A survey of cancer patients' interest in undertaking exercise to promote relaxation during radiotherapy for breast cancer and metastatic cancer.

BACKGROUND: Approximately 25-50% of patients undergoing radiotherapy (RT) experience psychological distress and anxiety, which can detrimentally affect both their quality of life and treatment outcomes. While previous research has demonstrated that relaxation exercises can enhance the tolerability of RT and alleviate associated stress and anxiety, the specific needs for such therapies in radiation oncology remain under-explored. This study aims to investigate the demand for and preferences toward relaxation exercises among radiotherapy patients, addressing a critical gap in patient-centered care. METHODS: A prospective pseudonymized survey study using a one-time paper-based questionnaire was conducted from 2022 to 2023 among patients undergoing curative-intent RT for breast cancer or patients undergoing palliative RT for bone metastases. Patients were asked in a 11-item questionnaire about their anxiety, pre-existing practice of relaxation exercises/interventions, their interest in relaxation exercises, and preferences on the type and format of instruction. Data were analyzed descriptively. RESULTS: 100 patients (74 female and 26 male) responded, of whom 68 received curative-intent adjuvant RT and 32 palliative RT. Median age was 62 years. 78% of patients indicated a desire to be actively involved in their radiotherapy, but only 27% had used relaxation exercises prior to RT. 44.8% of both curatively and palliatively treated patients who wanted to be actively involved in their therapy desired to learn how to best relax. 56.4% of respondents were willing to spend extra time learning offered exercises. CONCLUSION: The survey indicates that patients undergoing RT, both for curative or palliative intent, desire relaxation exercises to relieve stress and anxiety from RT. It is therefore important to assess the need for relaxation interventions in individual patients and to develop suitable programs or collaborate with other healthcare professionals to meet these needs.

CARLA: Adjusted common average referencing for cortico-cortical evoked potential data.

Human brain connectivity can be mapped by single pulse electrical stimulation during intracranial EEG measurements. The raw cortico-cortical evoked potentials (CCEP) are often contaminated by noise. Common average referencing (CAR) removes common noise and preserves response shapes but can introduce bias from responsive channels. We address this issue with an adjusted, adaptive CAR algorithm termed "CAR by Least Anticorrelation (CARLA)". CARLA was tested on simulated CCEP data and real CCEP data collected from four human participants. In CARLA, the channels are ordered by increasing mean cross-trial covariance, and iteratively added to the common average until anticorrelation between any single channel and all re-referenced channels reaches a minimum, as a measure of shared noise. We simulated CCEP data with true responses in 0-45 of 50 total channels. We quantified CARLA's error and found that it erroneously included 0 (median) truly responsive channels in the common average with ≤42 responsive channels, and erroneously excluded ≤2.5 (median) unresponsive channels at all responsiveness levels. On real CCEP data, signal quality was quantified with the mean R2 between all pairs of channels, which represents inter-channel dependency and is low for well-referenced data. CARLA re-referencing produced significantly lower mean R2 than standard CAR, CAR using a fixed bottom quartile of channels by covariance, and no re-referencing. CARLA minimizes bias in re-referenced CCEP data by adaptively selecting the optimal subset of non-responsive channels. It showed high specificity and sensitivity on simulated CCEP data and lowered inter-channel dependency compared to CAR on real CCEP data.

Distributed representations of prediction error signals across the cortical hierarchy are synergistic.

A relevant question concerning inter-areal communication in the cortex is whether these interactions are synergistic. Synergy refers to the complementary effect of multiple brain signals conveying more information than the sum of each isolated signal. Redundancy, on the other hand, refers to the common information shared between brain signals. Here, we dissociated cortical interactions encoding complementary information (synergy) from those sharing common information (redundancy) during prediction error (PE) processing. We analyzed auditory and frontal electrocorticography (ECoG) signals in five common awake marmosets performing two distinct auditory oddball tasks and investigated to what extent event-related potentials (ERP) and broadband (BB) dynamics encoded synergistic and redundant information about PE processing. The information conveyed by ERPs and BB signals was synergistic even at lower stages of the hierarchy in the auditory cortex and between auditory and frontal regions. Using a brain-constrained neural network, we simulated the synergy and redundancy observed in the experimental results and demonstrated that the emergence of synergy between auditory and frontal regions requires the presence of strong, long-distance, feedback, and feedforward connections. These results indicate that distributed representations of PE signals across the cortical hierarchy can be highly synergistic.

