Virtual Screening of Small Molecules Targeting BCL2 with Machine Learning, Molecular Docking, and MD Simulation.

This study aimed to identify potential BCL-2 small molecule inhibitors using deep neural networks (DNN) and random forest (RF), algorithms as well as molecular docking and molecular dynamics (MD) simulations to screen a library of small molecules. The RF model classified 61% (2355/3867) of molecules as 'Active'. Further analysis through molecular docking with Vina identified CHEMBL3940231, CHEMBL3938023, and CHEMBL3947358 as top-scored small molecules with docking scores of -11, -10.9, and 10.8 kcal/mol, respectively. MD simulations validated these compounds' stability and binding affinity to the BCL2 protein.

Low-Dose Gamma Radiation Sterilization for Decellularized Tracheal Grafts.

One of the main key aspects in ensuring that a transplant evolves correctly is the sterility of the medium. Decellularized tracheal transplantation involves implanting an organ that was originally in contact with the environment, thus not being sterile from the outset. While the decellularization protocol (through detergent exposition [2% sodium dodecyl sulfate], continuous stirring, and osmotic shocks) is conducted in line with aseptic measures, it does not provide sterilization. Therefore, one of the main challenges is ensuring sterility prior to in vivo implantation. Although there are established gamma radiation sterilization protocols for inorganic materials, there are no such measures for organic materials. Additionally, the protocols in place for inorganic materials cannot be applied to organic materials, as the established radiation dose (25 kGy) would completely destroy the implant. This paper studies the effect of an escalated radiation dose in a decellularized rabbit trachea. We maintained the dose range (kGy) and tested escalated doses until finding the minimal dose at which sterilization is achieved. After determining the dose, we studied effects of it on the organ, both histologically and biomechanically. We determined that while 0.5 kGy did not achieve sterility, doses of both 1 kGy and 2 kGy did, with 1 kGy, therefore, being the minimal dose necessary to achieve sterilization. Microscopic studies showed no relevant changes compared to non-sterilized organs. Axial biomechanical characteristics were not altered at all, and only a slight reduction in the force per unit of length that the organ can radially tolerate was observed. We can therefore conclude that 1 kGy achieves complete sterilization of decellularized rabbit trachea with a minimal, if any, effects on the organ.

Affective temperaments and sexual functioning in euthymic patients with bipolar disorder.

Sexual functioning in bipolar disorder (BD) is dependent on multiple clinical and demographic determinants that can eventually lead to sexual dysfunction. However, the contribution of affective temperaments remains unstudied in this population. In this cross-sectional multicentric work, we studied the impact of temperament traits on sexual functioning in 100 euthymic BD outpatients treated only with mood stabilizers with or without benzodiazepines. Temperament was evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego - Autoquestionnaire (TEMPS-A) and sexual functioning with the Changes on Sexual Functioning Questionnaire (CSFQ-14). The effect of temperament on sexual functioning was analyzed using Bayesian ordinal regression models, which included age, gender, BD type, dominant polarity, metabolic syndrome, marital status, and affective symptomatology. Our results showed that hyperthymic traits predicted a significantly higher CSFQ-14 score for global sexual functioning (OR = 1.222; 95% CI [1.073, 1.431]), desire (OR = 1.164; 95% CI [1.025, 1.357]), arousal (OR = 1.278; 95% CI: [1.083, 1.551]), and orgasm (OR = 1.182; 95% CI [1.037, 1.365]). We did not find a significant contribution for other types of temperaments. Better sexual functioning was also associated with a better quality of life. Our findings highlight the importance of temperament traits in sexual functioning in euthymic BD, which may have implications in sexual dysfunction prevention.

Hemodynamic Tolerance of Virtual Reality Intradialysis Exercise Performed during the Last 30 Minutes versus the Beginning of the Hemodialysis Session.

