Chat GPT for the management of obstructive sleep apnea: do we have a polar star?

PURPOSE: This study explores the potential of the Chat-Generative Pre-Trained Transformer (Chat-GPT), a Large Language Model (LLM), in assisting healthcare professionals in the diagnosis of obstructive sleep apnea (OSA). It aims to assess the agreement between Chat-GPT's responses and those of expert otolaryngologists, shedding light on the role of AI-generated content in medical decision-making. METHODS: A prospective, cross-sectional study was conducted, involving 350 otolaryngologists from 25 countries who responded to a specialized OSA survey. Chat-GPT was tasked with providing answers to the same survey questions. Responses were assessed by both super-experts and statistically analyzed for agreement. RESULTS: The study revealed that Chat-GPT and expert responses shared a common answer in over 75% of cases for individual questions. However, the overall consensus was achieved in only four questions. Super-expert assessments showed a moderate agreement level, with Chat-GPT scoring slightly lower than experts. Statistically, Chat-GPT's responses differed significantly from experts' opinions (p = 0.0009). Sub-analysis revealed areas of improvement for Chat-GPT, particularly in questions where super-experts rated its responses lower than expert consensus. CONCLUSIONS: Chat-GPT demonstrates potential as a valuable resource for OSA diagnosis, especially where access to specialists is limited. The study emphasizes the importance of AI-human collaboration, with Chat-GPT serving as a complementary tool rather than a replacement for medical professionals. This research contributes to the discourse in otolaryngology and encourages further exploration of AI-driven healthcare applications. While Chat-GPT exhibits a commendable level of consensus with expert responses, ongoing refinements in AI-based healthcare tools hold significant promise for the future of medicine, addressing the underdiagnosis and undertreatment of OSA and improving patient outcomes.

Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment.

The ability to expand and activate natural Killer (NK) cells ex vivo has dramatically changed the landscape in the development of novel adoptive cell therapies for treating cancer over the last decade. NK cells have become a key player for cancer immunotherapy due to their innate ability to kill malignant cells while not harming healthy cells, allowing their potential use as an "off-the-shelf" product. Furthermore, recent advancements in NK cell genetic engineering methods have enabled the efficient generation of chimeric antigen receptor (CAR)-expressing NK cells that can exert both CAR-dependent and antigen-independent killing. Clinically, CAR-NK cells have shown promising efficacy and safety for treating CD19-expressing hematologic malignancies. While the number of pre-clinical studies using CAR-NK cells continues to expand, it is evident that solid tumors pose a unique challenge to NK cell-based adoptive cell therapies. Major barriers for efficacy include low NK cell trafficking and infiltration into solid tumor sites, low persistence, and immunosuppression by the harsh solid tumor microenvironment (TME). In this review we discuss the barriers posed by the solid tumor that prevent immune cell trafficking and NK cell effector functions. We then discuss promising strategies to enhance NK cell infiltration into solid tumor sites and activation within the TME. This includes NK cell-intrinsic and -extrinsic mechanisms such as NK cell engineering to resist TME-mediated inhibition and use of tumor-targeted agents such as oncolytic viruses expressing chemoattracting and activating payloads. We then discuss opportunities and challenges for using combination therapies to extend NK cell therapies for the treatment of solid tumors.

Efectividad de las Técnicas de Retratamiento Endodóntico en la Remoción de ementos Biocerámicos como Material de Obturación Radicular: Revisión Sistemática

El retratamiento no quirúrgico es la primera opción ante el fracaso del tratamiento endodóntico, por lo que se vuelve importante asegurar el completo retiro del material de relleno del conducto radicular, para mejorar el pronóstico del procedimiento. Los cementos biocerámicos en base a silicatos cálcicos han aparecido en los últimos años, caracterizados principalmente por su bioactividad, lo que adicionalmente se puede traducir en una mayor dificultad para su retiro del conducto radicular. El objetivo de esta revisión es determinar qué técnica de retratamiento es más efectiva en la eliminación de cementos selladores biocerámicos, en base al volumen de material remanente en el conducto radicular, evaluado a través del análisis de imágenes con micro-CT. Se realizó una revisión sistemática mediante la búsqueda de publicaciones en las bases de datos Pubmed, ScienceDirect y SciELO, de los últimos 10 años, en idioma español e inglés. Se incluyeron sólo estudios in vitro de dientes obturados con cemento biocerámico y diferentes técnicas de retratamiento endodóntico, en los que se evalúe la limpieza del conducto post eliminación del relleno mediante micro-CT. De un total de 174 artículos encontrados, 7 fueron seleccionados, analizados y se incluyeron en esta revisión sistemática. Los resultados de los estudios seleccionados no encuentran diferencias significativas en la eliminación de material entre las diferentes técnicas de retratamiento evaluadas. A pesar de la heterogeneidad presente en las metodologías de los artículos analizados, ninguna técnica de retratamiento ni técnicas complementarias lograron dejar completamente limpios los conductos radiculares, por lo que se sugiere realizar nuevos estudios en el futuro que evalúen nuevas técnicas de desobturación radicular.

