Sucralose and stevia consumption leads to intergenerational alterations in body weight and intestinal expression of histone deacetylase 3.

OBJECTIVES: It is unclear whether parental consumption of non-nutritive sweetener (NNS) can affect subsequent generations. The aim of this study was to determine whether chronic parental consumption of sucralose and stevia in mice affects body weight gain and liver and intestinal expression of histone deacetylase 3 (Hdac3) in these animals and in the subsequent first filial (F1) and second filial (F2) generations. METHODS: Male and female mice (n = 47) were divided into three groups to receive water alone or supplemented with sucralose (0.1 mg/mL) or stevia (0.1 mg/mL) for 16 wk (parental [F0] generation). F0 mice were bred to produce the F1 generation; then, F1 mice were bred to produce the F2 generation. F1 and F2 animals did not receive NNSs. After euthanasia, hepatic and intestinal expression of Hdac3 was determined by quantitative reverse transcription polymerase chain reaction. RESULTS: Body weight gain did not differ between the three groups in the F0 generation, but it was greater in the F1 sucralose and stevia groups than in the control group. Consumption of both NNSs in the F0 generation was associated with lower Hdac3 expression in the liver and higher in the intestine. Hepatic Hdac3 expression was normalized to the control values in the F1 and F2 animals of the sucralose and stevia groups. Intestinal expression was still higher in the F1 generations of the sucralose and stevia groups but was partially normalized in the F2 generation of these groups, compared with control. CONCLUSIONS: NNS consumption differentially affects hepatic and intestinal Hdac3 expression. Changes in hepatic expression are not transmitted to the F1 and F2 generations whereas those in intestinal expression are enhanced in the F1 and attenuated in the F2 generations.

Visualization and Identification of Silicone Oil Emulsification Using Dynamic Infrared Confocal Scanning Laser Ophthalmoscopy.

Introduction: Silicone oil (SO) is a crucial agent used as an intraocular tamponade in the treatment of complex vitreoretinal diseases. Despite its effectiveness, SO is prone to emulsification, which can lead to significant and sometimes irreversible complications in both the anterior and posterior segments of the eye. The detection and monitoring of SO emulsification are therefore of paramount importance. Traditional imaging modalities have limitations in visualizing SO, leading to the exploration of more advanced imaging techniques. This study introduces the application of dynamic infrared confocal scanning laser ophthalmoscopy (IRcSLO) for this purpose and evaluates its effectiveness. Case Presentation: We report on 2 patients who underwent pars plana vitrectomy with subsequent SO injection for the management of retinal detachment. Postsurgery, both patients were imaged using the Heidelberg Retina Tomography Spectralis IRcSLO. The focus was on the visualization of the SO status, including the presence and distribution of emulsified SO droplets. The IRcSLO imaging technique demonstrated its capability to effectively visualize emulsified SO droplets. Interestingly, this was also true for cases where the SO had been removed. The emulsified droplets were observed as micron-sized, spherical entities with a nonuniform distribution throughout the vitreous cavity. Conclusion: Dynamic IRcSLO has proven to be an effective imaging modality for visualizing the emulsification of SO, offering a novel perspective into the characterization of SO droplets. It facilitates the analysis of droplet count, motility, and precise localization within the vitreous cavity. The findings from the case presentations underscore the variability of SO emulsification patterns and the sensitivity of IRcSLO in detecting even minuscule emulsified droplets. This imaging technique has significant potential for future research, particularly in understanding the timing of emulsification, the factors contributing to it, and the development of possible preventive strategies. Additionally, it allows for a more in-depth analysis of the behavior of emulsified SO droplets across different SO viscosities, which could be instrumental in optimizing patient outcomes.

New 200° Single-Capture Color Red-Green-Blue Ultra-Widefield Retinal Imaging Technology: First Clinical Experience.

