Converting a Microarray Signature into a Diagnostic Test: A Trial of Custom 74 Gene Array for Clarification and Prediction the Prognosis of Gastric Cancer

Background

Gastric cancer (GC) is associated with high mortality rates and an unfavorable prognosis at advanced stages. In addition, there are no effective methods for diagnosing gastric cancer at an early stage or for predicting the outcome for the purpose of selecting patient-specific treatment options. Therefore, it is important to investigate new methods for GC diagnosis.

Methodology/Principal Findings

To facilitate its use in a diagnostic setting, a group of 74 genes with diagnostic and prognostic information was translated into a customized microarray containing a reduced set of 1,042 probes suitable for high throughput processing. In this report, we demonstrate for the first time that the custom mini-array can be used as a reliable diagnostic tool in gastric cancer. With an AUC value of 0.565 (95% CI 0.305-0.825) indicating a perfect test, the sensitivity and specificity of diagnosis from the ROC curve were calculated to be 70% and 80%, respectively.

Conclusions/Significance

The data clearly demonstrate the reproducibility and robustness of the small custom-made microarray. The array is an excellent tool for classifying and predicting the outcome of disease in gastric cancer patients.     

Reliability of School Surveys in Estimating Geographic Variation in Malaria Transmission in the Western Kenyan Highlands

Background

School surveys provide an operational approach to assess malaria transmission through parasite prevalence. There is limited evidence on the comparability of prevalence estimates obtained from school and community surveys carried out at the same locality.

Methods

Concurrent school and community cross-sectional surveys were conducted in 46 school/community clusters in the western Kenyan highlands and households of school children were geolocated. Malaria was assessed by rapid diagnostic test (RDT) and combined seroprevalence of antibodies to bloodstage Plasmodium falciparum antigens.

Results

RDT prevalence in school and community populations was 25.7% (95% CI: 24.4-26.8) and 15.5% (95% CI: 14.4-16.7), respectively. Seroprevalence in the school and community populations was 51.9% (95% CI: 50.5-53.3) and 51.5% (95% CI: 49.5-52.9), respectively. RDT prevalence in schools could differentiate between low (<7%, 95% CI: 0-19%) and high (>39%, 95% CI: 25-49%) transmission areas in the community and, after a simple adjustment, were concordant with the community estimates.

Conclusions

Estimates of malaria prevalence from school surveys were consistently higher than those from community surveys and were strongly correlated. School-based estimates can be used as a reliable indicator of malaria transmission intensity in the wider community and may provide a basis for identifying priority areas for malaria control.     

Meta-Analysis of Anti-Muscarinic Receptor Type 3 Antibodies for the Diagnosis of Sj?gren Syndrome

Purpose

To conduct a meta-analysis to evaluate the diagnostic value of anti-muscarinic receptor type 3 (M3R) antibodies in Sjögren syndrome (SS).

Methods

Two databases, PUBMED and the Cochrane Library, were systematically searched. Approximately 2,000 participants from several studies were included in this research. STATA 11.2 software and Meta-DiSc 1.4 was used to conduct the meta-analysis.

Results

Eleven studies were included in the meta-analysis. The pooled DOR was 13.00 (95% CI, 6.00–26.00). The sensitivity was 0.43 (95% CI, 0.28–0.58) and the specificity was 0.95 (95%CI, 0.91–0.97). The LR+ and LR- were 7.90 (95% CI, 4.70–13.40), 0.61 (95% CI, 0.46–0.79), respectively. The AUC was 0.89 (95% CI, 0.86–0.92).

Conclusion

The anti-M3R antibody had high specificity but relatively low sensitivity for the diagnosis of SS.     

Prenatal Glucocorticoid Treatment and Later Mental Health in Children and Adolescents

Background

Animal studies demonstrate a clear link between prenatal exposure to glucocorticoids (GC) and altered offspring brain development. We aim to examine whether prenatal GC exposure programs long-term mental health in humans.

Methods

Using propensity-score-matching, children prenatally exposed to synthetic glucocorticoids (sGC), n=37, and controls, n=185, were balanced on important confounders related to sGC treatment - gestational age and pre-pregnancy BMI. We also used mixed-effects modeling to analyse the entire cohort – matching each sGC case, n=37, to all possible controls, n=6079, on gestational age and sex. We obtained data from the Northern Finland Birth Cohort 1986 at four waves – pregnancy, birth, 8 and 16 years. Data on pregnancy and birth outcomes came from medical records. Mental health was assessed at 8 years by teachers with the Rutter B2 scale, and at 16 years by parents with the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale and adolescents by the Youth Self-Report (YSR) scale.

