Intraoperative radiotherapy after neurosurgical resection of brain metastases as institutional standard treatment- update of the oncological outcome form a single center cohort after 117 procedures.

PURPOSE: Stereotactic radiotherapy (SRT) is the predominant method for the irradiation of resection cavities after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50 kV x-rays is an alternative way to irradiate the resection cavity focally. We have already reported the outcome of our first 40 IORT patients treated until 2020. Since then, IORT has become the predominant cavity treatment in our center due to patients´ choice. METHODS: We retrospectively analyzed the outcomes of all patients who underwent resection of BM and IORT between 2013 and August 2023 at Augsburg University Medical Center (UKA). RESULTS: We identified 105 patients with 117 resected BM treated with 50 kV x-ray IORT. Median diameter of the resected metastases was 3.1 cm (range 1.3 - 7.0 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including three-monthly MRI of the brain. Mean FU was 14 months, with a median MRI FU for patients alive of nine months. Median overall survival (OS) of all treated patients was 18.2 months (estimated 1-year OS 57.7%). The observed local control (LC) rate of the resection cavity was 90.5% (estimated 1-year LC 84.2%). Distant brain control (DC) was 61.9% (estimated 1-year DC 47.9%). Only 16.2% of all patients needed WBI in the further course of disease. The observed radio necrosis rate was 2.6%. CONCLUSION: After 117 procedures IORT still appears to be a safe and appealing way to perform cavity RT after neurosurgical resection of BM with low toxicity and excellent LC.

Comparison of Climate Impact, Clinical Outcome, and Cost-Efficiency of Pediatric Transumbilical Laparoscopic Assisted Appendectomy vs Standard 3-Port Laparoscopic Appendectomy.

BACKGROUND: Healthcare is responsible for 8.5% of US greenhouse gas emissions. These impacts must be mitigated while maintaining clinical excellence. This study compares clinical outcomes, cost-efficiency, and climate impact of trans-umbilical laparoscopic assisted appendectomy (TULAA) versus 3-port laparoscopic appendectomy (LA). STUDY DESIGN: Institutional Review Board approval was obtained. Appendectomies performed between Jan 1, 2020 and December 31, 2022 at a tertiary children's hospital were reviewed. Data abstracted included clinical characteristics, operative approach and findings, supplies and equipment utilized, and complications. For analysis TULAA was combined with cases converted to LA (TULAA+C). To determine a surgical site infection (SSI) increase of ≤ 2.5%, a minimum sample size of 479 patients per group was needed to achieve a power of 80%. A composite supply list for each approach was determined by averaging supplies from cases reviewed. The composite was used to calculate cost-efficiency and climate impact. Life cycle assessment was used to determine the carbon footprint (according to ISO 14067) of supplies and equipment. RESULTS: Analysis was performed on 1,611 appendectomies: 497 LA and 1,114 TULAA+C (932 TULAA, 182 converted). Except for BMI, there were no clinically significant differences between groups. SSI did not increase with TULAA+C (n=15, 1.3%) versus LA (n=6, 1.2%), p=0.81. TULAA+C ($369.21/case) was more cost efficient than LA ($879.30/case) and TULAA+C (24.8 kg CO2e) produced fewer emissions than LA (27.4 kg CO2e). CONCLUSIONS: While patient safety and excellent clinical outcomes must remain the top priority in healthcare, the current environmental crisis demands consideration of climate impacts. When clinical non-inferiority can be demonstrated, treatment options with a fewer greenhouse gas emissions should be chosen.

Comparative Efficacy of Flow Diverter Devices in the Treatment of Carotid Sidewall Intracranial Aneurysms: a Retrospective, Multicenter Study.

