Tobramycin Systemic Absorption in Lung Transplant Recipients Treated With Inhaled Tobramycin: A Cohort Study.

Inhaled tobramycin treatment has been associated with nephrotoxicity in some case reports, but limited data are available about serum levels and its possible systemic absorption in lung transplant recipients (LTR). We conducted a single-center, observational and retrospective study of all adult (>18 years old) LTR treated with inhaled tobramycin for at least 3 days between June 2019 and February 2022. Trough serum levels were collected and >2 µg/mL was considered a high drug level. The primary outcome assessed the presence of detectable trough levels, while the secondary outcome focused on the occurrence of acute kidney injury (AKI) in individuals with detectable trough levels. Thirty-four patients, with a median age of 60 years, were enrolled. The primary indications for treatment were donor bronchial aspirate bacterial isolation (18 patients) and tracheobronchitis (15 patients). In total, 28 patients (82%) exhibited detectable serum levels, with 9 (26%) presenting high levels (>2 µg/mL). Furthermore, 9 patients (26%) developed acute kidney injury during the treatment course. Median trough tobramycin levels were significantly elevated in invasively mechanically ventilated patients compared to non-ventilated individuals (2.5 µg/mL vs. 0.48 µg/mL) (p < 0.001). Inhaled tobramycin administration in LTRs, particularly in those requiring invasive mechanical ventilation, may result in substantial systemic absorption.

Characterization and real-live results of nebulized voriconazole: A single-center observational study. / [Artículo traducido] Caracterización y resultados del uso de voriconazol nebulizado en un entorno real: un estudio observacional unicéntrico.

OBJECTIVE: Pulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. METHOD: This is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. RESULTS: The pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, nine adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 hours. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. CONCLUSION: Voriconazole nebulization is well tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy.

Characterization and real-live results of nebulized voriconazole: A single-center observational study.

OBJECTIVE: Pulmonary administration of voriconazole involves advantages, including optimization of lung penetration and reduction of adverse effects and interactions. However, there is scarce evidence about its use and there are no commercial presentations for nebulization. We aim to characterize a compounded voriconazole solution for nebulization and describe its use in our center. METHOD: This is a retrospective observational study including patients who received nebulized voriconazole to treat fungal lung diseases (infection or colonization). Voriconazole solution was prepared from commercial vials for intravenous administration. RESULTS: The pH and osmolarity of voriconazole solutions were adequate for nebulization. Ten patients were included, 9 adults and a child. The dosage was 40 mg in adults and 10 mg in the pediatric patient, diluted to a final concentration of 10 mg/ml, administered every 12-24 h. The median duration of treatment was 139 (range: 26-911) days. There were no reported adverse effects and the drug was not detected in plasma when nebulized only. CONCLUSION: Voriconazole nebulization is well-tolerated and it is not absorbed into the systemic circulation; further research is needed to assess its efficacy.

Knee Osteonecrosis After SARS-CoV-2 Virus Infection.

ABSTRACT: Osteonecrosis after COVID-19 infection is a complex pathology with multifactorial origin. Factors such as infection itself with associated coagulopathy, as well as genetic mechanisms, and medications used for its treatment such as corticosteroids, may also be involved. The variability in the presentation makes diagnosis difficult, which, if done soon, can help delay progression and reduce morbidity and the need for surgery.This report presents a case of knee osteonecrosis in a female patient who did not have previous knee pathology on imaging tests. She was diagnosed by magnetic resonance imaging months after hospital admission for SARS-CoV-2 pneumonia, which required high-dose corticosteroid treatment.

Pentafluorocyclopropanation of (Hetero)arenes Using Sulfonium Salts: Applications in Late-Stage Functionalization.

The evaluation of the pentafluorocyclopropyl group as a chemotype in crop protection and medicinal chemistry has been hampered in the past by the lack of suitable methodologies that enable the practical incorporation of this moiety into advanced synthetic intermediates. Herein, we report the gram-scale synthesis of an unprecedented sulfonium salt, 5-(pentafluorocyclopropyl)dibenzothiophenium triflate, and its use as a versatile reagent for the photoinduced C-H pentafluorocyclopropylation of a broad series of non-previously functionalized (hetero)arenes through a radical mediated mechanism. The scope and potential benefits of the protocol developed are further demonstrated by the late-stage introduction of the pentafluorocyclopropyl unit into biologically relevant molecules and widely used pharmaceuticals.

