Atypical Manifestations of Visceral Leishmaniasis in Children

Abstract Visceral leishmaniasis (VL) or kala-azar is an endemic parasitic disease caused predominantly, in its Mediterranean type, by Leishmania infantum. Fever and splenomegaly are the most common clinical manifestations, detected in more than 80% of patients. We present two cases with atypical manifestations, without fever and with spleen nodules in the context of an outbreak of VL in Spain

STAT6 variants associate with relapse of fosinophilic esophagitis in patients receiving long-term proton pump inhibitor therapy

Background & Aims: Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. Methods: We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (<15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of <15 and ≤5. Results: Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012. Conclusions: Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy

High Potential of Facial Biomarkers to Diagnose Psychotic Disorders

Schizophrenia (SCZ) and Bipolar Disorder (BP) are severe psychiatric disorders (PD) that affect more than 3% of the world's population and are among the leading causes of disability worldwide. Current diagnostic systems represent these PD as independent categorical entities. However, recent studies propose that both disorders would be two different manifestations of the same psychotic spectrum continuum. Differential diagnosis is mainly based on their clinical presentation, and reliable biomarkers remain an unmet clinical need. Since the brain and the face are derived from the same ectodermal origins and their development is intimately integrated through common genetic signaling, facial biomarkers emerge as one of the most promising biological risk factors for PD. Here, we assessed the potential of facial anatomy in predicting the diagnosis of SCZ and BP. Analyses were performed in a sample of 180 adults distributed in three groups of BP patients (n=46), SCZ patients (n=67), and CNT (n=67) matched by age and premorbid IQ. Faces were manually annotated from reconstructions of magnetic resonance scans. Facial shape correctly discriminated patients with BP and SCZ, even when facial differences between patients and CNT were so subtle that are not recognizable to the untrained eye or by exploratory multivariate statistical techniques. After cross-validation, 62-65% of patients were correctly diagnosed based on face shape. This percentage is similar to the discriminatory power of other genetic and brain biomarkers. Using Artificial Neural Networks, we tested a machine learning algorithm based on facial morphology to diagnose SCZ. The overall accuracy in diagnostic classification was greater than 90%, whereas the precision ranged between 70-95% depending on the model. We also trained a Support Vector Machine classification algorithm to diagnose BP. Results showed that BP is harder to diagnose from facial biomarkers than SCZ, achieving a 72% accuracy. Euclidean Distance Matrix Analysis (EDMA) detected local facial differences involving the eyes, nose and mouth, and the relative separation/position between them. Facial anomalies were more abundant in SCZ patients, with 43-48% distances across the whole face significantly different from control subjects. In BP, the percentage of facial anomalies was lower, 24-32%, especially in women. Some facial differences were common to SCZ and BP, although the sense of change could be different among disorders. Remarkably, EDMA showed facial patterns that are disorder and gender-specific. These results demonstrate that an analysis of the spectrum of psychotic disorders under a gender perspective is crucial to further understand these disorders and to identify reliable biomarkers that can lead to early PD diagnosis

MIC of amoxicillin/clavulanate according to CLSI and EUCAST: discrepancies and clinical impact in patients with bloodstream infections due to Enterobacteriaceae

[Objectives] To compare results of amoxicillin/clavulanate susceptibility testing using CLSI and EUCAST methodologies and to evaluate their impact on outcome in patients with bacteraemia caused by Enterobacteriaceae.[Patients and methods] A prospective observational cohort study was conducted in 13 Spanish hospitals. Patients with bacteraemia due to Enterobacteriaceae who received empirical intravenous amoxicillin/clavulanate treatment for at least 48 h were included. MICs were determined following CLSI and EUCAST recommendations. Outcome variables were: failure at the end of treatment with amoxicillin/clavulanate (FEAMC); failure at day 21; and 30 day mortality. Classification and regression tree (CART) analysis and logistic regression were performed.[Results] Overall, 264 episodes were included; the urinary tract was the most common source (64.7%) and Escherichia coli the most frequent pathogen (76.5%). Fifty-two isolates (19.7%) showed resistance according to CLSI and 141 (53.4%) according to EUCAST. The kappa index for the concordance between the results of both committees was only 0.24. EUCAST-derived, but not CLSI-derived, MICs were associated with failure when considered as continuous variables. CART analysis suggested a ‘resistance’ breakpoint of > 8/4 mg/L for CLSI-derived MICs; it predicted FEAMC in adjusted analysis (OR = 1.96; 95% CI: 0.98–3.90). Isolates with EUCAST-derived MICs >16/2 mg/L independently predicted FEAMC (OR = 2.10; 95% CI: 1.05–4.21) and failure at day 21 (OR= 3.01; 95% CI: 0.93–9.67). MICs >32/2 mg/L were only predictive of failure among patients with bacteraemia from urinary or biliary tract sources.[Conclusions] CLSI and EUCAST methodologies showed low agreement for determining the MIC of amoxicillin/clavulanate. EUCAST-derived MICs seemed more predictive of failure than CLSI-derived ones. EUCAST-derived MICs >16/2 mg/L were independently associated with therapeutic failure.The study was funded by the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain (Fondo de investigación en salud; PI10/02021) co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015).Peer reviewe

Acceptability and feasibility of a virtual community of practice to primary care professionals regarding patient empowerment: A qualitative pilot study

Background: Virtual communities of practice (vCoPs) facilitate online learning via the exchange of experiences and knowledge between interested participants. Compared to other communities, vCoPs need to overcome technological structures and specific barriers. Our objective was to pilot the acceptability and feasibility of a vCoP aimed at improving the attitudes of primary care professionals to the empowerment of patients with chronic conditions. Methods: We used a qualitative approach based on 2 focus groups: one composed of 6 general practitioners and the other of 6 practice nurses. Discussion guidelines on the topics to be investigated were provided to the moderator. Sessions were audio-recorded and transcribed verbatim. Thematic analysis was performed using the ATLAS-ti software. Results: The available operating systems and browsers and the lack of suitable spaces and time were reported as the main difficulties with the vCoP. The vCoP was perceived to be a flexible learning mode that provided up-to-date resources applicable to routine practice and offered a space for the exchange of experiences and approaches. Conclusions: The results from this pilot study show that the vCoP was considered useful for learning how to empower patients. However, while vCoPs have the potential to facilitate learning and as shown create professional awareness regarding patient empowerment, attention needs to be paid to technological and access issues and the time demands on professionals. We collected relevant inputs to improve the features, content and educational methods to be included in further vCoP implementation. Trial registration: ClinicalTrials.gov, NCT02757781. Registered on 25 April 2016.This study was financed by Instituto de Salud Carlos III and Cofinanced by Fondo Europeo de Desarrollo Regional (FEDER). Ministerio de Economía y Competitividad. Gobierno de España. (PI15/00164, PI15/00586, PI15/00566

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Caracterización de compuestos TiO2 nanoparticulado/vidrio de bajo punto de fusión

Resumen del trabajo presentado al LVII Congreso Nacional de la Sociedad Española de Cerámica y Vidrio (SECV), celebrado en la Universitat Jaume I de Castellón del 26 al 29 de octubre de 2020.Peer reviewe

Lead-free low-melting-point glass as bonding agent for TiO2 nanoparticles

This work is a study of the properties of TiO2-anatase nanoparticles attached by a low-melting point inorganic glass (530°C). Unlike other low-melting glasses, this composition does not contain any toxic metal. Likewise, it shows an excellent wettability on ceramic nanoparticles. A small addition of 5 vol% of glass remarkably enhances the mechanical strength of the composites with respect to pure TiO2 calcined at the same temperature, becoming twice this value. Self-cleaning properties analyzed using the methylene blue 385 nm UV-A photodegradation test showed that, after different UV-light periods, the photo-efficiency of TiO2-anatase was not altered by the presence of this glass.This work was supported by CSIC under grant 201960E103 and by the Spanish Ministry of Science Innovation and Universities (MCIU/AEI/FEDER, UE) under award RTI2018-094958-B-I00. Dr. Borrell acknowledges the Spanish Ministry of Economy and Competitiveness for her RyC contract (RYC-2016-20915).Peer reviewe