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Abstract Colorectal cancer (CRC) is a devastating disease, ranking as the second leading cause of cancer-related deaths worldwide. Immune checkpoint inhibitors (ICIs) have emerged as promising treatments; however, their efficacy is largely restricted to a subgroup of microsatellite instable (MSI) CRCs. In contrast, microsatellite stable (MSS) CRCs, which account for the majority of cases, exhibit variable and generally weaker response to ICIs, with only a subset demonstrating exceptional responsiveness. Identifying novel cancer-specific tissue (CST) markers predictive of immunotherapy response is crucial for refining patient selection and overcoming treatment resistance. In this study, we developed clinically relevant CRC organoids and autologous immune system interaction platforms to model ICI response. We conducted a comprehensive molecular characterization of both responder and non-responder models, identifying CST markers that predict ICI response. Validation of these findings was performed using an independent cohort of patient specimens through multiplex immunofluorescence. Furthermore, we demonstrated that knocking out a key gene from the identified predictive signature in resistant organoids restored immune sensitivity and induced T-cell-mediated apoptosis. Overall, our results provide novel insights into the mechanisms underlying immunotherapy resistance and suggest new markers for enhancing patient selection. These findings may pave the way for new therapeutic options in MSS patients, potentially broadening the cohort of individuals eligible for immunotherapy.

Abstract Background Cancer navigation programs aim to support, educate, and empower patients and families, addressing barriers to diagnostics, treatment, and care. Navigators engage with people to ensure timely access to services and resources. While promising for older people with cancer, these programs are scarce in Europe, and research on their effectiveness and implementation is limited. We describe the protocol of the EU NAVIGATE randomized controlled trial, aimed to evaluate (1) effectiveness and cost-effectiveness of NavCare-EU, an intervention that aims to support older people with cancer throughout their illness trajectory, spanning the continuum of supportive, palliative, and end-of-life care, and (2) the intervention’s implementation processes and feasibility of its integration into different health care systems in Europe, contextual barriers and facilitators for effective and sustainable implementation, and mechanisms involved in reaching the outcomes. Methods We will conduct a multisite pragmatic fast-track randomized controlled trial with embedded convergent mixed-method process evaluation in Belgium, Ireland, Italy, Netherlands, Poland, and Portugal. The study targets people with cancer and declining health, 70 years or older, and their close family caregivers. The trial compares the NavCare-EU intervention plus standard care with standard care alone. We will perform a baseline measurement prior to randomization and follow-up measurements at 12 weeks, 24 weeks, and 48 weeks in intervention and control group, and an additional measurement at 72 weeks in the control group. Primary outcomes, measured at 24 weeks are (1) the older person’s global health status/quality of life, a 2-item subscale from EORTC-QLQ-C30 (revised) measuring health-related quality of life, (2) level of social support measured with Medical Outcomes Study Social Support Survey (MOS-SSS scale). The study will include at least 246 older persons with completed global health status/quality of life at 24 weeks. Discussion The EU NAVIGATE trial will cross-nationally test the effectiveness and cost-effectiveness of a navigation intervention for older people with cancer and their family caregivers, and its implementation in different health care systems in Europe. As continuity and access to health, social, and community care is a priority for patients and caregivers, the trial is timely and critically needed. Trial registration Clinicaltrials.gov: identifier NCT06110312 (2023/10/31).

Current therapies show limited efficacy against peritoneal metastases (PM) from pancreatic cancer. Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has emerged as a novel intraperitoneal drug delivery method. Recently, a dose-escalation study identified the safe dose of Nabpaclitaxel for PIPAC administration, an ideal intraperitoneal chemotherapy agent against pancreatic cancer. Combining systemic NabPaclitaxel-Gemcitabine with NabPaclitaxel-PIPAC may enhance disease control in pancreatic cancer patients with PM.

