Diagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID-19 vaccines: A systematic review and meta-analysis.

For persons with immediate allergic reactions to mRNA COVID-19 vaccines, skin testing (ST) to the vaccine/excipients (polyethylene glycol[PEG] and polysorbate 80 [PS]) has been recommended, but has unknown accuracy. To assess vaccine/excipient ST accuracy in predicting all-severity immediate allergic reactions upon re-vaccination, systematic review was performed searching Medline, EMBASE, Web of Science, and the WHO global coronavirus database (inception-Oct 4, 2021) for studies addressing immediate (≤4 h post-vaccination) all-severity allergic reactions to 2nd mRNA COVID-19 vaccination in persons with 1st dose immediate allergic reactions. Cases evaluating delayed reactions, change of vaccine platform, or revaccination without vaccine/excipient ST were excluded. Meta-analysis of diagnostic testing accuracy was performed using Bayesian methods. The GRADE approach evaluated certainty of the evidence, and QUADAS-2 assessed risk of bias. Among 20 studies of mRNA COVID-19 first dose vaccine reactions, 317 individuals underwent 578 ST to any one or combination of vaccine, PEG, or PS, and were re-vaccinated with the same vaccine. Test sensitivity for either mRNA vaccine was 0.2 (95%CrI 0.01-0.52) and specificity 0.97 (95%CrI 0.9-1). PEG test sensitivity was 0.02 (95%CrI 0.00-0.07) and specificity 0.99 (95%CrI 0.96-1). PS test sensitivity was 0.03 (95%CrI 0.00-0.0.11) and specificity 0.97 (95%CrI 0.91-1). Combined for use of any of the 3 testing agents, sensitivity was 0.03 (95%CrI 0.00-0.08) and specificity was 0.98 (95%CrI 0.95-1.00). Certainty of evidence was moderate. ST has low sensitivity but high specificity in predicting all-severity repeat immediate allergic reactions to the same agent, among persons with 1st dose immediate allergic reactions to mRNA COVID-19 vaccines. mRNA COVID-19 vaccine or excipient ST has limited risk assessment utility.

A Clinically Meaningful Interpretation of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II and III Data.

RATIONALE AND OBJECTIVES: This study aimed to calculate the multiple-level likelihood ratios (LRs) and posttest probabilities for a positive, indeterminate, or negative test result for multidetector computed tomography pulmonary angiography (MDCTPA) ± computed tomography venography (CTV) and magnetic resonance pulmonary angiography (MRPA) ± magnetic resonance venography (MRV) for each clinical probability level (two-, three-, and four-level) for the nine most commonly used clinical prediction rules (CPRs) (Wells, Geneva, Miniati, and Charlotte). The study design is a review of observational studies with critical review of multiple cohort studies. The settings are acute care, emergency room care, and ambulatory care (inpatients and outpatients). MATERIALS AND METHODS: Data were used to estimate pulmonary embolism (PE) pretest probability for each of the most commonly used CPRs at each probability level. Multiple-level LRs (positive, indeterminate, negative test) were generated and used to calculate posttest probabilities for MDCTPA, MDCTPA + CTV, MRPA, and MRPA + MRV from sensitivity and specificity results from Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II and PIOPED III for each clinical probability level for each CPR. Nomograms were also created. RESULTS: The LRs for a positive test result were higher for MRPA compared to MDCTPA without venography (76 vs 20) and with venography (42 vs 18). LRs for a negative test result were lower for MDCTPA compared to MRPA without venography (0.18 vs 0.22) and with venography (0.12 vs 0.15). In the three-level Wells score, the pretest clinical probability of PE for a low, moderate, and high clinical probability score is 5.7, 23, and 49. The posttest probability for an initially low clinical probability PE for a positive, indeterminate, and negative test result, respectively, for MDCTPA is 54, 5 and 1; for MDCTPA + CTV is 52, 2, and 0.7; for MRPA is 82, 6, and 1; and for MRPA + MRV is 72, 3, and 1; for an initially moderate clinical probability PE for MDCTPA is 86, 22, and 5; for MDCTPA + CTV is 85, 10, and 4; for MRPA is 96, 25, and 6; and for MRPA + MRV is 93, 14, and 4; and for an initially high clinical probability of PE for MDCTPA is 95, 47, and 15; for MDCTPA + CTV is 95, 27, and 10; for MRPA is 99, 52, and 17; and for MRPA + MRV is 98, 34, and 13. CONCLUSIONS: For a positive test result, LRs were considerably higher for MRPA compared to MDCTPA. However, both a positive MRPA and MDCTPA have LRs >10 and therefore can confirm the presence of PE. Performing venography reduced the LR for a positive and negative test for both MDCTPA and MRPA. The nomograms give posttest probabilities for a positive, indeterminate, or negative test result for MDCTPA and MRPA (with and without venography) for each clinical probability level for each of the CPR.