BACKGROUND AND OBJECTIVE: We investigated the additive clinical benefits of a new ultra-widefield (UWF) red-green-blue (RGB) imaging technology. PATIENTS AND METHODS: This was a retrospective, observational, single-center study of 86 consecutive patients (172 eyes). UWF red-green (RG) and RGB images were taken using a new Optos California (Optos Plc). This scanning laser ophthalmoscope uses wavelengths of 635 nm, 532 nm, and 488 nm for the red (R), green (G), and blue laser (B), respectively. The same device can image both in UWF RG and RGB simultaneously. RESULTS: The new Optos California provides a well-balanced, three-channel color image that is clinically useful in imaging and identifying vitreoretinal, retinal, and chorioretinal pathologies. The combination of the images captured by each laser source produces a final composite image that more accurately reflects the natural colors of the fundus. The addition of blue light provides additional detail to visualize the vitreoretinal interface and superficial retina, both within the posterior pole and in the periphery. CONCLUSIONS: This new device allows for both RG and RGB imaging of the retina, providing valuable information on the anatomy of the vitreoretinal interface, retina, retinal pigment epithelium, and their abnormalities. Both techniques complement each other and can be useful in daily practice, allowing clinicians to choose the preferred imaging technique depending on specific findings and conditions. [Ophthalmic Surg Lasers Imaging Retina 2023;54:714-718.].

Dietoterapia en artritis reumatoide: Revisión de la evidencia

La artritis reumatoide (RA), es una enfermedad crónica reumática, caracterizada por un daño articular progresivo y manifestaciones extraarticulares, que pueden desencadenar una discapacidad. La etiología de las patologías autoinmunes, incluyendo la RA, es compleja, abarcando factores de tipo genético, hormonal, dietarios y ambientales. Sin embargo, los mecanismos fisiológicos por los que estos agentes contribuyen a la patogenia aún no están definidos completamente. Estudios sugieren un impacto de la disbiosis del microbioma intestinal en la patogénesis de la artritis reumatoide sugiriendo también la alteración de la permeabilidad intestinal como una posible causa. Esta se puede relacionar con patrones dietarios influyentes en la prevención de esta patología así como una propuesta de tratamiento complementario al manejo farmacológico tradicional, considerando el riesgo aumentado de estos pacientes de desarrollar síndrome metabólico y "caquexia reumatoide", una acumulación de tejido adiposo acompañado de una disminución de tejido muscular debido a los cambios catabólicos debido a la inflamación crónica e inactividad física a consecuencia de las dificultades motoras. Ante evidencia reciente que propone patrones de alimentación e intervenciones dietarias como tratamiento complementario a la terapia farmacológica en el manejo de la RA, la siguiente revisión narrativa cualitativa se propone revisar la efectividad de intervenciones propuestas en términos de dolor y actividad de enfermedad, encontrando dentro de la amplia heterogeneidad de intervenciones propuestas, aquellos patrones dietéticos con efecto modulador de la microbiota intestinal como la dieta mediterránea y sus variaciones en contexto de la promoción de un estilo de vida serían positivas como terapia complementaria a esta patología.

Rheumatoid arthritis (RA) is a chronic rheumatic disease characterised by progressive joint damage and extra-articular manifestations that can lead to disability. The aetiology of autoimmune diseases, including RA, is complex, involving genetic, hormonal, dietary, and environmental factors. However, the physiological mechanisms by which these agents contribute to pathogenesis have not yet been fully defined. More recent studies suggest an impact of gut microbiome dysbiosis on the pathogenesis of autoimmune diseases in both animal and human models, including rheumatoid arthritis, also suggesting altered intestinal permeability as a possible cause. This modification of the gut microbiome may be related to influential diet patterns in the prevention of this pathology, as well as a proposed complementary treatment to traditional pharmacological treatment, also considering the increased risk for these patients of developing metabolic syndrome and "rheumatoid cachexia", an accumulation of adipose tissue accompanied by a decrease in muscle tissue due to catabolic changes due to chronic inflammation and physical inactivity as a consequence of motor difficulties in RA. With the emergence of recent evidence proposing dietary interventions and eating patterns as adjunctive treatment to drug therapy in the management of RA, the following narrative qualitative review proposes reviewing recent evidence on the effectiveness of various proposed dietary interventions in the treatment of rheumatoid arthritis in terms of pain and disease activity, finding between a high heterogeneity of proposed interventions, those dietary patterns with modulating effect on the gut microbiome as Mediterranean diet and its variations in the context of promoting a healthy lifestyle would be positive as a complementary therapy for this disease.

New Imaging Technology for Simultaneous Multiwavelength-UWF Fundus Fluorescein Angiography and Indocyanine Green Angiography With Navigated Central and Peripheral SS-OCT.

