Cytochrome b5 reductase 3 overexpression and dietary nicotinamide riboside supplementation promote distinctive mitochondrial alterations in distal convoluted tubules of mouse kidneys during aging.

The kidney undergoes structural and physiological changes with age, predominantly studied in glomeruli and proximal tubules. However, limited knowledge is available about the impact of aging and anti-aging interventions on distal tubules. In this study, we investigated the effects of cytochrome b5 reductase 3 (CYB5R3) overexpression and/or dietary nicotinamide riboside (NR) supplementation on distal tubule mitochondria. Initially, transcriptomic data were analyzed to evaluate key genes related with distal tubules, CYB5R3, and NAD+ metabolism, showing significant differences between males and females in adult and old mice. Subsequently, our emphasis focused on assessing how these interventions, that have demonstrated the anti-aging potential, influenced structural parameters of distal tubule mitochondria, such as morphology and mass, as well as abundance, distance, and length of mitochondria-endoplasmic reticulum contact sites, employing an electron microscopy approach. Our findings indicate that both interventions have differential effects depending on the age and sex of the mice. Aging resulted in an increase in mitochondrial size and a decrease in mitochondrial abundance in males, while a reduction in abundance, size, and mitochondrial mass was observed in old females when compared with their adult counterparts. Combining both the interventions, CYB5R3 overexpression and dietary NR supplementation mitigated age-related changes; however, these effects were mainly accounted by NR in males and by transgenesis in females. In conclusion, the influence of CYB5R3 overexpression and dietary NR supplementation on distal tubule mitochondria depends on sex, genotype, and diet. This underscores the importance of incorporating these variables in subsequent studies to comprehensively address the multifaceted aspects of aging.

Social costs associated with fibromyalgia in Spain.

BACKGROUND: Fibromyalgia is a chronic rheumatic disease of unknown aetiology, highly disabling and mainly affecting women. The aim of our work is to estimate, on a national scale, the economic impact of this disease on the employment of patients and non-professional (informal) care dimension. METHODS: Survey on Disabilities, Autonomy and Dependency carried out in Spain in 2020/21 was used to obtain information on disabled individuals with AD and their informal caregivers. Six estimation scenarios were defined as base case, depending on whether the maximum daily informal caregiving time was censored or not, and on the approach chosen for the valuation of informal caregiving time (contingent valuation and replacement time). Another six conservative scenarios were developed using the minimum wage for the estimation of labour losses. RESULTS: Our estimates range from 2,443.6 (willingness to pay, censored informal care time) to 7,164.8 million euros (replacement cost, uncensored informal care time) (base year 2021). Multivariate analyses identified that the degree of dependency of the person suffering from fibromyalgia is the main explanatory variable for both the probability of being employed and the time spent in informal care. Conservative scenarios estimates range from 1,807 to 6,528 million euros. CONCLUSIONS: The high economic impact revealed should help to position a health problem that is relatively unknown in society and for which there are significant research and care gaps to be filled.

PPARG is dispensable for bovine embryo development up to tubular stages.

Following blastocyst hatching, ungulate embryos undergo a prolonged preimplantation period termed conceptus elongation. Conceptus elongation constitutes a highly susceptible period for embryonic loss and the embryonic requirements during this process are largely unknown, but multiple lipid compounds have been identified in the fluid nourishing the elongating conceptuses. Peroxisome proliferator-activated receptors (PPARs) mediate the signaling actions of prostaglandins and other lipids and, between them, PPARG has been pointed out to play a relevant role on conceptus elongation by a functional study that depleted PPARG in both uterus and conceptus. The objective of this study has been to determine if embryonic PPARG is required for bovine embryo development. To that aim, we have generated bovine PPARG KO embryos in vitro by two independent gene ablation strategies and assess their developmental ability. In vitro development to Day (D) 8 blastocyst was unaffected by PPARG ablation, as total, inner cell mass and trophectoderm cell numbers were similar between WT and KO D8 embryos. In vitro post-hatching development to D12 was also comparable between different genotypes, as embryo diameter, epiblast cell number, and embryonic disc formation and hypoblast migration rates were unaffected by the ablation. The development to tubular stages equivalent to E14 was assessed in vivo, following a heterologous embryo transfer experiment, observing that the development of extra-embryonic membranes and of the embryonic disc was not altered by PPARG ablation. In conclusion, PPARG ablation did not impaired bovine embryo development up to tubular stages.

