Exploring microbiota-gut-brain axis biomarkers linked to autism spectrum disorder in prenatally chlorpyrifos-exposed Fmr1 knock-out and wild-type male rats.

Fmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like phenotype in preclinical studies. Gestational exposure to chlorpyrifos (CPF) has been associated with ASD diagnosis in humans and ASD-like behaviors in rodents and linked to the microbiota-gut-brain axis. In this study, we have used both Fmr1-KO and wild-type male rats (F2 generation) at postnatal days (PND) 7 and 40 obtained after F1 pregnant females were randomly exposed to 1 mg/kg/mL/day of CPF or vehicle. A nuclear magnetic resonance (NMR) metabolomics approach together with gene expression profiles of these F2 generation rats were employed to analyze different brain regions (such as prefrontal cortex, hippocampus, and cerebellum), whole large intestine (at PND7) and gut content (PND40). The statistical comparison of each matrix spectral profile unveiled tissue-specific metabolic fingerprints. Significant variations in some biomarker levels were detected among brain tissues of different genotypes, including taurine, myo-inositol, and 3-hydroxybutyric acid, and exposure to CPF induced distinct metabolic alterations, particularly in serine and myo-inositol. Additionally, this study provides a set of metabolites associated with gastrointestinal dysfunction in ASD, encompassing several amino acids, choline-derived compounds, bile acids, and sterol molecules. In terms of gene expression, genotype and gestational exposure to CPF had only minimal effects on decarboxylase 2 (gad2) and cholinergic receptor muscarinic 2 (chrm2) genes.

Corrigendum: NK cell subsets changes in partial remission and early stages of pediatric type 1 diabetes.

[This corrects the article DOI: 10.3389/fimmu.2020.611522.].

[Abordaje y atención a la cronicidad con tecnologías digitales en las políticas sanitarias en España]. / Approach and attention to chronicity with digital technologies in health policies in Spain.

OBJECTIVE: From the healthcare policies that support Public Health strategies, technology implementation in healthcare is an innovative element to address chronicity. Its introduction is not uniform across Spain, despite of the existence of digital strategic implementation and national chronicity plans. The aim of this paper was to explore the current deployment of autonomic strategies for chronicity and the implementation of digital tools for telemonitoring and user support. METHODS: A descriptive cross-sectional study was conducted through documental review of autonomous strategies in digital health and chronicity care, available until 2020. Consequently, a consultation was carried out to eighteen experts addressing autonomic availability, benefits and barriers to healthcare digitalization. RESULTS: The expert consultation revealed that, in fifteen autonomous communities, the use and the enhancement of digital technologies were addressed and in nine the focus was on promoting digital transformation. Eleven communities are working on updates, fourteen have health-related digital applications, thirteen allow users checking their test results, ten allow them to carry out administrative procedures, nine deliver patient support resources, and three provide telematic communication channels. 38.89% of the consulted refered not knowing about the existence of any follow-up and monitoring programs in their community. The 60% identified a gap in digital competencies among citizens and the lack of resources, as main barriers to implementation. CONCLUSIONS: There exists disparity in the update of strategies to address chronicity and the introduction of digital technologies. Many of them are currently updating, which is an opportunity to provide efficient responses that incorporate digital tools.