Intention and preference to use long-acting injectable PrEP among MSM in the Netherlands: a diffusion of innovation approach.

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is efficacious in preventing HIV among men-who-have-sex-with-men (MSM) and will be soon available in Europe. This study investigated the intention and preference to use LAI-PrEP among MSM in the Netherlands by employing a diffusion of innovation approach. This study had a cross-sectional design nested within a cohort study established in 2017 to understand oral PrEP use among MSM. 309 MSM completed the survey on their awareness, interest, intention, and preference for LAI-PrEP in June 2022. Among them, 83% showed high/very-high interest in, and 63% showed high/very-high intention to use LAI-PrEP. A repeated innovator effect from the early adopters to LAI-PrEP was not observed. Early adopters did not show increased intention to use LAI-PrEP compared to other MSM subgroups, but neither did PrEP-naïve nor PrEP-discontinued MSM. However, among the 218 current oral PrEP users, suboptimal adherence was associated with preference for LAI-PrEP but not with intention to use it. In conclusion, our findings indicated that an effective, available, and affordable LAI-PrEP would be welcomed in the Netherlands, but that its introduction may not significantly expand PrEP coverage. However, the introduction of LAI-PrEP in the Netherlands could prove beneficial to MSM with suboptimal adherence to oral PrEP.

Preclinical Performance of the Combined Application of Two Robotic Systems in Microsurgery: A Two-center Study.

Background: Recent advancements in the development of robotic devices increasingly draw the attention toward the concept of robotic microsurgery, as several systems tailored to open microsurgery are being introduced. This study describes the combined application of a novel microsurgical robot, the Symani, with a novel robotic microscope, the RoboticScope, for the performance of microvascular anastomoses in a two-center preclinical trial. Methods: Six novices, residents, and experienced microsurgeons (n = 18) performed five anastomoses on 1.0-mm-diameter silicone vessels with a conventional versus combined robotic approach, resulting in 180 anastomoses. Microsurgical performance was evaluated, analyzing surgical time, subjective satisfaction with the anastomosis and robotic setup, anastomosis quality using the anastomosis lapse index score, microsurgical skills using the Structured Assessment of Microsurgery Skills score, and surgical ergonomics using the Rapid Entire Body Assessment score. Results: All participants significantly improved their performance during the trial and quickly adapted to the novel systems. Surgical time significantly decreased, whereas satisfaction with the anastomosis and setup improved over time. The use of robotic systems was associated with fewer microsurgical errors and enhanced anastomosis quality. Especially novices demonstrated accelerated skill acquisition upon robotic assistance compared with conventional microsurgery. Moreover, upper extremity positioning was significantly improved. Overall, the robotic approach was subjectively preferred by participants. Conclusions: The concept of robotic microsurgery holds great potential to improve precision and ergonomics in microsurgery. This two-center trial provides promising evidence for a steep learning curve upon introduction of robotic microsurgery systems, suggesting further pursuit of their clinical integration.

Detecting Metastatic Patterns of Oligometastatic Breast Cancer: A Comparative Analysis of 18F-FDG PET/CT and Conventional CT Imaging.

Metastasis-directed therapy has the potential to improve progression-free and overall survival in oligometastatic disease (OMD). For breast cancer, however, randomized trials have failed so far to confirm this finding. Because the concept of metastasis-directed therapy in OMD is highly dependent on the accuracy of the imaging modality, we aimed to assess the impact of 18F-FDG PET/CT on the definition of OMD in breast cancer patients. Methods: Eighty patients with a total of 150 18F-FDG PET/CT images (between October 2006 and January 2022) were enrolled in this retrospective study at the Technical University of Munich. The inclusion criteria were OMD, defined as 1-5 distant metastases, at the time of 18F-FDG PET/CT. For the current study, we systemically compared the metastatic pattern on 18F-FDG PET/CT with conventional CT. Results: At the time of 18F-FDG PET/CT, 21.3% of patients (n = 32) had a first-time diagnosis of metastatic disease, 40.7% (n = 61) had a previous history of OMD, and 38% (n = 57) had a previous history of polymetastatic disease. In 45.3% of cases, the imaging modality (18F-FDG PET/CT vs. conventional CT) had an impact on the assessment of whether OMD was present. An identical metastatic pattern was observed in only 32% of cases.18F-FDG PET/CT detected additional metastases in 33.3% of cases, mostly in the nonregional lymph node system. Conclusion: The use of 18F-FDG PET/CT had a substantial impact on the definition of OMD and detection of metastatic pattern in breast cancer. Our results emphasize the importance of establishing a standardized definition for imaging modalities in future trials and clinical practices related to metastasis-directed therapy in breast cancer patients.