How to Perform a Systematic Review and Meta-analysis of Diagnostic Imaging Studies.

A systematic review is a comprehensive search, critical evaluation, and synthesis of all the relevant studies on a specific (clinical) topic that can be applied to the evaluation of diagnostic and screening imaging studies. It can be a qualitative or a quantitative (meta-analysis) review of available literature. A meta-analysis uses statistical methods to combine and summarize the results of several studies. In this review, a 12-step approach to performing a systematic review (and meta-analysis) is outlined under the four domains: (1) Problem Formulation and Data Acquisition, (2) Quality Appraisal of Eligible Studies, (3) Statistical Analysis of Quantitative Data, and (4) Clinical Interpretation of the Evidence. This review is specifically geared toward the performance of a systematic review and meta-analysis of diagnostic test accuracy (imaging) studies.

A Clinically Meaningful Interpretation of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) Scintigraphic Data.

RATIONALE AND OBJECTIVES: Pulmonary embolism (PE) is a common condition associated with significant morbidity and mortality. Diagnostic test characteristics reported in terms of sensitivity and specificity are difficult to translate at the clinical level. More relevant measures are likelihood ratios (LRs), which can convert a pretest into a posttest probability. The aim of our study was to calculate the LRs and posttest probabilities for multiple-level test result for ventilation/perfusion (V/Q) lung scintigraphy and for perfusion scintigraphy combined with chest radiography using modified Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II and the Prospective Investigative Study of Pulmonary Embolism Diagnosis (PISAPED) criteria for each clinical probability level for the most commonly used clinical prediction rules (CPR) using the PIOPED data. MATERIALS AND METHODS: PE pretest probability was estimated for the most commonly used CPRs (Wells, Geneva, Miniati, and Charlotte) at each clinical probability level (two-, three-, and four-level). Multiple-level LRs (high, indeterminate, low, very low probability, and normal) and the positive, indeterminate, and negative results for V/Q scintigraphy, and the positive, indeterminate, and negative results for perfusion scintigraphy were generated and used to calculate posttest probabilities based on the sensitivity and specificity data from PIOPED for each clinical probability level (low, intermediate, and high) for each CPR. Nomograms were also created. RESULTS: The LRs for a positive V/Q and perfusion scintigraphy test using modified PIOPED II and PISAPED criteria were 20.6, 11, and 23.7, and for a negative test result were 0.15, 0.16, and 0.2, respectively. In the three-level Wells score, the posttest probability for an initial low clinical probability PE for a positive, indeterminate, and negative test result, respectively, for V/Q scintigraphy is 56, 5, and 0.9; for perfusion scintigraphy with modified PIOPED 40, 7, and 0.9, and with PISAPED 59, not available (N/A), and 1.2; for an initial moderate clinical probability PE for V/Q scintigraphy 86, .22, and 4; for perfusion scintigraphy with modified PIOPED 77, 26, and 5, and with PISAPED 88, N/A, and 6; for an initial high clinical probability of PE for V/Q scintigraphy 95, 48, and 13; and for perfusion scintigraphy with modified PIOPED 92, 53, and 13, and with PISAPED 96, N/A, and 16. CONCLUSIONS: With LRs >10, a positive test result for V/Q and perfusion scintigraphy can confirm the presence of PE. Only a normal test result has low enough LR to exclude PE.

Molecular Imaging in the Management of Adrenocortical Cancer: A Systematic Review.

Adrenocortical cancer (ACC) is an uncommon primary neoplasm of the adrenal cortex with dismal prognosis. It often presents with symptoms and signs of adrenal cortical hormone hypersecretion and abdominal mass effect or is incidentally detected as an adrenal mass on imaging performed for other indications. Endocrine evaluation, comprehensive staging, and meticulous resection are crucial to ensure the best possible outcome. Despite extensive initial surgical resection, local and distant metastases are not uncommon with disappointing 5-year survival, although progress is being made at high-volume centers. Accurate restaging of recurrent disease is important to guide further management. Mitotane, external beam radiation and chemotherapy, and newer anticancer systemic treatments are used as adjunctives for inoperable disease and distant metastases. Contrast-enhanced CT and MRI are first-line imaging modalities for evaluation of ACC to characterize adrenal masses and to determine tumor resectability. Emerging literature supports F-FDG PET/CT use to determine the malignant potential of adrenal masses. In patients with a diagnosis of ACC, FDG PET/CT is sensitive for detecting metastatic disease, and its tumor accumulation has been correlated to pathology, Weiss scores, and prognosis. Metomidate, labeled with C for PET or with I for SPECT/CT, allows characterization of an adrenal mass as being of adrenocortical origin with high specificity. Taking advantage of its adrenocortical avidity, metomidate has been labeled with I for radionuclide therapy in a subset of ACC. In this review, we describe how nuclear medicine imaging, and specifically PET, can assist surgical management of ACC.

