Population PK modeling of certolizumab pegol in pregnant women with chronic inflammatory diseases.

Certolizumab pegol (CZP; CIMZIA™) is the only Fc-free tumor necrosis factor inhibitor with data from a clinical study demonstrating no to minimal placental transfer. The pharmacokinetics (PK) of certolizumab pegol during pregnancy and postpartum in women with chronic inflammatory diseases were assessed using a population PK model based on data from the CHERISH study (NCT04163016), a longitudinal, prospective, open-label PK phase IB study. Model development was performed in NONMEM using a frequentist prior approach, with prior information based on a population PK model for certolizumab pegol in non-pregnant adult patients (NCT04740814). A one-compartment model with first-order absorption (Ka = 0.236 1/day) and linear elimination (CL/F = 0.416 L/day) from the central compartment (V/F = 7.86 L) best described certolizumab pegol PK in the CHERISH study. The structural model parameters were estimated with good precision (RSE < 25%). Baseline BW was included as a covariate on CL/F and V/F. Pregnancy trimester and time-varying log-transformed anti-drug antibody (ADA) titer were identified as the only significant covariates for CL/F with a comparable influence on CL/F. Individuals with higher ADA titer (75th percentile) during pregnancy exhibited CL/F up to 1.43-fold higher relative to individuals postpartum that showed median levels of ADA titer. However, the confidence interval for the combined effect of pregnancy stage and ADA titer effects on CL/F overlapped with the CL/F range of the typical individual postpartum. In addition, simulations showed a large overlap in certolizumab pegol concentrations between pregnant and non-pregnant adults. The findings of this population PK analysis support the maintenance of established certolizumab pegol dosing regimens throughout pregnancy.

Guía mexicana para el diagnóstico y el tratamiento del hemangioma infantil.

Infantile hemangioma is a benign vascular tumor, the most common in childhood, whose natural evolution is the disappearance of the lesion in the pediatric age and which has effective and safe treatments that limit its growth and favor its disappearance at younger ages. Infantile hemangioma continues to be a reason for attention to complications, due to erroneous diagnoses, lack of knowledge of the condition, late referral or fear of the effects of the medications used for its treatment. Furthermore, its presence is normalized without taking into account that it can cause uncertainty, anxiety, feelings of guilt and, as a consequence, a significant impact on the quality of life, mainly in the parents or caregivers of the child. The need for a clinical practice guideline in our country arises from the high presentation of late-remitted complications in infantile hemangioma even with the availability of adequate treatments, the continuous evolution of medicine and the appearance of new evidence. Throughout the guide you will find recommendations regarding the diagnosis, treatment and follow-up of patients with infantile hemangioma, taking into account the paraclinical tests that can be performed, topical or systemic management options, as well as adjuvant therapies. For the first time, objective tools for patient follow-up are included in a guide for the management of infantile hemangioma, as well as to help the first contact doctor in timely referral.

El hemangioma infantil es un tumor vascular benigno, el más frecuente de la infancia, cuya evolución natural favorece la desaparición de la lesión en la misma edad pediátrica y que cuenta con tratamientos eficaces y seguros que limitan su crecimiento y favorecen su desaparición a edades más tempranas. Continúa siendo motivo de atención de complicaciones, debido a diagnósticos erróneos, desconocimiento del padecimiento, referencia tardía o temor de los efectos de los fármacos utilizados para su tratamiento. Además, se normaliza su presencia sin tomar en cuenta que puede llegar a causar incertidumbre, ansiedad, sentimientos de culpa y, como consecuencia, importante afectación de la calidad de vida, principalmente en los padres o cuidadores del niño. La necesidad de una guía de práctica clínica en nuestro país surge ante la alta presentación de complicaciones del hemangioma infantil referidas de manera tardía aun con la disponibilidad de tratamientos adecuados, la evolución continua de la medicina y la aparición de nueva evidencia. A lo largo de la guía se encontrarán recomendaciones en relación con el diagnóstico, el tratamiento y el seguimiento de los pacientes con hemangioma infantil, tomando en cuenta los paraclínicos que pueden realizarse, las opciones de manejo tópico o sistémico, y las terapias adyuvantes. Por primera vez se incluyen en una guía para el manejo del hemangioma infantil herramientas objetivas para el seguimiento de los pacientes, así como para ayudar al médico de primer contacto en su referencia oportuna.

