Combined Merkel Cell Carcinoma and Squamous Cell Carcinoma: A Systematic Review.

Combined Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC) have classically been regarded as more aggressive than conventional, pure, Merkel cell polyomavirus (MCPyV)-positive MCC. It is still unknown whether combined MCC and SCC are more aggressive than pure, MCPyV-negative MCC, and the origin of both the SCC and MCC elements of these combined tumors has not been elucidated. The main objective of this systematic review was to assess whether combined MCC and SCC tumors are associated with a worse prognosis than pure MCC; the secondary goals were the characterization of the clinical and histopathological features of these combined neoplasms. A total of 38 studies, including 152 patients, were selected for review. In total, 76% of the cases were MCPyV-negative, whereas 4% were MCPyV-positive. The most frequent histopathological pattern was that of an SCC in situ combined with a dermal MCC (36%), followed by both an in situ and invasive SCC combined with a dermal MCC (20%). Forty-seven percent of all cases fitted in the morphology of the so-called "collision tumors". Three combined MCC cases that would fit in the morphological category of collision tumors presented both squamous and neuroendocrine elements in their respective nodal metastases. The mean overall survival was 36 months, comparable to that of pure, MCPyV-negative MCC. This review found similarly aggressive behavior for combined MCC and SCC and pure, MCPyV-negative MCC. Preliminary data strongly suggest that all MCPyV-negative MCC tumors, whether combined or pure, are part of a common spectrum.

Molecular Profile of Subungual Melanoma: A MelaNostrum Consortium Study of 68 Cases Reporting BRAF, NRAS, KIT, and TERT Promoter Status.

BACKGROUND: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. OBJECTIVES: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. METHODS: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or next-generation sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. RESULTS: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3%) and KIT (10%), followed by NRAS (7.6%), and TERTp (3.8%). Their prevalence was similar to that of non-subungual acral melanoma but higher in SM located on the hand than on the foot. CONCLUSIONS: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot.

Topical Imiquimod in Primary Cutaneous Extramammary Paget's Disease: A Systematic Review.

Extramammary Paget's disease (EMPD) is subclinical in extent and multifocal in nature. There is no global consensus for treatment, so its management represents a challenge in clinical practice. Therefore, we conducted a systematic review through the main electronic databases to assess the effectiveness of topical imiquimod in cutaneous EMPD and to discuss its management. Finally, 24 studies involving a total of 233 EMPD patients treated with topical imiquimod were selected. The topical imiquimod response rate was 67%, and the complete response (CR) rate was 48%. Patients were treated with a three-four times a week regimen in most cases, ranging between 2 to 52 weeks. In addition, imiquimod was applied as an adjunctive treatment in 21 patients, achieving a CR rate of 71%. Consequently, imiquimod therapy could achieve a good response ratio as a first-line treatment, as adjuvant and neo-adjuvant therapy, and as a treatment for recurrent disease. The heterogeneity between studies and the lack of a control arm made it impossible to conduct a meta-analysis. To improve the quality of evidence on EMPD, multicenter studies are essential to collect a larger number of patients and, consequently, obtain high-quality evidence to standardize treatment. The Prospero registration number is CRD42023447443.

Scalable High-Mobility Graphene/hBN Heterostructures.

Graphene-hexagonal boron nitride (hBN) scalable heterostructures are pivotal for the development of graphene-based high-tech applications. In this work, we demonstrate the realization of high-quality graphene-hBN heterostructures entirely obtained with scalable approaches. hBN continuous films were grown via ion beam-assisted physical vapor deposition directly on commercially available SiO2/Si and used as receiving substrates for graphene single-crystal matrixes grown by chemical vapor deposition on copper. The structural, chemical, and electronic properties of the heterostructure were investigated by atomic force microscopy, Raman spectroscopy, and electrical transport measurements. We demonstrate graphene carrier mobilities exceeding 10,000 cm2/Vs in ambient conditions, 30% higher than those directly measured on SiO2/Si. We prove the scalability of our approach by measuring more than 100 transfer length method devices over a centimeter scale, which present an average carrier mobility of 7500 ± 850 cm2/Vs. The reported high-quality all-scalable heterostructures are of relevance for the development of graphene-based high-performing electronic and optoelectronic applications.

