Erratum: Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas.

[This corrects the article DOI: 10.1016/j.omton.2024.200787.].

Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas.

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and (2) a mouse cohort harboring GL261-5 tumors used to mechanistically evaluate the importance of CD4+ T cells in relation to viroimmunotherapy efficacy. Microbiota assessment indicated significant differences in the structure of the gut bacterial communities in viroimmunotherapy-treated animals with higher survival compared with control or indoximod-treated animals. Moreover, viroimmunotherapy-treated mice with prolonged survival had a higher abundance of Bifidobacterium. The CD4+ T cell depletion was associated with gut dysbiosis, lower mouse survival, and lower antitumor efficacy of the therapy. These findings suggest that microbiota modulation along the gut-glioma axis contributes to the clinical efficacy and patient survival of viroimmunotherapy treated animals.

Chimeric oncolytic adenovirus evades neutralizing antibodies from human patients and exhibits enhanced anti-glioma efficacy in immunized mice.

Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain. We found that immunoglobulins colocalized with viral proteins upon local oncolytic virotherapy of brain tumors, warranting a strategy to prevent virus neutralization and maximize oncolysis. Thus, we generated a chimeric virus, Delta-24-RGD-H43m, by replacing the capsid protein HVRs from the serotype 5-based Delta-24-RGD with those from the rare serotype 43. Delta-24-RGD-H43m evaded neutralizing anti-Ad5 antibodies and conferred a higher rate of long-term survival than Delta-24-RGD in glioma-bearing mice. Importantly, Delta-24-RGD-H43m activity was significantly more resistant to neutralizing antibodies present in sera of glioma patients treated with Delta-24-RGD during a phase 1 clinical trial. These findings provide a framework for a novel treatment of glioma patients that have developed immunity against Delta-24-RGD.

Targeting Innate Immunity in Glioma Therapy.

Currently, there is a lack of effective therapies for the majority of glioblastomas (GBMs), the most common and malignant primary brain tumor. While immunotherapies have shown promise in treating various types of cancers, they have had limited success in improving the overall survival of GBM patients. Therefore, advancing GBM treatment requires a deeper understanding of the molecular and cellular mechanisms that cause resistance to immunotherapy. Further insights into the innate immune response are crucial for developing more potent treatments for brain tumors. Our review provides a brief overview of innate immunity. In addition, we provide a discussion of current therapies aimed at boosting the innate immunity in gliomas. These approaches encompass strategies to activate Toll-like receptors, induce stress responses, enhance the innate immune response, leverage interferon type-I therapy, therapeutic antibodies, immune checkpoint antibodies, natural killer (NK) cells, and oncolytic virotherapy, and manipulate the microbiome. Both preclinical and clinical studies indicate that a better understanding of the mechanisms governing the innate immune response in GBM could enhance immunotherapy and reinforce the effects of chemotherapy and radiotherapy. Consequently, a more comprehensive understanding of the innate immune response against cancer should lead to better prognoses and increased overall survival for GBM patients.

Genome-wide CRISPR-Cas9 screen analyzed by SLIDER identifies network of repressor complexes that regulate TRIM24.

TRIM24 is an oncogenic chromatin reader that is frequently overexpressed in human tumors and associated with poor prognosis. However, TRIM24 is rarely mutated, duplicated, or rearranged in cancer. This raises questions about how TRIM24 is regulated and what changes in its regulation are responsible for its overexpression. Here, we perform a genome-wide CRISPR-Cas9 screen by fluorescence-activated cell sorting (FACS) that nominated 220 negative regulators and elucidated a regulatory network that includes the KAP1 corepressor, CNOT deadenylase, and GID/CTLH E3 ligase. Knocking out required components of these three complexes caused TRIM24 overexpression, confirming their negative regulation of TRIM24. Our findings identify regulators of TRIM24 that nominate previously unexplored contexts for this oncoprotein in biology and disease. These findings were enabled by SLIDER, a new scoring system designed and vetted in our study as a broadly applicable tool for analysis of CRISPR screens performed by FACS.

