Universitair Ziekenhuis Ghent

This paper builds upon our previous work on photonic reservoir computing, presenting an enhanced artificial neural network (NN) integrated on a photonic integrated circuit (PIC) for the intelligent monitoring of optical signals. The NN employs the reservoir computing paradigm on optical signals, with a photonic reservoir and a digital readout for modulation format identification (MFI). Our focus is on the identification of dual-polarized wavelength-division multiplexing (WDM) signals with symbol rates between 32 and 35 GBd, covering modulation formats including 4QAM, and 16QAM. Experimental results demonstrate the system's robust MFI capabilities, achieving high accuracy across various signal formats. These findings highlight the potential of integrated photonic NNs in enhancing the performance and efficiency of optical communication systems.

Local full‐thickness resection techniques for rectal cancer are limited by lesion size, location, or poor margin delineation. We aimed to evaluate the feasibility of endoscopic knife‐assisted full‐thickness resection (kFTR) guided by the pocket‐detection method (PDM) for deeply invasive rectal cancer. Consecutive posterior‐lateral rectal lesions suspected of deep submucosal invasion treated at a tertiary care center from February to October 2024 were retrospectively included. kFTR guided by PDM involved creating a submucosal pocket to detect and isolate the suspected invasive component (muscle‐retracting sign), followed by muscularis propria incision and full‐thickness resection. Technical success, accuracy of detecting deep submucosal invasion, and en‐bloc resection rates were 100%. The median procedure time was 141.5 [IQR 123.7–179.5] minutes and the median hospitalization was 1 [IQR 1–7] day. No adverse events occurred. Histopathology showed R1‐vertical margin in patient 1 (pT2 adenocarcinoma) and R0 resection in patients 2, 3, and 4 (pT1bsm3) after refinement of the procedure to include a ≥3 mm muscularis propria margin around the suspected invasive component. There was no recurrence at the first endoscopic follow‐up of patients 1, 2, and 4. Patient 3 was sent to surgical low anterior resection due to multiple high‐risk histological features. The previous kFTR did not impair surgery (no residual rectal carcinoma and 1/17 positive lymph nodes). Endoscopic kFTR guided by the PDM may be a feasible organ‐preserving treatment for the detection and resection of deeply invasive posterior rectal cancer. Future studies are needed to ascertain whether rectal kFTR could represent a viable alternative to conventional surgical local excision techniques.

Extracorporeal Membrane Oxygenation (ECMO) has evolved significantly over the decades, from its early experimental stages to its current use as a standard of care in intensive care medicine. ECMO devices continue to evolve rapidly. „Building on the past – a bridge to the future” emphasises balance: moving forward with a vision for the future, while drawing strength and guidance from what has come before. Understanding the past in the development of the ECMO device components such as oxygenators and pumps will guide future innovations, as will the lessons learned from complications such as clotting or the advances in anticoagulation management. The future development will bring significant improvements in portability, safety, efficiency, and accessibility of ECMO. Advances in AI-driven monitoring and predictive models, biocompatible materials, and expanded clinical applications will make ECMO a more effective and widespread tool for managing critical heart and lung failure. These innovations are likely to make ECMO available earlier, in more settings, and safer for a wider range of patients, ensuring that it continues to save lives in an increasingly diverse range of medical situations.