OBJECTIVE: La implementación de tecnologías digitales supone un elemento innovador para el abordaje de la cronicidad, como parte de las estrategias de Salud Pública. Su implantación es variable a nivel autonómico, pese a existir un plan nacional. Este trabajo pretendió conocer el despliegue de las estrategias autonómicas sobre cronicidad, así como de la implementación de opciones de telemonitorización y apoyo al usuario. METHODS: Se realizó un estudio descriptivo transversal mediante revisión documental de las estrategias autonómicas de salud digital y abordaje de la cronicidad disponibles hasta 2020. Se realizó una posterior consulta a dieciocho personas expertas sobre disponibilidad autonómica, beneficios y barreras a la digitalización de la atención sanitaria. RESULTS: La consulta a personas expertas reveló que quince comunidades autónomas abordaron el uso y la potenciación de tecnologías digitales y nueve trabajaron en favorecer la trasformación digital. Once comunidades trabajan en actualizaciones, catorce tienen aplicaciones digitales de salud, trece permiten a los ciudadanos consultar resultados de pruebas, diez permiten trámites administrativos, nueve ofrecen recursos de apoyo al paciente y tres disponen de canales telemáticos de comunicación. El 38,89% de los consultados refirió no conocer los programas de seguimiento y monitorización en su comunidad. El 60% identificó a la falta de competencias digitales de la ciudadanía y a la falta de recursos como barreras de su implantación. CONCLUSIONS: Existe disparidad en la actualización de estrategias para el abordaje de la cronicidad y la implantación de tecnologías digitales. Muchas de ellas se están actualizando, lo que supone una oportunidad para dar respuestas eficientes que incorporen las herramientas digitales.

Corrigendum: Candidate biomarkers for the prediction and monitoring of partial remission in pediatric type 1 diabetes.

[This corrects the article DOI: 10.3389/fimmu.2022.825426.].

Diagnosis and treatment of myocarditis and inflammatory cardiomyopathy. Consensus document of the SEC-Working Group on Myocarditis.

Myocarditis is defined as myocardial inflammation and its etiology is highly diverse, including infectious agents, drugs, and autoimmune diseases. The clinical presentation also varies widely, extending beyond the classic clinical picture of acute chest pain, and includes cases of cardiomyopathy of unknown cause whose etiology may be inflammatory. Because certain patients may benefit from targeted treatments, the search for the etiology should begin when myocarditis is first suspected. There remain several areas of uncertainty in the diagnosis and treatment of this disease. Consequently, this consensus document aims to provide clear recommendations for its diagnosis and treatment. Hence, a diagnostic algorithm is proposed, specifying when non-invasive diagnosis with cardiac MR is appropriate vs a noninvasive approach with endomyocardial biopsy. In addition, more novel aspects are discussed, such as when to suspect an underlying genetic etiology. The recommendations cover the management of myocarditis and inflammatory cardiomyopathy, both for general complications and specific clinical entities.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69±10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P<.001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39±0.89 pre- and 0.18±0.57 postadoption (P<.001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P<.001). The mean number of visits per patient was 0.47±1.11 pre- and 0.16±0.51 postadoption (P<.001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

A quantitative comparative surgical analysis of the endoscopic transorbital approach and frontotemporal-orbitozygomatic approach for extradural exposure of the cavernous sinus.

