.

MON-329 Diagnostic Utility of Overnight High Dose Dexamethasone Suppression Test for Differentiating the Etiology of ACTH Dependent Cushing’s Syndrome

Background:Bilateral inferior petrosal sinus sampling (BIPSS) has been the gold standard in differentiating a pituitary vs. an ectopic source of ACTH in Cushing’s syndrome however, it has many limitations. The ON-HDDST being simple to perform and the tests of choice in resource poor setting. The primary aim of our study was to consolidate the present knowledge regarding the diagnostic utility of ON-HDDST in localizing the source of ACTH.Method:We retrospectively studied 88 patients with ACTH dependent Cushing syndrome who underwent ONHDDST. Patient were considered as Cushing disease (CD) if either of the 3 criteria were met a) histopathological confirmed b) a central to peripheral gradient >2 was seen in BIPSS or c) pituitary adenoma ≥ 6mm seen in MRI of pituitary. Patient were considered as ectopic ACTH syndrome if the tumor was localized at any peripheral location by imaging or histopathological confirmed after surgery or if BIPSS shown a central to peripheral gradient of <2. Result: Out of total 88 ACTH dependent Cushing syndrome patients, 68 (77.3%) were proven CD and 20 (22.7%) were ectopic. There was no difference in basal serum cortisol however, S. Cortisol after ONHDDST was significantly different between the two with a median of 547.7 nmol/l (341-770) in ectopic vs 273.5 nmol/l (142-689) in CD (p=0.02). A positive response to ONHDDST (≥50% suppression) was seen in about 44 (65%) patients with CD and 5 (25%) patients with ectopic disease (p = 0.002). Among CD patient, 35 (76.1%) of those with microadenoma, 7 (43.8%) amongst macroadenoma and 2 (33%) patient with no visible tumor on MRI shown positive response to ONHDDST. In ectopic group, cortisol suppressibility was seen in 3 (50%) patient with occult tumor but only in 2(14.3%) patient with. ROC curve plotted for percentage suppression of cortisol after ONHDDST shown as AUC equal to 0.68 (p = 0.01). The best test parameters with sensitivity (65%), specificity (85%) and Accuracy (69%) were seen at 50% cutoff level as were the likelihood ratio for positive test (4.3), AUC (0.75), PPV (93.6%), NPV (41.4%). Conclusion: Our study has shown that ONHDDST has poor diagnostic value in differentiating between CD and ectopic ACTH syndrome whatever be the cutoff level of the cortisol suppression. However, this can still be utilized in setups where no alternative is available. For etiologic confirmation, another test with better sensitivity and specificity is preferable.

Value of CCNA1 promoter methylation in triaging ASC-US cytology.

Background:Using HPV testing to triage ASC-US still has some problems of unnecessary colposcopy in many cases. A previous study reported that methylation of CCNA1, a tumor suppressor gene, can differentiate between low and high grade lesions. This study was designed to evaluate the diagnostic values and application of CCNA1 methylation in the patients with ASC-US group. Materials and Methods:Cross sectional analytic study was conducted in the patients with ASC-US cytology. HPV DNA testing and CCNA1 promoter methylation testing were performed. The patients were sent for colposcopic examination and biopsy. Biopsy results were considered as gold standard. Diagnostic test of HPV test and CCNA1 methylation test were calculated for sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), likelihood ratio for test positive and negative and 95% confidence interval. Results:One hundred and seventy patients were enrolled. Mean age was 39.7 years old. HR-HPV was positive in 70% of the patients. HPV type 16, type 18 and non-16,18 were 12.4%, 4.7% and 42.4%, respectively. CIN2+ were found in 12.4% (21 cases). CCNA1 promoter methylation was positive in 5 cases. CCNA1 had high specificity 99.3%, NPV 89.2% and PPV 80% in detection of CIN2+ but sensitivity was 19%. Likelihood ratio for positive test was 28.4 and likelihood ratio for negative test was 0.8. HPV test had sensitivity of 90.5% and NPV of 95.9% but low specificity and PPV as 31.5% and 15.7%, respectively. Conclusion:CCNA1 promoter methylation testing had very high specificity, likelihood ratio for the positive test and PPV (99.3%, 28.4 and 80.0, respectively). Therefore, CCNA1 promoter methylation test may be used in the HPV DNA positive cases to classify the urgency of colposcopy and the colposcopist should pay more attention to CCNA1 positive patients because of their higher chance to identify the significant lesions.

