Approaches for the treatment of perforated peptic ulcers: a network meta-analysis of randomised controlled trials - study protocol.

INTRODUCTION: Perforated peptic ulcers are a life-threatening complication associated with high morbidity and mortality. Several treatment approaches are available. The aim of this network meta-analysis (NMA) is to compare surgical and alternative approaches for the treatment of perforated peptic ulcers regarding mortality and other patient-relevant outcomes. METHODS AND ANALYSIS: A systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, ClinicalTrials.gov trial registry and ICTRP will be conducted with predefined search terms.To address the question of the most effective treatment approach, an NMA will be performed for each of the outcomes mentioned above. A closed network of interventions is expected. The standardised mean difference with its 95% CI will be used as the effect measure for the continuous outcomes, and the ORs with 95% CI will be calculated for the binary outcomes. ETHICS AND DISSEMINATION: In accordance with the nature of the data used in this meta-analysis, which involves aggregate information from previously published studies ethical approval is deemed unnecessary. Results will be disseminated directly to decision-makers (eg, surgeons, gastroenterologists) through publication in peer-reviewed journals and presentation at conferences. PROSPERO REGISTRATION NUMBER: CRD42023482932.

Effects of Physical Activity Interventions on Strength, Balance and Falls in Middle-Aged Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Weak lower body strength and balance impairments are fundamental risk factors for mobility impairments and falls that can be improved by physical activity (PA). Previous meta-analyses have focused on these risk factors in adults aged ≥ 65 years. Yet, the potential of PA for improving these risk factors in middle-aged populations has not been systematically investigated. This systematic review and meta-analysis aim to examine the effect of general and structured PA on lower limb strength, postural balance and falls in middle-aged adults. METHODS: A computerized systematic literature search was conducted in the electronic databases MEDLINE, CINAHL, Web of Science and Cochrane Library. PA intervention types were classified according to the ProFaNE taxonomy. Randomized controlled trials exploring the effects of PA on strength (e.g., leg press one-repetition-maximum), balance (e.g., single limb stance) and falls (e.g., fall rates) in adults aged 40-60 years were systematically searched and included in a network analysis. Moderator analyses were performed for specific subgroups (age, sex, low PA). The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database (PEDro) Scale. RESULTS: Out of 7170 articles screened, 66 studies (median PEDro score 5) with 3387 participants were included. Strong, significant effects on muscle strength were found for strength (SMD = 1.02), strength-aerobic (SMD = 1.41), strength-endurance (SMD = 0.92) and water-based (SMD = 1.08) training (52 studies, I2 = 79.3%). Strength training (SMD = 1.16), strength-aerobic (SMD = 0.98) and 3D training (SMD = 1.31) improved postural balance (30 studies, I2 = 88.1%). Moderator analyses revealed significant effects of specific intervention types on certain subgroups and subdomains of strength and balance. No studies were found measuring falls. CONCLUSIONS: Structured PA interventions in middle-aged adults improve strength and balance outcomes related to functional impairments and falls. Strength training increases both strength and balance and can be recommended to prevent age-related functional decline. However, the interpretability of the results is limited due to considerable heterogeneity and the overall low methodological quality of the included studies. Long-term trials are needed to determine the preventive potential of PA on strength, balance and falls. This meta-analysis may inform guidelines for tailored training during middle age to promote healthy aging. Prospero registration: CRD42020218643.

Systematic Review on Abdominal Penetrating Atherosclerotic Aortic Ulcers: Outcomes of Endovascular Repair.