OBJECTIVE: Recently, the endoscopic superior eyelid transorbital approach (SETA) has emerged as a potential alternative to access the cavernous sinus (CS). Several previous studies have attempted to quantitatively compare the traditional open anterolateral skull base approaches with transorbital exposure; however, these comparisons have been limited to the area of exposure provided by the bone opening and trajectory, and fail to account for the main avenues of exposure provided by subsequent requisite surgical maneuvers. The authors quantitatively compare the surgical access provided by the frontotemporal-orbitozygomatic (FTOZ) approach and the SETA following applicable periclinoid surgical maneuvers, evaluate the surgical exposure of key structures in each, and discuss optimal approach selection. METHODS: SETA and FTOZ approaches were performed with subsequent applicable surgical maneuvers on 8 cadaveric heads. The lengths of exposure of cranial nerves (CNs) II-VI and the cavernous internal carotid artery; the areas of the space accessed within the supratrochlear, infratrochlear, and supramaxillary (anteromedial) triangles; the total area of exposure; and the angles of attack were measured and compared. RESULTS: Exposure of the extradural CS was comparable between approaches, whereas access was significantly greater in the FTOZ approach compared with the SETA. The lengths of extradural exposure of CN III, V1, V2, and V3 were comparable between approaches. The FTOZ approach provided marginally increased exposure of CNs IV (20.9 ± 2.36 mm vs 13.4 ± 3.97 mm, p = 0.023) and VI (14.1 ± 2.44 mm vs 9.22 ± 3.45 mm, p = 0.066). The FTOZ also provided significantly larger vertical (44.5° ± 6.15° vs 18.4° ± 1.65°, p = 0.002) and horizontal (41.5° ± 5.40° vs 15.3° ± 5.06°, p < 0.001) angles of attack, and thus significantly greater surgical freedom, and provided significantly greater access to the supratrochlear (p = 0.021) and infratrochlear (p = 0.007) triangles, and significantly greater exposure of the cavernous internal carotid artery (17.2 ± 1.70 mm vs 8.05 ± 2.37 mm, p = 0.001). Total area of exposure was also significantly larger in the FTOZ, which provided wide access to the lateral wall of the CS as well as the possibility for intradural access. CONCLUSIONS: This is the first study to quantitatively identify the relative advantages of the FTOZ and transorbital approaches at the target region following requisite surgical maneuvers. Understanding these data will aid in selecting an optimal approach and maneuver set based on target lesion size and location.

Evolution of Diagnoses, Survival, and Costs of Oncological Medical Treatment for Non-Small-Cell Lung Cancer over 20 Years in Osona, Catalonia.

Non-small-cell lung cancer (NSCLC) has experienced several diagnostic and therapeutic changes over the past two decades. However, there are few studies conducted with real-world data regarding the evolution of the cost of these new drugs and the corresponding changes in the survival of these patients. We collected data on patients diagnosed with NSCLC from the tumor registry of the University Hospital of Vic from 2002 to 2021. We analyzed the epidemiological and pathological characteristics of these patients, the diverse oncological treatments administered, and the survival outcomes extending at least 18 months post-diagnosis. We also collected data on pharmacological costs, aligning them with the treatments received by each patient to determine the cost associated with individualized treatments. Our study included 905 patients diagnosed with NSCLC. We observed a dynamic shift in histopathological subtypes from squamous carcinoma in the initial years to adenocarcinoma. Regarding the treatment approach, the use of chemotherapy declined over time, replaced by immunotherapy, while molecular therapy showed relative stability. An increase in survival at 18 months after diagnosis was observed in patients with advanced stages over the most recent years of this study, along with the advent of immunotherapy. Mean treatment costs per patient ranged from EUR 1413.16 to EUR 22,029.87 and reached a peak of EUR 48,283.80 in 2017 after the advent of immunotherapy. This retrospective study, based on real-world data, documents the evolution of pathological characteristics, survival rates, and medical treatment costs for NSCLC over the last two decades. After the introduction of immunotherapy, patients in advanced stages showed an improvement in survival at 18 months, coupled with an increase in treatment costs.

Mental Health Nursing Student's Perception of Clinical Simulation about Patients at Risk of Suicide: A Qualitative Study.

Suicide is a serious public health problem, with a global mortality rate of 1.4% of all deaths worldwide and the leading cause of unnatural death in Spain. Clinical simulation has proven to be a beneficial tool in training nursing students. Such experiences allow them to develop cognitive and affective skills that are fundamental for the detection of warning signs and the use of interventions in cases of people who want to take their own lives. Working in a mental health environment can be difficult for nursing students; therefore, the purpose of this study was to explore the perceptions of nursing students on the approach, management, and intervention of suicidal crisis through clinical mental health simulation. METHODS: qualitative descriptive phenomenological study through focus groups and reflective narratives in a sample of 45 students. A thematic analysis was performed using ATLAS-ti. RESULTS: After the analysis, three themes were obtained: (a) management and handling of emotions, (b) identification of suicide motives, and (c) intervention in suicidal crisis. DISCUSSION: Clinical simulation in mental health allows students to exercise clinical judgment reasoning, detect warning signs for a better treatment approach, and provide tools for effective intervention and management of patient care. The results of this study indicate that nursing students face challenges in approaching mental health clinical simulation due to a lack of prior exposure.