Near Field Detection and Peak Frequency Metric for Substrate and Activation Mapping of Ventricular Arrhythmias in 2- and 3-Dimensional Circuits.

BACKGROUND: Successful ventricular arrhythmia (VA) ablation requires identification of functionally critical sites during contact mapping. Estimation of the peak frequency (PF) component of the EGM may improve correct near field (NF) annotation to identify circuit segments on the mapped surface. In turn, assessment of near- and far field (FF) EGMs may delineate the 3-dimensional path of a VT circuit. METHODOLOGY: A proprietary NF detection algorithm was applied retrospectively to scar-related re-entry VT maps and compared to manually reviewed maps employing first deflection (FDcorr) for VT activation maps and last deflection (LD) for substrate maps. VT isthmus location and characteristics mapped with FDcorr vs. NF were compared. Omnipolar low voltage areas, late activating areas and deceleration zones in LD vs NF substrate maps were compared. On substrate maps, PF estimation was compared between isthmus and bystander-sites. Activation mapping with entrainment and/or VT termination with RF ablation confirmed critical sites. RESULTS: 18 patients with high-density VT activation and substrate maps (55.6% ischemic) were included. NF detection correctly located critical parts of the circuit in 77.7% of the cases compared to manually reviewed VT maps as reference. In substrate maps NF detection identified deceleration zones in 88.8% of cases which overlapped with FDcorr VT isthmus in 72.2% compared to 83.3% overlap of DZ assessed by LD. Applied to substrate maps, PF as a stand-alone feature did not differentiate VT isthmus-sites from low voltage bystander-sites. Omnipolar voltage was significantly higher at isthmus-sites with longer EGM durations compared to low voltage bystander-sites. CONCLUSION: The NF algorithm may enable rapid high-density activation mapping of VT circuits in the near field of the mapped surface. Integrated assessment and combined analysis of near and far field EGMs could support characterisation of 3-dimensional VT circuits with intramural segments. For scar-related substrate mapping, PF as a stand-alone EGM feature did not enable the differentiation of functionally critical sites of the dominant VT from low voltage bystander sites in this cohort.

[Inhaled levodopa: from evidence to experience]. / Levodopa inhalada: de la evidencia a la experiencia.

Most patients with Parkinson's disease experience motor fluctuations or 'off' periods, which impact on their daily activities, increase their disability and diminish their quality of life. They suffer from these fluctuations despite multiple adjustments to the schedules, doses and intake of medication. In this context, on-demand or rescue treatments are necessary to attempt to improve 'off' periods, with drugs that have the pharmacokinetic advantage of a much faster onset of action because their routes of administration are not oral. There are currently three on-demand therapies for the treatment of fluctuations: subcutaneous apomorphine, inhaled levodopa and sublingual apomorphine. Of the three alternatives, subcutaneous apomorphine generally has the fastest onset of action, sublingual apomorphine provides the longest clinical effect, and inhaled levodopa has the most favourable side effect profile. Each of these drugs has its own characteristics: the time before onset of action, the duration of action and different side effect profiles. The choice for each patient will depend on their individual needs and circumstances. To mark the first year of the introduction of inhaled levodopa, we review these therapies, focusing on the experience with this new dosage form of levodopa.

