Accurate and safe diagnosis and treatment of neoplastic biliary lesions using a novel 9F and 11F digital single-operator cholangioscope.

Background and study aims Digital single-operator cholangioscopy (DSOC) allows the diagnosis of biliary duct disorders and treatment for complicated stones. However, these technologies have limitations such as the size of the probe and working channel, excessive cost, and low image resolution. Recently, a novel DSOC system (eyeMAX, Micro-Tech, Nanjing, China) was developed to address these limitations. We aimed to evaluate the usefulness and safety of a novel 9F and 11F DSOC system in terms of neoplastic diagnostic accuracy based on visual examination, ability to evaluate tumor extension and to achieve complete biliary stone clearance, and procedure-related adverse events (AEs). Patients and methods Data from ≥ 18-year-old patients who underwent DSOC from July 2021 to April 2022 were retrospectively recovered and divided into a diagnostic and a therapeutic cohort. Results A total of 80 patients were included. In the diagnostic cohort (n = 49/80), neovascularity was identified in 26 of 49 patients (46.9%). Biopsy was performed in 65.3% patients with adequate tissue sample obtained in 96.8% of cases. Biopsy confirmed neoplasia in 23 of 32 cases. DSOC visual impression achieved 91.6% sensitivity and 87.5% specificity in diagnosing neoplasms. In the therapeutic cohort (n = 43/80), 26 of 43 patients required lithotripsy alone. Total stone removal was achieved in 71% patients in the first session. Neither early nor late AEs were documented in either the diagnostic or therapeutic cohort. Conclusions The novel DSOC device has excellent diagnostic accuracy in distinguishing neoplastic biliary lesions as well as therapeutic benefits in the context of total stone removal, with no documented AEs.

Assessing Endoscopic Ultrasound-Guided Radiofrequency Ablation in Unresectable Pancreatic Ductal Adenocarcinoma: A Single-Center Historic Cohort Study.

BACKGROUND: /aims: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as an alternative for the local treatment of unresectable pancreatic ductal adenocarcinoma (PDAC). We aim to assess the feasibility and safety of EUS-RFA in patients with unresectable PDAC. METHODS: The following was a historic cohort compounded by locally advanced (LA) and metastatic (m) PDAC naïve patients, who underwent EUS-RFA between October 2019 to March 2022. EUS-RFA was performed with a 19-g needle electrode with a 10 mm active tip for energy delivery. Study primary endpoints were feasibility, safety, and clinical follow-up; secondary endpoints were performance status (PS), local control (LC) and overall survival (OS). RESULTS: Twenty-six patients were selected: 15/26 LA-PDAC and 11/26 mPDAC. Technical success was achieved in all patients with no major adverse events. Six months after EUS-RFA, OS was 11/26 (42.3%), with significant PS improvement (P=.03). LC was achieved, with tumor reduction from 39.5 to 26 mm (P=.04). Post-treatment hypodense necrotic area was observed at six-month follow-up in 11/11 alive cases. Metastatic disease was a significant factor for OS worsening (HR 5.021; IC 95% 1.589 - 15.87; P=.004) CONCLUSIONS: EUS-RFA of pancreatic adenocarcinoma is a minimally invasive and safe technique that may have an important role as targeted therapy for local treatment of unresectable cases, as well as an alternative for poor surgical candidates. Also, RFA may play a role in downstaging cancer with potential OS increase in non-metastatic cases. Large prospective cohorts are required to evaluate this technique in clinical practice.

Full-depth evaluation of the bile duct with a 7F cholangioscope and its possibility for guiding therapeutics.

