Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Anti-tumor activity of a novel LAIR1 antagonist in combination with anti-PD-1 to treat collagen-rich solid tumors.

We recently reported that resistance to PD-1-blockade in a refractory lung cancer-derived model involved increased collagen deposition and the collagen-binding inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), and thus we hypothesized that LAIR1 and collagen cooperated to suppress therapeutic response. Here, we report LAIR1 is associated with tumor stroma and is highly expressed by intratumoral myeloid cells in both human tumors and mouse models of cancer. Stroma-associated myeloid cells exhibit a suppressive phenotype and correlate with LAIR1 expression in human cancer. NGM438, a novel humanized LAIR1 antagonist monoclonal antibody, elicits myeloid inflammation and allogeneic T cell responses by binding to LAIR1 and blocking collagen engagement. Further, a mouse-reactive NGM438 surrogate antibody sensitized refractory KP mouse lung tumors to anti-PD-1 therapy and resulted in increased intratumoral CD8+ T cell content and inflammatory gene expression. These data place LAIR1 at the intersection of stroma and suppressive myeloid cells and support the notion that blockade of the LAIR1/collagen axis can potentially address resistance to checkpoint inhibitor therapy in the clinic.

Afectación iatrogénica de la motilidad ocular por fármacos antitumorales inhibidores de los puntos de control / Iatrogenic impairment of ocular motility by immune checkpoint inhibitors

Se encontraron 4 revisiones sistemáticas que incluían este tipo de iatrogenia ocular, así como numerosos reportes de casos aislados. Los efectos adversos reportados comprenden: paresias oculomotoras, neuropatía óptica, atrofia óptica, síndromes miasteniformes, pseudo-orbitopatía tiroidea, síndrome del ápex orbitario e hipofisitis. La mayoría se manejaron sin interrupción o con interrupción parcial del tratamiento oncológico. Se requirieron tratamientos sistémicos agresivos para el manejo adecuado de la iatrogenia ocular.Es imprescindible que el oftalmólogo se familiarice con los nuevos tratamientos oncológicos ICI, capaces de provocar iatrogenia sobre la motilidad ocular grave e incapacitante para el paciente. La comunicación de efectos adversos con los tratamientos empleados puede ayudar al manejo más adecuado de estos pacientes. La investigación debe ir orientada al diagnóstico diferencial complejo y a optimizar las decisiones sobre los tratamientos oncológicos. (AU)

Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile.We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events.It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments. (AU)

Iatrogenic affectation of ocular motility by immune checkpoint inhibitors.

Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile. We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events. It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments.

Aproximaciones a la epidemiología de la neuropatía óptica hereditaria de Leber en la comunidad autónoma de Madrid a través de una encuesta a los neuroftalmólogos / Approaches to the epidemiology of NOHL in the region of Madrid: Survey of neuro-ophthalmologists

Objective To estimate the epidemiology of Leber's optic neuropathy (NOHL) in the Region of Madrid. Material and methodsThe neuro-ophthalmologists who work at public hospitals of the CAM were interviewed by telephone. They were asked about the number of patients with NOHL that they had diagnosed during the time that they had been responsible for the neuro-ophthalmology department of that public hospital. The time worked and the population attended by the hospital were used to calculate the number of patient-years in follow-up by each center during the corresponding period. The basic information of each case (date of birth, mutation, and date of visual loss) was registered to avoid duplications. Results Our work estimates a global incidence of 2.34 cases for 10,000,000 inhabitants-year and a prevalence estimated from incidence of one case for each 106,682 inhabitants. This prevalence was very similar in all the studied areas and considerably lower than that reported by other studies. Conclusion This work constitutes the first approach to the epidemiology of this disease in Spain. The prevalence of NOHL in the region of Madrid is probably lower than that reported in the literature in other regions. The prevalence and the incidence were homogeneously low in the 26 studied areas. (AU)