Comparison between three different diagnostic criteria in evaluating metabolic syndrome: An experience from college students of Kolkata, India

Background: Metabolic syndrome (MS) is gradually surging particularly among Asian Indians. Documented data on comparative studies based on different definitions with respect to MS prevalence among college students are few. Aim: The aim of this is to find the validity and degree of agreement between three different diagnostic criteria recommended by the International Diabetes Federation (IDF), the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), and the Consensus definition for Asian Indians (CDAI). Materials and Methods: A cross-sectional study was conducted among 477 college students aged 18–24 years of Kolkata selected by systematic random sampling from August 2011 to December 2014. Three different criteria, i.e., IDF, NCEP-ATP III, and CDAI, were used. Individuals signed a consent form before the study. Using IDF as a reference standard, validity of other criteria was measured by sensitivity and specificity. Cohen's kappa (κ) coefficient was used to identify the degree of agreement between three different definitions. Statistical analysis was performed using SPSS software, version 19.0. P ≤ 0.05 was considered statistically significant. Results: The prevalence of MS among college students was highest using the CDAI criteria (5.7%), followed by the IDF criteria (4.5%) and the NCEP-ATP III criteria (2.9%) being significantly higher in females (P ≤ 0.05). Using IDF as a reference standard, the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of positive test for CDAI were 100%, 98.9%, 81.5%, 100%, and 90.9, respectively; whereas, for the NCEP-ATP III criteria, these were 45.5%, 99.1%, 71.4%, 97.4%, and 50.56, respectively. IDF presented “almost perfect” agreement in relation to the CDAI with κ of 0.892 (95% CI: 0.798–0.986, P = 0.000) and “moderate” agreement with respect to the NCEP-ATP III criteria with κ of 0.539 (95% CI: 0.339–0.739, P = 0.000). Conclusion: At least 2.9% of the Kolkata college students studied had MS. The CDAI criteria were superior to the NCEP-ATP III criteria for predicting MS in this population, when compared with the IDF criteria.

Sensitivity of total protein creatinine ratio in urine for diagnosis diabetic nephropathy

Diabetic nephropathy is one of diabetic complication characterized by proteinuria and impaired renal function. Confirmation of diagnosis based either on urine value of albumin excretion rate (AER) 30-300 mg/24 hours or albumin creatinine ratio (ACR) 30-300 mg/g or total protein creatinine ratio (TPCR) 150-500 mg/g. It is reported that TPCR measurement is more acceptable since it is convenient, fast and does not require special preparation. The aim of this study is to investigate the accuracy of TPCR for diagnosis of diabetic nephropathy among type 2 diabetic patients.This was a diagnostic test study which involves 86 type 2 diabetic patients where urine TPCR value equal or more than 150mg/g was independently and blindly compared with AER as a refference standard to diagnose diabetic nephopathy. The inclusion criteria were type 2 diabetic patients that suspected suffer from diabetic nephropathy (long of illness is more than 4 years) and agree to participate in this study. Those whom were suffer from at least on of the following diseases urinary tract infection, congestive heart failure, liver dysfunction, pregnancy, multiple myeloma , microangiopathy hemolytic anemia (MAHA) and incomplete data were excluded from the study. The results of the study were analyzed using 2x2 table in order to calculate sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio for positive test result/LR(+),likelihood ratio for negative test result/LR(-),and accuracy. The average of TPCR among diabetic nephropathy patient was 248.07 mg/g. It was significantly higher as compared to those non diabetic nephropathy patient (103.52 mg/g). It was found 75 true positive result, 9 true negative result, and 2 false positive result. The result showed that TPCR had a sensitivity, specificity, positive predictive value, and negative predictive value of 97.4%, 100%, 100%, and 81,8% respectively to diagnose diabetic nephropathy.Total Protein Creatinine Ratio (TPCR) with value equal or more than 150 mg/g in the morning sample urine can be used to diagnose diabetic nephropathy. Keywords : diabetic nephropathy, total protein creatinine ratio, sensitivity, albumin excretion rate, diagnostic test study