Tunable J-type aggregation of silicon phthalocyanines in a surface-anchored metal-organic framework thin film.

Organic chromophores and semiconductors, like anthracene, pentacene, perylene, and porphyrin, are prone to aggregation, and their packing in the solid state is often hard to predict and difficult to control. As the condensed phase structures of these chromophores and semiconductors are of crucial importance for their optoelectronic functionality, strategies to control their assembly and provide new structural motifs are important. One such approach uses metal-organic frameworks (MOFs); the organic chromophore is converted into a linker and connected by metal ions or nodes. The spatial arrangement of the organic linkers can be well-defined in a MOF, and hence optoelectronic functions can be adjusted accordingly. We have used such a strategy to assemble a phthalocyanine chromophore and illustrated that the electronic inter-phthalocyanine coupling can be rationally tuned by introducing bulky side grounds to increase steric hindrance. We have designed new phthalocyanine linkers and using a layer-by-layer liquid-phase epitaxy strategy thin films of phthalocyanine-based MOFs have been fabricated and their photophysical properties explored. It was found that increasing the steric hindrance around the phthalocyanine reduced the effect of J-aggregation in the thin film structures.

Ertapenem blood concentration: A retrospective cohort study to analyse risk of neurotoxicity.

AIMS: Several cases of ertapenem-related neurotoxicity have been published in the current literature. However, studies evaluating the ertapenem blood concentration (EBC) as a risk of these adverse events are scarce. We aimed to evaluate the relationship between the trough EBC and the risk of neurological toxicity. METHODS: This was a retrospective study, including patients who underwent ertapenem treatment between October 2019 and February 2021. We excluded patients in the critical care unit and those whose blood samples were not properly taken in order to analyse ertapenem trough concentration. We also excluded patients whose clinical follow-up was not properly realized for the entire period of ertapenem treatment. The main outcome was the presence of any suspicious neurological side effect owing to ertapenem administration and its relationship with the plasma concentration. Secondary outcomes were to identify clinical and analytical data contributing to a higher risk of neurotoxicity. RESULTS: The initial cohort comprised 158 individuals. For the final analysis we evaluated 102 patients, reporting a neurological alteration in 13/102 (12.7%). Mean trough EBC was significantly higher in patients showing neurotoxicity in comparison with those who did not (37.8 mcg mL-1 , standard deviation [SD] ± 35.7 vs. 14.6 mcg mL-1 , SD ± 15.2; P = .002). In multivariable logistic regression analysis, EBC (odds ratio [OR] = 1.07; P = .006), a moderate renal insufficiency (OR = 9.2; P = .02) and a history of previous neurologic disease (OR = 9.9; P = .02) were identified as risk factors of neurological alteration during ertapenem treatment. CONCLUSIONS: In patients at risk, determining the ertapenem plasma concentration may help to minimize the risk of neurotoxicity.

Analysis of Variables That Influence the Walkability of School Environments Based on the Delphi Method.

Walkability is determined the presence or absence of factors such as quality sidewalks, pedestrian crossings, traffic, etc. The ability to walk to the school environment may be one of the variables that promotes active commuting levels. The aim of this study was to examine the walkability of school environments using the Delphi method. This study used the Delphi method to measure the walkability. A total of 18 experts were selected. First, a list of variables was designed by the control group and sent three times to the experts. Later, the items were analyzed qualitatively and quantitatively to test the consensus of the experts. The list of variables that influence walkability showed a good consensus among the experts at the end of the process. This list was formed by 48 items and organized in six factors: traffic and safety (eleven items), signage (eight items), sidewalk (ten items), transport consistency (five items), activity (five items), and finally, urban planning (nine items). The experts agreed on the need to analyze the environments of educational centers and measure the variables that affect walkability. This study has identified the most important barriers. In the future, a measurement instrument should be developed that allows centers to be compared with others in terms of their levels of walkability. Moreover, it might be a resource for more policies to be developed with the aim to promote active commuting to school.