[National Survey on the Activity of Lung Function Laboratories. Effects During the SARS-COV-2 Pandemic]. / Encuesta sobre la actividad de los laboratorios de función pulmonar. Efectos durante la pandemia por SARS-CoV-2.

Introduction: Following the SARS-CoV-2 pandemic in March 2020, pulmonary function testing (PFT) laboratories underwent a transformation, with a reduction in the number of tests or closure in some cases. The aim of this work was to know the activity of PFT in Spain and the modification of this activity due to the pandemic. Material and methods: A protocolised survey was carried out to members of the PFT laboratories through the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Results: Thirty-nine hospitals in Spain responded. The pulmonary function tests most frequently performed in the PFT laboratories were forced spirometry with bronchodilator test (100%), body plethysmography (97.4%), CO transfer capacity (97.4%), respiratory muscle strength measured in the mouth (97.4%), 6-minute walking test (94.7%), measurement of exhaled fraction of nitric oxide (92.3%) and incremental exercise test (71.8%).The pandemic led to a significant decrease in the number of tests (35.4%) during 2020 with subsequent recovery in 2021, without reaching pre-pandemic values.The most important changes were increased examination times, working with personal protective equipment and ventilation of the rooms. The performance of the nasopharyngeal swab for SARS-CoV2 testing prior to the tests was not homogeneous in the PFT laboratories. Conclusions: Most hospitals are sufficiently equipped to perform the most common pulmonary function tests. The pandemic resulted in a loss of activity in all hospitals.

Nontoxic effects of thymol, carvacrol, cinnamaldehyde, and garlic oil on dung beetles: A potential alternative to ecotoxic anthelmintics.

The sustainability of the traditional extensive livestock sector will only be possible if healthy dung-decomposing insect communities are preserved. However, many current pharmaceutical anthelmintics are harmful to dung beetles, their presence can have a negative impact on biological systems. Phytochemical anthelmintics are an alternative to ecotoxic synthetic pharmaceutical anthelmintics, although ecotoxicological tests of their possible indirect effects on dung beetles are required to demonstrate their viability. In this study, the potential ecotoxicity of thymol, carvacrol, cinnamaldehyde and garlic oil (diallyl disulfide and diallyl trisulfide) were tested for the first time. Inhibition of antennal response was measured as a relevant parameter by obtaining relevant toxicity thresholds derived from concentration‒response curves, such as the IC50. All phytochemical compounds tested were demonstrated to be suitable alternative candidates to the highly ecotoxic compound ivermectin, considering their non-toxicity to nontarget organisms. Residues of the phytochemical antiparasitics found in cattle droppings were extremely low, even undetectable in the case of diallyl disulfide and diallyl trisulfide. Furthermore, our results showed that none of the phytochemical compounds have ecotoxic effects, even at extremely high concentrations, including those almost 1000 times higher than what is most likely to be found in dung susceptible to ingestion by dung beetles in the field. We can conclude that the four selected phytochemical compounds meet the requirements to be considered reliable alternatives to ecotoxic veterinary medicinal products, such as ivermectin.

Diferencias e influencia en la Conducta Adaptativa por las regiones colombianas

La presente investigación tuvo por objetivo describir las diferencias e influencia de las regiones colombianas en las Habilidades Adaptativas Específicas y Dominios de la Conducta Adaptativa en niños colombianos entre 0-15 años, sin alteraciones en el neurodesarrollo y sin etiología de daño cerebral. Participaron padres y profesores de 2081 niños, divididos por 4 regiones geográficas: Andina, Caribe, Orinoquía y Pacífico. Se aplicó el cuestionario de conducta adaptativa ABAS-II en sus versiones Infantil padres a los padres de niños de 0 a 1,11 años, y las versiones escolar padres y escolar profesores a los padres y profesores de niños de 2 a 15 años. Los resultados indicaron que existen diferencias estadísticamente significativas entre los menores de las diferentes regiones, siendo los resultados más altos los de la región Pacífico y los más bajos los de la región Orinoquía. Con estos resultados se considera que es importante tener en cuenta los aspectos culturales, sociales, ambientales e históricos de cada región del país para la evaluación de su conducta adaptativa, entendiendo que estas diferencias no marcan o indican mayor susceptibilidad a patología, sino variaciones culturales dentro de los términos considerados como lo esperado.