Screening for older emergency department inpatients at risk of prolonged hospital stay: the brief geriatric assessment tool.

BackgroundThe aims of this study were 1) to confirm that combinations of brief geriatric assessment (BGA) items were significant risk factors for prolonged LHS among geriatric patients hospitalized in acute care medical units after their admission to the emergency department (ED); and 2) to determine whether these combinations of BGA items could be used as a prognostic tool of prolonged LHS.MethodsBased on a prospective observational cohort design, 1254 inpatients (mean age ± standard deviation, 84.9±5.9 years; 59.3% female) recruited upon their admission to ED and discharged in acute care medical units of Angers University Hospital, France, were selected in this study. At baseline assessment, a BGA was performed and included the following 6 items: age ≥85years, male gender, polypharmacy (i.e., ≥5 drugs per day), use of home-help services, history of falls in previous 6 months and temporal disorientation (i.e., inability to give the month and/or year). The LHS in acute care medical units was prospectively calculated in number of days using the hospital registry.ResultsArea under receiver operating characteristic (ROC) curves of prolonged LHS of different combinations of BGA items ranged from 0.50 to 0.57. Cox regression models revealed that combinations defining a high risk of prolonged LHS, identified from ROC curves, were significant risk factors for prolonged LHS (hazard ratio >1.16 with P>0.010). Kaplan-Meier distributions of discharge showed that inpatients classified in high-risk group of prolonged LHS were discharged later than those in low-risk group (P<0.003). Prognostic value for prolonged LHS of all combinations was poor with sensitivity under 77%, a high variation of specificity (from 26.6 to 97.4) and a low likelihood ratio of positive test under 5.6.ConclusionCombinations of 6-item BGA tool were significant risk factors for prolonged LHS but their prognostic value was poor in the studied sample of older inpatients.

A Study to Compare the Nutritional Status Assessed by CAN Score and Ponderal Index against WHO Intrauterine Growth Curves among Newborns at Birth in Selected Hospital of Ambala, Haryana

The neonatal morbidity and mortality is closely related to the nutritional status of newborn at birth and early identification of malnutrition with appropriate tool and technique can reduce the mortality rate. Descriptive and comparative survey design was used to assess and compare the Nutritional status of newborns at birth by CAN Score and Ponderal Index against WHO Intrauterine growth curves at MMIMS&R Hospital, Mullana Ambala. Sixty newborns were selected by purposive sampling from NICU and postnatal wards. The data was collected by Performa for newborn and maternal characteristics, WHO Intrauterine Growth Curves, Ponderal Index and observation sheet of CAN Score. Findings revealed that Ponderal Index (48.4%) classified more newborns as malnourished as compared to CAN Score (25%) with regard to WHO Intrauterine growth curves (21.6%). Ponderal Index has higher Sensitivity (76.9%) and lower Specificity (59.5%) than CAN Score (38.4%, 78.7%) respectively whereas Positive predictive value and Negative predictive value of Ponderal Index (34.4%, 90.3%) was higher than CAN Score (33.3%,82.2%). The likelihood ratio of Positive test of Ponderal Index (1.89) was higher than CAN Score (1.80) and likelihood ratio of Negative test of Ponderal Index (0.38) was lower than CAN Score (0.78) test indicating that Ponderal Index can act more sensitive indicator of assessing malnutrition than CAN Score. The main conclusion of the study is that Ponderal Index may be a simple clinical index but sensitive predictor for identifying malnutrition and for prediction of neonatal morbidity associated with it, without the aid of any sophisticated equipments.