Background: Exercise improves the physical function of people suffering from chronic kidney disease on hemodialysis (HD). Virtual reality is a new type of intradialysis exercise that has a positive impact on physical function. Intradialysis exercise is recommended during the first 2 h, but its safety in the last part of the dialysis session is unknown. Methods: This was a pilot sub-study of a clinical trial. Several hemodynamic control variables were recorded, including blood pressure, heart rate, and intradialytic hypotensive events. These variables were recorded during three different HD sessions, one HD session at rest, another HD session with exercise during the first two hours, and one HD session with exercise during the last 30 min of dialysis. The intradialysis virtual reality exercise was performed for a maximum of 30 min. Results: During exercise sessions, there was a significant increase in heart rate (6.65 (4.92, 8.39) bpm; p < 0.001) and systolic blood pressure (6.25 (0.04,12.47) mmHg; p < 0.05). There was no difference in hemodynamic control between the sessions with exercise during the first two hours and the sessions with exercise during the last 30 min. There was no association between intra-dialytic hypotensive events at rest (five events) or exercise at any point (two vs. one event(s), respectively). Conclusion: performing exercise with virtual reality at the end of a hemodialysis session is not associated with hemodynamic instability.

Diagnostic accuracy of C-reactive protein, procalcitonin and neutrophils for the early detection of anastomotic leakage after colorectal resection: a multicentric, prospective study.

AIM: The aim was to determine the accuracy of C-reactive protein (CRP), procalcitonin and neutrophils in the early detection (fourth postoperative day) of anastomotic leakage (AL) after colorectal surgery. METHODS: We conducted a multicentre, prospective study that included a consecutive series of patients who underwent colorectal resection with anastomosis without ostomy (September 2015 to December 2017). CRP, procalcitonin and neutrophil values on the fourth postoperative day after colorectal resection along with the postoperative outcome (60-day AL, morbidity and mortality) were prospectively included in an online, anonymous database. RESULTS: The analysis ultimately included 2501 cases. The overall morbidity and mortality was 30.1% and 1.6%, respectively, and the AL rate was 8.6%. The area under the receiver operating characteristic curve values (95% CI) for detecting AL were 0.84 (0.81-0.87), 0.75 (0.72-0.79) and 0.70 (0.66-0.74) for CRP, procalcitonin and neutrophils, respectively. The best cut-off level for CRP was 119 mg/l, resulting in 70% sensitivity, 81% specificity and 97% negative predictive value. After laparoscopic resection, the accuracy for CRP and procalcitonin was increased, compared with open resection. The combination of two or three of these biomarkers did not significantly increase their accuracy. CONCLUSION: On the fourth postoperative day, CRP was the most reliable marker for excluding AL. Its high negative predictive value, especially after laparoscopic resection, allows for safe hospital discharge on the fourth postoperative day. The routine use of procalcitonin or neutrophil counts does not seem to increase the diagnostic accuracy.

Mathematical simulation of Doppler changes in late-onset smallness; progression patterns of cerebral and umbilical anomalies define two types of late-onset fetal growth restriction.

OBJECTIVE: To evaluate the progression of Doppler abnormalities in fetuses with late-onset fetal smallness (SGA) that become growth restricted (FGR). METHODS: 524 Doppler examinations of the umbilical and cerebral arteries systems, belonging to 442 late-onset SGA fetuses after week 34, were studied, evaluating by means of the statistical difference with the respective abnormal centiles, the pattern of progression into abnormal Doppler values and the distribution and cumulative sum of Doppler anomalies according to the interval to delivery. RESULTS: Only one third (33.5%, N = 148) of late-onset SGA fetuses presented Doppler anomalies, suggesting that most were of constitutional origin. The most frequent progression pattern into abnormal Doppler (N = 127, 85.81%) was that in which only one system (umbilical or cerebral) became abnormal. Half of fetuses debuted with abnormal umbilical flow (52%, N = 77) and half with cerebral anomalies (47.97%, N = 71), which were more likely to appear later and at shorter intervals to delivery (p = .007). These progression patters defined two varieties of late-onset FGR (type I and II) with similar outcome but different birth weight centiles (BW centile = 2.51, SD 2.91 versus 3.97, SD 3.17, p < .01). CONCLUSION: Two thirds of late-onset fetal smallness occurs without hemodynamic changes. In half of the remaining cases an initial cerebral vasodilation defines a group of fetuses with similar outcome but higher BW centile.

