This roadmap reviews CARDIO4Cities, a whole-of-city approach designed to reduce cardiovascular risk and disease at population level. As urbanization accelerates globally - with 68% of the global population projected to live in cities by 2050 - cities across income settings face a growing burden of cardiovascular disease, yet often lack operational models that translate evidence into scalable action. CARDIO4Cities responds to this gap by combining a simple, standardized population-health framework with locally adaptable implementation pathways that can be embedded within existing city systems. The approach is organized around six reinforcing pillars: quality and coordination of Care, Access to early diagnosis and management of cardiovascular risk factors, policy Reform, Data and technology, Intersectoral collaboration, and local Ownership. Rather than relying on new parallel infrastructures, CARDIO4Cities integrates evidence-based interventions into routine health services and leverages non-traditional community and private-sector actors, enabling replication across cities with varying levels of health-system maturity and resources. This document provides city health officials and their partners with a step-by-step implementation pathway, including governance structures, target-setting frameworks, intervention design processes, monitoring systems, and scaling strategies. Evaluations from the first three implementation cities-São Paulo (Brazil), Dakar (Senegal), and Ulaanbaatar (Mongolia)-demonstrated significant improvements in hypertension control and reductions in acute cardiovascular events within one to two years. Modeling projected that, without further CARDIO4Cities interventions, 2.7-7.9% of premature deaths would be averted over the subsequent decade, at costs meeting WHO-CHOICE cost-effectiveness thresholds. These results, achieved in diverse geographic, economic, and health-system contexts, illustrate the transferability of the model across income settings. Since standardization of the approach, CARDIO4Cities has expanded to more than 40 cities worldwide, including major cities in Europe and the Americas, equipping city leaders with operational guidance to implement evidence-based cardiovascular population health programs adapted to local contexts and resources. We position CARDIO4Cities as a replicable and scalable model for improving cardiovascular population health across diverse urban contexts, from resource-constrained cities initiating basic risk-factor detection to data-rich cities advancing toward precision population health.
To evaluate clinical and immunological characteristics associated with adverse perinatal outcomes among pregnant people living with HIV (PPLH). This retrospective cohort study included singleton pregnancies of PPLH followed between 2006 and 2019 at a Brazilian tertiary referral center for high-risk pregnancies. Clinical and HIV-related data, including viral load (VL), CD4+ cell count, lymphopenia, and opportunistic infections (OI), were obtained from medical records. The primary endpoint was a composite adverse perinatal outcome defined as preterm birth (PTB) and/or low birth weight (LBW). Multivariable logistic regression was performed to identify factors independently associated with adverse outcomes. A total of 167 pregnancies were analyzed. The prevalence of the composite adverse perinatal outcome was 28.1%. Adverse outcomes were associated with previous opportunistic infection (p = 0.049), gestational opportunistic infection (p = 0.019), higher baseline viral load (p = 0.049), baseline lymphopenia (p = 0.002), lower body mass index (p = 0.044), lower CD4 cell count at 34 weeks (p = 0.014), and lack of viral suppression at 34 weeks (p = 0.008). In multivariable analysis, baseline VL (adjusted OR = 1.73, 95% CI = 1.10-2.99) and baseline lymphopenia (adjusted OR = 7.67, 95% CI = 1.37-42.8) remained independently associated with adverse perinatal outcomes. Adverse perinatal outcomes remain frequent among PPLH. Baseline viral load and lymphopenia were independently associated with PTB and/or LBW, highlighting the importance of early viral suppression and immune stabilization during pregnancy.