PURPOSE: To systematically review existing evidence on outcomes of endovascular repair of abdominal atherosclerotic penetrating aortic ulcers (PAUs). MATERIAL AND METHODS: Cochrane Central Registry of Registered Trials (CENTRAL), MEDLINE (via PubMed), and Web of Science databases were systematically searched. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol (PRISMA-P 2020). The protocol was registered in the international registry of systematic reviews (PROSPERO CRD42022313404). Studies reporting on technical and clinical outcomes of endovascular PAU repair in 3 or more patients were included. Random effects modeling was used to estimate pooled technical success, survival, reinterventions, and type 1 and type 3 endoleaks. Statistical heterogeneity was assessed using the I2 statistic. Pooled results are reported with 95% confidence intervals (CIs). Study quality was assessed using an adapted version of the Modified Coleman Methodology Score. RESULTS: Sixteen studies including 165 patients with a mean/median age ranging from 64 to 78 years receiving endovascular therapy for PAU between 1997 and 2020 were identified. Pooled technical success was 99.0% (CI: 96.0%-100%). In all, 30-day mortality was 1.0% (CI: 0%-6.0%) with an in-hospital mortality of 1.0% (CI: 0.0%-13.0%). There were no reinterventions, type 1, or type 3 endoleaks at 30 days. Median/mean follow-up ranged from 1 to 33 months. Overall, there were 16 deaths (9.7%), 5 reinterventions (3.3%), 3 type 1 (1.8%), and 1 type 3 endoleak (0.6%) during follow-up. The quality of studies was rated low according to the Modified Coleman score at 43.4 (+/- 8.5) of 85 points. CONCLUSION: There is low-level evidence on outcomes of endovascular PAU repair. While in the short-term endovascular repair of abdominal PAU seems safe and effective, mid-term and long-term data are lacking. Recommendations with regard to treatment indications and techniques in asymptomatic PAU should be made cautiously. CLINICAL IMPACT: This systematic review demonstrated that evidence on outcomes of endovascular abdominal PAU repair is limited. While in the short-term endovascular repair of abdominal PAU seems safe and effective, mid-term and long-term data are lacking. In the context of a benign prognosis of asymptomatic PAU and lacking standardization in current reporting, recommendations with regard to treatment indications and techniques in asymptomatic PAUs should be made cautiously.

Minimally invasivE versus open total GAstrectomy (MEGA): study protocol for a multicentre randomised controlled trial (DRKS00025765).

INTRODUCTION: The only curative treatment for most gastric cancer is radical gastrectomy with D2 lymphadenectomy (LAD). Minimally invasive total gastrectomy (MIG) aims to reduce postoperative morbidity, but its use has not yet been widely established in Western countries. Minimally invasivE versus open total GAstrectomy is the first Western multicentre randomised controlled trial (RCT) to compare postoperative morbidity following MIG vs open total gastrectomy (OG). METHODS AND ANALYSIS: This superiority multicentre RCT compares MIG (intervention) to OG (control) for oncological total gastrectomy with D2 or D2+LAD. Recruitment is expected to last for 2 years. Inclusion criteria comprise age between 18 and 84 years and planned total gastrectomy after initial diagnosis of gastric carcinoma. Exclusion criteria include Eastern Co-operative Oncology Group (ECOG) performance status >2, tumours requiring extended gastrectomy or less than total gastrectomy, previous abdominal surgery or extensive adhesions seriously complicating MIG, other active oncological disease, advanced stages (T4 or M1), emergency setting and pregnancy.The sample size was calculated at 80 participants per group. The primary endpoint is 30-day postoperative morbidity as measured by the Comprehensive Complications Index. Secondary endpoints include postoperative morbidity and mortality, adherence to a fast-track protocol and patient-reported quality of life (QoL) scores (QoR-15, EUROQOL EuroQol-5 Dimensions-5 Levels (EQ-5D), EORTC QLQ-C30, EORTC QLQ-STO22, activities of daily living and Body Image Scale). Oncological endpoints include rate of R0 resection, lymph node yield, disease-free survival and overall survival at 60-month follow-up. ETHICS AND DISSEMINATION: Ethical approval has been received by the independent Ethics Committee of the Medical Faculty, University of Heidelberg (S-816/2021) and will be received from each responsible ethics committee for each individual participating centre prior to recruitment. Results will be published open access. TRIAL REGISTRATION NUMBER: DRKS00025765.

A comparison of methods for enriching network meta-analyses in the absence of individual patient data.

