Tecnologias em saúde da hanseníase no âmbito da Atenção Primária à Saúde: revisão de escopo / Leprosy health technologies in Primary Health Care: a scoping review / Tecnologías en salud de la lepra en el ámbito de la Atención Primaria a la Salud: revisión del alcance

Objetivo: mapear as tecnologias em saúde para manejo no cuidado à pessoa com hanseníase na Atenção Primária à Saúde. Método: revisão de escopo baseada na metodologia do JBI, em seis bases de dados, seguindo a checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Foram incluídos estudos publicados em qualquer idioma, com diferentes abordagens metodológicas. Resultados: os 14 estudos incluídos na revisão mostram que a aplicabilidade de tecnologias para o manejo do cuidado a pessoa com hanseníase na Atenção Primária à Saúde, possibilitam a confirmação de diagnóstico, acompanhamento, monitoramento e prevenção de incapacidades. Conclusão: nota-se que tecnologia em saúde se apresentam como ferramentas que auxiliam no processo de cuidado na assistência a pessoas com hanseníase, a fim de permitir aos profissionais de saúde conhecimento sobre a doença, proporcionando qualidade na sua prática de saúde.

Objective: to map health technologies for managing the care of people with leprosy in Primary Health Care. Method: scoping review based on the JBI methodology in six databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Studies published in any language were included, with different methodological approaches. Results: the 14 studies included in the review show that the applicability of technologies for the management of care for people with leprosy in Primary Health Care makes it possible to confirm diagnosis, follow-up, monitoring, and prevention of disabilities. Conclusion: it has been noted that health technologies are tools that help in the process of caring for people with leprosy, to provide health professionals with knowledge about the disease, improving quality of health practice.

Objetivo: mapear las tecnologías en salud para el manejo en el cuidado a la persona con lepra en la Atención Primaria a la Salud. Método: revisión del alcance basada en la metodología del JBI, en seis bases de datos, siguiendo la checklist Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Se han incluido estudios publicados en cualquier idioma, con diferentes enfoques metodológicos. Resultados: los 14 estudios incluidos en la revisión muestran que la aplicabilidad de tecnologías para el manejo del cuidado a la persona con lepra en la Atención Primaria a la Salud posibilita la confirmación de diagnóstico, seguimiento, monitoreo y prevención de incapacidades. Conclusión: se percibe que las tecnologías en salud se presentan como herramientas que ayudan en el proceso de cuidado en la asistencia a personas con lepra, con fines de permitir a los profesionales de salud el acceso al conocimiento sobre la enfermedad, proporcionando calidad en su práctica de salud.

Biomonitoring of firefighters' exposure to priority pollutant metal(loid)s during wildland fire combat missions: Impact on urinary levels and health risks.

Wildland firefighters are exposed to metal(loid)s released during wildfires through vegetation combustion, which also promotes remobilization of accumulated anthropogenic metal(loid)s. Studies biomonitoring metal(loid)s exposure promoted exclusively by wildfire suppression activities are lacking. This work aimed to characterize, for the first time, the impact of real-life wildland firefighting operations on urinary levels of priority pollutant metal(loid)s [14 included in ATSDR, 11 in USEPA, and 4 in Human Biomonitoring for Europe Initiative priority lists] in firefighters. Spot urines were sampled pre-exposure (105 non-smokers, 76 smokers) and post-exposure to firefighting activities (20 non-smokers, 25 smokers); among those, paired samples were collected from 14 non-smoking and 24 smoking firefighters. Smokers displayed significantly higher baseline levels of zinc (28 %), lithium (29 %), cadmium (55 %), rubidium (13 %), and copper (20 %) than non-smokers. Following wildfire suppression, the concentration of the WHO potentially toxic metal(loid)s rose from 2 % to 3 % in smokers and 2 % to 5 % in non-smokers (up to 4 % for all firefighters and up to 5 % in paired samples). Levels of nickel (33-53 %), antimony (45-56 %), and cesium (40-47 %) increased significantly post-exposure in non-smokers (in all firefighters and in paired samples), whose urinary concentrations were generally more impacted by wildfire emissions than those of smokers. Arsenic (80 %) displayed the only significant increase post-exposure in smokers, being the best discriminant of exposure to wildfire emissions in these subjects. Significant positive correlations were found for age and/or career length with cadmium, lead, barium, strontium, and mercury, and for body mass index with arsenic. The reference/guidance values were exceeded for arsenic, zinc, cesium, nickel, antimony, cadmium, lead, thallium, mercury, copper, and cobalt in 1-90 % of firefighters suggesting augmented health risks due to wildfire combating and emphasizing the need of mitigation strategies. This study also provides biomonitoring data to help setting reference values for the occupationally exposed part of population.