Results

Prenatal sGC treatment was consistently associated with adverse mental health in childhood and adolescence, as shown by both the propensity-score method and mixed-effects model. Using the propensity-score-matched subsample, linear multiple regression showed prenatal sGC was significantly linked with general psychiatric disturbance (B=8.34 [95% CI: .23-16.45]) and inattention (B= .97 [95% CI: .16-1.80]) at 8 years after control for relevant confounders. Similar findings were obtained at 16 years, but did not reach statistical significance. Mediation by birthweight/placental weight was not detected.

Conclusions

This study is the first to prospectively investigate the long-term associations between prenatal exposure to sGC treatment and mental health in children and adolescents. We report an association between prenatal exposure to sGC and child mental health, supportive of the idea that sGC has a programming effect on the fetal brain.     

Factors Associated with the Occurrence of Cardiac Arrest after Emergency Tracheal Intubation in the Emergency Department

Objectives

Emergency tracheal intubation has achieved high success and low complication rates in the emergency department (ED). The objective of this study was to evaluate the incidence of post-intubation CA and determine the clinical factors associated with this complication.

Methods

A matched case-control study with a case to control ratio of 1∶3 was conducted at an urban tertiary care center between January 2007 and December 2011. Critically ill adult patients requiring emergency airway management in the ED were included. The primary endpoint was post-intubation CA, defined as CA within 10 minutes after tracheal intubation. Clinical variables were compared between patients with post-intubation CA and patients without CA who were individually matched based on age, sex, and pre-existing comorbidities.

Results

Of 2,403 patients who underwent emergency tracheal intubation, 41 patients (1.7%) had a post-intubation CA within 10 minutes of the procedure. The most common initial rhythm was pulseless electrical activity (78.1%). Patients experiencing CA had higher in-hospital mortality than patients without CA (61.0% vs. 30.1%; p<0.001). Systolic hypotension prior to intubation, defined as a systolic blood pressure ≤90 mmHg, was independently associated with post-intubation CA (OR, 3.67 [95% CI, 1.58–8.55], p = 0.01).

Conclusion

Early post-intubation CA occurred with an approximate 2% frequency in the ED. Systolic hypotension before intubation is associated with this complication, which has potentially significant implications for clinicians at the time of intubation.     

Assessment of Dynamic Cerebral Autoregulation in Patients with Basilar Artery Stenosis

Background and Aims

Previous studies have shown impaired cerebral autoregulation (CA) in carotid and middle cerebral artery (MCA) stenosis/occlusion. Little is known about CA in patients with basilar artery (BA) stenosis. We therefore investigated dynamic CA patterns in BA stenosis using transfer function analysis (TFA).

Methods

We measured spontaneous oscillations of blood flow velocity (CBFV) in the right posterior cerebral artery (PCA), and left MCA and mean arterial pressure (ABP) continuously in 25 patients with BA stenosis (moderate n=16 with 50-69% occlusion and severe n=9 with ≥70% occlusion) and 22 healthy volunteers in supine position during 6 circles per minute deep breath. Analysis was based on the ‘black-box’ model of transfer function deriving phase and gain in both PCA and MCA.

Results

Though changes of phase shift and gain between the patients and healthy controls were observed in MCA, the differences are however not significant. Phase shift in PCA was significantly decreased in severe stenosis when comparing with healthy controls and moderate stenosis (4.2±34.2° VS 41.1±40.4°, 4.2±34.2° VS 34.2±27.2°, both p<0.05), whilst the gain in PCA is increased for moderate BA stenosis and decreased for severe BA stenosis. Furthermore, we found that phase shift were almost abolished in patients with ischemic stroke who developed unfavorable clinical outcome (mRs>2) on the 90 days after stroke onset.

Conclusion

Dynamic CA in PCA reduces in patients with severe BA stenosis and those with ischemic stroke who present poor outcome in 90 days after stroke onset. Phase shift might be a sensitive index prompting impaired CA in posterior circulation.     

Angiopoietin-2 and Biliary Diseases: Elevated Serum,but Not Bile Levels Are Associated with Cholangiocarcinoma

Background

The diagnosis of cholangiocarcinoma (CC) is challenging especially in patients with primary sclerosing cholangitis (PSC) and often delayed due to the lack of reliable markers. Angiopoietin-2 (Angpt-2) has been employed as a biomarker of angiogenesis and might be involved in tumor neoangiogenesis.