Non-surgical retreatment is the first option in the case of endodontic treatment failure, so it becomes important to ensure complete removal of the root canal filling material, to improve the prognosis of the procedure. Bioceramic cements based on calcium silicate have appeared in recent years, characterized mainly for their bioactivity, which can additionally translate into greater difficulty in their removal from the root canal. The aim of this review is to determine which retreatment technique is most effective in the removal of bioceramic sealer cements, evaluated through micro-CT image analysis. A systematic review was performed by searching for publications in Pubmed, ScienceDirect and SciELO databases, of the last 10 years in Spanish and English. Only in vitro studies of teeth filled with bioceramic cement and different endodontic retreatment techniques were included, in which the cleaning of the canal after removal of the filling was evaluated by micro- CT. From a total of 174 articles found, 7 were selected, analyzed and included in this systemic review. The results of the included studies did not find significant differences in the removal of material between the different retreatment techniques evaluated. Despite the heterogeneity in the methodologies of the studies, no retreatment technique or complementary techniques were able to completely clean the root canals, it is therefore suggested that new studies be carried out in the future to evaluate new techniques.

Seguimiento de la paciente con diagnóstico de cáncer de mama. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacionalde Cancerología - Colombia / Follow-up of the patient with breast cancer history. Review of the evidence and approach at the Instituto Nacional de Cancerología - Colombia

Los supervivientes de cáncer se definen como aquellos individuos que han completado su tratamiento inicial y no tienen evidencia de la enfermedad. Para el caso de las pacientes supervivientes de cáncer de mama, el seguimiento involucra no sólo la vigilancia de la recaída locorregional y a distancia, así como la tamización de segundos primarios mamarios, sino también la evaluación de los efectos relacionados con las terapias recibidas. Hoy en día, existe controversia sobre cuál debe ser el método, la frecuencia, la duración y tipo de personal de la salud que realice el seguimiento de estas pacientes. Las guías de las distintas sociedades científicas muestran una variabilidad importante en las recomendaciones a este respecto. Este documento pretende revisar la mejor evidencia disponible sobre los procedimientos para la detección de la recaída locorregional, de las metástasis a distancia, de un segundo cáncer de mama contralateral y de los eventos adversos relacionados con los tratamientos para el cáncer de mama. Adicionalmente, se examinan los porcentajes y sitios de recidiva tumoral con relación al estadio clínico y a la biología tumoral

Cancer survivors are defined as those individuals who have completed their initial treatment and have no evidence of disease. In the case of breast cancer survivors, follow-up involves not only surveillance of locoregional and distant relapse, as well as screening for second primary breast cancers, but also evaluation of the effects related to the therapies received. Nowadays, there is controversy about what should be the method, the frequency, the duration and the type of health personnel that carry out the follow-up of these patients. The guides of the different scientific societies show a significant variability in the recommendations in this regard. This document aims to review the best available evidence on procedures for the detection of locoregional relapse, distant metastases, contralateral second breast cancer, and adverse events related to breast cancer treatments. Additionally, the percentages and sites of tumor recurrence are examined in relation to clinical stage and tumor biology

Tratamiento sistémico para el cáncer de mama HER2 positivo avanzado. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Systemic treatment for advanced HER2 positive breast cancer. Review of the evidence and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

El cáncer de mama es la neoplasia más frecuente y de mayor mortalidad en las mujeres en todo el mundo. El receptor 2 del factor de crecimiento epidérmico humano (HER2) se sobreexpresa en aproximadamente el 20% de las pacientes con cáncer de mama y se asocia a mayor riesgo de recidiva tumoral y mortalidad. Antes del desarrollo de los anticuerpos monoclonales dirigidos contra HER2, el cáncer de mama HER2 positivo estaba asociado con un pronóstico desfavorable. El uso de las terapias dirigidas anti HER2 ha mejorado significativamente las tasas de supervivencia global tanto en el escenario adyuvante como en la enfermedad metastásica. En los últimos años han surgido nuevos medicamentos que bloquean esta vía de señalización, lo cual ha permitido establecer varias líneas de tratamiento con terapia anti HER2 en las pacientes con enfermedad metastásica. Por esta razón, las unidades funcionales de Oncología Clínica/Seno y Tejidos Blandos tomaron la decisión de realizar una revisión de la evidencia científica disponible a octubre de 2021, para establecer las recomendaciones en el abordaje terapéutico de las pacientes con cáncer de mama metastásico HER2 positivo en el Instituto Nacional de Cancerología (INC).

