[Results of all-inside arthroscopic meniscal sutures, mid-term review]. / Resultado de suturas meniscales por técnica artroscópica ''todo adentro'', revisión a mediano plazo.

INTRODUCTION: all-in meniscal suture devices have evolved and simplified meniscal repair. In this study we will formulate the following research questions: what is the rate of survival and failure? What are the risk factors associated with failure? And what are the functional results after meniscal repair surgery? MATERIAL AND METHODS: ambispective study from 2001 to 2021 of patients with repairable meniscal injury with all-in meniscal suture devices. The survival and failure ratio were obtained with the Kaplan-Meier test, the risk factors associated with meniscal suture failure were assessed with the logistic regression test, and the pre- and post-surgical functional results were estimated with the test. t-Student. RESULTS: in 20 years of follow-up of 316 menisci repaired with all-in meniscal sutures, a survival rate of 95.9% was obtained. The absence of injury to the anterior horn of the meniscus was shown to be a protective factor [OR = 0.12], together with not practicing impact sports [OR = 0.2]. Post-surgery IKDC and Tegner-Lysholm results were shown to be very good to excellent (p < 0.0001). CONCLUSION: all-in meniscal suture devices are and will continue to be front-line weapons in the repair of meniscal tears. In 20 years of follow-up, a lower failure rate was evidenced, associated with excellent functional results.

INTRODUCCIÓN: los dispositivos de suturas meniscal todo adentro han evolucionado y simplificado la reparación meniscal. En este estudio formulamos las siguientes preguntas de investigación: ¿cuál es la tasa de supervivencia y falla?, ¿cuáles son los factores de riesgo asociado a falla? y ¿cuáles son los resultados funcionales posterior a la cirugía de reparación meniscal? MATERIAL Y MÉTODOS: estudio ambispectivo desde el 2001 al 2021 de pacientes con lesión meniscal reparable con dispositivos meniscales de sutura todo adentro. La razón de supervivencia y falla se obtuvo con el test de Kaplan-Meier, los factores de riesgo asociado con falla de la sutura meniscal se valoraron con el test de regresión logística y los resultados funcionales pre y postquirúrgicos fueron estimados con la prueba t-Student. RESULTADOS: en 20 años de seguimiento de 316 menisco reparados con suturas meniscal todo adentro se obtuvo que la razón de supervivencia de 95.9%. La ausencia de lesión del cuerno anterior del menisco se mostró como un factor protector [OR = 0.12], junto a la no práctica de deportes de impacto [OR = 0.2]. Se mostraron resultados del IKDC y Tegner-Lysholm posterior a la cirugía de muy buenos a excelentes (p < 0.0001). CONCLUSIÓN: los dispositivos de sutura de meniscal todo adentro son y seguirán siendo armas de primera línea en la reparación de las roturas meniscales. En 20 años de seguimiento se evidenció una menor tasa de falla, asociados con excelentes resultados funcionales.

Sequence analysis of exons 30 and 31 of LAMA3 gene variants and its association with human papillomavirus infection predisposition: no evidence was found.

OBJECTIVE: Human papillomavirus (HPV) is associated with cervical cancer. For the infection to occur, most HPV types depend on interactions with heparan sulfate proteoglycans (HSPGs); however, non-HSPGs receptors are also involved. Laminin 332 is a crucial component of the epidermis's base membrane. It has shown interactions with HPV that suggest its function as a transient viral receptor in the extracellular matrix (ECM). We provide new information about Laminin 332 and HPV by identifying LAMA3 gene allelic variants from exons 30 and 31 and their distribution among women with and without HPV infection. PATIENTS AND METHODS: We included 192 cervical cancer scrape samples from two groups of patients, 96 samples from patients with a low-grade squamous intraepithelial lesion (LSIL) and 96 samples from HPV-negative samples without LSIL. Identification of the HPV type was performed using an LCD-Array kit. Exons 30 and 31 of LAMA3 were amplified by PCR and analyzed by Sanger's sequencing. RESULTS: We identified a wide range of HPV types. The most frequent low-risk (lrHPV) HPV types were 6, 42, 44, and 90. For high-risk (hrHPV) HPV were 16, 31, 56, and 66. Only the genetic variant rs1131521 was identified in both groups. However, no significant association was observed between rs1131521 and the study groups. CONCLUSIONS: A single silent polymorphism was identified in both groups with similar frequency, whereas no mutations related to increased epithelial friability were identified.