Amyloid deposition in Parkinson's disease and cognitive impairment: a systematic review.

BACKGROUND: Varying degrees of cortical amyloid deposition are reported in the setting of Parkinsonism with cognitive impairment. We performed a systematic review to estimate the prevalence of Alzheimer disease (AD) range cortical amyloid deposition among patients with Parkinson's disease with dementia (PDD), Parkinson's disease with mild cognitive impairment (PD-MCI) and dementia with Lewy bodies (DLB). We included amyloid positron emission tomography (PET) imaging studies using Pittsburgh Compound B (PiB). METHODS: We searched the databases Ovid MEDLINE, PubMed, Embase, Scopus, and Web of Science for articles pertaining to amyloid imaging in Parkinsonism and impaired cognition. We identified 11 articles using PiB imaging to quantify cortical amyloid. We used the metan module in Stata, version 11.0, to calculate point prevalence estimates of patients with "PiB-positive" studies, that is, patients showing AD range cortical Aß-amyloid deposition. Heterogeneity was assessed. A scatterplot was used to assess publication bias. RESULTS: Overall pooled prevalence of "PiB-positive" studies across all three entities along the spectrum of Parkinson's disease and impaired cognition (specifically PDD, PD-MCI, and DLB) was 0.41 (95% confidence interval [CI], 0.24-0.57). Prevalence of "PiB-positive" studies was 0.68 (95% CI, 0.55-0.82) in the DLB group, 0.34 (95% CI, 0.13-0.56) in the PDD group, and 0.05 (95% CI, -0.07-0.17) in the PD-MCI group. CONCLUSIONS: Substantial variability occurs in the prevalence of "PiB-positive" studies in subjects with Parkinsonism and cognitive impairment. Higher prevalence of PiB-positive studies was encountered among subjects with DLB as opposed to subjects with PDD. The PD-MCI subjects showed overall lower prevalence of PiB-positive studies than reported findings in non-PD-related MCI. © 2015 International Parkinson and Movement Disorder Society.

Parathyroid adenoma localization with 99mTc-sestamibi SPECT/CT: a meta-analysis.

PURPOSE: The aim of the study was to determine the diagnostic utility of parathyroid scintigraphy with technetium-99m (99mTc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) for localization of parathyroid adenoma. MATERIALS AND METHODS: We performed a systematic search of medical databases PubMed and Medline/OVID for literature on 99mTc-sestamibi SPECT/CT parathyroid scintigraphy, using the search terms hyperparathyroidism, parathyroid adenoma/hyperplasia, SPECT/CT, and SPECT-CT. Citations for 981 articles and 128 abstracts of full articles were reviewed by two coauthors for relevance. Twenty-four peer-reviewed studies on SPECT/CT parathyroid scintigraphy qualified for inclusion. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality. Meta-analytical techniques were used to obtain pooled estimates of the parathyroid adenoma localization rate using a random-effects model. RESULTS: A total of 24 studies published between January 2003 and March 2014 with 1276 patients (334 men, 762 women, and 180 of unspecified sex) met the inclusion criteria. Data on the test performance of dual-phase 99mTc-sestamibi SPECT/CT showed an estimated pooled sensitivity (per-patient analysis) of 0.86 [confidence interval (CI) 0.81-0.90]. Sensitivity of SPECT/CT was superior to that of SPECT (0.74; CI 0.66-0.82) and planar (0.70; CI 0.61-0.80) techniques. Heterogeneity was present in the reported literature (I2=80.3%). The rate of ectopic parathyroid adenomas ranged between 4 and 20% and SPECT/CT was superior to SPECT and planar imaging for localization of ectopic sites. CONCLUSION: Utilization of SPECT/CT fusion imaging for 99mTc-sestamibi parathyroid scintigraphy improves the test performance compared with planar and SPECT imaging; it assists preoperative planning for a minimally invasive surgical approach for the neck and is of value in subgroups with ectopic glands or coexisting nodular thyroid disease.

Comparing the effectiveness of competing tests for reducing colorectal cancer mortality: a network meta-analysis.

