Molecular structure and selective theophylline complexation by conformational change of diethyl N,N'-(1,3-phenylene)dicarbamate.

The receptor ability of diethyl N,N'-(1,3-phenylene)dicarbamate (1) to form host-guest complexes with theophylline (TEO) and caffeine (CAF) by mechanochemistry was evaluated. The formation of the 1-TEO complex (C12H16N2O4·C7H8N4O2) was preferred and involves the conformational change of one of the ethyl carbamate groups of 1 from the endo conformation to the exo conformation to allow the formation of intermolecular interactions. The formation of an N-H...O=C hydrogen bond between 1 and TEO triggers the conformational change of 1. CAF molecules are unable to form an N-H...O=C hydrogen bond with 1, making the conformational change and, therefore, the formation of the complex impossible. Conformational change and selective binding were monitored by IR spectroscopy, solid-state 13C nuclear magnetic resonance and single-crystal X-ray diffraction. The 1-TEO complex was characterized by IR spectroscopy, solid-state 13C nuclear magnetic resonance, powder X-ray diffraction and single-crystal X-ray diffraction.

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID).

BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival. METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.

Synthetic Polyisoprene Rubber as a Mimic of Natural Rubber: Recent Advances on Synthesis, Nanocomposites, and Applications.

Up to now, rubber materials have been used in a wide range of applications, from automotive parts to special-design engineering pieces, as well as in the pharmaceutical, food, electronics, and military industries, among others. Since the discovery of the vulcanization of natural rubber (NR) in 1838, the continuous demand for this material has intensified the quest for a synthetic substitute with similar properties. In this regard, synthetic polyisoprene rubber (IR) emerged as an attractive alternative. However, despite the efforts made, some properties of natural rubber have been difficult to match (i.e., superior mechanical properties) due not only to its high content of cis-1,4-polyisoprene but also because its structure is considered a naturally occurring nanocomposite. In this sense, cutting-edge research has proposed the synthesis of nanocomposites with synthetic rubber, obtaining the same properties as natural rubber. This review focuses on the synthesis, structure, and properties of natural and synthetic rubber, with a special interest in the synthesis of IR nanocomposites, giving the reader a comprehensive reference on how to achieve a mimic of NR.

Indolealkylamines in the venom of the scorpion Thorellius intrepidus.

Scorpions are a group of arthropods that strike fear in many people due to their severe medical symptoms, even death, caused by their venomous stings. Even so, not all scorpion species contain harmful venoms against humans but still have valuable bioactive molecules, which could be used in developing new pharmaceutical leads for treating important diseases. This work conducted a comprehensive analysis of the venom from the scorpion Thorellius intrepidus. The venom of T. intrepidus was separated by size exclusion chromatography, and four main fractions were obtained. Fraction IV (FIV) contained small molecules representing over 90% of the total absorbance at 280 nm. Analysis of fraction FIV by RP-HPLC indicated the presence of three main molecules (FIV.1, FIV.2, and FIV.3) with similar UV absorbance spectra profiles. The molecular masses of FIV.1, FIV.2, and FIV.3 were determined, resulting in 175.99, 190.07, and 218.16 Da, respectively. Further confirmation through 1H-NMR and 13C-NMR analyses revealed that these molecules were serotonin, N-methylserotonin, and bufotenidine. These intriguing compounds are speculated to play a pivotal role in self-defense and increasing venom toxicity and could also offer promising biotechnological applications as small bioactive molecules.

Differences in Mortality Among Patients With Asthma and COPD Hospitalized With COVID-19.

BACKGROUND: It remains unclear whether patients with asthma and/or chronic obstructive pulmonary disease (COPD) are at increased risk for severe coronavirus disease 2019 (COVID-19). OBJECTIVE: Compare in-hospital COVID-19 outcomes among patients with asthma, COPD, and no airway disease. METHODS: A retrospective cohort study was conducted on 8,395 patients admitted with COVID-19 between March 2020 and April 2021. Airway disease diagnoses were defined using International Classification of Diseases, 10th Revision codes. Mortality and sequential organ failure assessment (SOFA) scores were compared among groups. Logistic regression analysis was used to identify and adjust for confounding clinical features associated with mortality. RESULTS: The median SOFA score in patients without airway disease was 0.32 and mortality was 11%. In comparison, asthma patients had lower SOFA scores (median 0.15; P < .01) and decreased mortality, even after adjusting for age, diabetes, and other confounders (odds ratio 0.65; P = .01). Patients with COPD had higher SOFA scores (median 0.86; P < .01) and increased adjusted odds of mortality (odds ratio 1.40; P < .01). Blood eosinophil count of 200 cells/µL or greater, a marker of type 2 inflammation, was associated with lower mortality across all groups. Importantly, patients with asthma showed improved outcomes even after adjusting for eosinophilia, indicating that noneosinophilic asthma was associated with protection as well. CONCLUSIONS: COVID-19 severity was increased in patients with COPD and decreased in those with asthma, eosinophilia, and noneosinophilic asthma, independent of clinical confounders. These findings suggest that COVID-19 severity may be influenced by intrinsic immunological factors in patients with airway diseases, such as type 2 inflammation.

Two-photon isomerization properties of donor-acceptor Stenhouse adducts.

Donor-acceptor Stenhouse adducts (DASAs) are important photo-responsive molecules that undergo electrocyclic reactions after light absorption. From these properties, DASAs have received extensive attention as photo-switches with negative photochromism. Meanwhile, several photochemical applications require isomerization events to take place in highly localized volumes at variable depths. Such focused photoreactions can be achieved if the electronic excitation is induced through a non-linear optical process. In this contribution we describe DASAs substituted with extended donor groups which provide them with significant two-photon absorption properties. We characterized the photo-induced transformation of these DASAs from the open polymethinic form to their cyclopentenic isomer with the use of 800 nm femtosecond pulses. These studies verified that the biphotonic excitation produces equivalent photoreactions as linear absorbance. We also determined these DASAs' two-photon absorption cross sections from measurements of their photoconverted yield after biphotonic excitation. As we show, specific donor sections provide these systems with important biphotonic cross-sections as high as 615 GM units. Such properties make these DASAs among the most non-linearly active photo-switchable molecules. Calculations at the TDDFT level with the optimally tuned range-separated functional OT-CAM-B3LYP, together with quadratic response methods indicate that the non-linear photochemical properties in these molecules involve higher lying electronic states above the first excited singlet. This result is consistent with the observed relation between their two-photon chemistry and the onset of their short wavelength absorption features around 400 nm. This is the first report of the non-linear photochemistry of DASAs. The two-photon isomerization properties of DASAs extend their applications to 3D-photocontrol, non-linear lithography, variable depth birefringence, and localized drug delivery schemes.

Crystal structure and characterization of the sulfamethazine-piperidine salt.

Sulfamethazine [N1-(4,6-dimethylpyrimidin-2-yl)sulfanilamide] is an antimicrobial drug that possesses functional groups capable of acting as hydrogen-bond donors and acceptors, which make it a suitable supramolecular building block for the formation of cocrystals and salts. We report here the crystal structure and solid-state characterization of the 1:1 salt piperidinium sulfamethazinate (PPD+·SUL-, C5H12N+·C12H13N4O2S-) (I). The salt was obtained by the solvent-assisted grinding method and was characterized by IR spectroscopy, powder X-ray diffraction, solid-state 13C NMR spectroscopy and thermal analysis [differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)]. Salt I crystallized in the monoclinic space group P21/n and showed a 1:1 stoichiometry revealing proton transfer from SUL to PPD to form salt I. The PPD+ and SUL- ions are connected by N-H+...O and N-H+...N interactions. The self-assembly of SUL- anions displays the amine-sulfa C(8) motif. The supramolecular architecture of salt I revealed the formation of interconnected supramolecular sheets.

Synthesis of a New Co Metal-Organic Framework Assembled from 5,10,15,20-Tetrakis((pyridin-4-yl) phenyl)porphyrin "Co-MTPhPyP" and Its Application to the Removal of Heavy Metal Ions.

The synthesis of a Co metal-organic framework assembled from 5,10,15,20-tetrakis((pyridin-4-yl)phenyl)porphyrin; TPhPyP) "Co-MTPhPyP" is reported. The TPhPyP ligand was synthesized via aldehyde condensation in 28% yield and characterized by 1H nuclear magnetic resonance (1H NMR), Fourier-transform infrared (FTIR), high-resolution mass spectrometry (HRMS), and UV-visible spectroscopy (UV-vis). Co-MTPhPyP was prepared by the solvothermal method from TPhPyP and CoCl2·H2O in 55% yield and characterized by X-ray powder diffraction (XRD), FTIR, thermogravimetric analysis (TGA), field-emission scanning electron microscopy with energy-dispersive X-ray (FESEM-EDS), X-ray photoelectron spectroscopy (XPS), and dynamic light scattering (DLS), showing a particle size distribution of 418 ± 58 nm. The sorption properties of the Co-MTPhPyP for the effective removal of Pb(II) and Cu(II) were evaluated in an aqueous medium and Cthe results showed uptake capacities of 383.4 and 168 mg of the metal g-1 after 2 h, respectively. Kinetic studies of Pb(II) adsorption by Co-MTPhPyP were adjusted to the pseudo-second-order model with a maximum adsorption capacity of 458.8 mg g-1 at 30 min of exposition.

Primary care referral patterns for patients with asthma: analysis of real-world data.

OBJECTIVE: To identify features related to management of patients prior to referral from primary care physicians (PCPs) to pulmonologists and allergists. METHODS: This is an analysis of patient claims data from Symphony Health (2013-2018). To characterize referrals, a longitudinal cohort included 12 months with no asthma claims prior to the index date, followed by 36 months of observation. We also assessed a cross-sectional cohort for 12 months at the end of the observational period to characterize disease control and treatment patterns. Referral was defined as the first appearance of a claim from an allergist or pulmonologist for a patient's initial visit for asthma. Descriptive statistics were used to analyze the data. RESULTS: The majority of patients with asthma were managed by PCPs (60%), followed by pulmonologists (16%) and allergists (8%). Forty-three percent had uncontrolled asthma. Only 8% were referred to specialists within the first 24 months after initial diagnosis, of which 76% were seen by pulmonologists and 24% by allergists. Referrals resulted in treatment change in 55%-68% of the cases. Patients who received a referral were more likely to be on oral corticosteroids (OCS) and/or have more hospitalizations/ED visits. CONCLUSIONS: About one-third of the patients managed by PCPs received intermittent and/or chronic OCS prior to referral, which may be an indication of uncontrolled disease. The referral patterns in this analysis illustrate underutilization of specialists in the consultation and management of patients with uncontrolled asthma.

Asthma exacerbations during the pandemic: Time to rethink clinical markers.

Background: Reductions in asthma exacerbations during the coronavirus disease 2019 (COVID-19) pandemic may have an impact on clinical trial enrollment and outcomes. Objective: Our aim was to review clinical studies and reports evaluating asthma exacerbations before and during the COVID-19 pandemic. Methods: We reviewed clinical studies conducted with biologics over the past decade that evaluated asthma exacerbations as the primary end point. We also reviewed recent clinical reports evaluating asthma exacerbations during the COVID-19 pandemic. Results: We showed that studies requiring at least 2 exacerbations in the prior year resulted in a higher number of exacerbations on study in the placebo arm, and conversely, those studies in which exacerbations were not required for entering the study failed to meet the primary end point. This result confirmed that history of prior exacerbations is a good maker to predict future exacerbations. In addition, a review of the literature confirmed a reduction of asthma exacerbations during the COVID-19 pandemic. The data presented are descriptive; no formal statistics were used. Conclusion: Because of the COVID-19 pandemic, historical exacerbations may no longer be the best predictor for exacerbations in a clinical trial or clinical practice. Other clinical markers associated with exacerbations, such as blood eosinophil count and fractional exhaled nitric oxide level, should be considered for enrollment in clinical studies assessing asthma exacerbations.

