The Cultural Landscape & Heritage Paradox; Protection and Development of the Dutch Archeological-Historical Landscape and its European Dimension

To what extent can we know past and mainly invisible landscapes, and how we can use this still hidden knowledge for actual sustainable management of landscape’s cultural and historical values. It has also been acknowledged that heritage management is increasingly about ‘the management of future change rather than simply protection’. This presents us with a paradox: to preserve our historic environment, we have to collaborate with those who wish to transform it and, in order to apply our expert knowledge, we have to make it suitable for policy and society. The answer presented by the Protection and Development of the Dutch Archaeological-Historical Landscape programme (pdl/bbo) is an integrative landscape approach which applies inter- and transdisciplinarity, establishing links between archaeological-historical heritage and planning, and between research and policy. This is supported by two unifying concepts: ‘biography of landscape’ and ‘action research’. This approach focuses upon the interaction between knowledge, policy and an imagination centered on the public. The European perspective makes us aware of the resourcefulness of the diversity of landscapes, of social and institutional structures, of various sorts of problems, approaches and ways forward. In addition, two related issues stand out: the management of knowledge creation for landscape research and management, and the prospects for the near future. Underlying them is the imperative that we learn from the past ‘through landscape’

Which surgical technique may yield the best results in large, infected, segmental non-unions of the tibial shaft?:A scoping review

Purpose: Infected nonunion of the tibia with a large segmental bone defect is a complex and challenging condition for the patient and surgeon. This scoping review was conducted to identify existing evidence and knowledge gaps regarding this clinical scenario. Secondly, the objective of this study was to search for a valid recommendation on the optimal treatment. Methods: A comprehensive search was conducted in the bibliographic databases: PubMed, Embase.com, and Web of Science Core Collection. Studies reporting on bone transport techniques, the Masquelet technique, and vascularized fibular grafts in bone defects greater than 5 cm were included. Bone healing results and functional results were compared according to duration of nonunion, infection recurrence, bone consolidation, complication rate, external fixation time, and time until full weight-bearing. Results: Of the 2753 articles retrieved, 37 studies could be included on bone transport techniques (n = 23), the Masquelet technique (n = 7), and vascularized fibular grafts (n = 7). Respective bone union percentages were 94.3%, 89.5%, and 96.5%. The percentages of infection recurrence respectively were 1.6%, 14.4% and 7.0%, followed by respectively 1.58, 0.78, and 0.73 complications per patient. Conclusion: Bone transport was found to be the most widely studied technique in the literature. Depending on the surgeon’s expertise, vascularized fibular grafts may be held as a favourable alternative. This review indicates that further high-quality research on large bone defects (≥ 5 cm) in patients with infected tibial nonunions is necessary to gain more insight into the potentially beneficial results of vascularized fibular grafts and the Masquelet technique.</p

Which surgical technique may yield the best results in large, infected, segmental non-unions of the tibial shaft?:A scoping review

Purpose: Infected nonunion of the tibia with a large segmental bone defect is a complex and challenging condition for the patient and surgeon. This scoping review was conducted to identify existing evidence and knowledge gaps regarding this clinical scenario. Secondly, the objective of this study was to search for a valid recommendation on the optimal treatment. Methods: A comprehensive search was conducted in the bibliographic databases: PubMed, Embase.com, and Web of Science Core Collection. Studies reporting on bone transport techniques, the Masquelet technique, and vascularized fibular grafts in bone defects greater than 5 cm were included. Bone healing results and functional results were compared according to duration of nonunion, infection recurrence, bone consolidation, complication rate, external fixation time, and time until full weight-bearing. Results: Of the 2753 articles retrieved, 37 studies could be included on bone transport techniques (n = 23), the Masquelet technique (n = 7), and vascularized fibular grafts (n = 7). Respective bone union percentages were 94.3%, 89.5%, and 96.5%. The percentages of infection recurrence respectively were 1.6%, 14.4% and 7.0%, followed by respectively 1.58, 0.78, and 0.73 complications per patient. Conclusion: Bone transport was found to be the most widely studied technique in the literature. Depending on the surgeon’s expertise, vascularized fibular grafts may be held as a favourable alternative. This review indicates that further high-quality research on large bone defects (≥ 5 cm) in patients with infected tibial nonunions is necessary to gain more insight into the potentially beneficial results of vascularized fibular grafts and the Masquelet technique.</p