BACKGROUND: The comparative efficacy and safety of first-generation flow diverters (FDs), Pipeline Embolization Device (PED) (Medtronic, Irvine, California), Silk (Balt Extrusion, Montmorency, France), Flow Re-direction Endoluminal Device (FRED) (Microvention, Tustin, California), and Surpass Streamline (Stryker Neurovascular, Fremont, California), is not directly established and largely inferred. PURPOSE: This study aimed to compare the efficacy of different FDs in treating sidewall ICA intracranial aneurysms. METHODS: We conducted a retrospective review of prospectively maintained databases from eighteen academic institutions from 2009-2016, comprising 444 patients treated with one of four devices for sidewall ICA aneurysms. Data on demographics, aneurysm characteristics, treatment outcomes, and complications were analyzed. Angiographic and clinical outcomes were assessed using various imaging modalities and modified Rankin Scale (mRS). Propensity score weighting was employed to balance confounding variables. The data analysis used Kaplan-Meier curves, logistic regression, and Cox proportional-hazards regression. RESULTS: While there were no significant differences in retreatment rates, functional outcomes (mRS 0-1), and thromboembolic complications between the four devices, the probability of achieving adequate occlusion at the last follow-up was highest in Surpass device (HR: 4.59; CI: 2.75-7.66, p < 0.001), followed by FRED (HR: 2.23; CI: 1.44-3.46, p < 0.001), PED (HR: 1.72; CI: 1.10-2.70, p = 0.018), and Silk (HR: 1.0 ref. standard). The only hemorrhagic complications were with Surpass (1%). CONCLUSION: All the first-generation devices achieved good clinical outcomes and retreatment rates in treating ICA sidewall aneurysms. Prospective studies are needed to explore the nuanced differences between these devices in the long term.

Titanium-Coated Polyetheretherketone Cages Vs Full Titanium Cages for Stand-Alone 1- or 2-Level Anterior Cervical Discectomy and Fusion: A Comparative Study.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) for the surgical treatment of cervical degenerative disease often includes an intervertebral cage, which restores disc height and lordosis while promoting fusion . Cage materials include titanium (TTN) or polyetheretherketone (PEEK). Controversy in material selection stems from higher fusion rates with TNN, despite a higher subsidence rate, while PEEK cages demonstrate superior preservation of interspace height. Combining the advantages of both materials, TTN-coated PEEK (TCPEEK) cages were developed, featuring a PEEK core with similar stiffness to the bone, enveloped with a TTN coat, improving osteointegration. However, the potential superiority of TCPEEK over TTN cages has not been investigated. This study aimed to compare clinical and radiographic outcomes following single- or double-level ACDF using either TTN or TCPEEK cages. METHODS: This retrospective single-center study included patients undergoing single- or double-level ACDF between 2017 and 2019. Clinical outcomes included the Neck Disability Index and revision surgery incidence. Radiographic parameters included cervical and segmental lordosis, C2 to C7 sagittal vertical axis, fusion, subsidence, and adjacent segment degeneration at a minimum 12-month follow-up. RESULTS: A total of 45 patients (16 TTN; 29 TCPEEK) and 58 cervical levels (21 TTN; 37 TCPEEK) were included. Both cages significantly improved Neck Disability Index scores (TTN -10.0; TCPEEK -14.1) without significant differences. Two single-level TCPEEK patients required revision surgery due to non-union. In the radiological assessments, no significant difference was found for subsidence rates (TTN 52.4%; TCPEEK 56.8%), adjacent segment degeneration, cervical and segmental lordosis, and changes in C2 to C7 sagittal vertical axis. Though not statistically significant, fusion rates trended slightly higher with TTN (90.5%) vs TCPEEK cages (86.5%). CONCLUSION: TTN and TCPEEK cages achieve satisfactory clinical and radiological outcomes in single- or double-level ACDF. This finding suggests that the choice between them can be based on other factors, such as surgeon preference or availability, rather than specific material properties. CLINICAL RELEVANCE: This study found that the selection of ACDF cage material did not affect clinical outcomes.

Comparative analysis of mechanical thrombectomy outcomes of middle cerebral artery M1, M2 superior and M2 inferior occlusion strokes.