El papel de la rehabilitación pulmonar en el manejo de los pacientes pos COVID 19 / The role of pulmonary rehabilitation in the management of post-COVID 19 patients

A septiembre de 2022, el SARS COV 2 ha causado cerca de 606 millones de casos confirmados y 6.500.000 muertes de acuerdo con cifras publicadas por la Organización Mundial de la Salud (OMS) (1). Esta pandemia, en su dramática dimensión ha obligado a la comunidad científica a la generación rápida y frenética de conocimiento alrededor de la naturaleza de la COVID 19, su fisiopatología, su transmisibilidad, su presentación y curso clínico, la búsqueda de tratamientos efectivos y el desarrollo de vacunas para su prevención. A pesar de algunos ensayos y publicaciones que en medio del desconcierto ignoraron el rigor científico, la respuesta de la ciencia ha sido rápida como nunca en la historia de la humanidad, oportuna y eficaz, hasta conducirnos a presagiar el sueño de estar transitando hacia el anhelado final.

As of September 2022, SARS COV 2 has caused about 606 million confirmed cases and 6,500,000 deaths according to figures published by the World Health Organization (WHO) (1). This pandemic, in its dramatic dimension, has forced the scientific community to generate rapid and frantic knowledge about the nature of COVID 19, its pathophysiology, its transmissibility, its presentation and clinical course, the search for effective treatments, and the development of vaccines for its prevention. Despite some essays and publications that in the midst of confusion ignored scientific rigor, the response of science has been quick as never in the history of humanity, timely and effective, leading us to foreshadow the dream of moving towards the longed-for final.

Clinical and hemodynamic outcomes and mortality risk factors in patients undergoing pulmonary thromboendarterectomy / Resultados clínicos y hemodinámicos y factores de riesgo de mortalidad en pacientes sometidos a tromboendarterectomía pulmonar

Abstract Background: Pulmonary thromboendarterectomy is the current treatment of choice in patients with chronic thromboembolic pulmonary hypertension. The objective of the present study was to analyze the clinical and hemodynamic outcomes and the risk factors for mortality in a cardiovascular center in Colombia. Methods: Cohort study, conducted between 2001 and 2019. All operated patients were included in the study. Risk factors associated with mortality were established by means of a multivariate regression using the COX method and survival was established using the Kaplan-Meier method. p < 0.05 was considered statistically significant. Results: Seventy-three patients were operated. Median age was 51 years, 55% of females, 79% had functional Class III and IV. The mean pulmonary arterial pressure was 50 mmHg and 640 dyn.s.cm−5 for pulmonary vascular resistance (PVR). After the intervention, there was a decrease in mean pulmonary artery pressure (p ≤ 0.001) and in PVR (p = 0.357); 21% had evidence of residual pulmonary hypertension. Only 8% and 6% continued with functional Class III and IV at 6 and 12 months, respectively. There were 15 deaths (19.1%; 12% at 30 days). The factors associated with mortality were the diastolic diameter of the right ventricle measured postoperatively (hazard ratio [HR] 10.88 95% confidence interval [CI] 1.97-62, p = 0.007), time of invasive mechanical ventilation (HR 1.06 95% CI 1.02-1.09 p = 0.004), and the presence of complications during the surgical procedure (HR 5.62 95% CI 1.94-16.22 p = 0.001). Conclusions: Pulmonary thromboendarterectomy is associated with excellent clinical and hemodynamic outcomes. The mortality risk factors found are not those usually described in the literature.

Resumen Antecedentes: La tromboendarterectomía pulmonar es el tratamiento de elección actual en pacientes con hipertensión pulmonar tromboembólica crónica. El objetivo del presente estudio fue analizar los resultados clínicos y hemodinámicos y los factores de riesgo de mortalidad en un centro cardiovascular de Colombia. Métodos: Estudio de cohorte entre 2001 y 2019. Se incluyeron todos los pacientes operados. Los factores de riesgo asociados a la mortalidad se establecieron mediante una regresión multivariante mediante el método COX y la supervivencia se estableció mediante el método de Kaplan-Meier. Los valores de p < 0.05 se consideraron estadísticamente significativos. Resultados: se operaron 73 pacientes. La mediana de edad fue de 51 años, 55% mujeres, 79% tenían clase funcional III y IV. La presión arterial pulmonar media fue de 50 mmHg y 640 dyn.s.cm−5 para la resistencia vascular pulmonar. Después de la intervención, hubo una disminución en la presión arterial pulmonar media (p ≤ 0.001) y en la resistencia vascular pulmonar (p = 0.357). El 21% tenía evidencia de hipertensión pulmonar residual. Solo el 8% y el 6% continuaron con clase funcional III y IV a los 6 y 12 meses respectivamente. Hubo 15 muertes (19.1%; 12% a los 30 días). Los factores asociados con la mortalidad fueron el diámetro diastólico del ventrículo derecho medido en el postoperatorio (HR 10.88 IC 95% 1.97-62, p = 0.007), el tiempo de ventilación mecánica invasiva (HR 1.06 IC 95% 1.02-1.09 p = 0.004) y el presencia de complicaciones durante el procedimiento quirúrgico (HR 5.62 IC 95% 1.94-16.22 p = 0.001). Conclusiones: La tromboendartectomía pulmonar se asocia con excelentes resultados clínicos y hemodinámicos. Los factores de riesgo de mortalidad encontrados no son los habitualmente descritos en la literatura.

Crystal structures of cocrystals of 2,7-dihydroxynaphthalene with isoniazid and piracetam.

Cocrystals of 2,7-dihydroxynaphthalene (DHN, or naphthalene-2,7-diol) with isoniazid (pyridine-4-carbohydrazide) (INH), denoted DHN-INH [C10H8O2·C6H7N3O, (I)], and piracetam [2-(2-oxopyrrolidin-1-yl)acetamide] (PIR), denoted DHN-PIR [C10H8O2·C6H10N2O2, (II)], were obtained by the solvent-assisted grinding method and characterized by IR spectroscopy, powder X-ray diffraction and single-crystal X-ray diffraction. Cocrystal (I) crystallized in the triclinic space group P-1 and showed a 2:2 stoichiometry. DHN and INH molecules are connected by O-H...N(pyridine) and O-H...N(hydrazide) hydrogen bonds. Cocrystal (II) crystallized in the space group Pca21 with a 1:1 stoichiometry. DHN and PIR molecules are connected by O-H...O=C hydrogen bonds. The supramolecular architecture of cocrystal (I) showed interlinked supramolecular tapes; meanwhile, in cocrystal (II), interlinked supramolecular sheets were observed.

Results of a Phase 2b Trial With GB001, a Prostaglandin D2 Receptor 2 Antagonist, in Moderate to Severe Eosinophilic Asthma.