Expired Tidal Volume and Respiratory Rate During Postnatal Stabilization of Newborn Infants Born at Term via Cesarean Delivery.

Objective: To retrieve evolving respiratory measures in the first minutes after birth in normal neonates born at term using a respiratory function monitor. Study design: We evaluated newborn babies delivered at term via cesarean after uncomplicated pregnancies. Immediately after birth, a respiratory function monitor with an adapted flowmeter and a face mask were applied at 2, 5, and 10 minutes after birth for 90 seconds in each period. We analyzed expired and inspired tidal volume, respiratory rate (RR), percentage of leakage, and number of analyzed breaths in each individual infant's recording using a respiratory research software. Results: A total of 243 infants completed the study. The final data set included 59 058 (48.35%) valid observations for each of the variables representing the analysis of 32 801 breaths. With these data, we constructed a reference range with 10th, 25th, 50th, 75th, and 90th percentiles for expired tidal volume and RR. Tidal volumes plateaued earlier in female than in male infants. No correlation with delayed cord clamping, gestational age, maternal morbidity, or indication for cesarean delivery were established. Conclusions: We have constructed a reference range with percentiles for inspired and expired tidal volumes and RR in newborn babies born at term for the first 10 minutes after birth. Reference ranges can be employed for research and can be useful in the clinical setting to guide positive pressure ventilation in the delivery room.

Plasma isoprostanoids assessment as Alzheimer's disease progression biomarkers.

Alzheimer's Disease (AD) is the most common neurodegenerative disease worldwide. So, there is a need to identify AD early diagnosis and monitoring biomarkers in blood samples. The aim of this study was to analyse the utility of lipid peroxidation biomarkers in AD progression evaluation. Participants (n = 19) were diagnosed with AD at early stages (Time 0, T0), and they were re-evaluated 2 years later (Time 1, T1). Plasma biomarkers from AD patients were determined at both times. Some analytes, such as dihomo-isoprostanes (17-epi-17-F2t-dihomo-IsoP, 17-F2t-dihomo-IsoP, Ent-7(RS)-7-F2t-dihomo-IsoP), and neuroprostanes (10-epi-10-F4t-NeuroP) showed very high probability of showing an increasing trend over time. Baseline values allowed to develop an affordable preliminary regression model to predict long-term cognitive status. So, some lipid peroxidation biomarkers would deserve consideration as useful progression AD biomarkers. The developed prediction model would constitute an important minimally invasive approach in AD personalized prognosis and perhaps could have some interest also in experimental treatments evaluation.

Relationship between Skin Temperature, Electrical Manifestations of Muscle Fatigue, and Exercise-Induced Delayed Onset Muscle Soreness for Dynamic Contractions: A Preliminary Study.

Delayed onset muscle soreness (DOMS) indicates the presence of muscle damage and impairs force production and control. Monitorization of DOMS is useful to improving recovery intervention plans. The magnitude of DOMS may relate to muscle fatigue, which can be monitored by surface electromyography (EMG). Additionally, growing interest has been expressed in determining whether the skin temperature over a muscle group during exercise to fatigue could be a non-invasive marker for DOMS. Here we determine whether skin temperature and manifestations of muscle fatigue during exercise are correlated and can predict DOMS after concentric-eccentric bicep curl exercises. We tested 10 young adults who performed concentric-eccentric bicep curl exercises to induce muscle damage in the biceps brachialis to investigate the relationship between skin temperature and fatigue during exercise and DOMS after exercise. Muscle activation and skin temperature were recorded during exercise. DOMS was evaluated 24 h after exercise. Data analysis was performed using Bayesian regression models with regularizing priors. We found significant muscle fatigue and an increase in skin temperature during exercise. DOMS was observed 24 h after exercise. The regression models showed no correlation of changes in skin temperature and muscle fatigue during exercise with DOMS 24 h after exercise. In conclusion, our preliminary results do not support a relationship between skin temperature measured during exercise and either muscle fatigue during exercise or the ability to predict DOMS 24 h after exercise.