The existing information supports the use of this material as described in this safety assessment. β-Naphthyl isobutyl ether was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Target data and data from read-across analog β-naphthyl methyl ether (CAS # 93-04-9) show that β-naphthyl isobutyl ether is not expected to be genotoxic. Data on β-naphthyl isobutyl ether provide a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity endpoint. Data on read-across analog β-naphthyl methyl ether (CAS # 93-04-9) provide a calculated MOE >100 for the reproductive toxicity endpoint. Data show that there are no safety concerns for β-naphthyl isobutyl ether for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; β-naphthyl isobutyl ether is not expected to be photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to β-naphthyl isobutyl ether is below the TTC (0.47 mg/day). The environmental endpoints were evaluated; β-naphthyl isobutyl ether was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients (RQs), based on its current volume of use (VoU) in Europe (EU), North America (NA), Asia-Pacific (AP), and South America (SA) (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.
To explore the correlations between endocrine-metabolic characteristics and body fat distribution, appetite, growth, and memory in children with Prader-Willi Syndrome (PWS). Forty-six children with PWS and forty-six with simple obesity were studied, alongside a healthy control group. Researchers measured physical development, hyperphagia, memory, hormone levels, and lipid profiles. They compared endocrine-metabolic differences across groups and examined correlations between these indicators and body fat, appetite, growth, and memory in children with PWS. The PWS group presented overweight, growth retardation, increased body fat, elevated hyperphagia scores and reduced memory scores relative to simple obesity and healthy control groups, with distinct plasma metabolic and endocrine profiles (higher ghrelin, Triglycerides [TG], Total Cholesterol [TC], Low-Density Lipoprotein Cholesterol [LDL-C], Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] and C-peptide; lower Insulin-like Growth Factor-1 [IGF-1], Triiodothyronine [T3], Thyroxine [T4], Thyroid-Stimulating Hormone [TSH] and High-Density Lipoprotein Cholesterol [HDL-C]). Correlation analyses confirmed positive associations of ghrelin, cortisol, and HOMA-IR with Fat Mass Index (FMI); of cortisol and HOMA-IR with hyperphagia score; of TSH, TG, HOMA-IR, and C-peptide with Body Mass Index (BMI); and of IGF-1 and T3 with memory score, as well as negative associations of IGF-1 with FMI and hyperphagia score; of HDL-C with BMI; and of ghrelin with memory score (all p < 0.05). Children with PWS present major endocrine-metabolic abnormalities associated with abnormal body fat, hyperphagia, growth retardation, and memory impairment, which help clarify multisystem damage in hereditary obesity and guide targeted clinical interventions.
Nonvolatile and polar fractions, largely composed of NSO heteroatom-containing compounds, play a key role in petroleum characterization by providing insights into organic geochemical parameters, such as thermal maturity and depositional environment, as well as physicochemical properties, including acidity and basicity. Electrospray ionization in the negative ion mode coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI(-) FT-ICR MS) applied to undisturbed whole oil samples has been established as a gold-standard technique for oil characterization, owing to its ability to directly ionize a broad range of polar compounds. However, the large volume and complexity of the resulting data pose significant challenges for data preprocessing, analysis, and visualization. In this study, we compared two distinct data preprocessing methodologies and show them to provide deeper insight into their application in FT-ICR MS petroleomics for inter-basin discrimination. We used lacustrine oils from two Brazilian Pre-salt basins as a case study.
The impact of government financial assistance and substance use is contested by 2 competing hypotheses: the "income effect" posits that cash transfers could facilitate substance consumption, while the "stress-relief hypothesis" posits that cash transfers alleviate poverty-related stress that contributes to substance use. We conducted a scoping review of 46 studies (2000-2025) evaluating US cash and near-cash safety net programs on substance use outcomes, following PRISMA-ScR guidance. Evidence was most robust for tax credits, the Earned Income Tax Credit and Child Tax Credit, reducing tobacco use, particularly among lower-educated mothers. Evidence was suggestive but design-limited for Unemployment Insurance buffering overdose mortality in contexts of job loss, as most studies were ecological. Findings on alcohol and opioid outcomes were generally limited or null. Restrictions in near-cash supports, including drug-felony bans on the Supplemental Nutrition Assistance Program, were associated with higher rates of opioid misuse and substance use disorders. Disbursement design also mattered: lump-sum disability payments and synchronous COVID-era stimulus disbursements were linked to short-term spikes in overdose mortality ("check effect"), while stable, smaller benefits supported treatment retention. The US safety net plays a meaningful role in substance-related outcomes, with evidentiary strength varying considerably by program and substance.