Combined Predictive Model for Endoscopic Third Ventriculostomy Success in Adults and Children.

BACKGROUND: The selection of patients in whom endoscopic third ventriculostomy (ETV) can be effective remains poorly defined. The ETV success score (ETVSS) and the presence of bowing of the third ventricle have been identified as independent factors for predicting success, each with limitations. The objective of this study is to elaborate a combined predictive model to predict ETV success in a mixed cohort of patients. METHODS: Demographic, intraoperative, postoperative, and radiologic variables were analyzed in all ventriculostomies performed consecutively at a single institution from December 2004 to December 2022. Qualitative and quantitative measurements of preoperative, immediate, and late postoperative magnetic resonance imaging were conducted. Univariate analysis and logistic regression models were performed. RESULTS: 118 ETVs were performed in the selected period. Of these procedures, 106 met the inclusion criteria. The overall success rate was 71.7%, with a median follow-up of 3.64 years (interquartile range, 1.06-5.62). The median age was 36.1 years (interquartile range, 11.7-53.5). 35.84% were children (median, 7.81 years). Among the 80 patients with third ventricle bowing, the success rate was 88.8% (P < 0.001). Larger third ventricle dimensions on preoperative mid-sagittal magnetic resonance imaging were associated with increased ETV success. The model with the best receiver operating characteristic curves, with an area under the curve of 0.918 (95% confidence interval, 0.856-0.979) includes sex, ETVSS, presence of complications, and third ventricle bowing. CONCLUSIONS: The presence of bowing of the third ventricle is strongly associated with a higher ETV success rate. However, a combined predictive model that integrates it with the ETVSS is the most appropriate approach for selecting patients for ETV.

Safety of Plasma Rich in Growth Factors (PRGF) as additive to healthy human sperm samples: a pilot study.

OBJECTIVE: The aim of our study was to assess if the addition of PRGF to healthy human sperm affects its motility and vitality. METHODS: This was a prospective study, with 44 sperm donors on whom sperm analysis was performed. Nine mL of blood was collected and PRGF was obtained using PRGF-Endoret® technology. The influence of different dilutions of PRGF (5%, 10%, 20%, 40%) applied to 15 sperm donors was compared, and sperm motility was assessed after 30 minutes. In the second part of the study, 29 sperm donors were studied to analyze the influence of 20% dilution of PRGF at 15, 30 and 45 minutes in fresh and thawed sperm samples. Motility was assessed after the addition of PRGF and after analysis each aliquot was frozen. After thawing, concentration and motility were assessed at the same time periods. RESULTS: There were no differences in sperm motility in fresh samples between dilutions of PRGF when assessed 30 minutes after administration, nor between them, nor when compared to the control group immediately prior to treatment. No trend was observed between motility and PRGF dilution in linear regression analysis. There were no significant differences in thawed samples. CONCLUSIONS: The administration of 20% PRGF dilution had no effect on sperm motility compared to samples without PRGF. In addition, there was no change in sperm vitality when comparing samples with and without PRGF. More studies focusing on subnormal sperm samples, analyzing different PRGF concentrations and increasing the number of study variables are needed.

Baseline NT-proBNP levels as a predictor of short-and long-term prognosis in COVID-19 patients: a prospective observational study.

