Combining Amplitude Spectrum Area with Previous Shock Information Using Neural Networks Improves Prediction Performance of Defibrillation Outcome for Subsequent Shocks in Out-Of-Hospital Cardiac Arrest Patients

Objective

Quantitative ventricular fibrillation (VF) waveform analysis is a potentially powerful tool to optimize defibrillation. However, whether combining VF features with additional attributes that related to the previous shock could enhance the prediction performance for subsequent shocks is still uncertain.

Methods

A total of 528 defibrillation shocks from 199 patients experienced out-of-hospital cardiac arrest were analyzed in this study. VF waveform was quantified using amplitude spectrum area (AMSA) from defibrillator''s ECG recordings prior to each shock. Combinations of AMSA with previous shock index (PSI) or/and change of AMSA (ΔAMSA) between successive shocks were exercised through a training dataset including 255shocks from 99patientswith neural networks. Performance of the combination methods were compared with AMSA based single feature prediction by area under receiver operating characteristic curve(AUC), sensitivity, positive predictive value (PPV), negative predictive value (NPV) and prediction accuracy (PA) through a validation dataset that was consisted of 273 shocks from 100patients.

Results

A total of61 (61.0%) patients required subsequent shocks (N = 173) in the validation dataset. Combining AMSA with PSI and ΔAMSA obtained highest AUC (0.904 vs. 0.819, p<0.001) among different combination approaches for subsequent shocks. Sensitivity (76.5% vs. 35.3%, p<0.001), NPV (90.2% vs. 76.9%, p = 0.007) and PA (86.1% vs. 74.0%, p = 0.005)were greatly improved compared with AMSA based single feature prediction with a threshold of 90% specificity.

Conclusion

In this retrospective study, combining AMSA with previous shock information using neural networks greatly improves prediction performance of defibrillation outcome for subsequent shocks.     

The Diagnostic Accuracy of Urine Lipoarabinomannan Test for Tuberculosis Screening in a South African Correctional Facility

Background

We evaluated the diagnostic accuracy of the urine lipoarabinomannan (LAM) antigen detection assay (Clearview TB-ELISA) to screen for tuberculosis in a South African correctional facility.

Methods

Between September 2009 and October 2010, male offenders were screened for tuberculosis (symptoms, chest radiograph, two spot sputum specimens for microscopy and culture), and urine tested for LAM. Sensitivity, specificity and predictive values of LAM were calculated using definite and probable tuberculosis combined as our gold standard.

Findings

33/871 (3.8%) participants (26% HIV-positive) had tuberculosis. Amongst HIV-positive vs. HIV-negative offenders the sensitivity and specificity of LAM was 7.1% vs. 0% and 98.5% vs. 99.8% respectively.

Conclusion

Urine LAM ELISA has inadequate sensitivity for TB screening in this population.     

Evaluating the Quality of Cardiopulmonary Resuscitation in the Emergency Department by Real-Time Video Recording System

Objectives

To compare cardiopulmonary resuscitation (CPR) quality between manual CPR and miniaturized chest compressor (MCC) CPR. To improve CPR quality through evaluating the quality of our clinical work of resuscitation by real-time video recording system.

Methods

The study was a retrospective observational study of adult patients who experienced CPR at the emergency department of Shanghai Tenth People’s Hospital from March 2013 to August 2014. All the performance of CPR were checked back by the record of “digital real-time video recording system”. Average chest compression rate, actual chest compression rate, the percentage of hands-off period, time lag from patient arrival to chest compression, time lag from patient arrival to manual ventilation, time lag from patient arrival to first IV establish were compared. Causes of chest compression hands-off time were also studied.

Results

112 cases of resuscitation attempts were obtained. Average chest compression rate was over 100 compression per minute (cpm) in the majority of cases. However, indicators such as percentage of hands-off periods, time lag from patient arrival to the first manual ventilation and time lag from patient arrival to the first IV establish seemed to be worse in the manual CPR group compared to MCC CPR group. The saving of operators change time seemed to counteract the time spent on MCC equipment. Indicators such as percentage of hands-off periods, time lag between patient arrival to the first chest compression, time lag between patient arrival to the first manual ventilation and time lag from patient arrival to the first IV establish may influence the survival.