BACKGROUND: The M1 middle cerebral artery (MCA) commonly bifurcates into an M2 superior and an M2 inferior segment. However, MCA anatomy is highly variable rendering classification for mechanical thrombectomy (MT) trials difficult. Safety and effectiveness of M2 MCA stroke thrombectomy stratified by M2 MCA anatomy remains to be explored. METHODS: Large vessel occlusion strokes undergoing MT between 02/2016-08/2022 were reviewed (n=784). M1 (n=431) and M2 MCA (n=118) occlusions were assessed. Among M2 MCA occlusions only prototypical MCA bifurcation anatomy cases were included (n=99). Dominance was assessed based on angiography. Procedural and outcome data was compared between M1, M2 superior and M2 inferior MCA occlusions. RESULTS: Baseline demographics and periprocedural criteria of M2 superior (n=56) and M2 inferior (n=43) occlusion MTs were comparable. Among M2 inferior cases, the occluded branch was dominant in 41/43 (95.3%) but only in 37/56 (66.1%) among M2 superior cases (p<0.001). The 90-day favorable functional outcome (mRS 0-2) and mortality (mRS 6) rates were 60.0% and 8.9% in the M2 superior, 42.9% and 32.6% in the M2 inferior, and 44.1% and 26.0% in the M1 group (n=431). Compared to M2 superior, M2 inferior favorable outcome rates were lower (p=0.094) and mortality rates were higher (p=0.003) and resembled M1 outcome rates (p=0.750 and p=0.355, respectively). CONCLUSION: In setting of prototypical MCA bifurcation anatomy, thrombectomy of dominant M2 inferior occlusions had outcome rates like M1 occlusions. In contrast, M2 superior occlusions had significantly lower mortality rates and a trend towards better favorable functional outcome rates.

Multicenter external validation of prediction models for clinical outcomes after spinal fusion for lumbar degenerative disease.

BACKGROUND: Clinical prediction models (CPM), such as the SCOAP-CERTAIN tool, can be utilized to enhance decision-making for lumbar spinal fusion surgery by providing quantitative estimates of outcomes, aiding surgeons in assessing potential benefits and risks for each individual patient. External validation is crucial in CPM to assess generalizability beyond the initial dataset. This ensures performance in diverse populations, reliability and real-world applicability of the results. Therefore, we externally validated the tool for predictability of improvement in oswestry disability index (ODI), back and leg pain (BP, LP). METHODS: Prospective and retrospective data from multicenter registry was obtained. As outcome measure minimum clinically important change was chosen for ODI with ≥ 15-point and ≥ 2-point reduction for numeric rating scales (NRS) for BP and LP 12 months after lumbar fusion for degenerative disease. We externally validate this tool by calculating discrimination and calibration metrics such as intercept, slope, Brier Score, expected/observed ratio, Hosmer-Lemeshow (HL), AUC, sensitivity and specificity. RESULTS: We included 1115 patients, average age 60.8 ± 12.5 years. For 12-month ODI, area-under-the-curve (AUC) was 0.70, the calibration intercept and slope were 1.01 and 0.84, respectively. For NRS BP, AUC was 0.72, with calibration intercept of 0.97 and slope of 0.87. For NRS LP, AUC was 0.70, with calibration intercept of 0.04 and slope of 0.72. Sensitivity ranged from 0.63 to 0.96, while specificity ranged from 0.15 to 0.68. Lack of fit was found for all three models based on HL testing. CONCLUSIONS: Utilizing data from a multinational registry, we externally validate the SCOAP-CERTAIN prediction tool. The model demonstrated fair discrimination and calibration of predicted probabilities, necessitating caution in applying it in clinical practice. We suggest that future CPMs focus on predicting longer-term prognosis for this patient population, emphasizing the significance of robust calibration and thorough reporting.

Photodegradation of Organic Solar Cells under Visible Light and the Crucial Influence of Its Spectral Composition.

While wavelength-dependent photodegradation of organic solar cells (OSCs) under visible light is typically discussed in terms of UV/blue light-activated phenomena, we recently demonstrated wavelength-dependent degradation rates up to 660 nm for PM6:Y6. In this study, we systematically investigated this phenomenon for a broad variety of devices based on different donor:acceptor combinations. We found that the spectral composition of the light used for degradation, tuned in a spectral range from 457 to 740 nm and under high irradiances of up to 30 suns, has a crucial influence on the device stability of almost all tested semiconductors. The relevance of this phenomenon was investigated in the context of simulated AM1.5 illumination with metal halide lamps and white LEDs. It is concluded that the current stability testing protocols in OSC research have to be adjusted to account for this effect to reveal the underlying physics of this still poorly understood mechanism.

TREM2 protects from atherosclerosis by limiting necrotic core formation.

Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications, myocardial infarction and stroke, are the leading cause of mortality worldwide [1], [2]. Recent studies have identified Triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions [3], to be highly expressed in macrophage foam cells in experimental and human atherosclerosis [4]. However, the role of TREM2 in atherosclerosis is not fully known. Here, we show that hematopoietic or global TREM2 deficiency increased, whereas TREM2 agonism decreased necrotic core formation in early atherosclerosis. We demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages, and to the survival of lipid-laden macrophages, indicating a crucial role of TREM2 in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions, thereby controlling plaque necrosis.

Fluorescence-Based Proteoliposome Methods to Monitor Redox-Active Transition Metal Transmembrane Translocation by Metal Transporters.

Transmembrane transition metal transporter proteins are central gatekeepers in selectively controlling vectorial metal cargo uptake and extrusion across cellular membranes in all living organisms, thus playing key roles in essential and toxic metal homeostasis. Biochemical characterization of transporter-mediated translocation events and transport kinetics of redox-active metals, such as iron and copper, is challenged by the complexity in generating reconstituted systems in which vectorial metal transport can be studied in real time. We present fluorescence-based proteoliposome methods to monitor redox-active metal transmembrane translocation upon reconstitution of purified metal transporters in artificial lipid bilayers. By encapsulating turn-on/-off iron or copper-dependent sensors in the proteoliposome lumen and conducting real-time transport assays using small unilamellar vesicles (SUVs), in which selected purified Fe(II) and Cu(I) transmembrane importer and exporter proteins have been reconstituted, we provide a platform to monitor metal translocation events across lipid bilayers in real time. The strategy is modular and expandable toward the study of different transporter families featuring diverse metal substrate selectivity and promiscuity.

Skeletal muscle quality predicts overall survival in advanced liver hepatocellular carcinoma treated with SIRT and sorafenib: A subanalysis of the SORAMIC trial.

BACKGROUND AND AIMS: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC. METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis. RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04. CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS. IMPACT AND IMPLICATIONS: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.

Implications of therapy interruption on monthly migraine days and modified migraine disability assessment in patients treated with erenumab for chronic and episodic migraine: SQUARE study interim results.

BACKGROUND: There are limited real-world data in Switzerland examining the impact of erenumab, a fully human IgG2 monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor, on migraine-related quality of life. OBJECTIVE: This 18-month interim analysis of 172 patients with episodic or chronic migraine from the SQUARE study provides first prospective insights on the impact of mandatory erenumab treatment interruption, following Swiss-reimbursement requirements, in a real-world clinical setting in Switzerland. FINDINGS: Recruited patients receiving 70 or 140 mg erenumab underwent treatment interruption on average 11.2 months after therapy onset with a mean duration of 4 months. There were sustained improvements in mean monthly migraine days (MMD) and migraine disability (mMIDAS) during initial treatment with erenumab. Treatment interruption was associated with a temporary worsening of condition. Symptoms ameliorated upon therapy reuptake reaching improvements similar to pre-break within 3 months. CONCLUSIONS: Treatment interruption was associated with a temporary worsening of condition, which improved again after therapy restart.

Implementation of health-related quality of life in the German TraumaRegister DGU® - first results of a pilot study.