To estimate the prevalence of eating disorders (EDs) and disordered eating (DE) among athletes across training levels and assessment methods and to identify moderators associated with prevalence estimates. Systematic review, meta-analysis and meta-regression conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Scopus, Web of Science and SportDiscus were searched from inception to December 2024. Studies were eligible if they included active athletes of any sex, age, sport discipline or training level and reported the prevalence of ED and/or DE using standardised assessments, including clinical diagnoses or structured diagnostic interviews for ED, and self-report instruments with established cut-off values for DE. Studies were excluded if they involved retired athletes, participants with pre-existing ED diagnoses, included fewer than 25 participants, reused data or were non-peer-reviewed. From 1582 identified records, 190 studies (58 335 athletes, 34 628 women) were included in the systematic review and 127 high-quality studies (43 006 athletes) in the meta-analysis. The pooled prevalence of ED/DE was 20.0% (95% CI 17.0% to 23.0%). Subgroup analyses showed no significant differences according to training level or screening method (clinical interview or diagnosis vs self-reported instruments). However, prevalence varied significantly by instrument: Eating Disorder Examination yielded the lowest prevalence estimates (11.9%), whereas Eating Disorder Inventory yielded the highest (28.3%). Meta-regression showed that a higher proportion of women and more recent publication years were associated with higher prevalence estimates. Approximately one in five athletes experience ED or DE, underscoring the magnitude of this issue in sport. These findings highlight the need for validated, athlete-specific screening instruments and tailored prevention and intervention strategies.
Changes in energy metabolism are commonly observed in bipolar disorder (BD) and have been linked to a more severe clinical course. 'Metabolic jet lag' (MJL) is a state of shift in circadian patterns of energy homeostasis, expressed through behavioral changes such as irregular meal timing. However, the relationship between MJL and the pathophysiology of BD remains unknown. The objective of this study is to determine the feasibility of an investigation assessing the association between MJL, evaluated through eating rhythm disruption, and markers of illness burden in ten individuals with DSM-5-defined BD type 1. This is a 14-day longitudinal, naturalistic study that used the smartphone application 'RxFood' to elaborate a personalized, time-stamped "feedogram" for each participant. Illness burden and severity parameters were collected at baseline, and the Acceptability E-Scale was administered at the endpoint. Eating rhythm disruption scores were calculated based on a novel analytical approach applied to the "feedogram" data. The use of 'RxFood' demonstrated excellent feasibility and acceptability (94%) in individuals with BD and captured 628 eating occasions over the study period. Eating rhythm disruption scores varied between participants and correlated with the number of manic episodes (r = 0.718, p = 0.019), although the association was not significant after correcting for multiple comparisons. Ecological momentary assessment of eating rhythms is feasible in individuals with BD. Larger investigations evaluating the association between eating rhythm disruption and clinical illness trajectories are needed to delineate the role of MJL in the pathophysiology of BD.