Beyond community engagement: perspectives on the meaningful involvement of people with HIV and affected communities (MIPA) in HIV cure research in The Netherlands.

BACKGROUND: Meaningful involvement of people with HIV and affected communities in HIV cure research is essential to ensuring that cure research efforts are conducted transparently, socially justly, and ethically. This study set out to investigate how people with HIV and affected communities are involved in cure research in the Netherlands and explore what can be done to optimize involvement and engagement. METHODS: Eighty-five semi-structured online, telephone, and face-to-face interviews were conducted with people with HIV (N = 30), key populations (N = 35), and key informants (KI; N = 20) in the field of HIV. The interviews were analyzed using reflexive thematic analysis. RESULTS: Awareness of the meaningful involvement of people with HIV (MIPA) efforts was low among people with HIV and key populations, which contrasted with KI, who exhibited greater awareness. People with HIV and KI emphasized the importance of MIPA in ensuring the representation of lived experiences in HIV cure research and fostering trust between communities and researchers. Practical implementations of MIPA were unclear, ultimately resulting in difficulties defining MIPA beyond clinical trial participation. People with HIV and key populations also doubted their skills and self-efficacy to make meaningful contributions when confronted with involvement beyond participating in research and clinical trials. CONCLUSIONS: MIPA is crucial for improving the quality, transparency, and ethical conduct of HIV cure research. It emphasizes the need for increased awareness and funding, standardized guidelines to ensure meaningful involvement, and combat tokenism and misconceptions.

Socio-economic inequities in mental health problems and wellbeing among women working in the apparel and floriculture sectors: testing the mediating role of psychological capital, social support and tangible assets.

BACKGROUND: It is still unknown whether the mechanisms proposed by the Reserve Capacity Model (RCM) explaining socio-economic health and wellbeing inequities in high income countries can be applied to low-income countries. This study investigates whether different reserve capacities (intra-, inter-personal, and tangible) can explain the association between relative socio-economic position (SEP) and wellbeing outcome measures among Ethiopian women working in Foreign Direct Investment (FDI). METHOD: Using a cross-sectional design, we collected quantitative survey data among 2,515 women working in the apparel and floriculture sectors in Ethiopia, measuring GHQ-12 mental health problems, multi-dimensional wellbeing, relative SEP, psychological capital (PsyCap), social support (emotional and financial social support network), and tangible assets (e.g., owning mobile phone, having access to toilet facilities). We used cluster-adjusted structural equation modelling to test whether PsyCap, social support, and/or tangible assets mediate the association between relative SEP (IV) and GHQ-12 mental health problems and multi-dimensional wellbeing (DVs). RESULTS: PsyCap and the size of the financial support network significantly mediate the socio-economic gradient in both wellbeing outcomes. The size of the emotional social support network shows no association with multi-dimensional wellbeing and shows an unexpected negative association with GHQ-12 mental health problems scores, including a significant mediation effect. Tangible assets show no association with the wellbeing outcome measures and do not mediate socio-economic mental health problems and wellbeing inequities. CONCLUSIONS: The RCM can be applied in low-income countries, although in unexpected ways. Similar to findings from high-income countries, PsyCap and size of the financial social support network show significant mediation effects in explaining mental health problems and wellbeing inequities in Ethiopia. These reserves could therefore serve as a buffer for socio-economic inequities in mental health and wellbeing and can therefore assist in decreasing these inequities for women working in FDI sectors in Ethiopia.

[Robot-assisted Microsurgery for Autologous Breast Reconstruction - Robotic Breast Reconstruction]. / Roboter-assistierte Mikrochirurgie zur autologen Brustrekonstruktion.