Breast cancer is the most common neoplasm and the one with the highest mortality in women worldwide. Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20% of breast cancer patients and is associated with an increased risk of tumor recurrence and mortality. Before the development of monoclonal antibodies directed against HER2, HER2-positive breast cancer was associated with a poor prognosis. The use of anti-HER2 targeted therapies has significantly improved overall survival rates both in the adjuvant setting and in metastatic disease. In recent years, new drugs have emerged that block this signaling pathway, which has made it possible to establish several lines of treatment with anti-HER2 therapy in patients with metastatic disease. For this reason, the clinical oncology/breast and soft tissue functional units made the decision to conduct a review of the available scientific evidence as of October 2021 to establish recommendations for the therapeutic approach to patients with HER2-positive metastatic breast cancer in the National Cancer Institute (INC).

Criterios para la identificación de síndromes de cáncer de mama hereditarios. Revisión de la literatura y recomendaciones para el Instituto Nacional de Cancerología - Colombia / Criteria for the identification of hereditary breast cancer syndromes. Review of the literature and recommendations for the Instituto Nacional de Cancerología - Colombia

Introducción. Los síndromes de cáncer de mama hereditario (SCMH) corresponden a un 5% a 10% de todos los casos de la enfermedad, en su mayoría explicados por mutaciones en los genes BRCA1 y BRCA2. Se han publicado múltiples guías y recomendaciones internacionales actualizadas, con el fin de dar lineamientos para seleccionar los casos con sospecha de un SCMH. Como antecedentes locales, el Instituto Nacional de Cancerología de Colombia cuenta con un "Programa institucional para la identificación y manejo de familias con sospecha de cáncer hereditario", con fines asistenciales, dentro del cual el cáncer de mama es la patología más remitida al servicio de genética (55%; 540/986). En el 21% de los casos con cáncer de mama que cumplieron criterios NCCN se diagnosticó un SCMH, la mayoría asociados a mutaciones en los genes BRCA1 y BRCA2 (12,3%) y en menor proporción a otros genes de susceptibilidad al cáncer de mama (8,6%).Objetivo. Identificar los criterios de selección más implementados para diagnosticar los casos de cáncer de mama hereditarios a través de una revisión de la literatura, y realizar un consenso Institucional sobre las indicaciones de remisión a consejería genética y solicitud de pruebas para fines diagnósticos y de tratamiento sistémico con iPARP. Materiales y métodos. Se realizó una revisión narrativa de la literatura científica publicada en los últimos 10 años, al 30 de agosto del 2021, sobre la prevalencia de mutaciones germinales en los genes BRCA1 y BRCA2, y en otros genes no BRCA, en pacientes con cáncer de mama, obteniéndose en total 146 y seleccionándose un total de 41 artículos. En el interior de las unidades funcionales de mama y tejidos blandos, genética y oncología clínica, se presentó la evidencia disponible, realizando una discusión amplia entre las tres unidades y finalmente se definieron las indicaciones para remisión a genética, para solicitar estudios genéticos y de tratamiento sistémico con iPARP.Resultados. Según lo reportado en la literatura, los principales criterios de sospecha de un SCMH deben incluir: el subtipo triple negativo, la presentación bilateral, la edad muy temprana de diagnóstico y los antecedentes familiares (AF) de cáncer de mama antes de los 50 años o cáncer de ovario a cualquier edad.Conclusiones. Se adoptan las recomendaciones de la NCCN para la remisión a consejería genética y solicitud de estudios genéticos para identificar cáncer de mama hereditario, y se establecen los criterios del estudio OlympiA para la solicitud de estudios genéticos con el fin de guiar el tratamiento sistémico con iPARP en el Instituto Nacional de Cancerología. Lo anterior permitirá que desde nuestra Institución se ofrezca adecuadamente este servicio a la población colombiana.

