Awareness of bone strength in patients with neuromuscular disorders: ERN EURO-NMD clinician survey and European patient survey

Bone strength is reduced In various neuromuscular disorders (NMDs). We aimed to assess the awareness and practice of bone strength management in NDMs among clinicians and patients. We performed two online surveys; among health care providers (HCPs) of the European Reference Network for Neuromuscular Disorders (ERN EURO-NMD) and among patients. The survey among 52 HCPs showed that awareness of potentially impaired bone strength in people with NMDs was reasonable to good: the vast majority of HCPs asked often or almost always about bone fractures during history-taking (81 %). Bone strength was less often assessed: often or almost always at diagnosis (50 %) and at follow-up (58 %). Medical training on this topic was considered poor to very poor in 50 % of HCPs. Prevention and treatment of reduced bone strength was variable and multidisciplinary care was sub-optimal. The survey among 581 patients provided important additional insights. Many patients were followed-up outside ERN EURO-NMD centers and treatment was variable. These parallel surveys provided a broad view on the awareness and management of bone strength in people with NMDs. The findings are expected to increase the appreciation of this important aspect of NMD care, and direct future research foci and care guidelines

Trachelectomy and Cerclage Placement as Fertility-Sparing Surgery for Cervical Cancer-An Expert Survey

Background/Objectives: Fertility-sparing surgery (FSS) is a standard practice for managing early stage cervical cancer, yet significant variation exists in clinical approaches worldwide. Our objective was to ascertain current practices and preferences for cerclage use among expert centers globally regarding FSS in patients with early stage cervical cancer. Methods: We conducted a cross-sectional survey from May to July 2023 involving expert centers identified through their scientific contributions and participation in international workgroups and conferences.. The survey, comprising 27 questions, evaluated existing practices in FSS. Results: Out of the centers surveyed, 21 (36.2%) gynecologic oncologists responded. For tumors 2 cm, 47.6% utilized neoadjuvant chemotherapy before trachelectomy. Others did not offer FSS or performed an abdominal radical trachelectomy. Over time, there has been a shift towards less radical surgeries for tumors <2 cm and increased use of neoadjuvant chemotherapy for larger tumors. Some abandoned the minimally invasive surgical approach. Nearly all experts (90.5%) placed a cerclage immediately following trachelectomy. Conclusions: The majority of experts opt for radical trachelectomy in early stage cervical cancer, with immediate cerclage placement being a common practice. However, considerable international variations highlight the urgent need for standardized guidelines and further research to optimize treatment strategies, balancing oncological safety with fertility outcomes

Absolute measurement of fast and slow neuronal signals with fluorescence lifetime photometry at high temporal resolution

The concentrations of extracellular and intracellular signaling molecules, such as dopamine and cAMP, change over both fast and slow timescales and impact downstream pathways in a cell-type specific manner. Fluorescence sensors currently used to monitor such signals in vivo are typically optimized to detect fast, relative changes in concentration of the target molecule. They are less well suited to detect slowly-changing signals and rarely provide absolute measurements of either fast and slow signaling components. Here, we developed a system for fluorescence lifetime photometry at high temporal resolution (FLIPR) that utilizes frequency-domain analog processing to measure the absolute fluorescence lifetime of genetically-encoded sensors at high speed but with long-term stability and picosecond precision in freely moving mice. We applied FLIPR to investigate dopamine signaling in two functionally distinct regions in the striatum, the nucleus accumbens core (NAC) and the tail of striatum (TOS). We observed higher tonic dopamine levels at baseline in the TOS compared to the NAC and detected differential and dynamic responses in phasic and tonic dopamine to appetitive and aversive stimuli. Thus, FLIPR enables simple monitoring of fast and slow time-scale neuronal signaling in absolute units, revealing previously unappreciated spatial and temporal variation even in well-studied signaling systems

Sexuality and bleeding in von Willebrand disease

Background: Sexuality is a fundamental aspect of quality of life, often impacted by chronic or inherited diseases like von Willebrand disease (VWD), an inherited bleeding disorder characterized by mucosal bleeding, including heavy menstrual bleeding (HMB). To date, no studies have investigated the impact of VWD on sexuality. Objectives: This study aimed to identify sexual restrictions and symptoms in VWD patients, differentiating between men and women and between premenopausal and nonmenstruating women. Methods: We performed a nationwide, multicenter, prospective cohort study, the Willebrand in the Netherlands-Prospective study, including adult VWD patients (>18 years) who completed questionnaires on sexuality and health-related quality of life (SF-36). Additional data were collected via blood tests and a self-reported bleeding assessment tool (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool). Results: We included 549 VWD patients with a median age of 51 years (IQR, 37-66 years), of whom the majority were women (n = 347; 63.2%). Patients were diagnosed with type 1 (57.2%), type 2 (39.2%), or type 3 VWD (3.6%). Sexual restrictions due to VWD were reported by 3.5% of men (n = 7) and 9.8% of women (n = 34; P < .01). Bleeding during sexual activity was reported by 33.1% (n = 115) of women. Premenopausal patients more often reported sexual restrictions than nonmenstruating patients (15.5% vs 5.2%, P = .01), with HMB as the most important determinant (odds ratio, 1.60; 95% CI, 1.12-2.46). Most patients (n = 455; 82.9%) reported that sexuality was not discussed during routine clinic visits. Conclusion: Women with VWD experience more sexual restrictions than men and report more postcoital bleeding than the general population. Premenopausal women are particularly affected, mostly due to HMB. This highlights the need for health care providers to address sexual health during consultations and treat HMB to improve overall care for VWD patients