The present research aimed to describe the differences and influence of Colombia geographic regions on Specific Adaptive Skills and Domains of Adaptive Behavior in Colombian children between 0-15 years of age without neurodevelopmental alterations and without etiology of cerebral disease. 2081 Colombian children´s parents and teachers participated, divided into 4 regions: Andean, Caribbean, Orinoquía and Pacific. The ABAS-II questionnaire was applied the chindren´s parent version to parents of children from 0 to 1,11 years and the school parents`and school teachers` versions to parents and teachers of children from 2 to 15 years of age. The results indicated that there are statistically significance differences between the children of the different regions, the highest results being those of the Pacific region and the lowest those of the Orinoquía region. It is considered with the results that it is important to take into account the cultural, social, environmental and historical aspects of each region of the country for the evaluation of their adaptive behavior; these differences do not mark or indicate greater susceptibility to pathology, but rather cultural variations within of the terms considered as the expected.

Lateralized overgrowth as a guiding sign of abdominal neoplasms for pediatric orthopedic surgeons.

OBJECTIVES: This study aims to increase the awareness of the association between lateralized overgrowth (LO) and abdominal tumor among the pediatric orthopedic community and to evaluate its incidence in our center. PATIENTS AND METHODS: Between January 1997 and December 2021, a total of 166 patients with Wilms tumors and hepatoblastomas were retrospectively analyzed. Data including age, sex, initial clinical signs (hematuria, abdominal mass with or without general discomfort), type of asymmetric regional body overgrowth (isolated or in relation with any syndrome), and tumor stage at diagnosis were recorded. In addition, age at which asymmetric regional body overgrowth was described and age at the time of tumor diagnosis were noted. RESULTS: Of a total of 166 patients, 133 were diagnosed with Wilms tumors (nephroblastomas) and 33 were diagnosed with hepatoblastomas. In 94% of the cases, the initial clinical signs were an abdominal mass and/or hematuria. Overall, five (3%) patients presented with LO. Four patients with Wilms tumor presented it at the initial clinical examinations. In three of these cases (2.3%), we found it isolated and, in the remaining patient (0.75%), it was associated with Beckwith-Wiedemann spectrum. Only one patient affected from hepatoblastoma (3%) presented with an isolated LO at the time of tumor diagnosis. CONCLUSION: Our study results show an incidence of LO in relation to intra-abdominal tumors of 3%. The latest updates recommend genetic testing to identify subgroups with a higher risk for tumor development that are more likely to benefit from tumor protocol surveillance.

Pulmonary Embolism (PE) Prevalence in Mexican-Mestizo Patients With Severe SARS-COV-2 (COVID-19) Pneumonia At A Tertiary-Level Hospital: A Review.

Since the report of the first case of COVID-19 in Wuhan, China, on December 31, 2019, several associated thrombotic complications have been reported, mainly venous thromboembolic events, and myocardial infarctions, in addition to peripheral arterial thrombosis and cerebral vascular events, which have been attributed to a hypercoagulable state. We aimed to know the prevalence and prognostic biomarkers in patients with pulmonary thromboembolism (PE) and SARS Cov-2 pneumonia. Hospitalized patients with SARS Cov-2 pneumonia who have had clinical, biomarker, and imaging data (chest angiography) of pulmonary thromboembolism were included. Descriptive statistics and prevalence rates were calculated. For the analysis between the groups, the paired Student's t and the Wilcoxon test were performed. CT angiography was performed on 26 patients at our institution, with a diagnosis of severe pneumonia secondary to SARS-CoV2. 9 of the patients (34.6%) had a venous thromboembolic disease. Type 2 DM was the most frequent comorbidity up to 55.5% of the total; it was followed by obesity and overweight in 55.5%, and in third place, by systemic arterial hypertension in 33.3% of the cases, 1 (11.1%) patient had chronic kidney disease and 1 (11.1%) patient with a history of cancer, only 1 patient met criteria and was treated with thrombolysis. 6 (66.6%) of the patients had segmental PE, 3 (33.3%) patients had subsegmental PE, and 4 (44.4%) patients presented pulmonary infarction.

