Enabling personalized perioperative risk prediction by using a machine-learning model based on preoperative data.

Preoperative risk assessment is essential for shared decision-making and adequate perioperative care. Common scores provide limited predictive quality and lack personalized information. The aim of this study was to create an interpretable machine-learning-based model to assess the patient's individual risk of postoperative mortality based on preoperative data to allow analysis of personal risk factors. After ethical approval, a model for prediction of postoperative in-hospital mortality based on preoperative data of 66,846 patients undergoing elective non-cardiac surgery between June 2014 and March 2020 was created with extreme gradient boosting. Model performance and the most relevant parameters were shown using receiver operating characteristic (ROC-) and precision-recall (PR-) curves and importance plots. Individual risks of index patients were presented in waterfall diagrams. The model included 201 features and showed good predictive abilities with an area under receiver operating characteristic (AUROC) curve of 0.95 and an area under precision-recall curve (AUPRC) of 0.109. The feature with the highest information gain was the preoperative order for red packed cell concentrates followed by age and c-reactive protein. Individual risk factors could be identified on patient level. We created a highly accurate and interpretable machine learning model to preoperatively predict the risk of postoperative in-hospital mortality. The algorithm can be used to identify factors susceptible to preoperative optimization measures and to identify risk factors influencing individual patient risk.

How robust are the STRONGER and STIL-STRONGER studies?

In 2020, the Sugammadex vs Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER) study provided evidence for the first time that use of sugammadex is associated with fewer postoperative pulmonary complications than use of neostigmine. In a recent publication in the British Journal of Anaesthesia, a secondary analysis of the same data, the Association Between Neuromuscular Blockade Reversal Agent Choice and Postoperative Pulmonary Complications (STIL-STRONGER) study, has produced similar evidence of the advantages of sugammadex over neostigmine in high-risk and older patients undergoing prolonged, elective surgery. Here we consider the implications of the detailed statistical analysis used in these two studies and how its limitations could possibly have enhanced the statistical differences between the two drugs with respect to postoperative pulmonary complications.

PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients.

BACKGROUND: PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. MATERIAL AND METHODS: The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. RESULTS: The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; p = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR >2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; p = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; p = 0.014). CONCLUSION: In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

Prognostic and predictive value of PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in locally advanced NSCLC treated with simultaneous radiochemotherapy in the randomized, multicenter, phase III German Intergroup lung Trial (GILT).

OBJECTIVES: Immune checkpoint inhibition after radiochemotherapy (RTCT) has become a new standard of care for locally advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression. However, little is known about the prognostic role of immune response markers in this setting. We analysed PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in tumour biopsies from the multicenter German Intergroup Lung Trial (GILT), which previously randomised patients with stage III NSCLC to RTCT with or without consolidation chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed tumour biopsies from patients treated in the GILT trial. PD-L1 expression was analysed using the Ventana SP263 assay and TiL score (low, intermediate, high) and pattern (excluded, inflamed, desert) were assessed. The primary endpoint of the biomarker analysis was PFS in patients with PD-L1 ≥ 1% vs. PD-L1 < 1% NSCLC. Secondary endpoints explored the prognostic relevance of additional PD-L1 expression levels and TiL score and pattern. RESULTS: Biopsies were available from 92 patients treated with RTCT. Patients with available tumor tissue did not differ significantly from the whole study population. PD-L1 scores from 78 samples were available for analysis. There was no difference in PFS in the PD-L1 < 1% vs. PD-L1 ≥ 1% subgroups. TiL score was available in 66 patients. Patients with high TiL score showed favourable overall survival compared to the low TiL subgroup. This trend was most pronounced in those patients treated with consolidative chemotherapy. CONCLUSION: In this analysis, PD-L1 expression did not correlate with PFS following RTCT. However, patients with TiLs > 10% were found to have longer overall survival, especially for those patients treated with consolidation chemotherapy after the end of RTCT. Further analyses to explore the prognostic and predictive relevance of TiLs in the context of consolidative checkpoint inhibition with durvalumab are required.

Microbiota alteration at different stages in gastric lesion progression: a population-based study in Linqu, China.

