Pharmacological Inhibition of p-21 Activated Kinase (PAK) Restores Impaired Neurite Outgrowth and Remodeling in a Cellular Model of Down Syndrome.

Down syndrome (DS) is characterized by the trisomy of chromosome 21 and by cognitive deficits that have been related to neuronal morphological alterations in humans, as well as in animal models. The gene encoding for amyloid precursor protein (APP) is present in autosome 21, and its overexpression in DS has been linked to neuronal dysfunction, cognitive deficit, and Alzheimer's disease-like dementia. In particular, the neuronal ability to extend processes and branching is affected. Current evidence suggests that APP could also regulate neurite growth through its role in the actin cytoskeleton, in part by influencing p21-activated kinase (PAK) activity. The latter effect is carried out by an increased abundance of the caspase cleavage-released carboxy-terminal C31 fragment. In this work, using a neuronal cell line named CTb, which derived from the cerebral cortex of a trisomy 16 mouse, an animal model of human DS, we observed an overexpression of APP, elevated caspase activity, augmented cleavage of the C-terminal fragment of APP, and increased PAK1 phosphorylation. Morphometric analyses showed that inhibition of PAK1 activity with FRAX486 increased the average length of the neurites, the number of crossings per Sholl ring, the formation of new processes, and stimulated the loss of processes. Considering our results, we propose that PAK hyperphosphorylation impairs neurite outgrowth and remodeling in the cellular model of DS, and therefore we suggest that PAK1 may be a potential pharmacological target.

Long-term Clinical Outcomes of a Spanish Cohort of Metastatic Renal Cell Carcinoma Patients with a Complete Response to Sunitinib.

INTRODUCTION: The long-term clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) and a complete response (CR) to the tyrosine kinase inhibitor (TKI) sunitinib are poorly known. The characteristics of these patients could reveal previously undetected associations with clinical variables. PATIENTS AND METHODS: This observational, retrospective study (ATILA) used data from a registry of patients with mRCC who had received first-line sunitinib and had achieved CR from 2007 to 2018 in Spain. RESULTS: Sixty-two patients with CR were included; 48 patients (77.4%) received sunitinib in monotherapy and 14 (22.6%) combined with or followed by local treatment. Median age was 58.5 years (range, 32-81). Most patients (79.0%) had clear cell histology and had undergone previous nephrectomy (90.3%). The majority (70.2%) had an intermediate IMDC prognosis, 23% favorable and 7.0% poor. The median time on treatment with sunitinib was 28.2 months (IQR, 16.7-41.0) and the median time to CR was 10.9 months (IQR, 7.2-19.3). After a median follow-up of 8 years (range, 3-13 years), the median PFS was not reached. The overall median duration of complete response was 64.1 months (IQR, 32.2-99.4). The tolerance and safety profile of sunitinib was consistent with previous reports. CONCLUSION: Durable CR to sunitinib was observed in patients regardless the prognosis group, metastasis site or histology type, with 75% of patients remaining in CR after 10 years. CLINICALTRIALS: gov: NCT03916458.

Intervenciones de terapia ocupacional con personas mayores en procesos finales de vida en hospitales públicos / Intervenções de terapia ocupacional com pessoas idosas em processos de fim de vida em hospitais públicos / Occupational therapy interventions with elderly people at the end-of-life processes in public hospitals

Resumen Introducción La intervención de terapia ocupacional con personas mayores en procesos de fin de vida en contextos hospitalarios presenta escasa documentación científica en Chile. Dado el aumento de la población mayor, la alta prevalencia de enfermedades crónicas en ella y las tasas de mortalidad hospitalaria, se identifica la necesidad de revisar las intervenciones que se realizan en los procesos de fin de vida de las personas mayores. Objetivo Caracterizar intervenciones de terapia ocupacional con personas mayores que cursan su proceso de fin de vida, desde la percepción de terapeutas ocupacionales dedicados/as al área, en contextos hospitalarios públicos de Chile. Método La investigación es de tipo cualitativa enmarcada dentro del paradigma constructivista bajo el enfoque fenomenológico, utilizando como técnica de recolección de información la entrevista semiestructurada y posterior análisis de contenido. La muestra de estudio está compuesta por terapeutas ocupacionales que ejercen su labor en hospitales públicos del país. Resultados Se identifica a terapeutas ocupacionales como agentes que otorgan cuidados humanizantes y acompañamiento durante las intervenciones en procesos de fin de vida, y a las familias como un facilitador del mismo. Se releva una visión integral de la persona en estos procesos. Conclusiones Existe consenso en el enfoque e intervenciones de terapia ocupacional identificadas por las/os participantes, y resulta similar a lo descrito en la literatura internacional. Faltan lineamientos de política pública local que permitan definir de mejor manera el rol profesional en este contexto.

