The role of viral diagnostic tests in respiratory tract infections: moving forward.

The increased knowledge on virology and the increased potential of their diagnostic has risen several relevant question about the role of an early viral diagnosis and potential early treatment on the management of respiratory tract infections (RTI). In order to further understand the role of viral diagnostic tests in the management of RTI, a panel of experts was convened to discuss about their potential role, beyond what had been agreed in Influenza. The objective of this panel was to define the plausible role of aetiologic viral diagnostic into clinical management; make recommendations on the potential expanded use of such tests in the future and define some gaps in the management of RTI. Molecular Infection Viral Diagnostic (mIVD) tests should be used in all adult patients admitted to Hospital with RTI, and in paediatric patients requiring admission or who would be referred to another hospital for more specialised care. The increased use of mIVD will not only reduce the inappropriate use of antibiotics so reducing the antibiotic microbe resistance, but also will improve the outcome of the patient if an aetiologic viral therapy can be warranted, saving resource requirements and improving patient flows. Implementing IVD testing in RTI has various organizational benefits as well, but expanding its use into clinical settings would need a cost-effectiveness strategy and budget impact assessment.

Designing UAV Swarm Experiments: A Simulator Selection and Experiment Design Process.

The rapid advancement and increasing number of applications of Unmanned Aerial Vehicle (UAV) swarm systems have garnered significant attention in recent years. These systems offer a multitude of uses and demonstrate great potential in diverse fields, ranging from surveillance and reconnaissance to search and rescue operations. However, the deployment of UAV swarms in dynamic environments necessitates the development of robust experimental designs to ensure their reliability and effectiveness. This study describes the crucial requirement for comprehensive experimental design of UAV swarm systems before their deployment in real-world scenarios. To achieve this, we begin with a concise review of existing simulation platforms, assessing their suitability for various specific needs. Through this evaluation, we identify the most appropriate tools to facilitate one's research objectives. Subsequently, we present an experimental design process tailored for validating the resilience and performance of UAV swarm systems for accomplishing the desired objectives. Furthermore, we explore strategies to simulate various scenarios and challenges that the swarm may encounter in dynamic environments, ensuring comprehensive testing and analysis. Complex multimodal experiments may require system designs that may not be completely satisfied by a single simulation platform; thus, interoperability between simulation platforms is also examined. Overall, this paper serves as a comprehensive guide for designing swarm experiments, enabling the advancement and optimization of UAV swarm systems through validation in simulated controlled environments.

Role and structure of the small subunit forming heterodimers with laccase-like enzymes.

Unlike laccases sensu stricto, which are usually monomeric enzymes, laccase-like enzymes recently re-classified as Novel Laccases (NLACs) are characterized by the formation of heterodimers with small proteins (subunits) of unknown function. Here the NLAC from Pleurotus eryngii (PeNL) and a small protein selected from the fungal genome, that is homologous to reported POXA3 from Pleurotus ostreatus, were produced in Aspergillus oryzae separately or together. The two proteins interacted regardless of whether the small subunit was co-expressed or exogenously added to the enzyme. The stability and catalytic activity of PeNL was significantly enhanced in the presence of the small subunit. Size exclusion chromatography-multi angle light scattering (SEC-MALS) analysis confirmed that the complex PeNL-ss is a heterodimer of 77.4 kDa. The crystallographic structure of the small protein expressed in Escherichia coli was solved at 1.6 Å resolution. This is the first structure elucidated of a small subunit of a NLAC. The helix bundle structure of the small subunit accommodates well with the enzyme model structure, including interactions with specific regions of NLACs and some amino acid residues of the substrate-binding loops.

Reconstrucción microquirúrgica en pandemia por Covid-19 / MICROSURGICAL RECONSTRUCTION IN THE COVID - 19 PANDEMIC

Introducción: la Pandemia por SARS CoV ­ 2 (COVID ­ 19) tuvo un impacto significativo en el desarrollo de los servicios quirúrgicos en general y obligo a establecer protocolos de actuación para las distintas patologías a fin de cuidar al máximo los recursos humanos y la capacidad instalada de los hospitales para hacer frente a esta contingencia mundial. Objetivos: presentar una casuística de 7 pacientes con reconstrucción microquirúrgica de patología de cabeza y cuello en estadios avanzados y patología de miembros inferiores durante la pandemia por COVID - 19. Materiales y Métodos: trabajo retrospectivo, se revisaron las historias clínicas físicas y digitales. Se incluyeron 5 pacientes con patología avanzada de cabeza y cuello y 2 pacientes con patología de miembros inferiores. Resultados: cinco pacientes fueron operados por patología avanzada de cabeza y cuello: 3 pacientes con carcinomas escamosos de cavidad oral estadio IVa, 1 paciente con carcinoma escamoso de piel avanzado estadio IV y 1 paciente con fractura compleja de maxilar inferior por herida de arma de fuego con fistula oro-cutánea crónica, con exposición del material de osteosíntesis, mala oclusión y pérdida de peso importante por dificultad para alimentación. Dos pacientes fueron operados por patología de miembros inferiores en tercio inferior de pierna, uno por fractura expuesta grave con defecto de tejidos blandos y el otro por una ulcera arterial. Conclusión: la cirugía reconstructiva microquirúrgica puede realizarse con buenos niveles de seguridad para el personal de salud y para los pacientes afectados por patologías avanzadas de cabeza y cuello y otras patologías que requieran colgajos libres. Es fundamental respetar estrictamente los protocolos para evitar los contagios en el medio intrahospitalario, entendiendo que debe considerarse todo paciente que ingrese al hospital como COVID (+) hasta que se demuestre lo contrario

Introduction: the SARS CoV ­ 2 (COVID ­ 19) Pandemic had a significant impact on the development of surgical services in general and forced the establishment of action protocols for the different pathologies in order to take maximum care of human resources and capacity. installed in hospitals to deal with this global contingency. Objectives: to present a casuistry of 7 patients with microsurgical reconstruction of head and neck pathology in advanced stages and lower limb pathology during the COVID - 19 pandemic. Materials and Methods: retrospective work, physical and digital medical records were reviewed. Five patients with advanced head and neck disease and 2 patients with lower limb disease were included. Results: five patients underwent surgery for advanced head and neck disease: 3 patients with stage IVa squamous cell carcinoma of the oral cavity, 1 patient with stage IV advanced squamous cell carcinoma of the skin, and 1 patient with a complex fracture of the lower jaw due to a gunshot wound. with chronic oro-cutaneous fistula, with exposure of the osteosynthesis material, poor occlusion and significant weight loss due to difficulty feeding. Two patients underwent surgery for pathology of the lower limbs in the lower third of the leg, one for a severe open fracture with a soft tissue defect and the other for an arterial ulcer. Conclusion: microsurgical reconstructive surgery can be performed with good levels of safety for health personnel and for patients affected by advanced pathologies of the head and neck and other pathologies that require free flaps. It is essential to strictly respect the protocols to avoid contagion in the hospital environment, understanding that every patient who enters the hospital must be considered as COVID (+) until proven otherwise.

Assessing the exposure risk of large pelagic fish to oil spills scenarios in the deep waters of the Gulf of Mexico.

Exposure risk is assessed based on modeling suitable habitat of large pelagic fish and oil spill scenarios originating at three wells located in the western GM's deep waters. Since the fate of the oil depends on the oceanographic conditions present during the accident, as well as the magnitude and duration of the spill, which are not known a priori, the scenarios used are a statistical representation of the area in which oil spilled from the well could be found, given all possible outcomes. The ecological vulnerability assessment identified a subset of bony fish with low-medium vulnerability and elasmobranchs with medium-high vulnerability. The oiling probability and exposure risk of both bony fish and elasmobranchs hotspots vary by well analyzed. Thus, these results provide essential information for a risk management plan for the assessed species and others with economic or conservation importance distributed in the GM and worldwide.

Cefiderocol, a new antibiotic against multidrug-resistant Gram-negative bacteria.

Cefiderocol is a novel catechol-substituted siderophore cephalosporin that binds to the extracellular free iron, and uses the bacterial active iron transport channels to penetrate in the periplasmic space of Gram-negative bacteria (GNB). Cefiderocol overcomes many resistance mechanisms of these bacteria. Cefiderocol is approved for the treatment of complicated urinary tract infections, hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in the case of adults with limited treatment options, based on the clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In the CREDIBLE-CR trial, a higher all-cause mortality was observed in the group of patients who received cefiderocol, especially those with severe infections due to Acinetobacter spp. Further phase III clinical studies are necessary in order to evaluate cefiderocol´s efficacy in the treatment of serious infections.

Effects of raster terrain representation on GIS shortest path analysis.

Spatial analysis extracts meaning and insights from spatially referenced data, where the results are highly dependent on the quality of the data used and the manipulations on the data when preparing it for analysis. Users should understand the impacts that data representations may have on their results in order to prevent distortions in their outcomes. We study the consequences of two common data preparations when locating a linear feature performing shortest path analysis on raster terrain data: 1) the connectivity of the network generated by connecting raster cells to their neighbors, and 2) the range of the attribute scale for assigning costs. Such analysis is commonly used to locate transmission lines, where the results could have major implications on project cost and its environmental impact. Experiments in solving biobjective shortest paths show that results are highly dependent on the parameters of the data representations, with exceedingly variable results based on the choices made in reclassifying attributes and generating networks from the raster. Based on these outcomes, we outline recommendations for ensuring geographic information system (GIS) data representations maintain analysis results that are accurate and unbiased.

Adequacy and prognostic impact of treatment for severe exacerbation of chronic obstructive pulmonary disease. / Adecuación e impacto pronóstico del tratamiento de las exacerbaciones graves de la enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To define the clinical characteristics of patients hospitalised in pneumology and internal medicine departments for chronic obstructive pulmonary disease (COPD) exacerbation, to assess the compliance with the recommendations of the clinical practice guidelines and to determine the impact on the patients' prognosis. METHODOLOGY: We conducted a retrospective longitudinal study that randomly included patients hospitalised for COPD exacerbation in a tertiary hospital. We collected demographic and clinical variables (degree of dyspnoea and obstruction, previous exacerbations, comorbidities), readmission and mortality data and criteria for compliance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and the Spanish COPD guidelines (GesEPOC). We performed a univariate, multivariate and survival analysis. RESULTS: The study included 108 patients, and the mean age was 71.48±11.65 years. The readmission rate was 26.4% at 3 months and 43.4% at 1 year. The hospital mortality rate was 3.9%, the mortality rate at 3 months was 21.9%, and the mortality rate at 1 year was 27.4%. The patients hospitalised in the internal medicine department had higher mortality during hospitalisation (p=.043), at 3 months (p=.028) and at 1 year (p=.007) compared with the rates for the pneumology department. Overall compliance with the clinical guidelines was 63% for the clinical evaluation (less for the patients in internal medicine: 56.1% vs. 73.8%, p=.063). For the treatment, the compliance was 26.9% for GOLD and 28.7% for GesEPOC. Compliance with the GOLD guidelines in the use of corticosteroids was associated with a lower rate of long-term readmissions (p=.041) and hospital mortality (p=.007) and 3-month mortality (p=.05). CONCLUSIONS: The clinical profile of the patients is currently similar to that previously reported, but their clinical progression was poorer. Overall compliance with the clinical guidelines for drug treatment was low, and only appropriate use of systemic steroids was associated with a reduction in early mortality and in medium-term readmissions.

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study.

BACKGROUND: We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. METHODS: From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. RESULTS: The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered "high risk" for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid-related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. CONCLUSIONS: The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid-related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

Anticoagulant treatment of medical patients with complex clinical conditions. / Tratamiento anticoagulante en pacientes médicos con situaciones clínicas complejas.

There is scarce available information on the treatment or prophylaxis with anticoagulant drugs of outpatients with medical diseases and complex clinical conditions. There are no clinical practice guidelines and/or specific recommendations for this patient subgroup, which are frequently treated by internists. Complex clinical conditions are those in which, due to comorbidity, age, vital prognosis or multiple treatment with drugs, a clinical situation arises of disease-disease, disease-drug or drug-drug interactions that is not included within the scenarios that commonly generate the scientific evidence. The objective of this narrative review is collecting and adapting of the clinical guidelines recommendations and systematic reviews to complex clinical conditions, in which the direct application of recommendations based on studies that do not include patients with this complexity and comorbidity could be problematic.

Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment.

OBJECTIVE: Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-centre designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicentre cohort of intermediate-risk kidney transplant (KT) recipients. METHODS: We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction pre-emptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T cells were counted through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and immediate early-1 peptides (mean of six measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T cells were calculated at baseline and day 15. RESULTS: Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8+ T-cell count <1.0 cells/µL had greater risk of CMV events (adjusted hazard ratio (aHR) 2.84; p 0.054). When the CMI assessment was performed in the immediate post-transplant period (day 15), the presence of <2.0 CD8+ T cells/µL (aHR 2.18; p 0.034) or <1.0 CD4+ T cells/µL (aHR 2.43; p 0.016) also predicted the subsequent development of a CMV event. In addition, lower counts of CMV-specific CD4+ (but not CD8+) T cells at days 60 and 180 were associated with a higher incidence of late-onset events. CONCLUSIONS: Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.

Highlights in solid transplant infectious diseases 2015-2017.

Solid organ transplant recipients have an increased risk of developing infections due to the lifelong treatment with immunosuppressive drugs. Herein we review recent (2015-2017) and relevant published advances in the field of bacterial, viral and fungal-infections in this population. We also address the most up-to-date immunological assays that can predict the risk of infection. Finally, we review current guidelines and how they improve the usual clinical care.

Pneumocystis jirovecii infection in patients with acute interstitial pneumonia. / Infección por Pneumocystis jirovecii en pacientes con neumonía intersticial aguda.

OBJECTIVE: Acute interstitial pneumonia (AIP) is a severe disease of unknown etiology. Pneumocystis jirovecii is an atypical opportunistic fungus able to colonize patients with chronic pulmonary disease and inducing alveolar macrophage activation. The aim of this study was to evaluate the possible association between Pneumocystis jirovecii and AIP. SUBJECTS AND METHODS: The presence of P. jirovecii in bronchoalveolar lavage fluid in the four confirmed cases of AIP identified in a tertiary-care hospital over a period of nine years was studied using a 2-step nested-PCR protocol assay. RESULTS: P. jirovecii was identified in the four cases. None of them had HIV infection. Two of the patients were treated empirically with trimethoprim-sulfamethoxazole, the only survivor was being one of them. CONCLUSIONS: Our data suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to evaluate the role of the pathogen in the physiopathology of this disease.

Delphi-RAND consensus of the Spanish Society of Internal Medicine on the controversies in anticoagulant therapy and prophylaxis in medical diseases. INTROMBIN Project (Uncertainty in thromboprophylaxis in internal medicine). / Consenso Delphi-RAND de la Sociedad Española de Medicina Interna sobre controversias en terapia y profilaxis anticoagulante en enfermedades médicas. Proyecto INTROMBIN (INcertidumbre en TROMBoprofilaxis en Medicina INterna).

The aim of this study was to determine the opinion of internists on the management of anticoagulation and thromboembolism prophylaxis in complex clinical scenarios in which the risk-benefit ratio of surgery is narrow and to develop a consensus document on the use of drugs anticoagulant therapy in this patient group. To this end, we identified by consensus the clinical areas of greatest uncertainty, a survey was created with 20 scenarios laid out in 40 clinical questions, and we reviewed the specific literature. The survey was distributed among the internists of the Spanish Society of Internal Medicine (SEMI) and was completed by 290 of its members. The consensus process was implemented by changing the Delphi-RAND appropriateness method in an anonymous, double-round process that enabled an expert panel to identify the areas of agreement and uncertainty. In our case, we also added the survey results to the panel, a methodological innovation that helps provide additional information on the standard clinical practice. The result of the process is a set of 19 recommendations formulated by SEMI experts, which helps establish guidelines for action on anticoagulant therapy in complex scenarios (high risk or active haemorrhage, short life expectancy, coexistence of antiplatelet therapy or comorbidities such as kidney disease and liver disease), which are not uncommon in standard clinical practice.

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.