In addition to Helicobacter pylori (H.pylori), gastric microbiota may be involved in carcinogenesis process. However, the longitudinal study to assess changes in the gastric microbiota associated with the development of gastric carcinogenesis is still limited. The aim of this study is to explore dynamic microbial alterations in gastric cancer (GC) development based on a 4-year endoscopic follow-up cohort in Linqu County, China. Microbial alterations were investigated by deep sequencing of the microbial 16S ribosomal RNA gene in 179 subjects with various gastric lesions, and validated in paired gastric biopsies prospectively collected before and after lesion progression and in non-progression controls. Significant differences were found in microbial diversity and community structure across various gastric lesions, with 62 candidate differential taxa between at least two lesion groups. Further validations identified Helicobacter, Bacillus, Capnocytophaga and Prevotella to be associated with lesion progression-to-dysplasia (DYS)/GC (all P < 0.05), especially for subjects progressing from intestinal metaplasia (IM) to DYS/GC. The combination of the four genera in a microbial dysbiosis index showed a significant difference after lesion progression-to-DYS/GC compared to controls (P = 0.027). The panel including the four genera identified subjects after progression-to-DYS/GC with an area under the receiver-operating curve (AUC) of 0.941. Predictive significance was found before lesion progression-to-DYS/GC with an AUC = 0.776 and an even better AUC (0.927) for subjects progressing from IM to DYS/GC. Microbiota may play different roles at different stages in gastric carcinogenesis. A panel of bacterial genera associated with gastric lesions may help to assess gastric microbial dysbiosis and show potential predictive values for lesion progression. Our findings provide new clues for the microbial mechanism of H.pylori-associated carcinogenesis.

Fixed or adjustable sling in the treatment of male stress urinary incontinence: results from a large cohort study.

BACKGROUND: Fixed and adjustable male slings for the treatment of male urinary stress incontinence became increasingly popular during the last decade. Although fixed slings are recommended for the treatment of mild to moderate stress urinary incontinence, there is still a lack of evidence regarding the precise indication for an adjustable male sling. Furthermore, there is still no evidence that one type of male sling is superior to another. However, both, adjustable and fixed slings, are commonly utilized in daily clinical practice. This current investigation aims to evaluate the differences between fixed and adjustable male slings regarding indications, complication rates and functional outcome in the treatment of male stress urinary incontinence in current clinical practice. METHODS: A total of 294 patients with a fixed and 176 patients with an adjustable male sling were evaluated in a multicenter single arm cohort trial. Data collection was performed retrospectively according the medical record. Functional outcome was prospectively analyzed by standardized, validated questionnaires. Descriptive statistics was performed to present patient characteristics, complication rates and functional outcome. A chi2-test for categorical and independent t-test for continuous variables was performed to identify heterogeneity between the groups and to correlate preoperative characteristics with the outcome. A P value <0.05 was considered statistically significant. RESULTS: Patients with higher degree of urinary incontinence (P<0.001) and risk factors such as history of pelvic irradiation (P<0.001) or prior surgery for urethral stricture (P=0.032) were more likely to receive an adjustable MS. Complication rates were comparable except for infection (P=0.009, 0 vs. 2.3%) and pain (P=0.001, 1.7% vs. 11.3%) which occurred more frequently in adjustable slings. Functional outcome according validated questionnaires demonstrated no differences between fixed and adjustable male slings. CONCLUSIONS: Adjustable male slings are more frequently utilized in patients with higher degree of incontinence and risk factors compared to fixed slings. No differences could be identified between functional outcome which may imply an advantage for adjustability. However, pain and infection rates were significantly higher in adjustable MS and should be considered in the decision process for sling type.

Effect of Helicobacter pylori on gastrointestinal microbiota: a population-based study in Linqu, a high-risk area of gastric cancer.

OBJECTIVE: Gastrointestinal microbiota may be involved in Helicobacter pylori-associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection. DESIGN: Deep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment, relative to 49 H. pylori negative subjects. RESULTS: In H. pylori positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in H. pylori positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between Helicobacter and Fusobacterium, Neisseria, Prevotella, Veillonella, Rothia were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased Bifidobacterium after successful H. pylori eradication and more upregulated drug-resistant functional orthologs after failed treatment. CONCLUSION: H. pylori infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful H. pylori eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.

A Simulation Study Comparing Different Statistical Approaches for the Identification of Predictive Biomarkers.

Identification of relevant biomarkers that are associated with a treatment effect is one requirement for adequate treatment stratification and consequently to improve health care by administering the best available treatment to an individual patient. Various statistical approaches were proposed that allow assessing the interaction between a continuous covariate and treatment. Nevertheless, categorization of a continuous covariate, e.g., by splitting the data at the observed median value, appears to be very prevalent in practice. In this article, we present a simulation study considering data as observed in a randomized clinical trial with a time-to-event outcome performed to compare properties of such approaches, namely, Cox regression with linear interaction, Multivariable Fractional Polynomials for Interaction (MFPI), Local Partial-Likelihood Bootstrap (LPLB), and the Subpopulation Treatment Effect Pattern Plot (STEPP) method, and of strategies based on categorization of continuous covariates (splitting the covariate at the median, splitting at quartiles, and using an "optimal" split by maximizing a corresponding test statistic). In different scenarios with no interactions, linear interactions or nonlinear interactions, type I error probability and the power for detection of a true covariate-treatment interaction were estimated. The Cox regression approach was more efficient than the other methods for scenarios with monotonous interactions, especially when the number of observed events was small to moderate. When patterns of the biomarker-treatment interaction effect were more complex, MFPI and LPLB performed well compared to the other approaches. Categorization of data generally led to a loss of power, but for very complex patterns, splitting the data into multiple categories might help to explore the nature of the interaction effect. Consequently, we recommend application of statistical methods developed for assessment of interactions between continuous biomarkers and treatment instead of arbitrary or data-driven categorization of continuous covariates.

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study.

BACKGROUND: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. METHODS: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. FINDINGS: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53-2·26; ARRadj -4·4%, 95% CI -5·5 to -3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15-1·49; ARRadj -2·6%, 95% CI -3·9 to -1·4) and the administration of reversal agents (1·23, 1·07-1·41; -1·9%, -3·2 to -0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85-1·25; ARRadj -0·3%, 95% CI -2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82-1·31; -0·4%, -3·5 to 2·2) was associated with better pulmonary outcomes. INTERPRETATION: We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications. FUNDING: European Society of Anaesthesiology.

Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer.

Significant evidence has accumulated that DNA-methylation of the paired-like homeodomain transcription factor 2 (PITX2) gene can serve as a prognostic and predictive biomarker in breast cancer. PITX2 DNA-methylation data have been obtained so far from microarray and polymerase chain reaction (PCR)-based research tests. The availability of an analytically validated in vitro methylation-specific real-time PCR assay format (therascreen PITX2 RGQ PCR assay) intended for the determination of the percent methylation ratio (PMR) in the (PITX2) promoter 2 prompted us to investigate whether the clinical performance of these different assay systems generate comparable clinical outcome data. Mathematically converted microarray data of a previous breast cancer study (n = 204) into PMR values leads to a PITX2 cut-off value at PMR 14.73. Recalculation of the data to experimentally equivalent PMRs with the PCR PITX2 assay leads to a cut-off value at PMR 12 with the highest statistical significance. This cut-off predicts outcome of high-risk breast cancer patients to adjuvant anthracycline-based chemotherapy (n = 204; Hazard Ratio 2.48; p < 0.001) comparable to microarray generated results (n = 204; Hazard ratio 2.32; p < 0.0001). The therascreen PITX2 RGQ PCR assay is an analytically validated test with high reliability and robustness and predicts outcome of high-risk breast cancer patients to anthracycline-based chemotherapy.

Ice water test in multiple sclerosis: A pilot trial.

OBJECTIVES: To investigate the significance of the ice water test in patients with multiple sclerosis and to evaluate a novel ice water test nomogram in a large patient cohort. METHODS: A total of 201 ice water tests of patients with multiple sclerosis were retrospectively evaluated. Incontinence episodes in 24 h and sex were correlated with the ice water test. Furthermore, an ice water test nomogram was developed in order to categorize the detrusor overactivity in severity degrees. Descriptive statistics were carried out for population characteristics. Correlations of categorical variables were calculated by the χ2 -test. The independent t-test was carried out for correlations of continuous variables. Furthermore, the data were evaluated in the novel ice water test nomogram. RESULTS: The patient population consisted of 141 (70.1%) women and 60 (39.9%) men. A clinically positive ice water test (maximum detrusor pressure >15 cmH2 O) was identified in 75 patients (37.3%). Significantly more men presented a clinically positive ice water test (P = 0.006). In 16.5%, the ice water test unmasked an involuntary detrusor contraction, although routine cystometry did not show any detrusor overactivity. The ice water test nomogram could be successfully applied. The incontinence episodes and maximum detrusor pressure correlated positively with a higher categorization in the nomogram. Therapeutic interventions and follow-up controls could be successfully illustrated by the nomogram. CONCLUSIONS: The ice water test is a simple tool for unmasking non-identified detrusor overactivity in neurogenic bladder dysfunction. A severity categorization of the detrusor overactivity can be facilitated by the use of the ice water test nomogram. After further validation, the ice water test could be ultimately used in future as objective assessment for bladder dysfunction.

Association Between Gut Microbiota and Helicobacter pylori-Related Gastric Lesions in a High-Risk Population of Gastric Cancer.

Eradication of Helicobacter pylori has been found to be effective for gastric cancer prevention, but uncertainties remain about the possible adverse consequences such as the potential microbial dysbiosis. In our study, we investigated the association between gut microbiota and H. pylori-related gastric lesions in 47 subjects by deep sequencing of microbial 16S ribosomal RNA (rRNA) gene in fecal samples. The dominant phyla in fecal samples were Bacteroidetes, Firmicutes, and Proteobacteria with average relative abundances of 54.77, 31.37 and 12.91%, respectively. Microbial diversity analysis showed that observed species and Shannon index were increased in subjects with past or current H. pylori infection compared with negative subjects. As for the differential bacteria, the average relative abundance of Bacteroidetes was found to significantly decrease from H. pylori negative (66.16%) to past infection group (33.01%, p = 0.007), as well as from normal (76.49%) to gastritis (56.04%) and metaplasia subjects (46.83%, p = 0.027). For Firmicutes and Proteobacteria, the average relative abundances showed elevated trends in the past H. pylori infection group (47.11, 20.53%) compared to negative group (23.44, 9.05%, p = 0.068 and 0.246, respectively), and similar increased trends were also found from normal (18.23, 5.05%) to gastritis (35.31, 7.23%, p = 0.016 and 0.294, respectively) or metaplasia subjects (32.33, 20.07%, both p < 0.05). These findings suggest that the alterations of fecal microbiota, especially the dominant phyla of Bacteroidetes, Firmicutes and Proteobacteria, may be involved in the process of H. pylori-related gastric lesion progression and provide hints for future evaluation of microbial changes after H. pylori eradication.

The AdVance and AdVanceXP male sling in urinary incontinence: is there a difference?

PURPOSE: To compare the efficacy and perioperative complications of the AdVanceXP with the original AdVance male sling. METHODS: We retrospectively enrolled 109 patients with an AdVance and 185 patients with an AdVanceXP male sling. The baseline characteristics and complication rates were analyzed retrospectively. Functional outcome and quality of life were evaluated prospectively by standardized, validated questionnaires. The Chi2-test for categorical and Mann-Whitney U test for continuous variables were performed to identify heterogeneity between the groups. RESULTS: Regarding operation time, there was no significant difference between the slings (p = 0.146). The complication rates were comparable in both groups except for postoperative urinary retention. This occurred significantly more often in patients with the AdVanceXP (p = 0.042). During follow-up, no differences could be identified regarding ICIQ-SF, PGI or I-QoL or number of pad usage. CONCLUSIONS: The AdVance and AdVanceXP are safe and effective treatment options for male stress urinary incontinence. However, the innovations of the AdVanceXP sling did not demonstrate a superiority over the original AdVance sling regarding functional outcome.

The TiLOOP® Male Sling: Did We Forejudge.

INTRODUCTION: To evaluate the safety and efficacy of the TiLOOP® male sling (pfm medical, Cologne, Germany) used in the treatment for male stress urinary incontinence (SUI). MATERIAL AND METHODS: We retrospectively evaluated a total of 34 patients with a TiLOOP® male sling. Perioperative complication rates were assessed and validated questionnaires were prospectively evaluated to assess quality of life and satisfaction rate. Outcome and complication rates were analysed by using descriptive statistics. Correlation of continence outcome and risk factors was performed with the chi-square test. A p value below 0.05 was considered statistically significant. RESULTS: The majority of patients (70.6%) were diagnosed with mild or moderate male SUI. During surgery, one instance (2.9%) of intraoperative urethral injury was observed. There were no immediate postoperative complications. The mean follow-up time was 44.6 months. An improvement of male SUI was reported by 61.9% of the patients and 38.1% reported no change according the Patient Global Impression of Improvement. The mean perineal pain score was 0.5 according to the international index of pain. CONCLUSIONS: The TiLOOP® is a safe treatment option for male SUI in our cohort with a low complication rate. However, the functional outcome of the TiLOOP® was inferior when compared to the outcome of the AdVance® male sling.

Clinical Validation of PITX2 DNA Methylation to Predict Outcome in High-Risk Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy.

Background: Breast cancer patients at high risk for recurrence are treated with anthracycline-based chemotherapy, but not all patients do equally benefit from such a regimen. To further improve therapy decision-making, biomarkers predicting outcome are of high unmet medical need. Methods: The percent DNA methylation ratio (PMR) of the promoter gene coding for the Paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time polymerase chain reaction (PCR) test. The multicenter study was conducted in routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue from 205 lymph node-positive breast cancer patients treated with adjuvant anthracycline-based chemotherapy. Results: The cut-off for the PITX2 methylation status (PMR = 12) was confirmed in a randomly selected cohort (n = 60) and validated (n = 145) prospectively with disease-free survival (DFS) at the 10-year follow-up. DFS was significantly different between the PMR ≤ 12 versus the PMR > 12 group with a hazard ratio (HR) of 2.74 (p < 0.001) in the validation cohort and also for the patient subgroup treated additionally with endocrine therapy (HR 2.47; p = 0.001). Conclusions: Early-stage lymph node-positive breast cancer patients with low PITX2 methylation do benefit from adjuvant anthracycline-based chemotherapy. Patients with a high PITX2 DNA methylation ratio, approximately 30%, show poor outcome and should thus be considered for alternative chemotherapy regimens.

Validation of a Novel Immunoline Assay for Patient Stratification according to Virulence of the Infecting Helicobacter pylori Strain and Eradication Status.

Helicobacter pylori infection shows a worldwide prevalence of around 50%. However, only a minority of infected individuals develop clinical symptoms or diseases. The presence of H. pylori virulence factors, such as CagA and VacA, has been associated with disease development, but assessment of virulence factor presence requires gastric biopsies. Here, we evaluate the H. pylori recomLine test for risk stratification of infected patients by comparing the test score and immune recognition of type I or type II strains defined by the virulence factors CagA, VacA, GroEL, UreA, HcpC, and gGT with patient's disease status according to histology. Moreover, the immune responses of eradicated individuals from two different populations were analysed. Their immune response frequencies and intensities against all antigens except CagA declined below the detection limit. CagA was particularly long lasting in both independent populations. An isolated CagA band often represents past eradication with a likelihood of 88.7%. In addition, a high recomLine score was significantly associated with high-grade gastritis, atrophy, intestinal metaplasia, and gastric cancer. Thus, the recomLine is a sensitive and specific noninvasive test for detecting serum responses against H. pylori in actively infected and eradicated individuals. Moreover, it allows stratifying patients according to their disease state.

Cut-off optimization for 13C-urea breath test in a community-based trial by mathematic, histology and serology approach.

The performance of diagnostic tests in intervention trials of Helicobacter pylori (H.pylori) eradication is crucial, since even minor inaccuracies can have major impact. To determine the cut-off point for 13C-urea breath test (13C-UBT) and to assess if it can be further optimized by serologic testing, mathematic modeling, histopathology and serologic validation were applied. A finite mixture model (FMM) was developed in 21,857 subjects, and an independent validation by modified Giemsa staining was conducted in 300 selected subjects. H.pylori status was determined using recomLine H.pylori assay in 2,113 subjects with a borderline 13C-UBT results. The delta over baseline-value (DOB) of 3.8 was an optimal cut-off point by a FMM in modelling dataset, which was further validated as the most appropriate cut-off point by Giemsa staining (sensitivity = 94.53%, specificity = 92.93%). In the borderline population, 1,468 subjects were determined as H.pylori positive by recomLine (69.5%). A significant correlation between the number of positive H.pylori serum responses and DOB value was found (rs = 0.217, P < 0.001). A mathematical approach such as FMM might be an alternative measure in optimizing the cut-off point for 13C-UBT in community-based studies, and a second method to determine H.pylori status for subjects with borderline value of 13C-UBT was necessary and recommended.

Risk Factors for Failure of Male Slings and Artificial Urinary Sphincters: Results from a Large Middle European Cohort Study.

INTRODUCTION: We analysed the impact of predefined risk factors: age, diabetes, history of pelvic irradiation, prior surgery for stress urinary incontinence (SUI), prior urethral stricture, additional procedure during SUI surgery, duration of incontinence, ASA-classification and cause for incontinence on failure and complications in male SUI surgery. MATERIALS AND METHODS: We retrospectively identified 506 patients with an artificial urinary sphincter (AUS) and 513 patients with a male sling (MS) in a multicenter cohort study. Complication rates were correlated to the risk factors in univariate analysis. Subsequently, a multivariate logistic regression adjusted to the risk factors was performed. A p value <0.05 was considered statistically significant. RESULTS: A history of pelvic irradiation was an independent risk factor for explantation in AUS (p < 0.001) and MS (p = 0.018). Moreover, prior urethral stricture (p = 0.036) and higher ASA-classification (p = 0.039) were positively correlated with explantation in univariate analysis for AUS. Urethral erosion was correlated with prior urethral stricture (p < 0.001) and a history of pelvic irradiation (p < 0.001) in AUS. Furthermore, infection was correlated with additional procedures during SUI surgery in univariate analysis (p = 0.037) in MS. CONCLUSIONS: We first identified the correlation of higher ASA-classification and explantation in AUS. Nevertheless, only a few novel risk factors had a significant influence on the failure of MS or AUS.

Quality of life in women of non-reproductive age with transvaginal mesh repair for pelvic organ prolapse: A cohort study.

BACKGROUND: Transvaginal mesh repair has been discredited due to high complications rates in the past years. Therefore, we evaluated the quality of life (QoL) and complication rates after transvaginal mesh (TVM) repair for pelvic organ prolapse (POP). METHODS: A total of 148 women who underwent TVM repair for symptomatic POP were retrospectively enrolled. Complication rates and functional outcomes were retrospectively assessed and validated, standardised questionnaires were used prospectively for evaluation of QoL. Univariate analysis by the chi(2)-test as well as a multivariate Cox regression analysis was conducted to predict mesh exposure using various variables as predictors. RESULTS: Intraoperative complications with bowel or bladder injury appeared in 3.4%. Mesh exposure occurred in 2.7% whereas surgical revision was necessary only in 1.4%. No predictor for mesh exposure could be identified. Postoperative complications according to Clavien-Dindo classification ≥ III occurred in only 2.8%. An improvement of POP-symptoms was reported by 84.6% according the "patients' global impression of improvement" (PGI-I) and 88.2% women would repeat the surgery. The results of the "prolapse-quality of life"-questionnaire were comparable to asymptomatic women. Only 33% reported vaginal pain with a mean vaginal pain score of 0.6 according the international index of pain. Of sexually active women, 29% reported sexual impairments and mean score of sexual impairment was 1.52. CONCLUSION: Low complication rates and a quality of life comparable to asymptomatic women following TVM repair could be achieved in our cohort. However, a high number of sexual impairments was identified although the impact of impairment was marginal.

A large randomised controlled intervention trial to prevent gastric cancer by eradication of Helicobacter pylori in Linqu County, China: baseline results and factors affecting the eradication.

OBJECTIVE: To clarify the full range of benefits and adverse consequences of Helicobacter pylori eradication as a strategy for gastric cancer prevention, the community-based intervention trial was launched in Linqu County, China. DESIGN: A total of 184,786 residents aged 25-54 years were enrolled in this trial and received (13)C-urea breath test. H. pylori positive participants were assigned into two groups, either receiving a 10-day quadruple anti-H. pylori treatment or lookalike placebos together with a single dosage of omeprazole and bismuth. RESULTS: The prevalence of H. pylori in trial participants was 57.6%. A total of 94,101 subjects completed the treatment. The overall H. pylori eradication rate was 72.9% in the active group. Gender, body mass index, history of stomach disease, baseline delta over baseline-value of (13)C-urea breath test, missed medication doses, smoking and drinking were independent predictors of eradication failure. The missed doses and high baseline delta over baseline-value were important contributors in men and women (all Ptrend<0.001). However, a dose-response relationship between failure rate and smoking or drinking index was found in men (all Ptrend<0.001), while high body mass index (Ptrend<0.001) and history of stomach disease were significant predictors in women. The treatment failure rate increased up to 48.8% (OR 2.87, 95% CI 2.24 to 3.68) in men and 39.4% (OR 2.67, 95% CI 1.61 to 4.42) in women with multiple factors combined. CONCLUSIONS: This large community-based intervention trial to eradicate H. pylori is feasible and acceptable. The findings of this trial lead to a distinct evaluation of factors influencing eradication that should be generally considered for future eradication therapies. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-10000979 in accordance with WHO ICTRP requirements.