Effect of tocilizumab versus standard of care in adults hospitalized with moderate-severe COVID-19 pneumonia.

Introduction and objectives: Tocilizumab is an interleukin-6 receptor-blocking agent proposed for the treatment of severe COVID-19; however, limited data are available on their efficacy. The aim of this study was to assess the effect of tocilizumab on the outcomes of patients with COVID-19 pneumonia by using propensity-score-matching (PSM) analysis. Methods: A retrospective observational analysis of hospitalized COVID-19 adult patients admitted to the Vall d'Hebron Hospital was performed between March and April 2020. We used the logistic regression to analyze the effect of tocilizumab on mortality, as main outcome, and PSM analysis to further validate their effect. Secondary outcomes were length-of-stay (LOS) and intensive-care-unit (ICU) stay. Same outcomes were also assessed for early tocilizumab administration, within 72 h after admission. Patients were selected by matching their individual propensity for receiving therapy with tocilizumab, conditional on their demographic and clinical variables. Results: A total of 544 COVID-19 patients were included, 197 (36.2%) were treated with tocilizumab of whom 147 were treated within the first 72 h after admission; and 347 were included in the control group. After PSM analyses, the results showed no association between tocilizumab use and overall mortality (OR = 1.03, 95%CI: 0.63-1.68). However, shorter ICU-stay in the tocilizumab group was found compared to the control group (Coefficient -4.27 95%CI: -6.63 to -1.92). Similar results were found in the early tocilizumab cohort. Conclusions: The administration of tocilizumab in patients with moderate to severe COVID-19 did not reduce the risk of mortality in our cohort of patients, regardless of the time of administration.

Introducción y objetivos: El tocilizumab es un agente bloqueador del receptor de la interleucina 6 propuesto para el tratamiento de la COVID-19 grave; sin embargo, se dispone de datos limitados sobre su eficacia. El objetivo de este estudio fue evaluar el efecto de tocilizumab en los resultados de los pacientes con neumonía por COVID-19 mediante un análisis de emparejamiento por propensity-score-matching (PSM, «puntuación de propensión¼). Métodos: Se realizó un análisis observacional retrospectivo de los pacientes adultos con COVID-19 ingresados en el Hospital Vall d'Hebron entre marzo y abril de 2020. Se utilizó la regresión logística para analizar el efecto de tocilizumab en la mortalidad, como resultado principal, y el análisis PSM para validar aún más su efecto. Los resultados secundarios fueron la duración de la estancia y la estancia en la unidad de cuidados intensivos (UCI). También se evaluaron los mismos resultados para la administración temprana de tocilizumab, dentro de las 72 h posteriores al ingreso. Los pacientes se seleccionaron mediante el emparejamiento de su propensión individual a recibir tratamiento con tocilizumab, condicionado a sus variables demográficas y clínicas. Resultados: Se incluyeron 544 pacientes de COVID-19, 197 (36,2%) fueron tratados con tocilizumab, de los cuales 147 fueron tratados dentro de las primeras 72 h tras el ingreso; y 347 fueron incluidos en el grupo control. Tras los análisis PSM, los resultados no mostraron ninguna asociación entre el uso de tocilizumab y la mortalidad global (OR = 1,03; IC del 95%: 0,63-1,68). Sin embargo, se encontró una menor estancia en la UCI en el grupo de tocilizumab en comparación con el grupo de control (coeficiente −4,27; IC del 95%: −6,63 − −1,92). Se encontraron resultados similares en la cohorte de tocilizumab temprano. Conclusiones: La administración de tocilizumab en pacientes con COVID-19 moderada a grave no redujo el riesgo de mortalidad en nuestra cohorte de pacientes, independientemente del momento de la administración.

Safety and Effectiveness of Isavuconazole Treatment for Fungal Infections in Solid Organ Transplant Recipients (ISASOT Study).

Isavuconazole (ISA) is an alternative treatment for Aspergillus spp. and other fungal infections, but evidence regarding its use in solid organ transplant recipients (SOTR) is scarce. All SOTR who received ISA for treatment of a fungal infection (FI) at our center from December 2017 to January 2021 were included. The duration of the treatment depended on the type of infection. All patients were followed up to 3 months after treatment. Fifty-three SOTR were included, and the majority (44, 83%) were lung transplant recipients. The most frequently treated FI was tracheobronchitis (25, 46.3%). Aspergillus spp. (43, 81.1%); specially A. flavus (16, 37.2%) and A. fumigatus (12, 27.9%), was the most frequent etiology. Other filamentous fungi including one mucormycosis, and four yeast infections were treated. The median duration of treatment was 81 days (IQR 15-197). Mild gamma-glutamyltransferase elevation was the most frequent adverse event (34%). ISA was prematurely discontinued in six patients (11.3%) due to mild hepatotoxicity (2), fatigue (2), gastrointestinal intolerance (1) and myopathy (1). The mean tacrolimus dose decrease was 30% after starting ISA. Seven patients received ISA with mTOR inhibitors with good tolerability. Two patients developed breakthrough FI (3.8%). Among patients who completed the treatment, 27 (50.9%) showed clinical cure and 15 (34.1%) presented fungal persistence. Three patients (6%) died while on ISA due to FI. ISA was well tolerated and appeared to be an effective treatment for FI in SOTR. IMPORTANCE We describe 53 solid organ transplant recipients treated with isavuconazole for fungal infections. Because its use in clinical practice, there is scarce data of its use in solid organ transplant recipients, where interactions with calcineurin inhibitors and mTOR and adverse drug events have limited the use of other triazoles. To the best of our knowledge, this is the first article describing the safety regarding adverse events and drug interactions of isavuconazole for the treatment of fungal infections in a cohort of solid organ transplant recipients. Also, although this is a noncomparative study, we report some real world effectivity data of these patients, including treatment of non-Aspergillus fungal infections.

Effect of tocilizumab versus standard of care in adults hospitalized with moderate-severe COVID-19 pneumonia.

INTRODUCTION AND OBJECTIVES: Tocilizumab is an interleukin-6 receptor-blocking agent proposed for the treatment of severe COVID-19; however, limited data are available on their efficacy. The aim of this study was to assess the effect of tocilizumab on the outcomes of patients with COVID-19 pneumonia by using propensity-score-matching (PSM) analysis. METHODS: A retrospective observational analysis of hospitalized COVID-19 adult patients admitted to the Vall d'Hebron Hospital was performed between March and April 2020. We used the logistic regression to analyze the effect of tocilizumab on mortality, as main outcome, and PSM analysis to further validate their effect. Secondary outcomes were length-of-stay (LOS) and intensive-care-unit (ICU) stay. Same outcomes were also assessed for early tocilizumab administration, within 72h after admission. Patients were selected by matching their individual propensity for receiving therapy with tocilizumab, conditional on their demographic and clinical variables. RESULTS: A total of 544 COVID-19 patients were included, 197 (36.2%) were treated with tocilizumab of whom 147 were treated within the first 72h after admission; and 347 were included in the control group. After PSM analyses, the results showed no association between tocilizumab use and overall mortality (OR=1.03, 95%CI: 0.63-1.68). However, shorter ICU-stay in the tocilizumab group was found compared to the control group (Coefficient -4.27 95%CI: -6.63 to -1.92). Similar results were found in the early tocilizumab cohort. CONCLUSIONS: The administration of tocilizumab in patients with moderate to severe COVID-19 did not reduce the risk of mortality in our cohort of patients, regardless of the time of administration.

Cardiorespiratory Fitness in Spanish Firefighters: Age Differences and Associations Between Fitness-Related Parameters.

OBJECTIVE: To evaluate the cardiorespiratory fitness and other fitness-related measures, and to analyze the differences among age groups. METHODS: This study was conducted on 104 firefighters. Maximal oxygen uptake (VO2 max) was assessed using the Shuttle Test and fitness was evaluated using appropriate physical tests. RESULTS: Mean VO2 max was 45.7 mL/kg/min and 60.6% of firefighters were over the minimum accepted standpoint to do effective work, however, the VO2 max decreased with increasing age. 35.6% of the firefighters were overweight. Age, weight, and total body fat were found to be significant predictors of VO2 max level in this population, with total body fat as strongest predictor. CONCLUSIONS: Healthy habits-based interventions tailored by age groups should be promoted, to improve cardiorespiratory fitness and body composition for safe work and to improve firefighters' health.

Nebulized Micafungin Treatment for Scopulariopsis/Microascus Tracheobronchitis in Lung Transplant Recipients.

Scopulariopsis/Microascus isolates cause infections with high mortality in lung transplant recipients. Treatment is challenging due to antimicrobial resistance. We describe two cases of Scopulariopsis/Microascus tracheobronchitis in lung transplant recipients successfully treated with nebulized micafungin. This antifungal was well tolerated and achieved high concentrations in epithelial lining fluid up to 14 h after nebulization without significant plasma concentrations. Nebulized micafungin may be a safe and effective option for the treatment of fungal tracheobronchitis.

A New Software for Quantifying Motor Deficit After Stroke: A Case-Control Feasibility Pilot Study.

Introduction: The degree of disability after stroke needs to be objectively measured to implement adequate rehabilitation programs. Here, we evaluate the feasibility of a custom-built software to assess motor status after stroke. Methods: This is a prospective, case-control pilot study comparing stroke patients with healthy volunteers. A workout evaluation that included trunk and upper limb movement was captured with Kinect® and kinematic metrics were extracted with Akira®. Trunk and joint angles were analyzed and compared between cases and controls. Patients were evaluated within the first week from stroke onset using the National Institutes of Health Stroke Scale (NIHSS), Fulg-Meyer Assessment (FMA), and modified Rankin Scale (mRS) scales; the relationship with kinematic measurements was explored. Results: Thirty-seven patients and 33 controls were evaluated. Median (IQR) NIHSS of cases was 2 (0-4). The kinematic metrics that showed better discriminatory capacity were body sway during walking (less in cases than in controls, p = 0.01) and the drift in the forearm-trunk angle during shoulder abduction in supination (greater in cases than in controls, p = 0.01). The body sway during walking was moderately correlated with NIHSS score (Rho = -0.39; p = 0.01) but better correlated with mRS score (Rho = -0.52; p < 0.001) and was associated with the absence of disability (mRS 0-1) (OR = 0.64; p = 0.02). The drift in the forearm-trunk angle in supination was associated with the presence of disability (mRS >1) (OR = 1.27; p = 0.04). Conclusion: We present a new software that detects even mild motor impairment in stroke patients underestimated by clinical scales but with an impact on patient functionality.

Health Advertising during the Lockdown: A Comparative Analysis of Commercial TV in Spain.

During the lockdown declared in Spain to fight the spread of COVID-19 from 14 March to 3 May 2020, a context in which health information has gained relevance, the agenda-setting theory was used to study the proportion of health advertisements broadcasted during this period on Spanish television. Previous and posterior phases were compared, and the period was compared with the same period in 2019. A total of 191,738 advertisements were downloaded using the Instar Analytics application and analyzed using inferential statistics to observe the presence of health advertisements during the four study periods. It was observed that during the lockdown, there were more health advertisements than after, as well as during the same period in 2019, although health advertisements had the strongest presence during the pre-lockdown phase. The presence of most types of health advertisements also changed during the four phases of the study. We conclude that, although many differences can be explained by the time of the year-due to the presence of allergies or colds, for instance-the lockdown and the pandemic affected health advertising. However, the effects were mostly visible after the lockdown, when advertisers and broadcasters had had time to adapt to the unexpected circumstances.

Relación entre el Índice de Masa Corporal y el nivel de actividad física en adolescentes / The Relationship Between Body Mass Index and the Physical Activity Level in Adolescents / Relação entre o Índice de Massa Corporal e o nível de atividade física em adolescentes

Resumen Objetivo. Analizar la relación entre el Índice de Masa Corporal (IMC) percibido y la actividad física (AF) en adolescentes. Método. Participaron 605 adolescentes con edades comprendidas entre los 12 y los 15 años. Se valoraron las variables percibidas para el peso, la altura y el nivel de AF mediante un cuestionario autoinformado. Resultados. Se encontraron asociaciones significativas entre el IMC percibido y el nivel de AF. El análisis de regresión mostró que el IMC percibido sirve para predecir el nivel de AF. El análisis de la covarianza demostró la existencia de diferencias significativas entre los adolescentes con sobrepeso y obesidad frente a los normopeso. Conclusión. Se ha demostrado que los adolescentes que realizan menos AF tienen una mayor probabilidad de sufrir sobrepeso y obesidad.

Abstract Objective. The objective of this research is to analyse the relationship between the perceived body mass index and physical activity in adolescents. Method. A total of 605 adolescent students between 12 and 15 years old participated. The variables for perceived weight, height and physical activity level were assessed using a self-report questionnaire. Results. The results showed significant associations between the perceived body mass index and the physical activity level. The regression analysis showed that the perceived body mass index serves to predict the physical activity level. The analysis of covariance, demonstrated the existence of significant differences between overweight and obese adolescents versus those of normal weight. Conclusion. It has been shown that adolescents who perform less PA are more likely to be overweight.

Resumo Escopo. Analisar a relação entre o Índice de Massa Corporal (IMC) percebido e a atividade física (AF) em adolescentes. Metodologia. Participaram 605 adolescentes com idades compreendidas entre os 12 e os 15 anos. Foram valoradas as variáveis percebidas para o peso, a altura e o nível de AF através de um questionário auto informado. Resultados. Foram achadas associações significativas entre o IMC percebido e o nível de AF. A Análise de regressão mostrou que o IMC percebido serve para predizer o nível de AF. A análise da covariância demostrou a existência de diferenças significativas entre os adolescentes com sobrepeso e obesidade frente aos normopeso. Conclusão. Foi demostrado que os adolescentes que realizam menos AF têm uma maior probabilidade de sofrer sobrepeso e obesidade.

Tigecycline-associated hypofibrinogenemia in a real-world setting.

Background Tigecycline is a broad-spectrum antibiotic used to treat infections that do not respond to first-line treatments. High-doses and extended treatments are common; therefore, adverse events might be more frequent and severe than those observed in clinical trials. Several case-reports have referred hypofibrinogenemia in patients who received tigecycline. Objective To analyse the impact of tigecycline use on coagulation parameters, and identify which variables could be related with this. Setting The study was performed at Hospital Universitari Vall Hebron, in Barcelona, Spain. Method Observational, retrospective study. All patients older than 18, who received tigecycline for > 72 h from January 2016 to March 2018 were included. Clinical and laboratory data from before, during and at the end of tigecycline treatment were retrospectively collected. Differences between means were analyzed using the paired-sample Student's t-test. Binary logistic regression was performed to identify risk factors for hypofibrinogenemia. Main outcome measure Mean difference in fibrinogen plasma concentration and INR, before and at the end of tigecycline treatment. Results 78 patients (mean age 65; SD ± 15.5 years) were identified. The most common indications for tigecycline treatment were abdominal (66%), respiratory tract (16%) and skin&soft tissue (10%) infections. High-dose tigecycline was used in 62% of cases and the median duration of treatment was 12 days. Hypofibrinogenemia occurred in 12 patients, 5 bleeding events were observed and 4 of them required fibrinogen administration. Tigecycline caused significant alterations in fibrinogen plasma concentration (mean decrease 1.76 g/L; IC 95% 1.36 to 2.15) as well as INR (mean increase 0.11; IC 95% 0.05 to 0.17). Both were recovered after treatment cessation. We identified duration of treatment > 4 weeks (OR = 6.6), high-dose tigecycline (OR = 4.75) and high protein C levels (OR = 4.2) as independent variables associated with fibrinogen decrease, but not renal impairment. Conclusions Tigecycline administration has been related with hypofibrinogenemia, especially when high-doses of tigecycline are used. Health professionals should be aware of the potentially severe tigecycline-associated hypofibrinogenemia and monitor coagulation during treatment, especially when high-doses of tigecycline are used.