Aim

To evaluate the diagnostic potential of Angpt-2 as a biomarker to detect patients with CC.

Methods

Bile and serum Angpt-2 levels were measured in patients with CC (n = 45), PSC (n = 74), CC complicating PSC (CC/PSC) (n = 11) and patients with bile duct stones (n = 37) in a cross sectional study. Diagnostic accuracy of Angpt-2 was compared to carbohydrate antigen 19-9 (CA19-9). Fluorescent immunohistochemistry from human CC liver tissue samples was performed to localize the origin of Angpt-2.

Results

Serum Angpt-2 concentration was significantly elevated in patients with CC compared to control patients (p<0.05). Diagnostic accuracy of Angpt-2 as determined by receiver operating characteristic (ROC) analysis resulted in a higher area under the curve (AUC) value compared to CA19-9 (AUC: 0.85 versus 0.77; 95% confidence interval (CI): 0.74–0.93 versus 0.65–0.87, respectively). Angpt-2 was also detectable in bile, but was not associated with the presence of CC. Immunohistochemistry revealed a strong induction of Angpt-2 expression in the tumor vasculature.

Conclusions

Circulating Angpt-2 in serum might be a promising protein candidate locally derived from the tumor vasculature in patients with CC. Measurement of Angpt-2 in serum may be useful for diagnosis and further clinical management of patients with CC.     

Fine-Needle Aspirates CYFRA 21-1 is a Useful Tumor Marker for Detecting Axillary Lymph Node Metastasis in Breast Cancer Patients

Introduction

To assess whether the value of CYFRA21-1 in the aspirates of ultrasonography-guided fine-needle aspiration biopsy (US-FNAB) can contribute to improving the performances of US-FNAB in the diagnosis of axillary lymph node (LN) metastasis in breast cancer patients.

Methods

US-FNAB was performed in 156 axillary LNs in 152 breast cancer patients (mean age: 51.4 years, range: 17–92 years). Concentrations of CYFRA21-1 were measured from washouts of the syringe used during US-FNAB. Tumor marker concentrations, US-FNAB, intraoperative sentinel node biopsy (SNB), and surgical pathology results were reviewed and analyzed. For comparison, the values of CEA and CA15-3 were also measured from washouts.

Results

Among the 156 LNs, 75 (48.1%) were benign, and 81 (51.9%) were metastases. Mean concentrations of CYFRA21-1 were significantly higher in metastasis compared to benign LNs (P<0.001). US-FNAB combined to CYFRA21-1 showed significantly higher sensitivity, NPV, and accuracy compared to US-FNAB alone (all values P<0.05). All diagnostic indices of US-FNAB combined to CYFRA21-1 were significantly higher compared to US-FNAB combined with CEA or CA15-3 (all P<0.001). Of the 28 metastatic LNs which showed metastasis on SNB, CYFRA21-1 showed higher positive rate of 75.0% (CEA or CA15-3∶60.7%, P = 0.076).

Conclusion

Measuring CYFRA 21-1 concentrations from US-FNAB aspirates improves sensitivity, NPV, and accuracy of US-FNAB alone, and may contribute to reducing up to 75.0% of unnecessary intraoperative SNB. Compared to CEA or CA15-3, CYFRA21-1 shows significantly higher performances when combined to US-FNAB in the preoperative diagnosis of LN metastasis in breast cancer patients.     

Dietary Methionine Intake and Risk of Incident Colorectal Cancer: A Meta-Analysis of 8 Prospective Studies Involving 431,029 Participants

Background

Methionine is one of the key components of one carbon metabolism. Experimental studies indicate that methionine may reduce inflammation-induced colon cancer. However, epidemiologic findings as to whether dietary methionine intake influences colorectal cancer incidence in humans are inconsistent.

Objective

To investigate the relationship between dietary methionine intake and risk of colorectal cancer by performing a meta-analysis of prospective studies.

Methods

Eligible studies were identified by searching PubMed and Embase and by reviewing the bibliographies of the retrieved publications. The summary risk estimates were computed using both a random- effects and a fixed-effects model.