Effects of Oleacein, a New Epinutraceutical Bioproduct from Extra Virgin Olive Oil, in LPS-Activated Murine Immune Cells.

The present study was designed to evaluate the immunomodulatory effects of the secoiridoid from extra virgin olive oil, oleacein (OLA), deepening into the possible signaling pathways involved in LPS-activated murine peritoneal macrophages. Moreover, we have explored OLA-induced epigenetic changes in histone markers and related cytokine production in murine LPS-stimulated murine splenocytes. Murine cells were treated with OLA in the presence or absence of LPS (5 µg/mL) for 18 or 24 h. OLA modulated the oxidative stress and the inflammatory response produced by LPS stimulation in murine peritoneal macrophages, by the inhibition of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IFN-γ, IL-17 and IL-18) and ROS production and the expression of pro-inflammatory enzymes such as iNOS, COX-2 and m-PGES1. These protective effects could be due to the activation of the Nrf-2/HO-1 axis and the inhibition of JAK/STAT, ERK and P38 MAPKs and inflammasome canonical and non-canonical signaling pathways. Moreover, OLA modulated epigenetic modifications throughout histone methylation deacetylation (H3K18ac) and (H3K9me3 and H3K27me) in LPS-activated spleen cells. In conclusion, our data present OLA as an interesting anti-inflammatory and antioxidant natural compound that is able to regulate histone epigenetic markers. Nevertheless, additional in vivo studies are required to further investigate the beneficial effects of this EVOO secoiridoid, which might be a promising epinutraceutical bioproduct for the management of immune-related inflammatory diseases.

Comparative analysis of the anthelmintic efficacy of European heather extracts on Teladorsagia circumcincta and Trichostrongylus colubriformis egg hatching and larval motility.

BACKGROUND: Gastrointestinal nematode (GIN) control is traditionally achieved with the use of anthelmintic drugs, however due to regulations in organic farming and the rise in anthelmintic resistance, alternatives are sought after. A promising alternative is the use of bioactive plant feeding due to the presence of plant secondary metabolites (PSMs) such as proanthocyanidins (PAs). This study focussed on the perennial shrub heather (Ericaceae family), a plant rich in PAs, highly abundant across Europe and with previously demonstrated anthelmintic potential. METHODS: In vitro assays were used to investigate heather's anthelmintic efficacy against egg hatching and larval motility. Heather samples were collected from five European countries across two seasons, and extracts were tested against two GIN species: Teladorsagia circumcincta and Trichostrongylus colubriformis. Polyphenol group-specific ultraperformance liquid chromatography-tandem mass spectrometry analysis was performed to identify relevant polyphenol subgroups present, including the PA concentration and size and ratio of the subunits. Partial least squares analysis was performed to associate efficacy with variation in PSM composition. RESULTS: Heather extracts reduced egg hatching of both GIN species in a dose-dependent manner by up to 100%, while three extracts at the highest concentration (10 mg/ml) reduced larval motility to levels that were not significantly different from dead larvae controls. PAs, particularly the procyanidin type, and flavonol derivatives were associated with anthelmintic activity, and the particular subgroup of polyphenols associated with the efficacy was dependent on the GIN species and life stage. CONCLUSIONS: Our results provide in vitro evidence that heather, a widely available plant often managed as a weed in grazing systems, has anthelmintic properties attributed to various groups of PSMs and could contribute to sustainable GIN control in ruminant production systems across Europe.

Poland syndrome: a new classification system based on a retrospective analysis of 74 cases.

LEVEL OF EVIDENCE: III.

Pre-operative prevalence of asymptomatic carriers of COVID-19 in hospitals in Catalonia during the first wave after the resumption of surgical activity.