Objetivo Estimar la epidemiología (incidencia y prevalencia) de la neuropatía óptica de Leber (NOHL) en la comunidad autónoma de Madrid (CM). Material y métodosLos neuroftalmólogos que trabajan en los hospitales públicos de la CAM fueron entrevistados telefónicamente. Se les preguntó por el número de pacientes con NOHL que habían diagnosticados durante el tiempo que han sido responsables de la consulta de neuroftalmología de ese hospital público. El tiempo trabajado y la población atendida por el hospital se utilizaron para calcular el número de habitantes-años en seguimiento por cada centro durante el periodo correspondiente y estimar la incidencia en cada área. La prevalencia estimada a partir de la incidencia (PEI) se calculó considerando que un paciente con NOHL vive unos 40 años con la enfermedad. Se registró la información básica de cada caso cuando estaba disponible (sexo, fecha de nacimiento, mutación, fecha de la pérdida visual) para evitar duplicaciones. Resultados Nuestro trabajo estima una incidencia global de 2,34 casos por cada 10.000.000 habitantes-año y una PEI de 1 caso por cada 106.682 habitantes. Esta prevalencia es inferior a la referida por otros estudios. Conclusión Este trabajo constituye la primera aproximación a la epidemiología de esta enfermedad en España. La prevalencia estimada de la NOHL en la CM es probablemente inferior a la reportada en la literatura en otras regiones. La prevalencia y la incidencia fueron homogéneamente bajas en las 26 áreas estudiadas. (AU)

Approaches to the epidemiology of NOHL in the region of Madrid: Survey of neuro-ophthalmologists.

OBJECTIVE: To estimate the epidemiology of Leber's optic neuropathy (NOHL) in the Region of Madrid. MATERIAL AND METHODS: The neuro-ophthalmologists who work at public hospitals of the CAM were interviewed by telephone. They were asked about the number of patients with NOHL that they had diagnosed during the time that they had been responsible for the neuro-ophthalmology department of that public hospital. The time worked and the population attended by the hospital were used to calculate the number of inhabitant-years in follow-up by each center during the corresponding period. The basic information of each case (date of birth, mutation, date of visual loss) was registered to avoid duplications. RESULTS: Our work estimates a global incidence of 2.34 cases for 10,000,000 inhabitants-year and a prevalence estimated from incidence of one case for each 106.682 inhabitants. This prevalence was very similar in all the studied areas and considerably lower than that reported by other studies. CONCLUSION: This work constitutes the first approach to the epidemiology of this disease in Spain. The prevalence of LHON in the region of Madrid, is probably lower than that reported in the literature in other regions. The prevalence and the incidence were homogeneously low in the 26 studied areas.

Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer.

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and effector tumor-infiltrating CD8+ T cells. Pharmacological inhibition of ATX, or the downstream receptor LPAR5, in combination with anti-PD-1 was sufficient to restore the antitumor immune response and efficaciously control lung tumor growth in multiple KP tumor models. Additionally, ATX was significantly correlated with inflammatory gene signatures, including a CD8+ cytolytic score in multiple lung adenocarcinoma patient data sets, suggesting that an activated tumor-immune microenvironment upregulates ATX and thus provides an opportunity for cotargeting to prevent acquired resistance to anti-PD-1 treatment. These data reveal the ATX/LPA axis as an immunosuppressive pathway that diminishes the immune checkpoint blockade response in lung cancer.

Short-term anti-plaque effect of a cymenol mouthwash analysed using the DenTiUS Deep Plaque software: a randomised clinical trial.