Importance Progression independent of relapse activity (PIRA) is a significant contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (MS). Prior studies have used varying PIRA definitions, hampering the comparability of study results. Objective To compare various definitions of PIRA. Design, Setting, and Participants This cohort study involved a retrospective analysis of prospectively collected data from the MSBase registry from July 2004 to July 2023. The participants were patients with MS from 186 centers across 43 countries who had clinically definite relapsing-remitting MS, a complete minimal dataset, and 3 or more documented Expanded Disability Status Scale (EDSS) assessments. Exposure Three-hundred sixty definitions of PIRA as combinations of the following criteria: baseline disability (fixed baseline with re-baselining after PIRA, or plus re-baselining after relapses, or plus re-baselining after improvements), minimum confirmation period (6, 12, or 24 months), confirmation magnitude (EDSS score at/above worsening score or at/above threshold compared with baseline), freedom from relapse at EDSS score worsening (90 days prior, 90 days prior and 30 days after, 180 days prior and after, since previous EDSS assessment, or since baseline), and freedom from relapse at confirmation (30 days prior, 90 days prior, 30 days before and after, or between worsening and confirmation). Main Outcome and Measure For each definition, we quantified PIRA incidence and persistence (ie, absence of a 3-month confirmed EDSS improvement over ≥5 years). Results Among 87 239 patients with MS, 33 303 patients fulfilled the inclusion criteria; 24 152 (72.5%) were female and 9151 (27.5%) were male. At the first visits, the mean (SD) age was 36.4 (10.9) years; 28 052 patients (84.2%) had relapsing-remitting MS, and the median (IQR) EDSS score was 2.0 (1.0-3.0). Participants had a mean (SD) 15.1 (11.9) visits over 8.9 (5.2) years. PIRA incidence ranged from 0.141 to 0.658 events per decade and persistence from 0.753 to 0.919, depending on the definition. In particular, the baseline and confirmation period influenced PIRA detection. The following definition yielded balanced incidence and persistence: a significant disability worsening compared with a baseline (reset after each PIRA event, relapse, and EDSS score improvement), in absence of relapses since the last EDSS assessment, confirmed with EDSS scores (not preceded by relapses within 30 days) that remained above the worsening threshold for at least 12 months. Conclusion and Relevance Incidence and persistence of PIRA are determined by the definition used. The proposed standardized definition aims to enhance comparability among studies.

Background Previous studies have indicated that progression independent of relapse activity (PIRA) is uncommon in patients with aquaporin- 4 antibody-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD). However, the patterns of disability accumulation in seronegative NMOSD are unknown. This study aimed to evaluate the prevalence of PIRA and relapse-associated worsening (RAW) in seronegative NMOSD. Methods We conducted a retrospective, multicentre cohort study of seronegative NMOSD patients from the MSBase registry. Inclusion criteria required at least three recorded expanded disability status scale (EDSS) scores: baseline, progression, and 6 months confirmed disability progression (CDP). For those with 6-month CDP, the presence or absence of relapse between baseline and progression determined the classification as RAW or PIRA, respectively. Descriptive statistics were employed to present the data. Results This study included 93 patients, with a median follow-up duration of 5.0 years (Q1 2.8, Q3 8.4). The cohort predominantly consisted of female patients (77.4%), with a median age of onset of 33.9 years (Q1 26.1, Q3 41.2). PIRA was observed in 1 case (1.1%), whilst RAW was documented in 7 cases (7.5%). Conclusion This international cohort study confirms that CDP is uncommon in seronegative NMOSD. Given more than three quarters of CDP occur due to RAW, therapeutic strategies should focus primarily on preventing relapses.

Background Mixed cryoglobulinemia is one of the most important extrahepatic manifestations of chronic hepatitis C infection. Aims and Methods We screened 111 HCV-infected patients and identified 40 with cryoglobulinemia, who later achieved sustained virologic response (SVR). We prospectively followed them regarding laboratory findings and clinical symptoms for a median [IQR] of 5 [3–10] years. Results Prior to antiviral treatment, the median serum cryoglobulin level was 297 (IQR: 61–1144) mg/L. In 25 patients type II, while in 15 type III cryoglobulinemia were found with significant difference in cryoglobulin levels (669 [297–2713] vs. 57 [33–123], respectively) (p < 0.001). Only 23 patients had clinical symptoms at the diagnosis, of whom 21 had cryoglobulinemic vasculitis and 2 non-Hodgkin's lymphoma (NHL), and 17 patients were asymptomatic. Cryoglobulin levels were monitored yearly after SVR. Median times to cryoglobulin disappearance were significantly different between type II and type III disease forms (36 vs. 12 months, pLog-Rank: 0.002). Improvement or complete cessation of complaints were parallel to the cryoglobulin disappearance. Vasculitis, in most cases (n = 16) and one NHL were cured spontaneously during follow-up observation. However, some patients required specific treatment, such as immunosuppression [n = 5] for vasculitis and combined chemotherapy [n = 1] for aggressive NHL. Relapses of cryoglobulinemia and related symptoms were detected in 2 patients. Importantly, polyneuropathy did not show improvement by any means. Conclusions Our results support that the monitoring of cryoglobulins is important even after SVR, especially in case of type II forms. Long-term complications such as severe vasculitis or NHL may still occur.

