München Klinik Harlaching

Introduction: The anatomy of the distal tibiofibular joint (DTFJ) has been demonstrated to influence the radiological outcome of reduction with syndesmotic screw fixation in the course of ankle fracture treatment. The objective of this study was to describe the anatomy of the DTFJ and to analyze the effect of incisura anatomy on syndesmotic stabilization with suture button systems (SBS), also in the context of their flexible nature of fixation. Materials and Methods: Forty-four (21 females, 23 males) consecutive postoperative bilateral computed tomography scans after stabilization of the DTFJ by SBS in the course of operative treatment of unstable ankle fractures were retrospectively analyzed. The anatomy of the DTFJ was evaluated by examining the following parameters: depth of the tibial incisura (DI), rotation of the incisura (ROI), Nault talar dome angle (NTDA), Leporjärvi clear space (LCS), anterior tibiofibular distance (antTFD), and fibula engagement (FE). The side-to-side (Δ) of LCS, NTDA, and antTFD, which analyzed the reduction result, were correlated with DI, FE, ROI, and NTDA, as well as the transverse offset (TO), reflecting the flexible nature of fixation. Results: Patients with slight overtightening (ΔLCS > −1 mm) showed a fibula that protruded less into the incisura on the native side (smaller FE) compared to symmetrical reduced patients and to patients with slight diastasis (p < 0.05). There was no relationship between the parameters describing the anatomy of the incisura and parameters assessing the parameter of the “flexible nature of fixation” (rs < 0.300). Regarding the anatomical parameters, it was observed that there were inter-individual differences of more than 4 mm (p > 0.05). Conclusions: The considerable inter-individual anatomical variability of the DTFJ was confirmed. The morphological configuration of the incisura has no impact on the immediate radiological reduction result after SBS stabilization of the DTFG, as determined by CT. The extent of the flexible nature of fixation is also not affected by the morphology of the incisura. Stabilization of the DTFJ can be performed regardless of the anatomical configuration.

The randomized FIRE-4.5 (AIO KRK0116) trial compared first-line therapy with FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan) plus either cetuximab or bevacizumab in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E-mutant metastatic colorectal cancer (mCRC) patients. This study was accompanied by a prospective translational project analyzing cell-free circulating tumor DNA (ctDNA) in plasma to test whether ctDNA analysis may help to guide clinical treatment decision making. FIRE-4.5 included mCRC patients with BRAF V600E mutation detected by tissue-based analyses. Liquid biopsies (LBs) were collected at baseline (pre-treatment) and during therapy. Digital droplet PCR (ddPCR) technology was applied for determination of BRAF mutations and the in vitro diagnostics (IVD)-certified ONCOBEAM RAS procedure for analysis of RAS mutations. The BRAF V600E variants in ctDNA were analyzable in 66 patients at start of the therapy, at baseline. No BRAF V600E mutations were detected in 26% (17/66) of patients and was associated with a significantly longer progression-free survival (PFS: 13.2 vs 6.5 months; HR 0.47; P = 0.014) and overall survival (OS: 36.8 vs 13.2 months; HR 0.35; P = 0.02) as compared to ctDNA mutant patients. Patients with detectable BRAF mutations showed a clear superiority of FOLFOXIRI plus bevacizumab with regard to PFS (10.4 vs 5.7 months; HR 0.4; P = 0.009) and OS (16.6 vs 11.6 months; HR 0.5; P = 0.15), while this was not the case for BRAF wild-type patients. Follow-up LBs were obtained from 51 patients. Patients converting from BRAF V600E mutant to a BRAF V600 wild-type status (36%, N = 18) had a superior PFS (8.6 vs 2.3 months; P = 0.0002) and OS (17.4 vs 5.1 months; P < 0.0001) compared to patients with stable or increased mutational allele frequency (12%, N = 6). Those patients also achieved a significantly greater disease control rate (89% vs 20%; P = 0.008). In conclusion, LB evaluating ctDNA is informative and may help to guide treatment in patients with BRAF V600E-mutated mCRC.

