Bioremediation of petroleum hydrocarbons polluted soil by spent mushroom substrates: Microbiological structure and functionality.

Spent mushroom substrate (SMS) holds valuable microbiota that can be useful in remediating polluted soils with hydrocarbons. However, the microorganisms behind the bioremediation process remain uncertain. In this work, a bioremediation assay of total petroleum hydrocarbons (TPHs) polluted soil by SMS application was performed to elucidate the microorganisms and consortia involved in biodegradation by a metabarcoding analysis. Untreated polluted soil was compared to seven bioremediation treatments by adding SMS of Agaricus bisporus, Pleurotus eryngii, Pleurotus ostreatus, and combinations. Soil microbial activity, TPH biodegradation, taxonomic classification, and predictive functional analysis were evaluated in the microbiopiles at 60 days. Different metagenomics approaches were performed to understand the impact of each SMS on native soil microbiota and TPHs biodegradation. All SMSs enhanced the degradation of aliphatic and aromatic hydrocarbons, being A. bisporus the most effective, promoting an efficient consortium constituted by the bacterial families Alcanivoraceae, Alcaligenaceae, and Dietziaceae along with the fungal genera Scedosporium and Aspergillus. The predictive 16 S rRNA gene study partially explained the decontamination efficacy by observing changes in the taxonomic structure of bacteria and fungi, and changes in the potential profiles of estimated degradative genes across the different treatments. This work provides new insights into TPHs bioremediation.

AR visualizations in laparoscopy: surgeon preferences and depth assessment of vascular anatomy.

Introduction: This study compares five augmented reality (AR) vasculature visualization techniques in a mixed-reality laparoscopy simulator with 50 medical professionals and analyzes their impact on the surgeon. Material and methods: ​​The different visualization techniques' abilities to convey depth were measured using the participant's accuracy in an objective depth sorting task. Demographic data and subjective measures, such as the preference of each AR visualization technique and potential application areas, were collected with questionnaires. Results: Despite measuring differences in objective measurements across the visualization techniques, they were not statistically significant. In the subjective measures, however, 55% of the participants rated visualization technique II, 'Opaque with single-color Fresnel highlights', as their favorite. Participants felt that AR could be useful for various surgeries, especially complex surgeries (100%). Almost all participants agreed that AR could potentially improve surgical parameters, such as patient safety (88%), complication rate (84%), and identifying risk structures (96%). Conclusions: More studies are needed on the effect of different visualizations on task performance, as well as more sophisticated and effective visualization techniques for the operating room. With the findings of this study, we encourage the development of new study setups to advance surgical AR.

Phantom study on surgical performance in augmented reality laparoscopy.

PURPOSE: Only a few studies have evaluated Augmented Reality (AR) in in vivo simulations compared to traditional laparoscopy; further research is especially needed regarding the most effective AR visualization technique. This pilot study aims to determine, under controlled conditions on a 3D-printed phantom, whether an AR laparoscope improves surgical outcomes over conventional laparoscopy without augmentation. METHODS: We selected six surgical residents at a similar level of training and had them perform a laparoscopic task. The participants repeated the experiment three times, using different 3D phantoms and visualizations: Floating AR, Occlusion AR, and without any AR visualization (Control). Surgical performance was determined using objective measurements. Subjective measures, such as task load and potential application areas, were collected with questionnaires. RESULTS: Differences in operative time, total touching time, and SurgTLX scores showed no statistical significance ([Formula: see text]). However, when assessing the invasiveness of the simulated intervention, the comparison revealed a statistically significant difference ([Formula: see text]). Participants felt AR could be useful for various surgeries, especially for liver, sigmoid, and pancreatic resections (100%). Almost all participants agreed that AR could potentially lead to improved surgical parameters, such as operative time (83%), complication rate (83%), and identifying risk structures (83%). CONCLUSION: According to our results, AR may have great potential in visceral surgery and based on the objective measures of the study, may improve surgeons' performance in terms of an atraumatic approach. In this pilot study, participants consistently took more time to complete the task, had more contact with the vascular tree, were significantly more invasive, and scored higher on the SurgTLX survey than with AR.

Prevalence of intestinal parasitism in preschool and school children in Colombia: Systematic review and meta-analysis.

OBJECTIVE: Intestinal parasitic infections (IPIs) are a public health challenge in developing countries such as Colombia, causing anaemia and delayed growth and development in children. We aimed to estimate the geographical and prevalence trend of IPIs in the last 30 years in school and preschool children in Colombia. METHODS: We conducted a systematic review and meta-analysis. We identified potential manuscripts through PubMed, EMBASE, Web of Science, LILACS, Scielo and Google Scholar on the IPIs prevalence in school and preschool children in Colombia. Articles included in the qualitative analysis were published between 1990 and 2020 in English or Spanish and met the inclusion criteria. Subsequently, a random-effects meta-analysis, a meta-regression and a trend analysis were performed. RESULTS: We identified 2292 articles; 109 were included in the qualitative review, and 79 articles were included in the meta-analysis. The estimated IPI prevalence was 55% (95% CI: 48-63). By age group, the prevalence in preschool children was 37% (95% CI: 26-49) and 66% (95% CI: 52-78) in schoolchildren. The prevalence by region was heterogeneous, with the Amazon being the highest (69%) and the Santanderes the lowest (28%). In the last 20 years, the prevalence of helminthiasis has decreased (from 64.66% in 1990-1995 to 22.09% in 2016-2020). CONCLUSION: The prevalence of IPIs is high (>30%) in three of the seven regions in Colombia. Biannual administration of mass deworming in schoolchildren is recommended in the Amazon region. Public policies aiming to control IPIs should be reinforced. Further prevalence studies should include Cesar, Guaviare, Vichada and Vaupés, where the epidemiology of IPIs is unknown. SUSTAINABLE DEVELOPMENT GOALS: Good health and wellbeing, clean water and sanitation, sustainable cities and communities.

Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology.

BACKGROUND: Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine kinases (RTKs) in this pathology remains poorly clarified. Here, we provide a systematic analysis of the RTK superfamily in the context of neuroblastoma pathogenesis. METHODS: Statistical correlations for all RTK family members' expression to neuroblastoma patient survival across 10 independent patient cohorts were annotated, synthesized, and ranked using the R2: Genomics Analysis and Visualization Platform. Gene expression of selected members across different cancer cell lines was further analyzed in the Cancer Cell Line Encyclopedia, part of the Cancer Dependency Map portal (depmap portal ( http://depmap.org )). Finally, we provide a detailed literature review for highly ranked candidates. RESULTS: Our analysis defined two subsets of RTKs showing robust associations with either better or worse survival, constituting potential novel players in neuroblastoma pathophysiology, diagnosis, and therapy. We review the available literature regarding the oncogenic functions of these RTKs, their roles in neuroblastoma pathophysiology, and potential utility as therapeutic targets. CONCLUSIONS: Our systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies.

Incidence of COVID-19 after pulmonary function tests: a retrospective cohort study.

INTRODUCTION: It has been proposed that exposure to pulmonary function tests (PFT) could be associated with a higher risk of viral transmission. The risk of the Coronavirus Disease 2019 (COVID-19) transmission after performing PFT is unknown. We aimed to assess the incidence  of COVID-19 after a PFT at an academic teaching facility in Buenos Aires, Argentina. MATERIALS AND METHODS: We conducted a retrospective cohort study including all consecutive adult patients that performed PFT between April 1, 2020 and September 30, 2020. Patients with prior COVID-19 were excluded. We defined a 15-day time window to  ascertain PFT related COVID-19. The primary outcome was ascertained by consulting a national database, which has information on all patients with nasopharyngeal swabs for SARS-CoV-2 in Argentina. RESULTS: We included 278 patients who performed a PFT. Fifty percent were women, the mean age was 54 years (SD 18), and the main comorbidities were obesity (31%), smoking (31%), hypertension (29%), and chronic lung disease (28%). The main indication for performing PFT was anesthetic preoperative risk assessment. Swabs were collected from 27 patients (10%). Twenty-two swabs (8%) were taken according to surgical protocols; five swabs (2%) were taken due to clinical suspicion of COVID-19, with only one testing positive. The cumulative incidence of COVID-19 after PFT was 0.36% (95% CI 0.01-20%). None of the technicians developed symptomatic disease. CONCLUSION: Given the right setting and strict adherence to international recommendations, the SARS-CoV-2 infection after having a PFT appears to be low, which follows that these procedures can be performed safely for both patients and staff.

Introducción: Se ha propuesto que las pruebas de función respiratorias (PFR) podrían estar asociadas con un mayor riesgo de transmisión viral. El riesgo de presentar la enfermedad por coronavirus 2019 (COVID-19) después de realizar una PFR es desconocido. El objetivo del estudio fue estimar la incidencia de COVID-19 después de llevar a cabo una PFR, en un Hospital Universitario de la ciudad Autónoma de Buenos Aires, Argentina. Se realizó una cohorte retrospectiva que incluyó a todos los pacientes que realizaron una PFR entre el 1 de abril de 2020 y el 30 de septiembre de 2020. Se excluyeron los pacientes con antecedentes de COVID-19. Definimos una ventana de tiempo de 15 días para determinar la presencia de COVID-19 relacionada con la realización de la PFR. El resultado primario se determinó consultando una base de datos nacional, que contiene información sobre todos los pacientes que se han realizado hisopados nasofaríngeos para detección del SARS-CoV-2 en Argentina. Materiales y métodos: Se incluyeron 278 pacientes, el 50% fueron mujeres, el promedio de edad fue de 54 años (DE 18) y las principales comorbilidades fueron: obesidad (31%), tabaquismo (31%), hipertensión (29%) y enfermedades respiratorias crónicas (28%). La principal indicación de la PFR fue la evaluación pre operatoria o anestésica. A 27 pacientes (10%) se les realizó un hisopado nasofaríngeo para búsqueda de SARS-CoV-2. Veintidós hisopados (8%) se solicitaron por evaluación pre quirúrgica, cinco hisopados (2%) por sospecha clínica de infección y solamente uno fue positivo. La incidencia de COVID-19 fue de 0.36% (IC95% 0.01-20%). Durante el período del estudio ninguno de los operadores que realizaron las PFR presentaron síntomas compatibles con COVID-19. Conclusión: Siguiendo las recomendaciones internacionales, la frecuencia de detección de COVID-19 después de las PFR parece ser bajo, por lo que estos procedimientos se podrían llevar a cabo de forma segura tanto para los pacientes como para el personal.

Estrategias para aumentar la disponibilidad de órganos destinados a trasplante pulmonar. Enfoque desde Argentina / Strategies to increase the availability of organs destined for lung transplantation. Approach from Argentina

Resumen Ante la escasez de donantes pulmonares, el aumento de los pacientes en lista de espera y el aumento de las muertes en lista de espera existen varias estrategias que buscan resolver estos problemas. Las estrategias de promoción son necesarias, continuas y transver sales a todo el proceso. Las de procuración implican mejora continua en la calidad de atención médica, siendo muy costo-efectivas en nuestro contexto. Las de distribución ya se emplean y han generado mejoras en el acceso al trasplante; deben ser constantemente evaluadas. Las de selección involucran mejoras a expensas de mayores costos a veces con consecuencias negativas, por lo que deben ser evaluadas caso a caso. El uso de EVLP es efectivo, aunque pareciera no ser una intervención costo-efectiva en nuestro medio debiendo emplearse otras estrategias previamente. La utilización de donantes a corazón parado es efectiva aunque requiere de una inversión en el sistema logístico que no parece ser viable por el momento en Argentina.

Abstract Given the shortage of lung donors and the increase in patients and deaths on the waiting lists, there are several strategies that could be carried out. Promotion strategies are necessary, continuous and transversal to the entire process. Strategies that attempt to enhance organ procurement involve continuous improvement in the quality of healthcare, which is highly profitable in our context. Interventions on grafts distribution are already in use and have generated improvements in access to lung transplantation. Laxity in the selection criteria generates higher costs, sometimes with negative consequences, so a case-by-case selection must be applied. Ex vivo lung perfusion is effective, although it does not appear to be a cost-effective intervention in our country, other strategies must be implemented previously. The use of non-heart-beating lung donors requires an investment in a logistics system that nowadays does not seem viable in Argentina.