BACKGROUND: Comparative effectiveness data pertaining to competing colorectal cancer (CRC) screening tests do not exist but are necessary to guide clinical decision making and policy. OBJECTIVE: To perform a comparative synthesis of clinical outcomes studies evaluating the effects of competing tests on CRC-related mortality. DESIGN: Traditional and network meta-analyses. Two reviewers identified studies evaluating the effect of guaiac-based fecal occult blood testing (gFOBT), flexible sigmoidoscopy (FS), or colonoscopy on CRC-related mortality. INTERVENTIONS: gFOBT, FS, colonoscopy. MAIN OUTCOME MEASUREMENTS: Traditional meta-analysis was performed to produce pooled estimates of the effect of each modality on CRC mortality. Bayesian network meta-analysis (NMA) was performed to indirectly compare the effectiveness of screening modalities. Multiple sensitivity analyses were performed. RESULTS: Traditional meta-analysis revealed that, compared with no intervention, colonoscopy reduced CRC-related mortality by 57% (relative risk [RR] 0.43; 95% confidence interval [CI], 0.33-0.58), whereas FS reduced CRC-related mortality by 40% (RR 0.60; 95% CI, 0.45-0.78), and gFOBT reduced CRC-related mortality by 18% (RR 0.82; 95% CI, 0.76-0.88). NMA demonstrated nonsignificant trends favoring colonoscopy over FS (RR 0.71; 95% CI, 0.45-1.11) and FS over gFOBT (RR 0.74; 95% CI, 0.51-1.09) for reducing CRC-related deaths. NMA-based simulations, however, revealed that colonoscopy has a 94% probability of being the most effective test for reducing CRC mortality and a 99% probability of being most effective when the analysis is restricted to screening studies. LIMITATIONS: Randomized trials and observational studies were combined within the same analysis. CONCLUSION: Clinical outcomes studies demonstrate that gFOBT, FS, and colonoscopy are all effective in reducing CRC-related mortality. Network meta-analysis suggests that colonoscopy is the most effective test.

Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis.

OBJECTIVE: Reliable biomarkers for amyotrophic lateral sclerosis (ALS) are needed, given the clinical heterogeneity of the disease. Here, we provide proof-of-concept for using multimodal magnetic resonance imaging (MRI) as a diagnostic biomarker for ALS. Specifically, we evaluated the added diagnostic utility of proton magnetic resonance spectroscopy (MRS) to diffusion tensor imaging (DTI). METHODS: Twenty-nine patients with ALS and 30 age- and gender-matched healthy controls underwent brain MRI which used proton MRS including spectral editing techniques to measure γ-aminobutyric acid (GABA) and DTI to measure fractional anisotropy of the corticospinal tract. Data were analyzed using logistic regression, t-tests, and generalized linear models with leave-one-out analysis to generate and compare the resulting receiver operating characteristic (ROC) curves. RESULTS: The diagnostic accuracy is significantly improved when the MRS data were combined with the DTI data as compared to the DTI data only (area under the ROC curves (AUC) = 0.93 vs. AUC = 0.81; P = 0.05). The combined MRS and DTI data resulted in sensitivity of 0.93, specificity of 0.85, positive likelihood ratio of 6.20, and negative likelihood ratio of 0.08 whereas the DTI data only resulted in sensitivity of 0.86, specificity of 0.70, positive likelihood ratio of 2.87, and negative likelihood ratio of 0.20. INTERPRETATION: Combining multiple advanced neuroimaging modalities significantly improves disease discrimination between ALS patients and healthy controls. These results provide an important step toward advancing a multimodal MRI approach along the diagnostic test development pathway for ALS.

Single-photon emission computed tomography/computed tomography as a problem-solving tool in patients with suspected acute cholecystitis.

AIM: The aim of this study was to evaluate our institutional experience with single-photon emission computed tomography/computed tomography (SPECT/CT) hepatobiliary imaging as a problem-solving tool in the workup of suspected acute cholecystitis. METHODS: We queried our radiology information system database for cases in which SPECT/CT had been performed as part of the routine hepatobiliary technetium Tc 99m iminodiacetic acid studies done for the evaluation of acute cholecystitis. Fifty-three consecutive patients who had SPECT/CT after planar imaging were included. This cohort represents cases that were considered problematic by the initial interpreting physician on the basis of planar images. The planar and SPECT/CT images were retrospectively reviewed independently and separately by 2 experienced nuclear medicine specialists who evaluated the planar images for visualization of the gallbladder on a binary scale (yes or no) and rated their level of confidence on an ordinal scale(unsure, somewhat sure, and sure). RESULTS: Single-photon emission CT/CT would have led to change in the management for interpreter 1 in a total of 23 cases (41%), with change from normal to abnormal scan findings (28%) and from abnormal to normal scan findings (13%). Similarly, SPECT/CT would have led to change in the management for interpreter 2 in a total of 23 cases (43%), with change from normal to abnormal scan findings (13%) and from abnormal to normal scan findings (30%). CONCLUSIONS: Although planar hepatobiliary scanning is usually sensitive and specific, there are occasionally problematic cases. In our experience, we found that the addition of SPECT/CT improved the interobserver agreement and may change management in patients with superimposed bowel activity and/or unusual gallbladder anatomy that can confound the planar interpretation.