Validity of Integrative Weaning Index of Discontinuation From Mechanical Ventilation in Iranian ICUs

Background: Today, usage of weaning index is a controversial issue. Proper use of these indexes is beneficial for prevention of the losses caused by weaning failure, rapid and reliable identification of patients who are potentially ready for spontaneous breathing and accelerating the weaning of mechanical ventilation. Objectives: This study is to determine the validity of integrative weaning index as a mechanical ventilation discontinuation predictor in patients hospitalized in the Iranian intensive care units. Patients and Methods: This scale was evaluated on 124 adult patients who were on mechanical ventilation for more than 24 hours, in two 24-hour phases, in six ICUs (Surgery-Trauma-Medical-Poisoning) of selected hospitals in Tehran, totaling 60 beds, by the researcher as a single blind test. Inclusion criteria were: Patient 18 to 80 years old, none of them suffering from neurological and neuromuscular diseases, none or a minimal dose of sedative drugs being used (15 - 18 points based on Palma and Cook criteria), non-addict or heavy smokers, not admitted in ICU-OH. The study was conducted from November 2011 to December 2012. The ventilators used were from Rafael brand. Results: There were 80 successful and 44 unsuccessful as well as 72 successful and 8 unsuccessful weaning cases in the first and second phase of the study, respectively. The area under the ROC curves for IWI was 0.967, with standard error of 0.020, 95% Confidence interval of 0.899 to 0.993 and Significance level of P = 0.001, SE = 94.59, SP = 66.67, PPV = 97.22, NPV = 50, DA = 92.5 and likelihood ratio of positive test being 2.84 besides the lowest likelihood ratio of negative test equal to 0.08), with Diagnostic odds ratio being 97% and Confidence interval of 0.82 to 0.97. Conclusions: Integrative weaning index has appropriate predictive validity for weaning patients from mechanical ventilation in Iranian intensive care units.

Dual Time Point Positron Emission Tomography/Computed Tomography Scan in Evaluation of Intrathoracic Lesions in an Area Endemic for Histoplasmosis and With High Prevalence of Sarcoidosis

BackgroundWe explored the role of dual time point fluorodeoxyglucose positron emission tomography/computed tomography (DTP PET/CT) scan in the differentiation of benign and malignant lung and mediastinal lesions. MethodsWe studied a sample of 72 consecutive patients who underwent DTP PET/CT scan for intrathoracic lesions. Information on demographics, initial and delayed maximum standardized uptake values (SUVmax) of lesions and final diagnosis were collected. Clinical criteria to diagnose benign lesions were defined as stability or regression of the lesion on follow-up after 2 years of initial detection. Sensitivity, specificity, predictive values and likelihood ratio and retention index were calculated using standard methods. ResultsSixty-three (87%) patients had increased SUVmax in delayed scan (1 hour after initial scan). Among the patients with increased delayed uptake, 51 (80%) had malignant lesion and 12 (20%) had nonmalignant lesions. All 9 patients whose SUVmax decreased on delayed scan had nonmalignant lesions. The increased SUV on delayed scan was 100% sensitive in diagnosis of cancer but was only 42% specific. The positive predictive value was 80%, whereas the negative predictive value was 100%. Likelihood ratio for positive test was 1.75. ConclusionsAll the lesions with decreased SUVmax in delayed PET scan were nonmalignant. This was true for both lung and mediastinal lesions. This could be a very helpful diagnostic finding in areas with high prevalence of benign conditions such as histoplasmosis and sarcoidosis. Multiple invasive diagnostic modalities could be prevented in a significant percentage of patients, with attendant decrease in morbidity and health care costs.