BACKGROUND: Up to 20% of COVID-19 patients can suffer COVID-19-related myocardial injury. Elevated cardiac biomarkers, such as hs-cTnT and NT-proBNP, have been related to worse short-term prognosis. However, data on NT-proBNP and long-term prognosis are scarce. We have evaluated the potential association of baseline age-adjusted NT-proBNP levels and outcomes at one-year follow-up in COVID-19 patients. METHODS: This was a single-center prospective study of 499 COVID-19 patients in whom NT-proBNP was assessed at hospital admission. NT-proBNP levels were age-adjusted and patients were classified as high or low NT-proBNP. Clinical and demographic characteristics, comorbidities, laboratory results, and in-hospital complications and mortality were compared between the two groups. Survivors of the acute phase of COVID-19 were followed up for one year from admission to detect readmissions and mortality. RESULTS: The 68 patients with high NT-proBNP levels at hospital admission were older, with more cardiovascular risk factors, cardiovascular disease, comorbidities, myocardial injury, and higher levels of inflammatory markers than patients with low NT-proBNP levels. They also had more in-hospital complications and a higher acute-phase mortality rate (60.3% vs. 10.2%, p < 0.001). High NT-proBNP levels were an independent marker of death during hospitalization (HR 1.95; CI 1.07-3.52). At one-year follow-up, high NT-proBNP levels were independently associated with mortality (HR 2.69; CI 1.47-4.89). Among survivors of the acute phase of COVID-19, there were no differences in hospital readmissions between those with high vs. low NT-proBNP levels, but survivors with high baseline NT-proBNP levels showed a higher 1-year mortality rate (7.4% vs. 1.3%, p = 0.018). CONCLUSIONS: High age-adjusted NT-proBNP levels at the time of hospital admission for COVID-19 are associated with poor short and long-term prognosis. High NT-proBNP seems also to be related to worse prognosis in survivors of the acute phase of COVID-19. A closer follow-up on these patients may be crucial.

Effectiveness of motor imagery in complex regional pain syndrome: A systematic review with meta-analysis.

OBJECTIVE: The purpose of this study was to determine the effects of motor imagery (MI) on pain intensity and disability in individuals with complex regional pain syndrome (CRPS). METHODS: A systematic search was conducted in various electronic databases to identify all relevant studies: PubMed, CINAHL, WOS, PEDro, CENTRAL, and Scopus. Randomized controlled trials assessing the effects of MI in individuals with CRPS were included. The risk of bias was assessed with the Cochrane Risk of Bias tool, the methodological quality was evaluated using PEDro scale, and the level of evidence was reported according to the GRADE. Between-groups standardized mean differences (SMD) were calculated. RESULTS: Six studies were included. The meta-analysis found moderate-quality evidence that MI improves pain intensity and related disability as immediate (pain: SMD -1.07, 95% CI: -1.53 to -0.60; disability: SMD 1.05, 95% CI: 0.59 to 1.51), short-term (pain: SMD -1.28, 95% CI: -2.14 to -0.42; disability: SMD 1.37; 95% CI: 0.16 to 2.58), and long-term effects (pain: SMD -1.18; 95% CI: -1.89 to -0.46; disability: SMD 1.18; 95% CI: 0.46 to 1.89), as compared with a comparison group. The risk of bias of the trials was relatively low, but the imprecision of the results downgraded the level of evidence. CONCLUSIONS: Moderate-quality evidence suggests a positive effect of MI for improving pain intensity and disability immediately after and at short-term in individuals with CRPS.

Long-Acting Injectable Second-Generation Antipsychotics in Seriously Ill Patients with Schizophrenia: Doses, Plasma Levels, and Treatment Outcomes.

This research studies the dose-plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people with schizophrenia. An observational, prospective, one-year follow-up study was carried out with patients (N = 68) with severe schizophrenia treated with paliperidone three-month (PP3M) or aripiprazole one-month (ARIM). Participants were divided into standard-dose or high-dose groups. PLs were divided into "standard PL" and "high PL" (above the therapeutic reference range, TRR) groups. The dose/PL relationship, and severity, hospitalizations, tolerability, compliance, and their relationship with doses and PLs were evaluated. There was no clear linear relationship between ARIM or PP3M doses and the PLs achieved. In half of the subjects, standard doses reached PLs above the TRR. The improvements in clinical outcomes (decrease in clinical severity and relapses) were related to high PLs, without worse treatment tolerability or adherence. All participants remained in the study, regardless of dose or PL. Clinical severity and hospitalizations decreased significantly more in those patients with high PLs. Considering the non-linear dose-PL relationship of ARIM and PP3M in people with severe schizophrenia, PLs above the TRR are linked to better treatment outcomes, without worse tolerability. The need in a notable number of cases for high doses to reach those effective PLs is highlighted.