Background and Aims: Digital single-operator cholangioscopy (DSOC) plays a critical role in directly visualizing and treating the bile duct system. Although various cholangioscopes with different external diameters are available for DSOC, certain challenging scenarios persist in which existing scopes fail to complete a thorough evaluation of the bile ducts. To overcome these limitations, we aimed to introduce and highlight the application of a novel 7F cholangioscope. Methods: In this review article we describe the novel 7F cholangioscope, provide its assembly and setup, and review cases in which the 7F cholangioscope was used for diagnostic and therapeutic guidance. Results: Four cases involving challenging biliary assessments were presented, all of which achieved technical and clinical success. No procedure-related adverse events were reported in any of these cases. Conclusions: The 7F cholangioscope can provide additional information regarding the biliary tree and guidance for treatment, overcoming the challenging assessment of small pancreatobiliary ducts and its strictures. Its potential use in cases of severe bile duct stenosis is recommended. However, further studies evaluating safety and efficacy are needed.

Effect of Pediococcus acidilactici and mango seed polyphenols on the fermentative profile of the indigestible fraction of yam bean.

Yam bean is an important source of dietary fiber and other components that comprise the total indigestible fraction (TIF), which can be fermented by the colonic microbiota and produce metabolites with beneficial health effects. Therefore, the objective of this study was to evaluate the in vitro colonic fermentation of yam bean TIF and the changes caused by the addition of a polyphenolic extract of mango seed and the lactic acid bacteria Pediococcus acidilactici. The mango seed extract was obtained by ultrasound-assisted extraction, and the microbial growth rate and viability of P. acidilactici were determined using a Neubauer chamber. Yam bean TIF was isolated by triple enzymatic hydrolysis and subjected to in vitro colonic fermentation in combination with treatments with mango seed extract and P. acidilactici suspensions. Changes in pH, total soluble phenols (TSP), and antioxidant capacity (AOX) were evaluated. Furthermore, the production of metabolites was quantified by HPLC-DAD-MS and GC-MS. The Growth rate of P. acidilactici was 0.1097 h-1 with 97.5 % viability at 7 h of incubation. All TIF treatments showed a high capacity of fermentation, and the addition of mango seed extract increased the TSP content and AOX in DPPH and FRAP assays. A total of Forty-six volatile metabolites were detected, with highlighting the presence of esters, benzenes, aldehydes, and short-chain fatty acids. Five phenolic compounds associated with mango by-products were quantified during all fermentation process, despite the concentration of the extract. P. acidilactici did not substantially modify the fermentative profile of TIF. However, further studies such as the evaluation of the abundance of microbial communities may be necessary to observe whether it can generate changes during colonic fermentation.

Development of convolutional neural network models that recognize normal anatomic structures during real-time radial-array and linear-array EUS (with videos).

BACKGROUND AND AIMS: EUS is a high-skill technique that requires numerous procedures to achieve competence. However, training facilities are limited worldwide. Convolutional neural network (CNN) models have been previously implemented for object detection. We developed 2 EUS-based CNN models for normal anatomic structure recognition during real-time linear- and radial-array EUS evaluations. METHODS: The study was performed from February 2020 to June 2022. Consecutive patient videos of linear- and radial-array EUS videos were recorded. Expert endosonographers identified and labeled 20 normal anatomic structures within the videos for training and validation of the CNN models. Initial CNN models (CNNv1) were developed from 45 videos and the improved models (CNNv2) from an additional 102 videos. CNN model performance was compared with that of 2 expert endosonographers. RESULTS: CNNv1 used 45,034 linear-array EUS frames and 21,063 radial-array EUS frames. CNNv2 used 148,980 linear-array EUS frames and 128,871 radial-array EUS frames. Linear-array CNNv1 and radial-array CNNv1 achieved a 75.65% and 71.36% mean average precision (mAP) with a total loss of .19 and .18, respectively. Linear-array CNNv2 obtained an 88.7% mAP with a .06 total loss, whereas radial-array CNNv2 achieved an 83.5% mAP with a .07 total loss. CNNv2 accurately detected all studied normal anatomic structures with a >98% observed agreement during clinical validation. CONCLUSIONS: The proposed CNN models accurately recognize the normal anatomic structures in prerecorded videos and real-time EUS. Prospective trials are needed to evaluate the impact of these models on the learning curves of EUS trainees.

[Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO) y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventana de oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos del embarazo y riesgo de enfermedad vascular.] / Consensus document of the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Opportunity window: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular disease.

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs), such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational age and/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developing vascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheral vascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOs when assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact, adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the other hand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality. Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOs could strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients. Various healthcare system options exist to improve the transition of care for women with APOs between different healthcare professionals and implement long-term VR reduction strategies. One potential process could involve incorporating the fourth-trimester concept into clinical recommendations and healthcare policies.

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE), tales como son los trastornos hipertensivos, el parto pretérmino, la diabetes gestacional, los defectos en el crecimiento fetal (feto pequeño para la edad gestacional y/o restricción del crecimiento), el desprendimiento de placenta y la pérdida fetal, y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura: cardiopatía coronaria, accidente cerebrovascular, enfermedad vascular periférica e insuficiencia cardíaca. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo y/o postparto y manteniéndolo a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto del cuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.

Use of an adapted bronchoscope for peroral endoscopic myotomy in a pediatric patient weighing less than 10 kg.

Video 1Customization of pediatric bronchoscope and peroral endoscopic myotomy settings.

Usefulness of artificial intelligence-assisted digital single-operator cholangioscopy as a second-opinion consultation tool during interhospital assessment of an indeterminate biliary stricture: a case report.

Video 1Application of a novel digital single-operator cholangioscopy-based convolutional neuronal network to detect neoplastic lesions as a second-opinion consultation tool between 2 hospitals and biopsy sampling.

EUS-guided drainage of a segment VI liver abscess using a lumen-apposing metal stent.

Video 1EUS-guided FNA and lumen-apposing metallic stent deployment.

Analysis of Antioxidant Constituents of Filtering Infusions from Oak (Quercus sideroxyla Bonpl. and Quercus eduardii Trel.) and Yerbaniz (Tagetes lucida (Sweet) Voss) as Monoamine Oxidase Inhibitors.

The antioxidant constituents of ancestral products with ethnobotanical backgrounds are candidates for the study of filtering infusions to aid in pharmacotherapies focused on the treatment of depression and anxiety. Monoamine oxidase A (MAO-A) is an enzyme that regulates the metabolic breakdown of serotonin and noradrenaline in the nervous system. The goal of this study was to evaluate in vitro and in silico the effect of antioxidant constituents of filtering infusions from yerbaniz (Tagetes lucida (Sweet) Voss) and oak (Quercus sideroxyla Bonpl. and Quercus eduardii Trel.) as monoamine oxidase inhibitors. Materials were dried, ground, and mixed according to a simplex-centroid mixture design for obtaining infusions. Differential analysis of the phenolic constituent's ratio in the different infusions indicates that among the main compounds contributing to MAO-A inhibition are the gallic, chlorogenic, quinic, and shikimic acids, quercetin glucuronide and some glycosylated derivatives of ellagic acid and ellagic acid methyl ether. Infusions of Q. sideroxyla Bonpl. leaves, because of their content (99.45 ± 5.17 µg/mg) and synergy between these constituents for MAO-A inhibition (52.82 ± 3.20%), have the potential to treat depression and anxiety. Therefore, future studies with pharmacological approaches are needed to validate them as therapeutic agents with applications in mental health care.

Biofunctionalization of natural extracts, trends in biological activity and kinetic release.

The health benefits provided by plant matrices is due to the presence of certain compounds that, in studies carried out in vitro and in vivo, have shown to have biological activity in certain conditions, not only as a natural treatment against various conditions, but also for the quality of preventing chronic diseases, these compounds, already identified and studied, they can increase their biological function by undergoing structural chemical modifications or by being incorporated into polymer matrices that allow, in the first instance, to protect said compound and increase its bioaccessibility, as well as to preserve or increase the biological effects. Although the stabilization of compounds is an important aspect, it is also the study of the kinetic parameters of the system that contains them, since, due to these studies, the potential application to these systems can be designated. In this review we will address some of the work focused on obtaining compounds with biological activity from plant sources, the functionalization of extracts through double emulsions and nanoemulsions, as well as their toxicity and finally the pharmacokinetic aspects of entrapment systems.