BACKGROUND: Prostaglandin D2 receptor 2 (DP2) antagonists inhibit prostaglandin D2-induced effects, including recruitment and activation of cells driving asthma pathogenesis. However, challenges identifying target population and end points persist. RESEARCH QUESTION: What is the effect of the DP2 antagonist GB001 on asthma worsening in patients with moderate to severe eosinophilic asthma? STUDY DESIGN AND METHODS: In this phase IIb, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multicenter study, GB001 or placebo was added to standard-of-care treatment in patients with moderate to severe asthma with a blood eosinophil count ≥ 250 cells/µL. Patients aged ≥ 18 years to < 75 years received one of four once-daily treatments (GB001 20 mg, 40 mg, or 60 mg or placebo). The primary end point was the proportion of patients who experienced asthma worsening by 24 weeks. Efficacy analyses were performed for the intention-to-treat population and safety analyses for patients who received at least one dose of study treatment. RESULTS: A total of 480 patients were treated. The ORs for asthma worsening for GB001 20 mg, 40 mg, and 60 mg vs placebo were 0.674 (95% CI, 0.398-1.142), 0.677 (95% CI, 0.399-1.149), and 0.651 (95% CI, 0.385-1.100), respectively. Analysis according to baseline blood eosinophil levels and/or fractional exhaled nitric oxide did not show greater treatment effects with higher values. Elevated liver aminotransferase levels and adverse events leading to discontinuation were more frequent for GB001 60 mg than with placebo, GB001 20 mg, and GB001 40 mg. INTERPRETATION: Although GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regardless of high/low type 2 phenotype. The overall safety profile was acceptable, although GB001 60 mg was associated with risk of liver injury. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03683576; URL: www. CLINICALTRIALS: gov.

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID).

BACKGROUND: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. METHODS: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. RESULTS: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). CONCLUSIONS: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival.

Clinical and hemodynamic outcomes and mortality risk factors in patients undergoing pulmonary thromboendarterectomy.

BACKGROUND: Pulmonary thromboendarterectomy is the current treatment of choice in patients with chronic thromboembolic pulmonary hypertension. The objective of the present study was to analyze the clinical and hemodynamic outcomes and the risk factors for mortality in a cardiovascular center in Colombia. METHODS: Cohort study, conducted between 2001 and 2019. All operated patients were included in the study. Risk factors associated with mortality were established by means of a multivariate regression using the COX method and survival was established using the Kaplan-Meier method. p < 0.05 was considered statistically significant. RESULTS: Seventy-three patients were operated. Median age was 51 years, 55% of females, 79% had functional Class III and IV. The mean pulmonary arterial pressure was 50 mmHg and 640 dyn.s.cm-5 for pulmonary vascular resistance (PVR). After the intervention, there was a decrease in mean pulmonary artery pressure (p ≤ 0.001) and in PVR (p = 0.357); 21% had evidence of residual pulmonary hypertension. Only 8% and 6% continued with functional Class III and IV at 6 and 12 months, respectively. There were 15 deaths (19.1%; 12% at 30 days). The factors associated with mortality were the diastolic diameter of the right ventricle measured postoperatively (hazard ratio [HR] 10.88 95% confidence interval [CI] 1.97-62, p = 0.007), time of invasive mechanical ventilation (HR 1.06 95% CI 1.02-1.09 p = 0.004), and the presence of complications during the surgical procedure (HR 5.62 95% CI 1.94-16.22 p = 0.001). CONCLUSIONS: Pulmonary thromboendarterectomy is associated with excellent clinical and hemodynamic outcomes. The mortality risk factors found are not those usually described in the literature.

Rhinovirus and asthma: Challenges and opportunities.

Human rhinoviruses (RVs) are the primary aetiological agent of the common cold. Generally, the associated infection is mild and self-limiting, but may also be associated with bronchiolitis in infants, pneumonia in the immunocompromised and exacerbation in patients with pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Viral infection accounts for as many as two thirds of asthma exacerbations in children and more than half in adults. Allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. The prevalence of RV-induced wheezing will likely continue to increase given that asthma affects a significant proportion of the population, with allergic asthma accounting for the majority. Several new respiratory viruses and their subgroups have been discovered, with various degrees of relevance. This review will focus on RV infection in the context of the epidemiologic evidence, genetic variability, pathobiology, clinical studies in the context of asthma, differences with other viruses including COVID-19 and current treatment interventions.