Conclusion

Our CPR quality remained to be improved. MCC may have a potentially positive role in CPR.     

The Role of Digital Rectal Examination for Diagnosis of Acute Appendicitis: A Systematic Review and Meta-Analysis

Background

Digital rectal examination (DRE) has been traditionally recommended to evaluate acute appendicitis, although several reports indicate its lack of utility for this diagnosis. No meta-analysis has examined DRE for diagnosis of acute appendicitis.

Objectives

To assess the role of DRE for diagnosis of acute appendicitis.

Data Sources

Cochrane Library, PubMed, and SCOPUS from the earliest available date of indexing through November 23, 2014, with no language restrictions.

Study Selection

Clinical studies assessing DRE as an index test for diagnosis of acute appendicitis.

Data Extraction and Synthesis

Two independent reviewers extracted study data and assessed the quality, using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Bivariate random-effects models were used for the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) as point estimates with 95% confidence intervals (CI).

Main Outcomes and Measures

The main outcome measure was the diagnostic performance of DRE for diagnosis of acute appendicitis.

Results

We identified 19 studies with a total of 7511 patients. The pooled sensitivity and specificity were 0.49 (95% CI 0.42–0.56) and 0.61 (95% CI 0.53–0.67), respectively. The positive and negative likelihood ratios were 1.24 (95% CI 0.97–1.58) and 0.85 (95% CI 0.70–1.02), respectively. The DOR was 1.46 (0.95–2.26).

Conclusion and Relevance

Acute appendicitis cannot be ruled in or out through the result of DRE. Reconsideration is needed for the traditional teaching that rectal examination should be performed routinely in all patients with suspected appendicitis.     

Prediction of Severe Acute Pancreatitis Using a Decision Tree Model Based on the Revised Atlanta Classification of Acute Pancreatitis

Objective

To develop a model for the early prediction of severe acute pancreatitis based on the revised Atlanta classification of acute pancreatitis.

Methods

Clinical data of 1308 patients with acute pancreatitis (AP) were included in the retrospective study. A total of 603 patients who were admitted to the hospital within 36 hours of the onset of the disease were included at last according to the inclusion criteria. The clinical data were collected within 12 hours after admission. All the patients were classified as having mild acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) based on the revised Atlanta classification of acute pancreatitis. All the 603 patients were randomly divided into training group (402 cases) and test group (201 cases). Univariate and multiple regression analyses were used to identify the independent risk factors for the development of SAP in the training group. Then the prediction model was constructed using the decision tree method, and this model was applied to the test group to evaluate its validity.

Results

The decision tree model was developed using creatinine, lactate dehydrogenase, and oxygenation index to predict SAP. The diagnostic sensitivity and specificity of SAP in the training group were 80.9% and 90.0%, respectively, and the sensitivity and specificity in the test group were 88.6% and 90.4%, respectively.

Conclusions

The decision tree model based on creatinine, lactate dehydrogenase, and oxygenation index is more likely to predict the occurrence of SAP.     

Opioids Contribute to Fracture Risk: A Meta-Analysis of 8 Cohort Studies

Objective

To evaluate the association between chronic opioid use for non-cancer pain and fracture risk by conducting a meta-analysis of cohort studies.

Methods

Cohort studies were identified by searching PubMed and EMBASE from their inception to July 2014. A fracture was considered an endpoint. The information was extracted by two authors independently. When the heterogeneity was significant, a random-effects model was used to calculate the overall pooled risk estimates.

Results

Eight cohort studies were included in the final meta-analysis. On the basis of the Newcastle-Ottawa Scale (NOS), six studies were considered to be of high quality. The overall combined relative risk for the use of opioids and fractures was 1.88 (95% confidence interval [CI] 1.51-2.34). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed.

Conclusions

This meta-analysis of cohort studies demonstrates that opioids significantly increase the risk of fractures.     

Elevated Endogenous Erythropoietin Concentrations Are Associated with Increased Risk of Brain Damage in Extremely Preterm Neonates

Background

We sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO) concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI).

Methods

Protein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks. We defined ISSI as a concentration in the top quartile of each of 25 inflammation-related proteins on two separate days a week apart. Hypererythropoietinemia (hyperEPO) was defined as the highest quartile for gestational age on postnatal day 14. Using logistic regression and multinomial logistic regression models, we compared risks of brain damage among neonates with hyperEPO only, ISSI only, and hyperEPO+ISSI, to those who had neither hyperEPO nor ISSI, adjusting for gestational age.

Results

Newborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55) Mental (OR 2.3; 95% CI 1.5-3.5) and/or Psychomotor (OR 2.4; 95% CI 1.6-3.7) Development Indices (MDI, PDI), and microcephaly at age two years (OR 2.4; 95%CI 1.5-3.8). Newborns with both hyperEPO and ISSI had significantly increased risks of ventriculomegaly, hemiparetic cerebral palsy, microcephaly, and MDI and PDI < 55 (ORs ranged from 2.2-6.3), but not hypoechoic lesions or other forms of cerebral palsy, relative to newborns with neither hyperEPO nor ISSI.

Conclusion

hyperEPO, regardless of ISSI, is associated with elevated risks of very low MDI and PDI, and microcephaly, but not with any form of cerebral palsy. Children with both hyperEPO and ISSI are at higher risk than others of very low MDI and PDI, ventriculomegaly, hemiparetic cerebral palsy, and microcephaly.     

Assessment of the Incremental Benefit of Computer-Aided Detection (CAD) for Interpretation of CT Colonography by Experienced and Inexperienced Readers

Objectives

To quantify the incremental benefit of computer-assisted-detection (CAD) for polyps, for inexperienced readers versus experienced readers of CT colonography.

Methods

10 inexperienced and 16 experienced radiologists interpreted 102 colonography studies unassisted and with CAD utilised in a concurrent paradigm. They indicated any polyps detected on a study sheet. Readers’ interpretations were compared against a ground-truth reference standard: 46 studies were normal and 56 had at least one polyp (132 polyps in total). The primary study outcome was the difference in CAD net benefit (a combination of change in sensitivity and change in specificity with CAD, weighted towards sensitivity) for detection of patients with polyps.

Results

Inexperienced readers’ per-patient sensitivity rose from 39.1% to 53.2% with CAD and specificity fell from 94.1% to 88.0%, both statistically significant. Experienced readers’ sensitivity rose from 57.5% to 62.1% and specificity fell from 91.0% to 88.3%, both non-significant. Net benefit with CAD assistance was significant for inexperienced readers but not for experienced readers: 11.2% (95%CI 3.1% to 18.9%) versus 3.2% (95%CI -1.9% to 8.3%) respectively.

Conclusions

Concurrent CAD resulted in a significant net benefit when used by inexperienced readers to identify patients with polyps by CT colonography. The net benefit was nearly four times the magnitude of that observed for experienced readers. Experienced readers did not benefit significantly from concurrent CAD.     

Scoring System for Mortality in Patients Diagnosed with and Treated Surgically for Differentiated Thyroid Carcinoma with a 20-Year Follow-Up

Background

Differentiated thyroid carcinoma (DTC) is associated with an increased mortality. Few studies have constructed predictive models of all-cause mortality with a high discriminating power for patients with this disease that would enable us to determine which patients are more likely to die.

Objective

To construct a predictive model of all-cause mortality at 5, 10, 15 and 20 years for patients diagnosed with and treated surgically for DTC for use as a mobile application.

Design

We undertook a retrospective cohort study using data from 1984 to 2013.

Setting

All patients diagnosed with and treated surgically for DTC at a general university hospital covering a population of around 200,000 inhabitants in Spain.

Participants

The study involved 201 patients diagnosed with and treated surgically for DTC (174, papillary; 27, follicular).

Exposures

Age, gender, town, family history, type of surgery, type of cancer, histological subtype, microcarcinoma, multicentricity, TNM staging system, diagnostic stage, permanent post-operative complications, local and regional tumor persistence, distant metastasis, and radioiodine therapy.

Main outcome measure

All-cause mortality.

Methods

A Cox multivariate regression model was constructed to determine which variables at diagnosis were associated with mortality. Using the model a risk table was constructed based on the sum of all points to estimate the likelihood of death. This was then incorporated into a mobile application.

Results

The mean follow-up was 8.8±6.7 years. All-cause mortality was 12.9% (95% confidence interval [CI]: 8.3–17.6%). Predictive variables: older age, local tumor persistence and distant metastasis. The area under the ROC curve was 0.81 (95% CI: 0.72–0.91, p<0.001).

Conclusion

This study provides a practical clinical tool giving a simple and rapid indication (via a mobile application) of which patients with DTC are at risk of dying in 5, 10, 15 or 20 years. Nonetheless, caution should be exercised until validation studies have corroborated our results.     

A Novel Testing Model for Opportunistic Screening of Pre-Diabetes and Diabetes among U.S. Adults

Objective

The study aim was to evaluate the performance of a novel simultaneous testing model, based on the Finnish Diabetes Risk Score (FINDRISC) and HbA1c, in detecting undiagnosed diabetes and pre-diabetes in Americans.

Research Design and Methods

This cross-sectional analysis included 3,886 men and women (≥ 20 years) without known diabetes from the U.S. National Health and Nutrition Examination Survey (NHANES) 2005-2010. The FINDRISC was developed based on eight variables (age, BMI, waist circumference, use of antihypertensive drug, history of high blood glucose, family history of diabetes, daily physical activity and fruit & vegetable intake). The sensitivity, specificity, and the receiver operating characteristic (ROC) curve of the testing model were calculated for undiagnosed diabetes and pre-diabetes, determined by oral glucose tolerance test (OGTT).

Results

The prevalence of undiagnosed diabetes was 7.0% and 43.1% for pre-diabetes (27.7% for isolated impaired fasting glucose (IFG), 5.1% for impaired glucose tolerance (IGT), and 10.3% for having both IFG and IGT). The sensitivity and specificity of using the HbA1c alone was 24.2% and 99.6% for diabetes (cutoff of ≥6.5%), and 35.2% and 86.4% for pre-diabetes (cutoff of ≥5.7%). The sensitivity and specificity of using the FINDRISC alone (cutoff of ≥9) was 79.1% and 48.6% for diabetes and 60.2% and 61.4% for pre-diabetes. Using the simultaneous testing model with a combination of FINDRISC and HbA1c improved the sensitivity to 84.2% for diabetes and 74.2% for pre-diabetes. The specificity for the simultaneous testing model was 48.4% of diabetes and 53.0% for pre-diabetes.

Conclusions

This simultaneous testing model is a practical and valid tool in diabetes screening in the general U.S. population.     

Systematic Review and Meta-Analysis of Outcomes after Cardiopulmonary Arrest in Childhood

Background

Cardiopulmonary arrest in children is an uncommon event, and often fatal. Resuscitation is often attempted, but at what point, and under what circumstances do continued attempts to re-establish circulation become futile? The uncertainty around these questions can lead to unintended distress to the family and to the resuscitation team.

Objectives

To define the likely outcomes of cardiopulmonary resuscitation in children, within different patient groups, related to clinical features.

Data Sources

MEDLINE, MEDLINE in-Process & Other non-Indexed Citations, EMBASE, Cochrane database of systematic reviews and Cochrane central register of trials, Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment database, along with reference lists of relevant systematic reviews and included articles.

Study Eligibility Criteria

Prospective cohort studies which derive or validate a clinical prediction model of outcome following cardiopulmonary arrest.

Participants and Interventions

Children or young people (aged 0 – 18 years) who had cardiopulmonary arrest and received an attempt at resuscitation, excluding resuscitation at birth.

Study Appraisal and Synthesis Methods

Risk of bias assessment developed the Hayden system for non-randomised studies and QUADAS2 for decision rules. Synthesis undertaken by narrative, and random effects meta-analysis with the DerSimonian-Laird estimator.