Glycemic variability in type 2 diabetes mellitus and acute coronary syndrome: liraglutide compared with insulin glargine: a pilot study.

OBJECTIVE: To explore the glucagon-like peptide-1 analogue liraglutide in the hospital setting in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome and to evaluate the safety and efficacy and its impact on hospitalization and short-term glycemic variability (GV). METHODS: A 12-week, open-label, prospective, randomized pilot clinical study with parallel groups that compared liraglutide (group 1) with glargine (group 2) and its impact on glycemic control and GV. RESULTS: Thirteen patients were included. During hospitalization, mean glucose was 164.75 mg/dL (standard deviation [SD] 19.94) in group 1 and 166.69 mg/dL (38.22) in group 2. GV determined by CV and SD was 20.98 (7.68) vs. 25.48 (7.19) and 34.37 (13.05) vs. 43.56 (19.53) in groups 1 and 2, respectively. Group 1 prandial insulin requirements during hospitalization were lower compared with group 2. Follow-up A1c in group 1 was 6.9% (-1.51%) and 6.5% in group 2 (-1.27). GV after discharge and hypoglycemia were lower in group 1 compared with group 2. CONCLUSIONS: Liraglutide seems to reduce GV in the acute phase of acute coronary syndrome, and patients achieved optimal control with a low incidence of hypoglycemia. These results support the need to explore liraglutide in a larger multicenter trial. Trial registration: The study was approved by the National Medical Ethics Committee of Spain. The study was registered at European Clinical Trials Database (EudraCT): 2014003298-40.

Analysis of SNP Array Abnormalities in Patients with DE NOVO Acute Myeloid Leukemia with Normal Karyotype.

Nearly 50% of patients with de novo acute myeloid leukemia (AML) harbor an apparently normal karyotype (NK) by conventional cytogenetic techniques showing a very heterogeneous prognosis. This could be related to the presence of cryptic cytogenetic abnormalities (CCA) not detectable by conventional methods. The study of copy number alterations (CNA) and loss of heterozygozity (LOH) in hematological malignancies is possible using a high resolution SNP-array. Recently, in clinical practice the karyotype study has been complemented with the identification of point mutations in an increasing number of genes. We analyzed 252 de novo NK-AML patients from Hospital La Fe (n = 44) and from previously reported cohorts (n = 208) to identify CCA by SNP-array, and to integrate the analysis of CCA with molecular alterations detected by Next-Generation-sequencing. CCA were detected in 58% of patients. In addition, 49% of them harbored CNA or LOH and point mutations, simultaneously. Patients were grouped in 3 sets by their abnormalities: patients carrying several CCA simultaneously, patients with mutations in FLT3, NPM1 and/or DNMT3A and patients with an amalgam of mutations. We found a negative correlation between the number of CCA and the outcome of the patients. This study outlines that CCA are present in up to 50% of NK-AML patients and have a negative impact on the outcome. CCA may contribute to the heterogeneous prognosis.

The Effectiveness of an Oral Sensorimotor Stimulation Protocol for the Early Achievement of Exclusive Oral Feeding in Premature Infants. A Randomized, Controlled Trial.