Objectives To explore the relationship between final expanded treatment in cerebral infarction (eTICI) score and the presence or absence of distal emboli on final angiography on clinical outcome after endovascular thrombectomy (EVT) for acute ischaemic stroke (AIS). Persistent distal emboli on angiography are commonly noted, yet not all patients with intermediate eTICI scores demonstrate clear angiographic emboli, raising the possibility that these angiographic differences may correlate with distinct mechanisms of ‘no-reflow’. Therefore, we sought to better understand the potential clinical impact of such angiographic markers in cases of incomplete reperfusion. Design We performed an exploratory retrospective analysis of a prospectively collected group of AIS patients who underwent EVT for M1 occlusions using the ASSIST Registry. Setting 71 sites in 11 countries participated in the registry. Participants A total of 650 patients with M1 occlusions were included. Main outcome measures We compared 90-day modified Rankin scale (mRS) scores based on eTICI score as well as the presence or absence of distal emboli on final angiography. Results Clinical outcome based only on eTICI score revealed a shift in 90-day mRS, with a significant difference across eTICI scores in predicting 90-day mRS 0–2. In the intermediate eTICI grades 2b67 and 2c, there was a trend towards better 90-day mRS when emboli were present on final angiography than when emboli were absent. However, pairwise comparisons between these levels were non-significant. Conclusion In patients with final eTICI 2b67 or 2c, those with persistent emboli trended towards better clinical outcomes. With intermediate eTICI reperfusion, identifying the presence or absence of distal emboli on final angiography may be useful in distinguishing patterns of incomplete reperfusion. These findings should be followed by investigations on correlation between angiography and other markers of microcirculatory ‘no-reflow’. Trial registration number NCT03845491.

Objectives: To summarize key contributions to current research in the field of Clinical Research Informatics (CRI) and to select the best papers published in 2023. Methods: A bibliographic search using a combination of MeSH descriptors and free-text terms on CRI was performed using PubMed, followed by a double-blind review in order to select a list of candidate best papers to be then peer-reviewed by external reviewers. After peer-review ranking, a consensus meeting between the two section editors and the editorial team was organized to finally conclude on the selected three best papers. Results: Among the 1,119 papers returned by the search, published in 2023, that were in the scope of the various areas of CRI, the full review process selected three best papers. The first best paper describes the process undertaken in Germany, under the national Medical Informatics Initiative, to define and validate a provenance metadata framework to enable the interpretation including quality assessment of health data reused for research. The authors of the second-best paper present a methodology for the generation of computable phenotypes and the covariates associated with success rates in e-phenotype validation. The third-best presents a review of published and accessible tools that enable the assessment of health data quality through an automated process. This year's survey paper marks the tenth anniversary of the CRI section of the Yearbook by reviewing the dominant themes within CRI over the past decade and the major milestone innovations within this field. Conclusions: The literature relevant to CRI in 2023 has largely been populated by publications that assess and enhance the reusability of health data for clinical research, in particular data quality assessment and metadata management.

Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse following antigen-targeted immunotherapy which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS following a host of antigen-targeted therapies (e.g., CD19, CD22, CD38 and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of post-immunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-ALL to AML, 17 (22.7%) cases of B-ALL to mixed phenotypic acute leukemia (MPAL)/acute leukemias of ambiguous lineage (ALAL), and 5 (6.7%) cases of rare LS presentation (i.e., T-cell ALL to AML). An additional 10 cases with incomplete changes in immunophenotype, referred to as "lineage drift" were also described. With a primary focus on the 70 cases of LS from B-ALL to AML or MPAL/ALAL, LS emerged at a median of 1.5 months (range, 0-36.5 months) post-immunotherapy, with 81.4% presenting with LS within the first 6 months from the most proximal immunotherapy. While the majority involved KMT2A rearrangements (n=45, 64.3%), other rare cytogenetic and/or molecular alterations were uniquely observed. Treatment outcomes were generally poor with < 40% remission rates. The median overall survival following LS diagnosis was 4.8 months. Outcomes were similarly poor for those with rare immunophenotypes of LS or "lineage drift." This global initiative robustly categorizes lineage changes post-immunotherapy and, through enhanced understanding, establishes a foundation for improving outcomes of LS.