Association of germline variants in telomere maintenance genes (POT1, TERF2IP, ACD, and TERT) with spitzoid morphology in familial melanoma: A multi-center case series.

Background: Spitzoid morphology in familial melanoma has been associated with germline variants in POT1, a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid differentiation. Objective: To assess if familial melanoma cases associated with germline variants in TMG (POT1, ACD, TERF2IP, and TERT) commonly exhibit spitzoid morphology. Methods: In this case series, melanomas were classified as having spitzoid morphology if at least 3 of 4 dermatopathologists reported this finding in ≥25% of tumor cells. Logistic regression was used to calculate odds ratios (OR) of spitzoid morphology compared to familial melanomas from unmatched noncarriers that were previously reviewed by a National Cancer Institute dermatopathologist. Results: Spitzoid morphology was observed in 77% (23 of 30), 75% (3 of 4), 50% (2 of 4), and 50% (1 of 2) of melanomas from individuals with germline variants in POT1, TERF2IP, ACD, and TERT, respectively. Compared to noncarriers (n = 139 melanomas), POT1 carriers (OR = 225.1, 95% confidence interval: 51.7-980.5; P < .001) and individuals with TERF2IP, ACD, and TERT variants (OR = 82.4, 95% confidence interval: 21.3-494.6; P < .001) had increased odds of spitzoid morphology. Limitations: Findings may not be generalizable to nonfamilial melanoma cases. Conclusion: Spitzoid morphology in familial melanoma could suggest germline alteration of TMG.

Risk Factors Associated with Epilepsy Related to Cerebrovascular Disease: A Systematic Review and Meta-Analysis.

Background and Objective: Stroke is one of the most frequent neurological syndromes in the adult population and the cause of 10% of all diagnosed epilepsies. It is attributed to the origin of up to 50% of them in adults >60 years of age. Although a few risk factors have been described and considered when modeling predictive tools, this aspect is still clinically complex. The objective of this study is to describe and compare predictor scales of post stroke epilepsy (PSE) in adult patients with better performance. Methods: A systematic review and meta-analysis were performed of studies published between 2010 and 2020 and found in PubMed, Scopus, EMBASE, LILACS, BVS, Google Scholar, and CENTRAL databases. Sixteen studies were included with a total of 298,694 patients with a diagnosis of stroke, 5590 presented late seizures (LS). Results: Hemorrhage, cortical involvement, and early seizure were the elements most associated with the risk of presenting late seizures. The SeLECT score demonstrated a low risk of bias with a high predictive ability in patients with ischemic stroke (AUC: 0.77 [95% CI: 0.71-0.82]). In patients with hemorrhagic stroke, the CAVE score demonstrated adequate predictive ability (AUC: 0.81 [95% CI: 0.76-0.86]), but an uncertain risk of bias. Research has established risk factors for post ictal epilepsy; however, the numerous ways of assessing data in studies and the difference in their designs make the task of producing a predictive scale that covers the most important risk factors and is reliable for application in the clinical setting, regardless of stroke etiology, very arduous. Conclusion: Hemorrhage, cortical involvement, and early seizure are associated with an increased risk of post ictal epilepsy. Also, elements such as age, traditional vascular risk factors, and functional assessment failed to reflect statistical significance. Finally, further research is required to refine the available predictive tools.

Validation of a Hybrid Exoskeleton for Upper Limb Rehabilitation. A Preliminary Study.

Recovery of therapeutic or functional ambulatory capacity in patients with rotator cuff injury is a primary goal of rehabilitation. Wearable powered exoskeletons allow patients to perform repetitive practice with large movements to maximize recovery, even immediately after the acute event. The aim of this paper is to describe the usability, acceptability and acceptance of a hybrid exoskeleton for upper-limb passive rehabilitation using the System Usability Scale (SUS) questionnaire. This equipment, called ExoFlex, is defined as a hybrid exoskeleton since it is made up of rigid and soft components. The exoskeleton mechanical description is presented along with its control system and the way motion is structured in rehabilitation sessions. Seven patients (six women and one man) have participated in the evaluation of this equipment, which are in the range of 50 to 79 years old. Preliminary evidence of the acceptance and usability by both patients and clinicians are very promising, obtaining an average score of 80.71 in the SUS test, as well as good results in a questionnaire that evaluates the clinicians' perceived usability of ExoFlex.

Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development.

According to the divergent pathway model, cutaneous melanoma comprises a nevogenic group with a propensity to melanocyte proliferation and another one associated with cumulative solar damage (CSD). While characterized clinically and epidemiologically, the differences in the molecular profiles between the groups have remained primarily uninvestigated. This study has used a custom gene panel and bioinformatics tools to investigate the potential molecular differences in a thoroughly characterized cohort of 119 melanoma patients belonging to nevogenic and CSD groups. We found that the nevogenic melanomas had a restricted set of mutations, with the prominently mutated gene being BRAF. The CSD melanomas, in contrast, showed mutations in a diverse group of genes that included NF1, ROS1, GNA11, and RAC1. We thus provide evidence that nevogenic and CSD melanomas constitute different biological entities and highlight the need to explore new targeted therapies.

Sex differences in gut microbiota modulation of aversive conditioning, open field activity, and basolateral amygdala dendritic spine density.

Gut microbiota influence numerous aspects of host biology, including brain structure and function. Growing evidence implicates gut microbiota in aversive conditioning and anxiety-related behaviors, but research has focused almost exclusively on males. To investigate whether effects of gut dysbiosis on aversive learning and memory differ by sex, adult female and male C57BL/6N mice were orally administered a moderate dose of nonabsorbable antimicrobial medications (ATMs: neomycin, bacitracin, and pimaricin) or a control over 10 days. Changes in gut microbiome composition were analyzed by 16S rRNA sequencing. Open field behavior, cued aversive learning, context recall, and cued recall were assessed. Following behavioral testing, the morphology of basolateral amygdala (BLA) principal neuron dendrites and spines was characterized. Results revealed that ATMs induced gut dysbiosis in both sexes, with stronger effects in females. ATMs also exerted sex-specific effects on behavior and neuroanatomy. Males were more susceptible than females to microbial modulation of locomotor activity and anxiety-like behavior. Females were more susceptible than males to ATM-induced impairments in aversive learning and cued recall. Context recall remained intact, as did dendritic structure of BLA principal neurons. However, ATMs exerted a sex-specific effect on spine density. A second experiment was conducted to isolate the effects of gut perturbation to cued recall. Extinction was also examined. Results revealed no effect of ATMs on cued recall or extinction, suggesting that gut dysbiosis preferentially impacts aversive learning. These data shed new light on how gut microbiota interact with sex to influence aversive conditioning, open field behavior, and BLA dendritic spine architecture.

Distribution and clinical role of KIT gene mutations in melanoma according to subtype: a study of 492 Spanish patients.

BACKGROUND: KIT mutations are primarily associated with acral and mucosal melanoma, and have been reported to show higher prevalence in chronic sun-damaged (CSD) than non-CSD melanomas. OBJECTIVES: To investigate the prevalence of KIT mutations in melanoma according to subtype, and determine the clinical role of such mutations. MATERIALS & METHODS: We present results from a study of a Spanish population of 492 melanomas, classified according to the latest World Health Organization (WHO) guidelines. We analysed the mutational status of KIT and correlated with different clinical variables related to sun exposure and family history. RESULTS: KIT mutations were significantly more frequent in acral (3/36; 8.3%) and mucosal (4/8; 50%) melanomas than non-acral cutaneous melanomas. No significant difference was observed in KIT mutational status between CSD and non-CSD melanomas. CONCLUSION: Our results suggest that KIT mutations in melanoma tumours are unrelated to the development of nevi or chronic sun damage, but their presence is associated with aggressive melanomas which show ulceration, vascular invasiveness, and increased Breslow thickness. These findings are consistent with those reported by The Cancer Genome Atlas network.

Seguimiento a largo plazo tras disección submucosa endoscópica de lesiones colorrectales en una cohorte española / No disponible