Results

Eight eligible prospective cohort studies involving 431,029 participants and 6,331 colorectal cancer cases were identified. According to the random-effects model, the summary relative risks (RRs) for the highest compared with the lowest intake of methionine were 0.89 (95% confidence interval [CI] = 0.77-1.03) for colorectal cancer, 0.77 (95% CI = 0.64 - 0.92) for colon cancer, and 0.88 (95% CI = 0.55-1.42) for rectal cancer. In the stratified analysis, a significant inverse association between dietary methionine intake and risk of colorectal cancer was observed in studies with longer follow-up time (RR=0.81, 95% CI= 0.70- 0.95), in Western studies (RR= 0.83, 95% CI = 0.73 - 0.95) and in men (RR = 0.75, 95% CI= 0.57-0.99). We found no indication of publication bias.

Conclusion

This meta-analysis indicates that dietary methionine intake may be associated with decreased risk of colorectal cancer, especially colon cancer. More prospective studies with long follow-up time are needed to confirm these findings.     

“I Can't Find Anything Wrong: It Must Be a Pulmonary Embolism”: Diagnosing Suspected Pulmonary Embolism in Primary Care,a Qualitative Study

Background

Before using any prediction rule oriented towards pulmonary embolism (PE), family physicians (FPs) should have some suspicion of this diagnosis. The diagnostic reasoning process leading to the suspicion of PE is not well described in primary care.

Objective

to explore the diagnostic reasoning of FPs when pulmonary embolism is suspected.

Method

Semi-structured qualitative interviews with 28 FPs. The regional hospital supplied data of all their cases of pulmonary embolism from June to November 2011. The patient''s FP was identified where he/she had been the physician who had sent the patient to the emergency unit. The first consecutive 14 FPs who agreed to participate made up the first group. A second group was chosen using a purposeful sampling method. The topic guide focused on the circumstances leading to the suspicion of PE. A thematic analysis was performed, by three researchers, using a grounded theory coding paradigm.

Results

In the FPs'' experience, the suspicion of pulmonary embolism arose out of four considerations: the absence of indicative clinical signs for diagnoses other than PE, a sudden change in the condition of the patient, a gut feeling that something was seriously wrong and an earlier failure to diagnose PE. The FPs interviewed did not use rules in their diagnostic process.

Conclusion

This study illustrated the diagnostic role of gut feelings in the specific context of suspected pulmonary embolism in primary care. The FPs used the sense of alarm as a tool to prevent the diagnostic error of missing a PE. The diagnostic accuracy of gut feelings has yet to be evaluated.     

The Prognostic Value of Phosphorylated AKT Expression in Non-Small Cell Lung Cancer: A Meta-Analysis

Objectives

Phosphorylated AKT (p-AKT), constitutive activation of AKT, is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). However, the available results of p-AKT expression in NSCLC are heterogeneous. Therefore, a meta-analysis of published researches investigating the prognostic relevance of p-AKT expression in patients with NSCLC was performed.

Materials and Methods

A literature search via PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases was conducted. Data from eligible studies were extracted and included into meta-analysis using a random effects model.

Results

A total of 1049 patients from nine studies were included in the meta-analysis. Nine studies investigated the relationship between p-AKT expression and overall survival using univariate analysis, and five of these undertook multivariate analysis. The pooled hazard ratio (HR) for overall survival was 1.49 (95% confidence interval (CI): 1.01-2.20) by univariate analysis and 1.02 (95% CI: 0.54-1.95) by multivariate analysis.

Conclusion

Our study shows that positive expression of p-AKT is associated with poor prognosis in patients with NSCLC. However, adequately designed prospective studies need to perform.     

Higher Carbohydrate Antigen 125 Levels Are Associated with Increased Risk of Coronary Heart Disease in Elderly Chinese: A Population-Based Case-Control Study

Background

High carbohydrate antigen 125 (CA-125) level was reported to be associated with some cardiac dysfunctions, such as chronic heart failure, but the relationship between CA-125 level and coronary heart disease (CHD) risk remains unclear. The aim of this study was to explore the potential association in a Chinese older population.

Methods

In a population-based case-control study conducted in a Chinese older population, serum CA-125 levels were measured in 1177 diagnosed CHD patients and 3531 age and sex matched control subjects without CHD.