TITLE: Levodopa inhalada: de la evidencia a la experiencia.La mayoría de los pacientes con enfermedad de Parkinson sufren fluctuaciones motoras o períodos off, que impactan en sus actividades cotidianas, aumentan su discapacidad y empeoran su calidad de vida. A pesar de realizar múltiples ajustes en los horarios, en las dosis y en las tomas de medicación, no se consigue que estén libres de estas fluctuaciones. Es en este contexto en el que son necesarios los tratamientos a demanda o de rescate para tratar de mejorar los períodos off, con fármacos que tienen la ventaja farmacocinética de un inicio de acción mucho más rápido debido a que sus vías de administración no son orales. En la actualidad existen tres terapias a demanda para el tratamiento de las fluctuaciones: apomorfina subcutánea, levodopa inhalada y apomorfina sublingual. En general, la apomorfina subcutánea tiene un inicio de efecto más rápido, la apomorfina sublingual ofrece el efecto clínico más prolongado y la levodopa inhalada tiene el perfil de efectos secundarios más favorable entre las tres opciones. Cada uno de estos medicamentos tiene características únicas: tiempo de inicio, duración de acción y diferentes perfiles de efectos secundarios. La elección para cada paciente dependerá de sus necesidades y circunstancias individuales. Aprovechando el primer año de la introducción de la levodopa inhalada, revisamos estas terapias, centrándonos en la experiencia acumulada con esta nueva presentación galénica de levodopa.

Integration of QTL and transcriptome approaches for the identification of genes involved in tomato response to nitrogen deficiency.

Optimising plant nitrogen (N) usage and inhibiting N leaching loss in the soil-crop system is crucial to maintaining crop yield and reducing environmental pollution. This study aimed at identifying quantitative trait loci (QTLs) and differentially expressed genes (DEGs) between two N treatments in order to list candidate genes related to nitrogen-related contrasting traits in tomato varieties. We characterised a genetic diversity core-collection (CC) and a multi-parental advanced generation intercross (MAGIC) tomato population grown in greenhouse under two nitrogen levels and assessed several N-related traits and mapped QTLs. Transcriptome response under the two N conditions was also investigated through RNA sequencing of fruit and leaves in four parents of the MAGIC population. Significant differences in response to N input reduction were observed at the phenotypic level for biomass and N-related traits. Twenty-seven (27) QTLs were detected for three target traits (Leaf N content, leaf Nitrogen Balance Index and petiole NO3- content), ten and six at low and high N condition, respectively; while 19 QTLs were identified for plasticity traits. At the transcriptome level, 4,752 and 2,405 DEGs were detected between the two N conditions in leaves and fruits, respectively, among which 3,628 (50.6%) in leaves and 1,717 (71.4%) in fruit were genotype specific. When considering all the genotypes, 1,677 DEGs were shared between organs or tissues. Finally, we integrated DEGs and QTLs analyses to identify the most promising candidate genes. The results highlighted a complex genetic architecture of N homeostasis in tomato and novel putative genes useful for breeding tomato varieties requiring less N input.

Vibrational signatures of dynamic excess proton storage between primary amine and carboxylic acid groups.

Ammonium and carboxylic moieties play a central role in proton-mediated processes of molecular recognition, charge transfer or chemical change in (bio)materials. Whereas both chemical groups constitute acid-base pairs in organic salt-bridge structures, they may as well host excess protons in acidic environments. The binding of excess protons often precedes proton transfer reactions and it is therefore of fundamental interest, though challenging from a quantum chemical perspective. As a benchmark for this process, we investigate proton storage in the amphoteric compound 5-aminovaleric acid (AV), within an intramolecular proton bond shared by its primary amine and carboxylic acid terminal groups. Infrared ion spectroscopy is combined with ab initio Molecular Dynamics (AIMD) calculations to expose and rationalize the spectral signatures of protonated AV and its deuterated isotopologues. The dynamic character of the proton bond confers a fluxional structure to the molecular framework, leading to wide-ranging bands in the vibrational spectrum. These features are reproduced with remarkable accuracy by AIMD computations, which serves to lay out microscopic insights into the excess proton binding scenario.

A single administration of carbetocin before electroejaculation increases the insemination doses produced from each ejaculate in rams.

