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Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19). The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others.We report the preliminary results from the Vall d'Hebron cohort study at Vall d'Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed SARS-CoV-2 infection and who were treated with tocilizumab until March 25th.82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3-8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8-5.8) if tocilizumab was administered after the onset of ARDS.Early administration of tocilizumab in patients needing oxygen supplementation may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data regarding the precise timing in of initiation of the treatment with tocilizumab.Los tratamientos inmunomoduladores para la prevención del daño pulmonar están siendo ampliamente estudiados contra la COVID-19. El objetivo primario es evaluar la mortalidad a los 7 días después de la administración de tocilizumab. El objetivo secundario es el ingreso en UCI, el desarrollo de distrés respiratorio agudo e insuficiencia respiratoria aguda entre otros.Informamos sobre los resultados preliminares de la cohorte del Hospital Universitario Vall d’Hebron en Barcelona (España), que incluye todos los pacientes consecutivos con infección confirmada por SARS-CoV-2 y que recibieron tratamiento con tocilizumab hasta el 25 de marzo 2020.Ochenta y dos pacientes con COVID-19 recibieron al menos una dosis de tocilizumab. La edad media (±DE) fue de 59,1 (±19,8) años, el 63% eran hombres, 22% correspondía a paciente nacidos fuera de España, y la mediana (RIC) del índice de Charlson ajustado por edad en el momento basal fue de 3 (1-4) puntos. Sesenta y dos pacientes (75,6%) y 45 pacientes (54,9%) desarrollaron insuficiencia respiratoria y distrés respiratorio agudo respectivamente. La mediana de tiempo desde el inicio de los síntomas hasta el desarrollo de ditrés fue de 8 días (5-11). La mortalidad a los 7 días fue del 26,8% La hazard ratio de mortalidad fue del 3,3; IC 95% 1,3-8,5 (la hazard ratio de mortalidad ajustada por edad fue de 2,1; IC 95% 0,8-5,8) si el tocilizumab se administraba después del inicio del distrés respiratorio.La administración precoz de tocilizumab en pacientes con suplementos de oxígeno podría ser crítica para la recuperación de los pacientes. Nuestros datos podrían ayudar a tomar decisiones clínicas hasta que se disponga de más información sobre el momento adecuado para iniciar el tratamiento con tocilizumab.

Antecedentes y Objetivo El objetivo fue describir las características clínicas y el pronóstico de los pacientes con infección nosocomial por SARS-CoV-2. Métodos Se realizó un estudio observacional y prospectivo en un hospital de referencia. Se incluyeron todos los pacientes adultos diagnosticados de infección por SARS-CoV-2 nosocomial en octubre de 2020, definida como una PCR para SARS-CoV-2 negativa al ingreso y positiva a partir de los siete días de hospitalización. Resultados Se diagnosticaron 66 casos de infección por SARS-CoV-2 nosocomial: 39 (59%) hombres, edad mediana al diagnóstico de 74,5 años (RIC 56,8-83,1) y mediana del índice de comorbilidad de Charlson de 3 puntos (RIC 1-5). Veintisiete (41%) presentaron neumonía y 13 (20%) fallecieron durante el ingreso. La mortalidad a los 28 días fue del 33% (22 pacientes). La mortalidad a los 28 días en los 242 pacientes con infección por SARS-CoV-2 adquirida en la comunidad y hospitalizados durante el mismo periodo fue del 10%. Conclusiones Se deben extremar las medidas de prevención y detección precoz de brotes nosocomiales de COVID-19 para minimizar el impacto negativo de esta infección.

OBJECTIVES The aim of this study was to assess whether the use of topical pharyngeal anesthesia improves endoscopist- and patient-reported tolerance and satisfaction, the total dose of propofol used and the rate of adverse effects associated with this procedure. METHODS This double-blind randomized clinical trial was conducted in patients undergoing elective oesophagogastroduodenoscopy, who met the inclusion criteria. Patients were randomly assigned to receive five squirts of lidocaine 10% spray (50 mg, n = 268) or placebo (n = 271) 3 min before starting the procedure or sedation. The main outcome measures were patient- and endoscopist-reported tolerance, and additionally, satisfaction with the procedure, adverse events and supplementary propofol used. RESULTS In the lidocaine group, it was twice (odds ratio [OR] 2.136, 95% confidence interval [CI] 1.228-3.715) or three times (OR 3.311, 95% CI 1.623-6.757) more likely that the endoscopist rated the procedure as well tolerated and easy to intubate than as well tolerated but the patient difficult to intubate or as poorly tolerated, respectively. Further, in these patients, less propofol was used (80 vs. 100 mg, P = 0.001). Controls were more likely to cough during the intubation (OR 2.172, 95% CI 1.378-3.423) and the procedure (OR 1.989, 95% CI 1.325-2.984), as well as more likely to retch (OR 3.582, 95% CI 1.667-7.7). CONCLUSIONS Topical lidocaine may improve the procedure as rated by the endoscopist, as well as reduce the requirement for propofol and rate of adverse events such as retching and coughing. No adverse events associated with lidocaine administration were observed. ClinicalTrials registration no. NCT02733471.

OBJECTIVES Few data regarding follow-up of patients after COVID-19 discharge are available. We aim to describe the long-term outcomes of survivors of hospitalization for COVID-19 followed up first at an outpatient facility and subsequently by telephone. METHODS Observational prospective study conducted at a tertiary general hospital. Clinical and radiological progression was assessed and data recorded on a standardized reporting form. Patients were divided into three groups according to PaO2/FiO2 at hospitalization: PaO2/FiO2 > 300, PaO2/FiO2 300-200 and PaO2/FiO2 < 200. A logistic multivariate regression model was performed to identify factors associated with persistence of symptoms. RESULTS Facility follow-up: 302 patients were enrolled. Median follow-up was 45 days after discharge; 78% (228/294) of patients had COVID-19-related symptoms (53% asthenia, 56% respiratory symptoms) and 40% (122/302) had residual pulmonary radiographic lesions. PaO2/FiO2 300 was associated with resolution of chest radiographic lesions; OR = 0.56 (0.42 to 0.74), (p, Graphical abstract Image 1

Background: Intracerebral Hemorrhage (ICH) is one of the most feared complications after brain tumor surgery. Postoperative hemorrhage has been described in presence of a reduction of Factor XIII (FXIII) with normal routine coagulation tests in different fields. The primary objetive was to evaluate the influence of perioperative FXIII levels on ICH after brain surgery. Methods: A prospective, observational, 18-month study was conducted at a third-level hospital in Spain. It included all consecutive adults (18 years of age or alder) operated on elective brain tumor surgery with postoperative stay in the Neurointensive Care Unit (N-ICU). Informed consent from all participants and ethical approval were obtained. Younger than 18 years of age, informed refusal, death in the OR, incomplete blood sample or non-tumoral tissue were exclusion criteria. Three blood samples evaluated FXIII levels (A-presurgical, B-postsurgical and C-24 hours after surgery). ICH, as a primary outcome variable, was defined as bleeding that generates radiological signs of intracranial hypertension either by volume or by mass effect on the routine CT scan 24 hours after surgery. The influence of tumoral data and standard coagulation were also analized. Chi-square (χ2) and Fisher’s exact tests, Mann-Whitney U and T-Tests and multiple regression were used for inferential analysis. Results: The study included 109 patients. ICH was finally confirmed in 39 of them (35,78%). Inferential analisys determined statistical association between lenght of stay in ICU (p

Two transplant recipients (1 kidney and 1 hematopoietic stem cell) received maribavir (MBV) after cytomegalovirus (CMV) infection clinically resistant to standard therapy. Both patients achieved CMV DNA clearance within 30 and 18 days; however, the UL97 C480F variant emerged, causing recurrent CMV infection after a cumulative 2 months of MBV and 15 or 4 weeks of ganciclovir treatment, respectively. C480F was not detected under ganciclovir before MBV treatment. Recombinant phenotyping showed that C480F conferred the highest level of MBV resistance and ganciclovir cross-resistance, with impaired viral growth. Clinical follow-up and genotypic and phenotypic studies are essential for the assessment and optimization of patients with suspected MBV resistance.

The aim of the study was to analyze the epidemiological and clinical changes in EFIE. All definite IE episodes treated at a referral center between 2007 and 2018 were registered prospectively, and a trend test was used to study etiologies over time. EFIE cases were divided into three periods, and clinical differences between them were analyzed. All episodes of E. faecalis monomicrobial bacteremia (EFMB) between 2010 and 2018 and the percentage of echocardiograms performed were retrospectively collected. Six hundred forty-eight IE episodes were studied. We detected an increase in the percentage of EFIE (15% in 2007, 25.3% in 2018, P = 0.038), which became the most prevalent causative agent of IE during the last study period. One hundred and eight EFIE episodes were analyzed (2007–2010, n = 30; 2011–2014, n = 22; 2015–2018, n = 56). The patients in the last period were older (median 70.9 vs 66.5 vs 76.3 years, P = 0.015) and more frequently had an abdominal origin of EFIE (20% vs 13.6% vs 42.9%, P = 0.014), fewer indications for surgery (63.3% vs 54.6% vs 32.1%, P = 0.014), and non-significantly lower in-hospital mortality (30% vs 18.2% vs 12.5%, P = 0.139). There was an increase in the percentage of echocardiograms performed in patients with EFMB (30% in 2010, 51.2% in 2018, P = 0.014) and EFIE diagnoses (15% in 2010, 32.6% in 2018, P = 0.004). E. faecalis is an increasing cause of IE in our center, most likely due to an increase in the percentage of echocardiograms performed. The factors involved in clinical changes in EFIE should be thoroughly studied.

Noninfected prosthetic heart valves often display a characteristic pattern of diffuse and homogeneous distribution and mild fluorodeoxyglucose (FDG) uptake when evaluated by 18F-FDG positron emission tomography/computed tomography angiography (PET/CTA) at least during 1 year after implantation.

Resumen Introduccion y objetivos El objetivo del estudio fue determinar la prevalencia de patologia colorrectal en los pacientes con endocarditis infecciosa por Enterococcus faecalis (EIEF). Metodos Se realizo un estudio observacional, retrospectivo y multicentrico en 4 hospitales de referencia. Se incluyeron todos los episodios consecutivos de EIEF definitivas en adultos desde el momento en que se empezo a realizar una colonoscopia por protocolo en cada centro participante hasta octubre de 2018. Se recogieron los hallazgos endoscopicos de patologia colorrectal potencialmente causante de una bacteriemia. Resultados Se incluyeron 103 pacientes con EIEF; 83 (81%) eran varones, la edad mediana era 76 [rango intercuartilico, 67-82] anos, y la mediana del indice de Charlson ajustado por edad fue 5 [rango intercuartilico, 4-7]. El presunto origen de la infeccion fue desconocido en 63 (61%), urinario en 20 (19%), digestivo en 13 (13%), bacteriemia de cateter en 5 (5%), y otros en 2 (2%). En 78 (76%) pacientes se realizo una colonoscopia, y en 47 (60%) habia hallazgos endoscopicos que indicaban un potencial foco de bacteriemia. Treinta y nueve (83%) tenian una enfermedad colorrectal neoplasica, y 8 (17%) no neoplasica. De los 45 pacientes con puerta de entrada desconocida y colonoscopia, un posible origen gastrointestinal se identifico en 64%. En el subgrupo de 25 con foco de entrada conocido y colonoscopia, excluyendo aquellos con enfermedad colorrectal ya previamente diagnosticada, 44% tenian patologia colorrectal. Conclusiones Realizar una colonoscopia en la EIEF, sin tener en cuenta la puerta de entrada, puede ayudar a diagnosticar la enfermedad colorrectal en estos pacientes y evitar una nueva bacteriemia (y eventualmente endocarditis infecciosa) por el mismo u otro microorganismo.

Objectives To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. Design A prospective, observational study. Setting Tertiary referral hospital. Participants Singleton pregnancies with COVID-19 at >20+0 weeks. Methods Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. Main outcome measures Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. Results Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. Conclusions Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. Tweetable abstract This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.

Background Based on experimental studies showing synergism with β-lactams and glycopeptides, aminoglycosides have long been considered essential in the treatment of infective endocarditis (IE). However, their use is associated with a high risk of renal failure, especially in elderly patients. Aims The aim of this narrative review was to summarize the evidence to support reducing or even avoiding the use of aminoglycosides for the treatment of IE. We also analysed data supporting the use of aminoglycosides in specific subgroup of IE patients. Sources PubMed database was searched up to July 2019 to identify relevant studies. Contents Recent European Guidelines reduced the use of aminoglycosides in IE, no longer recommended in Staphylococcus aureus native-valve IE, and shortened to 2 weeks for IE related to Enterococcus faecalis and streptococci with penicillin MIC >0.125 μg/mL. In addition, an alternative regimen without aminoglycosides (ampicillin or amoxicillin plus ceftriaxone) is proposed for E. faecalis. Observational studies suggested that gentamicin would not be necessary in the case of staphylococcal prosthetic valve IE as long as rifampicin is maintained. Recent clinical studies showed that for streptococcal IE, gentamicin could be restricted to isolates with penicillin MIC >0.5 μg/mL. For the empirical and definitive treatment of E. faecalis IE, amoxicillin or ampicillin plus ceftriaxone may be considered, irrespective of high-level of aminoglycoside resistance. Implications In a scenario of progressive increase in the age and frailty of IE patients, the use of aminoglycosides can be reduced or avoided in ~90% cases. This should result in reduced incidence of renal failure, an important prognostic factor in IE.

The aim of this study was to evaluate the association between biomass formation and the clinical characteristics and prognosis of Staphylococcus aureus infective endocarditis (IE).We prospectively studied 209 S. aureus strains causing IE. Biomass formation was examined using the crystal violet assay and quantified spectrophotometrically. The average (SD) optical density of the biomass was compared for each clinical, microbiological (methicillin-resistance, vancomycin MIC≥1.5μg/ml) and molecular (clonal complex, agr type and agr dysfunction) variable according to their presence or absence. The primary clinical endpoints studied were in-hospital death, severe sepsis, persistent bacteraemia, symptomatic peripheral embolisms and prosthetic valve IE.Mean age was 66.1 years, 61.5% of patients were male and the median age-adjusted Charlson comorbidity index was 5 points (IQR 3-8). In-hospital mortality was 37.3%. Strains belonging to CC5 and CC22 had optical biomass densities [mean (SD) 1.573 (1.14) vs 0.942 (0.98) p0.001 and 1.720 (0.94) vs 1.028 (1.04) p=0.001, respectively]. Strains belonging to CC5 and CC22 had significantly higher optical biomass densities [1.369 (1.18) vs 0.920 (0.93) p=0.008]. No statistically significant differences were found in the clinical endpoints studied.High biomass production was associated with CC5 and CC22 but not with higher hospital mortality, septic complications, type of endocarditis, methicillin-resistance, elevated vancomycin MIC or agr dysfunction.

Enterococcus faecalis infective endocarditis (EFIE) is a complex entity in rapid evolution. Although largely relevant findings from recent studies have advanced the knowledge on EFIE and led to some changes in clinical guidelines, there are still a number of gaps to be filled. Coordinated, international, multicenter efforts are needed to obtain quality data that rend the health systems and scientific community prepared enough to understand and handle this infection. In this Perspective, some of the most relevant aspects concerning the epidemiology, clinical presentation and outcomes, diagnostic approaches and antibiotic therapy of EFIE are addressed. Also, several potential future clinical developments in the field are discussed.

Background Diagnosis of PVE by PET/CTA is based on visual and quantitative evaluation of morpho-metabolic features. The FDG uptake pattern is a main diagnostic criterion, but can be visually unclear and susceptible to subjectivity. The valve uptake index (VUI) is a new measure designed to provide a more objective indication of the distribution of metabolic activity. Purpose To validate the diagnostic accuracy of the valve uptake index (VUI) (SUVmax-SUVmean)/SUVmax, in patients with suspicion of prosthetic valve endocarditis (PVE). To establish a cut-off value that allows diagnosis of infection. Finally, to determine the incremental value of adding the VUI to the classic parameters for the diagnostis of PVE by PET/CT. Methods Retrospective analysis of 122 patients, with a conclusive diagnosis of definite or rejected PVE and who had undergone a cardiac PET/CTA scan. We measured the VUI and recorded the SUVmax, SUVratio, uptake pattern and the presence of endocarditis-related anatomic lesions. The diagnostic accuracy of these parameters was calculated. Results The VUI values were 0.54±0.1 vs. 0.36±0.08 in the definite PVE group vs. the rejected group, respectively (mean±SD; p0.45 showed a sensitivity, specificity and diagnostic accuracy for PVE of 85%, 90.3% and 87.4%, and significantly increased diagnostic ability for confirming endocarditis when combined with the standard diagnostic criteria. Conclusions The VUI had good diagnostic accuracy for PVE. The diagnostic power of currently used morphometabolic parametersis significantly increased by the addition of the VUI. Integration of the VUI in the diagnostic algorithm may clarify doubtful cases, and improve the diagnostic yield of PET/CTA. Funding Acknowledgement Type of funding sources: None.

BACKGROUND Post-ischemic inflammation contributes to worsening of ischemic brain injury and in this process, the inflammasomes play a key role. Inflammasomes are cytosolic multiprotein complexes which upon assembly activate the maturation and secretion of the inflammatory cytokines IL-1β and IL-18. However, participation of the NLRP3 inflammasome in ischemic stroke remains controversial. Our aims were to determine the role of NLRP3 in ischemia and to explore the mechanism involved in the potential protective effect of the neurovascular unit. METHODS WT and NLRP3 knock-out mice were subjected to ischemia by middle cerebral artery occlusion (60 minutes) with or without treatment with MCC950 at different time points post-stroke. Brain injury was measured histologically with 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS We identified a time-dependent dual effect of NLRP3. While neither the pre-treatment with MCC950 nor the genetic approach (NLRP3 KO) proved to be neuroprotective, post-reperfusion treatment with MCC950 significantly reduced the infarct volume in a dose-dependent manner. Importantly, MCC950 improved the neuro-motor function and reduced the expression of different pro-inflammatory cytokines (IL-1β, TNF-α), NLRP3 inflammasome components (NLRP3, pro-caspase-1), protease expression (MMP9) and endothelial adhesion molecules (ICAM, VCAM). We observed a marked protection of the blood-brain barrier (BBB), which was also reflected in the recovery of the tight junctions proteins (ZO-1, Claudin-5). Additionally, MCC950 produced a reduction of the CCL2 chemokine in blood serum and in brain tissue, which lead to a reduction in the immune cell infiltration. CONCLUSIONS These findings suggest that post-reperfusion NLRP3 inhibition may be an effective acute therapy for protecting the blood-brain barrier in cerebral ischemia with potential clinical translation.

In the article by J. Lifante et al (doi: 10.1002/jbio.202000154), published in J. Biophotonics 2020; 13:e202000154, a spectral feature corresponding to tissue reflectance was mistakenly attributed to autofluorescence. This corrigendum is published to correct the interpretation of the spectral data and images in the manuscript. This article is protected by copyright. All rights reserved.

Emergency abdominal surgery carries high morbidity and mortality rates in human medicine; however, there is less evidence characterizing the outcome of these surgeries as a single group in dogs. The aim of the study was to characterize the clinical course, associated complications and outcome of dogs undergoing emergency abdominal surgery. A retrospective study was conducted. Dogs undergoing emergency laparotomy were included in the study. Logistic regression analysis was performed to identify variables correlated with death and complications. Eighty-two dogs were included in the study. The most common reason for surgery was gastrointestinal foreign body. Overall 15-day mortality rate was 20.7% (17/82). Median (range) length of hospitalization was 3 (0.5 - 15) days. Of the 82 patients, 24 (29.3%) developed major complications and 66 (80.5%) minor complications. Perioperative factors significantly associated with death included tachycardia (P < 0.001), hypothermia (P < 0.001), lactate acidosis (P < 0.001), shock index > 1 (P < 0.001), leukopenia (P < 0.001), thrombocytopenia (P < 0.001) at admission; intraoperative hypotension (P < 0.001) and perioperative use of blood products (P < 0.001). The results of this study suggest that mortality and morbidity rates after emergency abdominal surgery in dogs are high.

Objectives To evaluate the association between compliance with previously published quality indicators (QIs) for the management of Staphylococcus aureus bacteraemia (SAB) and 30-day mortality. Methods We conducted a post hoc analysis of all adult patients with SAB who were hospitalized at a Spanish university hospital between 2013 and 2018. We evaluated the compliance with 7 QIs of SAB management (i.e., Infectious Diseases consultation, follow-up blood cultures, early source control, echocardiography, early cloxacillin or cefazolin, vancomycin monitoring, and appropriate treatment duration). The QIs compliance rate was considered good if ≥75% of the QIs recommended in each patient were performed. We studied the impact of different risk factors (including QIs compliance) on 30-day all-cause mortality adjusting by multivariable modeling and propensity-matched analysis. Results We included 441 patients with SAB. The QIs compliance rate was ≥75% in 361 patients (81.9%). A total of 95 patients (21.5%) died within 30 days after the index blood culture. In the multivariable model, the variables associated with 30-day mortality were: age (OR, 1.1; 95% CI, 1.0–1.1), Charlson comorbidity index (OR, 1.2; 95% CI, 1.1–1.4), persistent bacteraemia >72 h (OR, 6.0; 95% CI, 3.2–11.5), infective endocarditis (OR, 2.8; 95% CI, 1.2–6.7), and SAB of unknown source (OR, 3.3; 95% CI, 1.5–7.1). We did not find an association between a global QIs compliance rate of ≥75% or any individual QI with 30-day mortality. Conclusions SAB 30-day mortality remains high despite good adherence to previously published QIs for the management of SAB. Future research should focus on additional factors to further improve SAB-related mortality.

Carbapenems are considered the treatment of choice for extended-spectrum β-lactamase (ESBL)- or AmpC β-lactamase-producing Enterobacteriaceae bacteraemia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited. This study compared the 30-day mortality and clinical failure associated with the use of carbapenems versus alternative non-intravenous antibiotics for the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia. This 12-year retrospective study (2004–2015) included all patients with bacteraemia due to ESBL/AmpC-producing Enterobacteriaceae at a Spanish hospital. Given the lack of randomisation of initial therapies, a propensity score for receiving carbapenems was calculated. There were 1115 patients with a first episode of bacteraemia due to Escherichia coli or Klebsiella pneumoniae, of which 123 (11.0%) were ESBL/AmpC-positive. There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (trimethoprim/sulfamethoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared with the carbapenem group, patients treated with an alternative regimen had a shorter hospital stay [median (IQR) 7 (5–10) days vs. 12 (9–18) days; P < 0.001]. Use of an alternative non-intravenous therapy did not increase mortality (OR = 0.27, 95% CI 0.05–1.61; P = 0.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95 (95% CI 0.94–26.01; P = 0.059). Alternative non-intravenous carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia, allowing a reduction in carbapenem use. Use of trimethoprim/sulfamethoxazole in this series showed favourable results., CP, NF-H and JR-B are supported by Plan Nacional de I+D+i 2013?2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001 and 0003], which is co-financed by the European Regional Development Fund ?A way to achieve Europe?, Operative Programme Intelligent Growth 2014?2020.

Resumen Objetivo Estudiar la evolucion clinica de una serie de pacientes con hipervitaminosis B12. Metodo Estudio observacional retrospectivo de una cohorte de pacientes a lo largo de un ano, con seguimiento de sus historias clinicas en tres momentos: inicial, a los 6 meses y al ano. Emplazamiento Atencion Primaria y Hospitalaria del Area Oeste de Valladolid. Participantes Se parte de 102 pacientes de edad adulta, de los que se pierden 55 (mayoritariamente por reposicion parenteral), con procedencia de ambos niveles asistenciales, y valores de vitamina B12 > 970 pg/ml en sus analiticas del mes de enero de 2016 efectuadas en el laboratorio central del Hospital Rio Hortega de Valladolid. Se excluyen pacientes hematologicos y oncologicos. Mediciones principales Las variables recogidas son: edad, sexo, procedencia, valores de acido folico y vitamina B12, comorbilidades y patologias relacionadas. Se expresan en porcentajes. Resultados El 8,5% (3 casos) muestran patologia tumoral —valores proximos a los de la bibliografia—. La mortalidad es muy alta (25%, 12 pacientes), siendo la causa infecciosa la mas frecuente; incluso en el 41,6% (5 casos) podria actuar como reactante de fase aguda. Conclusiones La hipervitaminosis B12 puede comportarse como indicador de alerta inespecifico, por lo que precisa rastreo y seguimiento a lo largo de los meses.

What is known and objective Tocilizumab is an IL‐6 receptor inhibitor agent which has been proposed as a candidate to stop the inflammatory phase of infection by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). However, safety data of tocilizumab in pregnant women and their newborn are scarce. We aimed to describe maternal and neonatal safety outcomes associated with tocilizumab treatment in pregnant women with severe COVID‐19. Methods This is a retrospective study of severe COVID‐19 pregnant women, treated with tocilizumab in two Spanish hospitals between 1 March and 31 April 2020. Demographics, medical history, clinical and radiologic findings, treatment information and laboratory data of mothers and their newborns were collected from electronic medical records. Results and discussion A total of 12 pregnant women were identified to have received tocilizumab during pregnancy in the two hospitals. Median gestational age at admission was 27.7 weeks (interquartile range, 18.0–36.4). Most of them received lopinavir/ritonavir, azithromycin and hydroxychloroquine, two patients received corticosteroids and one received interferon beta 1B. All 12 pregnancies resulted in live births. Somatometric values were normal for all newborns, and evolution at 14 and 28 days was favourable for all of them. Hepatotoxicity was observed in 2 patients, which improved or resolved at discharge. Cytomegalovirus reactivation was detected in another patient who had also received corticosteroids for 15 days, causing a congenital infection in her newborn. Both hepatotoxicity and viral reactivation adverse events were classified as possibly related to tocilizumab administration according to Naranjo's causality algorithm. What is new and conclusions It does not appear that tocilizumab has detrimental effects for the mother and newborn. Close monitoring of infections should be considered, especially if other immunosuppressive agents are used., Evolution of cytomegalovirus viral load and serology tests in one pregnant patient, in which viral reactivation was detected. She received a single dose of tocilizumab and methylprednisolone therapy for 15 days. Baseline IgM antibodies and amniotic fluid polymerase‐chain‐reaction were negative, but they became positive 6 days after tocilizumab infusion and viral load was detected on day 13.

International audience; Background - Infective endocarditis (IE) in people who inject drugs (PWID) is an emergent public health problem. Objectives - The purpose of this study was to investigate IE in PWID and compare it with IE in non-PWID patients. Methods - Two prospective cohort studies (ICE-PCS and ICE-Plus databases, encompassing 8,112 IE episodes from 2000 to 2006 and 2008 to 2012, with 64 and 34 sites and 28 and 18 countries, respectively). Outcomes were compared between PWID and non-PWID patients with IE. Logistic regression analyses were performed to investigate risk factors for 6-month mortality and relapses amongst PWID. Results - A total of 7,616 patients (591 PWID and 7,025 non-PWID) were included. PWID patients were significantly younger (median 37.0 years [interquartile range: 29.5 to 44.2 years] vs. 63.3 years [interquartile range: 49.3 to 74.0 years]; p

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations, Background The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. Methods Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. Discussion There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population, The study has been awarded with a Spanish Government grant (Instituto de Salud Carlos III: COV20/00188). It covers the expenses for transporting, processing and analyzing samples, database creation and maintenance, and hiring support staff

Introduction Type 2N von Willebrand disease (VWD) is characterized by a decreased affinity of von Willebrand factor (VWF) for factor VIII (FVIII). Abnormal binding of FVIII to VWF (VWF:FVIIIB), results in low FVIII plasma levels, which can lead to a misdiagnosis of mild haemophilia A. Accurate diagnosis of type 2N VWD is essential for appropriate genetic counselling and therapy. This disease can be distinguished from haemophilia A by in vitro assays (measurement VWF:FVIIIB activity) and/or genetic analysis. Aim To identify the current challenges in the diagnosis and treatment of this type of VWD and provide an in-depth description of the phenotypes and mutations identified. Results Twenty-eight patients had at least one type 2N mutation, and 13 of these had a type 2N mutation combined with other variations. Three type 2N mutations were detected: p.Arg816Trp, p.Arg854Gln, and p.Arg763Ser. Two of these are the most frequently described mutations worldwide. This mutational spectrum differs from the broad spectrum seen in neighbouring France, where at least eight distinct 2N mutations have been found. In the PCM-EVW-ES cohort, 11 asymptomatic type 2N carriers with borderline FVIII plasma levels would probably have been excluded if the evaluation had been based on clinical and laboratory data only. Likewise, three patients with a severe phenotype would have been classified as homozygous for a 2N mutation if only the phenotype study had been performed. Conclusion The high detection yield and affordability of next-generation sequencing support the use of this technology as a first-line diagnostic tool in this setting.

Ensuring the nutritional demands of preterm (PT) infants during complementary feeding could contribute significantly to the infants’ long-term health and development. However, the dietary guidelines for complementary feeding in PT are scarce. Thus, describing dietary intake and identifying nutritional targets for these infants could be of great interest. The aim of this study is to assess the food intake and anthropometric parameters in a Mediterranean infant cohort from 6 to 24 months and to identify nutritional targets especially focused on late preterm infants. This is a longitudinal prospective study analyzing information from administered questionnaires about general characteristics and food frequency consumption in 115 infants (20 PT (32 to 36 gestational weeks), 95 full-term (FT)) at 6, 12 and 24 months of age. Results show that the differences in the prevalence of underweight observed in PT infants vs. FT infants are maintained for up to 6 months of age but disappear at 12 and 24 months. The age of inclusion of new foods and the average intake of the main food groups was not different from that of FTs. Although protein intake at 6 months was directly correlated with weight gain and growth in FT, these associations were not observed in PT. At the nutritional level, the low intake of vitamin D in preterm infants is noteworthy. These findings may be useful when designing new intervention strategies for this population group., This work was financed by PCIN-2015-233 (Project EarlyMicroHealth from the EU Joint Program Initiative HDHL) (MINECO/FEDER, UE) and by the University of Oviedo (Diet, Rhythms and Early Acquisition Microbiota (DREAMS) Project, REF. 2017/00001/003/005/013). Silvia Arboleya is the recipient of a Juan de la Cierva postdoctoral contract from the Spanish Ministry of Science and Innovation (Ref. IJCI-2017-32156) and María Gómez-Martín is the recipient of a predoctoral FPU contract (FPU18/03393) funded by the Spanish Ministry of Science, Innovation and Universities.

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Purpose Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown. Methods We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives. Results We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic. Conclusion Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus., INSERM, University of Paris; Rockefeller University; St. Giles Foundation; National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R37AI095983]; French National Research Agency (ANR) under the "Investments for the future" programFrench National Research Agency (ANR) [ANR-10-IAHU-01, ANR13-ISV3-0001-01, ANR-16-CE17-0005-01]; ECOS-NORD [C19S01-63407, SRC2017]; ANRHGDIFDFrench National Research Agency (ANR) [ANR-14-CE15-006-01]; ANR-IFNGPHOX [ANR-13-ISV3-0001-01]; GENMSMD [ANR-16-CE17-0005-01]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/11757-2, 2010/51814-0, 2012/51094-2]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)National Council for Scientific and Technological Development (CNPq) [303809/2010-8]; Instituto de Salud Carlos IIIInstituto de Salud Carlos IIIEuropean Commission [PI11/01086, PI14/00405]; European Regional Development Fund (ERDF)European Commission; Colombia-France (ECOS-NORD/COLCIENCIAS/MEN/ICETEX) [619-2013]; Diana Garcia de Olarte foundation PID; ColcienciasDepartamento Administrativo de Ciencia, Tecnologia e Innovacion Colciencias [713-2016, 111574455633]; "Poste d'accueil" INSERMInstitut National de la Sante et de la Recherche Medicale (Inserm); Imagine Institute, The Laboratory of Human Genetics of Infectious Diseases is supported in part by institutional grants from INSERM, University of Paris, The Rockefeller University and the St. Giles Foundation, the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) (R37AI095983), and grants from the French National Research Agency (ANR) under the "Investments for the future" program (ANR-10-IAHU-01) and IFNGPHOX (ANR13-ISV3-0001-01 for JB and ACN), GENMSMD (ANR-16-CE17-0005-01 for JB) grants, ECOS-NORD (C19S01-63407 for JB and JFR), and SRC2017 (for JB). CO-Q is supported by ANRHGDIFD (ANR-14-CE15-006-01). AG was supported by the ANR-IFNGPHOX (ANR-13-ISV3-0001-01), GENMSMD (ANR-16-CE17-0005-01), and the Imagine Institute. AC-N and EBO-J are supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP grants 2012/11757-2, 2010/51814-0, and 2012/51094-2) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ grant 303809/2010-8). MMG and RC are supported by Instituto de Salud Carlos III, grants PI11/01086 and PI14/00405, co-financed by the European Regional Development Fund (ERDF). JFR and AAA are supported by Colombia-France (ECOS-NORD/COLCIENCIAS/MEN/ICETEX; 619-2013, Diana Garcia de Olarte foundation PID and Colciencias grant 713-2016 #111574455633). JR was supported by "Poste d'accueil" INSERM and Imagine Institute.

Objectives: the aim of the study was to analyze the impact of COVID-19 on enteral nutrition prescription in the Community of Madrid during the first semester of 2020. Material and Methods: this is a descriptive study of enteral nutrition prescription in the first semester of 2020 and its comparison with the first semester of 2019. We included all the prescriptions in public hospitals of the Community of Madrid as recorded in public electronic databases. Results: there was an 8 % increase in the number of enteral nutrition prescriptions in March 2020 when compared with the previous months (p0.001). Then, in April and May 2020 we observed a 9 % decrease in enteral nutrition prescriptions (p0.001). Total costs in enteral nutrition showed a similar pattern, with an increase in March 2020 (p0.001) and a decrease in April and May 2020 (p0.001). When analyzing the data by patient age, those above 75 y.o. showed the highest decrease in enteral nutrition prescriptions (33.1 % higher than for those under 75 y.o.) in April and May 2020 (p0.001). Conclusions: the irruption of COVID-19 had a relevant impact on enteral nutrition prescription, especially among the elderly. Follow-up is needed to assess the long-term consequences of this in nutritional therapy.Objetivos: el objetivo de este estudio es analizar el impacto de la COVID-19 en el primer semestre del año 2020, con respecto a la prescripción de soportes nutricionales enterales, y su gasto en la Comunidad de Madrid. Material y métodos: estudio descriptivo y comparativo del consumo de productos de nutrición enteral prescritos en recetas oficiales electrónicas durante el primer semestre de los años 2019 y 2020 en los hospitales públicos de la Comunidad de Madrid. Resultados: al analizar la prescripción del número de envases totales durante el periodo estudiado, por meses, se observa un incremento del 8 % en la prescripción durante el mes de marzo, comparado con los meses previos (p0,001), seguido de un descenso del 9 % en los meses de abril y mayo (p0,001). El comportamiento de la evolución del gasto sigue el mismo patrón, con un incremento en el mes de marzo (p0.001) y un descenso en los meses de abril y mayo de similar magnitud (ambos, p0,001). Al analizar por grupos de edades, el grupo de edad de más de 75 años fue el grupo con la mayor caída en las prescripciones (33,1 % mayor que entre los menores de 75) en los meses de abril y mayo de 2020 (p0,001). Conclusiones: la COVID-19 afectó de forma importante a la prescripción del soporte nutricional, especialmente en el grupo de mayor edad. El seguimiento de la enfermedad nos permitirá profundizar en el papel de la nutrición a corto y largo plazo.

The early life gut microbiota has been reported to be involved in neonatal weight gain and later infant growth. Therefore, this early microbiota may constitute a target for the promotion of healthy neonatal growth and development with potential consequences for later life. Unfortunately, we are still far from understanding the association between neonatal microbiota and weight gain and growth. In this context, we evaluated the relationship between early microbiota and weight in a cohort of full-term infants. The absolute levels of specific fecal microorganisms were determined in 88 vaginally delivered and 36 C-section-delivered full-term newborns at 1 month of age and their growth up to 12 months of age. We observed statistically significant associations between the levels of some early life gut microbes and infant weight gain during the first year of life. Classifying the infants into tertiles according to their Staphylococcus levels at 1 month of age allowed us to observe a significantly lower weight at 12 months of life in the C-section-delivered infants from the highest tertile. Univariate and multivariate models pointed out associations between the levels of some fecal microorganisms at 1 month of age and weight gain at 6 and 12 months. Interestingly, these associations were different in vaginally and C-section-delivered babies. A significant direct association between Staphylococcus and weight gain at 1 month of life was observed in vaginally delivered babies, whereas in C-section-delivered infants, lower Bacteroides levels at 1 month were associated with higher later weight gain (at 6 and 12 months). Our results indicate an association between the gut microbiota and weight gain in early life and highlight potential microbial predictors for later weight gain., This work was funded by the EU Joint Programming Initiative—A Healthy Diet for a Healthy Life (JPI HDHL. http://www.healthydietforhealthylife.eu/; accessed on 14 July 2021. Project EarlyMicroHealth) and the Project AGL2017-83653R funded by the Spanish “Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) and FEDER” and by the European Research Council under the European Union’s Horizon 2020 research and innovation program (ERC starting grant, no. 639226). Silvia Arboleya is the recipient of a Juan de la Cierva Postdoctoral Contract from the Spanish Ministry of Science and Innovation (Ref. IJCI-2017-32156) funded by the Spanish Ministry of Science, Innovation and Universities.

Background and purposePost-ischemic inflammation contributes to worsening of ischemic brain injury and in this process, the inflammasomes play a key role. Inflammasomes are cytosolic multiprotein complexes which upon assembly activate the maturation and secretion of the inflammatory cytokines IL-1β and IL-18. However, participation of the NLRP3 inflammasome in ischemic stroke remains controversial. Our aims were to determine the role of NLRP3 in ischemia and to explore the mechanism involved in the potential protective effect of the neurovascular unit.MethodsWT and NLRP3 knock-out mice were subjected to ischemia by middle cerebral artery occlusion (60 minutes) with or without treatment with MCC950 at different time points post-stroke. Brain injury was measured histologically with 2,3,5-triphenyltetrazolium chloride (TTC) staining.ResultsWe identified a time-dependent dual effect of NLRP3. While neither the pre-treatment with MCC950 nor the genetic approach (NLRP3 KO) proved to be neuroprotective, post-reperfusion treatment with MCC950 significantly reduced the infarct volume in a dose-dependent manner. Importantly, MCC950 improved the neuro-motor function and reduced the expression of different pro-inflammatory cytokines (IL-1β, TNF-α), NLRP3 inflammasome components (NLRP3, pro-caspase-1), protease expression (MMP9) and endothelial adhesion molecules (ICAM, VCAM). We observed a marked protection of the blood-brain barrier (BBB), which was also reflected in the recovery of the tight junctions proteins (ZO-1, Claudin-5). Additionally, MCC950 produced a reduction of the CCL2 chemokine in blood serum and in brain tissue, which lead to a reduction in the immune cell infiltration.ConclusionsThese findings suggest that post-reperfusion NLRP3 inhibition may be an effective acute therapy for protecting the blood-brain barrier in cerebral ischemia with potential clinical translation.

Background Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. Aim To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. Methods Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. Results Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). Conclusion Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.

12 p.-5 fig., Optical probes operating in the second near-infrared window (NIR-II, 1,000-1,700 nm), where tissues are highly transparent, have expanded the applicability of fluorescence in the biomedical field. NIR-II fluorescence enables deep-tissue imaging with micrometric resolution in animal models, but is limited by the low brightness of NIR-II probes, which prevents imaging at low excitation intensities and fluorophore concentrations. Here, we present a new generation of probes (Ag2S superdots) derived from chemically synthesized Ag2S dots, on which a protective shell is grown by femtosecond laser irradiation. This shell reduces the structural defects, causing an 80-fold enhancement of the quantum yield. PEGylated Ag2S superdots enable deep-tissue in vivo imaging at low excitation intensities (, Authors thank Dr A. Benayas (CICECO, U. Aveiro, Portugal), Prof G. Lifante and Prof J. García Sole (UAM) for helpful discussions. This work has been founded by Ministerio de Economı́a y Competitividad-MINECO (MAT2017-83111R and MAT2016-75362-C3-1-R) and the Comunidad de Madrid (B2017/BMD-3867 RENIM-CM) co-financed by European Structural and Investment Fund. D.M.-G. thanks UCM-Santander for a predoctoral contract (CT17/17-CT18/17). We thank the staff at the ICTS-National Centre for Electron Microscopy at the UCM for the help in the electron microscopy studies and C.M. at the beamline BL22-CLAESS of the Spanish synchrotron ALBA for his help in the XANES experiments. We also thank J.G.I at the Ultrafast Laser Laboratory at UCM for his help and fruitful discussion. Y.S. acknowledges the support from the China Scholarship Council (CSC File No. 201806870023). Additional funding was provided by the European Commission Horizon 2020 project NanoTBTech, the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP18_38 (2018/0265). Ajoy K. Kar and Mark D. Mackenzie acknowledge support from the UK Engineering and Physical Sciences Research Council (Project CHAMP, EP/M015130/1). C. Jacinto thanks the financial support of the Brazilian agencies: CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) through the grants: Projeto Universal Nr. 431736/2018-9 and Scholarship in Research Productivity 1C under the Nr. 304967/20181; FINEP (Financiadora de Estudos e Projetos) through the grants INFRAPESQ-11 and INFRAPESQ-12; FAPEAL (Fundação de Amparo à Pesquisa do Estado de Alagoas) grant Nr. 1209/2016. H. D. A. Santos was supported by a graduate studentship from CNPq and by a sandwich doctoral program (PDSE-CAPES) developed at Universidad Autonoma de Madrid, Spain, Project Nr. 88881/2016-01.

BackgroundModulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID-19) despite the scarcity of evidence.MethodsWe report the preliminary results from the Vall d’Hebron prospective cohort study at Vall d’Hebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and who were treated with tocilizumab until March 25th. The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others.Results82 patients with COVID-19 received at least one dose of tocilizumab. The mean (± SD) age was 59.1 (19.8) years, 63% were male, 22% were of non-Spanish ancestry, and the median (IQR) age-adjusted Charlson index at baseline was 3 (1-4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5-11) days. The median time from symptom onset to the first dose of tocilizumab was 9 (7-11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3 to 8.5 (age-adjusted hazard ratio for mortality 2.1; 95% CI, 0.8 to 5.8) if tocilizumab was administered after the onset of ARDS.ConclusionTime from lung injury onset to tocilizumab administration may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data from clinical trials becomes available.Summary of the article’s main pointIn patient with COVID-19 and lung injury, time from lung injury onset to tocilizumab administration may be critical to patient recovery. Early administration of host-directed therapies may improve patient outcome.

This paper presents the results of research on typographical error analysis in two specialised bilingual paper dictionaries: Diccionario de terminos economicos, financieros y comerciales/ A Dictionary of Economic, Financial and Commercial Terms ( Ariel, 2012), and Diccionario de terminos juri dicos/A Dictionary of Legal Terms ( Ariel, 2012). A model of errors is described, including similar errors and errors that are repeated both intratextually and intertextually. The error frequency in A Dictionary of Economic, Financial and Commercial Terms is higher than the average error frequency in a reference corpus of fourteen dictionaries (mainly first editions). This indicates that repeated editions do not always guarantee a higher level of formal correctness. Our results also show that a high frequency of errors does not necessarily entail a high intratextual error repetition rate. On the other hand, we establish a relationship between typographical errors and the access function in dictionaries, as that kind of error can interfere with access to accurate lexicographical information and data retrieval (especially when they occur in lemmas or sublemmas).

“This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: https://pubs.acs.org/doi/full/10.1021/acsnano.9b08824, Luminescence nanothermometry has emerged over the past decade as an exciting field of research due to its potential applications where conventional methods have demonstrated to be ineffective. Preclinical research has been one of the areas that have benefited the most from the innovations proposed in the field. Nevertheless, certain questions concerning the reliability of the technique under in vivo conditions have been continuously overlooked by most of the scientific community. In this proof-of-concept, hyperspectral in vivo imaging is used to explain how unverified assumptions about the thermal dependence of the optical transmittance of biological tissues in the so-called biological windows can lead to erroneous measurements of temperature. Furthermore, the natural steps that should be taken in the future for a reliable in vivo luminescence nanothermometry are discussed together with a perspective view of the field after the findings here reported, This work was supported by the Spanish Ministry of Economy and Competitiveness under projects MAT2016-75362-C3-1-R, MAT2017-83111R, and MAT2017-85617-R, by the Instituto de Salud Carlos III (PI16/00812), and by the Comunidad Autónoma de Madrid (B2017/BMD-3867RENIMCM) and cofinanced by the European Structural and investment fund. Additional funding was provided by the European Union’s Horizon 2020 FET Open programme (grant agreement No 801305), the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP18_38 (2018/0265), and also COST action CA17140. Y. Shen acknowledges a scholarship from the China Scholarship Council (No. 201806870023)

GAMES Investigators., [Background] Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking., [Objectives] The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort., [Methods] This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses., [Results] Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse., [Conclusions] Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE.

It is only through an extreme concern for accuracy and the understanding of typographical errors that authors can turn specialised dictionaries into high quality reference works. This paper describes patterns of typographical error reproduction in three specialised English-Spanish dictionaries. We approach intratextual error reproduction (within a particular dictionary), either through related subentries or through non-related subentries. In addition, we compare the frequency of errors between dictionaries written by institutional lexicographers and works written by freelance professionals. The purpose is to provide a model for typographical error detection and analysis that may contribute to formal correctness in reference works. The reason is twofold: a) dictionaries are expected to be high-standard primary tools for language professionals; b) data quality is essential for a wide variety of utilities, ranging from dictionary writing systems and writing assistants to corpus tools. Los diccionarios especializados no pueden ser considerados obras de referencia de calidad si sus autores no prestan una especial atención a la corrección y si no entienden el fenómeno de la reproducción de las erratas. Este artículo describe patrones de reproducción de erratas en tres diccionarios especializados inglés-español. Abordamos la reproducción intratextual de erratas (en un diccionario en particular), tanto en subentradas relacionadas como no relacionadas. Además, comparamos la frecuencia de erratas en diccionarios elaborados por lexicógrafos institucionales con la de obras realizadas por profesionales independientes. El objetivo es ofrecer un modelo de detección y análisis de erratas que contribuya a la corrección formal en obras de referencia, por dos motivos: a) se supone que los diccionarios deben ser herramientas esenciales de alto nivel para los profesionales del lenguaje; b) la calidad de los datos es fundamental para una amplia gama de herramientas, desde programas de elaboración de diccionarios (dictionary writing systems) hasta asistentes de escritura y herramientas relacionadas con córpora.

The incidence of metabolic syndrome (MetS) is increasing worldwide which makes necessary the finding of new strategies to treat and/or prevent it. The aim of this study was to analyze the possible beneficial effects of a carob fruit extract (CSAT+&reg, ) on the cardiometabolic alterations associated with MetS in mice. 16-week-old C57BL/6J male mice were fed for 26 weeks either with a standard diet (chow) or with a diet rich in fats and sugars (HFHS), supplemented or not with 4.8% of CSAT+&reg, CSAT+&reg, supplementation reduced blood glucose, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and circulating levels of total cholesterol, low-density lipoprotein (LDL) cholesterol (LDL-c), insulin, and interleukin-6 (IL-6). In adipose tissue and skeletal muscle, CSAT+&reg, prevented MetS-induced insulin resistance, reduced macrophage infiltration and the expression of pro-inflammatory markers, and up-regulated the mRNA levels of antioxidant markers. Supplementation with CSAT+&reg, prevented MetS-induced hypertension and decreased the vascular response of aortic rings to angiotensin II (AngII). Moreover, treatment with CSAT+&reg, attenuated endothelial dysfunction and increased vascular sensitivity to insulin. In the heart, CSAT+&reg, supplementation reduced cardiomyocyte apoptosis and prevented ischemia-reperfusion-induced decrease in cardiac contractility. The beneficial effects at the cardiovascular level were associated with a lower expression of pro-inflammatory and pro-oxidant markers in aortic and cardiac tissues.

Fetal skin edema in the second trimester might be associated with maternal coronavirus disease 2019 (COVID-19)., BACKGROUND: The risk of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Positive reverse-transcription polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 infection in neonates and placental tissue have been reported, and immunoglobulin M antibodies have been detected in neonates born to mothers with infection. CASES: The first case is a woman at 22 3/7 weeks of gestation with coronavirus disease 2019 (COVID-19) who was admitted to the intensive care unit. In the second case, the patient remained at home with mild symptoms, starting at 20 weeks of gestation. In both cases, fetal skin edema was observed on ultrasound examination while maternal SARS-COV-2 RT-PCR test results were positive and resolved when maternal SARS-COV-2 RT-PCR test results became negative. The RT-PCR test result for SARS-CoV-2 in amniotic fluid was negative in both cases. The two pregnancies are ongoing and uneventful. CONCLUSION: Transient fetal skin edema noted in these two patients with COVID-19 in the second trimester may represent results of fetal infection or altered fetal physiology due to maternal disease or may be unrelated to the maternal illness.

Introduction: Adherence is a cornerstone of factor VIII prophylactic treatment. Information regarding the factors with potential influence on adherence is limited, particularly in adult patients. Aim: To assess adherence in adult patients with severe haemophilia A receiving prophylactic treatment in a real-life setting, and investigate the factors influencing adherence. Methods: Observational, prospective study including adult patients receiving factor VIII therapy in 15 Spanish centres. Patients recorded infusion doses on a logbook and answered various questionnaires to assess their health beliefs. Adherence rate was the percentage of infused doses over the prescribed ones. Self-perceived adherence was assessed using the VERITAS-Pro questionnaire, the psychometric properties of which were validated in the Spanish population. The relationship between adherence rate and treatment, clinical and demographic characteristics, health beliefs and perceived self-efficacy was investigated. Results: A total of 66 patients were followed up for 12 months. Mean adherence rate at the end of follow-up was 82.5%. Most of the study patients (n = 53, 80.3%) showed a moderate-to-high adherence rate (>70%). The VERITAS-Pro revealed a high perception of adherence. Multivariate analyses to predict treatment adherence identified the knee as a target joint and longer treatment duration as variables with significant (negative) influence on adherence. Adherence rate was not influenced by the patient's health beliefs or perceived self-efficacy. Conclusion: Most adult patients receiving factor VIII prophylactic treatment in Spain have moderate-to-high treatment adherence. Treatment duration and the knee as a target joint are factors with a moderate negative influence on treatment adherence.

Objective: To investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection. Patients and Methods: Retrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en Espana [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients. Results: One hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus. Conclusion: Our study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.

La hemofilia A (HA) supone una importante carga economica para el sistema sanitario, especialmente relevante en pacientes hemofilicos que desarrollan inhibidor. De cara al establecimiento de politicas sanitarias resulta importante disponer de informacion sobre el coste anual que supone el manejo de este grupo de pacientes. El presente estudio tiene como objetivo estimar el coste farmacologico medio anual de un paciente con HA e inhibidores, desde la perspectiva del Sistema Nacional de Salud. Se realizo un modelo economico para estimar el coste farmacologico anual asociado a terapia con agentes bypass (factor vii activado recombinante (rFVIIa) y concentrado de complejo protrombinico activado (aPCC)) en pacientes con HA e inhibidor. La poblacion se estratifico segun la edad: pacientes pediatricos (

To describe the demographic, clinical, and microbiological profile of native vertebral osteomyelitis (NVO) in aged patients as compared to that of younger patients, to identify differences that could motivate changes in clinical management. Retrospective, observational cohort study (1990–2015) including all adult patients with microbiologically confirmed NVO divided into 2 groups: aged (≥ 65 years) vs younger (18–64 years). 247 patients included, 138 aged and 109 younger. Relative to younger patients, the aged had higher rates of healthcare-related infection (40.6 vs 25.7%, p = 0.014), previous known heart valve disease (29.7 vs 9.2%, p

Purpose: To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). Methods: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. Results: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84–11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03–6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29–3.38) in the multivariable analysis. Conclusions: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Describe secular trends in the epidemiology and outcome of Clostridium difficile infection (CDI) at a tertiary hospital.All consecutive primary CDI episodes in adults (January 2006-December 2015) were included. CDI was diagnosed on the presence of diarrhoea and a positive stool test for C. difficile toxin A and/or B. To define trends, a time-series analysis was performed using yearly data on demographics, clinical characteristics, management, antimicrobial treatment, and outcome of CDI. Patients were followed-up for three months after the diagnosis.There were 724 CDI episodes. Over the period from 2006 to 2015, the incidence rose from 0.18 episodes/1000 admissions to 0.26 episodes (relative rate [RR] 1.43; 95%CI, 1.02-2.00; P = 0.035). Median Charlson comorbidity index increased from 2 (IQR 1-3) to 4 (IQR 2-4) (RR 1.65; 95%CI, 1.12-2.41; P = 0.005). Overall, 80.4% of patients received proton pump inhibitors (PPIs) prior to CDI, and the percentage of PPI discontinuations rose from 2.3% to 20.4% (RR 8.80; 95%CI 1.20-64.36; P = 0.006). Management of non-Clostridium antibiotics also changed: antibiotic withdrawals or switches increased from 4.2% to 29.2% (RR 7.00; 95%CI 1.68-29.15, P = 0.001). Regarding CDI treatment, the percentage of patients treated with metronidazole decreased (88.9% vs 52.6%) (RR 0.59 (0.48-0.73), P 0.001), whereas the percentage receiving vancomycin increased (1.9% vs 32.6%) (RR 17.62 (2.47-125.49), P 0.001). The percentages of cures, deaths, and first recurrences did not significantly change over the 10-year period.Changes in CDI management were associated with a stable prognosis (percentage of cures and first recurrences), even though affected patients had a greater number of comorbidities over time.