BACKGROUND: The effect of cymenol mouthwashes on levels of dental plaque has not been evaluated thus far. OBJECTIVE: To analyse the short-term, in situ, anti-plaque effect of a 0.1% cymenol mouthwash using the DenTiUS Deep Plaque software. METHODS: Fifty orally healthy participants were distributed randomly into two groups: 24 received a cymenol mouthwash for eight days (test group A) and 26 a placebo mouthwash for four days and a cymenol mouthwash for a further four days thereafter (test group B). They were instructed not to perform other oral hygiene measures. On days 0, 4, and 8 of the experiment, a rinsing protocol for staining the dental plaque with sodium fluorescein was performed. Three intraoral photographs were taken per subject under ultraviolet light. The 504 images were analysed using the DenTiUS Deep Plaque software, and visible and total plaque indices were calculated (ClinicalTrials ID NCT05521230). RESULTS: On day 4, the percentage area of visible plaque was significantly lower in test group A than in test group B (absolute = 35.31 ± 14.93% vs. 46.57 ± 18.92%, p = 0.023; relative = 29.80 ± 13.97% vs. 40.53 ± 18.48%, p = 0.024). In comparison with the placebo, the cymenol mouthwash was found to have reduced the growth rate of the area of visible plaque in the first four days by 26% (absolute) to 28% (relative). On day 8, the percentage areas of both the visible and total plaque were significantly lower in test group A than in test group B (visible absolute = 44.79 ± 15.77% vs. 65.12 ± 16.37%, p < 0.001; visible relative = 39.27 ± 14.33% vs. 59.24 ± 16.90%, p < 0.001; total = 65.17 ± 9.73% vs. 74.52 ± 13.55%, p = 0.007). Accounting for the growth rate with the placebo mouthwash on day 4, the above results imply that the cymenol mouthwash in the last four days of the trial reduced the growth rate of the area of visible plaque (absolute and relative) by 53% (test group A) and 29% (test group B), and of the area of total plaque by 48% (test group A) and 41% (test group B). CONCLUSIONS: The 0.1% cymenol mouthwash has a short-term anti-plaque effect in situ, strongly conditioning the rate of plaque growth, even in clinical situations with high levels of dental plaque accumulation.

Targeting immunosuppressive Ly6C+ classical monocytes reverses anti-PD-1/CTLA-4 immunotherapy resistance.

Introduction: Despite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way to improve response to ICB therapy. Results: Our results show that combination anti-PD-1/CTLA-4 produces an initial antitumor effect with evidence of an activated immune response. Upon extended treatment with anti-PD-1/CTLA-4 acquired resistance developed with an increase of the immunosuppressive populations, including T-regulatory cells, neutrophils and monocytes. Addition of anti-Ly6C blocking antibody to anti-PD-1/CTLA-4 was capable of completely reversing treatment resistance and restoring CD8 T cell activity in multiple KP lung cancer models and in the autochthonous lung cancer KrasLSL-G12D/p53fl/fl model. We found that there were higher classical Ly6C+ monocytes in anti-PD-1/CTLA-4 combination resistant tumors. B7 blockade illustrated the importance of dendritic cells for treatment efficacy of anti-Ly6C/PD-1/CTLA-4. We further determined that classical Ly6C+ monocytes in anti-PD-1/CTLA-4 resistant tumors are trafficked into the tumor via IFN-γ and the CCL2-CCR2 axis. Mechanistically we found that classical monocytes from ICB resistant tumors were unable to differentiate into antigen presenting cells and instead differentiated into immunosuppressive M2 macrophages or myeloid-derived suppressor cells (MDSC). Classical Ly6C+ monocytes from ICB resistant tumors had a decrease in both Flt3 and PU.1 expression that prevented differentiation into dendritic cells/macrophages. Conclusions: Therapeutically we found that addition of anti-Ly6C to the combination of anti-PD-1/CTLA-4 was capable of complete tumor eradication. Classical Ly6C+ monocytes differentiate into immunosuppressive cells, while blockade of classical monocytes drives dendritic cell differentiation/maturation to reinvigorate the anti-tumor T cell response. These findings support that immunotherapy resistance is associated with infiltrating monocytes and that controlling the differentiation process of monocytes can enhance the therapeutic potential of ICB.

Reduction of NrF2 as coadjuvant during the development of persistent periapical lesions.

BACKGROUND: Persistent periapical lesions (PPL) are the result of pulpar necrosis induced by bacterial infection resulting in bone degradation and culminating with the loss of dental piece. Pathological changes in the peripapice are associated with the presence of free radicals. The transcription factor Nrf2 is the main regulator of the endogenous antioxidant response against oxidative stress and has been implicated in the regulation of osteoclastogenesis.The aim is to determine the oxidative condition in samples from patients with Persistent Periapical Injuries as a detonating factor of tissue damage. MATERIAL AND METHODS: An observational, descriptive, cross-sectional study was carried out in samples with PPL (cases) and samples by removal of third molars (controls) obtained in the clinic of the specialty in endodontics, University of Guadalajara. Samples were submitted to histological staining with Hematoxylin-Eosin, lipoperoxide analysis, Superoxide Dismutase (SOD), Glutathione-Peroxidase (GPx) and Catalase (CAT) activities were determined by immunoenzymatic assays and NrF2 by Western Blot analysis. RESULTS: Samples from PPL patients histologically showed an increased presence of lymphocytes, plasma cells, and eosinophils, as well as a decrease in extracellular matrix proteins and fibroblast cells. There was a rise in lipid peroxidation, GPx and SOD activities, but an important decline (36%) in Catalase activity was observed (p<0.005); finally, NrF2-protein was diminished at 10.41%. All comparisons were between cases vs controls. CONCLUSIONS: The alterations in antioxidants endogenous NrF2-controlled are related to osseous destruction in patients with PPL.