The aim of the study was to determine the effect of carbetocin administration (a long-acting analog of oxytocin) 20 or 10 min before electroejaculation (EE) on the duration of semen collection procedure, quantitative and qualitative characteristics of the ejaculate, and stress biomarkers in rams. Semen was collected from 12 Corriedale rams (age, 2.5-5.5 years old) with EE, in a Latin-square design, administrating carbetocin (0.2 mg/100 kg of body weight i.v.) 20 or 10 min before EE, or without carbetocin administration (CB-20, CB-10, and CON treatments, respectively). Each treatment was applied to different rams every 3-4 days, allowing all the rams to receive all three treatments. Carbetocin administered 20 or 10 min before EE increased the number of sperm ejaculated (P = 0.01), the semen concentration (P = 0.02), the number of insemination doses collected in a single collection (P = 0.01), and the number of insemination doses collected/electrical pulses administered (P = 0.05) compared to control rams. Carbetocin administered 20 or 10 min before semen collection prolonged the time required for EE and the number of pulses administered during EE compared to CON rams (P < 0.03 for both). The CB-10 rams required the administration of more electrical pulses during ejaculation than CON rams (P = 0.001), and CB-20 treatment tended to require more electrical pulses than CON rams (P = 0.06). The volume of the ejaculate was greater in CB-10 than in CON rams (P = 0.01), and that of CB-20 treatment tended to be greater than CON rams (P = 0.08). The percentage of sperm with intact membrane was greater in CB-20 than in CON rams (P = 0.01). Total protein, albumin, and globulin concentrations were lower immediately after carbetocin administration 20 or 10 min before EE. The treatments did not affect cortisol concentration, glycemia, rectal and surface temperatures, heart rate, and facial expressions. Carbetocin administration before EE of rams improved the quantitative and qualitative characteristics of the ejaculate, duplicating the number of insemination doses collected. It can be a promising treatment to obtain a greater quantity of doses to inseminate with a lower frequency of semen collections, reducing the negative impacts of EE on animal welfare.

Efectos secundarios oculares de las terapias oncológicas. Revisión / Ocular side effects of oncological therapies: Review

Con el avance de la terapia contra el cáncer en los últimos años, ha aumentado el conocimiento de los mecanismos involucrados en esta enfermedad, lo que ha supuesto un aumento de la calidad de vida y de la supervivencia de los pacientes con afecciones tumorales anteriormente consideradas incurables o refractarias al tratamiento. El número de fármacos utilizados ha sufrido un aumento exponencial, y a pesar de que la toxicidad implícita es menor que la de la terapia antineoplásica convencional, conllevan la aparición de nuevos efectos adversos asociados, que el oftalmólogo debe reconocer y manejar.(AU)

With the advance of cancer therapy in recent years, the knowledge of the mechanisms involved in this disease has increased, which has meant an increase in the quality of life and survival of patients with tumor pathologies previously considered incurable or refractory to treatment. The number of drugs used has increased exponentially in number, and although the implicit toxicity is lower than that of conventional antineoplastic therapy, they lead to the appearance of new associated adverse effects that the ophthalmologist must recognize and manage.(AU)

Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population.

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.

Factors associated with the discrepancy between objective and subjective cognitive impairment in bipolar disorder.