Weibull ß value for the discernment of drug release mechanism of PLGA particles.

Mathematical models are used to characterize and optimize drug release in drug delivery systems (DDS). One of the most widely used DDS is the poly(lactic-co-glycolic acid) (PLGA)-based polymeric matrix owing to its biodegradability, biocompatibility, and easy manipulation of its properties through the manipulation of synthesis processes. Over the years, the Korsmeyer-Peppas model has been the most widely used model for characterizing the release profiles of PLGA DDS. However, owing to the limitations of the Korsmeyer-Peppas model, the Weibull model has emerged as an alternative for the characterization of the release profiles of PLGA polymeric matrices. The purpose of this study was to establish a correlation between the n and ß parameters of the Korsmeyer-Peppas and Weibull models and to use the Weibull model to discern the drug release mechanism. A total of 451 datasets describing the overtime drug release of PLGA-based formulations from 173 scientific articles were fitted to both models. The Korsmeyer-Peppas model had a mean Akaike Information Criteria (AIC) value of 54.52 and an n value of 0.42, while the Weibull model had a mean AIC of 51.99 and a ß value of 0.55, and by using reduced major axis regression values, a high correlation was found between the n and ß values. These results demonstrate the ability of the Weibull model to characterize the release profiles of PLGA-based matrices and the usefulness of the ß parameter for determining the drug release mechanism.

Reproducibility and usability assessment of the novel Fine Birth device for threatened preterm labor diagnosis.

BACKGROUND: Preterm delivery is considered the leading cause of mortality worldwide in children under 5 years old. Approximately 45 million pregnant women are hospitalized yearly for threatened preterm labor. However, only 50% of pregnancies complicated by threatened preterm labor end in delivery before the estimated date, classifying the rest as false threatened preterm labor. The ability of current diagnostic methods to predict threatened preterm labor is low (low positive predictive value), ranging between 8% and 30%. This highlights the need for a solution that accurately detects and differentiates between false and real threatened preterm labors in women who attend obstetrical clinics and hospital emergency departments with delivery symptoms. OBJECTIVE: Primarily, this aimed to assess the reproducibility and usability of a novel medical device, the Fine Birth, aimed at accurately diagnosing threatened preterm labor through the objective quantification of pregnant women's cervical consistency. Secondarily, this study aimed to evaluate the effect of training and the incorporation of a lateral microcamera on the device's reliability and usability outcomes. STUDY DESIGN: A total of 77 singleton pregnant women were recruited during their follow-up visits to the obstetrical and gynecologic departments at 5 Spanish hospitals. The eligibility criteria included pregnant women aged ≥18 years; women with a normal fetus and uncomplicated pregnancy; women without prolapse of membranes, uterine anomalies, previous cervical surgery, or latex allergy; and women signing the informed written consent. Cervical tissue stiffness was assessed using the Fine Birth device, whose technology is based on the propagation of torsional waves through the studied tissue. Cervical consistency measurements were taken for each woman until obtaining 2 valid measurements by 2 different operators. The intraobserver and interobserver reproducibilities of the Fine Birth measurements were assessed using the intraclass correlation coefficients with a 95% confidence interval and the Fisher test P value. The usability was evaluated on the basis of the clinicians' and participants' feedback. RESULTS: There was good intraobserver reproducibility (intraclass correlation coefficient, 0.88; 95% confidence interval, 0.84-0.95; Fisher test P value<.05). As the results obtained for the interobserver reproducibility did not reach the desired acceptable values (intraclass correlation coefficient of <0.75), a lateral microcamera was added to the Fine Birth intravaginal probe, and the operators involved in the clinical investigation received the corresponding training with the modified device. The analysis of 16 additional subjects demonstrated excellent interobserver reproducibility (intraclass correlation coefficient, 0.93; 95% confidence interval, 0.78-0.97) and an improvement after the intervention (P<.0001). CONCLUSION: The robust reproducibility and usability results obtained after the insertion of a lateral microcamera and the corresponding training make the Fine Birth a promising novel device to objectively quantify the patient's cervical consistency, diagnose threatened preterm labor, and, thus, predict the risk of spontaneous preterm birth. Further research is needed to demonstrate the clinical utility of the device.