Aims: This study is aimed to investigate the effectiveness of an oral stimulation protocol in preterm infants compared to usual care, to reduce the time for achieving safe full oral feeding.Methods: 47 preterm infants (25- 30 weeks of gestational age) were randomized into two groups. Babies of the EG (n = 24) received a 10-minute oral stimulation protocol while the CG (n = 23) received the standard care. The primary outcome were the days from the initiation of the intervention until the achievement of full oral feeding. Secondary outcomes were: days from the first day the intervention started until achieving a first oral intake of 30% in the first 5 minutes, days from the first day the intervention started until achieving a first oral intake of 100%, and days of hospitalization. A parametric survival model with Gaussian distribution was used.Results: The EG achieved full oral feeding 8.3 days before the CG (p = 0.013). EG also achieved the first oral intake of 30% in the first five minutes, 6.03 days before (p = 0.019) and of 100%, 5.88 days before (p = 0.040). EG also spent 6.9 days less hospitalized than CG (p = 0.028).Conclusion: Oral stimulation in preterm infants significantly shortens the time to achieve full oral feeding and reduces the length of hospitalization.

Efficacy Study of Anti-Endomysium Antibodies for Celiac Disease Diagnosis: A Retrospective Study in a Spanish Pediatric Population.

The aim of this study was to assess the efficacy of anti-endomysium antibodies (EMA) as a serological marker for celiac disease (CD) diagnosis in a pediatric population. A retrospective study of pediatric patients who underwent a CD serological markers study: EMA and anti-tissue transglutaminase antibodies (anti-TG2). Clinical symptomatology, degree of histological lesion, human leukocyte antigen (HLA) haplotype compatible with CD (HLA DQ2 and/or DQ8), and final diagnosis were taken into account. We included 445 patients who were classified in two groups according to the final diagnosis. Group 1: 232 children with CD, 91.4% of whom exhibited small intestinal villous atrophy, 228 being EMA-positive and four EMA-negative. Group 2: 213 children with a non-CD diagnosis, 212 EMA negative and one EMA positive. Both antibodies, EMA and anti-TG2, reached similar sensitivities, 98% and 99% respectively, while EMA had a higher specificity (99%) than anti-TG2 (93%). By using both markers combined, compared to using anti-TG2 alone, 5.7% of patients are better diagnosed. However, when we compare the efficacy of EMA and anti-TG2 in asymptomatic and symptomatic patients, the sensitivity of EMA is 98% irrespective of symptoms, thus higher than for anti-TG2 ≥10 × upper limit of normal (ULN) (respectively 77% and 84%). Our results support the use of EMA to increase CD diagnostic accuracy in a non-biopsy approach, especially in asymptomatic children.

Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although most cSCCs have good prognosis, a subgroup of high-risk cSCC has a higher frequency of recurrence and mortality. Therefore, the identification of molecular risk factors associated with this aggressive subtype is of major interest. In this work we carried out a global-scale approach to investigate the DNA-methylation profile in patients at different stages, from premalignant actinic keratosis to low-risk invasive and high-risk non-metastatic and metastatic cSCC. The results showed massive non-sequential changes in DNA-methylome and identified a minimal methylation signature that discriminates between stages. Importantly, a direct comparison of low-risk and high-risk stages revealed epigenetic traits characteristic of high-risk tumours. Finally, a prognostic prediction model in cSCC patients identified a methylation signature able to predict the overall survival of patients. Thus, the analysis of DNA-methylation in cSCC revealed changes during the evolution of the disease through the different stages that can be of great value not only in the diagnosis but also in the prognosis of the disease.

New screening approach for Alzheimer's disease risk assessment from urine lipid peroxidation compounds.