Association of obesity, diabetes, and hypertension with arsenic in drinking water in the Comarca Lagunera province (north-central Mexico).

Chronic endemic regional hydroarsenicism (CERHA) is a global issue that affects over 200 million people exposed to arsenic (As) in drinking water. This includes 1.75 million individuals residing in La Comarca Lagunera, a region in north-central Mexico. Arsenic levels in this region typically exceeds the WHO guideline of 10 µg L-1. Biochemical alterations related to the human As metabolism may increase the risk of overweight and obesity (O&O), type 2 diabetes (T2D), and hypertension (AHT). In our study, we investigated the role of As in drinking water as a risk factor for these metabolic diseases. We focused on populations with historically moderate (San Pedro) and low (Lerdo) drinking water As levels and people with no historical evidence of As water contamination. The exposure assessment to As was based on measurements of the drinking water (medians 67.2, 21.0, 4.3 µg L-1) and urinary As concentrations in women (9.4, 5.3, 0.8 µg L-1) and men (18.1, 4.8, 1.0 µg L-1). A significant correlation between As in drinking water and urine evidenced the As exposure in the population (R2 = 0.72). Adjusted odds ratios with 95% confidence intervals evidenced higher chances of being diagnosed with T2D (1.7, 1.2-2.0) and AHT (1.8, 1.7-1.9) in individuals living in San Pedro than those in Lerdo. Still, there was no significant association with obesity. Individuals living in CERHA towns were found to have a higher risk of obesity (1.3-1.9), T2D (1.5 to 3.3), and AHT (1.4 to 2.4) compared to those residing in non-CERHA towns. Finally, obesity is more probable in women [inverse of OR and 95%CI 0.4 (0.2-0.7)] compared to men, while men is more likely to be diagnosed with T2D [OR = 2.0 (1.4-2.3)] and AHT [OR = 2.0 (1.5-2.3)] than women, independently of the municipality.

ZEB1 Is Regulated by K811 Acetylation to Promote Stability, NuRD Complex Interactions, EMT, and NSCLC Metastasis.

Epithelial-to-mesenchymal transition results in loss of specialized epithelial cell contacts and acquisition of mesenchymal invasive capacity. The transcription repressor zinc finger E-box-binding homeobox 1 (ZEB1) binds to E-boxes of gene promoter regions to suppress the expression of epithelial genes. ZEB1 has inconsistent molecular weights, which have been attributed to posttranslational modifications (PTM). We performed mass spectrometry and identified K811 acetylation as a novel PTM in ZEB1. To define the role of ZEB1 acetylation in regulating function, we generated ZEB1 acetyl-mimetic (K811Q) and acetyl-deficient (K811R) mutant-expressing non-small cell lung cancer cell lines (NSCLC). We demonstrate that the K811R ZEB1 (125 kDa) has a shorter protein half-life than wild-type (WT) ZEB1 and K811Q ZEB1 (∼225 kDa), suggesting that lack of ZEB1 acetylation in the lower molecular weight form affects protein stability. Further, the acetylated form of ZEB1 recruits the nucleosome remodeling and deacetylase (NuRD) complex to bind the promoter of its target genes mir200c-141 and SEMA3F. RNA-sequencing revealed that WT ZEB1 and K811Q ZEB1 downregulate the expression of epithelial genes to promote lung adenocarcinoma invasion and metastasis, whereas the K811R ZEB1 does not. Our findings establish that the K811 acetylation promotes ZEB1 protein stability, interaction with other protein complexes, and subsequent invasion/metastasis of lung adenocarcinoma via epithelial-to-mesenchymal transition. IMPLICATIONS: The molecular mechanisms by which ZEB1 is regulated by K811 acetylation to promote protein stability, NuRD complex and promoter interactions, and function are relevant to the development of treatment strategies to prevent and treat metastasis in patients with NSCLC.