OBJECTIVE: Our aim was to assess central and peripheral retinal and choroidal diseases using novel simultaneous multiwavelength-ultra-widefield (MW-UWF) fundus fluorescein angiography (FFA)/indocyanine green angiography (ICGA) with navigated central and peripheral swept-source optical coherence tomography (SS-OCT) technology. METHODS: Retrospective evaluation was carried out of 30 consecutive patients (60 eyes) who underwent UWF red/green (RG), infrared (IR), FFA and ICGA with simultaneous navigated SS-OCT using Optos Silverstone (Optos PLC). Angiographic retinal and choroidal findings in vascular pathologies and their relationship with the vitreoretinal interface (VRI) were assessed. RESULTS: Simultaneous FFA with navigated SSOCT was performed in all patients and simultaneous FFA-ICGA with SS-OCT in 18 eyes (30%). Cross-sectional central and peripheral changes in the retina, choroid, and VRI corresponding with angiographic findings in several diseases were imaged. CONCLUSION: First-in-human study of a new technology providing UWF RG/FFA/ICGA with simultaneous navigated central and peripheral SS-OCT can guide clinical management and provide new insights and understanding of central and peripheral retinal and choroidal disease. [Ophthalmic Surg Lasers Imaging Retina 2023;54:401-410.].

The Functional Anatomy and Innervation of the Platysma is Segmental: Implications for Lower Lip Dysfunction, Recurrent Platysmal Bands, and Surgical Rejuvenation.

BACKGROUND: Despite the central role of the platysma in face and neck rejuvenation, much confusion exists regarding its surgical anatomy. OBJECTIVES: This study was undertaken to clarify the regional anatomy of the platysma and its innervation pattern and to explain clinical phenomena, such as the origin of platysmal bands and their recurrence, and the etiology of lower lip dysfunction after neck lift procedures. METHODS: Fifty-five cadaver heads were studied (16 embalmed, 39 fresh, mean age 75 years). Following preliminary dissections and macro-sectioning, a series of standardized layered dissections were performed, complemented by histology and sheet plastination. RESULTS: In addition to its origin and insertion, the platysma is attached to the skin and deep fascia across its entire superficial and deep surfaces. This composite system explains the age-related formation of static platysmal bands, recurrent platysmal bands after complete platysma transection, and recurrent anterior neck laxity after no-release lifting. The facial part of the platysma is primarily innervated by the marginal mandibular branch of the facial nerve, whereas the submandibular platysma is innervated by the "first" cervical branches, which terminate at the mandibular origin of the depressor labii inferioris. This pattern has implications for postoperative dysfunction of the lower lip, including pseudoparalysis, and potential targeted surgical denervation. CONCLUSIONS: This anatomical study, comprised of layered dissections, large histology, and sheet plastination, fully describes the anatomy of the platysma including its bony, fascial, and dermal attachments, as well as its segmental innervation including its nerve danger zones. It provides a sound anatomical basis for the further development of surgical techniques to rejuvenate the neck with prevention of recurrent platysmal banding.

New Terminology and Methodology for the Assessment of the Vitreous, Its Floaters and Opacities, and Their Effect on Vision: Standardized and Kinetic Anatomical and Functional Testing of Vitreous Floaters and Opacities (SK VFO Test).

OBJECTIVE: To introduce VFO and SK VFO Test: new, more representative terminology for symptoms of vitreous floaters/opacities (VFO) and new standardized kinetic (SK) anatomical-functional assessment. MATERIALS AND METHODS: Eight eyes underwent before-after limited vitrectomy (LV): best-corrected visual acuity, low-luminance visual acuity, Minnesota Low Vision Reading Chart near visual acuity in logMAR, contrast sensitivity function (CV1000E), and straylight measurements (SM) (HDA/LDA/C-Quant). SK infrared confocal scanning laser ophthalmoscopy (SK IRcSLO) and swept-source widefield optical coherence tomography (SS-WF-OCT) identified VFO and posterior vitreous detachment (PVD). SK IRcSLO was performed with gaze directed towards the extreme superior, inferior, and lateral directions. RESULTS: Anatomical-functional results after LV improved in 7 eyes (87.5%): objective scatter index (27.34%), disturbance index (47.97%) and C-Quant Log units (2.26%). Pre-LV SK IRcSLO and SS-WFOCT imaging identified dynamic well-defined VFO and PVD status (100%). A residual asymptomatic anterior cortical vitreous-induced shadowing ripple effect was detected post-LV. CONCLUSIONS: This is the first objective-standardized test accounting for VFO kinesis and intermittent effect. There is potential for personalizing treatment and establishing best candidates for laser or surgery. [Ophthalmic Surg Lasers Imaging Retina 2023;54:306-315.].