Novel CRISPR-Associated Gene-Editing Systems Discovered in Metagenomic Samples Enable Efficient and Specific Genome Engineering.

Development of medicines using gene editing has been hampered by enzymological and immunological impediments. We described previously the discovery and characterization of improved, novel gene-editing systems from metagenomic data. In this study, we substantially advance this work with three such gene-editing systems, demonstrating their utility for cell therapy development. All three systems are capable of reproducible, high-frequency gene editing in primary immune cells. In human T cells, disruption of the T cell receptor (TCR) alpha-chain was induced in >95% of cells, both paralogs of the TCR beta-chain in >90% of cells, and >90% knockout of ß2-microglobulin, TIGIT, FAS, and PDCD1. Simultaneous double knockout of TRAC and TRBC was obtained at a frequency equal to that of the single edits. Gene editing with our systems had minimal effect on T cell viability. Furthermore, we integrate a chimeric antigen receptor (CAR) construct into TRAC (up to ∼60% of T cells), and demonstrate CAR expression and cytotoxicity. We next applied our novel gene-editing tools to natural killer (NK) cells, B cells, hematopoietic stem cells, and induced pluripotent stem cells, generating similarly efficient cell-engineering outcomes including the creation of active CAR-NK cells. Interrogation of our gene-editing systems' specificity reveals a profile comparable with or better than Cas9. Finally, our nucleases lack preexisting humoral and T cell-based immunity, consistent with their sourcing from nonhuman pathogens. In all, we show these new gene-editing systems have the activity, specificity, and translatability necessary for use in cell therapy development.

Multicenter clinical trial for the resection of rectal polyps using a new laparoendoscopic hybrid transanal access device.

INTRODUCTION: Complex polyps require the use of advanced endoscopic techniques or minimally invasive surgery for their approach. In rectal polyps it is of special relevance to reach a consensus on the best approach to avoid under- or overtreatment that increases unnecessary morbidity and mortality. METHODS: We describe a prospective, multicenter, pilot clinical trial with a first-in-human medical device. It is hypothesized that UNI-VEC® facilitates transanal laparoendoscopic surgery for the removal of early rectal tumors. The primary objective is to evaluate that it is safe and meets the established functional requirements. Secondary objectives are to evaluate results, complications and level of satisfaction. RESULTS: 16 patients were recruited in 12 months with a minimum follow-up of 2 months. The mean size was 3.4 cm with the largest polyp being 6 cm. Regarding location, the mean was 6.6 cm from the anal margin. Endoscopic Mucosal Resection (EMR) (6.3%), Endoscopic Submucosal Dissection ESD (43.8%), REC (6.3%) and TAMIS (43.8%) were performed. The mean time was 73.25 min. The 56.3% used a 30° camera and 43.8% used the flexible endoscope as a viewing instrument. The 56.3% were benign lesions and 43.8% malignant. Complete resection is achieved in 87.5%. Regarding complications, mild bleeding (Clavien I) occurred in 25%, 6.3% and 21.4% at 24 h, 48 h and 7 days respectively. Continence was assessed according to the Wexner scale. At 7 days, 60% showed perfect continence, 26.7% mild FI and 13.3% moderate FI. At 30 days, 66.7% had perfect continence, 20% mild FI and 13.3% moderate FI. At 2 months, 4 patients were reviewed who at 30 days had a Wexner's degree higher than preoperative and perfect continence was demonstrated in 25% of the patients, 50% mild and 25% moderate. In no case did rectal perforation or major complications requiring urgent reintervention occur. As for the level of reproducibility, safety, level of satisfaction with the device and evaluation of the blister, the evaluation on a scale of 0-10 (9.43, 9.71, 9.29 and 9.50 respectively). All the investigators have previous experience with transanal devices. CONCLUSIONS: The study demonstrates the efficacy and safety of UNI-VEC® for the treatment of rectal lesions. It will facilitate the implementation of hybrid procedures that seek to solve the limitations of pure endoscopic techniques by allowing the concomitant use of conventional laparoscopic and robotic instrumentation with the flexible endoscope.