Trends and Variation in the Use of Radiotherapy in Non-metastatic Rectal Cancer:a 14-year Nationwide Overview from the Netherlands

Aims: This study describes nationwide primary radiotherapy utilisation trends for non-metastasised rectal cancer in the Netherlands between 2008 and 2021. In 2014, both colorectal cancer screening and a new guideline specifying prognostic risk groups for neoadjuvant treatment were implemented.Materials and methods: Patients with non-metastasised rectal cancer in 2008–2021 (n = 37 510) were selected from the Netherlands Cancer Registry and classified into prognostic risk groups. Treatment was studied over time and age. Multilevel logistic regression analyses were carried out to identify factors associated with (i) radiotherapy versus chemoradiotherapy use for intermediate rectal cancer and (ii) chemoradiotherapy without versus with surgery for locally advanced rectal cancer.Results: For early rectal cancer, the use of neoadjuvant radiotherapy decreased (15% to 5% between 2008 and 2021), whereas the use of endoscopic resections increased (8% in 2015, 17% in 2021). In intermediate-risk rectal cancer, neoadjuvant chemoradiotherapy (43% until 2011, 25% in 2015) shifted to radiotherapy (42% in 2008, 50% in 2015), the latter being most often applied in older patients. In locally advanced rectal cancer, the use of chemoradiotherapy without surgery increased (2–4% in 2008–2013, 17% in 2019–2021). Both neoadjuvant treatment in intermediate disease and omission of surgery following chemoradiotherapy in locally advanced disease varied with increasing age (odds ratio&gt;75vs&lt;50: 2.17, 95% confidence interval 1.54–3.06) and treatment region (Southwest and Northwest odds ratio 0.63, 95% confidence interval 0.42–0.93 and odds ratio 0.65, 95% confidence interval 0.44–0.95, respectively, compared with the North).Conclusion: Treatment patterns in non-metastasised rectal cancer significantly changed over time. Effects of both the national screening programme and the new treatment guideline were apparent, as well as a paradigm shift towards organ preservation (watch-and-wait). Observed regional variations may indicate adoption differences regarding new treatment strategies

Improvement of fatigue in generalised myasthenia gravis with zilucoplan

Background: Fatigue is a debilitating symptom of myasthenia gravis (MG). The impact of fatigue on MG can be assessed by Quality of Life in Neurological Disorders (Neuro-QoL) Short Form Fatigue scale. Transformation of raw Neuro-QoL fatigue scores to T-scores is a known approach for facilitating clinical interpretation of clinically meaningful and fatigue severity thresholds. Methods: In the Phase 3, double-blind, placebo-controlled RAISE study (NCT04115293), adults with acetylcholine receptor autoantibody-positive generalised MG (MG Foundation of America Disease Class II–IV) were randomised 1:1 to daily subcutaneous zilucoplan 0.3 mg/kg or placebo for 12 weeks. Patients completing RAISE could opt to receive zilucoplan 0.3 mg/kg in an ongoing, open-label extension study, RAISE-XT (NCT04225871). In this post-hoc analysis, we evaluated the long-term effect of zilucoplan on fatigue in RAISE patients who entered RAISE-XT. We report change in Neuro-QoL Short Form Fatigue T-scores and fatigue severity levels from RAISE baseline to Week 60. Results: Mean Neuro-QoL Short Form Fatigue T-scores improved from baseline to Week 12 in the zilucoplan group (n = 86) with a clinically meaningful difference versus placebo (n = 88; least squares mean difference: − 3.61 (nominal p-value = 0.0060]), and these improvements continued further to Week 60. At Week 12, more patients on zilucoplan (n = 34, 47.2%) experienced improvements in ≥ 1 fatigue severity level from baseline versus placebo (n = 23, 28.4%; p = 0.017). At Week 60, most (n = 55, 65.5%) patients had mild fatigue or none. Conclusion: Treatment with zilucoplan demonstrated statistical and clinically meaningful improvements in fatigue scores and severity versus placebo during RAISE, which were sustained to Week 60 in RAISE-XT

Long-term musculoskeletal function after Open Pelvic ring fractures in Children (OPEC); a multicentre, retrospective case series with follow-up measurement

Background: The proportion of Open Pelvic fractures in the paediatric population is relatively high. While operative fixation is the primary approach for managing Open Pelvic fractures in adults, there is limited literature on treatment outcomes in Children, particularly regarding long-term musculoskeletal, neurological, and urogenital function. Methods: This multicentre case series included paediatric patients (&lt;18 years old) with Open Pelvic ring fractures treated at one of two major trauma centres in the Netherlands between January 1, 2001 and December 31, 2021. Data collection involved clinical records and long-term assessments, including musculoskeletal function, growth disorders, urogenital function, sexual dysfunction, and sensory motor function. Results: A total of 11 patients were included, primarily females (73 %), with a median age at trauma of 12 years (P25–P75 7–14). Most patients had unstable Pelvic ring fractures resulting from high-energy trauma. Surgical interventions were common, with external fixation as the main initial surgical approach (n = 7, 70 %). Complications were observed in eight (73 %) patients. Musculoskeletal function revealed a range of issues in the lower extremity, daily activities, and mental and emotional domain. Long-term radiologic follow-up showed high rates of Pelvic malunion (n = 7, 64 %). Neurological function assessment showed motor and sensory function impairment in a subset of patients. Urogenital function was moderately affected, and sexual dysfunction was limited with most respondents reporting no issues. Conclusion: Paediatric Open Pelvic fractures are challenging injuries associated with significant short-term complications and long-term musculoskeletal and urogenital issues. Further research is needed to develop tailored treatment strategies and improve outcomes of these patients.</p

Update of the Minimum Information About BIobank Data Sharing (MIABIS) Core Terminology to the 3^rd Version

Introduction: The Minimum Information About BIobank Data Sharing (MIABIS) is a biobank-specific terminology enabling the sharing of biobank-related data for different purposes across a wide range of database implementations. After 4 years in use and with the first version of the individual-level MIABIS component Sample, Sample donor, and Event, it was necessary to revise the terminology, especially to include biobanks that work more in the data domain than with samples.Materials &amp; Methods: Nine use-cases representing different types of biobanks, studies, and networks participated in the development work. They represent types of data, specific sample types, or levels of organization that were not included earlier in MIABIS. To support our revision of the Biobank entity, we conducted a survey of European biobanks to chart the services they provide. An important stakeholder group for biobanks include researchers as the main users of biobanks. To be able to render MIABIS more researcher-friendly, we collected different sample/data requests to analyze the terminology adjustment needs in detail. During the update process, the Core terminology was iteratively reviewed by a large group of experts until a consensus was reached.Results: With this update, MIABIS was adjusted to encompass data-driven biobanks and to include data collections, while also describing the services and capabilities biobanks offer to their users, besides the retrospective samples. The terminology was also extended to accommodate sample and data collections of nonhuman origin. Additionally, a set of organizational attributes was compiled to describe networks.Discussion: The usability of MIABIS Core v3 was increased by extending it to cover more topics of the biobanking domain. Additionally, the focus was on a more general terminology and harmonization of attributes with the individual-level entities Sample, Sample donor, and Event to keep the overall terminology minimal. With this work, the internal semantics of the MIABIS terminology was improved

Association between prehospital end-tidal carbon dioxide levels and mortality in patients with suspected severe traumatic brain injury

Purpose: Severe traumatic brain injury is a leading cause of mortality and morbidity, and these patients are frequently intubated in the prehospital setting. Cerebral perfusion and intracranial pressure are influenced by the arterial partial pressure of CO2 and derangements might induce further brain damage. We investigated which lower and upper limits of prehospital end-tidal CO2 levels are associated with increased mortality in patients with severe traumatic brain injury. Methods: The BRAIN-PROTECT study is an observational multicenter study. Patients with severe traumatic brain injury, treated by Dutch Helicopter Emergency Medical Services between February 2012 and December 2017, were included. Follow-up continued for 1 year after inclusion. End-tidal CO2 levels were measured during prehospital care and their association with 30-day mortality was analyzed with multivariable logistic regression. Results: A total of 1776 patients were eligible for analysis. An L-shaped association between end-tidal CO2 levels and 30-day mortality was observed (p = 0.01), with a sharp increase in mortality with values below 35 mmHg. End-tidal CO2 values between 35 and 45 mmHg were associated with better survival rates compared to &lt; 35 mmHg. No association between hypercapnia and mortality was observed. The odds ratio for the association between hypocapnia (&lt; 35 mmHg) and mortality was 1.89 (95% CI 1.53–2.34, p &lt; 0.001) and for hypercapnia (≥ 45 mmHg) 0.83 (0.62–1.11, p = 0.212). Conclusion: A safe zone of 35–45 mmHg for end-tidal CO2 guidance seems reasonable during prehospital care. Particularly, end-tidal partial pressures of less than 35 mmHg were associated with a significantly increased mortality.</p

Epidemiology, Prehospital Characteristics and Outcomes of Severe Traumatic Brain Injury in The Netherlands:The BRAIN-PROTECT Study

Objective: A thorough understanding of the epidemiology, patient characteristics, trauma mechanisms, and current outcomes among patients with severe traumatic brain injury (TBI) is important as it may inform potential strategies to improve prehospital emergency care. The aim of this study is to describe the prehospital epidemiology, characteristics and outcome of (suspected) severe TBI in the Netherlands. Methods: The BRAIN-PROTECT study is a prospective observational study on prehospital management of patients with severe TBI in the Netherlands. The study population comprised all consecutive patients with clinical suspicion of TBI and a prehospital GCS score ≤ 8, who were managed by one of the 4 Helicopter Emergency Medical Services (HEMS). Patients were followed-up in 9 trauma centers until 1 year after injury. Planned sub-analyses were performed for patients with “confirmed” and “isolated” TBI. Results: Data from 2,589 patients, of whom 2,117 (81.8%) were transferred to a participating trauma center, were analyzed. The incidence rate of prehospitally suspected and confirmed severe TBI were 3.2 (95% CI: 3.1;3.4) and 2.7 (95% CI: 2.5;2.8) per 100,000 inhabitants per year, respectively. Median patient age was 46 years, 58.4% were involved in traffic crashes, of which 37.4% were bicycle related. 47.6% presented with an initial GCS of 3. The median time from HEMS dispatch to hospital arrival was 54 minutes. The overall 30-day mortality was 39.0% (95% CI: 36.8;41.2). Conclusion: This article summarizes the prehospital epidemiology, characteristics and outcome of severe TBI in the Netherlands, and highlights areas in which primary prevention and prehospital care can be improved

Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations

Palivizumab utilization, compliance, and outcomes were examined in infants with preexisting medical diseases within the Canadian Registry Database (CARESS) to aid in developing guidelines for potential “at-risk” infants in the future. Infants who received ≥1 dose of palivizumab during the 2006–2010 respiratory syncytial virus (RSV) seasons at 29 sites were recruited and utilization, compliance, and outcomes related to respiratory infection/illness (RI) events were collected monthly. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for premature infants ≤35 completed weeks gestational age (GA) who met standard approval criteria (group 1) compared to those with medical disorders (group 2) using Cox proportional hazards regression models with adjustment for potential confounding factors. Of 7,339 registry infants, 4,880 were in group 1 and 952 in group 2, which included those with Down syndrome (20.3%), upper airway anomalies (18.7%), pulmonary diseases (13.3%), and cystic fibrosis (12.3%). Group 2 were older at enrolment (10.2 ± 9.2 vs. 3.5 ± 3.1 months, p < 0.0005), had higher GA (35.9 ± 6.0 vs. 31.0 ± 5.4 weeks, p < 0.0005), and were less compliant with treatment intervals (69.4% vs. 72.6%, p = 0.048). A greater proportion of group 2 infants were hospitalized for RI (9.0% vs. 4.2%, p < 0.0005) and RSV (2.4% vs. 1.3%, p = 0.003) (unadjusted). Being in group 2 was associated with an increased risk of RI (HR = 2.0, 95%CI 1.5–2.5, p < 0.0005), but not RSV hospitalization (HR = 1.6, 95%CI 0.9–2.8, p = 0.106). In infants receiving palivizumab, those with underlying medical disorders, though not currently approved for prophylaxis, are at higher risk for RI events compared with preterm infants. However, risk of RSV hospitalizations is similar