Diagnostic accuracy of diffusion tensor imaging in amyotrophic lateral sclerosis: a systematic review and individual patient data meta-analysis.

RATIONALE AND OBJECTIVES: There have been a large number of case-control studies using diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS). The objective of this study was to perform an individual patient data (IPD) meta-analysis for the estimation of the diagnostic accuracy measures of DTI in the diagnosis of ALS using corticospinal tract data. MATERIALS AND METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane databases (1966-April 2011) were searched. Studies were included if they used DTI region of interest or tractography techniques to compare mean cerebral corticospinal tract fractional anisotropy values between ALS subjects and healthy controls. Corresponding authors from the identified articles were contacted to collect individual patient data. IPD meta-analysis and meta-regression were performed using Stata. Meta-regression covariate analysis included age, gender, disease duration, and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores. RESULTS: Of 30 identified studies, 11 corresponding authors provided IPD and 221 ALS patients and 187 healthy control subjects were available for study. Pooled area under the receiver operating characteristic curve (AUC) was 0.75 (95% CI: 0.66-0.83), pooled sensitivity was 0.68 (95% CI: 0.62-0.75), and pooled specificity was 0.73 (95% CI: 0.66-0.80). Meta-regression showed no significant differences in pooled AUC for each of the covariates. There was moderate to high heterogeneity of pooled AUC estimates. Study quality was generally high. Data from 19 of the 30 eligible studies were not ascertained, raising possibility of selection bias. CONCLUSION: Using corticospinal tract individual patient data, the diagnostic accuracy of DTI appears to lack sufficient discrimination in isolation. Additional research efforts and a multimodal approach that also includes ALS mimics will be required to make neuroimaging a critical component in the workup of ALS.

Comparative effectiveness of elastographic and B-mode ultrasound criteria for diagnostic discrimination of thyroid nodules: a meta-analysis.

OBJECTIVE: The purpose of this article is to present, through systematic review of recent literature, a comparative effectiveness analysis of ultrasound elastography versus B-mode ultrasound features for differentiating thyroid nodules. MATERIALS AND METHODS: We conducted an extensive literature search of PubMed and other medical and general purpose databases from January 1966 through March 2012. Eligible studies were published in English, reported diagnostic performance of elastography (using elasticity score or strain ratio) with or without B-mode ultrasound in differentiation of thyroid nodules, and used histology or cytology as the reference standard. Summary diagnostic performance measures were assessed for each of the elasticity measuring methods and ultrasound features by means of a bivariate random effects model. RESULTS: Twenty-four studies provided relevant information on more than 2624 patients and 3531 thyroid nodules (927 malignant and 2604 benign). Six ultrasound features (echogenicity, calcifications, margins, halo sign, shape, and color Doppler flow pattern) were compared with elasticity score and strain ratio. The respective sensitivities and specificities were as follows: elasticity score, 82% and 82%; strain ratio, 89% and 82%; hypoechogenicity, 78% and 55%; microcalcifications, 50% and 80%; irregular margins, 66% and 81%; absent halo sign, 56% and 57%; nodule vertical development, 46% and 77%; and intranodular vascularization, 40% and 61%. CONCLUSION: Evaluation of thyroid nodules with ultrasound elastography appears to be both more sensitive and specific than each of the ultrasound features. The former is a safe and effective technique that warrants further rigorous investigation or use in the clinical diagnosis of thyroid nodules.

Impact of breast mass size on accuracy of ultrasound elastography vs. conventional B-mode ultrasound: a meta-analysis of individual participants.

OBJECTIVES: To conduct an individual patient data meta-analysis comparing the diagnostic performance of ultrasound elastography (USE) versus B-mode ultrasound (USB) across size ranges of breast masses. METHODS: An extensive literature search of PubMed and other medical/general purpose databases from inception through August 2011 was conducted. Corresponding authors of published studies that reported a direct comparison of the diagnostic performance of USE using the elasticity score versus USB for characterisation of focal breast masses were contacted for their original patient-level data set. Summary diagnostic performance measures were compared for each test within and across three mass size groups (<10 mm, 10-19 mm, and >19 mm). RESULTS: The patient-level data sets were received from five studies, providing information on 1,412 breast masses. For breast masses <10 mm (n = 543; 121 malignant), the sensitivity/specificity of USE and USB were 76 %/93 % and 95 %/68 %, respectively. For masses 10-19 mm of size (n = 528; 247 malignant), sensitivity/specificity of USE and USB were 82 %/90 % and 95 %/67 %, respectively. For masses >19 mm of size (n = 325; 162 malignant), sensitivity/specificity of USE and USB were 74 %/94 % and 97 %/55 %, respectively. CONCLUSION: Regardless of the mass size, USE has higher specificity and lower sensitivity compared to USB in characterising breast masses. The performance of each of these two tests does not vary significantly by mass size.