Bone toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the retinoid system: A causality analysis anchored in osteoblast gene expression and mouse data.

Dioxin exposures impact on bone quality and osteoblast differentiation, as well as retinoic acid metabolism and signaling. In this study we analyzed associations between increased circulating retinol concentrations and altered bone mineral density in a mouse model following oral exposure to 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD). Additionally, effects of TCDD on differentiation marker genes and genes involved with retinoic acid metabolism were analysed in an osteoblast cell model followed by benchmark dose-response analyses of the gene expression data. Study results show that the increased trabecular and decreased cortical bone mineral density in the mouse model following TCDD exposure are associated with increased circulating retinol concentrations. Also, TCDD disrupted the expression of genes involved in osteoblast differentiation and retinoic acid synthesis, degradation, and nuclear translocation in directions compatible with increasing cellular retinoic acid levels. Further evaluation of the obtained results in relation to previously published data by the use of mode-of-action and weight-of-evidence inspired analytical approaches strengthened the evidence that TCDD-induced bone and retinoid system changes are causally related and compatible with an endocrine disruption mode of action.

Usability of Graphical Visualizations on a Tool-Mounted Interface for Spine Surgery.

Screw placement in the correct angular trajectory is one of the most intricate tasks during spinal fusion surgery. Due to the crucial role of pedicle screw placement for the outcome of the operation, spinal navigation has been introduced into the clinical routine. Despite its positive effects on the precision and safety of the surgical procedure, local separation of the navigation information and the surgical site, combined with intricate visualizations, limit the benefits of the navigation systems. Instead of a tech-driven design, a focus on usability is required in new research approaches to enable advanced and effective visualizations. This work presents a new tool-mounted interface (TMI) for pedicle screw placement. By fixing a TMI onto the surgical instrument, physical de-coupling of the anatomical target and navigation information is resolved. A total of 18 surgeons participated in a usability study comparing the TMI to the state-of-the-art visualization on an external screen. With the usage of the TMI, significant improvements in system usability (Kruskal-Wallis test p < 0.05) were achieved. A significant reduction in mental demand and overall cognitive load, measured using a NASA-TLX (p < 0.05), were observed. Moreover, a general improvement in performance was shown by means of the surgical task time (one-way ANOVA p < 0.001).

Effects of a high-fat diet and global aryl hydrocarbon receptor deficiency on energy balance and liver retinoid status in male Sprague-Dawley rats.

The physiological functions of the aryl hydrocarbon receptor (AHR) are only beginning to unfold. Studies in wildtype and AHR knockout (AHRKO) mice have recently disclosed that AHR activity is required for obesity and steatohepatitis to develop when mice are fed with a high-fat diet (HFD). In addition, a line of AHRKO mouse has been reported to accumulate retinoids in the liver. Whether these are universal manifestations across species related to AHR activity level is not known yet. Therefore, we here subjected wildtype and AHRKO male rats (on Sprague-Dawley background) to HFD feeding coupled with free access to 10% sucrose solution and water; controls received a standard diet and water. Although the HFD-fed rats consumed more energy throughout the 24-week feeding regimen, they did not get overweight. However, relative weights of the brown and epididymal adipose tissues were elevated in HFD-fed rats, while that of the liver was lower in AHRKO than wildtype rats. Moreover, the four groups exhibited diet- or genotype-dependent differences in biochemical variables, some of which suggested marked dissimilarities from AHRKO mice. Expression of pro- and anti-inflammatory genes was induced in livers of HFD-fed AHRKO rats, but histologically they did not differ from others. HFD reduced the hepatic concentrations of retinyl palmitate, 9-cis-4-oxo-13,14-dihydroretinoic acid and (suggestively) retinol, whereas AHR status had no effect. Hence, the background strain/line of AHRKO rat is resistant to diet-induced obesity, and AHR does not modulate this or liver retinoid concentrations. Yet, subtle AHR-dependent differences in energy balance-related factors exist despite similar weight development.

Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180): A postnatal follow-up study in rats.

PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions.

Pose-Dependent Weights and Domain Randomization for Fully Automatic X-Ray to CT Registration.

Fully automatic X-ray to CT registration requires a solid initialization to provide an initial alignment within the capture range of existing intensity-based registrations. This work addresses that need by providing a novel automatic initialization, which enables end to end registration. First, a neural network is trained once to detect a set of anatomical landmarks on simulated X-rays. A domain randomization scheme is proposed to enable the network to overcome the challenge of being trained purely on simulated data and run inference on real X-rays. Then, for each patient CT, a fully-automatic patient-specific landmark extraction scheme is used. It is based on backprojecting and clustering the previously trained network's predictions on a set of simulated X-rays. Next, the network is retrained to detect the new landmarks. Finally the combination of network and 3D landmark locations is used to compute the initialization using a perspective-n-point algorithm. During the computation of the pose, a weighting scheme is introduced to incorporate the confidence of the network in detecting the landmarks. The algorithm is evaluated on the pelvis using both real and simulated x-rays. The mean (± standard deviation) target registration error in millimetres is 4.1 ± 4.3 for simulated X-rays with a success rate of 92% and 4.2 ± 3.9 for real X-rays with a success rate of 86.8%, where a success is defined as a translation error of less than 30 mm .

Role of aryl hydrocarbon receptor (AHR) in overall retinoid metabolism: Response comparisons to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure between wild-type and AHR knockout mice.

Young adult wild-type and aryl hydrocarbon receptor knockout (AHRKO) mice of both sexes and the C57BL/6J background were exposed to 10 weekly oral doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; total dose of 200 µg/kg bw) to further characterize the observed impacts of AHR as well as TCDD on the retinoid system. Unexposed AHRKO mice harboured heavier kidneys, lighter livers and lower serum all-trans retinoic acid (ATRA) and retinol (REOH) concentrations than wild-type mice. Results from the present study also point to a role for the murine AHR in the control of circulating REOH and ATRA concentrations. In wild-type mice, TCDD elevated liver weight and reduced thymus weight, and drastically reduced the hepatic concentrations of 9-cis-4-oxo-13,14-dihydro-retinoic acid (CORA) and retinyl palmitate (REPA). In female wild-type mice, TCDD increased the hepatic concentration of ATRA as well as the renal and circulating REOH concentrations. Renal CORA concentrations were substantially diminished in wild-type male mice exclusively following TCDD-exposure, with a similar tendency in serum. In contrast, TCDD did not affect any of these toxicity or retinoid system parameters in AHRKO mice. Finally, a distinct sex difference occurred in kidney concentrations of all the analysed retinoid forms. Together, these results strengthen the evidence of a mandatory role of AHR in TCDD-induced retinoid disruption, and suggest that the previously reported accumulation of several retinoid forms in the liver of AHRKO mice is a line-specific phenomenon. Our data further support participation of AHR in the control of liver and kidney development in mice.

Associations of persistent organic pollutants in human adipose tissue with retinoid levels and their relevance to the redox microenvironment.

Humans are exposed to a myriad of chemical substances in both occupational and environmental settings. Persistent organic pollutants (POPs) have drawn attention for their adverse effects including cancer and endocrine disruption. Herein, the objectives were 1) to describe serum and adipose tissue retinol levels, along with serum retinol binding protein 4 (RBP4) concentrations, and 2) to assess the associations of adipose tissue POP levels with these retinoid parameters, as well as their potential interaction with the previously-observed POP-related disruption of redox microenvironment. Retinol was measured in both serum and adipose tissue along with RBP4 levels in serum samples of 236 participants of the GraMo adult cohort. Associations were explored by multivariable linear regression analyses and Weighted Quantile Sum regression. Polychlorinated biphenyls (PCBs) 180, 153 and 138 were related to decreased adipose tissue retinol levels and increased serum RBP4/retinol ratio. Dicofol concentrations > limit of detection were associated with decreased retinol levels in serum and adipose tissue. Additionally, increased adipose tissue retinol levels were linked to an attenuation in previously-reported associations of adipose tissue PCB-153 with in situ superoxide dismutase activity. Our results revealed a suggestive link between retinoids, PCBs and redox microenvironment, potentially relevant for both mechanistic and public health purposes.

Uso de metformina y un inhibidor de SGLT2 en el manejo de lipodistrofia congénita generalizada. Reporte de caso / Use of metformin and an SGLT2 inhibitor to treat congenital generalized lipodystrophy. Case report

Resumen Introducción. La lipodistrofia congénita generalizada (LCG) es un síndrome genético autosómico recesivo extremadamente raro que se caracteriza por ausencia generalizada de tejido adiposo, deficiencia en la producción de hormonas como la leptina y complicaciones metabólicas potencialmente serias como diabetes mellitus tipo 2 (DM2), esteatohepatitis e hipertrigliceridemia. Presentación del caso. Paciente femenina de 17 años con un diagnóstico tardío de LCG y con diabetes mellitus (erróneamente clasificada como tipo I), hipertrigliceridemia severa e infecciones a repetición. Luego de introducir metformina y un inhibidor del SGLT2 en el manejo de la paciente, se logró un adecuado control metabólico. Conclusión. Con frecuencia, el desconocimiento de algunas enfermedades huérfanas lleva a diagnósticos erróneos y, por tanto, a tratamientos inadecuados que en algunos casos pueden empeorar la condición clínica de los pacientes. Por lo anterior, en el caso de la LCG, es necesario que la comunidad médica tenga una mejor comprensión de sus aspectos diagnósticos y terapéuticos para brindar un diagnóstico y tratamiento oportunos.

Abstract Introduction: Generalized congenital lipodystrophy (GDL) is an extremely rare autosomal recessive genetic syndrome characterized by generalized absence of adipose tissue, deficient production of hormones such as leptin, and potentially serious metabolic complications such as type 2 diabetes mellitus (DM2), steatohepatitis and hypertriglyceridemia. Case presentation: This is the case of a 17-year-old female patient with a late diagnosis of GDL and with diabetes mellitus (erroneously classified as type 1), severe hypertriglyceridemia and recurrent infections. Adequate metabolic control was achieved after the introduction of metformin and an SGLT2 inhibitor. Conclusion: Lack of knowledge about some orphan diseases usually leads to misdiagnosis and, therefore, to inadequate treatments that may worsen the clinical condition of patients. Therefore, in the case of GDL, the medical community should have a better understanding of its diagnostic and therapeutic aspects in order to provide timely diagnosis and treatment.

Influencia de la enfermedad pulmonar obstructiva crónica en los componentes orgánicos volátiles en pacientes con cáncer de pulmón no microcítico / Influence of Chronic Obstructive Pulmonary Disease on Volatile Organic Compounds in Patients with Non-small Cell Lung Cancer

INTRODUCCIÓN: La etiología del cáncer de pulmón es multifactorial. La exposición al humo del tabaco y el papel que desempeñan los compuestos carcinógenos presentes en él explicarían la frecuente asociación de cáncer de pulmón con enfermedad pulmonar obstructiva crónica (EPOC), enfermedad igualmente muy ligada al tabaquismo. En ambas entidades se desencadena una inflamación mantenida debida al incremento del estrés oxidativo (por ejemplo, peroxidación lipídica), que genera sustancias de bajo peso molecular llamadas compuestos orgánicos volátiles (VOC), que son excretadas durante la respiración. La metabolómica de los VOC ofrece una medida indirecta del grado de estrés oxidativo. OBJETIVO: El objetivo de este trabajo es determinar la influencia relativa de la EPOC en el perfil de los VOC en pacientes con cáncer de pulmón no microcítico (CPNM), estudiando previamente la posible variación de los VOC en función de la histología. PACIENTES Y MÉTODOS: Se analizó el aire exhalado de 107 pacientes de CPNM, clasificados en 2 grupos: CPNM con EPOC y CPNM sin EPOC. La muestra de aire exhalado se recogió mediante BioVOC®) y se traspasó a tubos de desorción para su posterior análisis por cromatografía de gases y espectrometría de masas. Los VOC analizados fueron aldehídos lineales y ácidos carboxílicos. RESULTADOS Y CONCLUSIONES: No se han encontrado diferencias estadísticamente significativas de los VOC con respecto a la histología. Los pacientes con CPNM con EPOC presentan 1,7 (1,1-2,7) veces más probabilidad de detección de ácido propanoico (IC 95%: 1,22-6,2) que los pacientes CPNM sin EPOC (p = 0,013)