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Polygenic risk scores (PRSs) are increasingly being considered as tools to refine risk stratification in cardiovascular and cardiometabolic disease, but their clinical translation remains constrained by a central limitation: most currently available PRSs were derived in predominantly European-ancestry datasets and perform less well in admixed and underrepresented populations. This limitation reflects differences in allele frequencies, linkage disequilibrium structure, imputation performance, ancestry-specific effect sizes, and environmental context, and is especially consequential in recently admixed populations, in whom local ancestry and internal heterogeneity further complicate prediction. In this review, we examine recent methodological and translational advances in PRS development across diverse populations, with emphasis on coronary artery disease (CAD), blood pressure and hypertension, type 2 diabetes, obesity, and atrial fibrillation. We highlight the transition from single-ancestry prediction to multi-ancestry frameworks, as well as emerging approaches tailored to admixed genomes, including ancestry deconvolution-based and local-ancestry-aware models. Across traits, broader discovery resources and ancestry-aware methods have improved predictive performance beyond naive European transfer, but progress remains uneven. CAD currently represents the most mature phenotype, with the strongest evidence for clinically relevant gains from multi-ancestry PRS development and validation. Blood pressure and hypertension, as well as type 2 diabetes, show substantial methodological progress but remain limited by calibration, context dependence, and incomplete evidence for implementation. Obesity and atrial fibrillation are advancing rapidly, but their translational readiness remains less developed. We argue that admixed and underrepresented populations should not be viewed only as settings in which PRSs underperform, but as essential contexts for building more robust and clinically generalizable models. The next phase of precision cardiovascular medicine will depend not simply on improving prediction, but on demonstrating that PRS-informed risk assessment can be calibrated, interpretable, and clinically useful across the diverse populations in whom it is intended to guide care.
Chronic spontaneous urticaria (CSU) presents recurrent wheals and/or angioedema for more than six weeks without an identifiable trigger. Although mast cell activation and histamine release are well-established effector mechanisms, this model does not explain disease persistence, immune dysregulation, or treatment refractoriness. A deeper mechanistic framework is required to explain progression to chronic disease. To propose a stage-wise CSU chronification model, reframing the disease as a structured dermal immunothrombotic and autoimmune niche rather than an episodic mast cell-effector event, and to derive therapeutic implications. A narrative synthesis of ultrastructural, immunohistochemical, transcriptomic, and clinical evidence from the published clinical literature, including original studies from our group on acute drug-induced urticaria and antihistamine-refractory CSU was performed. Five sequential stages drive chronification: (1) FcεRI/BTK-dependent mast cell degranulation; (2) eosinophil tissue-factor activation of the coagulation-complement loop; (3) FXIIIa⁺ dendrocyte phagocytosis and T-cell priming via OX40/OX40L; (4) Th2-driven M2 macrophage polarization with autoantibody-mediated mast cell reactivation; and (5) JAK/STAT and IFN-λ1 signaling sustaining dermal immune niche. Transcriptomic hub genes and cytokine profiling further support this model. CSU reflects a structured immune architecture rather than isolated mast cell activation. This explains treatment refractoriness and supports targeting upstream checkpoints, including BTK, JAK, and OX40/OX40L for sustained control.
Continuous energy restriction (CER) effectively promotes body fat reduction; however, its effects on hunger regulation and the hedonic system (reward-related mechanisms) may compromise long-term weight maintenance. The gut microbiota has emerged as a potential target to support sustained weight loss; however, studies evaluating combined interventions, such as probiotics alongside CER, remain limited. This study aimed to evaluate whether probiotic supplementation enhanced the metabolic and behavioral effects of CER by examining appetite-related hormones (ghrelin, leptin, GLP-1, GIP, and PYY) and eating behavior parameters (emotional eating, cognitive restraint, and binge eating) in adult men with obesity. This was a 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial. We included adult males living with obesity, aged 25 to 44 years. The prescribed CER corresponded to a 30% reduction in total daily energy expenditure. Probiotic supplementation consisted of two 1 g sachets per day, each containing 1×109 Colony-Forming Units/day of Lactobacillus acidophilus NCFM (ATCC SD 5221), Lacticaseibacillus rhamnosus HN001 (ATCC SD 5675), Lacticaseibacillus paracasei Lpc-37 (ATCC SD 5275), and Bifidobacterium lactis HN019 (ATCC SD 5674). Primary outcomes included ghrelin and leptin levels. Secondary outcomes comprised glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, peptide YY (PYY), and adiponectin levels, as well as eating behavior dimensions and body composition. Binge eating, emotional eating, and cognitive restraint were assessed using the Three-Factor Eating Questionnaire. Of the 49 participants randomized, 38 were included in the final analysis, with hormonal outcomes available for 25 participants. Significant time effects were observed, indicating that changes were primarily driven by CER, regardless of supplementation group. Ghrelin levels increased over time in both groups (p = 0.045; η2p = 0.164), whereas leptin levels decreased significantly (p < 0.001; η2p = 0.463). Eating behavior improved over time, with reductions in binge eating (p < 0.001; η2p = 0.413) and emotional eating (p = 0.007; η2p = 0.289), and an increase in cognitive restraint (p < 0.001; η2p = 0.650). Absolute fat mass also declined significantly (p < 0.001; η2p = 0.718), with no significant group effects or group × time interactions across outcomes. These null findings should be interpreted with caution, as the study was underpowered for ghrelin and emotional eating, potentially limiting the detection of intervention effects. Twelve weeks of CER reduced fat mass and leptin levels and increased ghrelin concentrations, regardless of probiotic supplementation. Eating behavior scores also changed over time, with reductions in binge eating and emotional eating and an increase in cognitive restraint. However, no significant group or group × time interaction effects were observed, indicating that probiotic supplementation did not provide measurable additional benefits beyond CER for the outcomes assessed.
The term "food noise" has rapidly entered scientific, clinical, commercial, and public discourse, particularly in relation to appetite changes reported during treatment with glucagon-like peptide-1 receptor agonist (GLP-1) medications. Despite growing use of the construct and the emergence of dedicated measurement tools, limited evidence exists regarding its underlying mechanisms, whether it reflects a distinct phenomenon, and how it is experienced and interpreted in the context of everyday life. In this commentary, we critically examine current conceptualizations and measurement approaches to food noise, focusing on their theoretical grounding, psychometric development, clinical interpretation, and de-contextualization. We review how existing definitions relate to broader literature on food cue reactivity, food preoccupation, cravings, and intrusive food-related cognitions, and discuss whether food noise reflects a distinct construct or an overlapping dimension of established appetite-related processes. We highlight uncertainties surrounding current measurement instruments, including conceptual overlap with existing scales and limited evidence on clinical utility. Beyond psychometric concerns, we examine how meanings attached to food-related thoughts and "noise" may vary across contexts, raising challenges for translation of the construct. Rather than rejecting food noise as a potentially meaningful construct, we identify important unresolved questions and set priorities for future research, including stronger theoretical specification, mixed-methods instrument development grounded in lived experience, cross-cultural validation, consideration of its potential to reclassify common experiences as pathology, and clearer criteria for distinguishing and treating clinically significant food-related cognitions. We argue that this conceptual, methodological, and normative clarity is needed before food noise can be responsibly integrated into clinical use.
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Preeclampsia (PE) is a leading cause of maternal and perinatal morbimortality, particularly in low- and middle-income countries. Despite advances in clinical management, its etiology and pathogenesis remain unclear, and effective predictive biomarkers are lacking. The Brazilian Longitudinal Study for the Investigation of Preeclampsia (ECLIPSE-BRAZIL) is a prospective cohort designed to investigate genetic, immunological, hemostatic, biochemical, and angiogenic profiles in pregnant women at risk for PE, aiming to identify biomarkers that effectively and affordably predict PE risk early in pregnancy. ECLIPSE-BRAZIL follows 500 to 1,000 pregnant women receiving care at the High-Risk Prenatal Care clinics in Belo Horizonte and Divinópolis, Minas Gerais, Brazil. Clinical and laboratory assessments are conducted at four gestational stages and postpartum for PE cases. Clinical data, including sociodemographic, clinical and behavioral factors, and blood and urine samples are systematically collected. Plasma and urine levels of inflammatory markers, angiogenic factors, oxidative stress parameters, extracellular vesicles, microRNAs, endothelial and platelet markers will be analyzed. Participants are stratified by PE development and gestational age at diagnosis. Standardized criteria and data protocols ensure rigor, while quality check and audits enhance data reliability. To minimize follow-up loss, participants are contacted frequently, with flexible sampling and the use of hospital records. ECLIPSE-BRAZIL will provide novel insights into PE pathophysiology, improving disease prediction and management. By studying a diverse population, we will identify biological signatures to inform health innovations: development of cost-effective diagnostic tools, point-of-care tests and simple clinical algorithms to identify women at risk before symptoms become severe. Finally, we will provide a deeper understanding of biological mechanisms driving PE and its subtypes, including endothelial function and immune response, which may lead to the discovery of new therapeutic targets. ECLIPSE-BRAZIL represents a major advancement in PE research, integrating a comprehensive evaluation of clinical, biochemical, and molecular markers throughout pregnancy. Its findings may inform public health policies and improve clinical practices worldwide. Not applicable. This is an observational cohort study approved by the Research Ethics Committees, as documented under the following CAAE numbers: 12471918.0.0000.5149, 12471918.0.3002.5119, 12471918.0.3003.5130, 12471918.0.3006.5545.
