Underlying and proximate drivers of biodiversity changes in Mesoamerican biosphere reserves.

Protected areas are of paramount relevance to conserving wildlife and ecosystem contributions to people. Yet, their conservation success is increasingly threatened by human activities including habitat loss, climate change, pollution, and species overexploitation. Thus, understanding the underlying and proximate drivers of anthropogenic threats is urgently needed to improve protected areas' effectiveness, especially in the biodiversity-rich tropics. We addressed this issue by analyzing expert-provided data on long-term biodiversity change (last three decades) over 14 biosphere reserves from the Mesoamerican Biodiversity Hotspot. Using multivariate analyses and structural equation modeling, we tested the influence of major socioeconomic drivers (demographic, economic, and political factors), spatial indicators of human activities (agriculture expansion and road extension), and forest landscape modifications (forest loss and isolation) as drivers of biodiversity change. We uncovered a significant proliferation of disturbance-tolerant guilds and the loss or decline of disturbance-sensitive guilds within reserves causing a "winner and loser" species replacement over time. Guild change was directly related to forest spatial changes promoted by the expansion of agriculture and roads within reserves. High human population density and low nonfarming occupation were identified as the main underlying drivers of biodiversity change. Our findings suggest that to mitigate anthropogenic threats to biodiversity within biosphere reserves, fostering human population well-being via sustainable, nonfarming livelihood opportunities around reserves is imperative.

Advanced Machine Learning Techniques for Corrosion Rate Estimation and Prediction in Industrial Cooling Water Pipelines.

This paper presents the results of a study on data preprocessing and modeling for predicting corrosion in water pipelines of a steel industrial plant. The use case is a cooling circuit consisting of both direct and indirect cooling. In the direct cooling circuit, water comes into direct contact with the product, whereas in the indirect one, it does not. In this study, advanced machine learning techniques, such as extreme gradient boosting and deep neural networks, have been employed for two distinct applications. Firstly, a virtual sensor was created to estimate the corrosion rate based on influencing process variables, such as pH and temperature. Secondly, a predictive tool was designed to foresee the future evolution of the corrosion rate, considering past values of both influencing variables and the corrosion rate. The results show that the most suitable algorithm for the virtual sensor approach is the dense neural network, with MAPE values of (25 ± 4)% and (11 ± 4)% for the direct and indirect circuits, respectively. In contrast, different results are obtained for the two circuits when following the predictive tool approach. For the primary circuit, the convolutional neural network yields the best results, with MAPE = 4% on the testing set, whereas for the secondary circuit, the LSTM recurrent network shows the highest prediction accuracy, with MAPE = 9%. In general, models employing temporal windows have emerged as more suitable for corrosion prediction, with model performance significantly improving with a larger dataset.

Etiology and Outcome of Adult and Pediatric Acute Liver Failure in Europe.

Acute liver failure (ALF) is rare but life-threatening. Common causes include intoxications, infections, and metabolic disorders. Indeterminate etiology is still frequent. No systematic data on incidence, causes, and outcome of ALF across Europe are available. Via an online survey we reached out to European Reference Network Centers on rare liver diseases. Numbers and etiology of ALF cases during 2020 were retrieved and diagnostic and treatment availabilities assessed. In total, 455 cases (306 adult, 149 pediatric) were reported from 36 centers from 20 countries. Intoxication was the most common cause in adult and pediatric care. The number of cases with indeterminate etiology is low. Diagnostic tools and specific treatment options are broadly available within this network. This is the first approach to report on etiology and outcome of ALF in the pediatric and adult population in Europe. High diagnostic yield and standard of care reflects the expert status of involved centers.

High Incidence, Reinfections, and Active Syphilis in Populations Attending a Specialized HIV Clinic in Mexico, a Dynamic Cohort Study.

Syphilis, a sexually transmitted infection, has reemerged in many vulnerable groups around the world. The objective of the current study was to determine the prevalence and incidence of syphilis among people who attended a specialized HIV clinic in Mexico from 2011 to 2015. Databases from the laboratory were analyzed, and the following four groups were formed: people seeking HIV-1 voluntary counseling and testing (VCT), people in prison (PPr), people living with HIV (PLWH), and patients from primary care clinics (others). The diagnosis of syphilis was made using the reverse algorithm; antibody titers were examined to determine the stage of infection. Baseline data were analyzed and, with follow-up information, a retrospective dynamic cohort was formed. Factors associated with the seroprevalence of syphilis and active syphilis were evaluated by the chi-square test. Moreover, risk factors for the incidence of syphilis were described. A total of 81,863 baseline individuals were analyzed. The seroprevalence of syphilis was 9.9% in the VCT group, 8.2% in the PPr group, 37.0% in the PLWH group, and 8.7% in the others group; the prevalence of active syphilis was 1.7-13.1%. A total of 11,124 people were followed up. The incidence (cases per 100 person-years) was 3.5 among the VCT group, 16.0 among the PLWH group, and < 0.1 among both the PPr and others groups, respectively; moreover, the frequency of reinfections was 11.1-24.4%. The high prevalence and incidence of syphilis, active syphilis, and reinfections among men, transgender people, individuals aged 20-39 years, and people with a history of HIV or hepatitis B suggest that it is critical to improve prevention, diagnosis, and treatment measures to stop the reemergence of syphilis. There are also new factors such as methamphetamine use, group sex, or contacting partners over the internet that are associated with syphilis. In addition, HIV preexposure prophylaxis could contribute to the increased incidence of syphilis by providing false security in the prevention of STIs, thereby increasing risky sexual behaviors.

Comprehensive rehabilitation and job reintegration of people with severe mental illness in a Latin American country: REINTEGRA study protocol.

BACKGROUND: Despite the increasing use of comprehensive rehabilitation models for people with severe mental illness (SMI), there are still limitations to their implementation and replicability in a consensual way, particularly in Latin American countries. The REINTEGRA program aims to be a standardized model of comprehensive rehabilitation focused on psychosocial and cognitive improvement through a set of interventions on different areas of people's functionality, with the goal of reintegrating people with SMI into the labour market. In this paper we summarize the protocol for its subsequent implementation in a mental health institution in Mexico. METHOD: The protocol is based on a quasi-experimental, prospective longitudinal study, with a pragmatic or naturalistic control group. It will be carried out in three phases. Phase 1 consists of a series of interventions focused on psychosocial improvement; Phase 2 focuses on cognitive and behavioral improvement treatments; and Phase 3 targets psychosocial recovery through rehabilitation and reintegration into the labour market. The overall procedure will be monitored with standarized evaluations at different stages of the program. DISCUSSION: This study presents a model of integral rehabilitation of people with SMI. At the moment, one of the obstacles to overcome is the organization and procedural control of the different actors needed for its implementation (nurses, psychologists, doctors, companies, institutions, etc.). REINTEGRA will be the first comprehensive rehabilitation model that includes systematized procedures for job reinsertion for people with SMI in Mexico, which aims to be a standardized tool of easy adaptation and the replicability for other mental health centers and institutions.

Increased IL-12p70 and IL-8 Produced by Monocytes in Response to Streptococcus spp. and Actinomyces spp. Causals of Endodontic Primary Infections.

We sought to evaluate the effect of endodontic-causative microorganisms of primary infections on mononuclear cells such as CD14+, CD4+, CD8+, CD19+ and Tregs Foxp3+. Facultative anaerobic microorganisms were isolated from radicular conducts and peripheral blood samples, which were taken from patients with primary infections. Cellular cultures were performed with peripheral blood mononuclear cells (PBMC) with and without Actinomyces spp. and Streptococcus spp. during 48, 72, and 96 h of contact in culture (concentration 5 × 105 cells/well) in a round plate bound with 48 wells. Later, PBMC was collected for analysis by flow cytometry, with the monoclonal antibodies αCD14, αCD4, αCD8, αCD19 and αFoxp3, and acquired using an FACSCanto II cytometer. The supernatant of cellular cultures was analyzed for the quantification of inflammatory cytokines. Data analysis was performed in FlowJo v10.8.2 and FCAPArray software, and statistical analysis was performed using GraphPad v5.0. software. We observed an increase in the percentage of CD14+ cells in patients at different hours of cellular culture in the presence of both Actinomyces spp. and Streptococcus spp. microorganisms, compared to healthy controls. This study demonstrates the role played by the innate immune system in the pathogeny of endodontic primary infections, explaining the effects that generate the more common microorganisms in this oral pathology.

Hybrid Fluorescent Mass-Tag Nanotrackers as Universal Reagents for Long-Term Live-Cell Barcoding.

Barcoding and pooling cells for processing as a composite sample are critical to minimize technical variability in multiplex technologies. Fluorescent cell barcoding has been established as a standard method for multiplexing in flow cytometry analysis. In parallel, mass-tag barcoding is routinely used to label cells for mass cytometry. Barcode reagents currently used label intracellular proteins in fixed and permeabilized cells and, therefore, are not suitable for studies with live cells in long-term culture prior to analysis. In this study, we report the development of fluorescent palladium-based hybrid-tag nanotrackers to barcode live cells for flow and mass cytometry dual-modal readout. We describe the preparation, physicochemical characterization, efficiency of cell internalization, and durability of these nanotrackers in live cells cultured over time. In addition, we demonstrate their compatibility with standardized cytometry reagents and protocols. Finally, we validated these nanotrackers for drug response assays during a long-term coculture experiment with two barcoded cell lines. This method represents a new and widely applicable advance for fluorescent and mass-tag barcoding that is independent of protein expression levels and can be used to label cells before long-term drug studies.

A randomized, double blind, single dose, comparative study of the pharmacokinetics, safety and immunogenicity of MB02 (bevacizumab biosimilar) and reference bevacizumab in healthy male volunteers.

AIMS: The pharmacokinetic (PK) similarity between MB02, a proposed bevacizumab biosimilar, and reference bevacizumab approved from the USA (US-bevacizumab) and European Union (EU-bevacizumab) was evaluated. Safety and immunogenicity were also assessed. METHODS: In this phase 1, randomized, double blind, single dose, parallel group study, 114 healthy male volunteers were randomized 1:1:1 to receive a 3 mg/kg intravenous dose of MB02, US-bevacizumab or EU-bevacizumab, and evaluated for 100 days. PK similarity between MB02 and reference bevacizumab was determined using the standard bioequivalence criteria (0.80-1.25) for the area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC(0-∞) ) and the maximum observed serum concentration (Cmax ). RESULTS: Baseline demographics were similar across treatment groups. All study drugs exhibited similar PK profile. The 90% confidence interval for the geometric lead square means ratios for the primary parameters AUC(0-∞) and Cmax for MB02, US-bevacizumab and EU-bevacizumab were fully contained within the pre-defined bioequivalence limits for the 3 pairwise comparisons: AUC(0-∞) (MB02:US-bevacizumab 0.998 [0.944 to 1.05]; MB02:EU-bevacizumab 1.07 [1.00 to 1.14]; and US-bevacizumab:EU-bevacizumab 0.934 [0.884 to 0.988]) and Cmax (MB02:US-bevacizumab 0.983 [0.897 to 1.08]; MB02:EU-bevacizumab 1.06 [0.976 to 1.16]; and; US-bevacizumab: EU-bevacizumab 0.926 [0.851 to 1.01]). Treatment emergent adverse events were reported in 87 subjects (76.3%), most being mild and with comparable incidence among treatment groups. Thirty-three subjects (28.9%) reported 56 possibly related treatment emergent adverse events with comparable incidence across treatments, the most frequent being headache (10.5%) and fatigue (3.5%). Anti-drug antibody incidence was low and similar between treatment groups. CONCLUSIONS: This study demonstrates the PK similarity and bioequivalence of MB02 to the reference bevacizumab, whether approved from USA or EU. The safety and immunogenicity profile of MB02 was shown also to be similar to the bevacizumab reference product (NCT04238663).

Terminal Effector CD8 T Cells Defined by an IKZF2+IL-7R- Transcriptional Signature Express FcγRIIIA, Expand in HIV Infection, and Mediate Potent HIV-Specific Antibody-Dependent Cellular Cytotoxicity.

HIV-1 infection expands large populations of late-stage differentiated CD8 T cells that may persist long after viral escape from TCR recognition. In this study, we investigated whether such CD8 T cell populations can perform unconventional innate-like antiviral effector functions. Chronic untreated HIV-1 infection was associated with elevated numbers of CD45RA+CD57+ terminal effector CD8 T cells expressing FcγRIIIA (CD16). The FcγRIIIA+ CD8 T cells displayed a distinctive transcriptional profile between conventional CD8 T cells and NK cells, characterized by high levels of IKZF2 and low expression of IL7R This transcriptional profile translated into a distinct NKp80+ IL-7Rα- surface phenotype with high expression of the Helios transcription factor. Interestingly, the FcγRIIIA+ CD8 T cells mediated HIV-specific Ab-dependent cellular cytotoxicity (ADCC) activity at levels comparable with NK cells on a per cell basis. The FcγRIIIA+ CD8 T cells were highly activated in a manner that correlated positively with expansion of the CD8 T cell compartment and with plasma levels of soluble mediators of antiviral immunity and inflammation such as IP-10, TNF, IL-6, and TNFRII. The frequency of FcγRIIIA+ CD8 T cells persisted as patients initiated suppressive antiretroviral therapy, although their activation levels declined. These data indicate that terminally differentiated effector CD8 T cells acquire enhanced innate cell-like characteristics during chronic viral infection and suggest that HIV-specific ADCC is a function CD8 T cells use to target HIV-infected cells. Furthermore, as the FcγRIIIA+ CD8 T cells persist in treatment, they contribute significantly to the ADCC-capable effector cell pool in patients on antiretroviral therapy.

Root canal microorganisms and their antibiotic susceptibility in patients with persistent endodontic infections, with and without clinical symptoms.

Secondary/persistent infections are present in teeth with previous root canal treatment, and a great variety of anaerobic microorganisms has been observed in these infections. The antibiotics prescription is occasional; however, in some cases, it is essential, particularly when the general health condition of the patient is compromised. The aims of this study were to identify the associated microorganisms in diagnosis of persistent or secondary apical periodontitis and to evaluate the susceptibility level to the antibiotics most used. Fifteen patients with persistent or secondary apical periodontitis requiring endodontic re-treatment were included. Microbiological samples were taken from the root canals and incubated in thioglycollate under anaerobic conditions. Anaerobic CDC agar (formulated by the Center for Disease Control and Prevention) was employed as a culture medium and the microorganisms were identified using the API system. The microorganisms were subjected to antibiograms with three different antibiotics. Twenty-six microorganisms were identified, the most common genus was Enterococcus (26.8%), Streptococcus (19.22%), Aerococcus (19.1%), and Clostridium (11.4%). 48% of them were susceptible to amoxicillin, with 28% of resistance. For clavulanic acid/amoxicillin, the susceptibility occurred in 32%, with 28% of resistance; and for clindamycin, the susceptibility was present in 40%, with 52% of resistance. The most frequently detected associated microorganism for secondary infections was genus Enterococcus, which exhibited high resistance to the studied antibiotics.

Clinical and Economic Impact of Wound Care Using a Polyurethane Foam Multilayer Dressing.

OBJECTIVE: To study the impact of a newly introduced dressing on efficiency and quality of care in routine clinical practice in a Spanish community setting. DESIGN AND SETTING: An ambispective multicenter observational study was conducted in 24 primary care centers and 6 nursing homes in 4 different Spanish regions. The study was carried out between November 2017 and March 2019. PATIENTS AND INTERVENTION: A total of 128 wounds in 94 patients (primary care, n = 79; nursing home, n = 15) were analyzed before and 4 weeks after switching to the study dressing. OUTCOME MEASURES: Frequency of dressing changes; secondary outcomes were change in the mean wound area and weekly cost and patient and provider satisfaction. MAIN RESULTS: The mean number of dressing changes was significantly reduced with the study dressing from 3.14 ± 1.77 changes per week to 1.66 ± 0.87 (P < .001), a 47.1% reduction in frequency. Wound area significantly reduced from 9.90 ± 19.62 cm to 7.10 ± 24.33 cm. In addition, a 58.7% reduction in weekly costs was achieved with the intervention. Patients and providers agreed that their satisfaction with wound care improved. CONCLUSIONS: The use of the study dressing in routine clinical practice could lead to a major improvement in both efficiency and quality of wound care. Its use could reduce wound care-related costs through improvements in healing and a reduced frequency of dressing changes. It also enhanced the wound care experience from the perspective of both patients and providers.

Ways to perform an endoscopic tattoo. Prospective and randomized study in patients with colorectal neoplasm.

BACKGROUND AND AIMS: intraoperative identification of colonic lesions previously detected via colonoscopy may be difficult. Endoscopic tattooing facilitates identification, but there is no evidence regarding which is the best tattoo technique. The goal of the study was to describe the efficacy and safety of endoscopic tattooing and to detect technical and clinical factors associated with its efficacy. PATIENTS AND METHODS: a prospective and randomized study was performed. All tattoo candidate patients were included prior to surgery and randomized into four groups; tattoo at two or three injection points and with a volume of 1 or 1.5 ml of labeling. Multiple variables were registered. RESULTS: one hundred and ninety-five patients were included with an endoscopic tattoo and who subsequently underwent a surgical intervention, the mean age was 70.1 years and 67.2 % were male. The laparoscopic approach was applied in 57.9 % of cases. The intraoperative visibility of the endoscopic tattoo was 89.7 % and 30 % of rectal lesions were not visible. Excluding the rectum, the marking was visible intraoperatively in 92 % of patients, without significant differences according to the surgical approach, the type of marking or any of the variables collected. The tattoo was safe in 92.3 % of the cases. The adverse effect rate was 7.7 % and none of the complications were clinically significant. There were no significant differences between any variables collected in relation to adverse effects. CONCLUSIONS: endoscopic colon tattoo is safe and effective regardless of the technique used. We recommend the technique of two injection points and 1 ml of marking volume for its simplicity, efficiency and safety.

Chronic viral hepatitis C micro-elimination program using telemedicine. The Mexican experience.

BACKGROUND: hepatitis C virus (HCV) infection is a global health problem. Chronic infection induces the development of fibrosis and cirrhosis together with all the related complications. The use of direct-acting antiviral (DAA) drugs has proven highly effective. Telemedicine is a present-day resource that brings treatment closer to distant areas and may result in cost savings. OBJECTIVE: to implement a microelimination program for HCV using DAAs with the support of a telemedicine program to minimize expenses. PATIENTS AND METHODS: the program was developed at the Medical Services department of Petróleos Mexicanos (SMPM) with a national coverage; patients diagnosed with chronic hepatitis C were included. These were classified into locals and outsiders. Treatment for foreign patients was indicated, monitored and completed via telemedicine. Thus, avoiding their travel to the country's capital city, in order to save on transportation costs and travel allowances. RESULTS: a total of 136 patients, 74 locals and 62 outsiders, participated in the study. Transfer was avoided for 62 patients (45.5 %), which meant that telemedicine resulted in savings of 3,176.20 USD per patient, with overall savings of 196,924.40 USD from cost minimization. A total of 30 patients remained untreated due to lack of medication, hence the coverage amounted to 86 %. Sustained virological response (SVR) was achieved in 99 % of cases. Only two patients had treatment failure. Adverse events included headache and fatigue in 5 % of the cohort. CONCLUSIONS: with the aid of a telemedicine approach, significant savings were achieved by minimizing costs, since nearly half of patients were outsiders. Coverage reached 86 % and treatment with DAAs was successful for 99 % of our cases.

Reporter mice for isolating and auditing cell type-specific extracellular vesicles in vivo.

Extracellular vesicles (EVs) are abundant, lipid-enclosed vectors that contain nucleic acids and proteins, they can be secreted from donor cells and freely circulate, and they can be engulfed by recipient cells thus enabling systemic communication between heterotypic cell types. However, genetic tools for labeling, isolating, and auditing cell type-specific EVs in vivo, without prior in vitro manipulation, are lacking. We have used CRISPR-Cas9-mediated genome editing to generate mice bearing a CD63-emGFPloxP/stop/loxP knock-in cassette that enables the specific labeling of circulating CD63+ vesicles from any cell type when crossed with lineage-specific Cre recombinase driver mice. As proof-of-principle, we have crossed these mice with Cdh5-CreERT2 mice to generate CD63emGFP+ vasculature. Using these mice, we show that developing vasculature is marked with emerald GFP (emGFP) following tamoxifen administration to pregnant females. In adult mice, quiescent vasculature and angiogenic vasculature (in tumors) is also marked with emGFP. Moreover, whole plasma-purified EVs contain a subpopulation of emGFP+ vesicles that are derived from the endothelium, co-express additional EV (e.g., CD9 and CD81) and endothelial cell (e.g., CD105) markers, and they harbor specific miRNAs (e.g., miR-126, miR-30c, and miR-125b). This new mouse strain should be a useful genetic tool for generating cell type-specific, CD63+ EVs that freely circulate in serum and can subsequently be isolated and characterized using standard methodologies.

Identification of NK Cell Subpopulations That Differentiate HIV-Infected Subject Cohorts with Diverse Levels of Virus Control.

HIV infection is controlled immunologically in a small subset of infected individuals without antiretroviral therapy (ART), though the mechanism of control is unclear. CD8+ T cells are a critical component of HIV control in many immunological controllers. NK cells are also believed to have a role in controlling HIV infection, though their role is less well characterized. We used mass cytometry to simultaneously measure the levels of expression of 24 surface markers on peripheral NK cells from HIV-infected subjects with various degrees of HIV natural control; we then used machine learning to identify NK cell subpopulations that differentiate HIV controllers from noncontrollers. Using CITRUS (cluster identification, characterization, and regression), we identified 3 NK cell subpopulations that differentiated subjects with chronic HIV viremia (viremic noncontrollers [VNC]) from individuals with undetectable HIV viremia without ART (elite controllers [EC]). In a parallel approach, we identified 11 NK cell subpopulations that differentiated HIV-infected subject groups using k-means clustering after dimensionality reduction by t-neighbor stochastic neighbor embedding (tSNE) or linear discriminant analysis (LDA). Among these additional 11 subpopulations, the frequencies of 5 correlated with HIV DNA levels; importantly, significance was retained in 2 subpopulations in analyses that included only cohorts without detectable viremia. By comparing the surface marker expression patterns of all identified subpopulations, we revealed that the CD11b+ CD57- CD161+ Siglec-7+ subpopulation of CD56dim CD16+ NK cells are more abundant in EC and HIV-negative controls than in VNC and that the frequency of these cells correlated with HIV DNA levels. We hypothesize that this population may have a role in immunological control of HIV infection.IMPORTANCE HIV infection results in the establishment of a stable reservoir of latently infected cells; ART is usually required to keep viral replication under control and disease progression at bay, though a small subset of HIV-infected subjects can control HIV infection without ART through immunological mechanisms. In this study, we sought to identify subpopulations of NK cells that may be involved in the natural immunological control of HIV infection. We used mass cytometry to measure surface marker expression on peripheral NK cells. Using two distinct semisupervised machine learning approaches, we identified a CD11b+ CD57- CD161+ Siglec-7+ subpopulation of CD56dim CD16+ NK cells that differentiates HIV controllers from noncontrollers. These cells can be sorted out for future functional studies to assess their potential role in the immunological control of HIV infection.

Syphilis Infection Markers Among HIV Positive Individuals In The Mexico City HIV/AIDS Program.

OBJECTIVE: The aim of this study is to evaluate the prevalence of T. pallidum infection markers in HIV-positive individuals receiving highly active antiretroviral therapy (ART) in the Mexico City HIV/AIDS Program, as well as predictive characteristics. METHODS: The reverse serologic algorithm method was used for the T. pallidum diagnosis, and applied to 2,383 HIV-positive individuals. Socio-demographic characteristics, sexual practices, previous syphilis diagnosis, and length of antiretroviral treatment, were evaluated. Variables significantly associated with syphilis markers were analyzed using a logistic regression model. RESULTS: Prevalence of "active or resolved" and "probable active" infection markers were 44.2% and 28.8%, respectively. Predictive factors were: Clinic Specialized Condesa Iztapalapa (CECI), previous syphilis diagnosis, MSM, and receptive sex practices. CONCLUSIONS: The prevalence of T. pallidum infection markers was the highest ever reported in Mexico, and was related to specific sexual practices as well as previous syphilis diagnosis, elements which require preventive measures in the Mexico City HIV/AIDS Program.

The advocacy role of nurses in cardiopulmonary resuscitation.

BACKGROUND: The decision whether to initiate cardiopulmonary resuscitation may sometimes be ethically complex. While studies have addressed some of these issues, along with the role of nurses in cardiopulmonary resuscitation, most have not considered the importance of nurses acting as advocates for their patients with respect to cardiopulmonary resuscitation. RESEARCH OBJECTIVE: To explore what the nurse's advocacy role is in cardiopulmonary resuscitation from the perspective of patients, relatives, and health professionals in the Basque Country (Spain). RESEARCH DESIGN: An exploratory critical qualitative study was conducted from October 2015 to March 2016. Thematic analysis was used to analyse the data. PARTICIPANTS: Four discussion groups were held: one with patients and relatives (n = 8), two with nurses (n = 7 and n = 6, respectively), and one with physicians (n = 5). ETHICAL CONSIDERATIONS: Approval was obtained from the Basque Country Clinical Research Ethics Committee. FINDINGS: Three significant themes were identified: (a) accompanying patients during end of life in a context of medical dominance, (b) maintaining the pact of silence, and (c) yielding to legal uncertainty and concerns. DISCUSSION: The values and beliefs of the actors involved, as well as pre-established social and institutional rules reduced nurses' advocacy to that of intermediaries between the physician and the family within the hospital environment. On the contrary, in primary health care, nurses participated more actively within the interdisciplinary team. CONCLUSION: This study provides key information for the improvement and empowerment for ethical nursing practice in a cardiac arrest, and provides the perspective of patients and relatives, nurses and physicians.

High incidence of MDR and XDR Pseudomonas aeruginosa isolates obtained from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial.

OBJECTIVES: To characterize the antimicrobial susceptibility, molecular epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa isolates recovered from respiratory tract samples from patients with ventilator-associated pneumonia enrolled in the MagicBullet clinical trial. METHODS: Isolates were collected from 53 patients from 12 hospitals in Spain, Italy and Greece. Susceptibility was determined using broth microdilution and Etest. MALDI-TOF MS was used to detect carbapenemase activity and carbapenemases were identified by PCR and sequencing. Molecular epidemiology was investigated using PFGE and MLST. RESULTS: Of the 53 isolates, 2 (3.8%) were considered pandrug resistant (PDR), 19 (35.8%) were XDR and 16 (30.2%) were MDR. Most (88.9%) of the isolates from Greece were MDR, XDR or PDR, whereas fewer of the isolates from Spain (33.3%) and Italy (43.5%) showed antibiotic resistance. Three Greek isolates were resistant to colistin. Overall, the rates of resistance of P. aeruginosa isolates to imipenem, ciprofloxacin, ceftolozane/tazobactam and ceftazidime/avibactam were 64.1%, 54.7%, 22.6% and 24.5%, respectively. All isolates resistant to ceftolozane/tazobactam and ceftazidime/avibactam (Greece, n = 10; and Italy, n = 2) carried blaVIM-2. Spanish isolates were susceptible to the new drug combinations. Forty-eight restriction patterns and 27 STs were documented. Sixty percent of isolates belonged to six STs, including the high-risk clones ST-111, ST-175 and ST-235. CONCLUSIONS: MDR/XDR isolates were highly prevalent, particularly in Greece. The most effective antibiotic against P. aeruginosa was colistin, followed by ceftolozane/tazobactam and ceftazidime/avibactam. blaVIM-2 is associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam, and related to highly resistant phenotypes. ST-111 was the most frequent and disseminated clone and the clonal diversity was lower in XDR and PDR strains.

Biomarkers and clinical scores to identify patient populations at risk of delayed antibiotic administration or intensive care admission.

BACKGROUND: The performance of blood biomarkers (mid-regional proadrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate) and clinical scores (Sequential Organ Failure Assessment (SOFA), National Early Warning Score (NEWS), and quick SOFA) was compared to identify patient populations at risk of delayed treatment initiation and disease progression after presenting to the emergency department (ED) with a suspected infection. METHODS: A prospective observational study across three EDs. Biomarker and clinical score values were calculated upon presentation and 72 h, and logistic and Cox regression used to assess the strength of association. Primary outcomes comprised of 28-day mortality prediction and delayed antibiotic administration or intensive care (ICU) admission, whilst secondary outcomes identified subsequent disease progression. RESULTS: Six hundred eighty-four patients were enrolled with hospitalisation, ICU admission, and infection-related 28-day mortality rates of 72.8%, 3.4%, and 4.4%, respectively. MR-proADM and NEWS had the strongest association with hospitalisation and the requirement for antibiotic administration, whereas MR-proADM alone had the strongest association with ICU admission (OR [95% CI]: 5.8 [3.1 - 10.8]) and mortality (HR [95% CI]: 3.8 [2.2 - 6.5]). Patient subgroups with high MR-proADM concentrations (≥ 1.77 nmol/L) and low NEWS (< 5 points) values had significantly higher rates of ICU admission (8.1% vs 1.6%; p < 0.001), hospital readmission (18.9% vs. 5.9%; p < 0.001), infection-related mortality (13.5% vs. 0.2%; p < 0.001), and disease progression (29.7% vs. 4.9%; p < 0.001) than corresponding patients with low MR-proADM concentrations. ICU admission was delayed by 1.5 [0.25 - 5.0] days in patients with high MR-proADM and low NEWS values compared to corresponding patients with high NEWS values, despite similar 28-day mortality rates (13.5% vs. 16.5%). Antibiotics were withheld in 17.4% of patients with high MR-proADM and low NEWS values, with higher subsequent rates of ICU admission (27.3% vs. 4.8%) and infection-related hospital readmission (54.5% vs. 14.3%) compared to those administered antibiotics during ED treatment. CONCLUSIONS: Patients with low severity signs of infection but high MR-proADM concentrations had an increased likelihood of subsequent disease progression, delayed antibiotic administration or ICU admission. Appropriate triage decisions and the rapid use of antibiotics in patients with high MR-proADM concentrations may constitute initial steps in escalating or intensifying early treatment strategies.

Single-stage approach for the management of choledocolithiasis with concomitant cholelithiasis. Implementation of a protocol in a secondary hospital.

BACKGROUND: Current evidence shows that single-stage treatment of concomitant choledocholithiasis and cholelithiasis is as effective and safe as two-stage treatment. However, several studies suggest that single-stage approach requires shorter hospitalization time and is more cost-effective than the two-stage approach, even though it requires considerable training. This study aimed to evaluate the implementation of a protocol for managing concomitant choledocholithiasis and cholelithiasis using single-stage treatment. METHODS: A prospective cohort study of patients diagnosed with cholelithiasis and choledocholithiasis who were treated with the single-stage treatment - transcystic instrumentation, choledocotomy or intraoperative endoscopic retrograde cholangiopancreatography (ERCP) - between September 2010 and June 2017 was assessed. The primary outcomes were complications, hospital stay, operative time and recurrence rate. RESULTS: 164 patients were enrolled. 141 (86%) were operated laparoscopically. Preoperatively diagnosed stones were not found by intraoperative imaging or disappeared after "flushing" in 38 patients (23.2%). Surgical approach was transcystic in 45 patients (27.41%), choledochotomy in 74 (45.1%), intraoperative ERCP in 4 (2.4%), and bilioenteric derivation in 3 (1.8%). Mean hospitalization stay was 4.4 days. Mean operative time was 166 min 27 patients (16.5%) had complications and 1 patient was exitus (0.6%). Recurrence rate was 1.2%. CONCLUSIONS: Single-stage approach is a safe and effective management option for concomitant cholelithiasis and choledocolithiasis. Furthermore, a significant number of common bile duct stones pass spontaneously to duodenum or can benefit from a transcystic approach, with presumable low morbidity and cost-efficiency.