Biomarkers for personalised prevention of chronic diseases: a common protocol for three rapid scoping reviews.

INTRODUCTION: Personalised prevention aims to delay or avoid disease occurrence, progression, and recurrence of disease through the adoption of targeted interventions that consider the individual biological, including genetic data, environmental and behavioural characteristics, as well as the socio-cultural context. This protocol summarises the main features of a rapid scoping review to show the research landscape on biomarkers or a combination of biomarkers that may help to better identify subgroups of individuals with different risks of developing specific diseases in which specific preventive strategies could have an impact on clinical outcomes. This review is part of the "Personalised Prevention Roadmap for the future HEalThcare" (PROPHET) project, which seeks to highlight the gaps in current personalised preventive approaches, in order to develop a Strategic Research and Innovation Agenda for the European Union. OBJECTIVE: To systematically map and review the evidence of biomarkers that are available or under development in cancer, cardiovascular and neurodegenerative diseases that are or can be used for personalised prevention in the general population, in clinical or public health settings. METHODS: Three rapid scoping reviews are being conducted in parallel (February-June 2023), based on a common framework with some adjustments to suit each specific condition (cancer, cardiovascular or neurodegenerative diseases). Medline and Embase will be searched to identify publications between 2020 and 2023. To shorten the time frames, 10% of the papers will undergo screening by two reviewers and only English-language papers will be considered. The following information will be extracted by two reviewers from all the publications selected for inclusion: source type, citation details, country, inclusion/exclusion criteria (population, concept, context, type of evidence source), study methods, and key findings relevant to the review question/s. The selection criteria and the extraction sheet will be pre-tested. Relevant biomarkers for risk prediction and stratification will be recorded. Results will be presented graphically using an evidence map. INCLUSION CRITERIA: Population: general adult populations or adults from specific pre-defined high-risk subgroups; concept: all studies focusing on molecular, cellular, physiological, or imaging biomarkers used for individualised primary or secondary prevention of the diseases of interest; context: clinical or public health settings. SYSTEMATIC REVIEW REGISTRATION: https://doi.org/10.17605/OSF.IO/7JRWD (OSF registration DOI).

Long-term results with biosynthetic absorbable P4HB mesh in ventral abdominal wall repair: a multicentre analysis.

BACKGROUND: The aim of this multicentre study was to analyse the outcomes of biosynthetic absorbable poly-4-hydroxybutyrate (P4HB) prosthesis implantation in patients undergoing ventral hernia repair (VHR) in the context of different degrees of contamination. METHODS: From May 2016 to December 2021, a multicentre retrospective analysis of patients who underwent elective or urgent hernia repair with P4HB prosthesis was performed in seven hospitals in Spain and Portugal. Patients with a postoperative follow-up of less than 20 months and those within the theoretical period of prosthesis resorption were excluded from the study. Regarding the degree of contamination, patients were assessed according to the modified Ventral Hernia Working Group (VHWG) classification. Epidemiological data, hernia characteristics, surgical and postoperative variables (Clavien-Dindo classification) of these patients were analyzed. Risk factors related to long-term recurrence were studied by a multivariate analysis. RESULTS: In 236 cases of P4HB prosthesis implantation, repair in cases of Grade 3 was the most frequent (49.1%), followed by Grade 2 in 42.3% of cases and Grade 1 in 8.4%. The most frequent complications were Grade 1, with the majority occurring during the first year. The overall rate of surgical site occurrences (SSO) was 30%. The hernia recurrence rate was 14.4% (n = 34), with a mean postoperative follow-up time of 41 months (22-61). The multivariate analysis showed that the onlay location of the mesh (OR 1.07; CI 1.42-2.70, p = 0.004) was a significant independent risk factor for recurrence. CONCLUSIONS: The use of a P4HB bioresorbable mesh for the VHR with different degrees of contamination leads to favourable results overall, with an acceptable rate of hernia recurrence. The onlay location of the P4HB prosthesis is the main factor in recurrence in both elective and emergency settings.

The cardiomyopathy of cystic fibrosis: a modern form of Keshan disease.