ntroduction: Hereditary breast and ovarian cancer syndromes (HBOC) represents 5% to 10% of all breast cancer cases, and BRCA1andBRCA2 explain most of these syndromes. Multiple guidelines and updated recommendations have been published to define which patients should be selected for genetic testing based on a clinical suspicion of a HBOC syndrome. For context, the Instituto Nacional de Cancerología from Colombia developed an "Institutional Program for the identification and management of families with suspected hereditary cancer" for healthcare purposes, within which breast cancer is the most referred pathology to the genetics service (55%; 540/986). Inherited cancer was diagnosed in 21% of the patients with breast cancer who met NCCN criteria; most of these were associated with BRCA1 and BRCA2 mutations (12.3%) and to a lesser extent to other breast cancer susceptibility genes (8.6%).Objective: To identify the most implemented selection criteria to diagnose inherited breast cancer cases, through a review of the literature, and to achieve an institutional consensus on the indications for referral to genetic counseling and genetic testing for diagnostic and systemic treatment with PARPi.Materials and methods: A narrative review of the scientific literature published in the last 10 years as of August 30, 2021 on the prevalence of germline mutations in the BRCA1 and BRCA2 genes, and in other non-BRCA genes, in patients with breast cancer was carried out. Overall, 146 articles were first identified but only 41 were selected. Within the functional units of breast and soft tissue, genetics and clinical oncology, the available evidence was presented and a broad discussion was carried out; finally the indications for referral to genetic counseling, for genetic testing and for systemic treatment with PARPi were defined.Results: As reported in the literature, clinical criteria for HBOC syndrome should include: triple negative subtype, bilateral presentation, very early age of diagnosis and family history (FH) of breast cancer before 50 years of age or ovarian cancer at any age. Conclusions: The NCCN recommendations for referral to genetic counseling and ordering genetic testing to diagnose HBOC cases are adopted at the Instituto Nacional de Cancerología from Colombia, as well as the OlympiA study criteria for ordering genetic testing to guide systemic PARPi therapy. This will allow our Institution to adequately offer this service to the Colombian population.

Indicaciones para el uso de pertuzumab en cáncer de mama HER2 positivono metastásico en los escenarios neoadyuvante y adyuvante. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Indications for the use of pertuzumab in non-metastatic HER2-positive breast cancer in the neoadjuvant and adjuvant. Review of the literature and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

La adición de la terapia dirigida a la quimioterapia citotóxica en pacientes con cáncer de mama ha mejorado significativamente los desenlaces oncológicos en las pacientes con tumores HER2 positivo. El uso de pertuzumab durante el manejo neoadyuvante incrementa significativamente la respuesta patológica completa y en la actualidad permite emplear regímenes libres de antraciclinas con una eficacia similar y menores efectos cardiovasculares (en especial sobre la fracción de eyección). El beneficio en supervivencia libre de enfermedad invasiva, de adicionar pertuzumab en el escenario adyuvante en las pacientes sin tratamiento anti HER2 previo, está limitado a aquellas con ganglios positivos. La implementación de esquemas con bloqueo dual anti HER2, durante el tratamiento inicial del cáncer de mama HER2 positivo, mejora significativamente el pronóstico oncológico en este grupo de pacientes.

The addition of targeted therapy to cytotoxic chemotherapy in patients with breast cancer has significantly improved oncologic outcomes in patients with HER2-positive tumors. The use of pertuzumab during neoadjuvant management significantly increases the complete pathological response and currently allows the use of anthracycline-free regimens with similar efficacy and fewer cardiovascular effects (especially on ejection fraction). The benefit of pertuzumab in disease-free survival in the adjuvant setting for patients without prior anti-HER2 treatment is limited to those with positive nodes. The implementation of schemes with dual anti-HER2 blockade during the initial treatment of HER2-positive breast cancer significantly improves the oncological outcomes in this group of patients.

Estudios de extensión para la estadificación del cáncer de mama infiltrante. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Extension studies for the staging of infiltrating breast cancer. Review of evidence and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

La estadificación del cáncer de mama tiene como objetivo determinar la extensión de la enfermedad, definir el tratamiento y el pronóstico de la misma. La American Joint Committee on Cancer(AJCC) ha asignado el estadio utilizando el tamaño del tumor (T), la presencia de compromiso ganglionar (N), y la presencia o ausencia de metástasis a distancia (M). Con el advenimiento de la biología molecular, se integra a la estadificación anatómica la información pronóstica con el grado histológico, el estado de los receptores hormonales y el resultado del receptor de HER2. En el Instituto Nacional de Cancerología (INC), la incorporación del TNM pronóstico trajo consigo un aumento de estadio en el 14,47% de los casos y una disminución en el 40,3%; este resultado se atribuyó en parte al mayor porcentaje de tumores localmente avanzados dentro de la institución. Por subtipo biológico, los tumores luminales presentan mayor riesgo de metástasis óseas, los tumores triple negativo a pulmón y sistema nervioso central; y los tumores HER2 a SNC, hígado y pulmón. Teniendo en cuenta este compromiso a distancia, los métodos de estadificación comúnmente utilizados son gammagrafía ósea (GO), radiografía de tórax (RxT), ecografía hepática (UH) y/o tomografía computarizada (TC). En el caso de identificar hallazgos sospechosos en estos exámenes o si el cuadro clínico del paciente lo sugiere, se realizan estudios adicionales como TC o resonancia magnética nuclear (RMN). Los cambios en la estadificación clínica y la biología del cáncer de mama motivaron a las Unidades de Seno y Tejidos Blandos y Oncología Clínica del Instituto Nacional de Cancerología a revisar la evidencia científica disponible para recomendar la pertinencia de los estudios de extensión.

