Intrathecal Antibody Production in Two Cases of Yellow Fever Vaccine Associated Neurotropic Disease in Argentina

During the period 2007?2008 several epizootics of Yellow fever with dead of monkeys occurredin southeastern Brasil, Paraguay, and northeastern Argentina. In 2008 after a Yellow fever outbreak an exhaustive prevention campaign took place in Argentina using 17D live attenuatedYellow fever vaccine. This vaccine is considered one of the safest live virus vaccines, although serious adverse reactions may occur after vaccination, and vaccine-associated neurotropicdisease are reported rarely. The aim of this study was to confirm two serious adverseevents associated to Yellow fever vaccine in Argentina, and to describe the analysis performedto assess the origin of specific IgM against Yellow fever virus (YFV) in cerebrospinalfluid (CSF). Both cases coincided with theYellow fever vaccine-associated neurotropicdisease case definition, being clinical diagnosis longitudinal myelitis (case 1) and meningoencephalitis (case 2). Specific YFV antibodies were detected in CSF and serum samples in both cases by IgM antibody-capture ELISA. No other cause of neurological disease wasidentified. In order to obtain a conclusive diagnosis of central nervous system (CNS) infection the IgM antibody index (AIIgM) was calculated. High AIIgM values were found in both cases indicating intrathecal production of antibodies and, therefore, CNS post-vaccinal YFV infection could be definitively associated to YFV vaccination.Fil: Pires Marczeski, Fanny Clara. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Martinez, Valeria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Nemirovsky, Corina. Hospital Italiano; ArgentinaFil: Padula, Paula Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentin

Person-to-Person Transmission of Andes Virus

Epidemiologic and genetic data show that person-to-person spread likely took place during the prodromal phase or shortly after it ended

First Evidence of Akodon-Borne Orthohantavirus in Northeastern Argentina

Orthohantaviruses (genus Orthohantavirus, family Hantaviridae) are the etiologic agents of Hantavirus Pulmonary Syndrome in the Americas. In South America, orthohantaviruses are highly diverse and are hosted by sigmodontine rodents (subfamiliy Sigmodontinae, family Cricetidae), an also diverse group of rodents. The aims of this work were to (1) identify orthohantavirus hosts and (2) to study the spatial and temporal variations in the prevalence of infection and their associations with community, environmental and individual characteristics, in different environments of Misiones province, northeastern Argentina. Live-capture sessions were carried out during two years in different land uses, with a trapping effort of 31,653 trap nights. We captured 719 individuals from the species Akodon montensis, Rattus rattus, Mus musculus, Calomys tener, Thaptomys nigrita, Oligoryzomys nigripes, Euryoryzomys russatus, Oligoryzomys flavescens, Brucepattersonius sp., and Juliomys pictipes. Antibodies against orthohantavirus were detected in Akodon montensis in one natural protected and one periurban areas, and it was the most abundant species in almost every study sites. We observed the presence of spatial focality of orthohantavirus infection and a positive association with host abundance suggesting the existence of a threshold density. At the individual level, large, reproductively active, and male individuals were more likely to have antibodies against orthohantavirus. This is the first record of orthohantavirus infection in A. montensis in Argentina, which shows the importance of investigations about emerging diseases.Fil: Burgos, Eliana Florencia. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Medicina Tropical.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vadell, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Medicina Tropical.; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Salomón, Oscar Daniel. Administracion Nacional de Laboratorios E Institutos de Salud "dr. Carlos G. Malbran". Instituto Nacional de Medicina Tropical.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez Villafañe, Isabel Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

Hantavirus Pulmonary Syndrome in Tucumán province associated to an unexpected viral genotype

We describe the characterization of the viral genotype involved in the first case of hantavirus pul-monary syndrome reported in Tucumán, a Northwestern province of Argentina. A 23-year-old woman, with no record of travel history and previously diagnosed with an antiphospholipid syndrome, died after 11 days of severe cardiopulmonary insufficiency. Among the four endemic regions of hantavirus pulmonary syndrome in Argentina, the Northwest Region has the highest incidence, exceeding 50% of all reported cases in the country. Until now, only Salta and Jujuy (2 out of the 6 provinces composing the Northwest Region), reported cases of hantavirus pulmonary syndrome, all of which occurred in the Yungas Forest area. Remarkably, the viral genotype characterized in this case showed higher nucleotide identity with the Andes-BsAs genotype most prevalent in Buenos Aires province, located 1400 km apart from Tucumán, than with any of the commonly found genotypes in the Northwest Region. The Andes-BsAs genotype has been associated with 30% lethality and interhuman transmission in Buenos Aires province. Interhuman transmission cannot be ruled out in the present case.Fil: Ciancaglini, Matías. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Torres Cabrero Clara. Hospital Italiano; ArgentinaFil: Alonso Daniel. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; ArgentinaFil: Bassi, Sabrina Cecilia. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Adm.nacional de Laboratorio E Instituto de Salud "dr.c.g.malbran". Instituto Nacional de Enfermedades Infecciosas. Departamento de Virologia; Argentin

Ampliación de la distribución del Orthohantavirus genotipo Pergamino: Primer registro en la Provincia de Entre Ríos, Argentina

Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease of the Americas. Eight native rodent species have been identified as HPS virus reservoirs in Argentina. The aim of this work was to detect the orthohantavirus genotypes present in a rodent community that inhabits a zone where a fatal HPS case occurred within an endemic locality of Central Argentina. We captured 27 rodents with a trapping effort of 723 trap nights. We detected 14.3% of infected Akodon azarae with the Pergamino genotype. This result expands the known distribution of this orthohantavirus. Although the Pergamino genotype has not been associated with human cases, the information about its distribution is relevant for risk assessment against potential changes in the virus infectivity.El síndrome pulmonar por hantavirus (SPH) es una enfermedad infecciosa emergente en América. Ocho especies de roedores nativos han sido identificadas como reservorios del virus causante del SPH en la Argentina. El objetivo de este trabajo fue detectar los genotipos de orthohantavirus presentes en una comunidad de roedores que habita en una zona donde ocurrió un caso fatal de SPH, en una localidad endémica de Argentina central. Se capturaron 27 individuos con un esfuerzo de 723 trampas-noche. Se detectó un 14,3% de Akodon azarae infectados con el genotipo pergamino. Este resultado amplía el conocido rango de distribución de este orthohantavirus. A pesar de que el genotipo pergamino no ha sido asociado con casos humanos hasta el momento, la información sobre su distribución es relevante para analizar el riesgo ante un potencial cambio en la infectividad del virus.Fil: Gomez Villafañe, Isabel Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; ArgentinaFil: Burgos, Eliana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Medicina Tropical; ArgentinaFil: Coelho, Rocío María. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Garcilazo Amatti, Jerónimo. Ministerio de Salud de la Nación. Dirección de Epidemiología; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; Argentin

Delayed viral clearance despite high number of activated T cells during the acute phase in Argentinean patients with hantavirus pulmonary syndrome

Background: The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction. Although an exacerbated immune response is thought to be implicated in pathogenesis, clear evidence is still elusive. As orthohantaviruses are not cytopathic CD8+ T cells are believed to be the central players involved in pathogenesis. Methods: Serum and blood samples from Argentinean HPS patients were collected from 2014 to 2019. Routine white blood cell analyses, quantification and characterization of T-cell phenotypic profile, viral load, neutralizing antibody response and quantification of inflammatory mediators were performed. Findings: High numbers of activated CD4+ and CD8+ T cells were found in all HPS cases independently of disease severity. We found increased levels of some proinflammatory mediators during the acute phase of illness. Nonetheless, viral RNA remained high, showing a delay in clearance from blood up to late convalescence, when titers of neutralizing antibodies reached a high level. Interpretation: The high activated phenotypic profile of T cells seems to be unable to resolve infection during the acute and early convalescent phases, and it was not associated with the severity of the disease. Thus, at least part of the activated T cells could be induced by the dysregulated inflammatory response in an unspecific manner. Viral clearance seems to have been more related to high titers of neutralizing antibodies than to the T-cell response. Funding: This work was supported mainly by the Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos Malbrán”. Further details of fundings sources is included in the appendix.Fil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Lewis, Lorena Cecilia. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; ArgentinaFil: Olivera, Camila Paula. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; ArgentinaFil: Rosario Anselmo, Constanza. Provincia del Chubut. Servicio de Salud Mental. Hospital Zonal de Esquel; ArgentinaFil: García, Marina. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Alonso, Daniel Oscar. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Dighero Kemp, Bonnie. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Sharma, Heema. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Kuhn, Jens H.. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Di Paola, Nicholas. Center For Genome Sciences, U.s. Army Medical Research; Estados UnidosFil: Sanchez Lockhart, Mariano. Center For Genome Sciences, U.s. Army Medical Research; Estados UnidosFil: Palacios, Gustavo. Center For Genome Sciences, U.s. Army Medical Research; Estados UnidosFil: Schierloh, Luis Pablo. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentin

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients

[Simple Summary] Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of circulating tumor cells and clusters from the central venous catheter and portal blood. Circulating tumor cells were isolated using an immunomagnetic selection and were detected by microscopy using immunocytochemistry staining. In conclusion, the circulating tumor cell number in portal blood identifies a death risk in patients with early pancreatic cancer.[Abstract] Background. Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). Methods. In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. Results. CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. Conclusions. CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.This research was funded by Carlos III Health Institute (Health Research Fund) grant number PI16/01465 and PI19/01821 (Co-financed by the European Regional Development Fund “A way to make Europe”)

Uso consensuado de un recurso escaso: desarrollo participativo de guías de buenas prácticas ganaderas para humedales patagónicos

El uso y manejo sostenible de humedales patagónicos (mallines), fuente estratégica de agua y forraje para la región, requiere cada vez mayor atención en un escenario de cambio climático e historia de desertificación que amenazan la provisión de servicios ecosistémicos. En este trabajo se presenta el avance en Patagonia del Proyecto de INTA “Humedales de la República Argentina”. En una primera instancia, se finalizó con el mapa de distribución probabilística de humedales, necesario para dar ubicación espacialmente explícita. En una segunda instancia, y conscientes de que sin consenso la aplicación de medidas puede no llegar a implementarse, se inició una etapa de coconstrucción participativa de una Guía de Buenas Prácticas (GBP) para mallines. Para ello, se generó una consulta electrónica masiva, abierta y exploratoria para indagar sobre los usuarios de mallines sus conocimientos acerca de sus bondades ecológico-productivas, su opinión acerca de 5 prácticas de manejo comúnmente difundidas y propuestas alternativas de uso y manejo no contempladas. Basados en esa información, en diciembre de 2022, se desarrolló de manera simultánea (nodos Bariloche, Esquel y Río Gallegos) el primer taller participativo de la región, invitando a representantes de diversos ámbitos (productivo, ambiental, científico, gubernamental, etc.) a participar del encuentro presencial. Los resultados preliminares muestran que las prácticas propuestas son, en general, las que prevalecen en el conocimiento mayoritario, que las prácticas alternativas propuestas muchas veces son variantes de estas primeras y que, dentro de este primer grupo, existen preferencias a la hora de ejecutarlas. Las dificultades en aplicación se caracterizaron principalmente como económicas, seguidas de falta de conocimiento de su aplicación o de los efectos generados. A partir de estos encuentros y la nueva información disponible, se está elaborando la versión inicial de las GBP para mallines de la Patagonia argentina. Se espera que sea un producto de utilidad para el uso sustentable de los recursos naturales de la región y que, a partir del seguimiento de su implementación y el diálogo constante con los usuarios, reciba las actualizaciones necesarias.EEA BarilocheFil: Enriquez, Andrea Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: Enriquez, Andrea Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; ArgentinaFil: Aramayo, Maria Valeria Del Lu. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: Buono, Gustavo Gabriel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Chubut; Argentina.Fil: Curcio, Matías Hernán. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agroforestal Esquel; ArgentinaFil: Fernandez, Manuela Teresa. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; ArgentinaFil: Fernandez, Manuela Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; ArgentinaFil: García Martínez, Guillermo Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agroforestal Esquel; ArgentinaFil: Navarro, María Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina.Fil: Paredes, Paula Natalia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Umaña, Fernando. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: Utrilla, Victor Ricardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Vargas, Paola Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Dirección Nacional Asistente Transferencia y Extensión; ArgentinaFil: Cremona, Maria Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; Argentin

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P &lt; 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P &lt; 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223