INTRODUCCIÓN: la disección submucosa endoscópica (DSE) en colon es una técnica en expansión en países occidentales. Existen pocos estudios con seguimiento a largo plazo. OBJETIVO: analizar supervivencia libre de enfermedad a largo plazo tras DSE y comparar las tasas de recidiva en función de diferentes factores. MATERIAL Y MÉTODOS: cohorte prospectiva de pacientes con DSE planeada entre septiembre de 2008 y diciembre de 2015. Cuando no fue posible técnicamente completar DSE se realizó disección híbrida en bloque o fragmentada. Se analizó la tasa de recurrencia a cinco años mediante curvas de Kaplan-Meier y se compararon en función de diferentes factores usando test de log-rank. RESULTADOS: se incluyó una cohorte inicial de 89 pacientes en los que se consiguió seguimiento en 69. De los 69 pacientes, en 31 (45 %) se realizó DSE; en once (16 %), DSE híbrida; y en 27 (39 %), DSE híbrida fragmentada. La mediana de seguimiento fue de 27 meses. La supervivencia libre de enfermedad a cinco años fue del 81 %. La media de endoscopias para eliminar la recurrencia fueron dos (rango 1-7) y ninguna requirió cirugía. La tasa de recidiva fue significativamente menor tras DSE "en bloque" respecto a fragmentada (15 % vs. 27 %, p = 0,036) y en resecciones R0 respecto a R1 (0 % vs. 26 %, p = 0,034). Las resecciones con márgenes laterales negativos en lesiones resecadas en bloque presentaron menor tasa de recidiva respecto a aquellas con márgenes afectos/desconocidos, que no alcanzaron la significación estadística (0 % vs. 28 %, p = 0,09). CONCLUSIONES: en nuestro estudio, la supervivencia libre de enfermedad a cinco años fue del 81 % y ningún paciente requirió cirugía durante el seguimiento. Las resecciones fragmentadas y R1 se asociaron de forma significativa con mayor tasa de recurrencia

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Disección submucosa endoscópica en lesiones gástricas epiteliales: resultados a largo plazo en una cohorte española / No disponible

INTRODUCCIÓN: la disección submucosa endoscópica sobre lesiones gástricas (DSE-G) es una técnica que permite la resección de tumores gástricos precoces en bloque, con una tasa de curación similar a la cirugía y una morbimortalidad menor. OBJETIVO: analizar la supervivencia total, la supervivencia libre de enfermedad y la tasa de recidiva en pacientes sometidos a DSE-G en una cohorte española a lo largo de su evolución clínica. MATERIAL Y MÉTODOS: estudio observacional prospectivo. Inclusión de pacientes sometidos a DSE-G de 2008 a 2015, con seguimiento entre seis y 60 meses. Se analizó la recurrencia a cinco años mediante curvas de Kaplan-Meier y los resultados fueron comparados entre diferentes factores (en bloque vs. resección fragmentada, resecciones curativas R0 vs. margen lateral afecto ML+) usando test log-rank. RESULTADOS: se analizaron 35 pacientes sometidos a DSE-G, con una mediana de seguimiento de 33,62 meses. Se identificaron cuatro recidivas en este periodo (11,4%), tres de ellas tratadas mediante nueva DSE-G. La presencia de ML+ en la pieza histológica se relacionó con mayor tasa de recidiva local durante el seguimiento (p = 0,06). Las resecciones fragmentadas presentaron un mayor riesgo de recidiva pero sin detectarse diferencias estadísticamente significativas (p = 0,49). No se registraron fallecimientos por neoplasia gástrica ni gastrectomía por persistencia de enfermedad en este periodo. La tasa de supervivencia global en nuestra serie fue de 94,3%. CONCLUSIONES: la DSE-G realizada en nuestro medio permite una tasa elevada de curación a largo plazo evitando la cirugía. Estos resultados se asemejan a las series europeas publicadas y aún se encuentran lejos de las tasas de curación y recidiva de las cohortes asiáticas. Los casos de recidiva local pueden ser controlados mediante endoscopia

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Endoscopic submucosal dissection for gastric epithelial lesions: long-term results in a Spanish cohort.