During drug development, a biomarker is sometimes identified as separating a patient population into those with more and those with less benefit from evaluated treatments. Consequently, later studies might be targeted, while earlier ones are performed in mixed patient populations. This poses a challenge in evidence synthesis, especially if only aggregated data are available. Starting from this scenario, we investigate three commonly used network meta-analytic estimation methods, the naive estimation approach, the stand-alone analysis, and the network meta-regression. Additionally, we adapt and modify two methods, which are used in evidence synthesis to combine randomized controlled trials with observational studies, the enrichment-through-weighting approach, and the informative prior estimation. We evaluate all five methods in a simulation study with 32 scenarios using bias, root-mean-squared-error, coverage, precision, and power. Additionally, we revisit a clinical data set to exemplify and discuss the application. In the simulation study, none of the methods was observed to be clearly favorable over all investigated scenarios. However, the stand-alone analysis and the naive estimation performed comparably or worse than the other methods in all evaluated performance measures and simulation scenarios and are therefore not recommended. While substantial between-trial heterogeneity is challenging for all estimation approaches, the performance of the network meta-regression, the enriching-through weighting approach and the informative prior approach was dependent on the simulation scenario and the performance measure of interest. Furthermore, as these estimation methods are drawing slightly different assumptions, some of which require the presence of additional information for estimation, we recommend sensitivity-analyses wherever possible.

Interventions to reduce the incidence of surgical site infection in colorectal resections: systematic review with multicomponent network meta-analysis (INTRISSI): study protocol.

OBJECTIVE: To assess the relative contribution of intravenous antibiotic prophylaxis, mechanical bowel preparation, oral antibiotic prophylaxis, and combinations thereof towards the reduction of surgical site infection (SSI) incidence in elective colorectal resections. METHODS AND ANALYSIS: A systematic search of randomised controlled trials comparing interventions to reduce SSI incidence will be conducted with predefined search terms in the following databases: MEDLINE, LILACS, Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR). Additionally, several online databases will be searched for ongoing trials, and conference proceedings and reference lists of retrieved articles will be hand searched. The title-abstract screening will be partly performed by means of a semiautomated supervised machine learning approach, which will be trained on a subset of the identified titles and abstracts identified through traditional screening methods.The primary analysis will be a multicomponent network meta-analysis, as we expect to identify studies that investigate combinations of interventions (eg, mechanical bowel preparation combined with oral antibiotics) as well as studies that focus on individual components (mechanical bowel preparation or oral antibiotics). By means of a multicomponent network meta-analysis, we aim at estimating the effects of the separate components along the effects of the observed combinations. To account for between-trial heterogeneity, a random-effect approach will be combined with inverse variance weighting for estimation of the treatment effects. Associated 95% CIs will be calculated as well as the ranking for each component in the network using P scores. Results will be visualised by network graphics and forest plots of the overall pairwise effect estimates. Comparison-adjusted funnel plots will be used to assess publication bias. ETHICS AND DISSEMINATION: Ethical approval by the Ethical Committee of the Medical Faculty of the Martin-Luther-University Halle-Wittenberg (ID of approval: 2021-148). Results shall be disseminated directly to decision-makers (eg, surgeons, gastroenterologists, wound care specialists) by means of publication in peer-reviewed journals, presentation at conferences and through the media (eg, radio, TV, etc). PROSPERO REGISTRATION NUMBER: CRD42021267322.

Nanopatterning of a Stimuli-Responsive Fluorescent Supramolecular Polymer by Thermal Scanning Probe Lithography.

The miniaturization of nanometer-sized multicolor fluorescent features is of continuous significance for counterfeit security features, data storage, and sensors. Recent advances in engineering of stimuli-responsive supramolecular polymeric materials that respond upon exposure to heat or mechanical force by changing their fluorescence characteristics open new opportunities as functional lithographic resists. Here, we demonstrate the patterning of a thermochromic supramolecular material by thermal scanning probe lithography (t-SPL), an emerging nanofabrication technique, which allows for ultrafast indentation with a heated probe, resulting in both fluorescent and topographic nanofeatures. t-SPL indentation reveals a linear relationship between the temperature at which material softening occurs and the indentation force in the range from 200 to 500 nN. The softening temperature decreases as the heating time increases from 4 µs to 1 ms, following time-temperature superposition behavior. Our results herein confirm that the fluorescence contrast, perceivable as a shift from red to green, was obtained by kinetic trapping of the dissociated state due to ultrarapid cooling when the probe is removed. We use t-SPL to create highly customized fluorescence patterns up to 40 × 40 µm2 in size with a spatial resolution of 86 nm and change the pitch size to modify the fluorescence intensity when observed by fluorescence microscopy. As an application, multifaceted security features with nanometer resolution are explored.