The staging of breast cancer has the objective to determine the extent of the disease, define treatment and prognosis. The American Joint Committee on Cancer (AJCC) has assigned the stage using the size of the tumor (T), the presence of lymph node involvement (N), and the presence or absence of distant metastases (M). With the advent of molecular biology, prognostic information with histological grade, hormone receptor status, and HER2 receptor is integrated with anatomic staging. In the National Institute of Cancerology (INC) the incorporation of TNM brought with it an increase in stage in 14.47% of cases and a decrease in 40.3%; this result was attributed in part to the higher percentage of locally advanced tumors within the institution. By biological subtype, luminal tumors have a higher risk of bone metastases, triple negative tumors to the lung and central nervous system; and HER2 tumors to CNS, liver and lung. Taking this distant involvement into account, the commonly used staging methods are bone scan (BS), chest radiography (CXR), liver ultrasound (UH) and/or computed tomography (CT) scans. In the case of identifying suspicious findings in these tests or if the patient's clinical condition suggests it, additional studies such as CT or magnetic resonance imaging (MRI) are performed. Changes in the clinical staging and biology of breast cancer motivated the Breast and Clinical Oncology Functional Unit of the National Cancer Institute to review the available scientific evidence to recommend the relevance of extension studies.

Endodoncia guiada estática, una opción para obliteración del canal pulpar: serie de casos / Static guided endodontics, an option for pulpal canal obliteration: a case series

En la práctica endodóntica, la etapa del acceso al canal radicular es fundamental para el éxito de las siguientes etapas del tratamiento. En casos de canales pulpares obliterados o calcificados (PCO), lograr encontrar la entrada a estos es un reto en la endodoncia convencional dado el alto riesgo de sufrir un accidente intraoperatorio. Actualmente, existen los tratamientos de endodoncia guiada o accesos guiados digitalmente, una alternativa innovadora y con múltiples beneficios para el abordaje de este tipo de dientes. El objetivo de este reporte de casos fue describir el protocolo de cuatro casos de accesos guiados estáticos para endodoncia en canales obliterados, indicando las ventajas y consideraciones del tratamiento. Se presenta un reporte de casos de cuatro pacientes atendidos entre julio 2021 y junio 2022, que requerían tratamientos endodónticos en dientes anteriores con canales pulpares obliterados. Para la realización de estos procedimientos se requirió una Tomografía Computarizada de Haz Cónico (CBCT) y el escaneo intraoral de la zona a tratar, para poder a través de la ayuda de un software, planificar virtualmente la dirección y longitud de acceso al conducto radicular. Posteriormente, se realizó la impresión en 3D de la guía estática, la cual dirige la entrada de la fresa que se utiliza para encontrar el acceso al canal radicular. En los cuatro casos clínicos en que se realizó la planificación virtual e impresión de la guía de acceso, fue posible encontrar el canal radicular en una sesión, pudiendo realizar el tratamiento endodóntico de manera exitosa y conservadora. En conclusión, la endodoncia guiada estática permite realizar los tratamientos endodónticos en PCO de manera segura, a pesar de la alta complejidad que presentaban.

SUMMARY: In endodontics, the access to the root canal is essential for the treatment success. Pulp canal obliteration (PCO) is a challenge for conventional endodontic treatments with a high risk of fracture of endodontic instruments.Currently, guided endodontic treatments, or digitally guided accesses, are novel alternatives with multiple benefits for the treatment of PCO. The objective of this case report is to describe the protocol for static guided access in PCO, indicating the advantages and considerations of the treatment. A case report of four patients treated between July 2021 and June 2022 is presented. These patients required endodontic treatments in anterior teeth with PCO. In order to virtually plan the direction and length of the access, using a software, we used a cone Beam Computed Tomography (CBCT) and an intraoral scan. Then, a 3D printing of the static guide was made, which directs the entry of the drill. With this method, it was possible to find the root canal in one session and perform the endodontic treatment successfully and conservatively. In conclusion, although static guided endodontics requires planification, it allows a safe endodontic treatment in patients with PCO.

Horizontal Transmission of Cytomegalovirus in a Rhesus Model Despite High-Level, Vaccine-Elicited Neutralizing Antibody and T-Cell Responses.

The development of a vaccine to prevent congenital human cytomegalovirus (HCMV) disease is a public health priority. We tested rhesus CMV (RhCMV) prototypes of HCMV vaccine candidates in a seronegative macaque oral challenge model. Immunogens included a recombinant pentameric complex (PC; gH/gL/pUL128/pUL130/pUL131A), a postfusion gB ectodomain, and a DNA plasmid that encodes pp65-2. Immunization with QS21-adjuvanted PC alone or with the other immunogens elicited neutralizing titers comparable to those elicited by RhCMV infection. Similarly, immunization with all 3 immunogens elicited pp65-specific cytotoxic T-cell responses comparable to those elicited by RhCMV infection. RhCMV readily infected immunized animals and was detected in saliva, blood, and urine after challenge in quantities similar to those in placebo-immunized animals. If HCMV evades vaccine-elicited immunity in humans as RhCMV evaded immunity in macaques, a HCMV vaccine must elicit immunity superior to, or different from, that elicited by the prototype RhCMV vaccine to block horizontal transmission.