Introduction: We conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF. Methods: We studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy. Results: We found a prevalence of 10% (CI 4.6%-15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases (p < 0.001 vs. CF controls). Selenium deficiency (Se < 60 µg/L) was associated with more severe LV dysfunction, higher prevalence of CF CMP, higher NTproBNP levels, and more severe pulmonary and digestive involvement. Conclusion: 10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients.

Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study.

INTRODUCTION: Prostatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. MATERIALS AND METHODS: PROSARC is a national (Spain) prospective observational study (May-2022-May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. RESULTS: A 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (p=0.666), decreased mean value of appendicular muscle mass (p=0.01) and increased percentage of fat mass (p=0.012). CONCLUSION: In patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

Integral Use of Red Wine Pomace after Hydrostatic High Pressure: Application of Two Consecutive Cycles of Treatment.

The influence of applying hydrostatic high pressure (HHP) to red grape pomace cv. Tempranillo was studied to obtain an ingredient rich in bioactive compounds for the manufacture of food products. Four treatments were investigated: (i) 600 MPa/1 s; (ii) 600 MPa/300 s, and other two treatments with 2 cycles of HHP: (iii) 2 cycles of 600 MPa/1 s; and (iv) 1 first cycle of 400 MPa/1 s and a second cycle 600 MPa/1 s. Treated pomace was stored at different temperatures (4 and 20 °C). The application of two consecutive cycles had no effect on the microorganisms' inactivation compared to only one cycle. Immediately after HHP, the phenolic compounds content was maintained. However, HHP had no influence on the polyphenol oxidase enzyme (PPO), and so the phenolic compounds were significantly reduced during storage. Hence, the shelf-life of red grape pomace was significantly reduced at both temperatures, although phenolic compounds were better preserved under refrigeration than at room temperature.

[Translated article] Mechanical resistance of polylactic acid bone matrices developed by 3D printing for the reconstruction of bone defects.

INTRODUCTION: Bone defects are one of the main limitations in orthopaedic surgery and traumatology. For this reason, multiple bone replacement systems have been developed, either by prosthetic implant or by substitution with osteoforming substances, whose limitations are their survival and lack of structurality, respectively. The objective of this work is the generation of a new material for the creation of biologically active structures that have sufficient tensile strength to maintain the structure during remodelling. MATERIAL AND METHODS: A new filament based on the fusion of natural polylactide acid (PLA) powder was designed for the generation of pieces by means of fused deposition modelling (FDM) on which to carry out tensile mechanical tests of osteosynthesis material. A total of 13 groups with different cortical thickness, filling and layer height were carried out, with 10 tensile tests in each group, defining the tensile breaking limit for each group. The regression lines for each group and their mechanical resistance to traction on the filament used were determined. RESULTS: The filament ratio per contact surface unit with the osteosynthesis used was the main determinant of the mechanical resistance to traction, either at the expense of the increase in cortical thickness or by the increase in the percentage of cancellous bone filling. Layer height had a minor effect on tensile strength. The regression value was high for cortical thickness and cancellous filling, being elements with a predictable biomechanical behaviour. CONCLUSIONS: The new methodology allows the creation of personalised neutral and implantable PLA bone matrices for the reconstruction of large bone defects by means of 3D printing by FDM with a mechanical resistance to traction greater than that of current biological support structures.

Clinical profile, management and outcomes of patients with cardiogenic shock undergoing transfer between centers in Spain.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the clinical profile, management, and prognosis of ST segment elevation myocardial infarction-related cardiogenic shock (STEMI-CS) requiring interhospital transfer, as well as the prognostic impact of structural variables of the treating centers in this setting. METHODS: This study included patients with STEMI-CS treated at revascularization-capable centers from 2016 to 2020. The patients were divided into the following groups: group A: patients attended throughout their admission at hospitals with interventional cardiology without cardiac surgery; group B: patients treated at hospitals with interventional cardiology and cardiac surgery; and group C: patients transferred to centers with interventional cardiology and cardiac surgery. We analyzed the association between the volume of STEMI-CS cases treated, the availability of cardiac intensive care units (CICU), and heart transplant with hospital mortality. RESULTS: A total of 4189 episodes were included: 1389 (33.2%) from group A, 2627 from group B (62.7%), and 173 from group C (4.1%). Transferred patients were younger, had a higher cardiovascular risk, and more commonly underwent revascularization, mechanical circulatory support, and heart transplant during hospitalization (P<.001). The crude mortality rate was lower in transferred patients (46.2% vs 60.3% in group A and 54.4% in group B, (P<.001)). Lower mortality was associated with a higher volume of care and CICU availability (OR, 0.75, P=.009; and 0.80, P=.047). CONCLUSIONS: The proportion of transfers in patients with STEMI-CS in our setting is low. Transferred patients were younger and underwent more invasive procedures. Mortality was lower among patients transferred to centers with a higher volume of STEMI-CS cases and CICU.