Resumo Introdução A intervenção da terapia ocupacional com idosos nos processos de fim de vida em contextos hospitalares apresenta pouca documentação científica no Chile. Diante do aumento da população idosa, da alta prevalência de doenças crônicas nesta população e das taxas de mortalidade hospitalar, identifica-se a necessidade de rever as intervenções realizadas nos processos de fim de vida do idoso. Objetivo Caracterizar as intervenções de terapia ocupacional com idosos em processo de fim de vida, a partir da percepção de terapeutas ocupacionais da área, em contextos hospitalares públicos no Chile. Método A pesquisa é do tipo qualitativo na perspectiva do paradigma construtivista sob a abordagem fenomenológica, utilizando-se de entrevista semiestruturada como técnica de coleta de informações e posterior análise de conteúdo. A amostra do estudo é composta por terapeutas ocupacionais que atuam em hospitais públicos no Chile. Resultados Os terapeutas ocupacionais são identificados como agentes que prestam atendimento humanizado e apoio durante as intervenções nos processos de fim de vida, e à família, principalmente como facilitadora deste processo. Nesses momentos, revela-se uma visão integral da pessoa. Conclusões Há consenso sobre a abordagem e intervenções da terapia ocupacional identificadas pelos participantes, sendo semelhante ao descrito na literatura estrangeira. Faltam diretrizes de políticas públicas locais que permitam uma melhor definição do papel do profissional nesse contexto.

Abstract Introduction The intervention of occupational therapy with elderly people in end-of-life processes in hospital contexts presents short scientific documentation in Chile. Given the increase in the elderly population, their high prevalence of chronic diseases, and the hospital mortality rates, the need to review the interventions carried out in the end-of-life processes of the elderly are identified. Objective To characterize occupational therapy interventions with elderly people who are in their end-of-life process, from the perception of occupational therapists dedicated to the area, in public hospital contexts in Chile. Method The research is of a qualitative type framed within the constructivist paradigm under the phenomenological approach, using the semi-structured interview as an information collection technique and subsequent content analysis. The study sample is made up of occupational therapists who work in public hospitals in the country. Results Occupational therapists are identified as agents that provide humanizing care and support during interventions in end-of-life processes, and families mainly as a facilitator of the same. In these processes, an integral vision of the person is revealed. Conclusions There is consensus on the occupational therapy approach and interventions identified by the participants, and it is similar to what is described in the international literature. There is a lack of local public policy guidelines that allow a better definition of the professional role in this context.

Ocular cysticercosis in pediatric patient / Cisticercose ocular em paciente pediátrico

ABSTRACT Ocular cysticercosis is a parasitic infection caused by Taenia solium. Its early diagnosis and treatment decreases the possibility of visual morbidity. It can either compromise the anterior chamber or the posterior segment, which translates into an very variable and interspecific presentation that changes depending on the site of the infection. It is important to report this case due to its low presentation rate and the fact that a high suspicion index is required to make an assertive and timely diagnosis. This is especially important in geographical areas that are endemic to this parasite due to the direct relationship between an early diagnosis and treatment and better visual outcomes. In this case report, we will discuss the multidisciplinary interventions of a pediatric patient in a high complexity hospital.

RESUMO A cisticercose ocular é uma infecção parasitária causada pela Taenia solium. O diagnóstico e tratamento precoces diminuem a possibilidade de morbidade visual. Ela pode comprometer a câmara anterior ou o segmento posterior, o que se traduz em uma apresentação muito variável e interespecífica, que muda dependendo do local da infecção. É importante relatar esse caso devido à sua baixa taxa de apresentação e ao fato de que é necessário um alto índice de suspeita para fazer um diagnóstico assertivo e oportuno. Isso é especialmente importante em áreas geográficas endêmicas para esse parasita, devido à relação direta entre diagnóstico e tratamento precoces e melhores resultados visuais. Neste relato de caso, discutiremos as intervenções multidisciplinares de um paciente pediátrico em um hospital de alta complexidade.

Contribución de las intervenciones de terapia ocupacional en el abordaje de personas mayores hospitalizadas en Unidades Geriátricas de Agudos: una revisión narrativa / Contribuição das intervenções da terapia ocupacional na abordagem do idoso internado em Unidades Geriátricas Agudas: uma revisão narrativa / Contribution of occupational therapy interventions in the approach of elderly people hospitalized in Acute Geriatric Units: a narrative review

Resumen Introducción Las Unidades Geriátricas de Agudos (UGAs) son unidades especializadas en atención de Personas Mayores (PM). Específicamente en Chile, existen pocos profesionales dedicados a esta área, pese a establecer más UGAs con un equipo interdisciplinario. Desde terapia ocupacional es posible un abordaje desde una perspectiva ocupacional, no obstante, se encontró escasa evidencia que explicite la contribución de terapia ocupacional en UGAs en el contexto chileno. Objetivo Resumir la contribución de las intervenciones realizadas por terapeutas ocupacionales a personas mayores hospitalizadas en Unidades Geriátricas de Agudos, revisando literatura nacional como internacional. Metodología Revisión bibliográfica narrativa, entre octubre del 2021 y enero del 2022. Resultados Los principales resultados destacan la contribución de terapia ocupacional para el abordaje de la fragilidad en PM, en intervenciones llevadas a cabo por equipos interdisciplinarios, la promoción y respeto por la autonomía e independencia (particularmente en Actividades de la Vida Diaria Básicas e Instrumentales), la recuperación funcional y la preparación del alta, contribuyendo a la reducción de las tasas de re-hospitalización. Conclusión La participación de la terapia ocupacional en UGAs aporta herramientas y fortalece las habilidades de las PM con el fin de permitirles desenvolverse efectivamente en sus ocupaciones, de forma independiente y autónoma en diversos contextos, principalmente en actividades de la vida diaria. Además, se busca concientizar sobre la importancia de aumentar la especialización en esta área y la necesidad de aumentar la cantidad de UGAs a nivel nacional.

Resumo Introdução As Unidades Geriátricas Agudas (UGAs) são unidades especializadas no atendimento ao idoso. Especificamente no Chile, há poucos profissionais dedicados a essa área, apesar de estabelecer unidades geriátricas mais agudas com equipe interdisciplinar. A partir da terapia ocupacional é possível uma abordagem a partir de uma perspectiva ocupacional, no entanto, foram encontradas poucas evidências que expliquem a contribuição da terapia ocupacional em UGAs no contexto chileno. Objetivo Resumir a contribuição das intervenções realizadas por terapeutas ocupacionais a idosos internados em UGAs, revisando a literatura nacional e internacional. Metodologia Revisão bibliográfica narrativa, entre outubro de 2021 e janeiro de 2022. Resultados Os principais resultados destacam a contribuição da terapia ocupacional no enfrentamento da fragilidade em idosos nas intervenções realizadas por equipes interdisciplinares, na promoção e respeito à autonomia e independência (particularmente nas Atividades Básicas e Instrumentais de Vida Diária), na recuperação funcional e na preparação para a alta, contribuindo para a redução das taxas de reinternação. Conclusão A participação da terapia ocupacional na UGAs fornece ferramentas e fortalece as habilidades dos idosos para permitir que eles realizem de forma eficaz em suas ocupações, de forma independente e autônoma em vários contextos, principalmente nas atividades da vida diária. Além disso, procura sensibilizar para a importância de aumentar a especialização nesta área e para a necessidade de aumentar o número de UGAs a nível nacional.

Abstract Introduction The Acute Geriatric Units (AGU) are units specialized in caring for the elderly people. Specifically in Chile, there are few professionals dedicated to this area, despite establishing more acute geriatric units with an interdisciplinary team. From occupational therapy, an approach from an occupational perspective is possible. However, little evidence was found that explains the contribution of occupational therapy in AGU in the Chilean context. Objetive Summarize the contribution of the interventions carried out by occupational therapists to elderly people hospitalized in AGU, reviewing national and international literature. Methodology Narrative bibliographic review, between October 2021 and January 2022. Results The main results highlight the contribution of occupational therapy to address frailty in older people in interventions carried out by interdisciplinary teams, the promotion and respect for autonomy and independence (in Basic and Instrumental Activities of Daily Living), the functional recovery and preparation for discharge, contributing to the reduction of rehospitalization rates. Conclusion The participation of occupational therapy in the AGU provides tools and strengthens the skills of older people in order to allow them to function effectively in their occupations, independently and autonomously in various contexts, mainly in activities of daily living. In addition, it seeks to raise awareness of the importance of increasing specialization in this area and the need to increase the number of AGU nationwide.