Introduction Bone marrow oedema (BME) on MRI of the sacroiliac joints (SIJ) commonly occurs after pregnancy. Our goal was to assess the evolution of BME over a period of 5 years and the potential development of structural lesions. Methods MRI-SIJ was performed after an uncomplicated vaginal delivery, with a follow-up 5 years later, evaluating both inflammatory and structural lesions. Results 19 women were assessed. Mean age was 35.3 years, with median body mass index of 20.8. Six subjects reported back pain, of which only one reported inflammatory back pain (IBP). No association was found between IBP and Spondyloarthritis Research Consortium of Canada (SPARCC) score (p=0.24), nor with a positive MRI according to the Assessment of SpondyloArthritis international Society (ASAS) definition at baseline (p=0.64). Thirty-two percent (6/19) presented with BME after 5 years, 3 of whom met the ASAS definition of a positive MRI-SIJ, irrespective of subsequent pregnancies. A new delivery during follow-up was linked to the total number of structural lesions at year 5, whereas mean weight gain across all pregnancies correlated with sclerosis. Sclerosis and erosions were more frequently detected by synthetic CT compared with T1-weighted MRI. Conclusions In postpartum women, no significant development of structural MRI lesions was observed 5 years after a single delivery, despite the presence of BME in a significant number of individuals postpartum and at follow-up. These results support the hypothesis that, unlike BME in SpA, childbirth-related mechanical stress-induced BME does not lead to structural lesions. However, subsequent pregnancies may contribute to their development.

Aim Worldwide, of all cancers, colorectal cancer has the fourth highest rate of mortality. Curative treatment for locally advanced or recurrent rectal cancer can require extended resections with sacrectomy, but this sugery can have major consequences for patients. The aim of this study was to investigate the oncological and functional outcomes after sacrectomy in patients with colorectal cancer. Method The protocol was registered in (PROSPERO), the international prospective register of systematic reviews. PubMed, Embase, The Cochrane Library, Scopus and Google Scholar were searched using a predetermined search strategy. Article selection, quality of evidence [Grading of Recommendation, Assessment, Development and Evaluation (GRADE)] and risk of bias [The Risk Of Bias In Non‐randomized Studies—of Interventions (ROBINS‐I)] were assessed by two independent reviewers. Studies reporting on sacrectomy for colorectal cancer were included. Oncological and functional outcomes after sacrectomy for colorectal cancer were the primary outcomes. Results Forty‐six articles with 1687 patients (1115 men; 506 women) were included. Median follow‐up was 31.4 months. Mean 30‐day mortality was 1.1%. After R0 resection, overall survival was achieved in 86.2%, 68.0% and 42.1% patients, and disease‐free survival was achieved in 75.0%, 51.0% and 43.0% patients, respectively, after 1, 3 and 5 years. Survival rates were lower after R1 or R2 resection. Most patients reported elimination of or significantly reduced pain after surgery, and 82.2% were able to walk independently, without the use of assistive devices. More patients were dependent on walking‐assist devices after high sacrectomy than after low sacrectomy. The most commonly reported bowel dysfunctions were bowel obstruction (22.3%) and fistula (4.6%). Bladder dysfunction was mainly reported as incontinence (8.3%) and neurogenic bladder (23.3%). No study included quality of life as an outcome. Conclusions The mortality was limited, and the morbidity rates were in concordance with published literature. The results suggest that R0 resection has higher survival rates than R1/R2 resections. Both short‐ and long‐term functional outcomes could have major impact on a patient's quality of life. Heterogeneity was high, and neither comparative analyses nor meta‐analysis could be performed.