BACKGROUND: Approximately 30,000 people are affected by severe injuries in Germany each year. Continuous progress in prehospital and hospital care has significantly reduced the mortality of polytrauma patients. With increasing survival rates, the functional outcome, health-related quality (hrQoL) of life and ability to work are now gaining importance. Aim of the study is, the presentation of the response behavior of seriously injured patients on the one hand and the examination of the factors influencing the quality of life and ability to work 12 months after major trauma on the other hand. Building on these initial results, a standard outcome tool shall be integrated in the established TraumaRegister DGU® in the future. METHODS: In 2018, patients [Injury Severity Score (ISS) ≥ 16; age:18-75 years] underwent multicenter one-year posttraumatic follow-up in six study hospitals. In addition to assessing hrQoL by using the Short-Form Health Survey (SF-12), five additional questions (treatment satisfaction; ability to work; trauma-related medical treatment; relevant physical disability, hrQoL as compared with the prior to injury status) were applied. RESULTS: Of the 1,162 patients contacted, 594 responded and were included in the analysis. The post-injury hrQoL does not show statistically significant differences between the sexes. Regarding age, however, the younger the patient at injury, the better the SF-12 physical sum score. Furthermore, the physically perceived quality of life decreases statistically significantly in relation to the severity of the trauma as measured by the ISS, whereas the mentally perceived quality of life shows no differences in terms of injury severity. A large proportion of severely injured patients were very satisfied (42.2%) or satisfied (39.9%) with the treatment outcome. It should be emphasized that patients with a high injury severity (ISS > 50) were on average more often very satisfied with the treatment outcome (46.7%). A total of 429 patients provided information on their ability to work 12 months post-injury. Here, 194 (45.2%) patients had a full employment, and 58 (13.5%) patients were had a restricted employment. CONCLUSION: The present results show the importance of a structured assessment of the postinjury hrQoL and the ability to work after polytrauma. Further studies on the detection of influenceable risk factors on hrQoL and ability to work in the intersectoral course of treatment should follow to enable the best possible outcome of polytrauma survivors.

Investigating migraine phenotype and dynamics in women with endometriosis: an observational pilot study.

INTRODUCTION: Migraine and endometriosis are chronic disabling pain conditions. There is evidence for a shared genetic background. Migraine phenotype and course in patients with the comorbidity are insufficient investigated. Both conditions can be treated with progestins. METHODS: For this observational study we included women with migraine and endometriosis, visiting our clinic from 2015 to 2021. We collected available information from charts and complemented these data by a structured phone interview to collect more specific information on migraine and the course of both diseases. RESULTS: From 344 patients fulfilling the inclusion criteria, 94 suffered from both, endometriosis and migraine. Migraine with aura was reported by 41% of the patients and was associated with earlier onset of migraine (age < 17 years (OR 6.54) and with a history of medication overuse headache (OR 9.9, CI 1.6-59.4). Present monthly migraine frequency (1.5 ± 2.6) was significantly lower than five years before the interview (2.9 ± 4.64). There was a correlation between medication overuse headache and use of analgesics more than 3 days/months for dysmenorrhoea (p < 0.03). ASRM endometriosis score was not associated with migraine characteristics. CONCLUSIONS: We conclude that the comorbidity of endometriosis is highly linked to migraine with aura. Migraine onset in these patients was earlier. Further studies are needed to explore, if the observed decrease in migraine frequency can be attributed to recent endometriosis surgery and to understand if early diagnosis and treatment of both conditions may contribute to improve the course of both conditions. Trial registration BASEC Nr. 2021-00285.

Automated detection of early signs of irreversible ischemic change on CTA source images in patients with large vessel occlusion.

PURPOSE: To create and validate an automated pipeline for detection of early signs of irreversible ischemic change from admission CTA in patients with large vessel occlusion (LVO) stroke. METHODS: We retrospectively included 368 patients for training and 143 for external validation. All patients had anterior circulation LVO stroke, endovascular therapy with successful reperfusion, and follow-up diffusion-weighted imaging (DWI). We devised a pipeline to automatically segment Alberta Stroke Program Early CT Score (ASPECTS) regions and extracted their relative Hounsfield unit (rHU) values. We determined the optimal rHU cut points for prediction of final infarction in each ASPECT region, performed 10-fold cross-validation in the training set, and measured the performance via external validation in patients from another institute. We compared the model with an expert neuroradiologist for prediction of final infarct volume and poor functional outcome. RESULTS: We achieved a mean area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of 0.69±0.13, 0.69±0.09, 0.61±0.23, and 0.72±0.11 across all regions and folds in cross-validation. In the external validation cohort, we achieved a median [interquartile] AUC, accuracy, sensitivity, and specificity of 0.71 [0.68-0.72], 0.70 [0.68-0.73], 0.55 [0.50-0.63], and 0.74 [0.73-0.77], respectively. The rHU-based ASPECTS showed significant correlation with DWI-based ASPECTS (rS = 0.39, p<0.001) and final infarct volume (rS = -0.36, p<0.001). The AUC for predicting poor functional outcome was 0.66 (95%CI: 0.57-0.75). The predictive capabilities of rHU-based ASPECTS were not significantly different from the neuroradiologist's visual ASPECTS for either final infarct volume or functional outcome. CONCLUSIONS: Our study demonstrates the feasibility of an automated pipeline and predictive model based on relative HU attenuation of ASPECTS regions on baseline CTA and its non-inferior performance in predicting final infarction on post-stroke DWI compared to an expert human reader.