Platelet-Rich Fibrin Membrane for Pterygium Surgery: Literature Review and Feasibility Assessment.

Pterygium is a common ocular disease caused by abnormal cellular proliferation leading to abnormal fibrovascular growth of the conjunctiva. The main treatment is surgical removal; however, despite the improvement of surgical techniques and development of adjuvant therapies, postoperative recurrence, which can be as high as 89%, remains a challenge. Currently, pterygium excision with conjunctival autograft remains the preferred surgical technique, although there is no gold standard technique to prevent pterygium recurrence. We have conducted a thorough and comprehensive review of the scientific literature regarding the use of PRF membranes in pterygium surgery. We aim to assess the safety, effectiveness, and applicability of platelet-rich fibrin membrane for primary pterygium surgery and assess its possible benefits in resource-limited settings.

Tendon Reconstruction With Cadaveric Allograft in a Patient With Flexor Tendon Injury Without Treatment for Six Months.

We present the case of an 18-year-old male patient with a penetrating lesion at zone II of the flexor compartment of the left hand. During surgery, complete reabsorption of the second deep and superficial flexor tendons was evidenced, prompting the decision to perform a two-stage procedure. First, a spacer was placed, and pulley reconstruction was performed. Six weeks later, we placed a cadaveric allograft and splint with the Kleinert-Duran technique for proper rehabilitation. Our case report highlights that a two-stage procedure with an allograft is a feasible technique resulting in good post-surgical functional status despite tendon reabsorption and six months between trauma and surgical intervention.

Expanded human NK cells armed with CAR uncouple potent anti-tumor activity from off-tumor toxicity against solid tumors.

Despite the remarkable success of chimeric antigen receptor (CAR)-T cells against hematologic malignancies, severe off-tumor effects have constrained their use against solid tumors. Recently, CAR-engineered natural killer (NK) cells have emerged as an effective and safe alternative. Here, we demonstrate that HER2 CAR-expression in NK cells from healthy donors and patients with breast cancer potently enhances their anti-tumor functions against various HER2-expressing cancer cells, regardless of MHC class I expression. Moreover, HER2 CAR-NK cells exert higher cytotoxicity than donor-matched HER2 CAR-T cells against tumor targets. Importantly, unlike CAR-T cells, HER2 CAR-NK cells do not elicit enhanced cytotoxicity or inflammatory cytokine production against non-malignant human lung epithelial cells with basal HER2 expression. Further, HER2 CAR-NK cells maintain high cytotoxic function in the presence of immunosuppressive factors enriched in solid tumors. These results show that CAR-NK cells may be a highly potent and safe source of immunotherapy in the context of solid tumors.

Actividad antioxidante en genotipos de Theobroma spp. (Malvaceae) en México / Antioxidant activity in genotypes of Theobroma spp. (Malvaceae) in Mexico

Abstract Introduction: The organoleptic qualities of aromatic species and their derived products are directly related to some characteristics of flavor, color and nutritional value and depend largely on their genetic origin and content of secondary metabolites. Objective: The antioxidant activity of different genotypes of Theobroma spp. from Mexico was evaluated in order to distinguish promising qualities for genetic improvement, and to differentiate phylogenetic traits, considering biochemical variables. Methods: The amount of phenols, flavonoids and antioxidant activity was determined by ABTS and DDPH, in addition to the content of anthocyanins, theobromine and caffeine in four species of Theobroma L., and 50 genotypes derived from T. cacao. The results were analyzed using an analysis of variance, means test, principal component analysis and cladistic analysis. Results: There are highly significant differences between genotypes. The phenol content ranged from 7.5-85 mg g-1; flavonoids 6.57-69.6 mg g-1, antioxidant activity by ABTS of 17.3-86.1 and by DDPH of 40.0-53.3; anthocyanin content of 0.01-3, caffeine of 1.8-6.7-and theobromine of 2.9-9.8 mg g-1. Principal component and cladistic analysis helped explain the variation found and distinguish evolutionary characters and phylogenetic brotherhoods. The variation in content of phenols, flavonoids, antioxidant activity, anthocyanins, theobromine and caffeine was mainly due to the degree of domestication, while for the group of genotypes derived from T. cacao (forastero, trinitario and criollo) it was the origin of the seeds. Conclusions: The degree of domestication influences the content of phenols and antioxidant capacity. The results suggest that the evaluated variables can help to form criteria for genetic improvement in the complex derived from T. cacao oriented to the selection of higher phenol content and greater antioxidant activity.