Clinical Indicators for Differential Diagnosis of Acute Lower Abdominal Pain in Women of Reproductive Age

Background: Acute lower abdominal pain in women of reproductive age is a challenging condition for clinical diagnosis. Computerized tomography yields high accuracy, but may not be cost-effective in low-middle income countries. Selective diagnostic approach based on clinical findings may be more appropriate. Methods: Medical record review was performed on patients aging between 15 - 50 years who admitted to the surgical department or obstetrics and gynecology (OB-GYN) unit because of acute lower abdominal pain during January to December 2008. Patients were eventually categorized into appendicitis, OB-GYN conditions, or non-specific abdominal pain (NSAP). Clinical indicators were studied for diagnostic values using polytomous logistic regression applied to likelihood ratio for positive test (LR + ) and confidence interval (CI). Results: Anorexia, nausea and vomiting, shifting of abdominal pain decreased the likelihood of OB-GYN conditions. Diarrhea increased the likelihood of NSAP. Right lower quadrant tenderness increased the likelihood of appendicitis but decreased the likelihood of OB-GYN conditions. Left lower quadrant tenderness decreased the likelihood of appendicitis but increased the likelihood of OB-GYN. Guarding or rebound tenderness increased the likelihood of appendicitis but reduced the likelihood of NSAP. Leucocytosis (white blood cell count &gt;= 10,000) increased the likelihood of appendicitis but reduced the likelihood of OB-GYN and NSAP. Neutrophil &gt;= 75% increased the likelihood of OB-GYN but decreased the likelihood of NSAP. Pregnancy reduced the likelihood of appendicitis and increased the likelihood of OB-GYN. Conclusion: Gastrointestinal symptoms, sites of abdominal tenderness, guarding or rebound tenderness, leucocytosis, neutrophil &gt;= 75% and pregnancy are clinical indicators that may help differentiating appendicitis, common OB-GYN conditions, or NSAP in acute lower abdominal pain in women of reproductive age. doi: http://dx.doi.org/10.4021/jcs179w

Derivation and validation of a Short Form of the Mini‐Mental State Examination for the screening of dementia in older adults with a memory complaint

To validate a Short Form of the Mini-Mental State Examination (SMMSE) as a screening test for dementia in older ambulatory individuals followed in a memory clinic for a memory complaint. A total of 202 cognitively healthy individuals, 100 individuals with a mild cognitive impairment and 304 demented individuals sent for a memory complaint by their primary care physician to a memory clinic were prospectively included in this cross-sectional study. They were randomized into derivation (n=303) and validation (n=303) groups. The SMMSE score was built from six memory items of MMSE, with a score ranging from 0 to 6 (i.e. best performance). The receiver operating characteristic curve showed an area under the curve of 0.98 for the derivation group and 0.97 for the validation group without differences between curves (P=0.254). The cut-off between the sensitivity and the specificity of the SMMSE score for clinically diagnosed dementia was ≤4. The performance of the SMMSE for the diagnosis of dementia was high in the derivation and validation groups: sensitivity at 93.1% and 93.8%, specificity at 93.8% and 90.5%, positive predictive value at 94.3% and 90.1%, negative predictive value at 92.5% and 94.0%, likelihood ratio of positive test at 14.9 and 9.8 and of negative test at 0.07 and 0.07, respectively. The Short Form of the Mini-Mental State Examination was a good screening test for dementia in older individuals followed in a memory clinic for a memory complaint. The next step should be the confirmation of its discriminative value in older primary care patients.

Use of PTEN protein dosage to predict for underlying germ-line PTEN mutations among patients presenting with thyroid cancer and Cowden-like phenotypes.