INTRODUCTION: The etiology of lung cancer is multifactorial. Exposure to tobacco smoke and the role played by the carcinogenic compounds that it contains would explain the common association between lung cancer and chronic obstructive pulmonary disease (COPD), a disease which is very much linked to tobacco use. In both diseases, sustained inflammation is caused by increased oxidative stress (for example, lipid peroxidation). This generates low molecular weight substances called volatile organic compounds (VOC) that are excreted during breathing. VOC metabolomics provides an indirect measure of oxidative stress. OBJECTIVE: The aim of this study was to establish the relative influence of COPD on the VOC profile in patients with non-small cell lung cancer (NSCLC), by first studying the possible variation of VOC associated with lung cancer histology. PATIENTS AND METHODS: Exhaled air was tested in 107 NSCLC patients, who were divided into 2 groups: NSCLC with COPD and non-COPD with NSCLC. The exhaled air sample was obtained with the BIOVOC® sampler, and transferred to desorption tubes for later analysis by thermal desorption-gas chromatography-mass spectrometry. The VOC analysis showed lineal aldehydes and carboxylic acids. RESULTS AND CONCLUSIONS: No statistically significant differences were found in VOC associated with histology. NSCLC and COPD patients present a 1.7-fold (1.1-2.7) probability of detection of propionic acid (95% CI: 1.22- 6.2) than patients without COPD or NSCLC (P = 0.013)

Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort).

BACKGROUND: The COVID-19 outbreak challenges the Spanish health system since March 2020. Some available therapies (antimalarials, antivirals, biological agents) were grounded on clinical case observations or basic science data. The aim of this study is to describe the characteristics and impact of different therapies on clinical outcomes in a cohort of severe COVID-19 patients. METHODS: In this retrospective, single-center, observational study, we collected sequential data on adult patients admitted to Hospital Universitario Quironsalud Madrid. Eligible patients should have a microbiological (positive test on RT-PCR assay from a nasal swab) or an epidemiological diagnosis of severe COVID-19. Demographic, baseline comorbidities, laboratory data, clinical outcomes, and treatments were compared between survivors and non-survivors. We carried out univariate and multivariate logistic regression models to assess potential risk factors for in-hospital mortality. FINDINGS: From March 10th to April 15th, 2020, 607 patients were included. Median age was 69 years [interquartile range, {IQR} 22; 65% male). The most common comorbidities were hypertension (276 [46·94%]), diabetes (95 [16·16%]), chronic cardiac (133 [22·62%]) and respiratory (114 [19·39%]) diseases. 141 patients (23·2%) died. In the multivariate model the risk of death increased with older age (odds ratio, for every year of age, 1·15, [95% CI 1·11 - 1·2]), tocilizumab therapy (2·4, [1·13 - 5·11]), C-reactive protein at admission (1·07, per 10 mg/L, [1·04 - 1·10]), d-dimer > 2·5 µg/mL (1·99, [1·03 - 3·86]), diabetes mellitus (2·61, [1·19 - 5·73]), and the PaO2/FiO2 at admission (0·99, per every 1 mmHg, [0·98 - 0·99]). Among the prescribed therapies (tocilizumab, glucocorticoids, lopinavir/ritonavir, hydroxychloroquine, cyclosporine), only cyclosporine was associated with a significant decrease in mortality (0·24, [0·12 - 0·46]; p<0·001). INTERPRETATION: In a real-clinical setting, inhibition of the calcineurin inflammatory pathway, NF-κΒ, could reduce the hyperinflammatory phase in COVID-19. Our findings might entail relevant implications for the therapy of this disease and could boost the design of new clinical trials among subjects affected by severe COVID-19. FUNDING: Hospital Universitario Quironsalud Madrid. Own fundings for COVID-19 research.