Improvement of health-related quality of life after closure of spinal CSF leaks in patients with spontaneous intracranial hypotension.

OBJECTIVE: Spontaneous intracranial hypotension (SIH) is an important cause of orthostatic headaches caused by spinal CSF leaks. It has a strong negative impact on patients' socioeconomic status and health-related quality of life (HRQOL). This study aimed to analyze the impact of surgical and endovascular treatments on patients' HRQOL. METHODS: The authors conducted a prospective, observational cohort study that included all patients treated for SIH with microsurgery or embolization, depending on the type of CSF leak, at their institution between April 2022 and May 2023. Patients were asked to complete a specifically designed questionnaire, as well as the 15D HRQOL questionnaire, before and 3 months after treatment. RESULTS: A total of 21 patients (14 female; mean age 51.7 years) were treated in the study period. There were 12 (57%) type 1 leaks, 3 (14%) type 2, and 6 (29%) type 3. While 20 (95.2%) leaks were localized in the thoracic spine, only 1 (4.8%) was found in the lumbar spine. All patients completed the questionnaires. Fifteen (71.4%) patients underwent microsurgery and 6 (28.6%) endovascular embolization. The mean 15D score improved from 0.802 before to 0.889 after treatment (p = 0.013). Compared with an age- and sex-matched general population, HRQOL was significantly impaired in patients with SIH before treatment. After treatment, the authors found no significant difference in the overall HRQOL between patients and the healthy population. Mean headache intensity on a numeric rating scale improved from 8.1 before treatment to 2.3 after treatment (p = 0.003). Patients reported that SIH had a notable impact on their social and working life. CONCLUSIONS: SIH has a considerable negative impact on HRQOL. Microsurgery or embolization can dramatically improve HRQOL, subjective perception of health, and headache intensity. Therefore, surgical or endovascular treatment should be considered given the improvement observed in HRQOL for patients with SIH.

Autoimmune diseases and atherosclerotic cardiovascular disease.

Autoimmune diseases are associated with a dramatically increased risk of atherosclerotic cardiovascular disease and its clinical manifestations. The increased risk is consistent with the notion that atherogenesis is modulated by both protective and disease-promoting immune mechanisms. Notably, traditional cardiovascular risk factors such as dyslipidaemia and hypertension alone do not explain the increased risk of cardiovascular disease associated with autoimmune diseases. Several mechanisms have been implicated in mediating the autoimmunity-associated cardiovascular risk, either directly or by modulating the effect of other risk factors in a complex interplay. Aberrant leukocyte function and pro-inflammatory cytokines are central to both disease entities, resulting in vascular dysfunction, impaired resolution of inflammation and promotion of chronic inflammation. Similarly, loss of tolerance to self-antigens and the generation of autoantibodies are key features of autoimmunity but are also implicated in the maladaptive inflammatory response during atherosclerotic cardiovascular disease. Therefore, immunomodulatory therapies are potential efficacious interventions to directly reduce the risk of cardiovascular disease, and biomarkers of autoimmune disease activity could be relevant tools to stratify patients with autoimmunity according to their cardiovascular risk. In this Review, we discuss the pathophysiological aspects of the increased cardiovascular risk associated with autoimmunity and highlight the many open questions that need to be answered to develop novel therapies that specifically address this unmet clinical need.

A Retrospective Cohort Analysis of Transarterial Chemoembolization for Hepatocellular Cancer at a Tertiary Center in Switzerland.