The road to successful implementation of innovation in radiotherapy: A research-based implementation protocol

Background and purpose: Radiotherapy (RT) is rapidly advancing, yet only 50 % of innovations are implemented promptly. Despite the availability of Implementation Science (ImpSci) theories, models, and frameworks (TMFs), a theory–practice gap persists in effectively applying these insights in RT clinical practice. This study aims to develop a consensus-based implementation protocol for RT innovations using validated ImpSci knowledge. Material and methods: A literature review of TMFs (May–August 2023) and 20 semi-structured interviews with Dutch RT professionals (August–December 2023) identified key RT components for implementation. These insights informed a draft RT implementation protocol, which was refined through a three-round international Delphi study (March–September 2024) involving 11 RT and 5 ImpSci experts. Consensus was determined using a 5-point Likert scale, analysing medians, interquartile ranges (IQRs), and percentage scoring. Results: The Knowledge-to-Action (KTA) Framework and input from expert interviews were used to draft the protocol. Delphi response rates were 100 %, 93.8 %, and 88.9 % across rounds. In round 1, 88.9 % of elements achieved consensus (median = 4.0, IQR = 0.0–1.3); only the application of a prediction model for timely implementation (step 3c) needed revision after rounds 1 and 2. In round 3, also for step 3c consensus was reached (median = 4.0, IQR = 0.3). The protocol includes defining innovation types, stakeholder analysis, tailored implementation strategies, and a phased evaluation plan to ensure sustainability. Conclusion: This is the first consensus-based RT innovation implementation protocol, addressing the theory–practice gap with a structured clinical approach. Future research should validate the protocol and assess the impact of preparation on implementation success

Proof-of-principle of a technology transfer of a dried blood virus neutralisation assay to a Gavi-eligible country

Background Global health clinical research is commonly led by high-income countries (HICs) as low- and middle-income countries (LMICs) face barriers to participate, including lack of financial and human capacity and lack of research environment. Respiratory syncytial virus (RSV) vaccine development is also led by HICs, while LMICs carry the burden of life-threatening disease. Representative trials and research capacity strengthening in LMICs are needed to ensure global vaccine access and equity. This study aims to transfer an RSV neutralisation assay, which uses live cells and virus with inherent high variation, to a country eligible to receive support from the Gavi, the Vaccine Alliance. Methods Using a train-the-trainer approach, a Ghanaian researcher was trained in the Netherlands on the dried blood-based RSV neutralisation assay. Subsequently, a Dutch researcher visited Ghana to support the process of adapting the technique to the Ghanaian setting. In a previously validated RSV neutralisation assay on dried blood, Hep-2 cells were infected with a serial dilution of sample-virus mixture to determine the half-maximal inhibitory concentration. Fifty-one dried blood and serum samples were tested in parallel in both countries to assess concordance. Results Training and technology transfer was deemed successful, which was defined as neutralisation measurements by the Ghana team and high concordance (Lin's concordance correlation coefficient (CCC)>0.8). Neutralising capacity measured in identical samples in Ghana and the Netherlands correlated highly (Lin's CCC=0.87; Spearman rho=0.89) but was systematically lower in Ghana than the Netherlands. Conclusion We show successful transfer of an RSV neutralisation assay, thereby strengthening the laboratory research capacity in a Gavi-eligible country. Reliable measurement of RSV neutralising antibodies in a Gavi-eligible country and the use of dried blood can contribute to inclusion of LMICs in RSV vaccine development and access

Trauma room requirements

Effective shock (or trauma) room management requires thorough preparation, staff competence, dedicated infrastructure and organised protocols. Shock rooms must be sufficiently equipped according to the hospital's designated level of care. This chapter outlines essential aspects, including equipment and facilities, staff qualifications and composition, and communication practices. Key areas including initial assessment, diagnostic procedures, emergency interventions, and future aspects in the care of severely injured patients are addressed, along with emerging innovations in trauma care

Multimodal Imaging of Structural Damage and Inflammation in Psoriatic Arthritis: A comparison of DMARD-Naive and DMARD-Failure Patients