Utilidad de la espirometría en los pacientes hospitalizados por la enfermedad pulmonar obstructiva crónica (EPOC) exacerbada / Usefulness of spirometry in hospitalized patients with Chronic Obstructive Pulmonary Disease (COPD) exacerbated

RESUMEN La espirometría es la prueba estándar para confirmar el diagnóstico de la enfermedad pulmonar obstructiva crónica (EPOC). En los servicios de hospitalización es frecuente encontrar pacientes que ingresan con sospecha de esta condición durante una exacerbación. Con base en las guías actuales, existe controversia sobre si se puede o no realizar la espirometría en este escenario. Objetivo: revisar la utilidad diagnóstica de la espirometría en pacientes hospitalizados con sospecha de EPOC exacerbada. Metodología: se realizó una revisión no sistemática hasta noviembre del 2019. Las bases de datos consultadas fueron PubMed, Cochrane, EMBASE, LILACS, Google Scholar. Se incluyeron estudios prospectivos en pacientes mayores de 18 años, en idioma inglés y español. Se encontraron 573 artículos y se seleccionaron 20 artículos de relevancia para la discusión. Conclusiones: en los pacientes hospitalizados por sospecha de EPOC exacerbada, la espirometría es una herramienta útil para confirmar el diagnóstico. El momento para realizarla es previo al egreso, una vez el paciente está estable. Anotamos que el VEF1 no sería útil para establecer la gravedad.

SUMMARY Spirometry is the standard test to confirm the diagnosis of Chronic Obstructive Pulmonary Disease (COPD). In hospitalization services it is common to find patients admitted with suspicion of this condition during an exacerbation. Based on current guidelines, there is controversy about use or not spirometry in this setting. Objective: To review the diagnostic utility of spirometry in hospitalized patients with suspected exacerbated COPD. Development: A nonsystematic review was carried out until November 2019. The databases consulted were PubMed, Cochrane, EMBASE, LILACS, Google Scholar. Prospective studies were included, in patients over 18 years of age, in English and Spanish. Were found 573 articles and 20 relevant articles were selected for discussion. Conclusions: In hospitalized patients with suspected exacerbated COPD, spirometry is a useful tool to confirm the diagnosis. The time to perform it would be prior to discharge, once the patient is stable. Of note, FEV1 would not be useful for establishing severity.

Impact of mepolizumab on exacerbations in severe asthma: Results from a U.S. insurance claims data base.

Background: In controlled clinical studies, mepolizumab has been shown to reduce exacerbation rates and the use of oral corticosteroids as well as improve asthma control and health-related quality of life compared with placebo in patients with severe eosinophilic asthma. However, real-world data on the impact of mepolizumab on clinical outcomes are limited. Objective: To evaluate the effect of mepolizumab on asthma exacerbations and asthma exacerbation-related costs in patients with severe asthma in U.S. clinical practice. Methods: This retrospective cohort study used U.S. administrative claims data from patients ages ≥12 years and with severe asthma at mepolizumab treatment initiation (index date; identification period, January 2015-June 2017) who had received two or more mepolizumab administrations within 180 days of the index date and had no evidence of treatment with another asthma biologic. The exacerbation rate and exacerbation-related costs were assessed in both the 12 months before mepolizumab initiation (baseline period) and the following 12 months (follow-up period). A clinical trial-like cohort was identified, defined as patients with two or more baseline exacerbations and ≥10 administrations during follow-up. Results: A total of 201 patients were included in the overall population and 74 patients in the clinical trial-like cohort. Mepolizumab significantly reduced the exacerbation rate between the baseline and follow-up periods in both the overall population and the clinical trial-like cohort (p < 0.001), which corresponded to 33.6% and 48.6% reductions, respectively. The rate of exacerbations in patients who required hospitalization between the baseline and follow-up periods was also reduced by 35.3% (p = 0.080) and 68.2% (p = 0.015) in the overall population and in the clinical trial-like cohort, respectively. Cost data were inconclusive. Conclusion: This study, which used real-world data, demonstrated that mepolizumab is associated with reductions in asthma exacerbations, in line with the findings from controlled clinical studies. These results provided further evidence of the effectiveness of mepolizumab in a real-world setting.