Childhood Obesity and Plasma Micronutrient Deficit of Chilean Children between 4 and 14 Years Old.

OBJECTIVE: To analyze the nutritional status and plasma levels of vitamins and minerals in a cohort of Chilean children between 4 and 14 years old from three cities in Chile (Santiago, Antofagasta, and Concepcion). DESIGN: This is a descriptive analysis of micronutrient levels in Chilean children as it relates to obesity and food consumption. SETTING: This study included 1235 children from schools in Santiago (central area), Antofagasta (northern area), and Concepcion (southern area) in Chile. RESULTS: Plasma levels of micronutrients revealed deficiencies in children from all these cities. Copper (26.4%) and calcium (33.0%) deficiencies were found in the children from Antofagasta, whereas iron (26.7%) and zinc (20.8%) deficiencies were found in the children from Concepcion and Santiago, respectively. The percentage of children with vitamin D deficiencies was exceptionally high in all cities (over 78%). The analysis of micronutrients and nutritional status revealed that vitamin D deficiencies were significantly higher (p = 0.02) in overweight children, particularly in Antofagasta. In the analysis of the nutritional status of children and their food consumption habits, the proportion of overweight and obesity was significantly higher (p = 0.001) in children that skipped breakfast compared to children that did not. Finally, children from low socioeconomic levels were significantly more overweight and obese compared to children from high socioeconomic levels (p < 0.05). CONCLUSIONS: this is the first study to describe plasma levels of micronutrients in Chilean children and adolescents. High percentages of obesity, overweight, and vitamin D deficiency were detected in children. These results are of significant relevance to future public health policies in Chile.

Cantidad, estabilidad y digestibilidad de hidratos de carbono tras el proceso de extrusión: Impacto sobre el índice glicémico de harinas de consumo habitual en Chile

Las harinas de trigo, maíz, lentejas y arroz son elementales para la formulación de distintos alimentos de alto consumo en la población chilena. El proceso de extrusión es ampliamente utilizado por la industria alimentaria para generar propiedades que permitan la reconstitución instantánea de harinas. Sin embargo, dicho proceso tecnológico; afecta la cantidad, la estabilidad y la digestibilidad de los hidratos de carbono (CHO) del ingrediente alimentario. Estas propiedades nutricionales impactan directamente en la respuesta glicémica de los individuos y en el índice glicémico (IG) de los alimentos. La presente revisión analiza el efecto de la extrusión sobre las propiedades nutricionales de los CHO de alimentos elaborados a partir de harinas de consumo habitual en Chile. Factores como la temperatura, y en menor grado, la humedad y velocidad utilizadas en el proceso de extrusión, junto con el origen del grano utilizado, determinan las propiedades nutricionales de CHO presente en harinas extruidas. El estudio, control y estandarización de estas variables operacionales permitiría estandarizar la elaboración industrial de productos extruidos, impactando favorablemente; sobre la velocidad de hidrólisis de almidón y el IG de harinas de trigo, maíz, lentejas o arroz; y de alimentos formulados a partir de ellas.

Flours from wheat, corn, lentils, and rice are essential for the formulation of various high-consumption foods in the Chilean population. The extrusion process is widely used by the food industry to generate properties that allow for the instant reconstitution of flours. However, this technological process affects the nutritional properties of the carbohydrates (CHO) in the food ingredient, including quantity, stability, and digestibility; characteristics that directly impact the glycemic response of individuals and the glycemic index of foods. This review analyzes the effect of extrusion on the nutritional properties of CHO in foods made from commonly consumed flours in Chile. Factors such as temperature, and to a lesser extent, humidity, and speed used in the extrusion process, along with the origin of the grain used, determine the healthy properties of CHO in extruded flours. The utility of adjusting the mentioned variables in the extrusion process would allow for the standardization of industrial scaling in the production of extruded foods that would positively impact the starch hydrolysis rate and glycemic index of wheat, corn, lentil, or rice flours, and foods formulated from them.

Faricimab in neovascular AMD: first report of real-world outcomes in an independent retina clinic.