Evaluation of the communication of nursing students in the simulated teleconsultation: A cross-sectional study.

INTRODUCTION: The COVID-19 pandemic presented universities with the challenge of virtualizing the teaching-learning process. Simulated teleconsultation has been used in undergraduate training, which allows nursing students to interact with simulated patients remotely. Studies have identified that distance imposes communication barriers on all elements-sender, receiver and message-and in both forms of transmission: verbal and nonverbal. OBJECTIVE: To describe the communication of nursing students in teleconsultation with simulated patients in the context of primary health care. METHODS: This was a descriptive, cross-sectional study of 92 fifth-year nursing students. The communication variable was measured with the Connect Identify Understand Agree Help scale. In the data analysis, the mean and standard deviation of the scores on the 29 items of the scale were determined, as were the mean values for the total scale and for the 3 domains of the scale. RESULTS: The items that presented an average of less than 1 were primarily those related to the Agree and Help to Act domain. The total mean was 1.15, and the means for the domains Connect, Identify and Understand Problems and Agree and Help to Act were 1.53, 0.90 and 1.28, respectively. A weakness in the exploration of the psychosocial context of the simulated patients was observed. CONCLUSIONS: The results of this study, which evaluated communication in the context of distance care, corroborate the evidence regarding communication in real or simulated face-to-face situations. Studies that compare communication in various teaching-learning contexts, whether real or virtual, face-to-face or at a distance, are recommended.

A Case Study to Dissect Immunity to SARS-CoV-2 in a Neonate Nonhuman Primate Model.

Most children are less severely affected by coronavirus-induced disease 2019 (COVID-19) than adults, and thus more difficult to study progressively. Here, we provide a neonatal nonhuman primate (NHP) deep analysis of early immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in blood and mucosal tissues. In addition, we provide a comparison with SARS-CoV-2-infected adult NHP. Infection of the neonate resulted in a mild disease compared with adult NHPs that develop, in most cases, moderate lung lesions. In concomitance with the viral RNA load increase, we observed the development of an early innate response in the blood, as demonstrated by RNA sequencing, flow cytometry, and cytokine longitudinal data analyses. This response included the presence of an antiviral type-I IFN gene signature, a persistent and lasting NKT cell population, a balanced peripheral and mucosal IFN-γ/IL-10 cytokine response, and an increase in B cells that was accompanied with anti-SARS-CoV-2 antibody response. Viral kinetics and immune responses coincided with changes in the microbiota profile composition in the pharyngeal and rectal mucosae. In the mother, viral RNA loads were close to the quantification limit, despite the very close contact with SARS-CoV-2-exposed neonate. This pilot study demonstrates that neonatal NHPs are a relevant model for pediatric SARS-CoV-2 infection, permitting insights into the early steps of anti-SARS-CoV-2 immune responses in infants.

Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases.

Background: The female reproductive tract (FRT) mucosa is the first line of defense against sexually transmitted infection (STI). FRT environmental factors, including immune-cell composition and the vaginal microbiota, interact with each other to modulate susceptibility to STIs. Moreover, the menstrual cycle induces important modifications within the FRT mucosa. Cynomolgus macaques are used as a model for the pathogenesis and prophylaxis of STIs. In addition, their menstrual cycle and FRT morphology are similar to women. The cynomolgus macaque vaginal microbiota is highly diverse and similar to dysbiotic vaginal microbiota observed in women. However, the impact of the menstrual cycle on immune markers and the vaginal microbiota in female cynomolgus macaques is unknown. We conducted a longitudinal study covering three menstrual cycles in cynomolgus macaques. The evolution of the composition of the vaginal microbiota and inflammation (cytokine/chemokine profile and neutrophil phenotype) in the FRT and blood was determined throughout the menstrual cycle. Results: Cervicovaginal cytokine/chemokine concentrations were affected by the menstrual cycle, with a peak of production during menstruation. We observed three main cervicovaginal neutrophil subpopulations: CD11bhigh CD101+ CD10+ CD32a+, CD11bhigh CD101+ CD10- CD32a+, and CD11blow CD101low CD10- CD32a-, of which the proportion varied during the menstrual cycle. During menstruation, there was an increase in the CD11bhigh CD101+ CD10+ CD32a+ subset of neutrophils, which expressed higher levels of CD62L. Various bacterial taxa in the vaginal microbiota showed differential abundance depending on the phase of the menstrual cycle. Compilation of the factors that vary according to hormonal phase showed the clustering of samples collected during menstruation, characterized by a high concentration of cytokines and an elevated abundance of the CD11bhigh CD101+ CD10+ CD32a+ CD62L+ neutrophil subpopulation. Conclusions: We show a significant impact of menstruation on the local environment (cytokine production, neutrophil phenotype, and vaginal microbiota composition) in female cynomolgus macaques. Menstruation triggers increased production of cytokines, shift of the vaginal microbiota composition and the recruitment of mature/activated neutrophils from the blood to the FRT. These results support the need to monitor the menstrual cycle and a longitudinal sampling schedule for further studies in female animals and/or women focusing on the mucosal FRT environment.