Resumen Introducción: Las cualidades organolépticas de las especies aromáticas y sus productos derivados se relacionan directamente con algunas características del sabor, color y valor nutricional y dependen en gran medida de su origen genético y contenido de metabolitos secundarios. Objetivo: Se evaluó la actividad antioxidante de diferentes genotipos de Theobroma spp. de México, con el fin de distinguir cualidades promisorias para el mejoramiento genético, y diferenciar rasgos filogenéticos, considerando variables bioquímicas. Métodos: Se determinó la cantidad de fenoles, flavonoides y actividad antioxidante mediante ABTS y DDPH, además de contenido de antocianinas, teobromina y cafeína en cuatro especies de Theobroma L., y 50 genotipos derivados de T. cacao. Resultados: Los resultados fueron analizados mediante un análisis de varianza, prueba de medias, análisis de componentes principales y análisis cladístico. Existen diferencias altamente significativas entre genotipos. El contenido de fenoles varió de 7.5-85 mg g-1; flavonoides 6.57-69.6-mg g-1, actividad antioxidante por ABTS de 17.3-86.1 y por DDPH de 40.0-53.3; el contenido de antocianinas de 0.01-3, cafeína de 1.8-6.7 y teobromina de 2.9-9.8 mg g-1. El análisis de componentes principales y cladístico ayudó a explicar la variación encontrada y distinguir caracteres evolutivos y hermandades filogenéticas. La variación en contenido de fenoles, flavonoides, actividad antioxidante, antocianinas, teobromina y cafeína estuvo dada principalmente por el grado de domesticación, mientras que para el grupo de genotipos derivados de T. cacao (forastero, trinitario y criollo) fue el origen de las semillas. Conclusión: El grado de domesticación influye en el contenido de fenoles y actividad antioxidante. Los resultados sugieren que las variables evaluadas pueden ayudar a formar criterios para el mejoramiento genético en el complejo derivado de T. cacao orientado a la selección de mayor contenido de fenoles y mayor actividad antioxidante.

Metabolic flexibility determines human NK cell functional fate in the tumor microenvironment.

NK cells are central to anti-tumor immunity and recently showed efficacy for treating hematologic malignancies. However, their dysfunction in the hostile tumor microenvironment remains a pivotal barrier for cancer immunotherapies against solid tumors. Using cancer patient samples and proteomics, we found that human NK cell dysfunction in the tumor microenvironment is due to suppression of glucose metabolism via lipid peroxidation-associated oxidative stress. Activation of the Nrf2 antioxidant pathway restored NK cell metabolism and function and resulted in greater anti-tumor activity in vivo. Strikingly, expanded NK cells reprogrammed with complete metabolic substrate flexibility not only sustained metabolic fitness but paradoxically augmented their tumor killing in the tumor microenvironment and in response to nutrient deprivation. Our results uncover that metabolic flexibility enables a cytotoxic immune cell to exploit the metabolic hostility of tumors for their advantage, addressing a critical hurdle for cancer immunotherapy.

Expanded human NK cells from lung cancer patients sensitize patients' PDL1-negative tumors to PD1-blockade therapy.

Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1-blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients' tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1- patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types.

Linfedema escrotal gigante en un paciente con falectomía parcial / Giant scrotal lymphedema in a patient with partial falectomy

Se describe el caso clínico de un paciente que, 7 años después de habérsele realizado una falectomía parcial con linfadenectomía inguinal superficial y quimioterapia (cisplatino 150) por un carcinoma epidermoide del pene, acudió al Servicio de Urología del Hospital General Docente Dr. Juan Bruno Zayas Alfonso en Santiago de Cuba por presentar un linfedema gigantesco de escroto, de origen obstructivo linfático, con marcada repercusión sobre la posición bípeda y la marcha. Se realizó el procedimiento quirúrgico (técnica de Homans con modificaciones) y el paciente evolucionó satisfactoriamente. Luego de 2 años de operado, se le dio el alta de la consulta externa, pues se consideró que había recuperado la capacidad físico-motora y su autoestima.

The case report of a patient is described who, 7 years after carrying out a partial falectomy with inguinal superficial lymphadenectomy and chemotherapy (cisplatin 150) due to an squamous cell carcinoma of the penis, he went to the Urology Service of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba presenting a giant scrotal lymphedema, of lymphatic obstructive origin, with marked repercussion on the biped position and during walking. The surgical procedure (Homans technique with modifications) was carried out and the patient had a satisfactory clinical course. Then after 2 years of surgery, he was discharged from the out-patient service, because it was considered that he had recovered the physical motor skills and his self-esteem.