PURPOSE: Assess short-term real-world outcomes in neovascular aged-related macular degeneration (nAMD) treated with novel faricimab. METHODS: Retrospective case series of nine patients with nAMD (11 eyes) treated with faricimab between May and November 2022. Treatment-naïve patients and non-naïve patients underwent logMAR best corrected visual acuity (BCVA), optical coherence tomography (OCT) DRI OCT-1 Triton (Topcon Corp, Tokyo, Japan), ultra-widefield (UWF) and fundus autofluorescence (FAF) (California Optomap, Optos plc, Dunfermline, Scotland, UK). Previous treatment intervals, number of intravitreal injections, sub/intra retinal fluid (SRF/IRF), central retinal thickness (CRT) and presence/changes in pigment epithelial detachments (PEDs) were recorded. RESULTS: Mean baseline BCVA and CRT values of patients who switched from other agents were 0.612 ± 0.75 logMAR and 256.16 ± 12.98 µm respectively, with a mean 36-day previous treatment interval. The median number of other previous anti-VEGF intravitreal injections was 8. Mean BCVA at one month significantly improved to 0.387 ± 0.54 logMAR, as well as CRT values which decreased to 245.43 ± 15.34 µm. In the 3 naïve patients, mean baseline BVCA and CRT values were 0.33 ± 0.29 and 874.67 ± 510.86 µm, respectively. At one month follow-up, mean BCVA improved to 0.30 ± 0.29 logMAR and mean CRT was 536.04 ± 36.15 µm. Overall, a significant improvement in BCVA of 0.21 ± 41 logMAR and 238.44 ± 114.9 µm was achieved at one month after the first faricimab intravitreal injection. In addition, a complete resolution of SRF was observed in 6 out of 8 eyes (75%) and of IRF in 2 out of 3 eyes (66.67%), respectively. Drusenoid PED morphology changes were observed in all patients and no drug-related adverse events were observed. CONCLUSION: Real-world outcomes showed improvement in BCVA and anatomic parameters at an early timepoint, demonstrating the efficacy and durability of faricimab in nAMD patients. Larger numbers of patients and longer follow-up are needed to determine whether the loading dose is required in all, what percentage of patients experience an improvement, and whether improvement it is maintained.

Benthic biota of Chilean fjords and channels in 25 years of cruises of the National Oceanographic Committee.

The CIMAR program (Marine Research Cruises to Remote Areas) run by the Chilean Navy through the National Oceanographic Committee has been developed since 1995, focused on Chilean fjord and channel zones (~41-56°S; "CIMAR-Fjords") and Chilean remote islands ("CIMAR-Islands"). Samples and data was collected on biotic and abiotic variables on all these cruises, both from the water column and benthos. Our work standardizes, compiles, and summarizes the published information on benthic organisms for twenty-one CIMAR-Fjords cruises developed in the first 25 years of the program, plus the Southern Ice Fields Cruise 1995 (precursor of the CIMAR program), which includes the distribution, abundance and geographic location of cruises sampling stations. The data set includes 8,854 records from 880 different localities, corresponding to 1,225 species from 24 different phyla (four kingdoms) and more than 150,000 individuals. Only two cruises did not record any benthic sampling. The fjords and channels of Chilean Patagonia have high biodiversity, so we hope that our data set will serve as a baseline for ecological studies and ecosystem conservation.

BRAF and NRAS prognostic values in conjunctival melanoma: analysis and literature review.

PURPOSE: Conjunctival melanoma is a rare and aggressive tumor with a propensity for regional and distant metastases. This study aimed to analyze BRAF/NRAS markers in conjunctival melanoma and their relationship with tumor recurrences and patient prognosis. METHODS: This retrospective, observational, single-center study included consecutive patients with an anatomopathological diagnosis of conjunctival melanoma, registered between January 1992 and December 2019. BRAF/NRAS mutations were analyzed using cobas®4800 kit (Roche®) in samples obtained by excisional or map biopsy. Additionally, the presence of other associated precancerous or tumor lesions was assessed. RESULTS: A total of 12 patients with positive histological samples for conjunctival melanoma were included (7 women, 5 men), with a mean age at diagnosis of 60 years and a mean evolution time of 6.38 ± 3.4 years. BRAF V600E mutation was observed in three biopsies (25%), similar to NRAS Q61X (25%). Recurrences occurred in all patients with positive BRAF or NRAS mutation, and five of these patients developed systemic dissemination (83.33%). Moreover, four of six patients with mutated BRAF or NRAS (66.66%) had histopathological findings of tumor or precancerous lesions. CONCLUSIONS: BRAF and NRAS mutations may be risk factors for recurrence and shorter survival in conjunctival melanoma, which would make these patients candidates for targeted therapies and comprehensive and individualized follow-up. All these data warrant standardized prospective studies.