Results

Serum CA-125 level was significantly higher in CHD patients than controls (P < 0.001) with adjustment for age, gender, smoking, drinking, BMI, physical activity, hypertension, dyslipidemia, diabetes mellitus, medication history and family history of CHD and myocardial infarction. CHD risk was doubled (OR: 2.10, 95%CI: 1.69-2.60) among subjects in the highest quartile compared to those in the lowest quartile of CA-125 level (P _trend < 0.001). Furthermore, CA-125 levels were associated with CHD risks in subjects with age over 60 years (OR: 2.19, 95%CI: 1.75-2.73), current smokers (OR: 2.29, 95%CI: 1.50-3.49), current drinkers (OR: 2.35, 95%CI: 1.57-3.53) and subjects with hypertension (OR: 2.04, 95%CI: 1.71-2.43).

Conclusions

Elevated serum CA-125 level might be associated with increased risk of coronary heart disease in the Chinese older population. Further investigations are needed to identify the possible biological role of CA-125 in CHD development in the future.     

Diagnosing Fatty Liver Disease: A Comparative Evaluation of Metabolic Markers,Phenotypes, Genotypes and Established Biomarkers

Background

To date, liver biopsy is the only means of reliable diagnosis for fatty liver disease (FLD). Owing to the inevitable biopsy-associated health risks, however, the development of valid noninvasive diagnostic tools for FLD is well warranted.

Aim

We evaluated a particular metabolic profile with regard to its ability to diagnose FLD and compared its performance to that of established phenotypes, conventional biomarkers and disease-associated genotypes.

Methods

The study population comprised 115 patients with ultrasound-diagnosed FLD and 115 sex- and age-matched controls for whom the serum concentration was measured of 138 different metabolites, including acylcarnitines, amino acids, biogenic amines, hexose, phosphatidylcholines (PCs), lyso-PCs and sphingomyelins. Established phenotypes, biomarkers, disease-associated genotypes and metabolite data were included in diagnostic models for FLD using logistic regression and partial least-squares discriminant analysis. The discriminative power of the ensuing models was compared with respect to area under curve (AUC), integrated discrimination improvement (IDI) and by way of cross-validation (CV).

Results

Use of metabolic markers for predicting FLD showed the best performance among all considered types of markers, yielding an AUC of 0.8993. Additional information on phenotypes, conventional biomarkers or genotypes did not significantly improve this performance. Phospholipids and branched-chain amino acids were most informative for predicting FLD.

Conclusion

We show that the inclusion of metabolite data may substantially increase the power to diagnose FLD over that of models based solely upon phenotypes and conventional biomarkers.     

CSF N-Glycan Profiles to Investigate Biomarkers in Brain Developmental Disorders: Application to Leukodystrophies Related to eIF2B Mutations

Background

Primary or secondary abnormalities of glycosylation have been reported in various brain diseases. Decreased asialotransferrin to sialotransferrin ratio in cerebrospinal fluid (CSF) is a diagnostic marker of leukodystrophies related to mutations of genes encoding translation initiation factor, EIF2B. We investigated the CSF glycome of eIF2B-mutated patients and age-matched normal individuals in order to further characterize the glycosylation defect for possible use as a biomarker.

Methodology/Principal Findings

We conducted a differential N-glycan analysis using MALDI-TOF/MS of permethylated N-glycans in CSF and plasma of controls and eIF2B-mutated patients. We found in control CSF that tri-antennary/bisecting and high mannose structures were highly represented in samples obtained between 1 to 5 years of age, whereas fucosylated, sialylated structures were predominant at later age. In CSF, but not in plasma, of eIF2B-mutated patient samples, we found increased relative intensity of bi-antennary structures and decreased tri-antennary/bisecting structures in N-glycan profiles. Four of these structures appeared to be biomarker candidates of glycomic profiles of eIF2B-related disorders.

Conclusion

Our results suggest a dynamic development of normal CSF N-glycan profiles from high mannose type structures to complex sialylated structures that could be correlated with postnatal brain maturation. CSF N-glycome analysis shows relevant quantitative changes associated with eIF2B related disorders. This approach could be applied to other neurological disorders involving developmental gliogenesis/synaptogenesis abnormalities.     

National Trends in Main Causes of Hospitalization: A Multi-Cohort Register Study of the Finnish Working-Age Population, 1976–2010

Background

The health transition theory argues that societal changes produce proportional changes in causes of disability and death. The aim of this study was to identify long-term changes in main causes of hospitalization in working-age population within a nation that has experienced considerable societal change.

