LC-HRMS and GC-MS Profiling of Urine Free Cortisol, Cortisone, 6Β-, and 18-Hydroxycortisol for the Evaluation of Glucocorticoid and Mineralocorticoid Disorders.

INTRODUCTION: Urine free cortisol measurements are routinely performed to evaluate hypercortisolism. Despite their analytical inaccuracy, immunoassay-based methods are frequently used. Advances in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) facilitate the incorporation of powerful diagnostic tools into clinical laboratories. In addition to its high analytical specificity and simultaneous analysis of different metabolites, accurate mass measurement allows for untargeted compound identification, which may help to identify clinically relevant metabolites or drugs. METHODS: The present study aimed to validate a simple routine LC-HRMS method to quantify cortisol, cortisone, 6ß-hydroxycortisol, and 18-hydroxycortisol simultaneously in human urine. Additionally, the study also validated a GC-MS method for the same steroids, evaluated their cross-reactivity with commercial cortisol immunoassays, and quantified the 24 h urine excretion in patients under clinical suspicion or follow-up for hypercortisolism. RESULTS: The LC-HRMS method involved liquid-liquid extraction using dichloromethane, micro-LC for chromatographic separation and detection using the accurate masses of the steroids, and simultaneous high-resolution full scan acquisition. The method presented acceptable linearity, precision, and accuracy. Significant interference from 6ß-hydroxycortisol and cortisone was demonstrated in the cortisol immunoassays, which impacted their reliability in the follow-up of patients with hypercortisolism and significant changes in these cortisol metabolites (i.e., due to drug-induced changes in CYP3A4 activity). CONCLUSION: A rapid and accurate routine LC-HRMS method was validated, which is useful for the evaluation of hypercortisolism and other disorders of glucocorticoid and mineralocorticoid metabolism.

Maintaining the permanence principle of death during normothermic regional perfusion in controlled donation after the circulatory determination of death: Results of a prospective clinical study.

One concern about the use of normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is that the brain may be perfused. We aimed to demonstrate that certain technical maneuvers preclude such brain perfusion. A nonrandomized trial was performed on cDCD donors. In abdominal normothermic regional perfusion (A-NRP), the thoracic aorta was blocked with an intra-aortic occlusion balloon. In thoracoabdominal normothermic regional perfusion (TA-NRP), the arch vessels were clamped and the cephalad ends vented to the atmosphere. The mean intracranial arterial blood pressure (ICBP) was invasively measured at the circle of Willis. Ten cDCD donors subject to A-NRP or TA-NRP were included. Mean ICBP and mean blood pressure at the thoracic and the abdominal aorta during the circulatory arrest were 17 (standard deviation [SD], 3), 17 (SD, 3), and 18 (SD, 4) mmHg, respectively. When A-NRP started, pressure at the abdominal aorta increased to 50 (SD, 13) mmHg, while the ICBP remained unchanged. When TA-NRP was initiated, thoracic aorta pressure increased to 71 (SD, 18) mmHg, but the ICBP remained unmodified. Recorded values of ICBP during NRP were 10 mmHg. In conclusion, appropriate technical measures applied during NRP preclude perfusion of the brain in cDCD. This study might help to expand NRP and increase the number of organs available for transplantation.

A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses.

The threat of spillovers of coronaviruses associated with the severe acute respiratory syndrome (SARS) from animals to humans necessitates vaccines that offer broader protection from sarbecoviruses. By leveraging a viral-genome-informed computational method for selecting immune-optimized and structurally engineered antigens, here we show that a single antigen based on the receptor binding domain of the spike protein of sarbecoviruses elicits broad humoral responses against SARS-CoV-1, SARS-CoV-2, WIV16 and RaTG13 in mice, rabbits and guinea pigs. When administered as a DNA immunogen or by a vector based on a modified vaccinia virus Ankara, the optimized antigen induced vaccine protection from the Delta variant of SARS-CoV-2 in mice genetically engineered to express angiotensin-converting enzyme 2 and primed by a viral-vector vaccine (AZD1222) against SARS-CoV-2. A vaccine formulation incorporating mRNA coding for the optimized antigen further validated its broad immunogenicity. Vaccines that elicit broad immune responses across subgroups of coronaviruses may counteract the threat of zoonotic spillovers of betacoronaviruses.