OBJECTIVES: To compare inflammatory and structural differences in active Psoriatic Arthritis (PsA) between disease-modifying antirheumatic drug (DMARD)-naive and DMARD-failure patients using diverse imaging approaches for future analyses. Additionally, to explore the influence of patient characteristics (clinical and demographic variables) on imaging findings. METHODS: Of the 80 patients included from the first cohort of the ongoing multicentre TOFA-PREDICT trial, 40 were DMARD-naive and 40 were DMARD-failure (csDMARD failure; 1 prior bDMARD excluding etanercept was allowed), all meeting classification criteria for PsA with a minimum disease duration of eight weeks. Baseline conventional radiographs of hands and feet, MRIs of both ankles, and whole-body 18F-FDG PET/CT were evaluated for inflammatory and structural imaging parameters, including Sharp-van der Heijde (SHS), Heel Enthesitis Magnetic Resonance Imaging Scoring System (HEMRIS) and Deauville synovitis scoring. Differences between groups and the influence of patient characteristics were examined with multiple linear regression. RESULTS: At baseline, patient characteristics were similar between groups. Imaging parameters showed limited inflammation and structural damage. Inflammatory imaging parameters were not significantly different (p> 0.200). Among structural parameters, only HEMRIS Achilles tendon structural damage was significantly different (p= 0.024, R2=0.071) and, SHS Joint Space Narrowing was not statistically significant (p= 0.050, R2=0.048) with higher values for both in DMARD-failures. After correction of patient characteristics, these differences in imaging disappeared (both p> 0.600). CONCLUSION: At baseline, PsA patient groups were comparable concerning structural and inflammatory imaging parameters, especially after correcting for patient characteristics. Thus, DMARD-naive and DMARD-failure patient groups may be combined in future PsA progression and treatment decision studies. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT: 2017-003900-28

Clinical features and outcomes in carriers of pathogenic desmoplakin variants

Background and Aims: Pathogenic variants in the desmoplakin (DSP) gene are associated with the development of a distinct arrhythmogenic cardiomyopathy phenotype not fully captured by either dilated cardiomyopathy (DCM), non-dilated left ventricular cardiomyopathy (NDLVC), or arrhythmogenic right ventricular cardiomyopathy (ARVC). Prior studies have described baseline DSP cardiomyopathy genetic, inflammatory, and structural characteristics. However, cohort sizes have limited full clinical characterization and identification of clinical and demographic predictors of sustained ventricular arrhythmias (VAs), heart failure (HF) hospitalizations, and transplant/death. In particular, the relevance of acute myocarditis-like episodes for subsequent disease course is largely unknown. Methods: All patients with pathogenic/likely pathogenic (P/LP) DSP variants in the worldwide DSP-ERADOS Network (26 academic institutions across nine countries) were included. The primary outcomes were the development of sustained VA and HF hospitalizations during follow-up. Fine-Gray regressions were used to test association between clinical and instrumental parameters and the development of outcomes. Results: Eight hundred patients [40.3 ± 17.5 years, 47.5% probands, left ventricular ejection fraction (LVEF) 49.5 ± 13.9%] were included. Over 3.7 [1.4-7.1] years, 139 (17.4%, 3.9%/year) and 72 (9.0%, 1.8%/year) patients experienced sustained VA and HF episodes, respectively. A total of 32.5% of individuals did not fulfil diagnostic criteria for ARVC, DCM, or NDLVC; their VA incidence was 0.5%/year. In multivariable regression, risk features associated with the development of VA were female sex [adjusted hazard ratio (aHR) 1.547; P = .025], prior non-sustained ventricular tachycardia (aHR 1.721; P = .009), prior sustained VA (aHR 1.923; P = .006), and LVEF ≤ 50% (aHR: 1.645; P = .032), while for HF, they were the presence of T-wave inversion in 3+ electrocardiogram leads (aHR 2.036, P = .007) and LVEF ≤ 50% (aHR 3.879; P < .001). Additionally, 70 (8.8%) patients experienced a myocardial injury episode at presentation or during follow-up. These episodes were associated with an increased risk of VA and HF thereafter (HR 2.394; P < .001, and HR 5.064, P < .001, respectively). Conclusions: Patients with P/LP DSP variants experience high rates of sustained VA and HF hospitalizations. These patients demonstrate a distinct clinical phenotype (DSP cardiomyopathy), whose most prominent risk features associated with adverse clinical outcomes are the presence of prior non-sustained ventricular tachycardia or sustained VA, T-wave inversion in 3+ leads on electrocardiogram, LVEF ≤ 50%, and myocardial injury events

The differential impact of early graft dysfunction in kidney donation after brain death and after circulatory death: Insights from the Dutch National Transplant Registry

Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes. Using competing risk and Cox-regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within 7 days after transplantation), slow graft function (3-day plasma creatinine decline less than 10% per day), and immediate graft function. In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios: DGF in DBD: 1.79 [1.04-2.91], P = .027, DGF in DCD: 1.84 [1.18-2.87], P = .008; Reference: no DGF). Slow graft function was associated with death-censored graft loss in DBD, but not significantly in DCD (adjusted hazard ratios DBD: 2.82 (1.34-5.93), P = .007, and DCD: 1.54 (0.72-3.35), P = .262; Reference: immediate graft function). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic