Highly Efficient Solar-Light-Driven Photodegradation of Metronidazole by Nickel Hexacyanoferrate Nanocubes Showing Enhanced Catalytic Performances.

Environmental pollution is a complex problem that threatens the health and life of animal and plant ecosystems on the planet. In this respect, the scientific community faces increasingly challenging tasks in designing novel materials with beneficial properties to address this issue. This study describes a simple yet effective synthetic protocol to obtain nickel hexacyanoferrate (Ni-HCF) nanocubes as a suitable photocatalyst, which can enable an efficient photodegradation of hazardous anthropogenic organic contaminants in water, such as antibiotics. Ni-HCF nanocubes are fully characterized and their optical and electrochemical properties are investigated. Preliminary tests are also carried out to photocatalytically remove metronidazole (MDZ), an antibiotic that is difficult to degrade and has become a common contaminant as it is widely used to treat infections caused by anaerobic microorganisms. Under simulated solar light, Ni-HCF displays substantial photocatalytic activity, degrading 94.3% of MDZ in 6 h. The remarkable performance of Ni-HCF nanocubes is attributeto a higher ability to separate charge carriers and to a lower resistance toward charge transfer, as confirmed by the electrochemical characterization. These achievements highlight the possibility of combining the performance of earth-abundant catalysts with a renewable energy source for environmental remediation, thus meeting the requirements for sustainable development.

Efficacy of photobiomodulation therapy combined with mobile health education in patients with head and neck cancer suffering from chronic xerostomia after radiotherapy: protocol for a three-arm, randomised, placebo-controlled, double-blinded study.

INTRODUCTION: The role of photobiomodulation (PBM) therapy for oral tissue damage induced by cancer treatment is currently unclear, and there is low-quality to moderate-quality evidence supporting the use of this approach for treating xerostomia and/or hyposalivation. Consequently, patients with head and neck cancer increasingly turn to basic oral hygiene to alleviate salivary gland dysfunction, and their adherence can be improved by mobile health (mHealth) education. The primary objective of this study will be to analyse the effects of different doses of PBM therapy (7.5 J/cm2 vs 3 J/cm2) plus mHealth education on quality of life (QoL), oral health, salivary secretion and salivary gland ultrasound assessment at postintervention and at the 6-month follow-up in patients with head and neck cancer after radiotherapy compared with those in control group. METHODS AND ANALYSIS: A prospective, three-arm, randomised, placebo-controlled, double-blinded study will be conducted among patients with head and neck cancer suffering from chronic xerostomia. A total of 20 patients per arm will be included and randomly assigned to receive 7.5 J/cm2 of PBM, 3 J/cm2 of PBM or placebo therapy. PBM therapy will be applied during 24 sessions at 22 points extra and intraorally two times per week for 3 months, combined with a mobile application (https://www.laxer.es). The assessments will be recorded at the beginning of the study, at postintervention and at the 6-month follow-up. The primary outcomes will be QoL, oral health, salivary secretion and salivary gland ultrasound. The pain pressure threshold, functional performance, mood and sleep quality will be secondary indicators. ETHICS AND DISSEMINATION: This study received ethics approval from the Andalusian Biomedical Research Ethics Portal (2402-N-21 CEIM/CEI Provincial de Granada) according to the Declaration of Helsinki for Biomedical Research. The results of this study will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05106608.

Evaluation of antibody-based preventive alternatives for respiratory syncytial virus: a novel multi-criteria decision analysis framework and assessment of nirsevimab in Spain.

BACKGROUND: Respiratory syncytial virus (RSV) is a highly infectious disease that poses a significant clinical and medical burden, as well as social disruption and economic costs, recognized by the World Health Organization as a public health issue. After several failed attempts to find preventive candidates (compounds, products, including vaccines), new alternatives might be available, one being nirsevimab, the first and only option approved for RSV prevention in neonates and infants during their first RSV season. The objective of this study was to develop a novel multi-criteria decision analysis (MCDA) framework for RSV antibody-based preventive alternatives and to use it to assess the value of nirsevimab vs. placebo as a systematic immunization approach to prevent RSV in neonates and infants during their first RSV season in Spain. METHODS: Based on a pre-established model called Vaccinex, an ad-hoc MCDA framework was created to reflect relevant attributes for the assessment of current and future antibody-based preventive measures for RSV. The estimated value of nirsevimab was obtained by means of an additive linear model combining weights and scores assigned by a multidisciplinary committee of 9 experts. A retest and three sensitivity analyses were conducted. RESULTS: Nirsevimab was evaluated through a novel framework with 26 criteria by the committee as a measure that adds value (positive final estimated value: 0.56 ± 0.11) to the current RSV scenario in Spain, by providing a high efficacy for prevention of neonates and infants. In addition, its implementation might generate cost savings in hospitalizations and to the healthcare system and increase the level of public health awareness among the general population, while reducing health inequities. CONCLUSIONS: Under a methodology with increasing use in the health field, nirsevimab has been evaluated as a measure which adds value for RSV prevention in neonates and infants during their first RSV season in Spain.

Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

A Modular and Convergent Synthetic Route to Supramolecular Cyclic Dimers Based on Amidinium-Carboxylate Interactions.

We describe herein the optimized design and modular synthetic approach towards supramolecularly programmed monomers that can form discrete macrocyclic species of controllable size and shape through amidinium-carboxylate interactions in apolar and polar media.

Rifampicin resistance conferring mutations among Mycobacterium tuberculosis strains in Rwanda.

Background: The World Health Organization-endorsed phenotypic and genotypic drug-susceptibility testing (gDST/pDST) assays for the detection of rifampicin-resistant (RR) tuberculosis (TB), may miss some clinically relevant rpoB mutants, including borderline mutations and mutations outside the gDST-targeted hotspot region. Sequencing of the full rpoB gene is considered the reference standard for rifampicin DST but is rarely available in RR-TB endemic settings and when done indirectly on cultured isolates may not represent the full spectrum of mutations. Hence, in most such settings, the diversity and trends of rpoB mutations remain largely unknown. Methods: This retrospective study included rpoB sequence data from a longitudinal collection of RR-TB isolates in Rwanda across 30 years (1991-2021). Results: Of 540 successfully sequenced isolates initially reported as RR-TB, 419 (77.6%) had a confirmed RR conferring mutation. The Ser450 Leu mutation was predominant throughout the study period. The Val170Phe mutation, not covered by rapid gDST assays, was observed in only four patients, three of whom were diagnosed by pDST. Along with the transition from pDST to rapid gDST, borderline RR-associated mutations, particularly Asp435Tyr, were detected more frequently. Borderline mutants were not associated with HIV status but presented lower odds of having rpoA-C compensatory mutations than other resistance-conferring mutations. Conclusion: Our analysis showed changes in the diversity of RR-TB conferring mutations throughout the study period that coincided with the switch of diagnostic tools to rapid gDST. The study highlights the importance of rapid molecular diagnostics reducing phenotypic bias in the detection of borderline rpoB mutations while vigilance for non-rifampicin resistance determinant region mutations is justified in any setting.

LDH/ADA ratio in pleural fluid for the diagnosis of infectious pleurisy.

Pleural effusion (PE) is a common medical concern, often requiring thoracentesis for a definitive diagnosis. An elevated pleural fluid adenosine deaminase (ADA) may indicate tuberculosis, but this is not always the case. This study aimed to evaluate the accuracy of biomarkers determined in pleural fluid and propose a new diagnostic strategy for PE in patients with high levels of ADA in pleural fluid. This retrospective analysis studied patients with PE who received thoracentesis for the first time with an ADA level of > 33 U/L in the pleural fluid analysis at two tertiary hospitals from March 2019 to March 2023. Demographic and clinical data, as well as pleural fluid biomarkers and their ratios, were studied and compared between different PE groups, and a decision tree was developed. During the study period, 259 patients were enrolled, with four different types of PE: parapneumonic (PPE) 155, tuberculosis (TPE) 41, malignant (MPE) 50, and miscellaneous 13. Biomarkers and their ratios performed well in the differential diagnosis of PE, with the LDH/ADA ratio distinguishing between PPE and non-PPE with sensitivity and specificity of 98.06% and 98.08%, respectively. The combination of LDH/ADA ratio, ADA, and mononuclear cell percentage was identified as important factors for creating a decision tree with an overall accuracy of 89.96%. The pleural fluid LDH/ADA ratio was a useful diagnostic for distinguishing PPE from non-PPE, and a decision tree with an accuracy of 89.96% was created to differentiate the four forms of PE in clinical situations.

Microwave-Assisted Synthesis of Zeolite A from Metakaolinite for CO2 Adsorption.

The global demand for energy and industrial growth has generated an exponential use of fossil fuels in recent years. It is well known that carbon dioxide (CO2) is mainly produced, but not only from fuels, which has a negative impact on the environment, such as the increasing emission of greenhouse gases. Thus, thinking about reducing this problem, this study analyzes microwave irradiation as an alternative to conventional heating to optimize zeolite A synthesis conditions for CO2 capture. Synthesis reaction parameters such as different temperatures (60-150 °C) and different time durations (1-6 h) were evaluated. The CO2 adsorption capacity was evaluated by CO2 adsorption-desorption isotherms at 25 °C and atmospheric pressure. The results showed that the synthesis of zeolite A by microwave irradiation was successfully obtained from natural kaolinite (via metakaolinization), reducing both temperature and time. Adsorption isotherms show that the most promising adsorbent for CO2 capture is a zeolite synthesized at 100 °C for 4 h, which reached an adsorption capacity of 2.2 mmol/g.

Association of periodontitis with cognitive decline and its progression: Contribution of blood-based biomarkers of Alzheimer's disease to this relationship.

AIM: To assess whether periodontitis is associated with cognitive decline and its progression as well as with certain blood-based markers of Alzheimer's disease. MATERIALS AND METHODS: Data from a 2-year follow-up prospective cohort study (n = 101) was analysed. Participants with a previous history of hypertension and aged ≥60 years were included in the analysis. All of them received a full-mouth periodontal examination and cognitive function assessments (Addenbrooke's Cognitive Examination (ACE) and Mini-Mental State Examination [MMSE]). Plasma levels of amyloid beta (Aß)1-40 , Aß1-42 , phosphorylated and total Tau (p-Tau and t-Tau) were determined at baseline, 12 and 24 months. RESULTS: Periodontitis was associated with poor cognitive performance (MMSE: ß = -1.5 [0.6]) and progression of cognitive impairment (hazard ratio [HR] = 1.8; 95% confidence interval: 1.0-3.1). Subjects with periodontitis showed greater baseline levels of p-Tau (1.6 [0.7] vs. 1.2 [0.2] pg/mL, p < .001) and Aß1-40 (242.1 [77.3] vs. 208.2 [73.8] pg/mL, p = .036) compared with those without periodontitis. Concentrations of the latter protein also increased over time only in the periodontitis group (p = .005). CONCLUSIONS: Periodontitis is associated with cognitive decline and its progression in elderly patients with a previous history of hypertension. Overexpression of p-Tau and Aß1-40 may play a role in this association.

Persistent pain management in an oncology population through pain neuroscience education, a multimodal program: PaiNEd randomized clinical trial protocol.

INTRODUCTION: Pain is one of the most persistent symptoms after cancer treatment. The central nervous system can erroneously stay in its alarm phase, altering the pain experience of patients who have cancer. Pain neuroscience education (PNE) with multimodal approaches may benefit these patients. OBJECTIVE: This protocol aims to determine the effectiveness of a PNE tool on pain, physical function and quality of life, as a supplement to a multimodal rehabilitation (MR) program in patients who had breast cancer (BC). METHODS: An 8-week double-blinded randomized controlled trial will be conducted, including 72 participants who had BC and who have persistent pain, randomized into three groups: PNE program + MR program, traditional biomedical information + MR program and control group. The PNE program will include educational content that participants will learn through a mobile app and the MR program will include a concurrent exercise program and manual therapy. The primary outcome will be the perceived pain assessed using the Visual Analogue Scale and secondary outcomes are others related to pain, physical function and quality of life. All outcomes will be evaluated at baseline, at the end of the intervention and 6 months after the end of intervention. DISCUSSION: The proposed study may help BC patients with persistent pain improve their pain experience, quality of life and provide for more adaptive pain-coping strategies. This protocol could propose an action guide to implement different integral approaches for the treatment of sequelae. This treatment option could be offered to this patient profile and it could be easily implemented in the healthcare systems due to its low costs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04877860. (February18, 2022).

An Efficient Procedure for Bonding Piezoelectric Transducers to Thermoplastic Composite Structures for SHM Application and Its Durability in Aeronautical Environmental Conditions.

Piezoceramic transducers (PCTs) bonded to carbon fiber-reinforced plastic (CFRP) composite structures must be durable as well as remain properly bonded to the structure in order to provide reliable data for accurate guided-wave-based structural health monitoring (SHM) of aeronautical components. The current method of bonding transducers to composite structures through epoxy adhesives faces some shortcomings, such as difficult reparability, lack of weldability, longer curing cycles, and shorter shelf life. To overcome these shortcomings, a new efficient procedure for bonding the transducers to thermoplastic (TP) composite structures was developed by utilizing TP adhesive films. Application-suitable TP films (TPFs) were identified and characterized through standard differential scanning calorimetry (DSC) and single lap shear (SLS) tests to study their melting behavior and bonding strength, respectively. Special PCTs called acousto-ultrasonic composite transducers (AUCTs) were bonded to high-performance TP composites (carbon fiber Poly-Ether-Ether-Ketone) coupons with a reference adhesive (Loctite EA 9695) and the selected TPFs. The integrity and durability of the bonded AUCTs in aeronautical operational environmental conditions (AOEC) were assessed in accordance to the standard Radio Technical Commission for Aeronautics DO-160. The AOEC tests performed were operating low and high temperatures, thermal cycling, hot-wet, and fluid susceptibility tests. The health and bonding quality of the AUCTs were evaluated by the electro-mechanical impedance (EMI) spectroscopy method and ultrasonic inspections. The AUCT defects were created artificially and their influence on the susceptance spectra (SS) was measured to compare them with the AOEC-tested AUCTs. The results show that a small change occurred in the SS characteristics of the bonded AUCTs in all of the adhesive cases after the AOEC tests. After comparing the changes in SS characteristics of simulated defects with that of the AOEC-tested AUCTs, the change is relatively smaller and therefore it can be concluded that no serious degradation of the AUCT or the adhesive layer has occurred. It was observed that the most critical tests among the AOEC tests are the fluid susceptibility tests, which can cause the biggest change in the SS characteristics. Comparing the performance of the AUCTs bonded with the reference adhesive and the selected TPFs in the AOEC tests, it was seen that some of the TPFs, e.g., Pontacol 22.100 outperforms the reference adhesive, while the other TPFs have similar performance to that of the reference adhesive. Therefore, in conclusion, the AUCTs bonded with the selected TPFs can withstand the operational and environmental conditions of an aircraft structure, and hence, the proposed procedure is easily installed, reparable, and a more reliable method of bonding sensors to aircraft structures.

Pérdida ponderal como debut de lipoblastoma mesentérico en un lactante / Weight loss as clinical presentation of mesenteric lipoblastoma in an infant

Introducción: el estancamiento ponderal durante el segundo año de vida es un motivo frecuente de consulta que requiere seguimiento y, en ocasiones, pruebas complementarias con el fin de descartar las causas más frecuentes a esta edad, tales como infecciones o síndromes malabsortivos. Se presenta el caso de un lactante con estancamiento ponderal de etiología poco frecuente. Caso clínico: varón que a partir de los 15 meses de edad comienza con pérdida ponderal, con apetito y estado general conservados, sin otros síntomas. Se objetiva un descenso de peso desde el percentil 75 hasta el percentil 25 a lo largo de tres meses, sin repercusión en la talla ni el perímetro cefálico. A la exploración física tenía aspecto desnutrido, con distensión y timpanismo abdominal. Se solicitan pruebas complementarias, incluyendo anticuerpos de celiaquía por sospecha de síndrome malabsortivo, que fueron normales. En la ecografía abdominal se observa imagen compatible con tumoración de gran tamaño. Ante estos hallazgos, se amplían pruebas de imagen mediante tomografía computarizada (TC) y resonancia magnética (RM) abdominales, donde se encuentra una imagen compatible con lipoblastoma mesentérico. Se interviene quirúrgicamente a los 20 meses, confirmándose en el estudio histológico el diagnóstico de sospecha. Conclusión: los lipoblastomas son tumores benignos, infrecuentes, prácticamente exclusivos de la edad pediátrica. Generalmente se localizan en zonas superficiales, siendo estos asintomáticos. Los de localización profunda, como el del caso descrito, son excepcionales y pueden producir síntomas secundarios a compresión local. El diagnóstico definitivo se realiza mediante estudio histológico, siendo la exéresis el tratamiento de elección (AU)