Diagnostic accuracy using diffusion tensor imaging in the diagnosis of ALS: a meta-analysis.

RATIONALE AND OBJECTIVES: A number of studies have reported decreases in fractional anistropy (FA) in amyotrophic lateral sclerosis using diffusion tensor imaging (DTI). The purpose of this study was to perform a meta-analysis in order to estimate the diagnostic test accuracy measures of DTI for the diagnosis of amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: We searched MEDLINE (1966-April 2011), EMBASE (1999-April 2011), CINAHL (1999-April 2011), and Cochrane (2005-April 2011) databases to identify studies that measured FA in ALS subjects. Human, single-center studies using a DTI region of interest (ROI) or tractography techniques were used to compare FA values along the brain corticospinal tracts between ALS subjects and healthy controls. There were no language restrictions. Independent extraction of articles by 2 authors using predefined data fields including study quality indicators. We identified 30 case-control studies that used region of interest or tractography DTI techniques. We applied binormal receiver operative characteristic (ROC) curve analysis to assign specificity and sensitivity for each study. We applied the bivariate mixed-effects regression model using the Markov Chain Monte Carlo Simulation to calculate summary estimates for the sensitivity and specificity. We used the metan module in Stata, version 11.0, to calculate the area under the ROC curve, diagnostic odds ratio and the test effectiveness summary estimates. RESULTS: The pooled sensitivity was 0.65 (95% CI 0.61-0.69); the pooled specificity, 0.67 (95% CI 0.63-0.72); the pooled diagnostic odds ratio, 1.88 (95% CI 1.46-2.30); the pooled test effectiveness, 1.04 (95% CI 0.81-1.27); and the pooled area under the ROC curve, 0.76 (95% CI 0.71-0.81). Subanalyses comparing magnetic resonance imaging (MRI) field strength (1.5T vs. 3.0T) and brain location (corticospinal tract average vs. internal capsule) revealed no significant differences in the test accuracy measures. Reference standard used for the diagnosis of ALS was the El Escorial criteria. There was at least moderate heterogeneity between the studies. True study quality is uncertain. CONCLUSION: The discriminatory capability of DTI to make a diagnosis of ALS is only modest. There were no significant differences in the diagnostic test accuracy summary estimates with respect to MRI field strength or brain location.

Accuracy of quantitative ultrasound elastography for differentiation of malignant and benign breast abnormalities: a meta-analysis.

The purpose of this study was to systematically review recent literature on diagnostic performance of strain ratio and length ratio, two different strain measurements in ultrasound elastography, for differentiating benign and malignant breast masses. A literature search of PubMed and other medical and general purpose databases from inception through January 2012 was conducted. Published studies that evaluated the diagnostic performance of ultrasound elastography alone reporting either strain ratio or length ratio for characterization of focal breast lesions and using cytology (fine needle aspiration) or histology (core biopsy) as a reference standard were included. Summary diagnostic performance measures were assessed using bivariate generalized linear mixed modeling. Nine studies reported strain ratio for 2,087 breast masses (667 cancers, 1,420 benign lesions). Summary sensitivity and specificity were 88 % (95 % Credible Interval (CrI), 84-91 %), and 83 % (95 % CrI, 78-88 %), respectively. The positive and negative likelihood ratios (LR) were 5.57 (95 % CrI, 3.85-8.01) and 0.14 (95 % CrI, 0.09-0.20), respectively. The inconsistency index for heterogeneity was 6 % (95 % CrI, 1-22 %) for sensitivity and 8 % (95 % CrI, 3-24 %) for specificity. Analysis of three studies reporting length ratio for 450 breast masses demonstrated sensitivity and specificity of 98 % (95 % CrI, 93-99 %) and 72 % (95 % CrI, 31-96 %), respectively. Strain ratio and length ratio have good diagnostic performance for distinguishing benign from malignant breast masses. Although, this performance may not be incrementally superior to that of breast imaging reporting and data system (BIRADS) in B-mode ultrasound, the application of USE using strain ratio or length ratio in combination with USB may have the potential to benefit the patients, and this requires further comparative effectiveness and cost-effectiveness analyses.

Utility of pretreatment mean apparent diffusion coefficient and apparent diffusion coefficient histograms in prediction of outcome to chemoradiation in head and neck squamous cell carcinoma.