Alzheimer Disease (AD) standard biological diagnosis is based on expensive or invasive procedures. Recent research has focused on some molecular mechanisms involved since early AD stages, such as lipid peroxidation. Therefore, a non-invasive screening approach based on new lipid peroxidation compounds determination would be very useful. Well-defined early AD patients and healthy participants were recruited. Lipid peroxidation compounds were determined in urine using a validated analytical method based on liquid chromatography coupled to tandem mass spectrometry. Statistical studies consisted of the evaluation of two different linear (Elastic Net) and non-linear (Random Forest) regression models to discriminate between groups of participants. The regression models fitted to the data from some lipid peroxidation biomarkers (isoprostanes, neuroprostanes, prostaglandines, dihomo-isoprostanes) in urine as potential predictors of early AD. These prediction models achieved fair validated area under the receiver operating characteristics (AUC-ROCs > 0.68) and their results corroborated each other since they are based on different analytical principles. A satisfactory early screening approach, using two complementary regression models, has been obtained from urine levels of some lipid peroxidation compounds, indicating the individual probability of suffering from early AD.

Correlation between impulse oscillometry parameters and asthma control in an adult population.

Purpose: Impulse oscillometry (IOS) has been proposed as an alternative test to evaluate the obstruction of small airways and to detect changes in airways earlier than spirometry. In this study, we sought to determine the utility and association of IOS parameters with spirometry and asthma control in an adult population. Patients and methods: Adults 14-82 years of age with asthma were classified into uncontrolled asthma (n=48), partially controlled asthma (n=45), and controlled asthma (n=49) groups, and characterized with fractional exhaled nitric oxide (FENO), IOS, and spirometry in a transversal analysis planned as a one-visit study. The basic parameters evaluated in IOS are resistance at 5 Hz (R5), an index affected by the large and small airway; resistance at 20 Hz (R20), an index of the resistance of large airways; difference between R5 and R20 (R5-R20), indicative of the function of the small peripheral airways; reactance at 5 Hz (X5), indicative of the capacitive reactance in the small peripheral airways; resonance frequency (Fres), the intermediate frequency at which the reactance is null, and reactance area (XA), which represents the total reactance (area under the curve) at all frequencies between 5 Hz to Fres. Results: There were statistical differences between groups in standard spirometry and IOS parameters reflecting small peripheral airways (R5, R10, R5-R20, Fres, XA and X5) (P<0.001). Accuracy of IOS and/or spirometry to discriminate between controlled asthma vs partially controlled asthma and uncontrolled asthma was low (AUC=0.61). Using linear regression models, we found a good association between spirometry and IOS. In order to evaluate IOS as an alternative or supplementary method for spirometry, we designed a predictive model for spirometry from IOS applying a penalized regression model (Lasso). Then, we compared the original spirometry values with the values obtained from the predictive model using Bland-Altman plots, and the models showed an acceptable bias in the case of FEV1/FVC, FEV1%, and FVC%. Conclusion: IOS did not show a discriminative capacity to correctly classify patients according to the degree of asthma control. However, values of IOS showed good association with values of spirometry. IOS could be considered as an alternative and accurate complement to spirometry in adults. In a predictive model, spirometry values estimated from IOS tended to overestimate in low values of "real" spirometry and underestimate in high values.

Relationship between structural damage with loss of strength and functional disability in psoriatic arthritis patients.

BACKGROUND: Evaluate the relationship between structural damage assessed by radiography or ultrasonography in the hands of patients with psoriatic arthritis (PsA) with loss of strength together with functional disability. METHODS: A cross-sectional study was conducted in patients with PsA involving the hands. Erosions and loss of radiographic joint space were measured in the dominant hand using a modified Sharp van der Heijde method and an ultrasound assessment. Hand strength was assessed with a dynamometer and disability was assessed using the Health Assessment Questionnaire (HAQ). The statistical analysis was performed using multiple linear regression models. FINDINGS: 76 patients were included with a mean age of 57 ±â€¯9.9 years, with 56.6% women. A statistically significant relationship was found between presence of erosions and reduction in lateral (p = 0.027) and tip (p = 0.030) pinch strength in the hand. This was also the case for loss of joint space and reduction in lateral (p = 0.012) and tip (p = 0.006) pinch strength. There was an association between total ultrasound (US) alterations and reduction in lateral pinch strength (p = 0.03). An association was also observed between erosions, loss of joint space and total US alterations and disability measured by the HAQ (p < 0.001; <0.001; 0.012, respectively). HAQ scores were associated with a decrease in mean lateral (p < 0.001) and tip (p < 0.001) pinch strength. INTERPRETATION: In patients with PsA involving the hands, structural alterations of the dominant hand assessed by conventional x-ray and ultrasound are associated with loss of strength measured objectively with dynamometry and greater disability also studied subjectively using the HAQ.