Artificial intelligence for diagnosing neoplasia on digital cholangioscopy: development and multicenter validation of a convolutional neural network model.

BACKGROUND: We aimed to develop a convolutional neural network (CNN) model for detecting neoplastic lesions during real-time digital single-operator cholangioscopy (DSOC) and to clinically validate the model through comparisons with DSOC expert and nonexpert endoscopists. METHODS: In this two-stage study, we first developed and validated CNN1. Then, we performed a multicenter diagnostic trial to compare four DSOC experts and nonexperts against an improved model (CNN2). Lesions were classified into neoplastic and non-neoplastic in accordance with Carlos Robles-Medranda (CRM) and Mendoza disaggregated criteria. The final diagnosis of neoplasia was based on histopathology and 12-month follow-up outcomes. RESULTS: In stage I, CNN2 achieved a mean average precision of 0.88, an intersection over the union value of 83.24 %, and a total loss of 0.0975. For clinical validation, a total of 170 videos from newly included patients were analyzed with the CNN2. Half of cases (50 %) had neoplastic lesions. This model achieved significant accuracy values for neoplastic diagnosis, with a 90.5 % sensitivity, 68.2 % specificity, and 74.0 % and 87.8 % positive and negative predictive values, respectively. The CNN2 model outperformed nonexpert #2 (area under the receiver operating characteristic curve [AUC]-CRM 0.657 vs. AUC-CNN2 0.794, P < 0.05; AUC-Mendoza 0.582 vs. AUC-CNN2 0.794, P < 0.05), nonexpert #4 (AUC-CRM 0.683 vs. AUC-CNN2 0.791, P < 0.05), and expert #4 (AUC-CRM 0.755 vs. AUC-CNN2 0.848, P < 0.05; AUC-Mendoza 0.753 vs. AUC-CNN2 0.848, P < 0.05). CONCLUSIONS: The proposed CNN model distinguished neoplastic bile duct lesions with good accuracy and outperformed two nonexpert and one expert endoscopist.

Characterization of Functionalized PLGA Nanoparticles Loaded with Mangiferin and Lupeol, and their Effect on BEAS-2B and HepG2 Cell Lines.

Lupeol (LP) and Mangiferin (MG) have beneficial effects on health. However, their pharmacokinetic properties can affect their bioavailability when administered orally. Therefore, their incorporation as a vehicle in a hybrid matrix of ZnO and PLGA could contribute to improving bioavailability. METHODS: This study aimed to develop this matrix and evaluate the optical and bioactive properties obtained by the solvent emulsion and evaporation methods. These were subjected to processes to evaluate their bioactivity in relation with topoisomerase. RESULTS: Functionalized treatment number 15 (TF15) showed the best results in studies of controlled release and encapsulation efficiency of lupeol (LP) and mangiferin (MG) (60.01 ± 1.24% and 57.71 ± 1.94%). The best treatment showed behavior as a topoisomerase II inhibitor (18.60 ± 1.55). The nanoparticles developed in this study did not show a cytotoxic effect on BEAS-2B, while HepG2, showed a decrease in viability (IC50 1549.96 ± 174.62 µg/mL). However, although the hemolytic activity is not shown after 1 h of exposure, morphological alterations caused by TF15 are observed at concentrations of 2500 and 1250 µg/mL. CONCLUSION: The TF15 treatment shown maintaining antitopoisomerasa activity does and does not cytotoxixity for healthy cells and slows down the growth of cancer cells.