PURPOSE: This study aimed to evaluate pretreatment whole-tumor mean apparent diffusion coefficient (ADC) and ADC histogram as predictors of outcome to chemoradiation in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Patients with HNSCC underwent pretreatment 3-T diffusion-weighted magnetic resonance imaging with calculation of mean ADC and ADC histograms. Outcomes were determined 2 years after chemoradiation. Positive outcome was defined as no abnormal 18-fluoro deoxy glucose uptake on posttherapy computed tomography-positron emission tomography (or abnormal uptake that was proven benign), no locoregional recurrence or metastatic disease, and no requirement for salvage surgery. Negative outcome was defined as residual abnormal 18-fluoro deoxy glucose avidity that was proven malignant, salvage surgery requirement, locoregional recurrence or metastatic disease, death, or a combination of these. A 2-sample t test was used to compare the mean ADC between patients with positive and negative outcomes. The ADC cut point for dividing the groups was determined by looking at its distribution. A Kaplan-Meier plot was produced, and a log-rank test was conducted with calculation of sensitivity, specificity, and positive and negative predictive values. RESULTS: Nine patients showed positive and 8 showed negative outcomes. Significant difference (P = 0.03) was seen in mean ADC (in 10 mm/s) between patients showing positive and negative outcomes (1.18 and 1.43, respectively). According to the log-rank test, tumors with greater than 45% of their volume below the ADC threshold of 1.15 × 10 mm/s were more likely to have a positive outcome (accuracy, 77%). CONCLUSIONS: Patients with HNSCC demonstrating lower pretreatment ADC and with greater than 45% of volume below ADC threshold of 1.15 × 10 mm/s may have better outcome to chemoradiation at 2 years.

Dual-source computed tomography angiography for diagnosis and assessment of coronary artery disease: systematic review and meta-analysis.

BACKGROUND: Development of an accurate test for noninvasive assessment of coronary arteries has been highly desirable. OBJECTIVES: We performed a systematic review of diagnostic accuracy of the dual-source computed tomography (DSCT) in the diagnosis of coronary artery disease (CAD). METHODS: Eight medical databases were searched for articles published from January 2005 through March 2011. Studies compared DSCT coronary angiography (DSCT-CA) and invasive coronary angiography, as the reference standard, in consecutive patients with suspected or known CAD, and relevant data were extracted by 2 independent reviewers. Summary diagnostic accuracies were calculated, and the effect of covariates on the diagnostic performance was evaluated by meta-regression. RESULTS: Twenty-five studies were included. In per-patient analysis (n = 2303), pooled sensitivity was 99% [95% confidence interval (CI), 97%-99%] with specificity of 89% (95% CI, 84%-92%). The summary positive (+LR) and negative (-LR) likelihood ratios were 8.6 (95% CI, 6.4-11.6) and 0.02 (95% CI, 0.01-0.03), respectively. In per-segment analysis (n = 32,615), pooled sensitivity was 94% (95% CI, 92%-96%) with specificity of 97% (95% CI, 96%--98%). Summary +LR and -LR were 30.2 (95% CI, 22.1-43.5) and 0.06 (95% CI, 0.04-0.08), respectively. CONCLUSIONS: DSCT-CA seems to be robust to elevate heart rates while maintaining a high level of diagnostic performance.

Ultrasonographic differentiation of malignant from benign breast lesions: a meta-analytic comparison of elasticity and BIRADS scoring.

There has been controversy regarding the accuracy of breast ultrasound elastography (USE) compared to conventional B-mode Ultrasound (USB). The purpose of this study was to conduct a direct comparative effectiveness analysis of USB versus USE or their combination in differentiating breast lesions through systematically reviewing recent literature. An extensive literature search of PubMed and other medical and general purpose databases from inception through August 2011 was conducted. Published studies that reported a direct comparison of the diagnostic performance of USE, using elasticity score versus USB, using breast imaging reporting and data system (BIRADS) for characterization of focal breast lesions were included. Summary diagnostic performance measures were assessed for each of the tests and their combination using bivariate generalized linear mixed modeling. The two tests were combined as: (1) conjunctive, where the outcome of the combination of tests is positive only if both test results are positive; (2) disjunctive, where the outcome of a combination of tests is negative only if both tests are negative. Twenty nine studies provided relevant information on 5,511 breast masses (2,065 cancers, 3,446 benign lesions). Sensitivity of USB, USE, and their conjunctive and disjunctive combinations were 96% (95% credible interval (CrI), 93-98%), 79% (95% CrI, 74-83%), 73% (95% CrI, 67-78%), and 99% (95% CrI, 98-99%), respectively. Specificity of USB, USE, and their conjunctive and disjunctive combinations were 70% (95% CrI, 55-83%), 88% (95% CrI, 82-92%), 97% (95% CrI, 95-99%), and 56% (95% CrI, 43-69%), respectively. The application of USE as a single test is not superior to USB alone. However, in low risk patients it is recommended to perform an USE following a positive USB result to decrease the rate of unnecessary biopsies.