INTRODUCTION: endoscopic submucosal dissection for gastric lesions (ESD-G) is a technique that allows en-bloc resection of early gastric tumors, with a cure rate similar to that of surgery but lower morbidity and mortality rates. OBJECTIVE: to assess total survival, disease-free survival and relapse rate during the course of disease in a Spanish cohort of patients undergoing ESD-G. MATERIAL AND METHODS: this was a prospective observational study of patients undergoing ESD-G from 2008 to 2015, with a follow-up ranging from six to 60 months. Recurrence at five years was analyzed using Kaplan-Meier curves and the results were compared according to several factors using the log-rank test. These included en-bloc versus piecemeal resection and R0 curative resection versus resection with affected lateral margins (LM+). RESULTS: a total of 35 patients undergoing ESD-G were assessed, with a median follow-up of 33.62 months. Four relapses were identified (11.4%) during this period, of which three were managed with repeat ESD-G. A histological specimen with LM+ was associated with a higher local relapse rate during follow-up (p = 0.06). Piecemeal resections had a higher relapse risk, although no statistically significant differences were identified (p = 0.49). No deaths from gastric cancer occurred and no gastrectomies due to persistent disease were performed during this period. The overall survival rate in our series was 94.3%. CONCLUSIONS: ESD-G in our setting provides high long-term cure rates, while avoiding surgery. These results are similar to those reported by the European series and remain far removed from the cure and relapse rates obtained in Asian cohorts. Local relapse cases may be monitored with endoscopy.

Long-term follow-up after endoscopic submucosal dissection of colorectal lesions in a Spanish cohort.

INTRODUCTION: ESD in the colon is an increasingly important technique in Western countries. There are few studies that include long term follow-up. AIM: to analyze the long term recurrence free survival rate after ESD and to compare recurrence rates according to different variables. METHODS: this was a prospective observational study of patients with a planned ESD from September 2008 to December 2015. When it was not possible to achieve an ESD, hybrid ESD was performed, either en bloc or piecemeal. Kaplan-Meier survival curves were used to assess the five year local recurrence free survival rate and the recurrence rate. The results were compared according to different factors. RESULTS: of the 89 patients scheduled for ESD who were initially enrolled in the study, 69 were finally included for follow-up. ESD was performed in 31 (45%) patients, KAR in eleven (16%) and pKAR in 27 (39%). The median follow-up was 27 months (range 6-60). The five year disease free survival rate was 81%. The average number of endoscopies needed to eliminate recurrence was two (range 2-7) and no patient required surgery for this reason. The recurrence rate was significantly higher in piecemeal resections vs en bloc resections (27% vs 15%, p = 0.036) and R1 resections vs R0 resections (26% vs 0%, p = 0.034). The presence of affected or unknown lateral margins in en bloc resections without other poor prognosis factors had higher recurrence rates but the difference was not statistically significant (28% vs 0%, p = 0.09). CONCLUSIONS: in our study, the five year disease free survival rate was 81% and no patient required surgery during follow-up. Piecemeal and R1 resections had significantly higher recurrence rates, as well as LM involvement, although this was not statistically significant.

Efficient Multiaxial Shoulder-Motion Tracking Based on Flexible Resistive Sensors Applied to Exosuits.

This article describes the performance of a flexible resistive sensor network to track shoulder motion. This system monitors every gesture of the human shoulder in its range of motion except rotations around the longitudinal axis of the arm. In this regard, the design considers the movement of the glenohumeral, acromioclavicular, sternoclavicular, and scapulothoracic joints. The solution presented in this work considers several sensor configurations and compares its performance with a set of inertial measurement units (IMUs). These devices have been put together in a shoulder suit with Optitrack visual markers in order to be used as pose ground truth. Optimal configurations of flexible resistive sensors, in terms of accuracy requirements and number of sensors, have been obtained by applying principal component analysis techniques. The data provided by each configuration are then mapped onto the shoulder pose by using neural network algorithms. According to the results shown in this article, a set of flexible resistive sensors can be an adequate alternative to IMUs for multiaxial shoulder pose tracking in open spaces. Furthermore, the system presented can be easily embedded in fabric or wearable devices without obstructing the user's motion.

Prevalence of surgical complications in gynecological surgery at the Hospital Universitario San José in Popayán, Colombia. 2015 / Prevalencia de complicaciones quirúrgicas en cirugía ginecológica, Hospital Universitario San José de Popayán, Colombia. 2015

Abstract Introduction: Every surgery has risk of complications; prognosis depends on prompt diagnosis and timely management. Objective: To determine the prevalence of surgical complications in gynecological surgery in a tertiary care hospital and to explore associated factors. Materials and methods: Prevalence study with secondary analysis of medical records of patients who underwent scheduled gynecological surgery. The outcome variable was complications reported during a period of less than 30 days. The universe was established, and clinical, biological and sociodemographic variables were collected. To determine prevalence, the total number of complications was taken as the numerator and the total number of records was used as the denominator. To explore associated factors, odds ratio (OR) was used as a measure of association with a 95% CI. Results: 591 records were reviewed, finding a surgical management of ectopic pregnancy prevalence of 3.8% (OR=3.73, CI95%: 2.4192.52). Obesity (OR 12.47, CI95%: 4.48-33.19) and gynecological surgery for malignancy (OR 3.73, CI95%: 1.14- 10.48) were associated with complications. Conclusion: The prevalence found in our institution was similar to what most studies have reported.