ZEB1 is regulated by K811 acetylation to promote stability, NuRD complex interactions, EMT, and NSCLC metastasis.

Epithelial-to-mesenchymal transition results in loss of specialized epithelial cell contacts and acquisition of mesenchymal invasive capacity. The transcription repressor zinc finger E-box-binding homeobox 1 (ZEB1) binds to E-boxes of gene promoter regions to suppress the expression of epithelial genes. ZEB1 has inconsistent molecular weights, which have been attributed to post-translational modifications (PTMs). We performed mass spectrometry and identified K811 acetylation as a novel PTM in ZEB1. To define the role of ZEB1 acetylation in regulating function, we generated ZEB1 acetyl-mimetic (K811Q) and acetyl-deficient (K811R) mutant-expressing non-small cell lung cancer cell lines (NSCLC). We demonstrate that the K811R ZEB1 (125 kDa) has a shorter protein half-life than wild-type (WT) ZEB1 and K811Q ZEB1 (&tilde225 kDa), suggesting that lack of ZEB1 acetylation in the lower molecular weight form affects protein stability. Further, the acetylated form of ZEB1 recruits the nucleosome remodeling and deacetylase (NuRD) complex to bind the promoter of its target genes mir200c-141 and SEMA3F. RNA-sequencing revealed that WT ZEB1 and K811Q ZEB1 downregulate the expression of epithelial genes to promote lung adenocarcinoma invasion and metastasis, while the K811R ZEB1 does not. Our findings establish that the K811 acetylation promotes ZEB1 protein stability, interaction with other protein complexes, and subsequent invasion/metastasis of lung adenocarcinoma via epithelial-to-mesenchymal transition. Implications: The molecular mechanisms by which ZEB1 is regulated by K811 acetylation to promote protein stability, NuRD complex and promoter interactions, and function are relevant to the development of treatment strategies to prevent and treat metastasis in NSCLC patients.

Entrenamiento quirúrgico con fantomas en cirugía de estrabismo / Surgical training with phantoms in strabismus surgery

Antecedentes y objetivo La simulación en el aprendizaje quirúrgico responde a necesidades éticas y pragmáticas. Nuestro propósito es describir los efectos sobre las habilidades quirúrgicas de la realización de un taller de entrenamiento quirúrgico en cirugía de estrabismo con fantomas. La preocupación por la seguridad del paciente obliga a plantearse el empleo de simuladores (virtuales y físicos tridimensionales) y modelos animales permite al aspirante practicar sin riesgos los procedimientos antes de enfrentarse a un caso real. Material y métodos Realización de un taller con contenido teórico previo y práctica real con fantomas diseñados para simular cirugía de estrabismo (globo ocular, 6 músculos, conjuntiva, párpado y cápsula de Tenon insertados en cráneo) de dimensiones anatómicas reales. Encuesta de satisfacción y evaluación subjetiva de aprendizaje por parte del alumno y del tutor experto según el modelo de evaluación de Kirkpatrick. Resultados Completaron la encuesta 100% de los 26 alumnos asistentes a dos cursos (15 alumnos en un curso y 11 alumnos en otro curso) y 100% de los tres tutores que participaron en ambos cursos; 20 eran médicos residentes y 20 especialistas en oftalmología. La satisfacción global de los alumnos fue de 8,2 (± 0,68). Conclusiones Según los resultados de la encuesta de evaluación de acciones formativas de Kirkpatrick, la percepción de alumnos y tutores es que el entrenamiento con fantomas en cirugía de estrabismo puede ayudar a mejorar las habilidades necesarias para una práctica segura e independiente. Siendo el objetivo último mejorar la seguridad del paciente (AU)