Successful cryopreservation in biodegradable containers of sperm from aquaculture Mediterranean fishes.

We aimed to evaluate the efficiency of hard-gelatin and hard-hydroxypropyl methylcellulose (HPMC) capsules as biodegradable alternative containers to plastic straws in European eel (Anguilla anguilla), gilthead seabream (Sparus aurata) and European sea bass (Dicentrarchus labrax) sperm cryopreservation. Sperm samples from each European eel (n = 12) were diluted 1:8:1 (sperm: extender P1+5 % egg yolk: methanol). Gilthead seabream (n = 12) samples were individually diluted in a cryoprotectant solution of 5 % Me2SO + NaCl 1 % plus BSA (10 mg mL-1) at a ratio of 1:6 (sperm: cryoprotectant solution). European sea bass (n = 10) sperm from each male was diluted in non-activating medium (NAM) at a ratio of 1:5.7 (sperm: NAM), and 5 % of Me2SO was added. The diluted European eel and sea bass sperm aliquots (0.5 mL) were individually filled in plastic straws (0.5 mL), hard-gelatin, and HPMC capsules (0.68 mL). Gilthead seabream diluted sperm (0.25 mL) were filled in plastic straws (0.25 mL) and identical capsules described. All samples were frozen in liquid nitrogen vapor and stored in a liquid nitrogen tank. Sperm kinetic parameters were evaluated by CASA-Mot software. Sperm membrane integrity was performed using a Live and Dead KIT and an epifluorescence microscope. To quantify DNA damage, the alkaline comet assay was performed and TailDNA (TD-%) and Olive Tail Moment (OTM) were evaluated by CaspLab software. Sperm cryopreservation of the three Mediterranean species in straws, gelatin, or HPMC capsules reduced the kinetic parameters and cell membrane integrity. Generally, the post-thawing samples cryopreserved in straws and capsules did not differ for the kinetic parameters and cell membrane integrity, except for European sea bass sperm, where the samples stored in gelatin capsules showed higher velocities (VCL - 100; VSL - 76; VAP - 90 µm s-1) than the sperm stored in HPMC capsules (VCL - 87; VSL - 59; VAP - 73 µm s-1). The cryopreservation process did not damage the sperm DNA of European eel and European sea bass, regardless of the containers used. On the other hand, gilthead seabream sperm cryopreserved in gelatin (TD - 9.8 %; OTM - 9.7) and HPMC (TD - 11.1 %; OTM - 11.2) capsules showed higher DNA damage than fresh samples (TD - 3.6 %; OTM - 2.7) and the sperm stored in straws (TD - 4.4 %; OTM - 5.2). The hard-gelatin and HPMC biodegradable capsules can be used as an alternative to straws for European eel, gilthead seabream, and European sea bass sperm cryopreservation.

Application of White-Wine-Pomace-Derived Ingredients in Extending Storage Stability of Fresh Pork Burgers.

White wine pomace, a by-product from winemaking, was stabilized after the application of thermal blanching (with the aim of deactivating the polyphenoloxidase enzyme), milling, and processing by hydrostatic high-pressure treatment (with the aim of reducing initial microbial loads while preserving phenolic compounds content). The valorized pomace (VP) ingredient was added at different proportions to pork burgers (0.5%, 1%, and 3% w/w) to improve their preservation, and the effect was compared to those produced by sulfites and with a control (without sulfites or VP). Burgers were vacuum-packed and refrigerated for 7 days. Microbiological, color, oxidation, and sensory parameters were analyzed. Neither sulfites nor VP reduced the microbial development of most microorganism groups evaluated (p > 0.05); however, both prevented coliform growth during storage (p < 0.01). The use of sulfites prevented the discoloration of burgers during storage, while VP had no effect (p < 0.001). On the contrary, VP limited lipid and protein oxidation development during storage (p > 0.05), while sulfites had no effect. Therefore, the use of VP from white wine production could have an antioxidant effect but a limited antimicrobial or color-protective effect for the preservation of pork burgers.

Subclonal Somatic Copy-Number Alterations Emerge and Dominate in Recurrent Osteosarcoma.

Multiple large-scale genomic profiling efforts have been undertaken in osteosarcoma to define the genomic drivers of tumorigenesis, therapeutic response, and disease recurrence. The spatial and temporal intratumor heterogeneity could also play a role in promoting tumor growth and treatment resistance. We conducted longitudinal whole-genome sequencing of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma. Each patient had at least one sample from a primary site and a metastatic or relapse site. Subclonal copy-number alterations were identified in all patients except one. In 5 patients, subclones from the primary tumor emerged and dominated at subsequent relapses. MYC gain/amplification was enriched in the treatment-resistant clones in 6 of 7 patients with multiple clones. Amplifications in other potential driver genes, such as CCNE1, RAD21, VEGFA, and IGF1R, were also observed in the resistant copy-number clones. A chromosomal duplication timing analysis revealed that complex genomic rearrangements typically occurred prior to diagnosis, supporting a macroevolutionary model of evolution, where a large number of genomic aberrations are acquired over a short period of time followed by clonal selection, as opposed to ongoing evolution. A mutational signature analysis of recurrent tumors revealed that homologous repair deficiency (HRD)-related SBS3 increases at each time point in patients with recurrent disease, suggesting that HRD continues to be an active mutagenic process after diagnosis. Overall, by examining the clonal relationships between temporally and spatially separated samples from patients with relapsed/refractory osteosarcoma, this study sheds light on the intratumor heterogeneity and potential drivers of treatment resistance in this disease. SIGNIFICANCE: The chemoresistant population in recurrent osteosarcoma is subclonal at diagnosis, emerges at the time of primary resection due to selective pressure from neoadjuvant chemotherapy, and is characterized by unique oncogenic amplifications.

3D phantom for image quality assessment of mammography systems.

Objective.To present an innovative approach for the design of a 3D mammographic phantom for medical equipment quality assessment, estimation of the glandular tissue percentage in the patient's breast, and emulation of microcalcification (µC) breast lesions.Approach.Contrast-to noise ratio (CNR) measurements, as well as spatial resolution and intensity-to-glandularity calibrations under mammography conditions were performed to assess the effectiveness of the phantom. CNR measurements were applied to different groups of calcium hydroxyapatite (HA) and aluminum oxide (AO)µCs ranging from 200 to 600µm. Spatial resolution was characterized using an aluminum plate contained in the phantom and standard linear figures of merit, such as the line spread function and modulation transfer function (MTF). The intensity-to-glandularity calibration was developed using an x-ray attenuation matrix within the phantom to estimate the glandular tissue percentage in a breast with a compressed thickness of 4 cm.Main results.For the prototype studied, the minimum confidence level for detecting HAµCs is 95.4%, while for AOµCs is above 68.3%. It was also possible to determine that the MTF of the commercial mammography machine used for this study at the Nyquist frequency is 41%. Additionally, a one-to-one intensity-to-glandularity calibration was obtained and verified with Monte-Carlo simulation results.Significance.The phantom provides traditional arrangements presented in accreditation phantoms, which makes it competitive with available devices, but excelling in regarding affordability, modularity, and inlays distribution. Moreover, its design allows to be positioned in close proximity to the patient's breast during a medical screening for a simultaneous x-ray imaging, such that the features of the phantom can be used as reference values to specify characteristics of the real breast tissue, such as proportion of glandular/adipose composition and/orµC type and size lesions.

Digital image analysis workflows for evaluation of cell behavior and tumor microenvironment to aid therapeutic assessment in high-risk neuroblastoma.

Digital pathology and artificial intelligence are promising emerging tools in precision oncology as they provide more robust and reproducible analysis of histologic, morphologic and topologic characteristics of tumor cells and the surrounding microenvironment. This study aims to develop digital image analysis workflows for therapeutic assessment in preclinical in vivo models. For this purpose, we generated pipelines that enable automatic detection and quantification of vitronectin and αvß3 in heterotopic high-risk neuroblastoma xenografts, demonstrating that digital analysis workflows can be used to provide robust detection of vitronectin secretion and αvß3 expression by malignant neuroblasts and to evaluate the possibility of combining traditional chemotherapy (etoposide) with extracellular matrix-targeted therapies (cilengitide). Digital image analysis added evidence for the relevance of territorial vitronectin as a therapeutic target in neuroblastoma, since its expression is modified after treatment, with a mean percentage of 60.44% in combined therapy tumors vs 45.08% in control ones. In addition, the present study revealed the efficacy of cilengitide for reducing αvß3 expression, with a mean αvß3 positivity of 34.17% in cilengitide treated material vs 66.14% in control and with less tumor growth when combined with etoposide, with a final mean volume of 0.04 cm3 in combined therapy vs 1.45 cm3 in control. The results of this work highlight the importance of extracellular matrix-focused therapies in preclinical studies to improve therapeutic assessment for high-risk neuroblastoma patients.

A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome.

Meningioma-1 is a transcription activator that regulates mammalian palate development and is required for appropriate osteoblast proliferation, motility, differentiation, and function. Microdeletions involving the MN1 gene have been linked to syndromes including craniofacial anomalies, such as Toriello-Carey syndrome. Recently, truncating variants in the C-terminal portion of the MN1 transcriptional factor have been linked to a characteristic and distinct phenotype presenting with craniofacial anomalies and partial rhombencephalosynapsis, a rare brain malformation characterized by midline fusion of the cerebellar hemispheres with partial or complete loss of the cerebellar vermis. It has been called MN1 C-terminal truncation (MCTT) syndrome or CEBALID (Craniofacial defects, dysmorphic Ears, Brain Abnormalities, Language delay, and Intellectual Disability) and suggested to be caused by dominantly acting truncated protein MN1 instead of haploinsufficiency. As a proto-oncogene, MN1 is also involved in familial meningioma. In this study, we present a novel case of MCTT syndrome in a female patient presenting with craniofacial anomalies and rhombencephalosynapsis, harboring a de novo pathogenic variant in the MN1 gene: c.3686_3698del, p.(Met1229Argfs*87).

Cerebral amyloid angiopathy-related inflammation: clinical features and treatment response in a case series.

INTRODUCTION: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an entity characterised by an inflammatory response to ß-amyloid deposition in the walls of cerebral microvessels. METHODS: We conducted a retrospective review of a series of patients with a diagnosis of CAA-ri according to histopathological study findings or clinical-radiological diagnostic criteria. RESULTS: The study included 7 patients (5 men) with a mean age of 79 years. Disease onset was acute or subacute in 6 patients. The most frequent symptoms were cognitive impairment (n = 6), behavioural alterations (n = 5), epileptic seizures (n = 5), focal neurological signs (n = 4), and headache (n = 2). Cerebrospinal fluid was abnormal in 3 patients (lymphocytic pleocytosis and high protein levels). The most frequent MRI findings were microbleeds (n = 7), subcortical white matter hyperintensities on T2-FLAIR sequences (n = 7), and leptomeningeal enhancement (n = 6). Lesions were bilateral in 3 patients and most frequently involved the parieto-occipital region (n = 5). Amyloid PET studies were performed in 2 patients, one of whom showed pathological findings. Two patients underwent brain biopsy, which confirmed diagnosis. All patients received immunosuppressive therapy. An initially favourable clinical-radiological response was observed in all cases, with 2 patients presenting radiological recurrence after treatment withdrawal, with a subsequent improvement after treatment was resumed. CONCLUSIONS: Early diagnosis of CAA-ri is essential: early treatment has been shown to improve prognosis and reduce the risk of recurrence. Although a histopathological study is needed to confirm diagnosis, clinical-radiological criteria enable diagnosis without biopsy.

Limbic encephalitis secondary to neuro-Behcet disease: an uncommon presentation. / Encefalitis límbica secundaria a neuro-Behçet: una presentación insólita.

INTRODUCTION: Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behcet's disease (BD) can present with heterogeneous neurological manifestations. However, LE is not considered a typical presentation of neuro-Behcet's disease (NBD). CASE REPORT: A 40-years-old male presented with new-onset subacute headaches, memory problems and apathy. A review of systems revealed an unrecorded past history of recurrent oral sores for years, recent malaise and fever, as well as an episode of bilateral panuveitis four months before presentation. His general and neurologic examination revealed slight fever, an isolated oral aphtha, anterograde amnesia and signs of bilateral retinal vasculitis. Brain magnetic resonance imaging displayed a pattern of limbic meningoencephalitis, and his cerebrospinal fluid showed mononuclear inflammation. The patient met BD diagnostic criteria. Considering LE is a very rare presentation of NBD, alternative etiologies were thoroughly assessed and excluded, including infectious, autoimmune and paraneoplastic encephalitis. Therefore, he was diagnosed with NBD, and he recovered well after immunosuppression. DISCUSSION: Only two cases of NBD presenting with LE have been previously reported. We report a third case of this rare presentation and compare it with the previous two. We aim to highlight this association and contribute to enlarge the rich clinical spectrum of NBD.

TITLE: Encefalitis límbica secundaria a neuro-Behçet: una presentación insólita.Introducción. La encefalitis límbica (EL) puede tener un amplio abanico de etiologías, más frecuentemente la infecciosa (sobre todo viral) o autoinmune. La enfermedad de Behçet (EB) puede presentarse con manifestaciones neurológicas heterogéneas. Sin embargo, la EL no se considera una presentación típica del neuro-Behçet (NB). Caso clínico. Varón de 40 años que consultó por cefalea de novo subaguda, problemas de memoria y apatía. La anamnesis por sistemas reveló una historia no conocida previamente de aftas orales recurrentes durante años, fiebre y afectación general reciente, así como un episodio de panuveítis bilateral cuatro meses antes de la presentación. Su exploración general y neurológica reveló febrícula, una afta oral aislada, amnesia anterógrada y signos de vasculitis retiniana bilateral. La resonancia magnética mostró un patrón de afectación de meningoencefalitis límbica y su líquido cefalorraquídeo presentaba inflamación mononuclear. El paciente cumplía los criterios diagnósticos de la EB. Considerando que la EL es una presentación muy rara del NB, se buscaron exhaustivamente y se excluyeron otras etiologías alternativas, incluyendo las encefalitis infecciosas, autoinmunes y paraneoplásicas. En consecuencia, el paciente se diagnosticó de NB y mostró una buena recuperación con tratamiento inmunosupresor. Discusión. Sólo dos casos de NB con presentación en forma de EL se han publicado previamente. Comunicamos el tercer caso de esta rara manifestación clínica de la EB y lo comparamos con los dos anteriores, con el objetivo de destacar dicha asociación y contribuir a expandir el rico espectro clínico del NB.

Treatment of pectus excavatum with vacuum bell during puberty. / Tratamiento del pectus excavatum con campana de succión durante la pubertad.

OBJECTIVE: To assess the efficacy of the vacuum bell during puberty, according to the daily hours of use and treatment duration. MATERIALS AND METHODS: A retrospective analysis of patients treated with vacuum bell during puberty in the 2010-2021 period was carried out. Several variables were collected, including baseline and final sinking, repaired sinking expressed in cm and as a percentage from baseline sinking, daily hours of use, treatment duration, and complications. Patients were categorized into groups according to the daily hours of use (≤ 3 hours; 4-5 hours; ≥ 6 hours) and treatment duration (6-12 months; 13-24 months; 25-36 months; > 36 months), and they were statistically analyzed. RESULTS: A total of 50 patients -41 male and 9 female- were studied, with a mean age of 12.5 years (range: 10-14 years). No significant differences among groups were observed in terms of baseline sinking, thoracic index, and final sinking. Repaired sinking did increase with the daily hours of use, with significant differences. Complications were mild. 3 patients withdrew from follow-up, and 5 out of the 25 patients who completed treatment achieved a good repair. CONCLUSIONS: To increase treatment efficacy, the vacuum bell should be used for 6 hours/day during puberty. This method is well-tolerated, causes mild complications, and may be an alternative to surgery in some cases.

OBJETIVO: Evaluar la eficacia de la campana de succión durante la pubertad, según las horas diarias de uso y la duración del tratamiento. MATERIAL Y METODOS: Se evaluaron retrospectivamente los pacientes tratados con campana de succión durante la pubertad en el periodo 2010-2021. Se recogieron diferentes variables, incluyendo el hundimiento inicial y final, el hundimiento corregido expresado en centímetros y en porcentaje con respecto al hundimiento inicial, las horas diarias de uso, la duración del tratamiento y las complicaciones. Se categorizaron los pacientes en grupos según las horas diarias de uso (≤ 3 horas; 4-5 horas; ≥ 6 horas) y la duración del tratamiento (6-12 meses; 13-24 meses; 25-36 meses; > 36 meses), y se analizaron estadísticamente. RESULTADOS: Se estudiaron un total de 50 pacientes; 41 varones y 9 mujeres, con una edad media de 12,5 años (rango 10-14 años). No se observaron diferencias significativas entre los diferentes grupos en relación con el hundimiento inicial, el índice torácico y el hundimiento final. El hundimiento corregido aumentó en relación con las horas diarias de uso, con diferencias significativas. Las complicaciones fueron leves, 3 pacientes abandonaron el seguimiento y 5 pacientes de los 25 que finalizaron el tratamiento, alcanzaron una buena corrección. CONCLUSIONES: Para aumentar la eficacia del tratamiento, el tiempo de uso de la campana de succión durante la pubertad debería alcanzar las 6 horas diarias. Este método es bien tolerado, presenta leves complicaciones y puede ser una alternativa a la cirugía en algunos casos.

Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in "freeze-all" approach.

OBJECTIVE: To determine the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders (25-35 follicles with a diameter of ≥12 mm on day of triggering) who received a gonadotropin-releasing hormone (GnRH) agonist to trigger final follicular maturation. METHODS: We used individual data from women who participated in four different clinical trials and were high responders to ovarian stimulation in a GnRH antagonist protocol in this retrospective combined analysis. All women were evaluated for signs and symptoms of OHSS using identical criteria based on Golan's system (1989). RESULTS: High responders (n = 77) were of different ethnicities. There were no differences in baseline characteristics between women with or without signs and symptoms of OHSS. Mean ± standard deviation baseline data were: age, 32.3 ± 3.5 years; anti-Müllerian hormone, 42.4 ± 20.7 pmol/L; antral follicle count, 21.5 ± 9.2. Before triggering, duration of stimulation was 9.5 ± 1.6 days and the mean number of follicles with a diameter of ≥12 mm and ≥17 mm was 26.5 ± 4.4 and 8.8 ± 4.7, respectively. Mean serum estradiol (17,159 pmol/l) and progesterone (5.1 nmol/l) levels were high at 36 h after triggering. Overall, 17/77 high responders (22%) developed signs and symptoms of mild OHSS which lasted 6-21 days. The most frequently prescribed medication was cabergoline to prevent worsening of OHSS. No severe OHSS occurred and no OHSS cases were reported as serious adverse events. CONCLUSIONS: High responders receiving GnRH agonist for triggering should be informed that they may experience signs and symptoms of mild OHSS.

Certification of protein biomarker standards using element MS and generic standards: Application to human cytokines.

The availability of protein standards and methods for their characterization, quantification, and purity assessment are currently a bottleneck in absolute quantitative proteomics. In this work, we introduce an absolute quantitative analytical strategy based on ICP-MS sulfur detection that uses sulfate as generic standard to quantify and certify the mass purity of protein standards. The methodology combines capillary chromatographic separation with parallel detection with ICP-MS and ESI-MS to determine proteoforms concentration and identity, respectively. The workability of the methodology was demonstrated using recombinant human cytokine standards IP-10 and Flt3L (2 batches), which are relevant biomarkers for carcinoma or inflammatory diseases. Every key factor (transport efficiency, column recovery, signal stability and internal standard suitability) was taken into account and certified BSA standard was used as quality control for validation purposes. Protein quantification values and resulting mass purity certification of IP-10 and one batch of Flt3L were very high (100 and 86%, respectively). Lower mass purity obtained for another batch of Flt3L (<70%) concurred with the finding of significant proteoforms resulted from oxidation processes as observed by parallel ESI-MS.

Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.