Resumen Introducción. Toda cirugía implica riesgo de complicaciones; el pronóstico depende de su pronto diagnóstico y manejo oportuno. Objetivo. Determinar la prevalencia de complicaciones quirúrgicas en cirugía ginecológica en un hospital de alta complejidad y explorar factores asociados. Materiales y métodos. Estudio de prevalencia con análisis secundario en el que se incluyeron historias de pacientes sometidas a cirugía ginecológica programada. La variable resultado fue la complicación reportada durante un periodo <30 días. Se tomó el universo y se recolectaron variables clínicas, biológicas y sociodemográficas. Para determinar la prevalencia se tomó como numerador el total de complicaciones y como denominador el total de historias; para explorar los factores asociados se utilizó el Odds Ratio como medida de asociación con un índice de confianza al 95%. Resultados. Se revisaron 591 historias clínicas y la prevalencia encontrada fue del 3.8% (IC95%: 2.3-5.4). La historia de manejo quirúrgico del ectópico (OR: 16.89; IC95%: 2.41-92.52), la obesidad (OR: 12.47; IC95%: 4.48-33.19) y la cirugía ginecología por malignidad (OR: 3.73; IC95%: 1.14-10.48) se asociaron con complicaciones. Conclusión: La prevalencia encontrada fue similar a la de la mayor parte de los estudios consultados.

Suitability of melanoma FFPE samples for NGS libraries: time and quality thresholds for downstream molecular tests.

The use of NGS in clinical practice for precision diagnosis requires a quality starting material. Despite the broadly established use of formalin-fixed paraffin-embedded (FFPE) samples in molecular testing, these usually have low-quality DNA. We established a method to determine the suitability of melanoma FFPE samples for an amplicon-based NGS custom panel analysis. DNA was extracted from unstained melanoma samples and wide local excision samples. Amplicon-based libraries were constructed and tested using time and quality parameters as variables. Time elapsed from sample retrieval >7 years, a quality control value > 5.63 and a DNA integrity value < 2.05 indicated samples were not suitable. A decision tree is provided with rate of samples suitable for analysis according to the combination of these parameters.

Binge-like ethanol treatment in adolescence impairs autophagy and hinders synaptic maturation: Role of TLR4.

Adolescence is a developmental period of brain maturation in which remodeling and changes in synaptic plasticity and neural connectivity take place in some brain regions. A different mechanism participates in adolescent brain maturation, including autophagy processes that play a role in synaptic development and plasticity. Alcohol is a neurotoxic compound whose abuse in adolescence causes TLR4 response activation by triggering neuroinflammation, neural damage and behavioral alterations. However, the potential participation of autophagy in long-term neurochemical and cognitive dysfunctions induced by binge ethanol drinking in adolescence is uncertain. We therefore evaluated whether binge ethanol drinking alters autophagy pathways by contributing to adolescent synaptic dysfunctions, and if the immune receptor TLR4 response participates in these events. With wild-type (WT) and TLR4-deficient (TLR4-KO) adolescent mice treated intermittently with ethanol (3.0 g/kg) for 2 weeks, we show that binge-like ethanol exposure in adolescence impairs autophagy machinery by increasing autophagy inhibitor mTOR by lowering LC3-II levels and accumulating p62. Inhibition of mTOR, by rapamycin, restores the levels of excitatory scaffolding synaptic proteins (PSD-95 or SHANK3), p62, and partly reestablishes the LC3-II levels in the prefrontal cortices of ethanol-treated WT mice. Elimination of the TLR4 receptors using TLR4-KO mice prevents autophagy dysfunctions and reduces the number or size of the synaptic connections induced by ethanol. These results suggest the role of autophagy dysfunctions in the structural synaptic plasticity alterations induced by binge alcohol in adolescence, and support the participation of the TLR4 response in these events.