INTRODUCTION: The COVID-19 pandemic led to the cancellation of non-essential surgical procedures in March 2020. With the resumption of surgical activity, patients undergoing surgery were one of the first population groups to be systematically tested for PCR. The aim of this study was to determine the prevalence of asymptomatic SARS-CoV-2 carriers after the resumption of non-essential surgical activity. METHODS: Retrospective multicenter observational study of patients scheduled for surgery or undergoing emergency surgery in Catalonia between 20 April and 31 May 2020. The microbiological results of preoperative PCR tests and clinical records were reviewed, and an epidemiological survey was conducted on patients with positive PCR for SARS-CoV-2. RESULTS: A total of 10,838 patients scheduled for surgery or who underwent emergency surgery were screened for COVID-19. One hundred and eighteen patients (1.09%) were positive for SARS-CoV-2 in the 72 h prior to surgery. The prevalence of asymptomatic carriers was 0.7% (IC95%: 0.6%-0.9%). The first week of the study presented the highest prevalence of asymptomatic carriers [1.9% (CI95%:1.1%-3.2%)]. CONCLUSIONS: The low levels of asymptomatic carriers of COVID-19 infection obtained in the surgical population of hospitals in Catalonia after the resumption of surgical activity, shows that most patients were able to undergo surgical procedures without the risks of COVID-19 associated complications in the perioperative period.

Scrotal arteriovenous malformation: Case report.

Scrotal arteriovenous malformations (AVM) are extremely rare, making them difficult and complex to diagnose, and a therapeutic challenge; few cases of this type have been reported in the literature. This article reports the case of a male patient, 12 years old, with congenital AVM and background of treatment with sclerotherapy and embolization: it was decided to perform a surgical resection, which was successful. Angiography is obligatory in arteriolar cases, and it was backed up with surgical AVM treatment, taking into account the great importance of pre-surgical embolization.

Bilateral carotid body tumor case: A novel preoperative management.

Paragangliomas are rare neuroendocrine neoplasms. The most common form of these tumors in head and neck are non-functional carotid body tumors. These neoplasms may present an extensive growth and compromise vital neurovascular structures in the neck, such as carotid vessels. Carotid body tumors usually present clinically as painless neck masses and occur most frequently in adults averaging 45 to 50 years, being the majority of these tumors unilateral and only 5% of all cases bilateral. The main treatment for carotid body paragangliomas is surgical resection, which can be extremely challenging due to tumor hypervascularity and significant blood loss. We present a bilateral carotid body tumor case in a 61-year-old woman who presented due to a pulsatile and painless mass in the right carotid region of the neck of 1-year of evolution. The tumor was found encasing the external carotid artery and classified as Shamblin II. A novel approach for preoperative management was performed, placing a covered graft-stent in the right common and proximal (C1) internal carotid arteries in order to splint and provide structural protection for carotid vessels during surgical resection and temporarily reduce blood flow of the carotid body tumor.

Impact of microscopic incomplete resection for colorectal liver metastases on surgical margin recurrence: R1-Contact vs R1 < 1 mm margin width.

BACKGROUND: Several studies highlighted an inferior outcome of R1 resection for colorectal cancer liver metastases (CRLM); it is still unclear whether directly involved margins (R1-contact) are associated with a poorer outcome compared to R1 < 1 mm. The aim of this study is to analyze the impact on surgical margin recurrence (SMR) of R1-contact vs R1 < 1 mm patients. METHODS: Patients who underwent surgery for CRLM between 2009-2018 with both R1 resections on final histology were included and compared in terms of recurrence and survival. Factors associated with SMR were assessed by univariate and multivariate analysis. RESULTS: Out of 477, 77 (17.2%) patients showed R1 resection (53 R1-Contact and 24 R1 < 1 mm). Overall recurrence rate was 79.2% (R1 < 1 mm = 70.8% vs R1-contact group = 83%, P = .222). Median disease-free survival (DFS) and disease-specific survival (DSS) were significantly higher in R1 < 1 mm vs R1-contact group (93 vs 55 months; P = .025 and 69 vs 46 months; P = .038, respectively). The SMR rate was higher in R1-contact compared to R1 < 1 mm group (30.2% vs 8.3%; P = .036). At univariate analysis, age, number of metastases, open surgical approach, RAS status, and R1-contact were associated with SMR. At multivariate analysis, R1-contact margin was the only factor independently associated with higher SMR (OR = 5.6; P = .046). CONCLUSIONS: R1-contact margin is independently associated with SMR after liver resection for CRLM. Patients with R1-contact margin will also experience poorer DFS and DSS.

Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease.

In this study, we aimed to modify the immune response in the long term after allogeneic bone marrow transplantation (allo-BMT) by using the proteasome inhibitor ixazomib (IXZ) at the late stages of the post-transplant period. This approach facilitated the immune reconstitution after transplantation. IXZ significantly prolonged survival and decreased the risk of chronic graft-versus-host disease (cGvHD) in two different murine models without hampering the graft-versus-leukemia (GvL) effect, as confirmed by bioluminescence assays. Remarkably, the use of IXZ was related to an increase of regulatory T cells both in peripheral blood and in the GvHD target organs and a decrease of effector donor T cells. Regarding B cells, IXZ treated mice had faster recovery of B cells in PB and of pre-pro-B cells in the bone marrow. Mice receiving ixazomib had a lower number of neutrophils in the GvHD target organs as compared to the vehicle group. In summary, delayed administration of IXZ ameliorated cGvHD while preserving GvL and promoted a pro-tolerogenic immune response after allo-BMT.

Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy.

Liver resection treats primary and secondary liver tumors, though clinical applicability is limited by the remnant liver mass and quality. Herein, major hepatic resections were performed in pigs to define changes associated with sufficient and insufficient remnants and improve liver-specific outcomes with somatostatin therapy. Three experimental groups were performed: 75% hepatectomy (75H), 90% hepatectomy (90H), and 90% hepatectomy + somatostatin (90H + SST). Animals were followed for 24 h (N = 6) and 5 d (N = 6). After hepatectomy, portal pressure gradient was higher in 90H versus 75H and 90H + SST (8 (3-13) mmHg vs. 4 (2-6) mmHg and 4 (2-6) mmHg, respectively, p < 0.001). After 24 h, changes were observed in 90H associated with stellate cell activation and collapse of sinusoidal lumen. Collagen chain type 1 alpha 1 mRNA expression was higher, extracellular matrix width less, and percentage of collagen-staining areas greater at 24 h in 90H versus 75H and 90H + SST. After 5 d, remnant liver mass was higher in 75H and 90H + SST versus 90H, and Ki-67 immunostaining was higher in 90H + SST versus 75H and 90H. As well, more TUNEL-staining cells were observed in 90H versus 75H and 90H + SST at 5 d. Perioperative somatostatin modified portal pressure, injury, apoptosis, and stellate cell activation, stemming changes related to hepatic fibrogenesis seen in liver remnants not receiving treatment.

Impact of the COVID-19 pandemic on the management of chronic noninfectious respiratory diseases.

Introduction: The COVID-19 pandemic has challenged health care across the world, not just by the severity of the disease and the high mortality rate but also by the consequences on the management of the patients with chronic diseases.Areas covered: This review summarizes the most up-to-date published data regarding the impact of COVID-19 on the management and outcomes of patients with chronic noninfectious respiratory illnesses including obstructive sleep apnea, asthma, chronic obstructive pulmonary disease, bronchiectasis, interstitial and pulmonary vascular diseases, and lung cancer.Expert opinion: Most of chronic respiratory diseases (except asthma and cystic fibrosis) are associated with more severe COVID-19 and poor outcomes but the mechanisms involved are not yet identified. The therapeutic management of the patients with chronic respiratory diseases and COVID-19 is similar to the other patients but the post-recovery course could be worse in this population and followed by the development of pulmonary fibrosis, bronchiectasis, and pulmonary hypertension. The pandemic highly impacted our usual medical activities by limiting the access to several diagnosis procedures, the necessity to develop new methods for the monitoring of the disease and adapt the therapeutic strategies. The long-term consequences of all these changes are still unknown.

CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells.

The impairment of the CFTR channel activity, a cAMP-activated chloride (Cl-) channel responsible for cystic fibrosis (CF), has been associated with a variety of mitochondrial alterations such as modified gene expression, impairment in oxidative phosphorylation, increased reactive oxygen species (ROS), and a disbalance in calcium homeostasis. The mechanisms by which these processes occur in CF are not fully understood. Previously, we demonstrated a reduced MTND4 expression and a failure in the mitochondrial complex I (mCx-I) activity in CF cells. Here we hypothesized that the activity of CFTR might modulate the mitochondrial fission/fusion balance, explaining the decreased mCx-I. The mitochondrial morphology and the levels of mitochondrial dynamic proteins MFN1 and DRP1 were analysed in IB3-1 CF cells, and S9 (IB3-1 expressing wt-CFTR), and C38 (IB3-1 expressing a truncated functional CFTR) cells. The mitochondrial morphology of IB3-1 cells compared to S9 and C38 cells showed that the impaired CFTR activity induced a fragmented mitochondrial network with increased rounded mitochondria and shorter branches. Similar results were obtained by using the CFTR pharmacological inhibitors CFTR(inh)-172 and GlyH101 on C38 cells. These morphological changes were accompanied by modifications in the levels of the mitochondrial dynamic proteins MFN1, DRP1, and p(616)-DRP1. IB3-1 CF cells treated with Mdivi-1, an inhibitor of mitochondrial fission, restored the mCx-I activity to values similar to those seen in S9 and C38 cells. These results suggest that the mitochondrial fission/fusion balance is regulated by the CFTR activity and might be a potential target to treat the impaired mCx-I activity in CF.

Pre-operative prevalence of asymptomatic carriers of COVID-19 in hospitals in Catalonia during the first wave after the resumption of surgical activity. / Prevalencia preoperatoria de portadores asintomáticos de COVID-19 en hospitales de Cataluña durante la primera ola tras el reinicio de la actividad quirúrgica.

INTRODUCTION: The COVID-19 pandemic led to the cancellation of non-essential surgical procedures in March 2020. With the resumption of surgical activity, patients undergoing surgery were one of the first population groups to be systematically tested for PCR. The aim of this study was to determine the prevalence of asymptomatic SARS-CoV-2 carriers after the resumption of non-essential surgical activity. METHODS: Retrospective multicenter observational study of patients scheduled for surgery or undergoing emergency surgery in Catalonia between 20 April and 31 May 2020. The microbiological results of preoperative PCR tests and clinical records were reviewed, and an epidemiological survey was conducted on patients with positive PCR for SARS-CoV-2. RESULTS: A total of 10,838 patients scheduled for surgery or who underwent emergency surgery were screened for COVID-19. One hundred and eighteen patients (1.09%) were positive for SARS-CoV-2 in the 72hours prior to surgery. The prevalence of asymptomatic carriers was 0.7% (95%CI: 0.6% - 0.9%). The first week of the study presented the highest prevalence of asymptomatic carriers [1.9% (95%CI: 1.1%-3.2%)]. CONCLUSIONS: The low levels of asymptomatic carriers of COVID-19 infection obtained in the surgical population of hospitals in Catalonia after the resumption of surgical activity, shows that most patients were able to undergo surgical procedures without the risks of COVID-19 associated complications in the perioperative period.

IL-6-based mortality risk model for hospitalized patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic. Because the severity of the disease is highly variable, predictive models to stratify patients according to their mortality risk are needed. OBJECTIVE: Our aim was to develop a model able to predict the risk of fatal outcome in patients with COVID-19 that could be used easily at the time of patients' arrival at the hospital. METHODS: We constructed a prospective cohort with 611 adult patients in whom COVID-19 was diagnosed between March 10 and April 12, 2020, in a tertiary hospital in Madrid, Spain. The analysis included 501 patients who had been discharged or had died by April 20, 2020. The capacity of several biomarkers, measured at the beginning of hospitalization, to predict mortality was assessed individually. Those biomarkers that independently contributed to improve mortality prediction were included in a multivariable risk model. RESULTS: High IL-6 level, C-reactive protein level, lactate dehydrogenase (LDH) level, ferritin level, d-dimer level, neutrophil count, and neutrophil-to-lymphocyte ratio were all predictive of mortality (area under the curve >0.70), as were low albumin level, lymphocyte count, monocyte count, and ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2). A multivariable mortality risk model including the SpO2/FiO2 ratio, neutrophil-to-lymphocyte ratio, LDH level, IL-6 level, and age was developed and showed high accuracy for the prediction of fatal outcome (area under the curve 0.94). The optimal cutoff reliably classified patients (including patients with no initial respiratory distress) as survivors and nonsurvivors with 0.88 sensitivity and 0.89 specificity. CONCLUSION: This mortality risk model allows early risk stratification of hospitalized patients with COVID-19 before the appearance of obvious signs of clinical deterioration, and it can be used as a tool to guide clinical decision making.