Liver transplantation (LT) has emerged as a potential therapeutic option for selected patients with unresectable liver-confined metastatic neuroendocrine tumors (NETs), although evidence remains limited, particularly in low- and middle-income countries. To describe the experience of a Brazilian referral center with orthotopic LT for metastatic NETs and to evaluate post-transplant outcomes. A retrospective descriptive cohort study was conducted, including patients who underwent deceased-donor LT between 2002 and 2025 at a tertiary referral center in Brazil. Among 2312 liver transplants, six patients transplanted for unresectable hepatic metastases from well-differentiated NETs were identified. Demographic, clinical, oncological, and transplant-related variables were analyzed, with outcomes assessed over a 5-year follow-up period. The cohort consisted predominantly of middle-aged men, with a median age of 47.5 years. All patients had preserved liver function at transplantation, reflected by low MELD-Na scores. The median Ki-67 index was 10% (range: 1%-20%). Overall survival was 100%, and tumor recurrence occurred in two patients (33.3%). Acute rejection was infrequent and successfully managed, with no cases of chronic rejection. Post-transplant complications were limited, mainly involving biliary events. Immunosuppressive regimens were predominantly tacrolimus-based, with selective use of mycophenolate and everolimus. LT for metastatic NETs was associated with excellent survival and low morbidity in this highly selected cohort. Despite the small sample size, these findings support LT as a feasible therapeutic option in carefully selected patients treated at specialized referral centers.
The responses underlying heightened sensitivity of young populations to deoxynivalenol (DON) toxicity remain uncharacterized in translational murine models. This study aimed to fill this gap by providing the first systematic, multi-organ (intestine, liver, and kidney) comparison of DON toxicity, contrasting the responses of prepubertal and adult mice. Prepubertal (21-day-old) and adult (65-day-old) Swiss mice (n = 10/group) were fed control or 10 mg/kg DON-contaminated diets for 15 or 28 days, respectively. Growth performance was monitored, and intestine, liver, and kidney were subsequently collected for histopathological, morphometric, and biochemical analyses. DON induced a severe, acute weight gain reduction (∼59.6%) in prepubertal mice, with no effect on adults or systemic biochemical profiles. DON toxicity was highly organ-specific: the prepubertal intestine mounted an adaptive response, coupling oxidative damage with compensatory antioxidant production and enterocyte hypertrophy, but without structural lesions. In contrast, the liver and kidney sustained direct histopathological damage in both age groups. However, their biochemical responses diverged: the liver showed a young-specific inflammatory signal, whereas the kidney remained biochemically silent despite the damage it sustained. This multi-organ comparison in mice shows that DON toxicity is age- and organ-specific, demonstrating that at the exposure dose used, prepubertal mice exhibit more pronounced toxic responses.