Abstract Background The SMILE study addresses a significant need in palliative oncology by evaluating the non-inferiority of a shortened, 3-fraction stereotactic body radiotherapy (SBRT) schedule against the traditional 5-fraction approach for non-spine bone metastases in terms of pain control. Optimizing SBRT could significantly enhance the quality of life for patients by providing effective pain relief while minimizing treatment sessions. Methods This international, multicenter phase III trial will randomize 162 patients to receive either a 3-fraction regimen (9 Gy per fraction) or a standard 5-fraction regimen (7 Gy per fraction). Outcomes, assessed at 3 months post-treatment, will focus on pain response, quality of life, and control of metastasis. With a hypothesis-driven design, the study will incorporate intent-to-treat and per-protocol analyses, incorporating appropriate measures for data integrity and handling of missing information. Discussion If the 3-fraction SBRT regimen demonstrates non-inferiority, it could streamline palliative care protocols, reduce patient burden, and set a new standard for treatment, reflecting a patient-centered approach in palliative radiation oncology. Trial registration The trial has been registered prospectively on ClinicalTrials.gov under the identifier NCT05406063, as of May 3, 2022.

Abstract Background Only a few cases of bilateral traumatic sternoclavicular dislocations have been reported in the literature. This injury is considered one of the rarest injuries of the human musculoskeletal system. Therefore, we present the first documented case of a cyclist with a third-degree open thoracic trauma (Gustilo–Anderson 3a) associated with a dislocated manubrium sterni fracture in the upper thoracic aperture, bilateral anterior dislocations of the sternoclavicular joints, rib fractures, and pleural ruptures. Case presentation The patient, a 27-year-old Caucasian male, incurred this injury while participating in a professional cycling race at Nürburgring, Germany and received immediate interdisciplinary surgical treatment and has encountered no complications. We conducted a 1-year follow-up and present the clinical findings of this follow up. Additionally, we conducted a comprehensive review of the existing literature on this injury. Conclusions Immediate interdisciplinary intervention, including surgical repair and meticulous postoperative care, facilitated successful patient recovery. This underscores the critical role of comprehensive trauma management in complex polytrauma cases. In conclusion, this case report highlights the rarity and complexity of a traumatic injury involving bilateral sternoclavicular dislocation, with this case being the first case reported with concomitant open thorax trauma. Our patient benefited greatly from immediate air-bound transportation to an interdisciplinary care provider, which houses both thoracic and trauma surgery departments.

Abstract Purpose The goal of this retrospective study was to perform a CT imaging assessment of thoracic pedicles to provide a representative understanding of pedicle morphology for pedicle-based fixation systems commonly used in orthopedics, trauma and neurosurgery. This study aimed to better understand the morphology of the spine and give spine surgeons a better understanding of thoracic spine anatomy. Methods In this study, we retrospectively measured the thoracic spine pedicles of a total of 16 males and 16 females, totaling in 768 individual pedicles. For the measurements, we used standardized planes in computed tomography imaging with a maximum slice thickness of 1 mm. Results In brief, we identified significant differences in various measurements of male and female pedicle morphology. The medial cortical wall of the pedicles was significantly thicker than the lateral wall, and, in both sexes, the thoracic vertebral body number four was the vertebra with the least amount of cortical bone in the pedicle. Conclusions Surgeons performing operations involving pedicle screw placement should be aware of the sex-specific differences in thoracic spine pedicle morphology noted in this research.

Abstract Background Spontaneous supratentorial intracerebral hemorrhage is the deadliest form of stroke with mortality rates over 50%. Currently, no sufficiently effective treatment to improve both mortality and functional outcome rates exists. However, it seems that minimally invasive surgery, especially endoscopic surgery, might be beneficial in improving survival and functional outcome rates, yet large confirmatory studies thereof are lacking. The aim of this trial is to compare whether early minimally invasive endoscopic surgery leads to improved functional outcome rates compared to the best medical treatment. Methods This is a prospective, parallel-arm, outcome assessor blinded multicenter trial across Switzerland. Endoscopic surgery will be compared to the best medical treatment in a 1:1 randomization over a total time of 12 months. The primary outcome is defined as improved functional outcome (mRS

The purpose of this scoping review is to synthesize knowledge of gamified online course design processes and practices extracted from the peer-reviewed research literature. The scoping review followed a systematic process involving five main stages: (a) identifying research questions, (b) identifying relevant studies, (c) study selection, (d) charting the data, and (e) collating, summarizing, and reporting the results. A total of 58 studies, published from 2013 through 2021 were included in this review. Five focus areas of gamified online course design were identified that include gamification elements, activities, tools, frameworks, and user attributes. The well-known ADDIE (Analyze, Design, Develop, Implement, Evaluate) framework was used as a conceptual lens through which gamified online course design processes were considered. This scoping review addresses a gap in the knowledge base by aggregating and interpreting current gamified online course design practices through the common language of a well-known instructional design framework.