BACKGROUND: With the introduction of novel surgical robots and surgical microscopes for the special needs of open microsurgery, the concept of robotic-assisted microsurgery is gaining popularity. While initial preclinical studies indicate a steep learning curve, favourable ergonomics and improved precision, albeit with an increased operating time, data on the clinical application of the new systems is still limited. This study describes our first clinical experience with robotic-assisted autologous breast reconstruction and outlines the opportunities and limitations of the approach. PATIENTS AND METHODS: Our retrospective data analysis included a total of 28 patients who underwent unilateral robotic-assisted autologous breast reconstruction between July 2022 and August 2023. We applied a combined approach using the Symani Surgical System together with the RoboticScope. Descriptive evaluation of patient characteristics, surgical data and complications was performed. RESULTS: Average patient age was 54.3±11.1 years and average BMI was 26.5±3.5 kg/m2. Twenty-six patients received a DIEP flap and 2 patients received a PAP flap, the flaps being connected to the internal mammary artery in 22 cases, to a perforator of the internal mammary artery in 5 cases, and to a branch of the thoracodorsal artery in one case. The average incision-suture time was 267±89 min, with an average ischaemia time of 86±20 min and duration of the arterial anastomosis of 29±12 min. In two cases, immediate intraoperative anastomosis revision was performed, but no flap loss occurred. CONCLUSION: The results of this study demonstrate the safe feasibility of robot-assisted autologous breast reconstruction using a combination of Symani and RoboticScope. In the future, special attention should be paid to minimally invasive techniques of flap harvest and connecting vessel preparation.

Scenarios of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data from the Netherlands, 2022.

BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.AimWe combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.ResultsThe seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks.ConclusionOur findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.

Acute to long-term characteristics of impedance recordings during neurostimulation in humans.

Objective.This study aims to characterize the time course of impedance, a crucial electrophysiological property of brain tissue, in the human thalamus (THL), amygdala-hippocampus, and posterior hippocampus over an extended period.Approach.Impedance was periodically sampled every 5-15 min over several months in five subjects with drug-resistant epilepsy using an investigational neuromodulation device. Initially, we employed descriptive piecewise and continuous mathematical models to characterize the impedance response for approximately three weeks post-electrode implantation. We then explored the temporal dynamics of impedance during periods when electrical stimulation was temporarily halted, observing a monotonic increase (rebound) in impedance before it stabilized at a higher value. Lastly, we assessed the stability of amplitude and phase over the 24 h impedance cycle throughout the multi-month recording.Main results.Immediately post-implantation, the impedance decreased, reaching a minimum value in all brain regions within approximately two days, and then increased monotonically over about 14 d to a stable value. The models accounted for the variance in short-term impedance changes. Notably, the minimum impedance of the THL in the most epileptogenic hemisphere was significantly lower than in other regions. During the gaps in electrical stimulation, the impedance rebound decreased over time and stabilized around 200 days post-implant, likely indicative of the foreign body response and fibrous tissue encapsulation around the electrodes. The amplitude and phase of the 24 h impedance oscillation remained stable throughout the multi-month recording, with circadian variation in impedance dominating the long-term measures.Significance.Our findings illustrate the complex temporal dynamics of impedance in implanted electrodes and the impact of electrical stimulation. We discuss these dynamics in the context of the known biological foreign body response of the brain to implanted electrodes. The data suggest that the temporal dynamics of impedance are dependent on the anatomical location and tissue epileptogenicity. These insights may offer additional guidance for the delivery of therapeutic stimulation at various time points post-implantation for neuromodulation therapy.

Mapping of the central sulcus using non-invasive ultra-high-density brain recordings.

Brain mapping is vital in understanding the brain's functional organization. Electroencephalography (EEG) is one of the most widely used brain mapping approaches, primarily because it is non-invasive, inexpensive, straightforward, and effective. Increasing the electrode density in EEG systems provides more neural information and can thereby enable more detailed and nuanced mapping procedures. Here, we show that the central sulcus can be clearly delineated using a novel ultra-high-density EEG system (uHD EEG) and somatosensory evoked potentials (SSEPs). This uHD EEG records from 256 channels with an inter-electrode distance of 8.6 mm and an electrode diameter of 5.9 mm. Reconstructed head models were generated from T1-weighted MRI scans, and electrode positions were co-registered to these models to create topographical plots of brain activity. EEG data were first analyzed with peak detection methods and then classified using unsupervised spectral clustering. Our topography plots of the spatial distribution from the SSEPs clearly delineate a division between channels above the somatosensory and motor cortex, thereby localizing the central sulcus. Individual EEG channels could be correctly classified as anterior or posterior to the central sulcus with 95.2% accuracy, which is comparable to accuracies from invasive intracranial recordings. Our findings demonstrate that uHD EEG can resolve the electrophysiological signatures of functional representation in the brain at a level previously only seen from surgically implanted electrodes. This novel approach could benefit numerous applications, including research, neurosurgical mapping, clinical monitoring, detection of conscious function, brain-computer interfacing (BCI), rehabilitation, and mental health.