Background There is a substantial body of literature addressing the prevention, acute management, and follow-up care of radiation induced dermatitis (RID). The quality and application of this evidence, however, is inconsistent and its interpretation varies widely. While several national guidelines have been developed to standardise practices locally, many of these resources are not publicly available. On behalf of the European Society for Radiotherapy and Oncology (ESTRO) Radiation Therapist (RTT) Committee, an international writing group consisting of 12 experts from radiotherapy and two patient representatives composed a recommendation document for the management of RID. Main body The consensus for these recommendations was generated based on available international guidelines, and supplemented with evidence-based review articles on the topic. These recommendations focus on the prevention and practical management of early stage RID by avoiding skin trauma and maintaining hygiene. Addressing pain and inflammation in higher grades is also covered. The current literature refutes some of the traditional recommendations, especially restricting washing as well as the use of deodorant or the potential dose build-up of lotions which has been included and rectified in recent guidelines. In addition, the importance of grading the severity, including a baseline assessment is presented. The benefit of clear, and non-contradictory communication within the multidisciplinary team as well as patient involvement (e.g. PROMs or similar) is highlighted. Furthermore, the importance of recognising different skin types and skin tones, and the impact on how RID changes these in their appearance is stressed. Conclusion This document provides practical, actionable recommendations for the clinical management of RID, referencing the supporting literature. These recommendations have, however, identified a lack of high-level evidence, especially for agent-specific recommendations.

Purpose: We investigated SAR441000 (mixture of four mRNAs encoding interleukin [IL]-12, single chain interferon [IF]-α-2b, granulocyte-macrophage colony-stimulating factor, and IL-15 sushi domain) alone or in combination with cemiplimab in patients with advanced solid tumors. Patients and Methods: SAR441000 was intratumorally administered weekly in a 4-week cycle in monotherapy and in a 3-week cycle at a pre-defined dose level (DL) with 350 mg cemiplimab (intravenously) every 3 weeks in combination therapy. The primary objective was to determine maximum tolerated or maximum administered dose (MAD), overall safety, tolerability, and objective response rate of SAR441000. Results: We enrolled 77 patients previously treated with anti-cancer therapies (escalation monotherapy: N=21; escalation combination: N=15; and expansion combination [PD-1 refractory melanoma]: N=41). MAD at DL8 was 4000 µg. The most common Grade ≥3 treatment-related adverse event was fatigue in escalation phase (monotherapy: 28.6%; combination therapy: 66.7%) and injection-site pain (31.7%) in expansion phase. In combination therapy, one patient in escalation and two in expansion phase achieved partial responses. At 4000 μg (highest dose) across all cohorts, the maximum fold change in plasma cytokine concentration was the highest and lowest for IFN-α-2 (74.9-folds) and IL-15 (1.96-folds), respectively. Increased blood IFN-γ and IP-10 levels were observed for most patients. Conclusions: Intratumoral administration of SAR441000 in combination with cemiplimab, was generally well tolerated with anti-tumor activity in loco-regional disease setting. Anecdotal evidence of pharmacodynamic immune-modulatory effect and distant non-injected lesion anti-tumor response was observed, without significant effect in patients with advanced solid tumors previously treated with anti-PD1 therapies.

The prefrontal-hippocampal pathways are integral to memory suppression, facilitating positive and adaptative responses following traumatic events. However, the role of these circuits in promoting resilience among adolescents remains largely unknown. This study used structural similarity analysis of MRI-based gray matter volume (GMV) to map connectivity networks centered on the hippocampus, investigating whether structural similarity between prefrontal regions and hippocampus were related to resilience in a cohort of 145 adolescents. Additionally, spatial correlation analyses of resilience-related structural similarity network and neurotransmitter distribution maps were conducted to identify molecular adaptations within prefrontal-hippocampal circuits associated with resilience. The results showed that higher resilience levels were correlated with stronger structural similarity between the prefrontal areas (i.e., middle frontal gyrus and orbitofrontal cortex) and hippocampus. Furthermore, the serotonergic neurotransmitter system, which modulates neural oscillations in prefrontal-hippocampal pathways, appears to be associated with resilience. The current findings suggest that structural and molecular adaptations within prefrontal-hippocampal circuits, which are implicated in the suppression of intrusive, unwanted memories, may foster resilience in young people. These insights advance our knowledge of the neurobiological markers of resilience, paving the way for more targeted and effective therapeutic interventions to bolster resilience and mitigate adverse outcomes in developmental populations.