Alcohol and cannabis consumption in patients with inflammatory bowel disease: prevalence, pattern of consumption and impact on the disease.

OBJECTIVES OF THE STUDY: There is little guidance regarding the impact of alcohol and cannabis on the clinical course of inflammatory bowel disease. The aim of this study was to assess the prevalence, sociodemographic characteristics and impact of alcohol and cannabis use on the clinical course of the disease. METHODS: We performed an analysis of prospectively collected data within the Swiss Inflammatory Bowel Disease Cohort Study with yearly follow-ups and substance-specific questionnaires. We analyzed the prevalence of use, the profile of users at risk for addiction and the impact of alcohol and cannabis on the course of the disease. RESULTS: We collected data of 2828 patients included between 2006 and 2018 and analyzed it according to their completion of specific surveys on alcohol and cannabis use. The prevalence of patient-reported active use was 41.3% for alcohol and 6% for cannabis. Heavy drinkers were over-represented among retired, married smokers receiving mostly aminosalicylates and less immunosuppression. In ulcerative colitis patients, low-to-moderate drinking was associated with less extensive disease. Cannabis users were often students with ileal Crohn's disease. CONCLUSION: A significant proportion of patients with inflammatory bowel disease consume alcohol or cannabis. Heavy alcohol consumption is most likely in male smokers >50 years, whereas young men with ileal disease rather use cannabis.

Inner mitochondrial membrane structure and fusion dynamics are altered in senescent human iPSC-derived and primary rat cardiomyocytes.

Dysfunction of the aging heart is a major cause of death in the human population. Amongst other tasks, mitochondria are pivotal to supply the working heart with ATP. The mitochondrial inner membrane (IMM) ultrastructure is tailored to meet these demands and to provide nano-compartments for specific tasks. Thus, function and morphology are closely coupled. Senescent cardiomyocytes from the mouse heart display alterations of the inner mitochondrial membrane. To study the relation between inner mitochondrial membrane architecture, dynamics and function is hardly possible in living organisms. Here, we present two cardiomyocyte senescence cell models that allow in cellular studies of mitochondrial performance. We show that doxorubicin treatment transforms human iPSC-derived cardiomyocytes and rat neonatal cardiomyocytes in an aged phenotype. The treated cardiomyocytes display double-strand breaks in the nDNA, have ß-galactosidase activity, possess enlarged nuclei, and show p21 upregulation. Most importantly, they also display a compromised inner mitochondrial structure. This prompted us to test whether the dynamics of the inner membrane was also altered. We found that the exchange of IMM components after organelle fusion was faster in doxorubicin-treated cells than in control cells, with no change in mitochondrial fusion dynamics at the meso-scale. Such altered IMM morphology and dynamics may have important implications for local OXPHOS protein organization, exchange of damaged components, and eventually the mitochondrial bioenergetics function of the aged cardiomyocyte.

Histerectomía mediante acceso vNOTES. Reporte de caso / Hysterectomy across vNOTES procedure. A case report

Resumen ANTECEDENTES: La cirugía mediante vNOTES (Vaginal Natural Orifices Transluminal Endoscopic Surgery, por sus siglas en inglés), practicada por primera vez en el 2010, es una técnica quirúrgica emergente que elimina el traumatismo quirúrgico en la pared abdominal mediante orificios naturales del cuerpo para la ejecución de procedimientos quirúrgicos. Debido a la falta de reportes con vNOTES en México se comunica el caso de una paciente en quien se aplicó este acceso, con buenos resultados. CASO CLÍNICO: Paciente de 60 años, asintomática, referida para tratamiento definitivo de una lesión intraepitelial cervical, porque no aceptó el conservador. La histerectomía se efectuó mediante el acceso vNOTES, con una duración de 100 minutos, sin contratiempos ni complicaciones posoperatorias. A las 24 horas se dio de alta del hospital hemodinámicamente estable y asintomática, y sin complicaciones tardías. CONCLUSIÓN: La histerectomía mediante el acceso VNOTES fue exitosa, sin complicaciones y con adecuada evolución posquirúrgica. La evidencia actual demuestra que el acceso mediante vNOTES para la histerectomía es un procedimiento eficaz y seguro que combina las ventajas de la vía vaginal con la vía laparoscópica.