This is a follow-up study to the pentaerythrityl tetranitrate randomized controlled multicenter trial that reports neonatal outcome data of newborns admitted to neonatal intensive care units and outcome data of the offspring at 12 months of age. We present data on adverse events reported during the study to document the safety of pentaerythrityl tetranitrate treatment during pregnancy. To further evaluate the effects of pentaerythrityl tetranitrate on neonatal and long-term outcomes, we present follow up data from of 240 children at 12 months of age, including information on height, weight, head circumference, developmental milestones, and the presence of chronic disease and of 144 newborns admitted to the neonatal intensive care unit during the trial. The pentaerythrityl tetranitrate trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of the nitric oxide-donor pentaerythrityl tetranitrate in the prevention of fetal growth restriction and perinatal death in pregnancies complicated by abnormal placental perfusion. Results at 12 months demonstrated that significantly more children were age appropriately developed without impairments in the pentaerythrityl tetranitrate group (P=.018). In addition, the presence of chronic disease was lower in the pentaerythrityl tetranitrate group (P=.041). Outcome data of the 144 newborns admitted to the neonatal intensive care unit did not reveal differences between the treatment and placebo groups. There were no differences in the number or nature of reported adverse events between the study groups. The analysis shows that study children born in the pentaerythrityl tetranitrate cohort have a clear advantage compared with the placebo group at the age of 12 months, as evidenced by the increased incidence of normal development without the presence of chronic disease. Although safety has been proven, further follow-up studies are necessary to justify pentaerythrityl tetranitrate treatment during pregnancies complicated by impaired uterine perfusion.

Due to their effect on aneurysm hemodynamics, flow diverters (FD) have become a routine endovascular therapy for intracranial aneurysms. Since over- and undersizing affect the device’s hemodynamic abilities, selecting the correct device diameter and accurately simulating FD placement can improve patient-specific outcomes. The purpose of this study was to validate the accuracy of virtual flow diverter deployments in the novel Derivo® 2 device. We retrospectively analyzed blood flows in ten FD placements for which 3D DSA datasets were available pre- and post-intervention. All patients were treated with a second-generation FD Derivo® 2 (Acandis GmbH, Pforzheim, Germany) and post-interventional datasets were compared to virtual FD deployment at the implanted position for implanted stent length, stent diameters, and curvature analysis using ANKYRAS (Galgo Medical, Barcelona, Spain). Image-based blood flow simulations of pre- and post-interventional configurations were conducted. The mean length of implanted FD was 32.61 (±11.18 mm). Overall, ANKYRAS prediction was good with an average deviation of 8.4% (±5.8%) with a mean absolute difference in stent length of 3.13 mm. There was a difference of 0.24 mm in stent diameter amplitude toward ANKYRAS simulation. In vessels exhibiting a high degree of curvature, however, relevant differences between simulated and real-patient data were observed. The intrasaccular blood flow activity represented by the wall shear stress was qualitatively reduced in all cases. Inflow velocity decreased and the pulsatility over the cardiac cycle was weakened. Virtual stenting is an accurate tool for FD positioning, which may help facilitate flow FDs’ individualization and assess their hemodynamic impact. Challenges posed by complex vessel anatomy and high curvatures must be addressed.

Pregnant women are at an increased risk of severe COVID-19 and adverse pregnancy outcomes; data on maternal long-term outcome is scarce. We analyzed long-term follow-ups on women who experienced a SARS-CoV-2 infection during pregnancy to evaluate post-COVID symptoms, particularly fatigue, and their association with quality of life (QoL). 773 women who enrolled in the CRONOS registry between April 2020 and August 2021 were contacted for follow-up from December 2022 to April 2023. Data was gathered through a web-based questionnaire. Subsequently, study coordinators matched the follow-up data with the existing CRONOS data. 110/773 (14%) women provided data. 20.9% experienced only acute symptoms during their SARS-CoV-2 infection in pregnancy, while 2.7% women experienced symptoms lasting longer than 4 weeks (long COVID). Symptoms lasting longer than 12 weeks (post-COVID) were reported by 63.6% women and occurred more often after severe COVID-19. Fatigue was the most frequently reported symptom (88%), with 55% of women still experiencing it more than one year after initial infection. 76% of women rated their QoL as "good" or "very good". Women experiencing post-COVID reported a significantly lower QoL. This is the first German long-term data on women after SARS-CoV-2 infection during pregnancy, showing a high rate of post-COVID, a persistence of fatigue, and the impact on QoL. Continuous monitoring of pregnant women with COVID-19 is needed to develop comprehensive management strategies.

