Cost effectiveness of commercial portable ex vivo lung perfusion at a low-volume US lung transplant center

Background: Portable ex vivo lung perfusion during lung transplantation is a resource-intensive technology. In light of its increasing use, we evaluated the cost-effectiveness of ex vivo lung perfusion at a low-volume lung transplant center in the USA. Methods: Patients listed for lung transplantation (2015–2021) in the United Network for Organ Sharing database were included. Quality-of-life was approximated by Karnofsky Performance Status scores 1-year post-transplant. Total transplantation encounter and 1-year follow-up costs accrued by our academic center for patients listed from 2018 to 2021 were obtained. Cost-effectiveness was calculated by evaluating the number of patients attaining various Karnofsky scores relative to cost. Results: Of the 13 930 adult patients who underwent lung transplant in the United Network for Organ Sharing database, 13 477 (96.7%) used static cold storage and 453 (3.3%) used ex vivo lung perfusion, compared to 30/58 (51.7%) and 28/58 (48.3%), respectively, at our center. Compared to static cold storage, median total costs at 1 year were higher for ex vivo lung perfusion (918 000 dollars vs. 516 000 dollars; p = 0.007) along with the cost of living 1 year with a Karnofsky functional status of 100 after transplant (1 290 000 dollars vs. 841 000 dollars). In simulated scenarios, each Karnofsky-adjusted life year gained by ex vivo lung perfusion was 1.00–1.72 times more expensive. Conclusions: Portable ex vivo lung perfusion is not currently cost-effective at a low-volume transplant centers in the USA, being 1.53 times more expensive per Karnofsky-adjusted life year. Improving donor lung and/or recipient biology during ex vivo lung perfusion may improve its utility for routine transplantation.</p

¿Son frecuentes las coinfecciones con Mycoplasma pneumoniae en pacientes con COVID-19? Una revisión sistemática

Comprender la proporción de coinfección por coronavirus (COVID-19) y Mycoplasma pneumoniae es crucial para tratar a los pacientes con COVID-19, garantizando el empleo responsable de antibióticos y minimizando las consecuencias negativas del uso excesivo. Además, este conocimiento podría tener un impacto en las pautas de manejo empírico de antibióticos en pacientes con COVID-19. Esta revisión sistemática tuvo como objetivo identificar la prevalencia de M. pneumoniae en pacientes con COVID-19. Para ello se realizó una búsqueda bibliográfica de estudios publicados en espanol ˜ o inglés utilizando el buscador PubMed. Se incluyeron 14 artículos de diferentes continentes (América, Asia y Europa), con un total de 5855 pacientes estudiados. La media de edad de los pacientes COVID-19 con M. pneumoniae fue de 48 anos ˜ (intervalo: 1 a 107 anos) ˜ y la mayoría de ellos fueron varones. La detección de M. pneumoniae confirmada por laboratorio en pacientes con COVID-19 varió del 0 al 33,3%. La mayoría de los pacientes refirieron fiebre, tos y disnea, y recibieron antibióticos empíricos. La coinfección bacteriana no se asoció con un aumento de la admisión en UCI ni de la mortalidad. La prevalencia de coinfección fue muy disímil según la población estudiada y los criterios diagnósticos empleados. Dada la heterogeneidad de resultados en los diferentes países, es importante desarrollar estudios en América Latina, como así también establecer definiciones estandarizadas para poder evaluar el impacto real de las coinfecciones en pacientes con COVID-19.Understanding the proportion of SARS-CoV-2 patients with Mycoplasma pneumoniaecoinfection is crucial for treating patients suffering from coronavirus disease (COVID-19), helpto ensure responsible use of antibiotics and minimize the negative consequences of overuse. Inaddition, this knowledge could have an impact on empirical antibiotic management guidelinesfor patients with COVID-19. This systematic review aimed to identify the prevalence of M.pneumoniae in patients with coronavirus disease 2019 (COVID-19).A bibliographic search of studies published in Spanish or English was conducted using thePubMed search engine. Fourteen articles from different continents (America, Asia and Europe)were included, involving a total of 5855 patients in these studies. The mean age of COVID-19patients with M. pneumoniae was 48 years old (range 1---107), most of whom were male. Thedetection of laboratory-confirmed M. pneumoniae infection varied between 0 and 33.3%. Mostof patients referred fever, cough, and dyspnea, and received empirical antibiotic treatment.Bacterial coinfection was not associated with increased ICU admission and mortality. The preva-lence of coinfection showed extremely dissimilar figures according to the population studied and diagnostic criteria. However, it is important to develop Latin American studies, given the heterogeneity observed in the studies conducted in different countries. Standardized definitionsshould be developed in order to be able to assess the impact of coinfections in patients with adiagnosis of COVID-19.Fil: Mosmann, Jessica Paola. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Frutos, Maria Celia. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Origlia, Javier Anibal. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Cátedra de Patología de Aves y Pilíferos; ArgentinaFil: Gallo Vaulet, Maria Lucia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: García, Miriam Gabriela. Hospital de Agudos Doctor Pedro Fiorito ; Gobierno de la Provincia de Buenos Aires;Fil: Vilar, Gabriela. Hospital de Agudos Doctor Pedro Fiorito ; Gobierno de la Provincia de Buenos Aires;Fil: Pérez, Celeste. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorio e Instituto de Salud ; ArgentinaFil: Madariaga, María Julia. Gobierno de la Ciudad Autónoma de Buenos Aires. Ministerio de Salud. Instituto de Zoonosis Luis Pasteur; ArgentinaFil: Cuffini, Cecilia Gabriela. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Cadario, María Estela. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorio e Instituto de Salud ; Argentin

Biliobronchial Fistula after Liver Surgery for Giant Hydatid Cyst

Background. Biliobronchial fistula (BBF) is a rare complication in the natural history of liver hydatid disease by Echinococcus granulosus. We present a case of BBF after resection of a giant liver hydatid cyst in a 72-year-old woman. Case Report. A total cystpericystectomy was done, leaving the left lateral section of the liver that was fixed to the diaphragm. Postoperatively, the patient developed obstructive jaundice. An ERCP showed an obstruction at the junction of the left biliary duct and the main biliary duct and contrast leak. At reoperation, the main duct was ischemic, likely due to torsion along its longitudinal axis. A hepatotomy was done at the hilar plate, and the biliary duct was dissected and anastomosed to a Roux-en-Y jejunal loop. She was discharged without complications. Five months later, the patient developed cholangitis and was successfully treated with antibiotics. However, she suffered repeated respiratory infections, and four months later she was admitted to the hospital with fever, cough, bilioptysis, and right lower lobe pneumonia. The diagnosis of BBF was confirmed with 99mTc Mebrofenin scintigraphy. At transhepatic cholangiography, bile duct dilation was seen, with a biliothoracic leak. She underwent dilatation of cholangiojejunostomy stricture with placement of an external-internal catheter. The catheter was removed 3.5 months later, and two years later the patient remains in very good condition. Conclusion. An indirect treatment of the BBF by percutaneous transhepatic dilation of the biliary stenosis avoided a more invasive treatment, with satisfactory outcome