1508 Background: Thyroid cancer is a major component of Cowden Syndrome (CS), a heritable syndrome characterized also by breast, uterine and kidney cancers. CS patients with an underlying germline PTEN mutation have a 70-fold increased risk of developing epithelial thyroid cancer. In contrast, &lt;1% of sporadic epithelial thyroid cancer harbor a germline PTEN mutation. Thus, cost-efficient markers capable of shortlisting thyroid cancers for CS genetic testing would be clinically useful. Here, we analyzed the relationship of patient PTEN protein levels in predicting the presence of germline PTEN mutations. Methods: We conducted a 5-year, multi-center prospective study of 2792 CS and CS-like patients, all of whom had comprehensive PTEN analysis done. Analysis of PTEN and downstream proteins by immunoblotting was performed on total protein lysates from patient-derived lymphoblast lines. We compared PTEN protein expression levels between patients with pathogenic PTEN mutations (PTENmut+), and those with variants of unknown significance (VUS) or wildtype PTEN. PTEN immunohistochemistry (IHC) was performed on available thyroid samples. Results: Of 2792 CS/CS-like patients, 722 had thyroid cancer. PTEN germline pathogenic mutations were present in 36/722 (5%) patients. PTENmut+ cases presented at an earlier age (35 vs 42 years; p=0.02). PTEN frameshift and truncation mutations accounted for 55% of mutations. 95% (19/20) of PTENmut+ patients had blood-PTEN protein levels in the lowest quartile as compared to 27% (90/330) of PTEN wildtype/PTEN VUS patients (p&lt;0.001). Low blood-PTEN levels predicted for PTENmut+ cases with a 99.6 % NPV (95%CI 97.7- 99.9) and a positive test likelihood ratio of 3.5 (95%CI 2.8-4.3). Affected thyroid tissues (n=22) from PTENmut+ cases showed loss of PTEN protein by IHC, correlating with patient blood PTEN levels (r2=0.30, p=0.016). Conclusions: Our study shows that PTEN protein dosage could serve as a molecular correlate predicting for germline PTEN mutation in CS and CS-like presentations of thyroid cancer. The clinical utility of PTEN IHC in identifying thyroid cancer patients for germline PTEN testing should be further explored.

The validity of 9 physical tests for full-thickness rotator cuff tears after primary anterior shoulder dislocation in ED patients

PurposeThis study was undertaken to validate the diagnostic values of 9 different physical tests in emergency department patients with primary anterior shoulder dislocation (PASD) to select the best screening test for full-thickness rotator cuff tear (FTRCT) after PASD. MethodsA prospective analysis of 49 consecutive patients with x-ray-confirmed PASD was performed. All patients were followed at an average of 6.9 days (ranged from 4 to 10 days) in the emergency department. On the day of follow-up, 9 physical tests (namely, Jobe test, external rotation lag sign test, infraspinatus muscle strength test, dropping test, drop test, liftoff test, internal rotation lag sign test, belly-press test, and belly-off test) followed by shoulder ultrasound scan were performed to detect FTRCT. ResultsThe prevalence of FTRCT after PASD is 37% (95% confidence interval [CI], 24%-52%). Fourteen percent of the patients with PASD were complicated with isolated supraspinatus tendon tear, whereas 22% were complicated with supraspinatus tendon tear combined with subscapularis and/or infraspinatus tendon tear. Jobe test has the highest sensitivity among the 9 physical tests being evaluated. The sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for positive test, and likelihood ratio for negative test of Jobe test as a screening test for FTRCT after PASD are 89% (95% CI, 64%-98%), 55% (95% CI, 36%-72%), 53% (95% CI, 35%-71%), 89% (95% CI, 65%-98%), 1.97 (95% CI, 1.29-2.99), and 0.20 (95% CI, 0.05-0.79), respectively. ConclusionsThe prevalence of FTRCT after PASD is 37% (95% CI, 24%-52%). Jobe test has the highest sensitivity (89% CI, 64%-98%) among the tests.

Longitudinal Analysis of Serial Liver Biopsies in Chronically Transfused Sickle Cell Disease

Abstract 1052▪▪This icon denotes a clinically relevant abstract Background:Chronic red cell transfusions are commonly used for the treatment and prevention of complications in sickle cell disease (SCD). Liver injury from transfusional iron overload is a recognized morbidity of chronic transfusion therapy, but little is known about the progression of liver injury over time in SCD. Methods:We conducted a retrospective cohort study of all chronically transfused people with SCD who had 2 or more serial liver biopsies at a single academic hospital. Subjects with viral hepatitis were excluded. Serum ferritin, serum ALT, chelation status, and transfusion volumes were extracted from the electronic record and validated against paper records in all subjects. Quantitative liver iron concentration (LIC) was determined at the time of biopsy by inductively coupled plasma-mass spectrometry. Core liver biopsy slides stained for iron and fibrosis were retrieved and scored in a blinded fashion by a hepatopathologist (RA) for total iron score (TIS, Deugnier, 2007) and fibrosis score (Ishak, 1995). Analyses evaluated how liver fibrosis changed over the first 2 biopsies and how changes in biomarkers correlated with changes in fibrosis. Cross sectional analyses assessed the relationship of biomarkers to the presence or absence of fibrosis. Ferritin was analyzed as an average of the 3 closest values ± 6 weeks of liver biopsy. Area under receiver operator characteristic curve (AUC) analysis, likelihood ratios for positive tests (LR+), and summary statistics were calculated using Stata v11.2. Results:26 people had at least 2 serial core liver biopsies for evaluation (n=70 biopsies total, range 2–7 biopsies per subject). Fibrosis was Ishak grade 0 or 1 in all biopsies. Median age at first biopsy was 13.3 years and median total transfusion duration was 9.4 years. The first 2 biopsies were obtained a median of 2.3 years apart. Evaluation of the first 2 biopsies showed that fibrosis was present in 7/26 initial biopsies and 3/26 second biopsies: fibrosis regressed in 6 subjects, developed in 2 subjects and persisted in 1 subject. Among non-chelated subjects at the time of first biopsy, 2/11 had fibrosis, as compared to 5/15 subjects who had received a mean of 3.7 years of chelation at the time of first biopsy (18% vs 33%, P=0.6). Eleven subjects had 3 or more serial biopsies performed during a median of 9.2 years of chronic transfusion. There was no consistent pattern of fibrosis development, nor was there an apparent association of fibrosis with LIC over time (Figure, asterisks indicate presence of fibrosis). On a cross-sectional basis, ALT performed better than ferritin in classifying fibrosis, with ALT having an AUC of 0.80 (95% CI 0.66–0.94) and ferritin having an AUC of 0.63 (95% CI 0.38–0.87). LIC performed poorly at discriminating fibrosis from no fibrosis (AUC 0.30; 95%CI 0.0–0.82). The highest positive likelihood ratios for fibrosis were for a ferritin cutoff of 5000 ng/mL (LR+ 5.7) and an ALT cutoff of 65 U/L (LR+ 5.2). Longitudinal analysis did not reveal any statistically significant relationship between changes in fibrosis status and changes in ferritin, ALT, LIC, TIS, and cumulative red cell transfusion volume. Summary:Among chronically transfused people with SCD, liver fibrosis most often does not persist or progress, as detected by serial core liver biopsies. On a cross-sectional basis, serum ALT >65 U/L and serum ferritin >5000 ng/mL are cutoffs associated with the highest likelihood of liver fibrosis. Cross-sectional or longitudinal measurements of LIC are not associated with fibrosis. Conclusion:The progression of liver fibrosis is minimal among people with SCD who receive chronic red cell transfusions for up to 17 years. Serum biomarkers may be used to inform when investigations for fibrosis are warranted. Disclosures:No relevant conflicts of interest to declare.

Non-sequential narrow band imaging for targeted biopsy and monitoring of gastric intestinal metaplasia

To evaluate the efficacy of non-sequential narrow band imaging (NBI) for a better recognition of gastric intestinal metaplasia (GIM). Previously diagnosed GIM patients underwent targeted biopsy from areas with and without GIM, as indicated by NBI, twice at an interval of 1 year. The authors compared the endoscopic criteria such as light blue crest (LBC), villous pattern (VP), and large long crest (LLC) with standard histology. The results from two surveillance endoscopies were compared with histology results for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio of positive test (LR+). The number of early gastric cancer cases detected was also reported. NBI targeted biopsy was performed in 38 and 26 patients during the first and second surveillance endoscopies, respectively. There were 2 early gastric cancers detected in the first endoscopy. No cancer was detected from the second study. Surgical and endoscopic resections were successfully performed in each patient. Sensitivity, specificity, PPV, NPV, and LR+ of all 3 endoscopic criteria during the first/second surveillance were 78.8%/91.3%, 82.5%/89.1%, 72.8%/77.8%, 86.8%/96.1, and 4.51/8.4, respectively. LBC provided the highest LR+ over VP and LLC. Non-sequential NBI is useful for GIM targeted biopsy. LBC provides the most sensitive reading. However, the optimal duration between two surveillance requires further study.

Baseline Illness Severity Does Not Alter Accuracy of Neonatal Sepsis Screen

We investigated the relationship between illness severity and accuracy of neonatal sepsis screen. Consecutive neonates with clinically suspected early onset sepsis (EOS) were enrolled and blood culture and sepsis screen [C-reactive protein, absolute neutrophil count, immature to total ratio (ITR) and microerythrocyte sedimentation rate] were performed. Exclusion criteria were prior antibiotic exposure, nonavailable reports, and contaminated cultures. Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE-II) was used to categorize neonates into "mild to moderate" (score <or=40) and "severe" (score >40) illness. Sepsis was defined as positive blood culture, and positive screen as >or=2 parameters positive. Of 125 subjects, 86 had mild to moderate and 39, severe illness. Twenty-eight (22%) subjects had sepsis. Sensitivity, specificity, negative predictive value, positive predictive value, likelihood ratio of positive test, and likelihood ratio of negative test of the sepsis screen and screen parameters were similar between the two groups. The sensitivity of the screen was 37.5% and 25% for mild to moderate illness and severe illness, respectively. Only ITR values correlated with SNAPPE-II scores in patients with "sepsis" (rho 0.4; P = 0.036). The severity of underlying illness does not alter the performance of the sepsis screen in diagnosing culture-positive EOS.

Clinical impact of whole body FDG-PET for recurrent biliary cancer: a multicenter study

To evaluate the clinical usefulness of positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) in patients with follow-up or suspected recurrent biliary cancer in a multicenter study. We performed a retrospective review of 50 patients who underwent FDG-PET (either integrated PET/CT or manual fusion of dedicated PET and CT) scans for post-treatment surveillance of biliary cancer. Recurrence was suspected in 40 of these patients on the basis of tumor marker levels, and/or findings of conventional imaging (group A). Clinical findings in the remaining 10 patients showed them to be disease-free (group B). The diagnostic performance and clinical impact of PET were analyzed. Recurrence was confirmed in 28 out of the 40 patients in group A, and 1 of the 10 patients in group B. Patient-based analysis showed that the sensitivity, specificity, and accuracy of PET for detecting recurrence were 86% (25/29), 91% (19/21), and 88% (44/50), respectively. The one patient with recurrence in group B was correctly interpreted by PET. Positive test likelihood ratio and negative test likelihood ratio were increased from 1.69 to 9.05, and 0.08 to 0.32, respectively, after PET study. The findings of PET resulted in a change of management for 10 out of the 50 patients (20%) by initiating an unplanned treatment strategy (n = 7), by obviating the need for planned diagnostic procedures (n = 2), or by changing the treatment plan (n = 1). FDG-PET/CT or PET with CT yielded helpful information in patients with suspected recurrent biliary cancer.