Introduction: loss weight in the second year of life is a frequent reason for consultation that requires follow-up and sometimes work up complementary in order to rule out the most frequent causes at this age, such as infections or malabsorptive diseases. We present the case of an infant with weight stagnation secondary to an unfrequent cause.Clinical case: a male began with weight loss at 15 months of age, with appetite and general condition preserved without other symptoms. A decrease in weight percentile was observed from 75th to the 25th percentile over three months without repercussions on height or head circumference. On physical examination, he appeared thinned, with abdominal distension and tympanism. Complementary tests, including celiac disease antibodies to suspected malabsorptive syndrome were ordered, without patological findings. Abdominal ultrasound showed an image compatible with a big tumor. With these findings, an abdominal CT scan and MRI were performed, and an image compatible with mesenteric lipoblastoma was found. Surgery was performed at 20 months, supporting the suspected diagnosis in the histological study.Conclusion: lipoblastomas are infrequent benign tumors, mainly exclusive of the pediatric age. Frecuently, they are located in superficial areas, and are asymptomatic. Those of deep localization, as the described case, are usually exceptional, and may present symptoms secondary to local compression. The definitive diagnosis is made by histological study and the removal the treatment of choice. (AU)

Pleural empyema secondary to perforated diverticulosis due to biliary neoplasia infiltration.

A long-term female smoker presented to the emergency department with cough, greenish mucus and dyspnoea, without fever. The patient also reported abdominal pain and significant weight loss in recent months. Laboratory tests showed leucocytosis with neutrophilia, lactic acidosis and a faint left lower lobe consolidation on chest X-ray, for which she was admitted to the pneumology department and started on broad-spectrum antibiotherapy. After 3 days of clinical stability, the patient deteriorated rapidly, with worsening of analytical parameters and coma. The patient died a few hours later. Given the rapid and unexplained evolution of the disease, a clinical autopsy was requested, which revealed a left pleural empyema caused by perforated diverticula by neoplastic infiltration of biliary origin.

PD-L1 immunoexpression and molecular characterization of histological subtypes in urothelial carcinoma.

INTRODUCTION: Urothelial carcinoma (UC) has histological subtypes whose phenotype reflects their molecular diversity, behavior and response to conventional therapy. Immune checkpoint inhibitors (ICIs) have improved the management of UC by evaluation of PD-L1. In the case of PD-L1 22C3, the initiation of ICI is considered from a combined positive score (CPS) greater than 10. However, UC subtypes with absent PD-L1 22C3 expression in cases with CPS>10 may not respond to these treatments. This study aims to establish a correlation between the PD-L1 immunoexpression and molecular alterations in divergent differentiation and histological subtypes of UC (UC-s). MATERIAL AND METHODS: Twenty-six samples of UC were detected from a total of 24 patients. Two pathologists performed separately an assessment of UC-s on hematoxylin-eosin as well as PD-L1 expression. Molecular study of each case was performed by next generation sequencing (NGS). A descriptive analysis of the variables included was conducted. RESULTS: Nine cases (34.61%) showed a CPS>10, some with negative PD-L1 immunoexpression in aggressive UC-s. The molecular study revealed alterations in genes belonging to the p53/cell cycle control, RAS, and DNA repair pathways, among others. None of the alterations were exclusive to any histological subtype. DISCUSSION: Special attention should be paid to CPS>10 cases that include histological subtypes of UC with divergent expression for PD-L1 as they may not respond to treatment with ICI. We recommend examining the proportion and PD-L1 status of each subtype, especially if it has aggressive behavior.

PD-L1 immunoexpression and molecular characterization of histological subtypes in urothelial carcinoma / Inmunoexpresión de PD-L1 y caracterización molecular de subtipos histológicos de carcinoma urotelial

Introduction: Urothelial carcinoma (UC) has histological subtypes whose phenotype reflects their molecular diversity, behavior and response to conventional therapy. Immune checkpoint inhibitors (ICIs) have improved the management of UC by evaluation of PD-L1. In the case of PD-L1 22C3, the initiation of ICI is considered from a combined positive score (CPS) greater than 10. However, UC subtypes with absent PD-L1 22C3 expression in cases with CPS>10 may not respond to these treatments. This study aims to establish a correlation between the PD-L1 immunoexpression and molecular alterations in divergent differentiation and histological subtypes of UC (UC-s). Material and methods: Twenty-six samples of UC were detected from a total of 24 patients. Two pathologists performed separately an assessment of UC-s on hematoxylin–eosin as well as PD-L1 expression. Molecular study of each case was performed by next generation sequencing (NGS). A descriptive analysis of the variables included was conducted. Results: Nine cases (34.61%) showed a CPS>10, some with negative PD-L1 immunoexpression in aggressive UC-s. The molecular study revealed alterations in genes belonging to the p53/cell cycle control, RAS, and DNA repair pathways, among others. None of the alterations were exclusive to any histological subtype. Discussion: Special attention should be paid to CPS>10 cases that include histological subtypes of UC with divergent expression for PD-L1 as they may not respond to treatment with ICI. We recommend examining the proportion and PD-L1 status of each subtype, especially if it has aggressive behavior.(AU)