Prion Switching in Response to Environmental Stress

Evolution depends on the manner in which genetic variation is translated into new phenotypes. There has been much debate about whether organisms might have specific mechanisms for “evolvability,” which would generate heritable phenotypic variation with adaptive value and could act to enhance the rate of evolution. Capacitor systems, which allow the accumulation of cryptic genetic variation and release it under stressful conditions, might provide such a mechanism. In yeast, the prion [PSI+] exposes a large array of previously hidden genetic variation, and the phenotypes it thereby produces are advantageous roughly 25% of the time. The notion that [PSI+] is a mechanism for evolvability would be strengthened if the frequency of its appearance increased with stress. That is, a system that mediates even the haphazard appearance of new phenotypes, which have a reasonable chance of adaptive value would be beneficial if it were deployed at times when the organism is not well adapted to its environment. In an unbiased, high-throughput, genome-wide screen for factors that modify the frequency of [PSI+] induction, signal transducers and stress response genes were particularly prominent. Furthermore, prion induction increased by as much as 60-fold when cells were exposed to various stressful conditions, such as oxidative stress (H2O2) or high salt concentrations. The severity of stress and the frequency of [PSI+] induction were highly correlated. These findings support the hypothesis that [PSI+] is a mechanism to increase survival in fluctuating environments and might function as a capacitor to promote evolvability

The high-resolution map of Oxia Planum, Mars; the landing site of the ExoMars Rosalind Franklin rover mission

This 1:30,000 scale geological map describes Oxia Planum, Mars, the landing site for the ExoMars Rosalind Franklin rover mission. The map represents our current understanding of bedrock units and their relationships prior to Rosalind Franklin’s exploration of this location. The map details 15 bedrock units organised into 6 groups and 7 textural and surficial units. The bedrock units were identified using visible and near-infrared remote sensing datasets. The objectives of this map are (i) to identify where the most astrobiologically relevant rocks are likely to be found, (ii) to show where hypotheses about their geological context (within Oxia Planum and in the wider geological history of Mars) can be tested, (iii) to inform both the long-term (hundreds of metres to ∼1 km) and the short-term (tens of metres) activity planning for rover exploration, and (iv) to allow the samples analysed by the rover to be interpreted within their regional geological context.The ExoMars Rosalind Franklin Mission is a partnership between ESA and NASA. The Rosalind Franklin Rover has eight instruments in its ‘Pasteur’ Payload, with Principal Investigators from seven countries all of whom we would like to thank for there support of this project. We would like to acknowledge the following funding bodies, people and institutions supporting the lead authors of this work. We thank the UK Space Agency (UK SA) for funding P. Fawdon, on grants; ST/W002736/1, ST/L00643X/1 and ST/R001413/1, MRB on grants; ST/T002913/1, ST/V001965/1, ST/R001383/1, ST/R001413/1, P. Grindrod on grants; ST/L006456/1, ST/R002355/1, ST/V002678/1 and J. Davis on grants ST/K502388/1, ST/R002355/1, ST/V002678/1 through the ongoing Aurora space exploration programme. C. Orgel was supported by the ESA Research Fellowship Program. Alessandro Frigeri: was funded by the Italian Space Agency (ASI) grant ASI-INAF number 2017-412-H.0 (ExoMars/Ma_MISS) and D. Loizeau was funded by the H2020-COMPET-2015 programme (grant 687302), C. Quantin-Nataf was supported by the French space agency CNES, I. Torres was supported by an ESA Young Graduate Traineeship, A. Nass was supported by Helmholtz Metadata Projects (#ZT-I-PF-3-008). We thank NASA and the HiRISE camera team for data collection support throughout the ExoMars landing site selection and charectorisation process. The USGS for the HiRISE DTM data and maintaining the ISIS and SOCET SET DEM workflows. The authors wish to thank the CaSSIS spacecraft and instrument engineering teams. CaSSIS is a project of the University of Bern and funded through the Swiss Space Office via ESA's PRODEX programme. The instrument hardware development was also supported by the Italian Space Agency (ASI) (ASI-INAF agreement no. I/2020-17-HH.0), INAF/Astronomical Observatory of Padova, and the Space Research Center (CBK) in Warsaw. Support from SGF (Budapest), the University of Arizona (Lunar and Planetary Lab.) and NASA are also gratefully acknowledged. Operations support from the UK Space Agency under grant ST/R003025/1 is also acknowledged. This research has made use of the USGS Integrated Software for Imagers and Spectrometers (ISIS) Technical support for setup of the Multi-Mission Geographic Information System for concurrent team mapping was provided by F. Calef (III) and T. Soliman at NASA JPL and S. de Witte at ESA-ESTEC.This work was supported by Agencia Estatal de Investigación [grant number ID2019-107442RB-C32, MDM-2017-0737]; Agenzia Spaziale Italiana [grant number 2017-412-H.0]; Bundesministerium für Wirtschaft und Technologie [grant number 50 QX 2002]; Centre National de la Recherche Scientifique; Centre National d’Etudes Spatiales; Euskal Herriko Unibertsitatea [grant number PES21/88]; Istituto Nazionale di Astrofisica [grant number I/ 060/10/0]; Ministerio de Economía y Competitividad [grant number PID2019-104205GB-C21]; Ministry of Science and Higher Education of the Russian Federation [grant number AAAA-A18-118012290370-6]; National Aeronautics and Space Administration [grant number NNX15AH46G]; Norges Forskningsråd [grant number 223272]; European Union's Horizon 2020 (H2020-COMPET-2015) [grant number 687302 (PTAL)]; Sofja Kovalevskaja Award of the Alexander von Humboldt Foundation; MINECO [grant number PID2019-107442RB-C32]; The Open University [grant number Space Strategic Research Area]; European Union's Horizon 2020 research and innovation programme [grant number 776276]; H2020-COMPET-2015 [grant number 687302]; The Research Council of Norway, Centres of Excellence funding scheme [grant number 223272]; Helmholtz Metadata Projects [grant number ZT-I-PF-3-008]; The Research Council of Norway [grant number 223272]; Swiss Space Office via ESA's PRODEX programme; Ines Torres was supported by an ESA Young Graduate Traineeship; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [grant number 200021_197293]; Science and Technology Facilities Council [grant number 1967420]; UK Space Agency [grant number ST/K502388/1, ST/R002355/1, ST/V002678/1]. The ExoMars Rosalind Franklin Mission is a partnership between ESA and NASA. The Rosalind Franklin Rover has eight instruments in its ‘Pasteur’ Payload, with Principal Investigators from seven countries all of whom we would like to thank for there support of this project. We would like to acknowledge the following funding bodies, people and institutions supporting the lead authors of this work. We thank the UK Space Agency (UK SA) for funding P. Fawdon, on grants; ST/W002736/1, ST/L00643X/1 and ST/R001413/1, MRB on grants; ST/T002913/1, ST/V001965/1, ST/R001383/1, ST/R001413/1, P. Grindrod on grants; ST/L006456/1, ST/R002355/1, ST/V002678/1 and J. Davis on grants ST/K502388/1, ST/R002355/1, ST/V002678/1 through the ongoing Aurora space exploration programme. C. Orgel was supported by the ESA Research Fellowship Program. Alessandro Frigeri: was funded by the Italian Space Agency (ASI) grant ASI-INAF number 2017-412-H.0 (ExoMars/Ma_MISS) and D. Loizeau was funded by the H2020-COMPET-2015 programme (grant 687302), C. Quantin-Nataf was supported by the French space agency CNES, I. Torres was supported by an ESA Young Graduate Traineeship, A. Nass was supported by Helmholtz Metadata Projects (#ZT-I-PF-3-008). We thank NASA and the HiRISE camera team for data collection support throughout the ExoMars landing site selection and charectorisation process. The USGS for the HiRISE DTM data and maintaining the ISIS and SOCET SET DEM workflows. The authors wish to thank the CaSSIS spacecraft and instrument engineering teams. CaSSIS is a project of the University of Bern and funded through the Swiss Space Office via ESA's PRODEX programme. The instrument hardware development was also supported by the Italian Space Agency (ASI) (ASI-INAF agreement no. I/2020-17-HH.0), INAF/Astronomical Observatory of Padova, and the Space Research Center (CBK) in Warsaw. Support from SGF (Budapest), the University of Arizona (Lunar and Planetary Lab.) and NASA are also gratefully acknowledged. Operations support from the UK Space Agency under grant ST/R003025/1 is also acknowledged. This research has made use of the USGS Integrated Software for Imagers and Spectrometers (ISIS) Technical support for setup of the Multi-Mission Geographic Information System for concurrent team mapping was provided by F. Calef (III) and T. Soliman at NASA JPL and S. de Witte at ESA-ESTEC.Peer reviewe