Agujero Timpánico bilateral. Análisis de caso desde la literatura / Bilateral tympanic hole. Case analysis from the literature

La pared del conducto auditivo externo (CAE) parte de la formación del hueso timpánico; integrándose posteriormente a la porción petrosa del hueso temporal. El agujero timpánico o foramen de Huschke corresponde a un defecto en la osificación en donde existe fusión incompleta de porciones anteriores y posteriores del anillo timpánico dejando una abertura que comunica el CAE hacia anterior. Su presencia es normal hasta los 5 años de edad, tiempo en que se debiese obliterar. Su incidencia es baja (3-24%), pero la persistencia en adulto, conlleva sintomatología inespecífica caracterizada por otalgia, dolor en articulación temporomandibular (ATM), tinnitus, hipoacusia o manifestaciones complejas como descarga salival en CAE durante la masticación. Clínicamente puede complicar procedimientos de infiltración y artroscopias de ATM. Rara vez ocasiona, en pacientes mayores de 50 años, herniación de la cabeza del cóndilo mandibular. Su diagnóstico puede ser clínico por medio de otoscopia, donde se observa protuberancia de tejido en pared anterior del CAE, que aumenta de tamaño con la boca cerrada. También puede ser imagenológico con una tomografía computarizada. El tratamiento incluye desde medidas conservadoras para manejo del dolor e inflamación, hasta quirúrgicas con la implantación de injertos, placas o prótesis para cerrar la estructura o para reemplazar el cóndilo mandibular. El presente estudio pretende aportar incidencia dentro del área de estudio. Se analiza por observación directa, cráneo seco, completo, masculino, edad entre 12 a 15 años (según morfología del cóndilo mandibular y erupción dental). Se observa agujero de Huschke, bilateral, ambos permeables de diámetro 4 mm en ambos casos, determinados con regla milimetrada. La relevancia del defecto se asocia a la práctica clínica de otorrinolaringólogos, cirujanos maxilofaciales y odontólogos, ya sea como diagnóstico diferencial asociado a los síntomas inespecíficos, como para procedimientos más invasivos en la zona tales como infiltraciones o artroscopias de ATM

The wall of the external auditory canal (EAC) starts from the formation of the tympanic bone; later it is integrated to the petrous portion of the temporal bone. The tympanic foramen or foramen of Huschke corresponds to a defect in ossification where there is incomplete fusion of the anterior and posterior portions of the tympanic ring leaving an opening that communicates the EAC to its anterior aspect. Its presence is normal until 5 years of age, when it should be absolutely obliterated. Its incidence is low (3-24%), but its persistence in adults leads to non specific symptoms characterized by otalgia, pain in the temporomandibular joint (TMJ), tinnitus, hearing loss, or complex manifestations such as salivary discharge in the CAE during mastication. Clinically, it may complicate TMJ infiltration and arthroscopy procedures. It rarely causes herniation of the mandibular condyle head in patients older than 50 years. Its diagnosis can be clinical by means of otoscopy, where tissue protrusion is observed in the anterior wall of the CAE, which increases in size when the mouth is closed. It can also be imaging with computed tomography. Treatment includes from conservative measures to treat pain and inflammation, to surgical measures with the implantation of grafts, plates or prosthesis to close the structure or to replace the mandibular condyle. The present study aims to provide incidence within the study area. It is analyzed by direct observation, dry skull, complete, male, age between 12 to 15 years (according to mandibular condyle morphology and dental eruption). Huschke's foramen was observed, bilateral, both permeable, diameter 4mm in both cases, determined with a millimeter ruler. The relevance of the defect is associated with the clinical practice of otolaryngologists, maxillofacial surgeons and dentists, either as a differential diagnosis associated with nonspecific symptoms, or for more invasive procedures in the area such as infiltrations or TMJ arthroscopies.

Potencial Afectación de las Glándulas Salivales en la Infección por SARS-CoV-2 (COVID-19)

RESUMEN: La nueva enfermedad por coronavirus 2019 (COVID-19) es la última patología de preocupación internacional. Originada en Wuhan, China, se extendió rápidamente a nivel mundial, razón por la cual fue declarada una emergencia de salud pública. Producida por SARS-CoV-2 pertenece al género de los betacoronavirus junto con SARS-CoV y MERS- CoV. Se ha demostrado que SARS-CoV-2 utiliza la enzima convertidora de la angiotensina 2 (ACE2) como receptor para el ingreso en una célula huésped. Diversos estudios han demostrado la expresión de este receptor en diversos órganos y tejidos, dentro de los cuales se han reportado la cavidad oral y las glándulas salivales, los cuales han recibido vital importancia en el último tiempo dada su importancia como potencial reservorio de este virus. El objetivo de esta revisión es conocer el rol de las glándulas salivales como potencial reservorio de SARS-COV-2 y sus manifestaciones asociadas.

ABSTRACT: The new coronavirus disease 2019 (COVID-19) is the latest pathology of international concern. Originating in Wuhan, China, it spread rapidly globally, which is why it was declared a public health emergency. Produced by SARS-CoV-2 it belongs to the genus of betacoronaviruses together with SARS-CoV and MERS-CoV. SARS-CoV-2 has been shown to use angiotensin converting enzyme 2 (ACE2) as a receptor for entry into a host cell. Various studies have demonstrated the expression of this receptor in various organs and tissues, within which the oral cavity and salivary glands have been reported, which have received vital importance in recent times due to their importance as a potential reservoir for this virus. The objective of this review is to understand the role of the salivary glands as a potential reservoir for SARS-CoV-2 and its associated manifestations.

Tratamiento conservador de osteonecrosis maxilar asociada a medicamentos refractaria mediante el uso de protocolo PENTO: reporte de un caso / Tratamento conservador da osteonecrose maxilar associada a medicamentos refratários usando o protocolo PENTO: relato de um caso / Conservative treatment of refractory medication-related osteonecrosis of the jaw using the PENTO protocol: A case report

Resumen Paciente de 78 años consulta por sangrado sin resolución, a nivel del reborde alveolar maxilar izquierdo. Con antecedentes de metástasis óseas tratadas con ácido zoledrónico endovenoso discontinuado por alta médica y tratamiento quirúrgico previo de osteonecrosis maxilar en sitio afectado. Se observó disrupción de continuidad con inflamación a nivel del reborde óseo, con salida de contenido hemático, purulento y necrótico. Radiográficamente se observó radiolucidez difusa y osteolítica del área afectada y tejido necrótico a nivel microscópico. Se realizó aseo del área afectada, enjuagues de clorhexidina 0,12%, administración de amoxicilina/acido clavulánico y de pentoxifilina 400 mg cada 12 horas y tocoferol 1000 UI cada 24 horas. Se evaluó al mes, donde se discontinua antibioterapia y se mantiene régimen establecido con controles cada 2 semanas. A los 6 meses se evidencia resolución completa, con cicatrización de la mucosa y del tejido óseo sin recidiva.

Resumo Paciente de 78 anos consultado por sangramento sem resolução, ao nível do rebordo alveolar superior esquerdo. Com história de metástases ósseas tratadas com ácido zoledrônico endovenoso descontinuado por alta médica e tratamento cirúrgico prévio de osteonecrose maxilar no local afetado. Foi observada interrupção da continuidade com inflamação ao nível da crista óssea, com extravasamento de sangue, conteúdo purulento e necrótico. Radiograficamente, radioluscência difusa e osteolítica da área afetada e tecido necrótico foram observadas ao nível microscópico. A área afetada foi limpa, enxágue com clorexidina 0,12%, amoxicilina / ácido clavulânico e 400 mg de pentoxifilina a cada 12 horas e 1000 UI de tocoferol a cada 24 horas. Foi avaliado em um mês, quando a antibioticoterapia é descontinuada e um regime estabelecido é mantido com controles a cada 2 semanas. Aos 6 meses, é evidenciada resolução completa, com cicatrização da mucosa e do tecido ósseo sem recorrência.

Abstract A 78-year-old patient seeks care for unresolved bleeding on the left maxillary alveolar ridge. He had a history of bone metastasis treated with IV zoledronic acid, which was discontinued after medical discharge and previous surgical treatment of osteonecrosis of the jaws in the affected site. Continuity disruption with inflammation at the bone ridge was observed, with blood, purulent, and necrotic exudate. The radiograph showed diffuse and osteolytic radiolucency of the affected area, and necrotic tissue was detected at a microscopic level. The affected area was rinsed with 0.12% chlorhexidine, 400 mg amoxicillin/clavulanic acid and pentoxifylline was administered every 12 hours, and tocopherol 1000 IU every 24 hours. The area was evaluated after a month. Antibiotic therapy was discontinued, and the patient continued to be monitored every two weeks. At six months, there is complete resolution, and mucosal and bone tissue healed without recurrence.

Recomendaciones en la Atención de Pacientes en Cirugía Maxilofacial Durante la Pandemia de COVID-19 (SARS-CoV-2) / Recommendations in the Care of Patients in Maxillofacial Surgery During the COVID-19 Pandemic (SARS-CoV-2)

RESUMEN: La nueva enfermedad por coronavirus 2019 (COVID-19) es la última patología de preocupación internacional. Originada en Wuhan, China, se extendió rápidamente a nivel mundial, razón por la cual fue declarada una emergencia de salud pública. Sus síntomas principales son fiebre, tos, dolor de garganta, dificultad respiratoria, fatiga, malestar general y la anosmia, que ha sido incorporada recientemente. Sin embargo, también se han descrito múltiples casos asintomáticos que han alarmado a la población general. Esta enfermedad, se caracteriza por su alta tasa de contagio y su mecanismo de propagación es el contacto cercano entre personas y a través de fluidos corporales como la saliva y secreciones de las vías aéreas. El personal de salud es especialmente vulnerable a la infección debido a su gran exposición a las secreciones oronasales de los pacientes, sobre todo, aquellas especialidades médicas y odontológicas cuyo campo de acción se centra en estas áreas, siendo la cirugía oral y maxilofacial una de ellas, teniendo un alto riesgo de transmisión de SARS-CoV-2. Por lo tanto, es fundamental para este personal, seguir protocolos de prevención y control de infecciones, junto con una correcta anamnesis, examen y diagnóstico de los pacientes que permita establecer una priorización en las atenciones quirúrgicas, disminuyendo la propagación del virus. El objetivo de esta revisión es conocer las recomendaciones básicas para la priorización de pacientes y el cuidado en los procedimientos quirúrgicos por parte del equipo de cirugía maxilofacial durante la pandemia por COVID-19.