Nefrectomía parcial laparoscópica: experiencia de 135 casos / Laparoscopic partial nephrectomy: experience of 135 cases

Introducción: La nefrectomía parcial laparoscópica (NPL) es considerada hoy una alternativa terapéutica para el manejo de tumores renales menores de 4 cm. Sus principales ventajas son permitir un excelente control oncológico, además de preservar la unidad renal. Por otro lado ha permitido acortar los tiempos de hospitalización, disminuir el dolor postquirúrgico y lograr menores tiempos de recuperación en los pacientes. El objetivo del presente estudio es presentar nuestra experiencia en nefrectomías parciales laparoscópicas durante los últimos 12 años. Materiales y métodos: Estudio retrospectivo de sometidos a NPL entre los años 2000 y 2012. En todos los casos la cirugía fue realizada por un mismo cirujano. Se obtuvo información demográfica de los pacientes, tamaño y ubicación del tumor, vía de abordaje, tiempo quirúrgico, sangrado intraoperatorio, tiempo de hospitalización y complicaciones. El análisis de los datos se llevo a cabo con el programa SPSS v17. Se consideró significativo un p<0.05.Resultados: En el periodo descrito se realizaron NPL en 135 pacientes (70.4 por ciento hombres). El promedio de edad fue de 56.9+/-12.8 años. Ochenta y dos cirugías fueron izquierdas y 53 derechas. Con respecto a la ubicación de la masa dentro del riñón, se encontraron un 25.2 por ciento en el polo superior, 46.7 por ciento en la porción media y 28.1 por ciento en el polo inferior. En el 40 por ciento de los casos los tumores se ubicaron en una posición calificada como técnicamente compleja. Con respecto al abordaje quirúrgico, un 42.2 por ciento fueron realizadas por vía transperitoneal y un 57.8 por ciento por vía retroperitoneal. Se realizaron 8 conversiones a cirugía abierta. El tamaño promedio de los tumores fue de 3.26+/-1.6 cm...

Introduction: Laparoscopic partial nephrectomy (LPN) has become the first-line surgical technique for the management of renal tumors smaller than 4 cm. Its main advantages are an excellent oncologic control together with the preservation of nephron units. Moreover it implies a shorter-length of hospital stay, less postoperative pain and shorter recovering times for patients. The aim of this report is to show our experience and compare it with the resuls reported in the international literature. Materials and methods: All patients that underwent LPN within years 2000 and 2010 were retrospectively studied. In all cases surgery was performed by the same surgeon. Data was collected retrospectively, including clinical and histopathologic information, as well as surgical and functional results. Results: One hundred and thirty five were included (70.4 percentmale). Mean age was 56.9 +/- 12.8 years. Eighty-two surgeries were left and 53 right. Regarding to the location of the mass within the kidney, 25.2 percent were found at the upper pole, 46.7 percent in the middle portion, and 28.1percent at the lower pole. In 40 percent of cases the tumor was located in a position described as technically complex. Regarding to the surgical approach, 42.2 percent were performed by transperitoneal and retroperitoneal 57.8 percent for. There were eight conversions to open surgery. The average tumor size was 3.26 +/- 1.6 cm. Mean operative time was 106.2 +/- 38.2 minutes. The median blood loss was 100cc (range <50-3000). Two patients required transfusion. Median hospital stay was 48 hours (range 23-120). Eleven patients (8.14 percent had complications related to surgery. The most of the cases (n = 5) were due to intraoperative bleeding. Conclusions: The LPN is a challenging surgical technique. The results of this study confirm that laparoscopic surgery is a safe technique for the management of renal tumors with a low rate of complications and shorter hospital stays.

Properties of voltage-gated Ca2+ currents measured from mouse pancreatic â-cells in situ

We used the single-microelectrode voltage-clamp technique to record ionic currents from pancreatic â-cells within intact mouse islets of Langerhans at 37C, the typical preparation for studies of glucose-induced "bursting" electrical activity. Cells were impaled with intracellular microelectrodes, and voltage pulses were applied in the presence of tetraethylammonium. Under these conditions, a voltage-dependent Ca2+ current (I Cav), containing L-type and non-L-type components, was observed. The current measured in situ was larger than that measured in single cells with whole-cell patch clamping, particularly at membrane potentials corresponding to the action potentials of â-cell electrical activity. The temperature dependence of I Cav was not sufficient to account for the difference in size of the currents recorded with the two methods. During prolonged pulses, the voltage-dependent Ca2+ current measured in situ displayed both rapid and slow components of inactivation. The rapid component was Ca2+-dependent and was inhibited by the membrane-permeable Ca2+ chelator, BAPTA-AM. The effect of BAPTA-AM on â-cell electrical activity then demonstrated that Ca2+-dependent inactivation of I Cav contributes to action potential repolarization and to control of burst frequency. Our results demonstrate the utility of voltage clamping â-cells in situ for determining the roles of ion channels in electrical activity and insulin secretion.