Background/Objectives: International guidelines recommend transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC). However, it is used outside these recommendations and has proven beneficial in prolonging survival. Since the role of TACE outside BCLC stage B is unclear, the present study analyzed the results of TACE performed at a tertiary center in Switzerland for different treatment groups, and aims to highlight the treatment outcomes for these groups. Methods: This retrospective cohort study includes 101 HCC patients undergoing TACE at our center. Patients were further subdivided into groups according to therapy combinations (therapies applied before and after index TACE). Kaplan-Meier survival curves were calculated for the Barcelona Center for Liver Cancer (BCLC) subgroups. Results: After TACE, the median survival was 28.1 months for BCLC 0, 31.5 months for BCLC A, 20.5 months for BCLC B, 10.8 for BCLC C, and 7.5 months for BCLC D. A lesion size larger than 55 mm was negatively associated with survival (HR 2.8, 95% CI 1.15-6.78). Complications occurred after TACE procedures: Clavien-Dindo I + II = 30, Clavien-Dindo > 3 = 2. Conclusions: TACE was performed in a substantial part of our cohort outside of routinely used treatment guidelines. The combination of the survival data and complication rate in these patients suggests it was a safe and beneficial strategy. Furthermore, our data show that in our cohort, the survival benefit associated with TACE was restricted to patients with a lesion size smaller than 55 mm.

First Clinical Experience with a New Device for the Removal of Cochlear Schwannomas.

Background: In most cases, intralabyrinthine schwannoma (ILS) occurs in patients with unilateral hearing deterioration or neurofibromatosis type II (NF II). The pattern of localization of these tumors varies but mostly affects the cochlea. Extirpation of the cochlear schwannoma, if hidden by the cochlea modiolus, is difficult under the aspect of complete removal. Therefore, a tissue removal device (TRD) was designed and tested in temporal bones. The principle of handling the new device is a pushing and pipe cleaner handling inside the cochlea. This present study aimed to describe the first in vivo experience with the newly developed TRD for removing cochlear intralabyrinthine schwannomas. Methods: In three patients, the TRD was used for the tumor removal of cochlear schwannomas. In two patients with a cochlear schwannoma in combination with a cochlea implantation and one patient suffering from NF II, a cochlear schwannoma was removed with the TRD. The access was performed with a posterior tympanotomy, an enlarged round window approach and an additional second turn access. The device was inserted and extracted gradually from the second turn access until the rings were visible in the second turn access. By pushing and pipe cleaner handling, the tumors were removed. An MRI control was performed on the day postoperatively with a T1 GAD sequence. Results: Tumor removal with the TRD was performed in a 15-min procedure without any complications. An MRI control confirmed complete removal on the postoperative day in all cases. Conclusions: In vivo handling of the device confirmed straightforward handling for the tumor removal. MRI scanning showed complete removal of the tumor by the TRD.

Safety and efficacy of Holmium-166 selective internal radiotherapy of primary and secondary liver cancer confirmed by real-world data.

Purpose: Holmium-166 has emerged as a promising option for selective internal radiotherapy (SIRT) for hepatic malignancies, but data on routine clinical use are lacking. The purpose of this study was to describe the safety and effectiveness of Holmium-166 SIRT in real-world practice through retrospective analysis of a multicenter registry. Methods: Retrospective analysis was conducted on Holmium-166 SIRT procedures performed between July 15, 2019, and July 15, 2021, across seven European centers. Treatment planning, treatment realization and post-treatment follow-up were conducted according to routine local practice. Safety and effectiveness data were extracted from the patients' health records. Primary endpoint analysis was assessed for the entire study population with separate analysis for subgroups with hepatocellular carcinoma, metastatic colorectal cancer and intrahepatic cholangiocarcinoma. Results: A total of 167 SIRT procedures in 146 patients (mean age 66 ± 11 years, 68% male) were retrospectively evaluated. Most common tumor entities were hepatocellular carcinoma (n=55), metastatic colorectal cancer (n=35), intrahepatic cholangiocarcinoma (n=19) and metastatic neuroendocrine tumors (n=10). Nine adverse events grade ≥ 3 according to Common Terminology Criteria for Adverse Events were recorded, including one fatal case of radioembolization-induced liver disease. Response rates and median overall survival for the above mentioned subgroups were comparable to results from previous Holmium-166 trials as well as to results from Yttrium-90 registries. Conclusion: This study confirms that the safety and effectiveness of Holmium-166 SIRT derived from prospective trials also applies in routine clinical practice, reinforcing its potential as a viable treatment option for primary and secondary liver cancer.