ABSTRACT: The new coronavirus disease 2019 (COVID-19) is the latest pathology of international concern. Originating in Wuhan, China, it spread rapidly worldwide, which is why it was declared a public health emergency. Its main symptoms are fever, cough, sore throat, shortness of breath, fatigue, general discomfort, and anosmia, which has been recently incorporated. However, multiple asymptomatic cases have also been described that have alarmed the general population. This disease is characterized by its high contagion rate and its propagation mechanism is close contact between people and through bodily fluids such as saliva and airway secretions. Health personnel are especially vulnerable to infection due to their high exposure to patients' oronasal secretions, especially those medical and dental specialties whose field of action focuses on these areas, oral and maxillofacial surgery being one of them, having a high risk of transmission of SARS-CoV-2. Therefore, it is essential for these personnel to follow infection prevention and control protocols, together with a correct anamnesis, examination, and diagnosis of patients, which allows prioritizing surgical care, reducing the spread of the virus. The objective of this review is to know the basic recommendations for patient prioritization and care in surgical procedures by the maxillofacial surgery team during the COVID-19 pandemic.

Detección de COVID -19 (SARS-CoV-2) mediante la saliva: una alternativa diagnóstica poco invasiva / Detection of COVID-19 (SARS-CoV-2) by saliva: a low-invasive diagnostic alternative

La nueva enfermedad por coronavirus, también denominada COVID 19 es la última enfermedad infecciosa de preocupación internacional. Originada en Wuhan, China, se extendió a nivel mundial, resultando en la pandemia 2019-2020 y una Emergencia de Salud Pública de Preocupación Internacional (ESPII) según lo declarado por la Organización Mundial de la Salud (OMS). Esta enfermedad suele cursar con fiebre, tos, dolor de garganta, dificultad respiratoria, fatiga y malestar general, sin embargo, también se han presentado casos asintomáticos. Su diagnóstico se realiza con una combinación tanto de exámenes clínicos, radiológicos y moleculares, donde la prueba de reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) ha sido el examen de elección para el análisis de material genético viral de muestras extraídas del tracto respiratorio superior. Se ha reportado que COVID-19 se transmite persona a persona o por contacto indirecto por gotas, lo que tiene fundamental importancia en procedimientos clínicos dentales y donde la saliva tendría una función crítica en la transmisión de SARS-CoV-2 en la población. Es por esto, que los diagnósticos salivales no invasivos podrían proporcionar una plataforma de detección rápida, temprana y poco invasiva de la infección por COVID-19. El objetivo de esta revisión es determinar los beneficios de la saliva como muestra no invasiva para el diagnóstico de COVID-19.

The new coronavirus disease, also called COVID 19, is the latest infectious disease of international concern. Originating in Wuhan, China, it spread globally, resulting in the 2019-2020 pandemic and a Public Health Emergency of International Concern (ESPII) as declared by the World Health Organization (WHO). This disease usually presents with fever, cough, sore throat, respiratory distress, fatigue and general discomfort; however, asymptomatic cases have been reported. The diagnosis is made with a combination of clinical, radiological and laboratory molecular tests, where the reverse transcriptase polymerase chain reaction (RT-PCR) test has been the alternative of choice for the analysis of viral genetic material from samples taken of upper respiratory tract. COVID-19 has been reported to be transmitted person-to-person or by indirect fluids drop contact, which is of fundamental importance for clinical dental procedures and where saliva would play a critical role in the transmission of SARS-CoV-2 from human to human. For this reason, non-invasive salivary diagnoses could provide a platform for rapid, early and non-invasive detection of COVID19 infection. The objective of this review is to determine the benefits of saliva as a non-invasive sample for the diagnosis of COVID-19.

La atención odontológica a pacientes COVID-19 positivo ¿Qué hacer ante una urgencia? / Dental care for COVID-19 positive patients: what to do in an emergency?

El pasado diciembre en China, se originó un brote de Neumonía producida por una nueva cepa viral de coronavirus o SARS-CoV-2, nunca antes vista en humanos, lo que despertó la atención en el mundo. Asimismo, el 30 de enero fue declarada una emergencia de salud pública de preocupación internacional por la OMS, marcando el inicio de una pandemia altamente patógena denominada ''enfermedad por coronavirus del 2019 (COVID-19)'' que se transmite de persona a persona por medio de secreciones respiratorias. Los principales síntomas que se presentan en los pacientes son: fiebre, tos, dolor de garganta, dificultad respiratoria, fatiga y malestar general; sin embargo existe un porcentaje de personas asintomáticas que representan un alto riesgo de contagio para los profesionales de la salud que trabajan en el área buco-nasal como lo son los cirujanos dentistas. En consecuencia, este estudio tiene como objetivo mostrar las medidas de protección que han sido exitosas en otros países para la atención de personas con COVID-19, de manera que los procedimientos sean realizados de una forma segura tanto para los pacientes como para el equipo de salud, evitando la propagación de la enfermedad.