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin.

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

Triple Dufourmentel hexagonal flap for scalp reconstruction.

Transposition flaps are some of the most commonly used flaps for reconstructing scalp defects. Limberg first described his rhomboid transposition flap in 1946. Dufourmentel flap was an improved version of the Limberg flap published in 1962 in which the base of the flap is widened to improve vascularisation. Transposition flaps are one of the best known and most widely used transposition flaps in reconstructive surgery. They have proven successful in different types of reconstructive and aesthetic situations as a full-thickness random transposition flap. Combination of three Dufourmentel flaps to reconstruct hexagonal defects has not been reported in the literature. It is a modification of the triple Limberg flap, in which, after removing a hexagonal defect, we reconstruct the primary defect with a triple Dufourmentel flap. This flap is very useful for reconstructing large scalp defects as it provides a large amount of skin tissue with high viability; however, given its versatility, it could be used in other anatomical areas. Ann Med Surg (Lond) 2021 7:102544; Plast Reconstr Surg 2015 136:163-164; Atlas Oral Maxillofac Surg Clin North Am 2020 28:17-22.

Tendencia de egresos hospitalarios con diagnóstico de accidente cerebrovascular agudo entre los años 2018-2021 en Chile: análisis descriptivo / Hospital discharge trend with diagnosis of acute stroke between the years 2018 and 2021 in Chile: descriptive analysis

Introducción: El accidente cerebrovascular (ACV) es una afección con alta morbimortalidad, producida por la interrupción de la perfusión cerebral. Este artículo tiene como objetivo analizar la tendencia de egresos hospitalarios por ACV agudo en el periodo 2018-2021 en Chile. Metodología: Estudio descriptivo observacional, que incluyó egresos hospitalarios con diagnóstico de ACV agudo en el periodo 2018-2021, en Chile (n=19.274), según datos del Departamento de Estadísticas e Información de Salud de Chile. Se calculó la tasa de egreso hospitalario (TEH) según variable, utilizando datos del censo chileno 2017. No requirió comité de ética. Resultados: El 2018 tuvo la mayor TEH por ACV agudo (28,99) y el 2021 la menor (26,39). El grupo de "80 años y más" presenta la mayor TEH, mientras que el de "5-9 años" la menor. La mayor y menor TEH las tienen las regiones de Ñuble (263,00) y Tarapacá (10,29), respectivamente. Discusión: La disminución de TEH durante dicho periodo podría deberse al fortalecimiento de la Ley de Urgencia, al Programa Nacional de Telesalud y el impacto de la reciente pandemia. A mayor edad, aumenta la prevalencia y gravedad de las comorbilidades, lo cual explicaría la mayor TEH en el grupo más longevo. La mayor TEH masculina podría ser porque los hombres presentan mayor cantidad y severidad de factores de riesgo. La mayor TEH en la región del Ñuble posiblemente sea por los elevados niveles de pobreza y ruralidad, y la menor TEH en Tarapacá podría relacionarse con la presencia de una población nacional más joven.

Introduction: Stroke (CVA) is a condition with high morbidity and mortality, produced by the interruption of cerebral perfusion. This article aims to analyze the trend of hospital discharges for acute stroke in the period 2018-2021 in Chile. Methodology: Descriptive observational study, which included hospital discharges with a diagnosis of acute stroke in the period 2018-2021, in Chile (n=19,274), according to data from the Chilean Department of Health Statistics and Information. The hospital discharge rate (HTE) was calculated according to variable, using data from the 2017 Chilean census. No ethics committee was required. Results: 2018 had the highest HTE for acute stroke (28.99) and 2021 the lowest (26.39). The group aged "80 years and older" had the highest TEH, while the group aged "5-9 years" had the lowest TEH. The regions of Ñuble (263.00) and Tarapacá (10.29) have the highest and lowest HTE, respectively. Discussion: The decrease in HTE during this period could be due to the strengthening of the emergency law, the National Telehealth Program and the impact of the recent pandemic. The higher the age, the higher the prevalence and severity of comorbidities, which would explain the higher HTE in the older group. The higher male HTE may be due to the fact that men have a greater number and severity of risk factors. The higher HTE in the Ñuble region is possibly due to the high levels of poverty and rurality, and the lower HTE in Tarapacá would be related to having a younger national population.