The high-resolution map of Oxia Planum, Mars; the landing site of the ExoMars Rosalind Franklin rover mission

This 1:30,000 scale geological map describes Oxia Planum, Mars, the landing site for the ExoMars Rosalind Franklin rover mission. The map represents our current understanding of bedrock units and their relationships prior to Rosalind Franklin’s exploration of this location. The map details 15 bedrock units organised into 6 groups and 7 textural and surficial units. The bedrock units were identified using visible and near-infrared remote sensing datasets. The objectives of this map are (i) to identify where the most astrobiologically relevant rocks are likely to be found, (ii) to show where hypotheses about their geological context (within Oxia Planum and in the wider geological history of Mars) can be tested, (iii) to inform both the long-term (hundreds of metres to ∼1 km) and the short-term (tens of metres) activity planning for rover exploration, and (iv) to allow the samples analysed by the rover to be interpreted within their regional geological context

The risk analysis index is an independent predictor of outcomes after lung cancer resection

Background: The Risk Analysis Index (RAI) is a frailty assessment tool based on an accumulation of deficits model. We mapped RAI to data from the Society of Thoracic Surgeons (STS) Database to determine whether RAI correlates with postoperative outcomes following lung cancer resection. Methodology/Principal findings: This was a national database retrospective observational study based on data from the STS Database. Study patients underwent surgery 2018 to 2020. RAI was divided into four increasing risk categories. The associations between RAI and each of postoperative complications and administrative outcomes were examined using logistic regression models. We also compared the performance of RAI to established risk indices (American Society of Anesthesiology (ASA) and Charlson Comorbidity Index (CCI)) using areas under the Receiver Operating Characteristic (ROC) curves (AUC). Results: Of 29,420 candidate patients identified in the STS Database, RAI could be calculated for 22,848 (78%). Almost all outcome categories exhibited a progressive increase in marginal probability as RAI increased. On multivariable analyses, RAI was significantly associated with an incremental pattern with almost all outcomes. ROC analyses for RAI demonstrated “good” AUC values for mortality (0.785; 0.748) and discharge location (0.791), but only “fair” values for all other outcome categories (0.618 to 0.690). RAI performed similarly to ASA and CCI in terms of AUC score categories. Conclusions/Significance: RAI is associated with clinical and administrative outcomes following lung cancer resection. However, its overall accuracy as a surgical risk predictor is only moderate and similar to ASA and CCI. We do not recommend routine use of RAI for assessment of individual patient risk for major lung resection.</p

Fair and equitable subject selection in concurrent COVID-19 clinical trials

Clinical trials emerged in rapid succession as the COVID-19 pandemic created an unprecedented need for life-saving therapies. Fair and equitable subject selection in clinical trials offering investigational therapies ought to be an urgent moral concern. Subject selection determines the distribution of risks and benefits, and impacts the applicability of the study results for the larger population. While Research Ethics Committees monitor fair subject selection within each trial, no standard oversight exists for subject selection across multiple trials for the same disease. Drawing on the experience of multiple clinical trials at a single academic medical centre in the USA, we posit that concurrent COVID-19 trials are liable to unfair and inequitable subject selection on account of scientific uncertainty, lack of transparency, scarcity and, lastly, structural barriers to equity compounded by implicit bias. To address the critical gap in the current literature and international regulation, we propose new ethical guidelines for research design and conduct that bolsters fair and equitable subject selection. Although the proposed guidelines are tailored to the research design and protocol of concurrent trials in the COVID-19 pandemic, they may have broader relevance to single COVID-19 trials