Results

More than 18,000 episodes in 16 data sets were reported. Meta-analysis was possible for survival and one neurological outcome; others were reported too inconsistently. In-hospital patients (average survival 37.2% (95% CI 23.7 to 53.0%)) have a better chance of survival following cardiopulmonary arrest than out-of-hospital arrests (5.8% (95% CI 3.9% to 8.6%)). Better neurological outcome was also seen, but data were too scarce for meta-analysis (17% to 71% ‘good’ outcomes, compared with 2.8% to 3.2%).

Limitation

Lack of consistent outcome reporting and short-term neurological outcome measures limited the strength of conclusions that can be drawn from this review.

Conclusions and Implications of Key Findings

There is a need to collaboratively, prospectively, collect potentially predictive data on these rare events to understand more clearly the predictors of survival and long-term neurological outcome.

Systematic Review Registration Number

PROSPERO 2013:CRD42013005102     

Interleukin-2 Receptor and Angiotensin-Converting Enzyme as Markers for Ocular Sarcoidosis

Purpose

To study the impact of soluble IL2 receptor (sIL2R), chest x-ray (CxR), and angiotensin-converting enzyme (ACE) as markers for sarcoidosis in uveitis patients.

Design

Retrospective study.

Methods

Serum concentrations of sIL2R and ACE were measured in patients with active uveitis. Those with elevated sIL2R and /or ACE values were examined for suspected systemic sarcoidosis.

Main Outcome Measure

Our main outcome parameters were the specificity and sensitivity of sIL2R, CxR and ACE in screening for ocular sarcoidosis.

Results

We measured 261 patients with uveitis for sarcoidosis using sIL2R and ACE between January 2008 and November 2011; sarcoidosis was been diagnosed using other tests (e.g. computer tomography, brochoalveolar lavage, biopsy) in 41 of 53 patients with elevated sIL2R values (>639 U/ml) and in one patient with normal sIL2R (582 U/ml). Their mean sIL2R value was 1310 U/ml, extending from 582 to 8659 U/ml. Only 9 patients, however, presented elevated ACE (>82 U/l). Their mean ACE value was 116.4 U/l, ranging from 84.1 to 175.5 U/l. IL2R specificity was 94% with 98% sensitivity. In contrast, ACE had a specificity of 99.5%, but a sensitivity of only 22%; the chest x-ray had a specificity of 100% with 50% sensitivity in detecting sarcoidosis. We observed the entire spectrum of uveitis: sixteen patients suffered from anterior, 8 from intermediate, 16 from posterior, and 2 from panuveitis.

Conclusions

An elevated level of soluble IL2R suggests sarcoidosis with uveitis more convincingly than ACE, making sIL2R a more effective marker parameter for sarcoidosis than ACE or chest x-ray in uveitis patients.     

Sensitivity and Specificity of a Novel Classifier for the Early Diagnosis of Dengue

Background

Dengue is the commonest arboviral disease of humans. An early and accurate diagnosis of dengue can support clinical management, surveillance and disease control and is central to achieving the World Health Organisation target of a 50% reduction in dengue case mortality by 2020.

Methods

5729 children with fever of <72hrs duration were enrolled into this multicenter prospective study in southern Vietnam between 2010-2012. A composite of gold standard diagnostic tests identified 1692 dengue cases. Using statistical methods, a novel Early Dengue Classifier (EDC) was developed that used patient age, white blood cell count and platelet count to discriminate dengue cases from non-dengue cases.

Results

The EDC had a sensitivity of 74.8% (95%CI: 73.0-76.8%) and specificity of 76.3% (95%CI: 75.2-77.6%) for the diagnosis of dengue. As an adjunctive test alongside NS1 rapid testing, sensitivity of the composite test was 91.6% (95%CI: 90.4-92.9%).

Conclusions

We demonstrate that the early diagnosis of dengue can be enhanced beyond the current standard of care using a simple evidence-based algorithm. The results should support patient management and clinical trials of specific therapies.     

Cost-Effectiveness Analysis of Endoscopic Ultrasound versus Magnetic Resonance Cholangiopancreatography in Patients with Suspected Common Bile Duct Stones

Background

Patients with suspected common bile duct (CBD) stones are often diagnosed using endoscopic retrograde cholangiopancreatography (ERCP), an invasive procedure with risk of significant complications. Using endoscopic ultrasound (EUS) or Magnetic Resonance CholangioPancreatography (MRCP) first to detect CBD stones can reduce the risk of unnecessary procedures, cut complications and may save costs.

Aim

This study sought to compare the cost-effectiveness of initial EUS or MRCP in patients with suspected CBD stones.

Methods

This study is a model based cost-utility analysis estimating mean costs and quality-adjusted life years (QALYs) per patient from the perspective of the UK National Health Service (NHS) over a 1 year time horizon. A decision tree model was constructed and populated with probabilities, outcomes and cost data from published sources, including one-way and probabilistic sensitivity analyses.

Results

Using MRCP to select patients for ERCP was less costly than using EUS to select patients or proceeding directly to ERCP ($1299 versus $1753 and $1781, respectively), with similar QALYs accruing to each option (0.998, 0.998 and 0.997 for EUS, MRCP and direct ERCP, respectively). Initial MRCP was the most cost-effective option with the highest monetary net benefit, and this result was not sensitive to model parameters. MRCP had a 61% probability of being cost-effective at $29,000, the maximum willingness to pay for a QALY commonly used in the UK.

Conclusion

From the perspective of the UK NHS, MRCP was the most cost-effective test in the diagnosis of CBD stones.     

An Outbreak of Bartonella bacilliformis in an Endemic Andean Community

Background

Bartonellosis affects small Andean communities in Peru, Colombia and Ecuador. Research in this area has been limited.

Methods

Retrospective review of 191 cases of bartonellosis managed in Caraz District Hospital, Peru, during the last outbreak (2003).

Results

The majority of cases (65%) were 14 years old and younger. There was a peak in acute cases after the rainy season; chronic cases presented more constantly throughout the year. The sensitivity of blood smear against blood culture in acute disease was 25%. The most commonly used treatment for chronic disease was rifampicin; chloramphenicol was used to treat most acute cases. Complications arose in 6.8% and there were no deaths.

Conclusions

Diagnostic and treatment algorithms for acute and chronic bartonellosis have been developed without a strong evidence base. Preparation of ready-to-go operational research protocols for future outbreaks would strengthen the evidence base for diagnostic and treatment strategies and enhance opportunities for control.     

The Impact of the Thai Motorcycle Transition on Road Traffic Injury: Thai Cohort Study Results

Objectives

The aim of this study was to investigate the impact of motorcycle to car transitioning and urbanisation on traffic injury rates in Thailand.

Design

Analysis of two consecutive surveys of a large national cohort study.

Setting

Thailand.

Participants

The data derived from 57,154 Thai Cohort Study (TCS) participants who provided relevant data on both the 2005 and 2009 surveys.

Primary and secondary outcome measures

Motorcycle and car traffic crash injury self-reported in 2009, with twelve months’ recall.

Results

In 2009, 5608(10%) participants reported a traffic crash injury. Most crashes involved a motorcycle (74%). Car access increased and motorcycle use decreased between 2005 and 2009. Among those who used a motorcycle at both time points, traffic injury incidence was 2.8 times greater compared to those who did not use a motorcycle at either time point. Multivariable logistic regression models were used to test longitudinal and cross sectional factors associated with traffic crash injury: in the adjusted model, cars were negatively and motorcycles positively associated with injury. Living in an urban area was not injury protective in the adjusted model of traffic crash injury.

Conclusions

Ongoing urbanisation in Thailand can be expected to lead to further reductions in road traffic injuries based on transition from motorcycles to cars in urban areas. Cities, however, do not provide an intrinsically safer traffic environment. To accommodate a safe transition to car use in Thailand, traffic infrastructural changes anticipating the growing car density in urban areas is warranted.     

Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and Colorectal Cancer: A Feasibility Study

Background

Cancer stem cells represent a population of immature tumor cells found in most solid tumors. Their peculiar features make them ideal models for studying drug resistance and sensitivity. In this study, we investigated whether cancer stem cells isolation and in vitro sensitivity assay are feasible in a clinical setting.

Methods

Cancer stem cells were isolated from effusions or fresh cancer tissue of 23 patients who progressed after standard therapy failure. Specific culture conditions selected for immature tumor cells that express markers of stemness. These cells were exposed in vitro to chemotherapeutic and targeted agents.