Underreporting and Underrepresentation of Racial and Ethnic Minority Patients in Lymphedema Clinical Trials: A Systematic Review.

The generalizability of findings from Clinical Trials (CTs) investigating lymphedema treatment modalities requires an accurate representation of the target population. This study aims to evaluate racial and ethnic reporting and representation in lymphedema CTs. A comprehensive systematic literature search was conducted during May 2023 using multiple databases, following the PRISMA guidelines. All CTs published from 2018 to 2023 were included. A total of 84 articles were included in this review, from which 6,546 participants were included in the analysis. Seventy-four (88.1%) articles addressed secondary lymphedema, of which 60 (81.1%) were related to breast cancer. Only 12 (13%) of CTs reported at some extend race or ethnicity. Of these, five (41.6%) reported race and two (16.6%) reported ethnicity according to FDA guidelines. White race had the highest pooled prevalence (80%; 95% CI 72-86%; I2=90%), followed by Black (7%; 95% CI 2- 15%; I2= 94.3%) and Asian (4%; 95% CI 1-8%; I2= 89.9%). In studies reporting ethnicity, participants were predominantly non-Hispanic (92.1%; 95% CI 90 - 94%). There is an underreporting and underrepresentation of racial and ethnic minorities among lymphedema CTs, limiting their generalizability. It is imperative to future development of strategies to enhance diversity in the study sample.

Estudio transversal de una base de datos sobre casos de COVID-19 y aplicación de indicadores epidemiológicos básicos bajo la modalidad de taller / Cross-sectional study of a COVID-19 cases data base and application of basic epidemiological indicators in a workshop modality

Introducción. La pandemia por COVID-19 ha evidenciado la importancia de la metodología epidemiológica, por lo que es significativo fortalecer su aprendizaje en todos los niveles formativos del área de ciencias de la salud. Objetivo. Aplicar metodología epidemiológica de carácter descriptivo y analítico para el estudio de una base de datos de casos COVID-19 en la República Mexicana. Material y métodos. Se realizó una búsqueda de bases de datos en sitios web oficiales sobre los casos de COVID-19, y se recuperó un archivo en formato Excel con la información de 65,536 casos al día 10 de abril del 2021 a las 01:14hrs. Posteriormente, se realizó análisis estadístico de las diferentes variables mediante el programa SPSS, versión 21 en español, consistente en cálculo de prevalencias, razón de productos cruzados (RPC) y medidas de asociación, en lo cual participaron alumnos del cuarto semestre de enfermería. Resultados. La prevalencia para el género masculino fue de 53 %, y para el femenino de 47 %, con una media aritmética de edad de 35 años. La Chi cuadrada entre género y resultado de laboratorio positivo fue de 6527.9, con un 99 % de probabilidad de que haya asociación entre las variables. Asimismo, para la relación hipertensión y resultado de laboratorio positivo la Chi cuadrada fue de 51.97. La RPC para diabetes y resultado de laboratorio positivo fue de 1.4. Conclusiones. La aplicación de indicadores epidemiológicos básicos representa una herramienta importante para el fenómeno epidemiológico COVID-19, pues establece una caracterización de la epidemia en nuestro país.

Introduction: The COVID-19 pandemic has evidenced the importance of epidemiological methodology, so it is significant to strengthen its learning at all educational levels in the area of health sciences. Objetive. Apply descriptive and analytical epidemiological methodology for the study of a database of COVID-19 cases in the Mexican Republic. Material and methods: A search of databases on official websites on COVID-19 cases was carried out, and an Excel format file was recovered with the information of 65,536 cases as of April 10, 2021 at 01:14 a.m. Subsequently, a statistical analysis of the different variables was carried out using the SPSS program, version 21 in Spanish, consisting of calculation of prevalence, ratio of cross products (RPC) and measures of association, in which fourth semester nursing students participated. Results: The prevalence for the male gender was 53%, and for the female 47%, with an arithmetic mean age of 35 years. The Chi square between gender and positive laboratory result was 6527.9, with a 99% probability of an association between the variables. Likewise, for the relationship between hypertension and a positive laboratory result, the Chi square was 51.97. The RPC for diabetes and positive laboratory result was 1.4. Conclusions: The application of basic epidemiological indicators represents an important tool for the epidemiological phenomenon COVID-19, since it establishes a characterization of the epidemic in our country.

Enhanced recovery after surgery (ERAS) in Latin America: The story so far.

Despite modern perioperative care, postoperative complications continue to play a significant role in patient's recovery. Implementation of enhanced recovery pathways has consistently demonstrated better outcomes, reduced complications, and improved length of stay across the globe. However, the literature is scarce with regard to the peaks and valleys encountered during the implementation of these programs in Latin America. The purpose of this review is to shed light on the development and establishment of enhanced recovery pathways in the region. Moreover, it discusses current challenges and future perspectives on perioperative optimization.

Efecto del slope tibial en la recuperación funcional, en pacientes sometidos a reconstrucción de ligamento cruzado anterior / Effect of tibial slope on functional recovery in patients undergoing anterior cruciate ligament reconstruction

Resumen: Introducción: El slope tibial (inclinación) se ha identificado como uno de los factores asociados a la falla del injerto tras una reconstrucción de ligamento cruzado anterior (LCA); sin embargo, su relación con los resultados funcionales ha sido poco estudiada. El objetivo de este estudio es determinar el efecto del slope tibial en la recuperación funcional, en pacientes sometidos a reconstrucción de LCA. Material y métodos: Se incluyeron los pacientes con lesión de LCA sometidos a reconstrucción primaria, de Mayo de 2018 a Mayo de 2019, midiendo el slope tibial y recabando los puntajes de IKDC y Lysholm. Se elaboró un análisis descriptivo de primera intención y para alcanzar los objetivos se realizó una comparativa de 25 pacientes con slope tibial normal seleccionados aleatoriamente contra 25 pacientes con slope tibial aumentado. Resultados: Se incluyeron 98 pacientes, 73 contaban con un slope tibial normal y 25 con un slope tibial aumentado. Los puntajes de IKDC y Lysholm al final del seguimiento fueron mejores en los pacientes con slope tibial normal. La falla del injerto sólo se identificó en el grupo con slope tibial aumentado. Por otro lado, al análisis comparativo con el grupo control demostró un mejor resultado funcional al final del seguimiento valorado por IKDC en el grupo con slope tibial normal. Conclusión: Los pacientes sometidos a reconstrucción de LCA y slope tibial aumentado tienen un resultado funcional inferior al año de seguimiento evaluado por IKDC en comparación con pacientes con slope tibial dentro de parámetros normales.

Abstract: Introduction: The tibial slope has been identified as one of the factors associated with graft failure after anterior cruciate ligament (ACL) reconstruction; however, its relationship with functional results has been little studied. The main purpose of this study is to determine the effect of the tibial slope on functional recovery in patients undergoing reconstruction of the anterior cruciate ligament. Material and methods: We included patients with a diagnosis of anterior cruciate ligament injury undergoing primary reconstruction, from May 2018 to May 2019, who had a complete radiographic and clinical record; also, the scores from questionnaires of the International Knee Documentation Committee (IKDC) and Lysholm scores were collected pre surgical procedures and throughout the one-year follow-up. The measurement of the tibial slope was performed in lateral knee X-rays from the electronic clinical record. A descriptive analysis of first intention was done, and to achieve the objectives, we compared 25 patients who had normal tibial slope that were selected randomly with 25 patients who had increased tibial slope. Results: A total of 98 patients were included, 73 had a normal tibial slope (equal to or less than 12 degrees) and 25 with an increased tibial slope (greater than 12 degrees), the average age in both groups was 28.43 years for the group with normal tibial slope and 28.26 for patients with increased tibial slope. Regarding the functional assessment, the IKDC and Lysholm scores at the end of the follow-up were better for patients with normal tibial slope. Graft failure was only identified in the group with increased tibial slope. On the other hand, the comparative analysis with the control group randomly selected who had normal tibial slope, showed a better functional result assessed by IKDC score at the end of the follow-up for the group with normal tibial slope. Conclusion: Patients undergoing ACL reconstruction and increased Tibial Slope have an inferior functional result at one year of follow-up assessed by IKDC, when compared with patients with normal tibial slope.

Inhalational lung diseases.

The term inhalational lung disease comprises a group of entities that develop secondary to the active aspiration of particles. Most are occupational lung diseases. Inhalational lung diseases are classified as occupational diseases (pneumoconiosis, chemical pneumonitis), hypersensitivity pneumonitis, and electronic-cigarette-associated lung diseases. The radiologic findings often consist of nonspecific interstitial patterns that can be difficult to interpret. Therefore, radiologists' experience and multidisciplinary teamwork are key to ensure correct evaluation. The role of the radiologist is fundamental in preventive measures as well as in diagnosis and management, having an important impact on patients' overall health. It is crucial to take into account patients' possible exposure to particles both at work and at home.

Hybrid natural orifice transluminal endoscopy surgery (NOTES) to perform bilateral ovariectomy in mares.

OBJECTIVES: To combine laparoscopic techniques with natural orifice transluminal endoscopic surgery (hybrid NOTES) to minimize number and enlargement of paralumbar laparoscopic portals for bilateral ovariectomy in standing, sedated mares. STUDY DESIGN: Case series. ANIMALS: Six horses. MATERIALS AND METHODS: Six mares with palpably normal ovaries were restrained in stocks, sedated, and had caudal epidural anesthesia performed. A 7.5 MHz ultrasound probe was used transvaginally to select placement of vaginotomy. An attempt was made to remove both ovaries with 70 cm esophageal forceps through the vaginotomy, while visualized and transected via ipsilateral paralumbar fossa laparoscopic portals. Surgical time, intraoperative, and postoperative complications were recorded. Vaginoscopy was performed at days 0, 3, 7, and 14 postoperatively. After 14 days, mares were euthanized and necropsied. RESULTS: Hybrid NOTES allowed successful bilateral ovariectomy in all six mares, with a mean surgical time of 70 ± 25 min. In two mares, one ovary was dislodged from the forceps during vaginotomy extraction. Abdominal retrieval of the ovary was successful with reapplication of forceps or a surgeon's hand via vaginotomy. At necropsy, five mares had no adhesions within the abdominal cavity or at the vaginotomy site. One mare in which hand retrieval of the ovary was necessary, developed an adhesion between the bladder and the vaginotomy. CONCLUSIONS: This technique appears to offer a safe alternative for bilateral ovariectomy with minimal postoperative complications. CLINICAL SIGNIFICANCE: Decreased number and size of paralumbar laparoscopic incisions could decrease complications associated with exteriorization of ovaries through the flank.

Evaluación radiográfica de la posición del túnel femoral y tibial en reconstrucción de ligamento cruzado anterior con técnica anatómica / Radiographic evaluation of femoral and tibial tunnel position in anterior cruciate ligament reconstruction with anatomic technique

Resumen: Introducción: En la reconstrucción de ligamento cruzado anterior se intenta reproducir ligamento nativo, realizar túneles independientes, optimizar los puntos de entrada y la efectividad de la anatomía; hacer mediciones radiográficas de rodilla, identificar la posición del túnel femoral y tibial en pacientes operados de reconstrucción de ligamento cruzado anterior con técnica anatómica. Material y métodos: Se identificaron pacientes en el período de Enero de 2018 a Diciembre de 2019. Se evaluaron de manera retrospectiva 98 pacientes. Mediciones radiográficas en fémur: se determinó el ángulo de inclinación del túnel, el sitio de inserción con respecto a la línea de Blumensaat y la distancia transósea. En tibia: la ubicación en porcentaje de la localización de platillo tibial en proyección anteroposterior y lateral, ángulo de túnel tibial. Resultados: Los pacientes postoperados fueron 98, masculinos (75.5%) y femeninos (24.5%). Postoperados en el año 2018 (57.15%) y en 2019 (42.85%). Rango de edad: el grupo afectado fue de 21-25 años, lado afectado: derecho en 57.15%. Mediciones radiográficas en fémur: el ángulo de inclinación del túnel fue de 45o, el porcentaje en la línea de Blumensaat fue de 20% y la distancia transósea fue 3.43 cm. En tibia la distancia porcentual en proyección anteroposterior fue de 44% y lateral de 28%. El ángulo en túnel tibial en proyección anteroposterior fue de 73º y lateral de 114º. Conclusión: La técnica anatómica es una buena opción para efectuar túneles con posición anatómica óptima. Realizar túneles independientes permite mejorar la cobertura de la huella anatómica normal, aumenta los grados y la inclinación de túneles y provoca lesiones agregadas.

Abstract: Introduction: Reconstruction of the anterior cruciate ligament attempts to reproduce the native ligament; make independent tunnels optimize the entry points and effectiveness the anatomy. Perform radiographic measurements of the knee, identify position of femoral and tibial tunnels in patients operated for reconstruction of anterior cruciate ligament with anatomical technique. Material and methods: Patients were identified in the period January 2018 to December 2019. 98 patients were retrospectively evaluated. Radiographic measurements in the femur, the inclination angle of the tunnel, the insertion site with respect to the Blumensaat line and the transosseous distance were determined. In tibia, the location in percentage of the tibial plateau location in anteroposterior and lateral view, tibial tunnel angle. Results: Postoperative patients were 98. (75.5%) male, female (24.5%). Postoperative in 2018 (57.15%) and 2019 (42.85%) Age range: affected group was 21-25 years, right side affected in 57.15%; Radiographic measurements in femur, the angle of inclination of the tunnel was 45o, percentage in the Blumensaat line was 20%, and the transosseous distance was 3.43 cm. In tibia the percentage distance in anteroposterior projection was 44%, and lateral 28%, The angle in tibial tunnel anteroposterior projection of 73 degrees, and lateral 114. Conclusion: The anatomical technique is a good option to perform tunnels with an optimal anatomical position. By making independent tunnels it allows to improve coverage of normal antomic footprint. Increases degrees and inclination of tunnels, causes added injuries.

SEOM clinical guidelines for anaemia treatment in cancer patients (2020).

Anaemia is defined by the presence of haemoglobin (Hb) levels < 13 g/dL in men and 12 g/dL in women. Up to 39% of cancer patients present it at the time of diagnosis and up to 40% have iron deficiency. Anaemia causes fatigue, functional deterioration and a reduction in the quality of life; it has also been associated with a poorer response to anti-tumour treatment and lower survival. Basic diagnostic tests for anaemia are simple and should be a routine part of clinical practice. These guidelines review the available evidence on the use of different therapies for treating anaemia: erythropoiesis-stimulating agents, iron supplements, and transfusion of blood products.

c-Abl activates RIPK3 signaling in Gaucher disease.

Gaucher disease (GD) is caused by homozygous mutations in the GBA1 gene, which encodes the lysosomal ß-glucosidase (GBA) enzyme. GD affects several organs and tissues, including the brain in certain variants of the disease. Heterozygous GBA1 variants are a major genetic risk factor for developing Parkinson's disease. The RIPK3 kinase is relevant in GD and its deficiency improves the neurological and visceral symptoms in a murine GD model. RIPK3 mediates necroptotic-like cell death: it is unknown whether the role of RIPK3 in GD is the direct induction of necroptosis or if it has a more indirect function by mediating necrosis-independent. Also, the mechanisms that activate RIPK3 in GD are currently unknown. In this study, we show that c-Abl tyrosine kinase participates upstream of RIPK3 in GD. We found that the active, phosphorylated form of c-Abl is increased in several GD models, including patient's fibroblasts and GBA null mice. Furthermore, its pharmacological inhibition with the FDA-approved drug Imatinib decreased RIPK3 signaling. We found that c-Abl interacts with RIPK3, that RIPK3 is phosphorylated at a tyrosine site, and that this phosphorylation is reduced when c-Abl is inhibited. Genetic ablation of c-Abl in neuronal GD and GD mice models significantly reduced RIPK3 activation and MLKL downstream signaling. These results showed that c-Abl signaling is a new upstream pathway that activates RIPK3 and that its inhibition is an attractive therapeutic approach for the treatment of GD.

Dynamics of clinical biomarkers as predictors of immunotherapy benefit in metastatic melanoma patients.

PURPOSE: Baseline LDH, derived neutrophil-lymphocyte ratio (dNLR) and immune-related adverse events (irAEs) are associated with outcomes of patients with metastatic melanoma (MM). We hypothesized whether dynamic shifts in LDH, dNLR and incidence of irAEs may impact the prognosis of MM patients treated with anti-CTLA4 or anti-PD1 as single agents. METHODS: Retrospective analysis of medical charts from MM patients with prospective monitoring of dNLR, LDH values and irAE incidence. Primary endpoint was overall survival (OS). RESULTS: Patients switching from either high dNLR (≥2.5) to low dNLR (HR: 0.14; 0.03-0.74; p = 0.02) or high LDH (≥1.5 × ULN) to low LDH levels (HR: 0.08; 0.01-0.68; p = 0.02) had significantly better OS than those with high dNLR or LDH scores at the end of cycle 2. Longer OS was also observed in patients developing irAEs ≥ grade 2 as compared to no irAEs (HR: 0.2; 0.05-0.89; p = 0.03). CONCLUSIONS: We found that major shifts in dNLR and LDH measures from baseline to cycle 2 measures and shifts from baseline to cycle 2 are significantly associated with OS in MM patients receiving single agent anti-PD1 therapy. Laboratory changes and clinical variables may help optimize prognostic estimates.

Bilateral ankyloblepharon: more than a simple malformation. / Anquilobléfaron bilateral: Algo más que una simple malformación.

"Ankyloblepharon filiforme adnatum" is a congenital anomaly characterized by partial or complete adhesion of upper and lower eyelids. The lid margins remain fused until the end of the fifth month of gestational age. Complete separation usually is completed about the seventh fetal month. Ankyloblepharon may be an isolated manifestation or may be associated with abnormalities in other organs and / or systems. The case is presented on a newborn male with family history of hypohydrotic ectodermal dysplasia (mother and maternal grandfather). It revealed extensible bands of skin in right and in left eye. Apart from this, he presented cleft lip, complete absence of palate, nail and ungueal dysplasia and supernumerary nipples.

Trastorno de hipoventilación central del sueño en pediatría: causas poco frecuentes / Central hypoventilation disorders sleep-related in pediatrics: unusual causes

Congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity syndrome with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) are rare causes of hypoventilation during sleep in the pediatric population. This group of disorders are characterized by the absence or decrease in the automatic control of ventilation, decreased sensitivity of chemoreceptors to CO2, causing hypoventilation during sleep and even in wakefulness, in the most severe cases. For these reasons it is important to diagnose and treat them promptly. The objective of this review is to provide current and complete literature, to be able to identify, treat and refer this group of children early, and thus reduce the complications and/or associated comorbidities in the short and long term, improving their quality of life.

El síndrome de hipoventilación central congénita (CCHS) y síndrome de obesidad de inicio rápido con disfunción hipotalámica, hipoventilación y desregulación autonómica (ROHHAD), son causas poco comunes de hipoventilación durante el sueño en la población pediátrica. Este grupo de trastornos se caracterizan por ausencia o disminución en el control automático de la ventilación, sensibilidad disminuida de los quimioreceptores al CO2, provocando hipoventilación durante el sueño e incluso en vigilia, en los casos más severos. Por estas razones es importante diagnosticarlos y tratarlos oportunamente. El objetivo de esta revisión es proporcionar literatura actual y completa, para poder identificar, tratar y referir a éste grupo de niños tempranamente, y así disminuir las complicaciones y/o comorbilidades asociadas a corto y largo plazo, mejorando su calidad de vida.