Methodology

National trends in all-cause hospitalization and hospitalizations for the five main diagnostic categories were investigated in the data obtained from the Finnish Hospital Discharge Register. The seven-cohort sample covered the period from 1976 to 2010 and consisted of 3,769,356 randomly selected Finnish residents, each cohort representing 25% sample of population aged 18 to 64 years.

Principal Findings

Over the period of 35 years, the risk of hospitalization for cardiovascular diseases and respiratory diseases decreased. Hospitalization for musculoskeletal diseases increased whereas mental and behavioral hospitalizations slightly decreased. The risk of cancer hospitalization decreased marginally in men, whereas in women an upward trend was observed.

Conclusions/Significance

A considerable health transition related to hospitalizations and a shift in the utilization of health care services of working-age men and women took place in Finland between 1976 and 2010.     

Identification of Locally Advanced Rectal Cancer with Low Risk of Local Recurrence

Background

The routine application of neoadjuvant chemoradiotherapy for T3N0 rectal cancer remains controversial. The aim of this study was to use clinical, Magnetic resonance imaging, and pathological parameters to identify a subgroup of patients with low risk of local recurrence who might be precluded from neoadjuvant chemoradiotherapy.

Methods

We retrospectively reviewed a prospectively maintained database of consecutive rectal cancer patients who underwent curative resection. 166 pathologic confirmed T3N0 rectal cancer patients with tumor located 5–12cm above the anal verge and preoperative circumferential resection margin>1mm were included in analysis. The primary outcomes measured were3- and 5-year local recurrence rates.

Results

Local recurrence was demonstrated during follow-up in 5 patients; the actuarial overall 3- and 5-year local recurrence rates were 2.5% and 3.4%, respectively. Inadequate sampling of lymph nodes (≤12) was associated with higher local recurrence (P = 0.03) in this group of patients.

Conclusion

For upper and middle T3N0 rectal cancer with preoperative circumferential resection margin>1mm, local recurrence rate after total mesorectal excision is low and surgery alone may be enough for this group of patients.     

A novel multiplexed immunoassay identifies CEA,IL-8 and prolactin as prospective markers for Dukes’ stages A-D colorectal cancers

Background

Current methods widely deployed for colorectal cancers (CRC) screening lack the necessary sensitivity and specificity required for population-based early disease detection. Cancer-specific protein biomarkers are thought to be produced either by the tumor itself or other tissues in response to the presence of cancers or associated conditions. Equally, known examples of cancer protein biomarkers (e.g., PSA, CA125, CA19-9, CEA, AFP) are frequently found in plasma at very low concentration (pg/mL-ng/mL). New sensitive and specific assays are therefore urgently required to detect the disease at an early stage when prognosis is good following surgical resection. This study was designed to meet the longstanding unmet clinical need for earlier CRC detection by measuring plasma candidate biomarkers of cancer onset and progression in a clinical stage-specific manner. EDTA plasma samples (1 μL) obtained from 75 patients with Dukes’ staged CRC or unaffected controls (age and sex matched with stringent inclusion/exclusion criteria) were assayed for expression of 92 human proteins employing the Proseek® Multiplex Oncology I proximity extension assay. An identical set of plasma samples were analyzed utilizing the Bio-Plex Pro™ human cytokine 27-plex immunoassay.

Results

Similar quantitative expression patterns for 13 plasma antigens common to both platforms endorsed the potential efficacy of Proseek as an immune-based multiplex assay for proteomic biomarker research. Proseek found that expression of Carcinoembryonic Antigen (CEA), IL-8 and prolactin are significantly correlated with CRC stage.

Conclusions

CEA, IL-8 and prolactin expression were found to identify between control (unaffected), non-malignant (Dukes’ A + B) and malignant (Dukes’ C + D) stages.

Electronic supplementary material

The online version of this article (doi:10.1186/s12014-015-9081-x) contains supplementary material, which is available to authorized users.     

Robotic versus Open Gastrectomy for Gastric Cancer: A Meta-Analysis

Aim

To evaluate the safety and efficacy of robotic gastrectomy versus open gastrectomy for gastric cancer.

Methods

A comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Knowledge was performed. Systematic review was carried out to identify studies comparing robotic gastrectomy and open gastrectomy in gastric cancer. Intraoperative and postoperative outcomes were also analyzed to evaluate the safety and efficacy of the surgery. A fixed effects model or a random effects model was utilized according to the heterogeneity.