Background and purpose Simulation in surgical learning responds to ethical and pragmatic needs. Our purpose is to describe the effects on surgical skills of conducting a surgical training workshop on strabismus surgery with phantoms. Concern for patient safety makes it necessary to consider the use of simulators (virtual and three-dimensional physical) and animal models that allow the applicant to safely practice the procedures before facing a real case. Material and methods Realization of a workshop with previous theoretical content and real practice with phantoms designed to simulate strabismus surgery (eyeball, six muscles, conjunctiva, eyelid and Tenon capsule inserted in the skull) of real anatomical dimensions. Satisfaction survey and subjective evaluation of learning by the student and the expert tutor according to the Kirkpatrick evaluation model. Results 100% of the 26 students attending two courses (15 students in one course and 11 students in another course) and 100% of the three tutors who participated in both courses completed the survey. Twenty were resident doctors and 20 specialists in ophthalmology. The overall satisfaction of the students was 8.2 (± 0.68). Conclusions According to the results of the Kirkpatrick training actions evaluation survey, the perception of students and tutors is that training with phantoms in strabismus surgery can help improve the skills necessary for safe and independent practice. The ultimate goal being to improve patient safety (AU)

Surgical training with phantoms in strabismus surgery.

BACKGROUND AND PURPOSE: Simulation in surgical learning responds to ethical and pragmatic needs. Our purpose is to describe the effects on surgical skills of conducting a surgical training workshop on strabismus surgery with phantoms. Concern for patient safety makes it necessary to consider the use of simulators (virtual and three-dimensional physical) and animal models that allow the applicant to safely practice the procedures before facing a real case. MATERIAL AND METHODS: Realization of a workshop with previous theoretical content and real practice with phantoms designed to simulate strabismus surgery (eyeball, 6 muscles, conjunctiva, eyelid and tenon capsule inserted in the skull) of real anatomical dimensions. Satisfaction survey and subjective evaluation of learning by the student and the expert tutor according to the Kirkpatrick evaluation model. RESULTS: Total, 100% of the 26 students attending two courses (15 students in one course and 11 students in another course) and 100% of the 3 tutors who participated in both courses completed the survey. 20 were resident doctors and 20 specialists in ophthalmology. The overall satisfaction of the students was 8.2 (±0.68). CONCLUSIONS: According to the results of the Kirkpatrick training actions evaluation survey, the perception of students and tutors is that training with phantoms in strabismus surgery can help improve the skills necessary for safe and independent practice. The ultimate goal being to improve patient safety.

Factores asociados al inicio de las relaciones sexuales en los adolescentes de los centros educativos de Cushcanday-Agallpampa y San Isidro-Otuzco, en el año 2021-2022

Objetivo: Determinar los factores asociados al inicio de las actividades sexuales en adolescentes de los centros educativos de Cushcanday-Agallpampa y San Isidro-Otuzco. Material y métodos: Entre septiembre de 2021 y marzo de 2022, se realizó un estudio observacional, analítico transversal en 265 escolares del nivel secundario de los centros educativos de Cushcanday-Agallpampa y San Isidro-Otuzco que cumplieron los criterios de inclusión aplicando como instrumento la encuesta sobre sexualidad. Resultados: 129 hombres y 126 mujeres. Con una edad media de 15.41 años. Con un 11% que ha iniciado su vida sexual. El factor de riesgo asociado de mayor peso para el inicio de la vida sexual es la nomofobia con un OR de 22.55 (IC = 5.24 - 96.97), seguido del analfabetismo, con un OR de 6.41 (IC = 1.22 - 6.74). La visita de páginas web sin contenido erótico es un factor protector para la coitarquia. Conclusiones: 1 de cada 10 adolescentes de la zona rural Cushcanday-Agallpampa y San Isidro-Otuzco-La Libertad ha iniciado su vida sexual. La nomofobia moderada en la adolescencia incrementa 22 veces el riesgo de tener relaciones sexuales. Los hijos de padres analfabeto tienen 6.41 veces mayor probabilidad de iniciar las relaciones sexuales en la adolescencia.