Biomechanical Evaluation of an Atraumatic Polymer-assisted Peripheral Nerve Repair System Compared with Conventional Neurorrhaphy Techniques.

Background: Microsuturing, the gold standard for peripheral nerve repair, can create tension and damage at the repair site, potentially impacting regeneration and causing neuroma formation. A sutureless and atraumatic polymer-assisted system was developed to address this challenge and support peripheral nerve repair. The system is based on a biocompatible and biodegradable biosynthetic polymer and consists of a coaptation chamber and a light-activated polymer for securing to the nerve. In this study, we compare the system's biomechanical performance and mechanism of action to microsutures and fibrin repairs. Methods: The system's fixation force was compared with microsutures and fibrin glue, and evaluated across various nerve diameters through tensile testing. Tension and tissue morphology at the repair site were assessed using finite element modeling and scanning electron microscopy. Results: The fixation force of the polymer-assisted repair was equivalent to microsutures and superior to fibrin glue. This force increased linearly with nerve diameter, highlighting the correlation between polymer surface contact area and performance. Finite element modeling analysis showed stress concentration at the repair site for microsuture repairs, whereas the polymer-assisted repair dissipated stress along the nerve, away from the repair site. Morphological analysis revealed nerve alignment with no tissue trauma for the polymer-assisted repair, unlike microsutures. Conclusions: The mechanical performance of the polymer-assisted coaptation system is suitable for peripheral nerve repair. The achieved fixation forces are equivalent to those of microsutures and superior to fibrin glue, minimizing stress concentration at the repair site and avoiding trauma to the severed nerve ends.

A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid ß (Aß)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage. Among these, a TAT-TrkB peptide with a lysine-lysine linker prevented TrkB-FL cleavage both in vitro and in vivo and rescued synaptic deficits induced by oligomeric Aß in hippocampal slices. Furthermore, this TAT-TrkB peptide improved the cognitive performance, ameliorated synaptic plasticity deficits and prevented Tau pathology progression in vivo in the 5XFAD mouse model of AD. No evidence of liver or kidney toxicity was found. We provide proof-of-concept evidence for the efficacy and safety of this therapeutic strategy and anticipate that this TAT-TrkB peptide has the potential to be a disease-modifying drug that can prevent and/or reverse cognitive deficits in patients with AD.

Real-world data on adjuvant capecitabine after standard neoadjuvant chemotherapy for triple negative breast cancer.

Objective: Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with triple-negative breast cancer (TNBC) with tumors > 1 cm or positive axillary nodes. Pathologic complete response (pCR) has been used as an endpoint to select patients for treatment scaling. This study aimed to examine the benefit of adding adjuvant capecitabine for TNBC patients who did not achieve pCR after standard NACT in a real-world scenario. Methods: This retrospective cohort study included all patients with TNBC who underwent NACT between 2010 and 2020. Clinicopathological data were obtained from the patient records. Univariate and multivariate analyses were conducted at the 5 years follow-up period. Results: We included 153 patients, more than half of whom had stage III (58.2%) and high-grade tumors (60.8%). The overall pCR rate was 34.6%, and 41% of the patients with residual disease received adjuvant capecitabine. Disease-specific survival (DSS) among the patients who achieved pCR was significantly higher (p<0.0001). Residual disease after NACT was associated with detrimental effects on DSS. In this cohort, we did not observe any survival benefit of adding adjuvant capecitabine for patients with TNBC subjected to NACT who did not achieve pCR (p=0.52). Conclusion: Our study failed to demonstrate a survival benefit of extended capecitabine therapy in patients with TNBC with residual disease after NACT. More studies are warranted to better understand the indication of systemic treatment escalation in this scenario.