Last December in China, an outbreak of pneumonia caused by a new viral strain of coronavirus or SARSCoV-2, never seen in humans, originated, which aroused worldwide attention. Likewise, on January 30, a public health emergency of international concern was declared by the WHO, marking the start of a highly pathogenic pandemic called "2019 coronavirus disease (COVID-19)" that is transmitted from person to person by means of respiratory secretions. The main symptoms that appear in patients are fever, cough, sore throat, shortness of breath, fatigue and general malaise; However, there is a percentage of asymptomatic people who represent a high risk of contagion for health professionals who work in the airway and digestive tract, such as dentist. Consequently, this study aims to show the necessary protection measures so that the health team can intervene in patients diagnosed with COVID-19 safely, avoiding the spread of the disease.

The distance from the peroneal tendons sheath to the sural nerve at the posterior tip of the fibula decreases from proximal to distal.

PURPOSE: The aim of this study is to compare the distance from the peroneal tendons sheath to the sural nerve in different points proximally and distally to the tip of the fibula. METHODS: Ten fresh-frozen lower extremities were dissected to expose the nerves and tendons. Having the posterior tip of the fibula as a reference, the distance between the tendons sheath and the sural nerve was measured in each point with a tachometer with three independent different observers. Two measures were taken distally at 1.5 and 2 cm from fibula tip and 3 measures were performed proximally at 2, 3, and 5 cm from fibula tip. Data were described using means, standard deviations, medians, and minimum and maximum values. RESULTS: The average distance between distance between the fibula tip and sural nerve is 16.6 ± 4.4 mm. The average distance between peroneal tendons sheath and the sural nerve at 5 cm, 3 cm, and 2 cm from the proximal fibular tip was 29.6 ± 3.2 mm, 24.2 ± 3.6 mm, and 19.7 ± 2.7 mm, respectively. The average distance between the peroneal tendons sheath and the sural nerve at 2 cm and 1.5 cm distal to fibular tip was 9.1 ± 3.5 mm and 7.8 ± 3.3 mm, respectively. CONCLUSION: The distance from the peroneal tendons sheath to the sural nerve decreases from proximal to distal. As the distance between the peroneal tendons sheath and the sural nerve decreases from proximal to distal, performing the tendoscopy portal more distally would increase the risk of nerve iatrogenic injury.

Andrographolide induces DNA damage in prostate cancer cells.

Prostate cancer (PCa) is the most common diagnosed cancer and is the third cause of cancer mortality in men in the USA. Andrographolide, a diterpenoid lactone isolated from Andrographis paniculata, has shown to possess anticarcinogenic activity in a variety of cancer cells. In this study, we examined the efficacy of Andrographolide in PCa using in vitro and in vivo models. Androgen-independent (PC3) and androgen-dependent (22RV1) cell lines were treated with Andrographolide to determine the effect in cell motility, cell proliferation and apoptosis. Andrographolide decreased PCa cell migration, decreased invasion, and increased cell apoptosis in vitro. Tumor growth was evaluated using an orthotopic xenograft model in which the prostates of SCID mice were injected with 22RV1, and mice were treated three times per week with Andrographolide 10 mg/kg. Andrographolide decreased tumor volume, MMP11 expression and blood vessels formation in vivo. Gene expression analysis identified cellular compromise, cell cycle, and "DNA recombination, replication and repair" as the major molecular and cellular functions altered in tumors treated with Andrographolide. Within DNA repair genes we confirmed increased expression of genes involved in DNA double strand break repair. Consistent with this observation we detected increased γH2AX in Andrographolide treated tumors and in cells in culture. Taken together, these data suggest that Andrographolide inhibits PCa by promoting DNA damage.