The unforeseen intracellular lifestyle of Enterococcus faecalis in hepatocytes.

Enterococcus faecalis is a bacterial species present at a subdominant level in the human gut microbiota. This commensal turns into an opportunistic pathogen under specific conditions involving dysbiosis and host immune deficiency. E. faecalis is one of the rare pathobionts identified to date as contributing to liver damage in alcoholic liver disease. We have previously observed that E. faecalis is internalized in hepatocytes. Here, the survival and fate of E. faecalis was examined in hepatocytes, the main epithelial cell type in the liver. Although referred to as an extracellular pathogen, we demonstrate that E. faecalis is able to survive and divide in hepatocytes, and form intracellular clusters in two distinct hepatocyte cell lines, in primary mouse hepatocytes, as well as in vivo. This novel process extends to kidney cells. Unraveling the intracellular lifestyle of E. faecalis, our findings contribute to the understanding of pathobiont-driven diseases.

Urgencia odontopediátrica asociada a Bola Adiposa de Bichat: informe de un caso / Pediatric dental emergency associated with Bichat ́s fat pad: a case report

Objetivo: Presentar la resolución quirúrgica de un caso clínico poco frecuente en un paciente pediátrico luego de ha- ber sufrido la herniación traumática de la Bola Adiposa de Bichat. Caso clínico: Un paciente de 3 años concurre a la guar- dia del Hospital Interzonal Especializado Materno Infantil "Don Victorio Tetamanti" de Mar del Plata, luego de haber sufrido un traumatismo que le provocó el desplazamiento par- cial de la Bola Adiposa de Bichat. Si bien este tipo de urgencias es poco frecuente, es impor- tante tener los conocimientos para un correcto diagnóstico y tratamiento (AU))

Aim: To present the surgical resolution of an infrequent clinical case in a pediatric patient who suffered traumatic herniation of Bichat's fat pad. Clinical case: A 3-year-old patient who visited the Emergency Service at the "Don Victorio Tetamanti" Hospital in Mar del Plata after suffering a trauma which caused the partial displacement of Bichat's fat pad. Although this type of emergency is quite rare, it is important to know how to per- form proper diagnosis and treatment (AU)

Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer.

INTRODUCTION: Topotecan is approved as second-line treatment for small cell lung cancer (SCLC). Irinotecan is also frequently used given its more convenient schedule and superior tolerability. Preclinical studies support disialoganglioside (GD2) as an SCLC target and the combination of dinutuximab, an anti-GD2 antibody, plus irinotecan in this setting. We tested dinutuximab/irinotecan versus irinotecan or topotecan as second-line therapy in relapsed/refractory (RR) SCLC. MATERIALS AND METHODS: Patients with RR SCLC and Eastern Cooperative Oncology Group performance status 0-1 were randomized 2:2:1 to receive dinutuximab 16-17.5 mg/m2 intravenous (IV)/irinotecan 350 mg/m2 IV (day 1), irinotecan 350 mg/m2 IV (day 1), or topotecan 1.5 mg/m2 IV (days 1-5) in 21-day cycles. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR; complete response [CR] + partial response [PR]), and clinical benefit rate (CBR; CR + PR + stable disease). Safety/tolerability were also assessed. RESULTS: A total of 471 patients were randomized to dinutuximab/irinotecan (n = 187), irinotecan (n = 190), or topotecan (n = 94). Age, sex, performance status, prior therapies, and metastatic disease sites were similar between groups. Survival and response rates were not improved for patients receiving dinutuximab/irinotecan versus those receiving irinotecan or topotecan (median OS 6.9 vs 7.0 vs 7.4 months [p = 0.3132]; median PFS 3.5 vs 3.0 vs 3.4 months [p = 0.3482]; ORR confirmed 17.1% vs 18.9% vs 20.2% [p = 0.8043]; and CBR 67.4% vs 58.9% vs 68.1% [p = 0.0989]), respectively. Grade 3/4 adverse events (≥5% receiving dinutuximab/irinotecan) included neutropenia, anemia, diarrhea, and asthenia. CONCLUSIONS: Dinutuximab/irinotecan treatment did not result in improved OS in RR SCLC versus irinotecan alone. Irinotecan administered every 21 days demonstrated comparable activity to topotecan administered daily × 5 every 21 days. CLINICALTRIALS: gov Identifier. NCT03098030.