Nanoscale Imaging and Measurements of Grain Boundary Thermal Resistance in Ceramics with Scanning Thermal Wave Microscopy.

Material thermal conductivity is a key factor in various applications, from thermal management to energy harvesting. With microstructure engineering being a widely used method for customizing material properties, including thermal properties, understanding and controlling the role of extended phonon-scattering defects, like grain boundaries, is crucial for efficient material design. However, systematic studies are still lacking primarily due to limited tools. In this study, we demonstrate an approach for measuring grain boundary thermal resistance by probing the propagation of thermal waves across grain boundaries with a temperature-sensitive scanning probe. The method, implemented with a spatial resolution of about 100 nm on finely grained Nb-substituted SrTiO3 ceramics, achieves a detectability of about 2 × 10-8 K m2 W-1, suitable for chalcogenide-based thermoelectrics. The measurements indicated that the thermal resistance of the majority of grain boundaries in the STiO3 ceramics is below this value. While there are challenges in improving sensitivity, considering spatial resolution and the amount of material involved in the detection, the sensitivity of the scanning probe method is comparable to that of optical thermoreflectance techniques, and the method opens up an avenue to characterize thermal resistance at the level of single grain boundaries and domain walls in a spectrum of microstructured materials.

Emerging trends on the uptake of fluorescent probes based on glucose analogs by cancer cells: From basic studies to therapeutics.

The cancer cell metabolism, notably characterized by the Warburg effect, has been the focus of intense investigation regarding the mechanisms of the uptake of glucose analogs, opening up perspectives for diagnosis and treatment of cancer disease. In this review, we delve into the ever-evolving landscape of cancer research, centering on fluorescent probes based on glucose analogs. These analogs, resulting from modifications in the carbohydrate structure with functional groups, have stood out as versatile molecules in applications ranging from disease comprehension to therapeutic innovation, especially when combined with fluorescent compounds. Fluorescence-based assays have provided valuable contributions to the revelation of complex biological mechanisms in life sciences. This review presents selected studies from about the past six years up to 2024 related to the use of glucose-based fluorescent probes, for the investigation of their uptake profile as well as for therapeutic purposes. We believe that these investigations offer insights into the intricate interaction between glucose analogs and cancer cell metabolism, guiding future research and clinical applications in this field.

Metabolomic Profiling of Adipose Tissue in Type 2 Diabetes: Associations with Obesity and Insulin Resistance.

The global prevalence of Type 2 Diabetes (T2D) poses significant public health challenges due to its associated severe complications. Insulin resistance is central to T2D pathophysiology, particularly affecting adipose tissue function. This cross-sectional observational study investigates metabolic alterations in subcutaneous adipose tissue (SAT) associated with T2D to identify potential therapeutic targets. We conducted a comprehensive metabolomic analysis of SAT from 40 participants (20 T2D, 20 ND-T2D), matched for sex, age, and BMI (Body Mass Index). Metabolite quantification was performed using GC/MS and LC/MS/MS platforms. Correlation analyses were conducted to explore associations between metabolites and clinical parameters. We identified 378 metabolites, including significant elevations in TCA cycle (tricarboxylic acid cycle) intermediates, branched-chain amino acids (BCAAs), and carbohydrates, and a significant reduction in the nucleotide-related metabolites in T2D subjects compared to those without T2D. Obesity exacerbated these alterations, particularly in amino acid metabolism. Adipocyte size negatively correlated with BCAAs, while adipocyte glucose uptake positively correlated with unsaturated fatty acids and glycerophospholipids. Our findings reveal distinct metabolic dysregulation in adipose tissue in T2D, particularly in energy metabolism, suggesting potential therapeutic targets for improving insulin sensitivity and metabolic health. Future studies should validate these findings in larger cohorts and explore underlying mechanisms to develop targeted interventions.

Identification and characterization of circulating and adipose tissue infiltrated CD20+T cells from subjects with obesity that undergo bariatric surgery.

T cells play critical roles in adipose tissue (AT) inflammation. The role of CD20+T cell in AT dysfunction and their contributing to insulin resistance (IR) and type 2 diabetes progression, is not known. The aim was to characterize CD20+T cells in omental (OAT), subcutaneous (SAT) and peripheral blood (PB) from subjects with obesity (OB, n = 42), by flow cytometry. Eight subjects were evaluated before (T1) and 12 months post (T2) bariatric/metabolic surgery (BMS). PB from subjects without obesity (nOB, n = 12) was also collected. Higher percentage of CD20+T cells was observed in OAT, compared to PB or SAT, in OB-T1. CD20 expression by PB CD4+T cells was inversely correlated with adiposity markers, while follicular-like CD20+T cells were positively correlated with impaired glucose tolerance (increased HbA1c). Notably, among OB-T1, IR establishment was marked by a lower percentage and absolute number of PB CD20+T cells, compared nOB. Obesity was associated with higher percentage of activated CD20+T cells; however, OAT-infiltrated CD20+T cells from OB-T1 with diabetes displayed the lowest activation. CD20+T cells infiltrating OAT from OB-T1 displayed a phenotype towards IFN-γ-producing Th1 and Tc1 cells. After BMS, the percentage of PB CD4+CD20+T cells increased, with reduced Th1 and increased Th17 phenotype. Whereas in OAT the percentage of CD20+T cells with Th1/17 and Tc1/17 phenotypes increased. Interestingly, OAT from OB pre/post BMS maintained higher frequency of effector memory CD20+T cells. In conclusion, CD20+T cells may play a prominent role in obesity-related AT inflammation.

The parkin V380L variant is a genetic modifier of Machado-Joseph disease with impact on mitophagy.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative spinocerebellar ataxia caused by a polyglutamine-coding CAG repeat expansion in the ATXN3 gene. While the CAG length correlates negatively with the age at onset, it accounts for approximately 50% of its variability only. Despite larger efforts in identifying contributing genetic factors, candidate genes with a robust and plausible impact on the molecular pathogenesis of MJD are scarce. Therefore, we analysed missense single nucleotide polymorphism variants in the PRKN gene encoding the Parkinson's disease-associated E3 ubiquitin ligase parkin, which is a well-described interaction partner of the MJD protein ataxin-3, a deubiquitinase. By performing a correlation analysis in the to-date largest MJD cohort of more than 900 individuals, we identified the V380L variant as a relevant factor, decreasing the age at onset by 3 years in homozygous carriers. Functional analysis in an MJD cell model demonstrated that parkin V380L did not modulate soluble or aggregate levels of ataxin-3 but reduced the interaction of the two proteins. Moreover, the presence of parkin V380L interfered with the execution of mitophagy-the autophagic removal of surplus or damaged mitochondria-thereby compromising cell viability. In summary, we identified the V380L variant in parkin as a genetic modifier of MJD, with negative repercussions on its molecular pathogenesis and disease age at onset.

Folic-Acid-Conjugated Poly (Lactic-Co-Glycolic Acid) Nanoparticles Loaded with Gallic Acid Induce Glioblastoma Cell Death by Reactive-Oxygen-Species-Induced Stress.

Glioblastoma (GBM) conventional treatment is not curative, and it is associated with severe toxicity. Thus, natural compounds with anti-cancer properties and lower systemic toxicity, such as gallic acid (GA), have been explored as alternatives. However, GA's therapeutic effects are limited due to its rapid metabolism, low bioavailability, and low permeability across the blood-brain barrier (BBB). This work aimed to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with folic acid (FA), as its receptor is overexpressed in BBB and GBM cells, for GA delivery to enhance its therapeutic efficacy. The preparation of NPs was optimized by a central composite design (CCD). The obtained NPs showed physicochemical features suitable for drug internalization in BBB and tumor cells (sizes below 200 nm, monodispersity, and negative surface charge) and the ability to maintain a slow and sustained release for 40 days. In vitro studies using a human GBM cell line (U215) revealed the NPs' ability to accumulate in the target cells, further promoting GA antiproliferative activity by inducing the production of intracellular reactive oxygen species (ROS). Furthermore, GA encapsulation in the developed nanosystems conferred higher protection to healthy cells.

The Global Impact of Multisystemic Vulnerabilities on Criminal Variety: A Cross-Continental Study in Young Adults.

Previous research has shown a robust association between different childhood and adolescent vulnerabilities and youth offending. However, these investigations have primarily focused on youths from high-income Western countries. Consequently, the generalizability of these findings to better inform global justice policies remains uncertain. This study aimed to address this gap by examining the relationship between individual, familial, and contextual vulnerabilities and criminal versatility during young adulthood, accounting for sociodemographic factors and cross-national differences. Data were derived from a diverse sample of 4,182 young adults (67% female; mean age = 18.96; SD = 0.81) residing in 10 countries across 5 continents who participated in the International Study of Pro/Antisocial Behavior in Young Adults. The Psychosocial and Family Vulnerability Questionnaire and the Adverse Childhood Experiences questionnaire were used to assess social and family adversity, and past-year criminal diversity was measured with the Criminal Variety Index. Results indicate that child maltreatment, substance abuse, and delinquent peers are global risk factors for criminal variety. Moreover, they are independent across males and females and among youths living in countries that are ranked differently on the Human Development Index (HDI). In addition, some childhood vulnerabilities showed different predictive ability across sexes (e.g., school failure), and across countries ranked differently on the HDI (e.g., family dysfunction). These findings suggest that certain childhood factors contribute to criminal behavior through transcultural mechanisms. Moreover, they highlight the importance of developing evidence-based policies that focus on transcultural risk factors to globally prevent criminal behavior.

Pressing issues for oral care quality improvement: findings from the EU DELIVER project.

BACKGROUND: While oral health often takes a backseat to other health domains, it silently affects nearly half of the Worldwide population. The DELIVER project, funded by the EU's Horizon Europe program, seeks to develop a blueprint model for improving the quality of oral health care for everyone. METHODS: Applying the Nominal Group Technique (NGT), 17 stakeholders from various backgrounds participated in identifying pressing issues for oral care quality improvement across practice, community, and policy levels. RESULTS: The results revealed significant differences at the different levels, with accessibility emerging as a prominent issue, encompassing affordability, availability, and acceptability of oral healthcare services. CONCLUSIONS: These findings emphasizes the need for policy reforms, increased investments, and a shift towards preventive and patient-centered dental care practices. It highlights the importance of collaborative efforts with multi-stakeholders and prioritizing pressing issues on a multi-level to drive positive change in improving oral care quality.

Renal sinus adipose tissue: exploratory study of metabolic features and transcriptome compared with omental and subcutaneous adipose tissue.

OBJECTIVE: The objective was to study metabolic characteristics and transcriptome of renal sinus adipose tissue (RSAT) located around renal arteries and veins. METHODS: Adipose tissue biopsies from RSAT, omental (OAT), and subcutaneous (SAT) depots were obtained from healthy kidney donors (20 female, 20 male). Adipocyte glucose uptake rate and cell size were measured, and gene expression analyses using transcriptomics were performed. RESULTS: RSAT adipocytes were significantly smaller, with a higher basal glucose uptake rate, than adipocytes from SAT and OAT. Transcriptomic analyses revealed 29 differentially expressed genes between RSAT and OAT (RSAT: 23 lower, 6 higher) and 1214 differentially expressed genes between RSAT and SAT (RSAT: 859 lower, 355 higher). RSAT demonstrated molecular resemblance to OAT, both exhibiting lower metabolic gene expression and higher expression of immune-related pathways, including IL-17, TNFα, and NF-κB signaling than SAT. Weighted gene coexpression network analysis associated RSAT with immune response and nucleic acid transport processes. Despite its location near the renal hilum, RSAT closely resembled OAT and there was a lack of expression in the classical brown adipose tissue genes. Gene enrichment analyses suggest an inflammatory environment in RSAT compared with SAT and, to some extent, OAT. CONCLUSIONS: The findings suggest specific RSAT functions that could impact renal function and, possibly, the development of renal and cardiometabolic disorders.

Association between Falls, Fear of Falling and Depressive Symptoms in Community-Dwelling Older Adults.

BACKGROUND: Longevity increases pose public health challenges, especially in managing falls and their psychological impacts on older adults. Limited evidence exists on the relationship between a fear of falling (FOF), previous falls, and depressive symptoms among community-dwelling older adults. OBJECTIVE: To evaluate the association between falls, FOF, and depressive symptoms in community-dwelling older adults. METHODS: This cross-sectional study, conducted in 2018, included 400 older adults from a Basic Health Unit in São Paulo, Brazil. The Geriatric Depression Scale (GDS-15) and the International Falls Efficacy Scale (FES-I) were used, along with self-report questionnaires on fall history. Linear and logistic regression were used to analyze the relationships between variables. RESULTS: The mean age was 75.2 (SD = 8.53) years, with 63.2% being female. Depressive symptoms were observed in 18.3% of the participants, while 90.5% reported a fear of falling (FOF). More than half (63.0%) experienced falls, with 49.5% occurring in the last year. Factors such as the female gender, negative health perceptions, and functional dependence were associated with depressive symptoms. Adjusted analyses indicated that both a fear of falling (FOF) (B = 0.043; p = 0.012) and a history of falls (B = 0.725; p = 0.015) were associated with depressive symptoms. CONCLUSIONS: Falls, FOF, and depressive symptoms are interlinked among older adults, underscoring the need for targeted interventions to improve their mental and physical health.

Comparative efficacy and safety of sodium fluorescein-guided surgery versus standard white light for resection of brain metastases: a systematic review and meta-analysis.

PURPOSE: Recent studies have investigated if the sodium fluorescein-guided (SFg) improves the extent of resection of BMs when compared to standard white light (sWL). Therefore, we aimed to assess the comparative efficacy and safety of SFg and sWL for resection of BMs. METHODS: We searched Medline, Embase, and Cochrane Library databases following Cochrane and PRISMA guidelines for studies reporting comparative data of SFg and WL resection of BMs. We pooled odds ratios (OR) with 95% confidence intervals under random effects and applied I² statistics and leave-one-out sensitivity analysis to assess heterogeneity. I² > 40% was considered significant for heterogeneity. RESULTS: Five studies involving 816 patients were included, of whom 390 underwent BMs resection with SFg and 426 with sWL, and ages ranging between 26 and 86.2 years old. Analysis revealed a statistically significant higher likelihood of complete resection in the SFg group when compared to the sWL group (OR = 2.15, 95%CI: 1.18-3.92, p = 0.01; I² = 47%). Sensitivity analysis revealed a consistent result in all five scenarios, with low heterogeneity in two of the five scenarios. Three studies reported significant improvement in OS in the SFg group, and the qualitative assessment of complications and procedure-related mortality did not provide sufficient information for conclusions. CONCLUSION: This systematic review and meta-analysis identified a higher likelihood of complete resection in the SFg group when compared to the standard sWL group. This study is the first to directly compare the impact of SFg and sWL on resection outcomes for BMs.