Metabolic and bariatric surgery (MBS) is highly effective for severe obesity but carries rare, serious risks, most notably venous thromboembolism (VTE), the leading cause of postoperative death. Strikingly, most VTE events occur after patients leave the hospital. Yet, despite guidelines, there is no global agreement on prevention strategies. This international expert consensus unites specialists worldwide to provide clarity and practical recommendations for safer outcomes in MBS. This study used a two-round modified Delphi process to unite 102 experts from 42 countries on thromboprophylaxis in MBS. Guided by evidence and ethical approval, participants, surgeons, hematologists, and pharmacologists reviewed 25 statements online. In the second round, the remaining three were revised and re-evaluated. This method ensured balanced input, minimized bias, and produced a robust international consensus to guide safer surgical practice. In round one, 22 of 25 statements met the ≥ 80% consensus threshold. In round two, the experts re-evaluated the remaining three statements, with one more reaching agreement. Overall, consensus was achieved on 23 of 25 statements. This international Delphi consensus achieved agreement on 23 of 25 statements (92%), offering evidence-based guidance for VTE prophylaxis in MBS. Key recommendations include individualized risk assessment, extended prophylaxis for high-risk patients, preference for LMWH, and growing support for direct oral anticoagulants (DOACs), especially apixaban. The consensus promotes personalized strategies over uniform protocols while highlighting research priorities on dosing, duration, and DOAC comparisons. Implementing these recommendations can standardize care, improve safety, and reduce VTE-related morbidity and mortality worldwide.
The diagnosis of Sjögren's disease (SD) relies on expert opinion and fulfillment of items in classification criteria sets, together with additional clinical, pathological, and laboratory evaluations. Imaging is not yet part of any criteria set, although sonography has recently demonstrated strong potential for inclusion as an additional item. Besides sonography, some evidence suggests that magnetic resonance (MR) imaging could also be a useful adjunct in diagnosing this disease. We describe and illustrate the findings of SD on conventional pulse sequences and MR sialography, as well as comment on their diagnostic performance. The role of advanced imaging techniques, including diffusion-weighted imaging (DWI) and proton-density fat fraction (PDFF) imaging, and evidence regarding how MR relates to other frequently requested complementary tests are also reviewed. We conclude by presenting several knowledge gaps that, in our opinion, need to be addressed before MR imaging can be included in the diagnostic workup of SD.
Training in neurosurgery is increasingly challenged by the complexity of cranial anatomy, the rarity of certain pathologies, ethical constraints on cadaveric dissection, and limited operative exposure. Advances in three-dimensional (3D) printing have enabled the development of patient-specific anatomical models derived from computed tomography and magnetic resonance imaging, offering realistic, reproducible platforms for surgical training and preoperative planning. This chapter reviews contemporary applications of 3D-printed, hybrid, and multimodal simulation models in neurosurgical education, with particular emphasis on complex craniofacial and encephalocele procedures. Through illustrative case reports-including frontoethmoidal and transsphenoidal meningoencephaloceles, metopic craniosynostosis, and late encephalocele correction-the chapter demonstrates how multimaterial 3D-printing, hybrid silicone-resin constructs, and integration with augmented and mixed reality can enhance spatial understanding, tactile feedback, and procedural rehearsal. Evidence from these cases indicates that patient-specific simulation can alter surgical strategy, reduce operative time and blood loss, and improve multidisciplinary communication. Educational benefits extend beyond surgeons to trainees and allied health professionals, supporting structured skill acquisition and competency-based assessment. The chapter also discusses the relevance of low-cost 3D-printing solutions for low- and middle-income countries, highlighting open-source software and affordable fabrication techniques as tools to reduce global disparities in neurosurgical care. Limitations related to cost, material fidelity, imaging quality, and technical expertise are addressed, alongside future directions for research and curriculum integration. Overall, 3D-printed and hybrid simulation models represent a transformative approach to neurosurgical training and patient-specific surgical planning, with significant implications for education, safety, and global health equity.