Results

Four studies involving 5780 patients with 520 (9.00%) cases of robotic gastrectomy and 5260 (91.00%) cases of open gastrectomy were included in this meta-analysis. Compared to open gastrectomy, robotic gastrectomy has a significantly longer operation time (weighted mean differences (WMD) =92.37, 95% confidence interval (CI): 55.63 to 129.12, P<0.00001), lower blood loss (WMD: -126.08, 95% CI: -189.02 to -63.13, P<0.0001), and shorter hospital stay (WMD = -2.87; 95% CI: -4.17 to -1.56; P<0.0001). No statistical difference was noted based on the rate of overall postoperative complication, wound infection, bleeding, number of harvested lymph nodes, anastomotic leakage and postoperative mortality rate.

Conclusions

The results of this meta-analysis suggest that robotic gastrectomy is a better alternative technique to open gastrectomy for gastric cancer. However, more prospective, well-designed, multicenter, randomized controlled trials are necessary to further evaluate the safety and efficacy as well as the long-term outcome.     

Systematic Review of the Performance of Rapid Rifampicin Resistance Testing for Drug-Resistant Tuberculosis

Introduction

Rapid tests for rifampicin resistance may be useful for identifying isolates at high risk of drug resistance, including multidrug-resistant TB (MDR-TB). However, choice of diagnostic test and prevalence of rifampicin resistance may both impact a diagnostic strategy for identifying drug resistant-TB. We performed a systematic review to evaluate the performance of WHO-endorsed rapid tests for rifampicin resistance detection.

Methods

We searched MEDLINE, Embase and the Cochrane Library through January 1, 2012. For each rapid test, we determined pooled sensitivity and specificity estimates using a hierarchical random effects model. Predictive values of the tests were determined at different prevalence rates of rifampicin resistance and MDR-TB.

Results

We identified 60 publications involving six different tests (INNO-LiPA Rif. TB assay, Genotype MTBDR assay, Genotype MTBDRplus assay, Colorimetric Redox Indicator (CRI) assay, Nitrate Reductase Assay (NRA) and MODS tests): for all tests, negative predictive values were high when rifampicin resistance prevalence was ≤ 30%. However, positive predictive values were considerably reduced for the INNO-LiPA Rif. TB assay, the MTBDRplus assay and MODS when rifampicin resistance prevalence was < 5%.

Limitations

In many studies, it was unclear whether patient selection or index test performance could have introduced bias. In addition, we were unable to evaluate critical concentration thresholds for the colorimetric tests.

Discussion

Rapid tests for rifampicin resistance alone cannot accurately predict rifampicin resistance or MDR-TB in areas with a low prevalence of rifampicin resistance. However, in areas with a high prevalence of rifampicin resistance and MDR-TB, these tests may be a valuable component of an MDR-TB management strategy.     

Prevalence of Diabetes in the Republic of Ireland: Results from the National Health Survey (SLAN) 2007

Background

Current estimates of diabetes prevalence in the Republic of Ireland (RoI) are based on UK epidemiological studies. This study uses Irish data to describe the prevalence of doctor-diagnosed diabetes amongst all adults aged 18+ years and undiagnosed diabetes amongst those aged 45+ years.

Methods

The survey of lifestyle attitudes and nutrition (SLAN) 2007 is based on a nationally representative sample of Irish adults aged 18+ years (n = 10,364). Self-reported doctor-diagnosed diabetes was recorded for respondents in the full sample. Diabetes medication use, measured height and weight, and non-fasting blood samples were variously recorded in sub-samples of younger (n = 967) and older (n = 1,207) respondents.

Results

The prevalence of doctor-diagnosed diabetes amongst adults aged 18+ years was 3.5% (95% CI 3.1% - 3.9%). After adjustment for other explanatory variables; the risk of self-reported doctor-diagnosed diabetes was significantly related to age (p < 0.0001), employment status (p = 0.0003) and obesity (p = 0.0003). Amongst adults aged 45+ years, the prevalence of doctor-diagnosed diabetes was 8.9% (95% CI 7.3% -10.5%) and undiagnosed diabetes was 2.8% (95% CI 1.4% - 4.1%). This represented 31.2% of diabetes cases in this age group.

Conclusion

Notwithstanding methodological differences, these prevalence estimates are consistent with those in the UK and France. However, the percentage of undiagnosed cases amongst adults aged 45+ years appears to be higher in the RoI. Increased efforts to improve early detection and population level interventions to address adverse diet and lifestyle factors are urgently needed.