Evaluation of the use of a nursing diagnosis Risk for Falls in the Community of Madrid (Spain) Primary Care System.

PURPOSE: The purpose of this study was to describe the use of the nursing diagnosis Risk for Falls in Primary Care System of the Community of Madrid. METHODS: A retrospective review of the clinical histories was carried out in 262 health centers from January 2005 to December 2015. The study population are the patients who have recorded in their electronic health record the nursing diagnosis Risk for Falls. FINDINGS: Frequency of use of the Risk for Falls ND in the Community of Madrid was 53,340 diagnoses, increasing from 650 nursing diagnosis in 2005 to 14,695 in 2015. NOC Nursing Outcomes total identified were 109,145, which represents an average of 2.05 NOC Nursing Outcomes per diagnosis. NOC Nursing Outcomes frequently appeared as follows: Fall Prevention Behavior (35.9%), Safe Home Environment (11.3%), and Risk Control (10.5%). NIC Nursing Interventions total identified were 104,293, representing an average of 1.96 NIC nursing interventions per diagnosis. NIC Nursing Interventions frequently appeared as follows: Fall Prevention (45.9%), Environmental Management: Safety (27%), and Risk Identification (5.8%). CONCLUSIONS: Nursing diagnosis of Risk for Falls and the care process related to this diagnosis is starting to be used by the primary care nurses of the Community of Madrid. IMPLICATION FOR NURSING PRACTICE: Risk factors related to the nursing diagnosis of risk for falls identified in our study can be addressed with activities that nurses must implement to prevent falls. Nursing methodology in general and specifically the diagnosis of risk for falls must be included in guides and protocols for the prevention of falls, and its use should be promoted by primary care nurses.

Diagnostic Performance of the Measurement of Skinfold Thickness for Abdominal and Overall Obesity in the Peruvian Population: A 5-Year Cohort Analysis.

The escalating prevalence of overall and abdominal obesity, particularly affecting Latin America, underscores the urgent need for accessible and cost-effective predictive methods to address the growing disease burden. This study assessed skinfold thicknesses' predictive capacity for overall and abdominal obesity in Peruvian adults aged 30 or older over 5 years. Data from the PERU MIGRANT 5-year cohort study were analyzed, defining obesity using BMI and waist circumference. Receiver operating characteristic curves and area under the curve (AUC) with 95% confidence intervals (CI) were calculated. Adults aged ≥ 30 (n = 988) completed the study at baseline, with 47% male. A total of 682 participants were included for overall and abdominal obesity analysis. The 5-year prevalence values for overall and abdominal obesity were 26.7% and 26.6%, respectively. Subscapular skinfold (SS) best predicted overall obesity in men (AUC = 0.81, 95% CI: 0.75-0.88) and women (AUC = 0.77, 95% CI: 0.67-0.88). Regarding abdominal obesity, SS exhibited the highest AUC in men (AUC = 0.83, 95% CI: 0.77-0.89), while SS and the sum of trunk skinfolds showed the highest AUC in women. In secondary analysis excluding participants with type-2 diabetes mellitus (DM2) at baseline, SS significantly predicted DM2 development in men (AUC = 0.70, 95% CI: 0.58-0.83) and bicipital skinfold (BS) did in women (AUC = 0.73, 95% CI: 0.62-0.84). The findings highlight SS significance as an indicator of overall and abdominal obesity in both sexes among Peruvian adults. Additionally, SS, and BS offer robust predictive indicators for DM2.

Plasmatic Levels and Response to Variable Doses of Monthly Aripiprazole and Three-Month Paliperidone in Patients with Severe Schizophrenia. Treatment Adherence, Effectiveness, Tolerability, and Safety.

Introduction: There is a need when optimizing antipsychotic treatment to know the plasmatic levels (PLs) achieved with the different doses and their relationship with effectiveness and toxicity, especially in patients with poor clinical progress. This study investigates the dose-PL-response relationship of monthly aripiprazole (AOM) and three-month paliperidone (PP3M). Methods: Observational, 52-week prospective study of patients with severe schizophrenia (CGI-S ≥ 5) treated with PP3M or AOM for at least one year before their inclusion in the study (N=68). Dose-PL relationship was determined. Subjects were included in standard-dose and high-dose (above labeled) and standard/therapeutic range-PLs and high-PLs (above range) groups. Treatment adherence, effectiveness (hospitalizations, severity), tolerability and safety were assessed. PLs and clinical response were evaluated. Results: No clear linear relationship was found between doses and PLs. In a considerable number of cases, standard doses achieved PLs above the therapeutic range. A significant clinical improvement was related to high PLs, without less safety, tolerability, or treatment compliance being involved. Clinical severity decreased more frequently in patients who received high doses and reached high PLs. Hospital admissions decreased significantly in those patients with high PLs. Conclusion: Taking into account the absence of a linear relationship between doses and PLs, the effectiveness in people with severe schizophrenia of AOM and PP3M depends on reaching high PLs, achieved with high doses, but also with standard doses in some cases, without leading to worse treatment tolerability, safety, or adherence.

Sellar xanthogranuloma as a diagnostic challenge: a report on five cases.

Xanthogranulomas are considered rare tumors, with their sellar and non-sellar frequency ranging from 1.6 to 7% among intracranial lesions, and described as a separate entity by the World Health Organization in 2000. The diagnosis of sellar xanthogranulomas is challenging, given their uncertain origin and clinical course. In addition, the limited reporting of sellar xanthogranuloma cases and the absence of characteristic images make these entities difficult to distinguish from other cystic lesions of the sellar region, such as adamantinomatous craniopharyngiomas, Rathke's cleft cysts, pituitary tumors, arachnoid cysts, epidermoid cysts, and dermoid cysts. Here, we describe the clinical presentation, radiological findings, immunohistochemical/histopathological analysis, and the ultrastructural examination by transmission electron microscopy of five sellar xanthogranulomas cases reported in two care centers in Cordoba, Argentina. Two males and three females between 37 and 73 years of age (average 51.8 years) presented with persistent headaches, generalized endocrine defects, and visual problems. MRI revealed cystic formations in the sellar region, which usually projected into adjacent tissues such as the suprasellar region or cavernous sinuses, and compressed other structures such as the optic chiasm, pituitary gland, and cranial nerves. All patients underwent surgical intervention to remove the tumor tissue. The histopathological analysis of the samples showed cellular tissue with a xanthogranulomatous appearance, inflammatory cellular infiltrate (mainly lymphocytes and macrophages), fibroblasts, abundant collagen fibers, and hemorrhages. An ultrastructural analysis helped to identify cellular infiltrates and granules resulting from tumor cell activity. The data support the hypothesis that sellar xanthogranulomas could occur as an inflammatory reaction secondary to the rupture and hemorrhage of a previous cystic process, thereby generating an expansion of the tumor body toward adjacent tissues. The information obtained from these cases contributes to the current knowledge about this disease's origin and clinical and histological evolution. However, the scarcity of patients and the observed phenotypic heterogeneity make its diagnosis still challenging. Undoubtedly, more investigations are needed to provide additional information in order to be able to achieve a more accurate diagnosis and effective treatment of this rare disease.