Introducción: El carcinoma urotelial (CU) presenta subtipos histológicos cuyo fenotipo refleja su diversidad molecular, su comportamiento y su respuesta al tratamiento. Los inhibidores de puntos de control inmunitario (ICI) han mejorado el manejo del CU mediante la evaluación de PD-L1. En el caso de PD-L1 22C3, se considera el inicio de ICI a partir de una puntuación positiva combinada (combined positive score [CPS]) mayor de 10. Sin embargo, los subtipos de CU con ausencia de expresión de PD-L1 22C3 en casos con CPS>10 podrían no responder a estos tratamientos. Este estudio pretende establecer una correlación entre la inmunoexpresión de PD-L1 y las alteraciones moleculares en áreas con diferenciación divergente y subtipos histológicos de CU (CU-s). Material y métodos: Se obtuvieron 26 muestras con CU de 24 pacientes. Dos patólogos evaluaron de manera independiente las CU-s en hematoxilina-eosina y la expresión de PD-L1. Se realizó el estudio molecular mediante Next Generation Sequencing (NGS). Se realizó un análisis descriptivo de las variables incluidas. Resultados: Nueve casos (34,61%) mostraron un CPS>10, algunos con PD-L1 negativo en los CU-s de comportamiento agresivo. El estudio molecular reveló alteraciones en genes de las vías de p53/control del ciclo celular, RAS y reparación del ADN, entre otras. Ninguna alteración fue exclusiva de algún CU-s. Discusión: Debe prestarse especial atención a los casos con CPS>10 que incluyan subtipos histológicos con expresión divergente para PD-L1, ya que podrían no responder al tratamiento con ICI. Se recomienda cuantificar la proporción y el estado de PD-L1 de cada subtipo, especialmente si es de comportamiento agresivo.(AU)

Isavuconazole for the Treatment of Invasive Mold Disease in Solid Organ Transplant Recipients: A Multicenter Study on Efficacy and Safety in Real-life Clinical Practice.

BACKGROUND: Isavuconazole has theoretical advantages over other mold-active triazoles for the treatment of invasive aspergillosis and mucormycosis after solid organ transplantation (SOT). The available clinical experience, nevertheless, is scarce. METHODS: We performed a retrospective study including all adult SOT recipients with proven or probable invasive mold disease (IMD) that received isavuconazole for ≥24 h as first-line or salvage therapy at 10 Spanish centers between September 2017 and November 2021. The primary efficacy outcome was clinical response (complete or partial resolution of attributable symptoms and findings) by weeks 6 and 12. Safety outcomes included the rates of treatment-emergent adverse events and premature isavuconazole discontinuation. RESULTS: We included 81 SOT recipients that received isavuconazole for a median of 58.0 days because of invasive aspergillosis (n = 71) or mucormycosis (n = 10). Isavuconazole was used as first-line (72.8%) or salvage therapy due because of previous treatment-emergent toxicity (11.1%) or refractory IMD (7.4%). Combination therapy was common (37.0%), mainly with an echinocandin or liposomal amphotericin B. Clinical response by weeks 6 and 12 was achieved in 53.1% and 54.3% of patients, respectively, and was more likely when isavuconazole was administered as first-line single-agent therapy. At least 1 treatment-emergent adverse event occurred in 17.3% of patients, and 6.2% required premature discontinuation. Daily tacrolimus dose was reduced in two-thirds of patients by a median of 50.0%, although tacrolimus levels remained stable throughout the first month of therapy. CONCLUSIONS: Isavuconazole is a safe therapeutic option for IMD in SOT recipients, with efficacy comparable to other patient groups.

Modification of the Textural Properties of Chitosan to Obtain Biochars for CO2-Capture Processes.