Clinical evaluation of a stereotactic system for single-stage deep brain stimulation surgery under general anesthesia: technical note.

OBJECTIVE: Conventional frame-based stereotactic systems have circumferential base frames, often necessitating deep brain stimulation (DBS) surgery in two stages: intracranial electrode insertion followed by surgical re-preparation and pulse generator implantation. Some patients do not tolerate awake surgery, underscoring the need for a safe alternative for asleep DBS surgery. A frame-based stereotactic system with a skull-mounted "key" in lieu of a circumferential base frame received US FDA clearance. The authors describe the system's application for single-stage, asleep DBS surgery in 8 patients at their institution and review its workflow and technical considerations. METHODS: Eight patients underwent DBS lead insertion and IPG implantation in a single surgical preparation under general anesthesia using the system. Postoperative CT imaging confirmed lead placement. RESULTS: Eight patients underwent implantation of 15 total leads targeting the ventral intermediate nucleus (4 patients), globus pallidus internus (GPi; 3 patients), and subthalamic nucleus (STN; 1 patient). Intraoperative microelectrode recording was conducted for GPi and STN targets. Postoperative CT imaging revealed a mean ± SD radial error of 1.24 ± 0.45 mm (n = 15 leads), without surgical complications. CONCLUSIONS: The stereotactic system facilitated safe and effective asleep, single-stage DBS surgery, maintaining traditional lead accuracy standards.

Tumor Contact With Internal Mammary Perforator Vessels as Risk Factor for Gross Internal Mammary Lymph Node Involvement in Patients With Breast Cancer.

PURPOSE: The identification of internal mammary lymph node metastases and the assessment of associated risk factors are crucial for adjuvant regional lymph node irradiation in patients with breast cancer. The current study aims to investigate whether tumor contact with internal mammary perforator vessels is associated with gross internal mammary lymph node involvement. METHODS AND MATERIALS: We included 297 patients with primary breast cancer and gross internal mammary (IMN+) and/or axillary metastases as well as 230 patients without lymph node metastases. Based on pretreatment dynamic contrast-enhanced magnetic resonance imaging, we assessed contact of the tumor with the internal mammary perforating vessels (IMPV). RESULTS: A total of 59 patients had ipsilateral IMN+ (iIMN+), 10 patients had contralateral IMN+ (cIMN+), and 228 patients had ipsilateral axillary metastases without IMN; 230 patients had node-negative breast cancer. In patients with iIMN+, 100% of tumors had contact with ipsilateral IMPV, with 94.9% (n = 56) classified as major contact. In iIMN- patients, major IMPV contact was observed in only 25.3% (n = 116), and 36.2% (n = 166) had no IMPV contact at all. Receiver operating characteristic analysis revealed that "major IMPV contact" was more accurate in predicting iIMN+ (area under the curve, 0.85) compared with a multivariate model combining grade of differentiation, tumor site, size, and molecular subtype (area under the curve, 0.65). Strikingly, among patients with cIMN+, 100% of tumors had contact with a crossing contralateral IMPV, whereas in cIMN- patients, IMPVs to the contralateral side were observed in only 53.4% (iIMN+) and 24.8% (iIMN-), respectively. CONCLUSIONS: Tumor contact with the IMPV is highly associated with risk of gross IMN involvement. Further studies are warranted to investigate whether this identified risk factor is also associated with microscopic IMN involvement and whether it can assist in the selection of patients with breast cancer for irradiation of the internal mammary lymph nodes.

Functional Mapping of Movement and Speech Using Task-Based Electrophysiological Changes in Stereoelectroencephalography.