OBJECTIVE: The aim of this study is to evaluate the discrepancy between objective cognitive measures and cognitive subjective complaints in a sample of euthymic patients with bipolar disorder (BD). METHODS: One hundred and sixteen participants (83 euthymic patients with BD and 33 healthy controls) were enrolled for this study. Patients were assessed with a comprehensive neuropsychological battery and they also reported their subjective cognitive complaints with the Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA). The discrepancy between objective and subjective data was calculated using a novel methodology proposed in a previous study (Miskowiak, 2016). Statistical analyses included Pearson correlations and multiple linear regression. RESULTS: Higher number of previous depressive episodes was identified as one variable associated with the global sensitivity composite score (Beta = 0.25; t = 2.1; p = 0.04) and with the verbal learning and memory sensitivity score (Beta = 0.26; t = 2.16; p = 0.03). That is, patients with more previous depressive episodes tend to over-report cognitive complaints. In contrast, higher number of previous hospitalizations was associated with stoicism in the global total score (Beta = -0.27; t = -2.24: p = 0.029) and in the domain of attention/processing speed (Beta = -0.34; t = -2.52; p = 0.016), indicating patients with more hospitalizations tend to report less cognitive complaints. DISCUSSION: Our study identified some factors that might help to explain the discrepancy between objective and subjective cognitive measures in BD, including number of previous depressive episodes and number of previous hospitalizations. This highlights the need of the combined use of both types of cognitive measures to make an accurate assessment of cognitive dysfunctions and their effective treatment.

Carbon capture from biomass flue gases for CO2 enrichment in greenhouses.

Heating and CO2 enrichment systems can improve yields in intensive greenhouse agriculture Combining both techniques, which are currently applied commercially, can potentially enhance their effect. The CO2 must be separated from the other noxious gases present (such as CO, NOX, and SO2) to avoid them becoming part of the supply. The CO2 is then provided to the greenhouse on demand in the same way as the heating. In this work, we show that an improved food productivity of a pilot-scale greenhouse system combined with CO2 capture by adsorption using activated carbon and heating with alternative fuel. The proposed system's overall performance was evaluated and optimized. The best values were 46.7 g/kg of CO2 storage capacity on the adsorbent bed, 99.99 % removal rate harmful gases from the gas supplied to the greenhouse, CO2 levels of 1851.0 ± 262.8 mg/Nm3 of the CO2 levels in the greenhouse, and an enrichment time of 2.18 ± 0.92 h/day. The system's effective performance over extended periods (November-February) was confirmed and the productivity of a crop species (tomato) was compared to a control, showing an increment of 18 %. The results indicate that this is a valuable option for increasing the crop yield. By integrating this combined system with advanced climate control strategies, it is possible to maximize the CO2 provided per day, leading to higher yields. The system proved to be stable under real pilot-scale conditions over winter periods (four months).

Efficient and repeatable in vitro fertilization in rabbits.

Rabbits constitute an interesting model to understand gamete interaction and test novel Artificial Reproductive Techniques, but in vitro fertilization (IVF) is particularly problematic in this species. We have conducted a series of experiments to develop a consistent IVF technique. Initially, we checked viability, acrosome integrity, capacitation and motility in ejaculated sperm purified by a density gradient and incubated at different times in three different media: Tyrode's Albumin Lactate Pyruvate (TALP), human tubal fluid (HTF), and Brackett and Oliphant (BO). Total and progressive motility at 10-24 h and linearity from 3 h onwards was significantly higher in BO medium compared to TALP and HTF. Subsequently, cumulus-oocyte complexes (COCs) collected 10 h after induction of ovulation were incubated with sperm in TALP, HTF or BO for 18 h with or without performing sperm pre-incubation for 6 h. Pronuclear formation rate at 18 h was significantly higher in BO compared to other media (∼84 % vs. 17-22 %) and was not improved by pre-incubation. As COCs recovery rate was low at 10 h after induction of ovulation, COCs were collected at 12 h and co-incubated with sperm in BO. Pronuclear formation rate was similar than those obtained in COCs collected at 10 h (∼85 %), and when embryos were allowed to develop in vitro, the protocol yielded high cleavage and blastocyst rates (91 and 59 %, respectively). In conclusion, ejaculated rabbit sperm purified in a density gradient fertilize efficiently COCs collected at 12 h in BO medium.

Laparoscopic intracorporeal rectus aponeuroplasty (LIRA) technique versus intraperitoneal onlay mesh (IPOM plus) for ventral hernia repair: a comparative analysis.

PURPOSE: Primary aim of this study is to compare the postoperative outcomes of the laparoscopic intracorporeal rectus aponeuroplasty (LIRA) technique to the intraperitoneal onlay mesh closing the defect (IPOM plus), in terms of recurrence and bulging rates at one-year follow-up; secondary aim is to compare the postoperative complications, seroma and pain at 30 days and one-year after surgery. METHODS: Patients with midline ventral hernia of 4-10 cm in width were included. Computed tomography scan was performed before, 1 and 12 months after surgery. Pain was evaluated using the visual analogue scale. RESULTS: Forty-five and forty-seven consecutive patients underwent LIRA and IPOM plus, respectively. Preoperatively, smoke habits and chronic obstructive pulmonary disease rates were statistically significantly higher in the LIRA group (p = 0.0001 and p = 0.012, respectively). Two bulgings (4.4%) occurred in the LIRA group, while in the IPOM plus group occurred 10 bulgings (21.3%) and three recurrences (6.4%) (p = 0.017 and p = 0.085, respectively). Postoperatively, seven (15.6%, Clavien-Dindo I) and four complications (8.5%, two Clavien-Dindo I, two Clavien-Dindo III-b) occurred in the LIRA and in the IPOM plus group, respectively (p = 0.298). One month after surgery, clinical seroma, occurred in five (11.1%) and eight patients (17%) in the LIRA and in the IPOM plus group, respectively (p = 0.416). During follow-up, pain reduction occurred, without statistically significant differences. CONCLUSIONS: In this study, even if we analysed a small series, LIRA showed lower bulging and recurrence rates in comparison to IPOM plus at one-year follow-up. Further prospective studies, with a large sample of patients and longer follow-up are required to draw definitive conclusions.

Ocular side effects of oncological therapies: Review.

With the advance of cancer therapy in recent years, the knowledge of the mechanisms involved in this disease has increased, which has meant an increase in the quality of life and survival of patients with tumor pathologies previously considered incurable or refractory to treatment. The number of drugs used has increased exponentially in number, and although the implicit toxicity is lower than that of conventional antineoplastic therapy, they lead to the appearance of new associated adverse effects that the ophthalmologist must recognize and manage.

Radiomic-based nonlinear supervised learning classifiers on non-contrast CT to predict functional prognosis in patients with spontaneous intracerebral hematoma.

PURPOSE: To evaluate if nonlinear supervised learning classifiers based on non-contrast CT can predict functional prognosis at discharge in patients with spontaneous intracerebral hematoma. METHODS: Retrospective, single-center, observational analysis of patients with a diagnosis of spontaneous intracerebral hematoma confirmed by non-contrast CT between January 2016 and April 2018. Patients with HIE > 18 years and with TCCSC performed within the first 24 h of symptom onset were included. Patients with secondary spontaneous intracerebral hematoma and in whom radiomic variables were not available were excluded. Clinical, demographic and admission variables were collected. Patients were classified according to the Modified Rankin Scale (mRS) at discharge into good (mRS 0-2) and poor prognosis (mRS 3-6). After manual segmentation of each spontaneous intracerebral hematoma, the radiomics variables were obtained. The sample was divided into a training and testing cohort and a validation cohort (70-30% respectively). Different methods of variable selection and dimensionality reduction were used, and different algorithms were used for model construction. Stratified 10-fold cross-validation were performed on the training and testing cohort and the mean area under the curve (AUC) were calculated. Once the models were trained, the sensitivity of each was calculated to predict functional prognosis at discharge in the validation cohort. RESULTS: 105 patients with spontaneous intracerebral hematoma were analyzed. 105 radiomic variables were evaluated for each patient. P-SVM, KNN-E and RF-10 algorithms, in combination with the ANOVA variable selection method, were the best performing classifiers in the training and testing cohort (AUC 0.798, 0.752 and 0.742 respectively). The predictions of these models, in the validation cohort, had a sensitivity of 0.897 (0.778-1;95%CI), with a false-negative rate of 0% for predicting poor functional prognosis at discharge. CONCLUSION: The use of radiomics-based nonlinear supervised learning classifiers are a promising diagnostic tool for predicting functional outcome at discharge in HIE patients, with a low false negative rate, although larger and balanced samples are still needed to develop and improve their performance.

Clasificadores de aprendizaje supervisado no lineales basados en radiómica de la TC cerebral sin contraste para predecir el pronóstico funcional en pacientes con hematoma intracerebral espontáneo / Radiomic-based nonlinear supervised learning classifiers on non-contrast CT to predict functional prognosis in patients with spontaneous intracerebral hematoma

Objetivo: Evaluar si clasificadores de aprendizaje supervisado no lineales basados en radiómica de la TC cerebral sin contraste (TCCSC) pueden predecir el pronóstico funcional al alta en pacientes con hematoma intracerebral espontáneo (HIE). Material y método: Análisis observacional retrospectivo y unicéntrico de pacientes con diagnóstico de HIE confirmado por TCCSC entre enero de 2016 y abril de 2018. Se incluyeron pacientes con HIE >18años y con TCCSC realizado dentro de las primeras 24horas del inicio de los síntomas. Se excluyeron los HIE secundarios y en los que no se disponía de las variables de radiómica. Se recogieron datos clínicos, demográficos y variables al ingreso. Los pacientes se clasificaron según la Escala Modificada de Rankin (mRS) al alta en buen (mRS0-2) y mal pronóstico (mRS3-6). Tras la segmentación manual de la TCCSC de cada HIE se obtuvieron las variables de radiómica. La muestra se dividió en una cohorte de entrenamiento y prueba y otra cohorte de validación (70-30%, respectivamente). Se usaron diferentes métodos de selección de variables y reducción de dimensionalidad, así como diferentes algoritmos para la construcción del modelo. Se realizaron 10 iteraciones de validación cruzada estratificada en la cohorte de entrenamiento y prueba y se calculó la media de los valores de área bajo la curva (AUC). Una vez entrenados los modelos, se calculó la sensibilidad de cada uno para predecir el pronóstico funcional al alta en la cohorte de validación. Resultados: Se analizaron 105 pacientes con HIE. Se evaluaron 105 variables de radiómica de cada paciente. Los algoritmos P-SVM, KNN-E y RF-10, en combinación con el método de selección de variables ANOVA, fueron los clasificadores con mejor rendimiento en la cohorte de entrenamiento y prueba (AUC: 0,798, 0,752 y 0,742, respectivamente)...(AU)

Purpose: To evaluate if nonlinear supervised learning classifiers based on non-contrast cerebral CT can predict functional prognosis at discharge in patients with spontaneous intracerebral hematoma (HIE). Methods: Retrospective, single-center, observational analysis of patients with a diagnosis of spontaneous intracerebral hematoma confirmed by non-contrast CT between January 2016 and April 2018. Patients with HIE >18years and with non-contrast CT performed within the first 24hours of symptom onset were included. Patients with secondary spontaneous intracerebral hematoma and in whom radiomic variables were not available were excluded. Clinical, demographic and admission variables were collected. Patients were classified according to the Modified Rankin Scale (mRS) at discharge into good (mRS0-2) and poor prognosis (mRS3-6). After manual segmentation of each spontaneous intracerebral hematoma, the radiomics variables were obtained. The sample was divided into a training and testing cohort and a validation cohort (70-30%, respectively). Different methods of variable selection and dimensionality reduction were used, and different algorithms were used for model construction. Stratified 10-fold cross-validation were performed on the training and testing cohort and the mean area under the curve (AUC) were calculated. Once the models were trained, the sensitivity of each was calculated to predict functional prognosis at discharge in the validation cohort. Results: 105 patients with spontaneous intracerebral hematoma were analyzed. 105 radiomic variables were evaluated for each patient. P-SVM, KNN-E and RF-10 algorithms, in combination with the ANOVA variable selection method, were the best performing classifiers in the training and testing cohort (AUC: 0.798, 0.752 and 0.742, respectively)...(AU)