Neonatal Immune System Ontogeny: The Role of Maternal Microbiota and Associated Factors. How Might the Non-Human Primate Model Enlighten the Path?

Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant's microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother-fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant's microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant's health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path.

Osimertinib in advanced EGFR-T790M mutation-positive non-small cell lung cancer patients treated within the Special Use Medication Program in Spain: OSIREX-Spanish Lung Cancer Group.

BACKGROUND: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain. METHODS: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016-December 2018) from 30 sites. PRIMARY OBJECTIVE: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources. RESULTS: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted. CONCLUSION: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events. TRIAL REGISTRATION: Clinical trial registration number: NCT03790397 .

High volume on line hemodiafiltration in dialysis pregnant patients: predilutional or postdilutional?

Although the frequency of pregnancy in women on chronic dialysis is extremely low, it is associated with severe maternal and perinatal morbidity and mortality. This situation represents a challenge for the therapeutic team, which requires multidisciplinary management, as well as measures to adequate dialysis treatment. Such efforts include increasing the time and frequency of dialysis session, maintaining low uremia levels and ensuring hemodynamic stability by avoiding intra-treatment arterial hypotension and hydro electrolytic fluctuations. Regarding the dialysis modality, literature makes references to hemodialysis or peritoneal dialysis in pregnancy women, but little is known about the of high volume online hemodiafiltration (HVHDF) as well as the appropriate type of replacement fluid (pre-dilution or post-dilution). We present two cases of patients who were pregnant while being treated with HVHDF modality and had a favorable evolution, where the decision to continue with this dialysis modality was motivated by a best hemodynamic stability and the highest clearance of all types of uremic toxins offered by HVHDF.

Efficacy and safety of Nivolumab in older patients with pretreated lung cancer: A subgroup analysis of the Galician lung cancer group.

BACKGROUND: Nivolumab is an anti PD1 immunotherapy drug approved for advanced Non-Small Cell Lung Cancer (NSCLC) patients who previously received at least one prior line of treatment. Older patients are often not represented in clinical trials and drugs with acceptable safety profiles are necessary. We aim to report the efficacy and safety profile of Nivolumab in the real-world older subgroup of the Galician lung cancer group study. PATIENTS AND METHODS: We retrospectively reviewed 188 advanced NSCLC patients treated with at least one prior therapy. We collected data from patients who were ≥70 years old treated with Nivolumab in second or subsequent lines. Patient characteristics, treatment efficacy (overall survival, progression-free survival, and response rate), and safety profile were reported. RESULTS: Thirty-eight patients aged ≥70 years were included in the subgroup analysis. The median age was 74.5 years, a high percentage of patients were males (95%), most had a Performance Status of 1 (79%) and only 13% were non-smokers. The predominant histology was adenocarcinoma (53%), and 18% of patients received 2 or more lines. The median Progression-Free Survival was 7.53 months (CI 4.3-17.3, p = 0.15) and the median Overall Survival was 14.85 months (CI 10.5-20.7, p = 0.44). The objective response rate was 42%. No new adverse events were reported in comparison to a global population. CONCLUSIONS: The efficacy and safety profile of Nivolumab in advanced NSCLC patients treated with at least one prior therapy and age ≥70 years old can be overlapped to a global population. Further prospective trials are needed to define and confirm these results.

PD-(L)1 Inhibitors in Combination with Chemotherapy as First-Line Treatment for Non-Small-Cell Lung Cancer: A Pairwise Meta-Analysis.

The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57-0.65, p < 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67-0.86; p < 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70-2.63, p < 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC.