Clinical and economic impact of 'ROS1-testing' strategy compared to a 'no-ROS1-testing' strategy in advanced NSCLC in Spain.

BACKGROUND: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain. METHODS: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. RESULTS: A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. CONCLUSIONS: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

Polyoxotungstate@Carbon Nanocomposites As Oxygen Reduction Reaction (ORR) Electrocatalysts.

The oxygen reduction reaction (ORR) has a crucial function as the cathode reaction in energy-converting systems, such as fuel cells (FCs), which contributes to a sustainable energy supply. However, the current use of precious Pt-based electrocatalysts (ECs) is a major drawback for the economic viability of fuel cells. Hence, it is urgent to develop cost-effective and efficient electrocatalysts (ECs) without noble metals to substitute the Pt-based ECs. Herein, we report the preparation and application as ORR electrocatalysts of four new nanocomposites based on sandwich-type phosphotungstate (TBA)7H3[Co4(H2O)2(PW9O34)2] (TBA-Co4(PW9)2) immobilized onto different carbon nanomaterials [single-walled carbon nanotubes (SWCNT), graphene flakes (GF), carbon nanotubes doped with nitrogen (N-CNT), and nitrogen-doped few layer graphene (N-FLG)]. In alkaline medium, the four nanocomposites studied presented comparable onset potentials (0.77-0.90 V vs RHE), which are similar to that observed for Pt/C (0.91 V vs RHE). Higher diffusion-limiting current densities ( jL,0.26V,1600 rpm = -168.3 mA cm-2 mg-1) were obtained for Co4(PW9)2@N-CNT, as compared to Pt/C electrode -130.0 mA cm-2 mg-1) and the other ECs (-45.0, -50.7, and -87.5 mA cm-2 mg-1 for Co4(PW9)2@SWCNT, Co4(PW9)2@GF, and Co4(PW9)2@N-FLG, respectively). All the Co4(PW9)2@CM ECs showed selectivity toward direct O2 reduction to water with the exception of Co4(PW9)2@GF where a mixture of the 2- and 4-electron mechanisms is observed. Furthermore, low Tafel slopes were obtained for all the nanocomposites (68-96 mV dec-1). Co4(PW9)2@CM ECs also showed excellent tolerance to methanol with no significant changes in current density, in contrast to Pt/C (decrease of ≈59% after methanol addition) and good long-term electrochemical stability with current retentions between 75 and 84%.

Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains.

BACKGROUND: Pseudomonas aeruginosa is an environmentally ubiquitous Gram-negative bacterium and important opportunistic human pathogen, causing severe chronic respiratory infections in patients with underlying conditions such as cystic fibrosis (CF) or bronchiectasis. In order to identify mechanisms responsible for adaptation during bronchiectasis infections, a bronchiectasis isolate, PAHM4, was phenotypically and genotypically characterized. RESULTS: This strain displays phenotypes that have been associated with chronic respiratory infections in CF including alginate over-production, rough lipopolysaccharide, quorum-sensing deficiency, loss of motility, decreased protease secretion, and hypermutation. Hypermutation is a key adaptation of this bacterium during the course of chronic respiratory infections and analysis indicates that PAHM4 encodes a mutated mutS gene responsible for a ~1,000-fold increase in mutation rate compared to wild-type laboratory strain P. aeruginosa PAO1. Antibiotic resistance profiles and sequence data indicate that this strain acquired numerous mutations associated with increased resistance levels to ß-lactams, aminoglycosides, and fluoroquinolones when compared to PAO1. Sequencing of PAHM4 revealed a 6.38 Mbp genome, 5.9 % of which were unrecognized in previously reported P. aeruginosa genome sequences. Transcriptome analysis suggests a general down-regulation of virulence factors, while metabolism of amino acids and lipids is up-regulated when compared to PAO1 and metabolic modeling identified further potential differences between PAO1 and PAHM4. CONCLUSIONS: This work provides insights into the potential differential adaptation of this bacterium to the lung of patients with bronchiectasis compared to other clinical settings such as cystic fibrosis, findings that should aid the development of disease-appropriate treatment strategies for P. aeruginosa infections.

Overexpression of MexCD-OprJ reduces Pseudomonas aeruginosa virulence by increasing its susceptibility to complement-mediated killing.

We evaluated the resistance to complement-mediated killing of a collection of isogenic Pseudomonas aeruginosa strains expressing different antimicrobial resistance phenotypes. Only the nfxB mutant demonstrated increased susceptibility to complement compared with that for the wild-type strain. This increment was due to the overexpression of MexCD-OprJ, which led to increased C3 opsonization and a reduced ability to infect the lungs of mice. Our results show that the acquisition of antibiotic resistance may alter the interplay of P. aeruginosa with the host immune system.

Long head of biceps tendon augmentation in rotator cuff repair enhances tendon healing, shoulder function and patient-reported outcomes one-year post-surgery.

Purpose: The aim is to determine the effect on healing and functionality of patients after 1 year of biceps augmentation of a rotator cuff repair (RCR) compared to RCR plus long head of the biceps (LHB) tenotomy. In addition, to analyse the main factors involved in the recovery after the surgery. Methods: A prospective, comparative, non-randomized study (Level of Evidence III) was conducted. Patients with repairable rotator cuff tears were allocated to either the control group, with a double row transosseous equivalent RCR with LHB tenotomy, or the RCR+augmentation with LHB group. Patients were evaluated for radiological (MRI), clinical (cuff size, Patte and Goutallier scales) and functional variables (Constant and American Shoulder and Elbow Surgeons [ASES] scales) before the intervention. At 1-year follow-up cuff healing was confirmed through MRI and functional evaluation with Constant, ASES, simple shoulder test [SST] and Disabilities of the Arm, Shoulder and Hand scales. Results: Seventy-seven patients underwent control or RCR+augmentation with LHB, there were no preoperative differences between the groups. After 1 year of the surgery, re-rupture occurred in 38.5% and 16% of the patients in control and RCR+augmentation with LHB groups, respectively (p = .026). Total functionality was higher (p < .05) in RCR+augmentation with LHB than in the control group: Constant, SST and ASES scales. Among the explored factors involved in healing, re-rupture occurred in 100% of the cases with high fatty degeneration. Besides, higher initial functionality (Constant scale) and RCR+augmentation with LHB increased the odds of healing (odds ratio [OR] = 1.12 [1.04-1.21]; OR = 5 [1, 61], respectively), while higher cuff length had a detrimental effect (OR = 0.92 [0.85-0.99]). Conclusion: RCR+augmentation with LHB achieves a higher healing percentage and a better functional evolution than RCR+LHB tenotomy, 1 year after cuff repair. Fatty degeneration, cuff length and initial functionality are the main factors involved in cuff healing. Level of Evidence: Level III randomized controlled trial.

Critical Factors Affecting the Selective Transformation of 5-Hydroxymethylfurfural to 3-Hydroxymethylcyclopentanone Over Ni Catalysts.

The ring-rearrangement of 5-hydroxymethylfurfural (HMF) to 3-hydroxymethylcyclopentanone (HCPN) was investigated over Ni catalysts supported on different carbon supports and metallic oxides with different structure and acid-base properties. Their catalytic performance was tested in a batch stirred reactor in aqueous solution at 180 °C and 30 bar of H2. Under these conditions, the HMF hydrogenation proceeds through three possible competitive routes: (i) a non-water path leading to the total hydrogenation product, 2,5-di-hydroxymethyl-tetrahydrofuran (DHMTHF), and two parallel acid-catalyzed water-mediated routes responsible for (ii) ring-opening and (iii) ring-rearrangement reaction products. All catalyst systems primarily produced HCPN, but reaction rates and product distribution were influenced by several variables, some of them intensely analyzed in this work. The most proper conditions resulted to be the presence of the medium/strong Lewis's acidity of a Ni/ZrO2 catalyst (initial TOF=5.99 min-1 and 73 % HCPN selectivity) or the Brønsted acidity originated by an oxidized high surface area graphite, Ni/HSAG-ox (initial TOF=5.92 min-1 and 87 % HCPN selectivity). However, too high density of acidic sites on the catalyst support (Ni/Al2O3) and sulfur impurities from the HMF feedstock led to catalyst deactivation by coke deposition and Ni poisoning, respectively.

Adsorption of cadmium (II) on organic xerogel microspheres: effect of adding sepiolite or vermiculite and operating conditions on the adsorption capacity.

The organic xerogel (OX) was synthesized through sol-gel polymerization of formaldehyde and resorcinol in inverse emulsion using Na2CO3 as a catalyst. Meanwhile, OX containing sepiolite (OX-Sep) and vermiculite (OX-Ver) were prepared similarly to OX but adding clays during synthesis. All materials were mesoporous and presented spherical morphology, and the surface of these materials exhibited an acidic character because the concentration of acidic sites was higher than those of basic sites. Cd(II) adsorption from aqueous solutions onto OX, OX-Sep, and OX-Ver was examined, and the OX-Sep showed the highest adsorption capacity towards Cd(II) of 189.7 mg/g, being 1.5, 2, and 36 times higher than that of OX-Ver, OX, and Sep. The OX-Sep capacity for adsorbing Cd(II) was significantly lessened by decreasing the pH from 7 to 4 and raising the ionic strength from 0.01 N to 0.1 N. This trend was ascribed to electrostatic attraction between the Cd+2 in water and the negatively charged surface of OX-Sep. Besides, desorption studies at pH 4 showed that the average desorption percentage of Cd(II) adsorbed on OX-Sep was 80%. The characterization results and the effect of the operating conditions on the adsorption capacity proved that electrostatic attraction and cation exchange play a crucial role in the adsorption mechanism.

Surfactant protein A blocks recognition of Pseudomonas aeruginosa by CKAP4/P63 on airway epithelial cells.

We used isogenic mutant strains that were deficient or over-expressed capsule to study the function of the alginate exopolysaccharide in the interaction of Pseudomonas aeruginosa with the human airway epithelial cells (AEC) in the presence or absence of surfactant protein A (SP-A). SP-A prevented the invasion of AEC by alginate-producing P. aeruginosa strains because of a direct effect on the AEC. Monoclonal antibodies to CKAP4/P63, the principal SP-A-binding receptor on AEC, or inhibition of its expression using specific siRNA reduced the invasion of both highly encapsulated and poorly encapsulated strains, but not the invasion of the acapsular mutant. Treatment of AEC with SP-A, monoclonal antibodies to CKAP4/P63, or CKAP4/P63-specific siRNA decreased the binding of purified alginate exopolysaccharide to AEC. Alginate binding to AEC reduced SP-A release by these cells. Because the alginate exopolysaccharide is surface-exposed, levels of SP-A may be crucial to modulate the interaction of P. aeruginosa with AEC.

Arthroscopic Superior Capsular Reconstruction With the Long Head of the Biceps Tendon to Reinforce the Repair of a Supraspinatus Tear and Increase Healing.

Rotator cuff tears continue to be a challenge for the shoulder surgeon since there is still a high rate of retears. To increase the rate of repair and decrease the number of retears, we present a technique, in which we reinforce a tension-free double-row repair of the supraspinatus with reconstruction of the superior capsule with the long head of the biceps (LHB). With this reinforcement of the cuff suture using the LHB, we increase both the biomechanics and biology of the repair and decrease the rate of reruptures.

Graphene-Type Materials for the Dispersive Solid-Phase Extraction Step in the QuEChERS Method for the Extraction of Brominated Flame Retardants from Capsicum Cultivars.

A new application of graphene-type materials as an alternative cleanup sorbent in a quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure combined with GC-ECD/GC-MS/GC-MS/MS detection was successfully used for the simultaneous analysis of 12 brominated flame retardants in Capsicum cultivar samples. The chemical, structural, and morphological properties of the graphene-type materials were evaluated. The materials exhibited good adsorption capability of matrix interferents without compromising the extraction efficiency of target analytes when compared with other cleanups using commercial sorbents. Under optimal conditions, excellent recoveries were obtained, ranging from 90 to 108% with relative standard deviations of <14%. The developed method showed good linearity with a correlation coefficient above 0.9927, and the limits of quantification were in the range of 0.35-0.82 µg/kg. The developed QuEChERS procedure using reduced graphite oxide (rGO) combined with GC/MS was successfully applied in 20 samples, and the pentabromotoluene residues were quantified in two samples.

Dynamics of Pd Subsurface Hydride Formation and Their Impact on the Selectivity Control for Selective Butadiene Hydrogenation Reaction.

Structure-sensitive catalyzed reactions can be influenced by a number of parameters. So far, it has been established that the formation of Pd-C species is responsible for the behavior of Pd nanoparticles employed as catalysts in a butadiene partial hydrogenation reaction. In this study, we introduce some experimental evidence indicating that subsurface Pd hydride species are governing the reactivity of this reaction. In particular, we detect that the extent of formation/decomposition of PdHx species is very sensitive to the Pd nanoparticle aggregate dimensions, and this finally controls the selectivity in this process. The main and direct methodology applied to determine this reaction mechanism step is time-resolved high-energy X-ray diffraction (HEXRD).

Nitrate reduction over a Pd-Cu/MWCNT catalyst: application to a polluted groundwater.

The influence of the presence of inorganic and organic matter during the catalytic reduction of nitrate in a local groundwater over a Pd-Cu catalyst supported on carbon nanotubes was investigated. It was observed that the catalyst performance was affected by the groundwater composition. The nitrate conversion attained was higher in the experiment using only deionized water as solvent than in the case of simulated or real groundwater. With exception of sulphate ions, all the other solutes evaluated (chloride and phosphate ions and natural organic matter) had a negative influence on the catalytic activity and selectivity to nitrogen.

Arthroscopic Treatment of Chronic Acromioclavicular Dislocation With Semitendinosus Autograft and Coracoclavicular Suspension Fixation.

The management of acromioclavicular dislocations remains controversial. On many occasions, these chronic dislocations are asymptomatic. However, there are patients who, despite good rehabilitation treatment, do present with pain, periscapular muscle fatigue, weakness, paresthesia or scapular dyskinesia. In these patients, surgical treatment is indicated.

Ability of final PET/CT to predict response to first-line treatment in real patients with classical Hodgkin lymphoma.

Up to 25% of patients with classical Hodgkin lymphoma (cHL) and a negative interim PET/CT will progress. Unfortunately, there are few published studies on the predictive value of PET/CT performed after finishing treatment. The objective of our study was to assess the role of the final PET/CT (fPET/CT) in predicting progression in a retrospective series of patients treated in the last 10 years with a homogeneous protocol (ABVD + / - radiotherapy). We reviewed a cohort of 227 patients with newly diagnosed cHL. fPET/CT was performed on 212 patients (93%). In patients with a positive fPET, progression-free survival at 60 months was 17% (94% if fPET was negative, p = 0.000). The positive and negative predictive values for the fPET were 76% and 94%, respectively (Fisher's exact test, p = 0.000). In the subgroup of patients with advanced-stage cHL, progression-free survival at 60 months was 91% with negative fPET and 0% with positive fPET (p = 0.000). However, fPET was negative in 19 of the 29 patients with a positive interim PET/CT (only 2 showed progression). In conclusion, fPET is a useful tool to predict treatment failure in patients with newly diagnosed cHL, especially advanced-stage disease.

Effect of the Carbon Support and Conditions on the Carbothermal Synthesis of Cu-Molybdenum Carbide and Its Application on CO2 Hydrogenation to Methanol.

The synthesis of methanol by carbon dioxide hydrogenation has been studied using copper-molybdenum carbides supported on high surface area graphite, reduced graphene oxide and carbon nanotubes. The synthesis conditions and the effect of the support were studied. The catalysts were prepared in situ using H2 or He at 600 °C or 700 °C. Both molybdenum carbide and oxycarbide were obtained. A support with less reactive carbon resulted in lower proportion of carbide obtained. The best results were achieved over a 5 wt.% Cu and 10 wt.% Mo on high surface area graphite that reached 96.3% selectivity to methanol.

Promotion of Ru or Ni on Alumina Catalysts with a Basic Metal for CO2 Hydrogenation: Effect of the Type of Metal (Na, K, Ba).

Ru and Ni on alumina catalysts have been promoted with a 10 wt% of alkali metal (K or Na) or alkaline earth metal (Ba) and tested in CO2 methanation. For the catalyst consisting of Ni and Ba, the variation of Ba loading while keeping Ni loading constant was studied. The promotion in terms of enhanced CH4 yield was found only for the addition of barium to 15 wt% Ni/Al2O3. In contrast, K and Na addition increased the selectivity to CO while decreasing conversion. For the Ru-based catalyst series, no enhancement in conversion or CH4 yield was attained by any of the alkaline metals. CO2 temperature-programed desorption (CO2-TPD) revealed that the amount of chemisorbed CO2 increased significantly after the addition of the base metal. The reactivity of COx ad-species for each catalyst was assessed by temperature-programed surface reaction (TPSR). The characterization revealed that the performance in the Sabatier reaction was a result of the interplay between the amount of chemisorbed CO2 and the reactivity of the COx ad-species, which was maximized for the (10%Ba)15%Ni/Al2O3 catalyst.

Preparation, Characterization, and Activity of Pd/PSS-Modified Membranes in the Low Temperature Dry Reforming of Methane with and without Addition of Extra Steam.

The external surface of a commercial porous stainless steel (PSS) was modified by either oxidation in air at varying temperatures (600, 700, and 800 °C) or coating with different oxides (SiO2, Al2O3, and ZrO2). Among them, PSS-ZrO2 appears as the most suitable carrier for the synthesis of the Pd membrane. A composite Pd membrane supported on the PSS-ZrO2 substrate was prepared by the electroless plating deposition method. Supported Ru catalysts were first evaluated for the low-temperature methane dry reforming (DRM) reaction in a continuous flow reactor (CR). Ru/ZrO2-La2O3 catalyst was found to be active and stable, so it was used in a membrane reactor (MR), which enhances the methane conversions above the equilibrium values. The influence of adding H2O to the feed of DRM was investigated over a Ru/ZrO2-La2O3 catalyst in the MR. Activity results are compared with those measured in a CR. The addition of H2O into the feed favors other reactions such as Water-Gas Shift (RWGS) and Steam Reforming (SR), which occur together with DRM, resulting in a dramatic decrease of CO2 conversion and CO production, but a marked increase of H2 yield.

Study of the Interaction of an Iron Phthalocyanine Complex over Surface Modified Carbon Nanotubes.

Carbon nanotubes (CNT) were prepared by a modified chemical vapor deposition (CVD) method. The synthesized carbon materials were treated with acidic and basic solutions in order to introduce certain surface functional groups, mainly containing oxygen (OCNT) or amine (ACNT) species. These modified CNTs (OCNT and ACNT) as well as the originally prepared CNT were reacted with a non-ionic Fe complex, Iron (II) Phthalocyanine, and three composites were obtained. The amount of metal complex introduced in each case and the interaction between the complex and the CNT materials were studied with the aid of various characterization techniques such as TGA, XRD, and XPS. The results obtained in these experiments all indicated that the interaction between the complex and the CNT was greatly affected by the functionalization of the latter.

Significant Decrease in Annual Cancer Diagnoses in Spain during the COVID-19 Pandemic: A Real-Data Study.

The COVID-19 pandemic has caused a profound change in health organizations at both the primary and hospital care levels. This cross-sectional study aims to investigate the impact of the COVID-19 pandemic in the annual rate of new cancer diagnosis in two university-affiliated hospitals. This study includes all the patients with a pathological diagnosis of cancer attended in two hospitals in Málaga (Spain) during the first year of pandemic. This study population was compared with the patients diagnosed during the previous year 2019. To analyze whether the possible differences in the annual rate of diagnoses were due to the pandemic or to other causes, the patients diagnosed during 2018 and 2017 were also compared. There were 2340 new cancer diagnosis compared to 2825 patients in 2019 which represented a decrease of -17.2% (p = 0.0001). Differences in the number of cancer patients diagnosed between 2018 and 2019 (2840 new cases; 0.5% increase) or 2017 and 2019 (2909 new cases; 3% increase) were not statistically significant. The highest number of patients lost from diagnosis in 2020 was in breast cancer (-26.1%), colorectal neoplasms (-16.9%), and head and neck tumors (-19.8%). The study of incidence rates throughout the first year of the COVID-19 pandemic shows that the diagnosis of new cancer patients has been significantly impaired. Health systems must take the necessary measures to restore pre-pandemic diagnostic procedures and to recover lost patients who have not been diagnosed.

Application of New Nanoparticle Structures as Catalysts.

Nanocatalysts, more precisely solids nanomaterials with catalytic properties to be used as heterogeneous catalysts, are an extended and very diverse group of nanostructured materials representing, at present, an active area of research with application in many catalyzed processes [...].