Limited access to transcranial Doppler screening and stroke prevention for children with sickle cell disease in Europe: Results of a multinational EuroBloodNet survey.

BACKGROUND: Ensuring equitable access to adequate standard of care for patients with rare hematological disease is one of the aims of the European Reference Network (ERN) EuroBloodNet. Stroke is one of the most devastating complications for children with sickle cell disease (SCD). For effective prevention of stroke risk, annual transcranial Doppler (TCD) according to a defined protocol is recommended for patients aged 2-16 years, with red blood cell transfusion therapy for those at risk. There is no information regarding screening for stroke risk and stroke prevention programs in Europe. METHODS: Seven SCD experts of five healthcare providers (HCPs) of ERN EuroBloodNet developed an online survey to assess the access to TCD screening and stroke prevention programs for children with SCD in Europe. RESULTS: Eighty-one experts in 77 HCPs from 16 European countries responded to 16 online questions. Thirty-two of 77 (51%) HCPs were EuroBloodNet reference centers, and 36% physicians reported not having a dedicated TCD/TCD imaging service for children with SCD. Only 30% of physicians provided estimates that all their patients received annual TCD according to the standard protocol due to lack of trained staff (43%), lack of TCD instruments (11%), refusal of patients due to logistical difficulties (22%), and lack of funds for dedicated staff or equipment (11%). CONCLUSIONS: This multinational European survey provides the first comprehensive picture of access to TCD screening and stroke prevention in European countries. Identifying the potential underlying causes of the lack of effective standardized screening, this survey also addresses possible dedicated actions to cover these needs.

Adverse skeletal related events in patients with bone-metastatic pheochromocytoma/paraganglioma.

Metastatic pheochromocytomas and paragangliomas (PPGLs) are frequently associated with skeletal complications. Primary objective: to describe the frequency of adverse skeletal related events (SREs) in PPGL patients with bone metastases (BMs). Secondary objectives: to 1) identify predictive and prognostic factors for SREs and 2) obtain information on the effectiveness of bone resorption inhibitors in reducing SRE risk and improving outcomes in term of survival and SREs time onset. In this retrospective multicenter, multinational study, 294 PPGL patients were enrolled. SREs occurred in 90 patients (31 %). Fifty-five patients (19 %) had bone fractures, 47 (16 %) had spinal cord compression, and 11 (4 %) had hypercalcemia. Twenty-two patients (7 %) had more than one SRE. Sixty-four patients (22 %) underwent surgery, and 136 (46 %) underwent radiotherapy. SREs occurred a median of 4.4 months after diagnosis of BM (range, 0-246.6 months). Independent factors associated with reduced risk of SREs in multivariable analysis were I-131-MIBG radionuclide therapy (hazard ratio [HR], 0.536 [95 % CI, 0.309-0.932]; P = .027) and absence of liver metastases (HR, 0.638 [95 % CI, 0.410-0.992]; P = .046). The median overall survival duration was 5.3 year. In multivariable analysis, age younger than 48 years at PPGL diagnosis (HR, 0.558 [95 % CI, 0.3877-0.806]; P = .002), absence of liver metastases (HR, 0.618 [95 % CI, 0.396-0.965]; P = .034), treatment with bisphosphonates or denosumab (HR, 0.598 [95 % CI, 0.405-0.884]; P = .010), and MIBG radionuclide therapy (HR, 0.444 [95 % CI, 0.274-0.718]; P = .001) were associated with a reduced risk of death. SREs occur frequently and early in bone-metastatic PPGL patients but do not negatively impact survival. MIBG radionuclide therapy and treatment with bone resorption inhibitors are associated with favorable outcome.