Characterization of adrenal masses by using FDG PET: a systematic review and meta-analysis of diagnostic test performance.

PURPOSE: To perform a systematic review and meta-analysis of published data to determine the diagnostic utility of adrenal fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing benign from malignant adrenal disease. MATERIALS AND METHODS: Data on FDG PET assessment in MEDLINE and other electronic databases (from inception to November 2009) and in subject matter-specific journals were evaluated and compared with histologic diagnoses and/or established clinical and imaging follow-up results. Methodologic quality was assessed by using Quality Assessment of Diagnostic Accuracy Studies criteria. Bivariate random-effects meta-analytical methods were used to estimate summary and subgroup-specific sensitivity, specificity, and receiver operating characteristic curves and to investigate the effects of study design characteristics and imaging procedure elements on diagnostic accuracy. RESULTS: A total of 1391 lesions (824 benign, 567 malignant) in 1217 patients from 21 eligible studies were evaluated. Qualitative (visual) analysis of 841 lesions (in 14 reports) and quantitative analyses based on standardized uptake values (SUVs) for 824 lesions (in 13 reports) and standardized uptake ratios (SURs) for 562 lesions (in eight reports) were performed. Resultant data were highly heterogeneous, with a model-based inconsistency index of 88% (95% confidence interval [CI]: 79%, 98%). Mean sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio values for differentiating between benign and malignant adrenal disease were 0.97 (95% CI: 0.93, 0.98), 0.91 (95% CI: 0.87, 0.94), 11.1 (95% CI: 7.5, 16.3), 0.04 (95% CI: 0.02, 0.08), and 294 (95% CI: 107, 805), respectively, with no significant differences in accuracy among the visual, SUV, and SUR analyses. CONCLUSION: Meta-analysis of combination PET-computed tomography (CT) reports revealed that FDG PET was highly sensitive and specific for differentiating malignant from benign adrenal disease. Diagnostic accuracy was not influenced by the type of imaging device (PET vs PET/CT), but specificity was dependent on the clinical status (cancer vs no cancer).

The prognostic power of the NOD2 genotype for complicated Crohn's disease: a meta-analysis.

OBJECTIVES: Crohn's disease is often purely inflammatory at presentation, but most patients develop strictures and fistulae over time (complicated disease). Many studies have suggested that nucleotide-binding oligomerization domain 2 (NOD2) mutations are associated with a varying but increased risk of complicated disease. An accurate and sufficiently powerful predictor of complicated disease could justify the early use of biological therapy in high-risk individuals. We performed a systematic review and meta-analysis to obtain accurate estimates of the predictive power of the identified mutations (such as p.R702W, P.G908R, and p.Leu1007fsX1008) in NOD2 for the risk of complicated disease. METHODS: An electronic search of MEDLINE, Embase, and Web of Science identified 917 relevant papers. Inclusion required specification of genetic mutations at the individual level and disease phenotypes by Vienna classification (inflammatory (B1), stricturing (B2), and fistulizing (B3)). A total of 49 studies met these criteria, which included 8,893 subjects, 2,897 of whom had NOD2 mutations. Studies were weighted by median disease duration. Studies not providing duration data were weighted at the level of the study with the shortest disease duration (3.9 years). RESULTS: The relative risk (RR) of the presence of any NOD2 mutant allele for complicated disease (B2 or B3) was 1.17 (95% confidence interval (95% CI) 1.10-1.24; P<0.001). P.G908R was associated with an RR of complicated disease of 1.33 (95% CI 1.11-1.60; P=0.002). NOD2 did not predict perianal disease (P=0.4). The RR of surgery was 1.58 (95% CI 1.38-1.80; P<0.001). There was substantial heterogeneity across all studies (I(2)=66.7%). On the basis of logistic regression of these data, the sensitivity of any mutation in predicting complicated disease was 36% and specificity was 73%, with the area under the receiver operating characteristic curve 0.56. CONCLUSIONS: The presence of a single NOD2 mutation predicted an 8% increase in the risk for complicated disease (B2 or B3), and a 41% increase with 2 mutations. Surgery risk is increased by 58% with any NOD2 mutation, whereas perianal disease was unchanged. The predictive power associated with a single NOD2 mutation is weak. The RR of any NOD2 mutations for complicated disease was only 17% across 36 studies. However, the presence of two NOD2 mutations had 98% specificity for complicated disease. These data provide insufficient evidence to support top-down therapy based solely on single NOD2 mutations, but suggest that targeted early-intensive therapy for high-risk patients with two NOD2 mutations might be beneficial, if prospective trials can demonstrate changes in the natural history in this subset of patients.