Introduction: Stereoelectroencephalography (sEEG) has become the predominant method for intracranial seizure localization. When imaging, semiology, and scalp EEG are not in full agreement or definitively localizing, implanted sEEG recordings are used to test candidate seizure onset zones (SOZs). Discovered SOZs may then be targeted for resection, laser ablation, or neurostimulation. If a SOZ is eloquent, resection and ablation are both contraindicated, so identifying functional representation is crucial for therapeutic decision making. Objective: We present a novel functional brain mapping technique that utilizes task-based electrophysiological changes in sEEG during behavioral tasks and test this in pediatric and adult patients. Methods: sEEG was recorded in twenty patients with epilepsy, aged 6-39 (12 female, 18 of 20 patients < 21 years old), who underwent implanted monitoring to identify seizure onset. Each performed 1) visually cued simple repetitive movements of the hand, foot, or tongue while electromyography was recorded, and 2) simple picture naming or verb generation speech tasks while audio was recorded. Broadband changes in the power spectrum of the sEEG were compared between behavior and rest. Results: Electrophysiological functional mapping of movement and/or speech areas was completed in all 20 patients. Eloquent representation was identified in both cortex and white matter, and generally corresponded to classically described functional anatomic organization as well as other clinical mapping results. Robust maps of brain activity were identified in healthy brain, regions of developmental or acquired structural abnormality, and SOZs. Conclusion: Task based electrophysiological mapping using broadband changes in the sEEG signal reliably identifies movement and speech representation in pediatric and adult epilepsy patients.

DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.

PURPOSE: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis. MATERIALS AND METHODS: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation). CONCLUSION AND RECOMMENDATIONS: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.

Thalamic stimulation induced changes in effective connectivity.

Deep brain stimulation (DBS) is a viable treatment for a variety of neurological conditions, however, the mechanisms through which DBS modulates large-scale brain networks are unresolved. Clinical effects of DBS are observed over multiple timescales. In some conditions, such as Parkinson's disease and essential tremor, clinical improvement is observed within seconds. In many other conditions, such as epilepsy, central pain, dystonia, neuropsychiatric conditions or Tourette syndrome, the DBS related effects are believed to require neuroplasticity or reorganization and often take hours to months to observe. To optimize DBS parameters, it is therefore essential to develop electrophysiological biomarkers that characterize whether DBS settings are successfully engaging and modulating the network involved in the disease of interest. In this study, 10 individuals with drug resistant epilepsy undergoing intracranial stereotactic EEG including a thalamus electrode underwent a trial of repetitive thalamic stimulation. We evaluated thalamocortical effective connectivity using single pulse electrical stimulation, both at baseline and following a 145 Hz stimulation treatment trial. We found that when high frequency stimulation was delivered for >1.5 hours, the evoked potentials measured from remote regions were significantly reduced in amplitude and the degree of modulation was proportional to the strength of baseline connectivity. When stimulation was delivered for shorter time periods, results were more variable. These findings suggest that changes in effective connectivity in the network targeted with DBS accumulate over hours of DBS. Stimulation evoked potentials provide an electrophysiological biomarker that allows for efficient data-driven characterization of neuromodulation effects, which could enable new objective approaches for individualized DBS optimization.

Engagement of HIV-negative MSM and partners of people with HIV in HIV cure (research): exploring the influence of perceived severity, susceptibility, benefits, and concerns.

ABSTRACTAs the prospect of an HIV cure is gaining prominence, engaging key populations affected by an HIV cure becomes essential. This study examined the engagement of HIV-negative men who have sex with men (MSM) and/or partners of people with HIV (PHIV) in the Netherlands. Interviews were conducted with 19 MSM not in relationships with a partner with HIV and 16 partners of PHIV and were thematically analyzed. Perspectives on the importance of an HIV cure were shaped by the perceived severity of HIV and the level of susceptibility to the virus. Despite concerns about potential new HIV infections and treatment intensity, most participants believed that an HIV cure could reduce HIV burden. Both HIV eradication and HIV suppression were regarded as acceptable outcomes. Engagement was demonstrated through actions like accessing information, participating in research, and showing support for partners or community members involved in HIV cure research. In conclusion, we found that most participants were engaged due to their heightened perception of HIV's severity. However, this engagement tended to remain passive due to their perceived low susceptibility to HIV, resulting in a scenario where the perceived importance of an HIV cure is high, while personal relevance remains low.