[Referrals to a gastroenterology outpatient clinic from primary care: evaluation of two programs]. / Derivación a las consultas de gastroenterología desde atención primaria: evaluación de dos programas.

OBJECTIVES: To analyze the effect of implementing a high-resolution clinic (HRC) and an increasing resolution capacity program in primary care (IRCPPC) for referrals to a gastroenterology outpatient clinic from primary care and the resources used. METHODS: A retrospective and observational study based on a review of referral sheets and databases was performed. We analyzed the number and reason for referrals, delay times and resource consumption in two periods: before (first 4 months of 2007) and after (first 4 months of 2009) the launch of the IRCPPC and HRC. RESULTS: In the first and second periods, 881 and 1076 patients, respectively, referred from primary health care were evaluated in the gastroenterology clinic, with a decrease in the delay time in the second period (80.8 ± 64.34 days vs 36.1 ± 29.12 days, p < 0.001). The most frequent reasons for referral were dyspepsia (27.7%), high-risk of colorectal cancer (17.1%), disturbance of bowel rhythm (18.2%), abdominal pain (16%), and gastroesophageal reflux (11.2%), with no differences between the two periods. Although delay times until the first visit (10.8 ± 9.03 days vs 42.8 ± 28.67 days, p < 0.001) and until discharge (39.6 ± 80.65 days vs 128.6 ± 135.34 days, p < 0.001) were lower in referrals to the HRC, the number of visits (3.6 ± 2.20 vs 3.2 ± 1.95, p = 0.015) and the cost of referrals (592.7 ± 421.50 € vs 486.0 ± 309.66 €, p < 0.001) was higher. CONCLUSIONS: In the study period the number of referrals increased, while the delay time decreased. Although the HRC reduces delay times, it is associated with an increase in health resource use.

[Effect of the implementation of a program to improve referrals by primary care on appropriateness and wait times in endoscopic examinations]. / Efecto de la implantación de un programa de mejora de la capacidad resolutiva de atención primaria en la adecuación y la demora de las exploraciones endoscópicas.

INTRODUCTION: Within a program to improve referrals by primary care (PC) in Ourense (Spain), we implemented practice guidelines on dyspepsia and rectal bleeding. Our aim was to evaluate the reasons for referral to endoscopy, the appropriateness of these referrals, and wait times. MATERIAL AND METHODS: We performed a retrospective cohort study in the Ourense health area between February 2009 and January 2010. The endoscopies performed with the indications of dyspepsia and rectal bleeding requested directly from PC were compared with those referred initially to specialist care (SC). The reasons for the referral, the priority of the endoscopy, compliance with the protocol, endoscopic finding and the wait time from referral were gathered. RESULTS: During the period analyzed, 158 upper gastrointestinal endoscopies (SC: 121; PC: 37) and 243 colonoscopies (SC: 193; PC: 50) were performed with the indications of dyspepsia and rectal bleeding. Among endoscopies, 34.5% and 77.7% were requested with high priority from PC and SC, respectively (p<0.001). The criteria for referral were met in 86.5% of upper gastrointestinal endoscopies and in 82% of colonoscopies requested from PC. No differences were found in endoscopic findings. The median wait time from referral was lower in upper gastrointestinal endoscopy (PC: 105±5.5 days, SC: 174±17.8 days; p: 0.003) and colonoscopies (PC: 101±11.8 days, SC: 187±9.6 days; p<0.001) referred from PC. CONCLUSIONS: The use of the program for improved referrals by PC reduces wait times. The examinations requested complied with the indications.