Abstract BACKGROUND: vNOTES surgery (Vaginal Natural Orifices Transluminal Endoscopic Surgery), first practiced in 2010, is an emerging surgical technique that eliminates surgical trauma to the abdominal wall by means of natural body orifices for the execution of surgical procedures. Due to the lack of reports with vNOTES in Mexico, we report the case of a patient in whom this access was applied, with good results. CLINICAL CASE: 60-year-old asymptomatic patient referred for definitive treatment of a cervical intraepithelial lesion, because she did not accept the conservative treatment. The hysterectomy was performed by vNOTES access, with a duration of 100 minutes, without setbacks or postoperative complications. At 24 hours she was discharged from the hospital hemodynamically stable and asymptomatic, and without late complications. CONCLUSION: Hysterectomy by VNOTES access was successful, without complications and with adequate postoperative evolution. Current evidence demonstrates that vNOTES access for hysterectomy is an effective and safe procedure that combines the advantages of the vaginal and laparoscopic routes.

BRAF and NRAS prognostic values in conjunctival melanoma: analysis and literature review / Análise do valor prognóstico dos marcadores BRAF e NRAS no melanoma da conjuntiva e revisão da literatura

ABSTRACT Purpose: Conjunctival melanoma is a rare and aggressive tumor with a propensity for regional and distant metastases. This study aimed to analyze BRAF/NRAS markers in conjunctival melanoma and their relationship with tumor recurrences and patient prognosis. Methods: This retrospective, observational, single-center study included consecutive patients with an anatomopathological diagnosis of conjunctival melanoma, registered between January 1992 and December 2019. BRAF/NRAS mutations were analyzed using cobas®4800 kit (Roche®) in samples obtained by excisional or map biopsy. Additionally, the presence of other associated precancerous or tumor lesions was assessed. Results: A total of 12 patients with positive histological samples for conjunctival melanoma were included (7 women, 5 men), with a mean age at diagnosis of 60 years and a mean evolution time of 6.38 ± 3.4 years. BRAF V600E mutation was observed in three biopsies (25%), similar to NRAS Q61X (25%). Recurrences occurred in all patients with positive BRAF or NRAS mutation, and five of these patients developed systemic dissemination (83.33%). Moreover, four of six patients with mutated BRAF or NRAS (66.66%) had histopathological findings of tumor or precancerous lesions. Conclusions: BRAF and NRAS mutations may be risk factors for recurrence and shorter survival in conjunctival melanoma, which would make these patients candidates for targeted therapies and comprehensive and individualized follow-up. All these data warrant standardized prospective studies.

RESUMO Objetivo: O melanoma da conjuntiva é um tumor raro e agressivo, com propensão à disseminação metastática regional e distante. Este estudo tem como objetivo analisar os marcadores BRAF e NRAS no melanoma da conjuntiva e sua relação com recidivas tumorais e com o prognóstico do paciente. Métodos: Este foi um estudo retrospectivo, observacional e unicêntrico de pacientes consecutivos com diagnóstico anatomopatológico de melanoma da conjuntiva feito entre janeiro de 1992 e dezembro de 2019. As mutações BRAF e NRAS foram analisadas com o kit cobas® 4800 (Roche®) em amostras obtidas através de biópsia excisional ou por mapa. Além disso, foi avaliada a presença de lesões pré-cancerosas ou tumorais associadas. Resultados: Foram incluídos 12 pacientes com amostras histológicas positivas para melanoma da conjuntiva (7 mulheres e 5 homens), com idade média ao diagnóstico de 60 anos e tempo médio de evolução de 6,38 ± 3,4 anos. A mutação BRAF V600E foi encontrada em 3 biópsias (25%), bem como a NRAS Q61X (25%). Ocorreram recidivas em todos os pacientes positivos para mutações de BRAF ou NRAS e 5 desses pacientes desenvolveram disseminação sistêmica (83,33%). Além disso, 4 dos 6 pacientes com BRAF ou NRAS mutante (66,66%) apresentaram achados histopatológicos de lesões tumorais ou pré-cancerosas. Conclusões: As mutações BRAF e NRAS podem ser fatores de risco para recorrência e menor sobrevida no melanoma da conjuntiva, o que tornaria esses pacientes candidatos a terapias direcionadas e a um acompanhamento mais abrangente e individualizado. Todos esses dados justificam mais estudos prospectivos padronizados.