Introduction: Prolonged mechanical ventilation (PMV) and weaning failure are factors associated with prolonged hospital length of stay and increased morbidity and mortality. In addition to the burden these places on patients and their families, it also imposes high costs on the public health system. The aim of this systematic review was to identify risk factors for PMV and weaning failure. Methods: The study was conducted according to PRISMA guidelines. After a comprehensive search of the COCHRANE Library, CINHAL, Web of Science, MEDLINE, and the LILACS Database a PubMed request was made on June 8, 2020. Studies that examined risk factors for PMV, defined as mechanical ventilation ≥96 h, weaning failure, and prolonged weaning in German and English were considered eligible; reviews, meta-analyses, and studies in very specific patient populations whose results are not necessarily applicable to the majority of ICU patients as well as pediatric studies were excluded from the analysis. This systematic review was registered in the PROSPERO register under the number CRD42021271038. Results: Of 532 articles identified, 23 studies with a total of 23,418 patients met the inclusion criteria. Fourteen studies investigated risk factors of PMV including prolonged weaning, 9 studies analyzed risk factors of weaning failure. The concrete definitions of these outcomes varied considerably between studies. For PMV, a variety of risk factors were identified, including comorbidities, site of intubation, various laboratory or blood gas parameters, ventilator settings, functional parameters, and critical care scoring systems. The risk of weaning failure was mainly related to age, previous home mechanical ventilation (HMV), cause of ventilation, and preexisting underlying diseases. Elevated PaCO₂ values during spontaneous breathing trials were indicative of prolonged weaning and weaning failure. Conclusion: A direct comparison of risk factors was not possible because of the heterogeneity of the studies. The large number of different definitions and relevant parameters reflects the heterogeneity of patients undergoing PMV and those discharged to HMV after unsuccessful weaning. Multidimensional scores are more likely to reflect the full spectrum of patients ventilated in different ICUs than single risk factors.

In this meta-analysis and systematic literature review of refractive outcomes after Descemet membrane endothelial keratoplasty (DMEK), the extent of the refractive shift and an overview of reasons for refractive shift after DMEK are provided. The PubMed library was screened for articles containing the terms “Descemet membrane endothelial keratoplasty,” “DMEK,” “Descemet membrane endothelial keratoplasty combined with cataract surgery,” “triple-DMEK” combined with “refractive outcomes,” “refractive shift,” and “hyperopic shift.” The refractive outcomes after DMEK were analyzed and compared using a fixed and random effects model. The overall mean change of the spherical equivalent outcome when compared with the preoperative value in cases of DMEK or when compared with the preoperative target refraction in cases of DMEK combined with cataract surgery was +0.43 diopters (D) (95% CI, 0.31-0.55). When DMEK is combined with cataract surgery, a target refraction of −0.5 D is recommended to achieve emmetropia. Changes in the posterior corneal curvature are identified as the main cause of the refractive hyperopic shift.

BACKGROUND: Optimal blood pressure (BP) management during endovascular stroke treatment is not well established. We studied whether an individualized approach for managing BP during endovascular stroke treatment gives a better clinical outcome than an approach with standardized systolic BP targets. METHODS: The INDIVIDUATE study (Individualized Blood Pressure Management During Endovascular Treatment of Acute Ischemic Stroke Under Procedural Sedation) is a randomized clinical trial with a prospective randomized open blinded end point (PROBE) design. Patients were recruited between October 1, 2020 and July 7, 2022 at a single center at a tertiary care university hospital. Patients were eligible, when they were suffering from acute ischemic stroke of the anterior circulation with occlusions of the internal carotid artery and middle cerebral artery and a National Institutes of Health Stroke Scale score of ≥8 receiving endovascular stroke treatment in procedural sedation. The intervention consists of an individualized BP management strategy, where preinterventional baseline systolic BP (SBP) values are used as intraprocedural BP targets. As a control, the standard treatment aims to maintain the intraprocedural SBP between 140 and 180 mm Hg. The main prespecified outcome is the proportion of favorable functional outcomes 90 days after stroke, defined as a modified Rankin Scale score of 0 to 2. RESULTS: Two hundred fifty patients were enrolled and included in the analysis, mean (SD) age was 77 (12) years, 142 (57%) patients were women, and mean (SD) National Institutes of Health Stroke Scale score on admission was 17 (5.2). In all, 123 (49%) patients were treated with individualized and 127 (51%) with standard BP management. Mean (SD) intraprocedural SBP was similar in the individualized versus standard BP management group (157 [19] versus 154 [18] mm Hg; P =0.16). The rate of favorable functional outcome after 3 months was not significantly different between the individualized versus the standard BP management group (25% versus 24%; adjusted odds ratio, 0.81 [95% CI, 0.41–1.61]; P =0.56). CONCLUSIONS: Among patients treated with endovascular stroke treatment due to an acute ischemic stroke of the anterior circulation, no significant difference was seen between the individualized BP management strategy, where intraprocedural SBP was targeted to baseline values, and the standardized regimen of targeting SBP between 140 and 180 mm Hg. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04578288.

After surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity. In this study, 105 patients receiving postoperative fSRT with 35 Gy in 7 fractions performed with Cyberknife were retrospectively reviewed. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analysed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors. Median follow-up was 20.8 months. One-year TIBC was 61.6% and one-year LC was 98.6%. Median OS was 28.7 (95%-CI: 16.9–40.5) months. In total, local progression (median time not reached) occurred in 2.0% and in 20.4% radiation-induced contrast enhancements (RICE) of the cavity (after median of 14.3 months) were diagnosed. Absence of extracranial metastases was identified as an independent prognostic factor for superior OS (p = <0.001) in multivariate analyses, while a higher Karnofsky performance score (KPS) was predictive for longer OS in univariate analysis (p = 0.041). Leptomeningeal disease (LMD) developed in 13% of patients. FSRT after surgical resection of BM is an effective and safe treatment approach with excellent local control and acceptable toxicity. Further prospective randomized trials are needed to establish standardized therapeutic guidelines.

Prolonged glucocorticoid therapy is the standard initial treatment for idiopathic nephrotic syndrome in children, but is associated with marked toxic effects. We aimed to assess whether a novel treatment protocol with mycophenolate mofetil is as effective as standard therapy with prednisone, while reducing the burden of glucocorticoid-related side-effects. INTENT was a multicentre, open-label, randomised, controlled, parallel-group, non-inferiority, phase 3 trial done in 37 community, municipal, and university hospitals in Germany. Patients aged 1-10 years with a first episode of steroid-sensitive nephrotic syndrome were randomly assigned (1:1) by a centralised web-based tool to receive either mycophenolate mofetil or prednisone (standard treatment), after remission induced by prednisone or prednisolone at a dose of 60 mg/m² body surface area (maximum 80 mg/day) within 28 days. Block randomisation (block size of eight) was stratified by age (<7 years or ≥7 years). Mycophenolate mofetil was given at 1200 mg/m² body surface area per day, twice daily, as a suspension (200 mg/mL) for a total treatment duration of 12 weeks. Prednisone was administered once, twice, or three times daily for 6 weeks at 60 mg/m² body surface area per day (maximum 80 mg). Thereafter, prednisone was given for a further 6 weeks at 40 mg/m² body surface area (maximum 60 mg) once daily in the morning on alternate days. The primary endpoint was the occurrence of a treated relapse during the 24-months of follow-up in the modified intention-to-treat population. The non-inferiority margin was 15%. This trial is registered with the European Union Drug Regulating Authorities Clinical Trials database (EudraCT 2014-001991-76) and has been completed. Between Oct 12, 2015, and April 23, 2021, 497 patients were screened for eligibility, 272 of whom were randomly assigned (136 to each group). The modified intention-to-treat population comprised 269 patients, of whom 173 (64%) were boys and 96 (36%) were girls (median age 4·0 years [IQR 2·0-5·0]). Mycophenolate mofetil was non-inferior to prednisone for the primary endpoint of treated relapse (106 [79·1%] of 134 vs 101 [74·8%] of 135; difference 4·3% [90% CIs -4·2 to 12·7]; p=0·019). At the end of the first 12 weeks of treatment, fewer glucocorticoid-related side-effects were observed in the mycophenolate mofetil group than the prednisone group, including arterial hypertension (78 [59·1%] of 132 vs 115 [87·1%] of 132; difference -28·0% [95% CI -37·7 to -17·5]), lower BMI (BMI Z score 0·16 [SD 0·85] vs 1·41 [1·02]; difference -1·24 [-1·47 to -1·02]), and fewer psychological abnormalities (37 [27·8%] of 133 vs 77 [57·9%] of 133; difference -30·1% [-40·9 to -18·4]). More patients in the mycophenolate mofetil group than in the prednisone group developed infections (93 [69·9%] of 133 vs 74 [55·6%] of 133; difference 14·3% [2·7 to 25·5]) and there was no statistically significant difference in the number of patients who developed at least one gastrointestinal disorder (22 [16·5%] of 133 vs 13 [9·8%] of 133; difference 6·8% [-1·5 to 14·8]). Our findings suggest that mycophenolate mofetil is non-inferior to standard prednisone treatment, with reduced glucocorticoid-related toxic effects. These findings could modify the initial standard of care for patients with steroid-sensitive nephrotic syndrome. German Federal Ministry of Education and Research.

Due to the dependency structure in the sampling process, adaptive trial designs create challenges in point and interval estimation and in the calculation of P‐values. Optimal adaptive designs, which are designs where the parameters governing the adaptivity are chosen to maximize some performance criterion, suffer from the same problem. Various analysis methods which are able to handle this dependency structure have already been developed. In this work, we aim to give a comprehensive summary of these methods and show how they can be applied to the class of designs with planned adaptivity, of which optimal adaptive designs are an important member. The defining feature of these kinds of designs is that the adaptive elements are completely prespecified. This allows for explicit descriptions of the calculations involved, which makes it possible to evaluate different methods in a fast and accurate manner. We will explain how to do so, and present an extensive comparison of the performance characteristics of various estimators between an optimal adaptive design and its group‐sequential counterpart.