Objective: To determine the factors associated with the beginning of sexual activities in adolescents from the educational centers of Cushcanday-Agallpampa and San Isidro-Otuzco. Material and methods: Between September 2021 and March 2022, an observational, cross-sectional analytical study was carried out in 265 secondary school students from the educational centers of CushcandayAgallpampa and San Isidro-Otuzco who met the inclusion criteria applying as an instrument the sexuality survey. Results: 129 men and 126 women with an average age of 15.41 years. With 11% who have started their sexual life. The risk factor associated with the greatest weight for the beginning of sexual life is nomophobia with an OR of 22.55 (CI = 5.24 - 96.97), followed by illiteracy, with an OR of 6.41 (CI = 1.22 - 6.74). Visiting web pages without erotic content is a protective factor for coitarche. Conclusions: 1 out of every 10 adolescents in the rural area Cushcanday-Agallpampa and San Isidro-Otuzco-La Libertad has started their sexual life. Moderate level nomophobia in adolescence increases the risk of having sexual intercourse by 22 times. Children of illiterate parents are 6.41 times more likely to start sexual relations in adolescence.

Tratamiento de la epífora funcional con toxina botulínica tipo A frente a la tira tarsal en un ensayo aleatorizado / Treatment for functional epiphora with botulinum toxin-A versus lateral tarsal strip in a randomized trial

Objetivo Comparar la eficacia de la inyección de toxina botulínica A (TBA) en la glándula lagrimal con la tira tarsal lateral (TTL) en la epífora funcional. Material y método Ensayo clínico aleatorizado. Diseño secuencial, paralelo y no ciego. Pacientes de 18 años o más con epífora funcional con un mínimo de 3 en la escala de Munk (EM) se incluyeron a grupo de TBA o TTL. Los cambios en la EM, el test de Schirmer y la calidad de vida se evaluaron a la semana 6 y hasta la semana 30. Se obtuvo el tiempo medio sin epífora y los acontecimientos adversos. Resultados El análisis final incluyó 25 pacientes, 12 (21 ojos) se asignaron a TBA (5U/0,05mL) y 13 (20 ojos) a TTL. A la semana 6 hubo un mayor descenso en la EM en el grupo de TBA frente a TTL (−2.48 vs. −1.55, p=0,0152) y a la semana 12 (−2,68 vs. −1,69, p=0,0267). Se observó un descenso significativo en el test de Shirmer a las semanas 2, 12 y 30 con TBA. La calidad de vida mejoró después de ambas intervenciones, sin diferencias significativas. El tiempo medio sin epífora en el grupo TBA fue de 26,2 semanas (7,7-36,6) y en el grupo TTL de 24,8 semanas (6,7-37,6), p=0,9368. Se observó ptosis temporal en un 25% (3/12) en el grupo TBA y un 23% (3/13) de molestias de la cicatriz quirúrgica en el grupo TTL, p=0,722. Ningún acontecimiento adverso fue severo. Conclusión La inyección de TBA en la glándula lagrimal es efectiva y segura en el tratamiento de la epífora funcional, con mayor descenso en la EM a las 6 y 12 semanas comparado con la TTL (AU)

Objective To compare the efficacy of botulinum toxin A (BoNTA) injection into the lacrimal gland versus lateral tarsal strip (LTS) for functional epiphora Material and methods Randomized clinical trial. Sequential, parallel, non-blinded study design. Patients aged 18 years or older with functional epiphora and a minimum score of 3 in Munk Scale (MS) were randomized to BoNTA or LTS group. Changes in MS, Schirmer test and quality of life were assessed at week 6 and during follow-up until week 30. The mean time without epiphora and the adverse events were recorded. Results The final analysis included 25 patients, 12 (21 eyes) assigned to BoNTA (5U/0.05mL) and 13 (20 eyes) to LTS. At 6 weeks there was an improvement in the MS in BoNTA versus LTS group (−2.48 vs. −1.55, P=.0152) and at 12 weeks (−2.68 vs. −1.69, P=.0267). A significant decrease was noted in the Schirmer test at week 2, 12 and 30 with BoNTA. The quality of life improved after both interventions without statistical significance. The mean duration of effectiveness in BoNTA group was 26.2 weeks (range 7.7-36.6) and in LTS group was 24.8 weeks (range 6.7-37.6), P=.9368. The main adverse events were temporary eyelid ptosis in 25% (3/12) of the BoNTA group and surgical scar discomfort in 23% (3/13) of the LTS group, P=.722. No adverse events were classified as severe. Conclusion BoNTA injection into the lacrimal gland is a safe and effective treatment for functional epiphora, with a greater decrease in MS at 6 and 12 weeks compared with LTS (AU)