Results

Cancer stem cells were extracted from liver metastases in 6 cases (25%), lung nodules in 2 (8%), lymph node metastases in 3 (12.5%) and pleural/peritoneal/pericardial effusion in 13 (54%). Cancer stem cells were successfully isolated in 15 patients (63%), including 14 with lung cancer (93.3%). A sensitivity assay was successfully performed in 7 patients (30.4%), with a median of 15 drugs/combinations tested (range 5-28) and a median time required for results of 51 days (range 37-95).

Conclusion

The approach used for the STELLA trial allowed isolation of cancer stem cells in a consistent proportion of patients. The low percentage of cases completing the full procedure and the long median time for obtaining results highlights the need for a more efficient procedure.

Trial Registration

ClinalTrials.gov NCT01483001     

Application of a New Genetic Deafness Microarray for Detecting Mutations in the Deaf in China

Objective

The aim of this study was to evaluate the GoldenGate microarray as a diagnostic tool and to elucidate the contribution of the genes on this array to the development of both nonsyndromic and syndromic sensorineural hearing loss in China.

Methods

We developed a microarray to detect 240 mutations underlying syndromic and nonsyndromic sensorineural hearing loss. The microarray was then used for analysis of 382 patients with nonsyndromic sensorineural hearing loss (including 15 patients with enlarged vestibular aqueduct syndrome), 21 patients with Waardenburg syndrome, and 60 unrelated controls. Subsequently, we analyzed the sensitivity, specificity, and reproducibility of this new approach after Sanger sequencing-based verification, and also determined the contribution of the genes on this array to the development of distinct hearing disorders.

Results

The sensitivity and specificity of the microarray chip were 98.73% and 98.34%, respectively. Genetic defects were identified in 61.26% of the patients with nonsyndromic sensorineural hearing loss, and 9 causative genes were identified. The molecular etiology was confirmed in 19.05% and 46.67% of the patients with Waardenburg syndrome and enlarged vestibular aqueduct syndrome, respectively.

Conclusion

Our new mutation-based microarray comprises an accurate and comprehensive genetic tool for the detection of sensorineural hearing loss. This microarray-based detection method could serve as a first-pass screening (before next-generation-sequencing screening) for deafness-causing mutations in China.     

Diagnostic Efficacy of Magnifying Endoscopy with Narrow-Band Imaging for Gastric Neoplasms: A Meta-Analysis

Background

Magnifying endoscopy with narrow-band imaging (ME-NBI) is a novel, image-enhanced endoscopic technique for differentiating gastrointestinal neoplasms and potentially enabling pathological diagnosis.

Objectives

The aim of this analysis was to assess the diagnostic performance of ME-NBI for gastric neoplasms.

Methods

We performed a systematic search of the PubMed, EMbase, Web of Science, and Cochrane Library databases for relevant studies. Meta-DiSc (version 1.4) and STATA (version 11.0) software were used for the data analysis. Random effects models were used to assess diagnostic efficacy. Heterogeneity was tested by the Q statistic and I² statistic. Meta-regression was used to analyze the sources of heterogeneity.

Results

A total of 10 studies, with 2151 lesions, were included. The pooled characteristics of these studies were as follows: sensitivity 0.85 (95% confidence interval [CI]: 0.81–0.89), specificity 0.96 (95% confidence interval [CI]: 0.95–0.97), and area under the curve (AUC) 0.9647. In the subgroup analysis, which compared the diagnostic efficacy of ME-NBI and white light imaging (WLI), the pooled sensitivity and specificity of ME-NBI were 0.87 (95% CI: 0.80–0.92) and 0.93 (95% CI: 0.90–0.95), respectively, and the area under the curve (AUC) was 0.9556. In contrast, the pooled sensitivity and specificity of WLI were 0.61 (95% CI: 0.53–0.69) and 0.65 (95% CI: 0.60–0.69), respectively, and the area under the curve (AUC) was 0.6772.

Conclusions

ME-NBI presents a high diagnostic value for gastric neoplasms and has a high specificity.