Azathioprine in hidradenitis suppurativa with inflammatory phenotype: a case series of 11 patients.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that negatively impacts the quality of life of patients. It presents as deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. Recently, two phenotypes have been described: a follicular phenotype and an inflammatory phenotype. Numerous medical treatments are available for hidradenitis suppurativa, with particular importance of antitumor necrosis factor antibodies. Due to the association of HS with other conditions with a pro-inflammatory state, particularly Crohn's disease, it has been suggested that azathioprine may have a role in the treatment of HS. OBJECTIVE: To assess the effectiveness of azathioprine monotherapy in patients with moderate-severe HS. METHODS: We retrospectively studied patients with HS treated with azathioprine in monotherapy. We performed both clinical and ultrasound evaluation at baseline as well as in the follow-up visits. Their baseline score on the iHS4 and DLQI scales and 12-16 weeks after starting the treatment were compared. We also registered the number of patients who achieved HiSCR. RESULTS: Six patients presented significant improvement, reducing their score in iHS4 and DLQI scales and achieving HiSCR. Another patient had clinical improvement, meaning reduction in iHS4 and DLQI, but without achieving HiSCR. Two patients stopped the treatment before week 12 because of adverse events. The remaining two patients presented no improvement. The median (Q3-Q1) baseline iHS4 score was 6 (12-6), and follow-up iHS4 score, 4 (6-2), being these differences statistically significant (P = 0.006). Median (Q3-Q1) baseline DLQI scores and 12-16 weeks after treatment were 17 (23-11) and 14 (18-9) although statistically nonsignificant (P = 0.099). CONCLUSION: We present a case series of 11 patients treated with azathioprine with good clinical and ultrasonographic response. We suggest that azathioprine may benefit a certain patient profile with the inflammatory phenotype.

Engineering of 3D printed personalized polypills for the treatment of the metabolic syndrome.

Metabolic syndrome is a collection of abnormalities, including at least three of the following insulin resistance, hypertension, dyslipidemia, type 2 diabetes, obesity, inflammation, and non-alcoholic fatty liver disease. 3D printed solid dosage forms have emerged as a promising tool enabling the fabrication of personalized medicines and offering solutions that cannot be achieved by industrial mass production. Most attempts found in the literature to manufacture polypills for this syndrome contain just two drugs. However, most fixed-dose combination (FDC) products in clinical practice required the use of three or more drugs. In this work, Fused deposition modelling (FDM) 3D printing technology coupled with hot-melt extrusion (HME) has been successfully applied in the manufacture of polypills containing nifedipine (NFD), as an antihypertensive drug, simvastatin (SMV), as an antihyperlipidemic drug, and gliclazide (GLZ) as an antiglycemic drug. Hanssen solubility parameters (HSPs) were utilized as predictors to guide the formation of amorphous solid dispersion between drug and polymer to ensure miscibility and enhanced oral bioavailability. The HSP varied from 18.3 for NFD, 24.6 for SMV, and 7.0 for GLZ while the total solubility parameter for the excipient mixture was 27.30.5. This allowed the formation of an amorphous solid dispersion in SMV and GLZ 3D printed tablets compared to NFD which was partially crystalline. Popypill showed a dual release profile combining a faster SMV release (< 6h) with a 24 h sustained release for NDF and GLZ. This work demonstrated the transformation of FDC into dynamic dose-personalized polypills.

Bronchial Stenosis After Lung Transplantation From cDCD Donors Using Simultaneous Abdominal Normothermic Regional Perfusion: A Single-center Experience.

BACKGROUND: Controlled donation after circulatory death (cDCD) has increased the number of lung donors significantly. The use of abdominal normothermic regional perfusion (A-NRP) during organ procurement is a common practice in some centers due to its benefits on abdominal grafts. This study aimed to assess whether the use of A-NRP in cDCD increases the frequency of bronchial stenosis in lung transplant (LT) recipients. METHODS: A single-center, retrospective study including all LTs was performed between January 1, 2015, and August 30, 2022. Airway stenosis was defined as a stricture that leads to clinical/functional worsening requiring the use of invasive monitoring and therapeutic procedures. RESULTS: A total of 308 LT recipients were included in the study. Seventy-six LT recipients (24.7%) received lungs from cDCD donors using A-NRP during organ procurement. Forty-seven LT recipients (15.3%) developed airway stenosis, with no differences between lung recipients with grafts from cDCD (17.2%) and donation after brain death donors (13.3%; P = 0.278). A total of 48.9% of recipients showed signs of acute airway ischemia on control bronchoscopy at 2 to 3 wk posttransplant. Acute ischemia was an independent risk factor for airway stenosis development (odds ratio = 2.523 [1.311-4.855], P = 0.006). The median number of bronchoscopies per patient was 5 (2-9), and 25% of patients needed >8 dilatations. Twenty-three patients underwent endobronchial stenting (50.0%) and each patient needed a median of 1 (1-2) stent. CONCLUSIONS: Incidence of airway stenosis is not increased in LT recipients with grafts obtained from cDCD donors using A-NRP.

Guiding Clinical Prescription of Topical Extemporaneous Formulations of Sodium Cromoglycate Based on Pharmaceutical Performance.

Cromoglycate (SCG) is widely used for allergy processes, and inflammatory states acting as a mast cell membrane stabilizer that inhibits the histamine and mediator release. Currently, SCG topical extemporaneous compounding formulations are prepared in hospitals and community pharmacies, as no industrial fabricated medicines are available in Spain. The stability of these formulations is unknown. Additionally, there are no clear guidelines on which concentration and vehicle are more suitable to enhance permeation across the skin. In this work, the stability of commonly prescribed topical SCG formulations in clinical practice was evaluated. Different vehicles commonly employed by pharmacists daily for formulating topical SCG were investigated (Eucerinum, Acofar Creamgel, and Beeler's base) at different concentrations, ranging from 0.2 to 2%. The stability of topical extemporaneous compounded SCG formulations can be extended for up to three months at room temperature (25 °C). Creamgel 2% formulations significantly improved the topical permeation of SCG across the skin, being 4.5-fold higher than formulations prepared with Beeler's base. The reason attributed to this performance can be related to the lower droplet size formed upon dilution in aqueous media combined with a lower viscosity, which facilitates its application and extensibility on the skin. The higher the SCG concentration in Creamgel formulations, the higher the permeability across both synthetic membranes and pig skin (p-value < 0.05). These preliminary results can be used as a guide to prompt a rational prescription of topical SCG formulations.

Short-Term Effectiveness, Safety, and Potential Predictors of Response of Secukinumab in Patients with Severe Hidradenitis Suppurativa Refractory to Biologic Therapy: A Multicenter Observational Retrospective Study.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Biologic drugs have a key role in the long-term anti-inflammatory treatment of moderate to severe patients due to their immunomodulatory properties. The aim of this study is to evaluate the effectiveness and safety of secukinumab in patients with moderate to severe HS after 16 weeks of treatment, and to explore potential predictors of clinical response to the drug. METHODS: Multicenter observational retrospective study. Patients treated with secukinumab 300 mg every 2 or 4 weeks who had completed at least 16 weeks of follow-up from nine hospitals based in southern Spain (Andalusia) were included in this study. Treatment effectiveness was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR). Information about adverse events was collected, the therapeutic burden of the patients was calculated as the summation of systemic medical treatments and surgical interventions (excluding incision and drainage) experienced until the start of secukinumab treatment. RESULTS: Forty-seven patients with severe HS were included for analysis. At week 16, 48.9% (23/47) of patients achieved HiSCR. Adverse events were present in 6.4% (3/47) of the patients. The multivariate analysis showed that female sex and, to a lesser extent, lower body mass index (BMI) and a lower therapeutic burden were potentially associated with a higher probability of HiSCR achievement. CONCLUSIONS: Favorable short-term effectiveness and safety of secukinumab in the treatment of severe HS patients were observed. Female sex, lower BMI and a lower therapeutic burden may be associated with a higher probability of achieving HiSCR.

Antimicrobial Stewardship Programs (ASPS) in pediatric primary care.

Antibiotic resistance is a major threat to global health. Optimizing the use of antibiotics is a key measure to prevent and control this problem. Antimicrobial Stewardship Programs (ASPs) are designed to improve clinical outcomes, minimize adverse effects and protect patients, and to ensure the administration of cost-effective treatments. Inappropriate use of antibiotics also occurs in pediatric clinical practice. For this reason, ASPs should include specific objectives and strategies aimed at pediatricians and families. Implementing these programs requires the involvement of institutions and policy makers, healthcare providers as well as individuals, adapting them to the characteristics of each healthcare setting. Pediatric primary care (PPC) faces specific issues such as high demand and immediacy, scarce specialized professional resources, difficulties to access regular training and to obtain feedback. This requires the design of specific policies and strategies to achieve the objectives, including structural and organizational measures, improvement of the information flow and accessibility to frequent trainings. These programs should reach all health professionals, promoting regular trainings, prescription support tools and supplying diagnostic tests, with adequate coordination between health care levels. Periodic evaluations and surveillance tools are useful to assess the impact of the actions taken and to provide feedback to health providers in order to adapt and improve their clinical practice to meet ASPs objectives.

Programas de optimización del uso de antibióticos (PROA) en pediatría de atención primaria / Antimicrobial Stewardship Programs (ASPS) in pediatric primary care

La resistencia a antibióticos supone una amenaza para la salud pública a nivel mundial. Su estrecha relación con el consumo de antibióticos hace necesaria la adopción de medidas para optimizar su uso. Los programas de optimización del uso de antibióticos (PROA) se diseñan para mejorar los resultados clínicos de los pacientes con infecciones, minimizar los efectos adversos asociados a su uso y garantizar la administración de tratamientos costo-eficientes. En la práctica clínica pediátrica el uso inadecuado de antibióticos es una realidad. Es por ello que los PROA deben incluir objetivos y estrategias específicos dirigidos a familias y pediatras. La implementación de estos programas requiere la implicación de instituciones, profesionales y población, adaptándolos a las características de cada ámbito asistencial. La atención primaria (AP) pediátrica presenta unas peculiaridades organizativas y asistenciales (hiperdemanda e inmediatez, escasos recursos profesionales especializados, dificultades en el acceso a la formación continuada y a la retroalimentación informativa) que exigen el diseño de medidas y estrategias propias para conseguir los objetivos fijados, que incluyan medidas estructurales, organizativas, de flujo de información y de formación continuada. Es necesario que estos programas alcancen a todos los profesionales, abordando la formación continuada, las herramientas de apoyo a la prescripción y el acceso a pruebas diagnósticas, con la adecuada coordinación interniveles. Se debe evaluar periódicamente el impacto de las distintas acciones en los objetivos planteados. La información generada debe revertir a los profesionales para que puedan adaptar su práctica clínica a la consecución óptima de los objetivos. (AU)

Antibiotic resistance is a major threat to global health. Optimizing the use of antibiotics is a key measure to prevent and control this problem. Antimicrobial Stewardship Programs (ASPs) are designed to improve clinical outcomes, minimize adverse effects and protect patients, and to ensure the administration of cost-effective treatments. Inappropriate use of antibiotics also occurs in pediatric clinical practice. For this reason, ASPs should include specific objectives and strategies aimed at pediatricians and families. Implementing these programs requires the involvement of institutions and policy makers, healthcare providers as well as individuals, adapting them to the characteristics of each healthcare setting. Pediatric primary care (PPC) faces specific issues such as high demand and immediacy, scarce specialized professional resources, difficulties to access regular training and to obtain feedback. This requires the design of specific policies and strategies to achieve the objectives, including structural and organizational measures, improvement of the information flow and accessibility to frequent trainings. These programs should reach all health professionals, promoting regular trainings, prescription support tools and supplying diagnostic tests, with adequate coordination between health care levels. Periodic evaluations and surveillance tools are useful to assess the impact of the actions taken and to provide feedback to health providers in order to adapt and improve their clinical practice to meet ASPs objectives. (AU)

Normothermic Regional Perfusion in Pediatric Controlled Donation After Circulatory Death Can Lead to Optimal Organ Utilization and Posttransplant Outcomes.

BACKGROUND: The benefits of normothermic regional perfusion (NRP) in posttransplant outcomes after controlled donation after the determination of death by circulatory criteria (cDCD) has been shown in different international adult experiences. However, there is no information on the use of NRP in pediatric cDCD donors. METHODS: This is a multicenter, retrospective, observational cohort study describing the pediatric (<18 y) cDCD procedures performed in Spain, using either abdominal NRP or thoracoabdominal NRP and the outcomes of recipients of the obtained organs. RESULTS: Thirteen pediatric cDCD donors (age range, 2-17 y) subject to abdominal NRP or thoracoabdominal NRP were included. A total of 46 grafts (24 kidneys, 11 livers, 8 lungs, 2 hearts, and 1 pancreas) were finally transplanted (3.5 grafts per donor). The mean functional warm ischemic time was 15 min (SD 6 min)' and the median duration of NRP was 87 min (interquartile range, 69-101 min). One-year noncensored for death kidney graft survival was 91.3%. The incidence of delayed graft function was 13%. One-year' noncensored-for-death liver graft survival was 90.9%. All lung and pancreas recipients had an excellent evolution. One heart recipient died due to a septic shock. CONCLUSIONS: This is the largest experience of pediatric cDCD using NRP as graft preservation method. Although our study has several limitations, such as its retrospective nature and the small sample size, its reveals that NRP may increase the utilization of cDCD pediatric organs and offer optimal recipients' outcomes.

Chronic critical illness after trauma injury: outcomes and experience in a trauma center.

OBJECTIVE: To determine the prevalence, risk factors and functional results of chronic critical illness (CCI) in polytrauma patients. DESIGN: Single-center observational retrospective study. SETTING: ICU at a tertiary hospital in Santander, Spain, between 2015 and 2019. PATIENTS: Adult trauma patients who survived beyond 48 h after injury. CCI was defined as the need for mechanical ventilation for at least 14 days or tracheostomy for difficult weaning. MEASUREMENTS AND MAIN RESULTS: About 62/575 developed CCI. These patients were characterized by higher ISS score [17 (SD 10) vs. 13.8 (SD 8.2); p < 0.001] and higher NISS (26 (SD 11) vs. 19.2 (SD 10.5); p = 0.001). CCI group had greater proportion of hospital-acquired infections (100% vs. 18.1%; p < 0.001), and acute kidney failure (33.9% vs. 22.8% p < 0.001). During the first 24 h of admission, CCI group required in a greater proportion surgical intervention (50% vs. 29%; p = 0.001), and blood products (31.3% vs. 20.5%; p < 0.047). Hospital ward stay was longer in CCI patients [9.5 days (IQR 5-16.9) vs. 43.9 (IQR 30.3-53) p < 0.001]. The CCI mortality was higher (19.5% vs. 8.1%; p = 0.004). Surgical intervention in the first 24 h (OR 2.5 95% CI 1.1-4.1), age (> 55 years) (OR 2.1 95%CI 1.1-4.2), ISS score (OR 1.1 95%CI 1.02-1.3), GCS score (OR 0.8 95%CI 0.4-23.2) and multiple organ failure (OR 9.5 95%CI 3.9-23.2) were predictors of CCI in the multivariate analysis. CONCLUSIONS: CCI after severe trauma appears in a considerable proportion of patients. Early identification and implementation of specific interventions could change the evolution of this process.

Clinical Thresholds for Pseudohyperkalemia and Pseudonormokalemia in Patients with Thrombocytosis.

Background: The lysis of platelets during in vitro coagulation leads to increased potassium concentrations.We aimed to establish the cut-off value for platelet count interfering serum potassium and to estimate the percentage of cases of pseudohyperkalemia and pseudonormokalemia in our hospital. Materials and methods: Individuals diagnosed with essential thrombocytosis (2010-2019) based on the WHO criteria for the classification of myeloid neoplasms and acute leukemia were considered.The cut-off value for the interference of platelet count on serum potassium results was calculated using the reference change value. Sensitivity and specificity were calculated using a ROC-curve, and the size of the effect by the Cohen's d.The clinical impact of both phenomena was assessed by reviewing the medical records of individuals classified as such, and also looking for potential cases in 2019 on the laboratory information system. Results: Fifty-four individuals with essential thrombocytosis were included. Potassium concentration correlated with platelet count (P-value<0.001; Spearman's ρ =0.394) in serum. The cut-off value of platelet count interfering potassium was 598x103/µL [CI95%: 533-662x103/µL], with an associated sensitivity and specificity of 0.67 [CI95%:0.52-0.80] and 0.58 [CI95%:0.42-0.72] respectively.The medical records of patients classified as pseudohyperkalemia or pseudonormokalemia did not include any medical action for the modification of potassium levels. In 2019, up to 0.14% of the total serum potassium determinations were susceptible to be pseudohyperkalemia or pseudonormokalemia. Conclusion: This study provides a cut-off value for platelet count interfering serum potassium concentrations, and brings to light not only pseudohyperkalemia-related issues, but also the pseudonormokalemia phenomenon, which usually goes unnoticed.

Alveolar Proteinosis in COVID-19: Clinical Case.

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disease characterized by accumulation of lipoprotein in lung surfactant in the alveolar space and terminal bronchioles, leading to impaired gas exchange and arterial hypoxemia. We present the case of a 51-year-old woman who was admitted with a diagnosis of severe SARS-CoV-2 pneumonia. Her condition did not improve with corticosteroids. A chest CT scan revealed ground-glass opacities in all lung lobes, with septal thickening. A differential diagnosis was proposed with other diseases. Bronchoscopy revealed milky bronchoalveolar lavage fluid, and staining with periodic acid-Schiff was positive, thus indicating PAP. Therefore, the patient underwent whole lung lavage, which led to clinical, radiological, and functional improvement. In the context of the COVID-19 pandemic, differential diagnosis ensures that appropriate attention is given to less prevalent entities such as PAP.

Drug Stability: ICH versus Accelerated Predictive Stability Studies.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), along with the World Health Organization (WHO), has provided a set of guidelines (ICH Q1A-E, Q3A-B, Q5C, Q6A-B) intended to unify the standards for the European Union, Japan, and the United States to facilitate the mutual acceptance of stability data that are sufficient for registration by the regulatory authorities in these jurisdictions. Overall, ICH stability studies involve a drug substance tested under storage conditions and assess its thermal stability and sensitivity to moisture. The long-term testing should be performed over a minimum of 12 months at 25 °C ± 2 °C/60% RH ± 5% RH or at 30 °C ± 2 °C/65% RH ± 5% RH. The intermediate and accelerated testing should cover a minimum of 6 months at 30 °C ± 2 °C/65% RH ± 5% RH (which is not necessary if this condition was utilized as a long-term one) and 40 °C ± 2 °C/75% RH ± 5% RH, respectively. Hence, the ICH stability testing for industrially fabricated medicines is rigorous and tedious and involves a long period of time to obtain preclinical stability data. For this reason, Accelerated Predictive Stability (APS) studies, carried out over a 3-4-week period and combining extreme temperatures and RH conditions (40-90 °C)/10-90% RH, have emerged as novel approaches to predict the long-term stability of pharmaceutical products in a more efficient and less time-consuming manner. In this work, the conventional ICH stability studies versus the APS approach will be reviewed, highlighting the advantages and disadvantages of both strategies. Furthermore, a comparison of the stability requirements for the commercialization of industrially fabricated medicines versus extemporaneous compounding formulations will be discussed.

Sensibilidad del test de diagnóstico rápido SARS-CoV-2 Panbio en Atención Primaria / Sensitivity of the Panbio COVID-19 rapid antigen detection test in primary care

Introducción y objetivos: los pediatras de Atención Primaria necesitamos técnicas de diagnóstico rápido (TDR) fiables para prevenir la propagación de la enfermedad COVID-19 mediante un cribado temprano y eficaz a la espera de una vacuna. El objetivo de este trabajo fue evaluar como novedad en Atención Primaria, tanto en adultos como niños, sintomáticos y contactos asintomáticos, la sensibilidad (S) de los test de antígeno SARS-CoV-2 Panbio del laboratorio Abbott respecto a la reacción en cadena de la polimerasa (PCR).Pacientes y métodos: se incluyeron 591 pacientes (222 menores de 14 años) (249 sintomáticos y 342 contactos). Se calculó la sensibilidad (S) y la especificidad (E) junto con sus intervalos de confianza (IC) del 95%. La independencia de los dos resultados ha sido analizada mediante el test de McNemar.Resultados: la S del test en adultos fue del 81% (IC 95%: 66,16-96,34) y en niños del 80% (IC 95%: 34,94-100) dentro de los 5 primeros días. En contactos se evaluó la S en los cinco primeros días, en adultos (68%; IC 95%: 51,13-86,37), del 5.º al 9.º día (85%) y en niños (66%; IC 95%: 30,31-100). El tipo de contacto más frecuente fue domiciliario en un 52% de los casos. La E fue 100% en todos los casos.Conclusiones: el test rápido de antígeno SARS-CoV-2 Panbio puede ser útil para diagnóstico de adultos y niños los primeros cinco días de inicio de síntomas, así como entre el 5.º y 9.º día tras el contacto con positivo COVID-19 confirmado, pendiente de interpretar en futuros estudios. (AU)

Introduction and objectives: primary care paediatricians need reliable rapid diagnostic techniques (RDTs) to prevent the spread of coronavirus disease 19 (COVID-19) through early and effective screening while awaiting a vaccine. The objective of this study was to evaluate the sensitivity (Sen) of the Abbott laboratory SARS-CoV-2 Panbio antigen test, newly introduced in primary care, in both adults and children (symptomatic and asymptomatic contacts) in comparison to the polymerase chain reaction (PCR) test.Sample and methods: the study included 591 patients (222 aged less than 14 years) from 7 primary care centres; of who 249 were symptomatic and 342 asymptomatic contacts. We calculated the Sen and specificity (Spe) with their 95% confidence intervals (CIs). We assessed the independence of the two results with the McNemar test.Results: the Sen of the test within 5 days from onset was 81% in adults (95% CI, 66.16-96.34) and 80% in children (95% CI: 34.94-100). In contacts, we assessed the Sen within 5 days, in adults (68%; 95% CI: 51.13- 86.37), in 5 to 9 days (85%) and in children (66%; 95% CI: 30.31-100). The most frequent source of exposure were household contacts (52% of the cases). The Spe was 100% in every case.Conclusions: the Panbio SARS-CoV-2 rapid antigen test can be useful for diagnosis in adults and children within 5 days of onset, and from days 5 to 9 in contacts of confirmed COVID 19 cases. Further studies are required for adequate interpretation of the latter result. (AU)

Multi-biomarker Assessment in a Native Species Psalidodon eigenmanniorum Under Inorganic Mercury and Recovery Scenarios.

The increasing contamination of water bodies with mercury raises concerns about its possible effects on aquatic organisms. The combined use of several biomarkers allows researchers to study the impact of a chemical at different levels of biological organization. In the present work, we determined the response of histological (gills and liver), somatic (condition factor and hepato-somatic index), and behavioral (predator-prey relationship, through the presentation of a computer-animated image) biomarkers in the native species Psalidodon eigenmanniorum exposed to 100 µg L-1 of inorganic Hg (IHg) during 96 h. We also assessed whether there was a change in the biomarkers analyzed after 7 days in Hg-free water compared with those exposed to IHg. In exposed fish, IHg caused damage to the gills and liver tissues. The condition factor showed no difference between IHg-exposed organisms and control organisms, while the hepato-somatic index was lower in IHg-exposed fish. As for the behavioral analyses, it was observed that the presentation of a stimulus induced changes in the behavioral responses of fish exposed to IHg, which showed a heightened state of alertness with respect to control. On the other hand, after 7 days in Hg-free water, the organisms generally showed no changes in biomarkers compared with IHg-exposed fish. Our results contribute new data on IHg toxicity in a native species and provide information on the plasticity of damage to reverse itself. Furthermore, this work provides baseline information for environmental assessments in water bodies where mercury is present.

Influencia de la vacunación antigripal y la comorbilidad en la evolución de los pacientes hospitalizados por COVID-19 / Influence of influenza vaccine and comorbidity on the evolution of hospitalized COVID-19 patients

Antecedentes y objetivo:El brote de la enfermedad COVID-19 está evolucionando en todo el mundo. El objetivo del estudio es evaluar la asociación entre la vacunación antigripal y el riesgo de mortalidad en pacientes con COVID-19 hospitalizados, así como otros factores de riesgo.Materiales y métodos:Estudio observacional retrospectivo. Se realizó entre pacientes hospitalizados con COVID-19 del Hospital La Mancha Centro entre el 5 y el 25 de marzo de 2020. Utilizamos una regresión logística multivariable para explorar la asociación entre la vacunación antigripal y la mortalidad por COVID y otros factores de riesgo.Resultados:Se incluyeron 410 pacientes. La vacunación antigripal no tuvo efecto entre los pacientes hospitalizados por COVID-19 (OR: 1,55 [IC 95%; 0,96-2,48; p = 0,071]). El aumento de la mortalidad intrahospitalaria se asoció con edad avanzada (OR: 1,05 [IC 95%; 1,02-1,07]), por cada aumento de año; p < 0,001, Charlson ≥ 3 (OR: 1,84 [IC 95%; 1,07-3,15, p = 0,027]) e insuficiencia cardíaca al ingreso (OR: 6 [IC 95%; 1,6-21,7; p = 0,007]).Conclusiones:La vacuna antigripal no tuvo efecto en la evolución de pacientes hospitalizados por COVID-19. Los factores de riesgo identificados fueron la edad avanzada, mayor comorbilidad e insuficiencia cardíaca al ingreso. (AU)

Background and objective:The COVID-19 coronavirus disease outbreak is evolving around the world. The aim of this study is to evaluate the association between influenza vaccination and the risk of mortality in hospitalized COVID-19 patients, as well as other risk factors.Materials and methods:Retrospective observational study. This study was conducted among hospitalized patients with COVID-19 at Hospital La Mancha Centro between March 5 and 25, 2020. Information on influenza vaccination was extracted from electronic medical records. We used a multivariate logistic regression to explore the association between influenza vaccination and mortality from COVID and other risk factors.Results:410 patients were included. Influenza vaccine had no effect among COVID-19 hospitalized patients [OR: 1.55 (95%CI: 0.96 – 2.48; p=0.071)]. Increasing hospital mortality was associated with older age [OR: 1.05 (95% CI 1.02–1.07), per year increase; p<0.001)], Charlson ≥3 [OR: 1.84 (95%CI: 1.07-3.15, p=0.027)] and heart failure on admission [OR: 6 (IC95%: 1.6 – 21.7; p=0.007)]Conclusions:Influenza vaccine had no effect among COVID-19 hospitalized patients. The risk factors identified were older age, higher comorbidity and heart failure on admission. (AU)