Maternal telomere length is shorter in intrauterine growth restriction versus uncomplicated pregnancies, but not in the offspring or in IVF-conceived newborns.

RESEARCH QUESTION: The study aimed to determine whether IVF or intrauterine growth restriction (IUGR) result in short neonatal telomeres, which could explain the higher risk of cardiovascular and metabolic disease described in these populations. DESIGN: This was an observational, analytical, cross-sectional, prospective study with controls in a tertiary hospital. The main outcome was to determine the leukocyte telomere length in 126 newborns and their mothers (n = 109). Newborns were conceived spontaneously or by IVF, and uncomplicated and IUGR pregnancies were studied. Telomere lengths were measured using high-throughput telomere quantitative fluorescent in-situ hybridization. RESULTS: There was no difference in average telomere length between newborns conceived by IVF or those with IUGR and spontaneously conceived healthy newborns (P = 0.466 and P = 0.732, respectively); this remained after controlling for confounders (P = 0.218 and P = 0.991, respectively). Mothers of newborns with IUGR had a shorter average telomere length than women with uncomplicated pregnancies (P = 0.023), which was confirmed after controlling for age, body mass index and smoking habit (P = 0.034). CONCLUSIONS: The results support the safety of IVF and IUGR in terms of the postnatal health of the newborns. The shorter telomeres of IUGR mothers may represent a higher cardiovascular risk, which would have clinical implications under the stress of pregnancy in otherwise healthy adults.

[Clinical usefulness of the non-invasive functional study of the lower urinary tract voiding phase as a predictor of resolution after the first endoscopic treatment of vesico-ureteral reflux in children older than 3 years.] / Utilidad del estudio funcional no invasivo de la fase de vaciado del tracto urinario inferior como factor predictor de la resolución tras el primer tratamiento endoscópico del reflujo vesico-ureteral en niños mayores de 3 años.

OBJECTIVES: To determine the usefulnessof voiding diary (VD), uroflowmetry with electromyography(UF-EMG), bladder wall thickness (before micturition)(VWTUS) and residual urine (PVR) (ultrasound measure)in predicting the outcome of the first endoscopic treatment(1ENDT) of vesicoureteral reflux (VUR) in children> 3 years. METHODS: Cross-sectional ambispective study of 48children with vesicoureteral reflux. Those with previousendoscopic treatment, age or neurological abnormalities and a history of urethralor abdominal surgery were excluded. The outcomevariable was the correctness (by isotopic cystography)three months after 1ENDT. Univariate and multivariateanalyses were performed through a Multilayer Perceptronnetwork and a logistic regression model EmpiricalBayesian penalized type LASSO Elastic net. Diagnosticaccuracy were determined. RESULTS: Mean age of the sample was 6.8 +/- 2.28years. The rate of VUR correction after 1ENDT was 77%.The variables selected by both methods were: VD-retentionist(OR 3.90), high PVR (OR 2.69), high VWTUS (OR4.44). Normal UF-EMG was a preventive variable (OR0.38). Diagnostic accuracy (pSp=48.7%), UF+EMG (Se=27.3%(Se=72.7% (AUC=0.8 cut point 20 ml),VWTUS (Se=81.8% (AUC=0.8 cut point4.6 mm). There were no statistical differences betweenPVR and VWTUS. Combined use of UF+EMG+PVR(Se=90.9%in predicting the persistence of VUR after 1ENDT inchildren > 3 years. After screening with a VD, UF-EMG+ RPM combination could be useful to detect these patientsand propose a treatment that improves bladdervoiding function prior to surgery.

OBJETIVOS: Determinar la utilidad deldiario miccional (DIM), la flujometría asociada a laelectromiografía (UF-EMG) y los parámetros ecográficoscomo son el espesor de la pared vesical premiciconal(EPVECO) y el residuo postmiccional (RPM) en la prediccióndel resultado del primer tratamiento endoscópico(1TEND) del Reflujo Vesico-Ureteral (RVU) en niños > 3años.MATERIAL Y MÉTODOS: Estudio transversal ambispectivode 48 niños con RVU. Criterios de exclusión: 1TENDprevio, edad y cirugía uretral o abdominal previas. Variableresultado: corrección del RVU (cistografía isotópica realizadatres meses después del 1TEND). Se realizaronanálisis univariante y multivariante mediante una red perceptrón multicapa y un modelo de regresión logísticapenalizada tipo Empirical Bayesian LASSO Elastic net.Se consideraron significativas las variables elegidas porambos métodos estadísticos. Se estudió el rendimientodiagnóstico de las pruebas individuales y combinadas. RESULTADOS: Media de edad: 6,8 +/- 2,28 años.Tasa de corrección del RVU traspredictoras de la persistencia del RVU tras 1TENDseleccionadas por ambos métodos: DIM-hábito retencionista(OR 3,90), RPM elevado (OR 2,69), EPVECOaumentado (OR 4,44). La UF-EMG sin alteracionesen el trazado se comportó como variable preventiva(OR 0,38). Rendimiento diagnóstico (p(Se=98% (Se=27,3%RPM (Se=72,7% (AUC=0,8 punto decorte óptimo 20 ml), EPVECO (Se=81,8%(AUC=0,8 punto de corte óptimo 4,6 mm).No existierondiferencias entre el uso del RPM y el EPVECO(p>0,05). Uso conjunto de UF-EMG+RPM (Se=90,9%Es=92%) (pCONCLUSIONES: El estudio funcional no invasivo dela fase de vaciado es útil en la predicción de la persistenciade RVU tras el 1TEND en niños >3 años. Trasel cribado con un diario miccional, la UF-EMG+RPMpodrían ser útiles para detectar a estos pacientes y plantearun tratamiento que mejore el vaciado vesical previoa la cirugía.

Does Metabolic Surgery Lead to Diabetes Remission in Patients with BMI < 30 kg/m2?: a Meta-analysis.

BACKGROUND: Bariatric surgery has demonstrated to be effective in remission of type 2 diabetes in obese patients, but it is unclear in non-obese patients. The aim of this study is to investigate if metabolic surgery is effective in diabetes resolution in patients with BMI < 30 kg/m2. MATERIALS AND METHODS: A systematic review was performed and the content of the PubMed, Ovid, and the Cochrane Library databases covering the period January 2008 to April 2018 was searched. Studies with metabolic surgery performed in patients with type 2 diabetes, BMI < 30 kg/m2 and a follow-up ≥ 6 months were included. Type 2 diabetes remission rate and metabolic parameters changes were measured. A meta-analysis was conducted with the selected studies. RESULTS: Twenty-six studies were included in the meta-analysis (1105 patients). The mixed-effects meta-analysis model for overall diabetes remission rate produced an estimate of 43% (95% IC 34-53%, p < 0.001). Moderator effects of the variables race, preoperative HbA1c, BMI, months of follow-up, duration of diabetes, and age on diabetes remission were also assessed, with no significant effects being found in any of them. A reduction in BMI (- 3.57 kg/m2), fasting blood glucose (- 55.93 mg/dL) and HbA1c (- 2.08%) was observed after surgery. CONCLUSIONS: Metabolic surgery could be effective in remission of type 2 diabetes in BMI < 30 kg/m2 patients but randomized and long-term studies are necessary. The scientific community should agree in a single definition of type 2 diabetes remission, in order to know the real effect of metabolic surgery in this group of patients.