Three chitosans with different morphologies have been used (commercial chitosan powder, chitosan in film form and chitosan in globular form synthesized by the freeze-dried method) for the synthesis of biochars. The pyrolytic treatment has revealed that the biochar synthesized from the chitosan formed by the freeze-dried method reaches the highest CO2-adsorption capacity (4.11 mmol/g at 0 °C and a pressure of 1 bar) due to this adsorbent is highly microporous. Moreover, this biochar is more resistant to the pyrolytic treatment in comparison to the biochars obtained from the commercial chitosan and chitosan in the form of film. CO2-adsorption studies at different temperatures have also shown that the adsorption capacity diminishes as the adsorption temperature increases, thus suggesting that the adsorption takes place by a physical process.

Analysis of response of severe eosinophilic asthmatic patients to benralizumab.

INTRODUCTION: Clinical trials and real-life studies have been published showing effectiveness of benralizumab in severe eosinophilic asthmatic patients. The aim of the present study is to describe super-responders to benralizumab in a series of 79 patients who completed at least 1 year of treatment, and to compare super-responders with non super-responders. METHODS: This is a multicenter study of the Register of Severe Asthma of the Region of Murcia (RE-ASGRAMUR) Group performed in eight hospitals under the conditions of routine clinical practice. Patients with zero exacerbations and no oral corticosteroid therapy for asthma were considered super-responders. We analyzed clinical, functional, and inflammatory parameters of selected patients. RESULTS: In all, 50 of the 79 patients (63%) met the super-responder criteria. In addition, 36% of the patients (26/71) were considered as complete responders to treatment (super--responder + Asthma Control Test [ACT] ≥ 20 + forced expiratory volume in 1 s [FEV1] ≥ 80%). The super--responders were significantly older in age (P = 0.0029), had higher eosinophils count (P = 0.0423), higher proportion of nasal polyps (P = 0.036), and they had less severe disease at baseline. After 1 year of treatment, the super-responders had higher levels of ACT questionnaire (23 vs 19, P = 0.0007) and better percentage of FEV1 (83 vs 75, P = 0.0359). CONCLUSION: Almost two of the three patients treated with benralizumab were super--responders after 1 year of treatment and 36% had a complete response. Super-responders were associated with older age, higher eosinophils count, had nasal polyposis as comorbidity, and had less severe disease at baseline. This data illustrated the good real-life response of patients with severe eosinophilic asthma to the treatment with benralizumab.

Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation.

Airway inflammation and remodelling are important pathophysiologic features in asthma and other respiratory conditions. An intact epithelial cell layer is crucial to maintain lung homoeostasis, and this depends on intercellular adhesion, whilst damaged respiratory epithelium is the primary instigator of airway inflammation. The Coxsackievirus Adenovirus Receptor (CAR) is highly expressed in the epithelium where it modulates cell-cell adhesion stability and facilitates immune cell transepithelial migration. However, the contribution of CAR to lung inflammation remains unclear. Here we investigate the mechanistic contribution of CAR in mediating responses to the common aeroallergen, House Dust Mite (HDM). We demonstrate that administration of HDM in mice lacking CAR in the respiratory epithelium leads to loss of peri-bronchial inflammatory cell infiltration, fewer goblet-cells and decreased pro-inflammatory cytokine release. In vitro analysis in human lung epithelial cells confirms that loss of CAR leads to reduced HDM-dependent inflammatory cytokine release and neutrophil migration. Epithelial CAR depletion also promoted smooth muscle cell proliferation mediated by GSK3ß and TGF-ß, basal matrix production and airway hyperresponsiveness. Our data demonstrate that CAR coordinates lung inflammation through a dual function in leucocyte recruitment and tissue remodelling and may represent an important target for future therapeutic development in inflammatory lung diseases.

A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike.

Delineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigate the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We show that ∼82% of SARS-CoV-2 S-reactive B cells harbor a naive phenotype, which represents an unusually high fraction of total human naive B cells (∼0.1%). Approximately 10% of these naive S-reactive B cells share an IGHV1-69/IGKV3-11 B cell receptor pairing, an enrichment of 18-fold compared to the complete naive repertoire. Following SARS-CoV-2 infection, we report an average 37-fold enrichment of IGHV1-69/IGKV3-11 B cell receptor pairing in the S-reactive memory B cells compared to the unselected memory repertoire. This class of B cells targets a previously undefined non-neutralizing epitope on the S2 subunit that becomes exposed on S proteins used in approved vaccines when they transition away from the native pre-fusion state because of instability. These findings can help guide the improvement of SARS-CoV-2 vaccines.