ObjectivesLittle is known about in-hospital-stroke (IHS) patients with large vessel occlusion and subsequent transfer to referral centres for endovascular therapy (EVT). However, this subgroup is highly relevant given the substantial amount of IHS, the ongoing trend towards greater use of EVT and lack of EVT possibilities in rural hospitals. The study objective is to explore the clinical outcomes of this vulnerable patient group, given that both IHS and interhospital transfer are associated with worse clinical outcomes due to a higher proportion of pre-existing conditions and substantial time delays during transfer.Design and settingProspectively collected data of patients receiving EVT after interhospital transfer from 14 rural hospitals of the Telemedical Stroke Network in Southeast Bavaria (TEMPiS) between February 2018 and July 2020 was analysed.Participants49 IHS and 274 out-of-hospital-stroke (OHS) patients were included.Outcome measuresBaseline characteristics, treatment times and outcomes were compared between IHS and OHS. The primary endpoint was a 3-month modified Rankin Scale (mRS).ResultsIn IHS patients, atrial fibrillation (55.3% vs 35.9%, p=0.012), diabetes (36.2% vs 21.1%, p=0.024) and use of oral anticoagulants (44.7% vs 20.8%, p<0.001) were more frequent. Stroke severity was similar in both groups. Treatment times from symptom onset to first brain imaging, therapy decision or EVT were shorter for IHS patients. IHS patients displayed worse clinical outcomes: 59.2% of IHS patients died within 3 months compared with 28.5% of OHS patients (p<0.001). They were less likely to achieve moderate outcomes (mRS 0–3) 3 months after stroke (20.4% vs 39.8%, p=0.010). After controlling for possible confounding variables, IHS was associated with worse clinical outcomes (adjusted OR 3.04 (95% CI 1.57 to 6.04), p<0.001).ConclusionsThe mortality of IHS patients after interhospital transfer and EVT was high and functional outcomes were worse compared with those of OHS patients. Further research is needed to ascertain whether IHS patients benefit from this therapeutic approach. A more careful selection of IHS patients for transfer and means to enable faster treatment should be considered.Trial registration numberNCT04270513; Post-results.

BRAFV600E mutation is associated with a poor outcome in metastatic colorectal cancer (mCRC). This clinical trial investigated the efficacy of triplet chemotherapy (fluorouracil, folinic acid, oxaliplatin, and irinotecan) combined with either cetuximab or bevacizumab in patients with previously untreated BRAFV600E-mutant mCRC. In this controlled, randomized, open-label phase II trial, 109 patients were randomly assigned, 107 of whom were included into the full analysis set (FAS). Patients were randomly assigned in a 2:1 ratio to receive either FOLFOXIRI plus cetuximab in the experimental arm (n = 72) or FOLFOXIRI plus bevacizumab in the control arm (n = 35). The primary end point was objective response rate (ORR) according to RECIST 1.1., evaluated in patients treated according to protocol (ATP population). Progression-free survival (PFS), overall survival (OS), toxicity, and feasibility were analyzed as secondary end points. Eighteen patients discontinued study treatment before the first tumor assessment, thus resulting in the ATP population of 89 patients. In these patients, ORR was 51% (30/59) in the cetuximab-based experimental arm and 67% (20/30) in the bevacizumab-based control arm (odds ratio, 1.93; 80% CI, 1.06 to 3.52; P = .92 [one-sided]). In the full analysis set, median PFS was significantly inferior in the experimental arm (6.7 months v 10.7 months; hazard ratio [HR], 1.89; P = .006). Median OS analyzed at an event rate of 64.5% showed a trend toward shorter survival in cetuximab-treated patients (12.9 months v 17.1 months; HR, 1.4; P = .20). To our knowledge, FIRE-4.5 is the first prospective and randomized study investigating first-line treatment of BRAFV600E-mutant mCRC. FOLFOXIRI plus cetuximab does not induce a higher ORR when compared with FOLFOXIRI plus bevacizumab in first-line treatment of BRAFV600E-mutant mCRC. Bevacizumab-based chemotherapy remains the preferable first-line treatment of patients with BRAFV600E-mutant mCRC.

Einleitung Ein früher vorzeitiger Blasensprung "PPROM" betrifft circa 3% aller Schwangerschaften vor Vollendung der 37+0 Schwangerschaftswoche [1]. Besonders im 2. und beginnenden 3. Trimenon ist dies bei den Feten mit erheblicher Morbidität und Mortalität aufgrund der noch fehlenden Lungenreife, sowohl auf alveolärer als auch auf vaskulärer Ebene, verbunden [2]. Mögliche Prädiktoren hinsichtlich des Outcomes der Frühgeborenen wurden bis dato nicht einheitlich festgelegt.