Point-of-care lung ultrasound assessment for risk stratification and therapy guiding in COVID-19 patients. A prospective non-interventional study.

Background Lung ultrasound is feasible for assessing lung injury caused by coronavirus disease 2019 (COVID-19). However, the prognostic meaning and time-line changes of lung injury assessed by lung ultrasound in COVID-19 hospitalised patients are unknown. Methods Prospective cohort study designed to analyse prognostic value of lung ultrasound in COVID-19 patients by using a quantitative scale (lung ultrasound Zaragoza (LUZ)-score) during the first 72 h after admission. The primary end-point was in-hospital death and/or admission to the intensive care unit. Total length of hospital stay, increase of oxygen flow and escalation of medical treatment during the first 72 h were secondary end-points. Results 130 patients were included in the final analysis; mean±sd age was 56.7±13.5 years. Median (interquartile range) time from the beginning of symptoms to admission was 6 (4–9) days. Lung injury assessed by LUZ-score did not differ during the first 72 h (21 (16–26) points at admission versus 20 (16–27) points at 72 h; p=0.183). In univariable logistic regression analysis, estimated arterial oxygen tension/inspiratory oxygen fraction ratio (PAFI) (hazard ratio 0.99, 95% CI 0.98–0.99; p=0.027) and LUZ-score >22 points (5.45, 1.42–20.90; p=0.013) were predictors for the primary end-point. Conclusions LUZ-score is an easy, simple and fast point-of-care ultrasound tool to identify patients with severe lung injury due to COVID-19, upon admission. Baseline score is predictive of severity along the whole period of hospitalisation. The score facilitates early implementation or intensification of treatment for COVID-19 infection. LUZ-score may be combined with clinical variables (as estimated by PAFI) to further refine risk stratification

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Manejo Clínico de la Neumonía Adquirida en la Comunidad en el Servicio de Urgencias del HCU Lozano Blesa

Introducción: La neumonía adquirida en la comunidad (NAC) es una infección de las vías aéreas inferiores prevalente en nuestro medio, oscilando su incidencia entre 2-15 casos/1.000 habitantes/año, siendo más frecuente en pacientes mayores de 65 años o con comorbilidades. El 40-60% de las NAC requerirán ingreso hospitalario, y de ellos entre el 2-10% será en la UCI, esta gran variabilidad entre el manejo clínico de la NAC, se puede deber a las diferencias en las tasas de ingreso, del diagnóstico microbiológico, de la solicitud de estudios complementarios y la elección del tratamiento antibiótico empírico o el resto de cuidados aplicados.Palabras clave: neumonía adquirida comunidad, servicio de urgencias, diagnóstico, tratamientoObjetivos: El objetivo principal del trabajo es conocer si se realizan los procedimientos diagnósticos y terapéuticos adecuados para neumonías, diagnosticadas en el Servicio de Urgencias Hospital Clínico Universitario.Material y métodos: Se realizó un estudio observacional, retrospectivo y descriptivo de casos incidentes de NAC atendidos en el Servicio de Urgencias del Hospital Clínico Universitario de Zaragoza desde 01/01/2018 al 30/06/2018, obteniendo una N= 285 pacientes. Se analizaron variables relacionados con el estado basal del paciente, la realización de pruebas complementarias y las pautas de antibioterapia empírica y corticoides sistémicos, así como la mortalidad tras el evento.Resultados: La edad media de nuestra muestra fue de 71,92 años con una desviación típica de 18,58. El destino de los 285 pacientes, 55 pacientes (19,6%) fueron dados de alta al domicilio, 220 pacientes (78,3%) fueron ingresados en planta convencional, 6 pacientes (2,1%) fueron ingresados en la unidad de cuidados intensivos y 4 de los pacientes se trasladaron a otro centro hospitalario. El 59,7% de los pacientes presentaban indicación de hemocultivos, siendo negativos el 88,7%. En el 76% de los casos no se realizaron cultivos de esputo. El antígeno de neumococo y legionella se recogió en el 33,9% de los pacientes, siendo negativa hasta el 69,4%. El test de la gripe se realizó en el 49,2%. Los valores medios de PCR en función del destino del paciente fueron: el 10,359,93 en los destinados a su domicilio, el 15,5012,77 a planta convencional y el 26,0211,47 a la unidad de cuidados intensivos. Los valores de la PCT, en pacientes destinados a domicilio fue de 0,070,04, a planta convencional 7,047,20 y a la unidad de cuidados intensivos fue de 8,424,82. En cuanto al tratamiento la adherencia a la guía de antibioterapia empírica fue del 52,58% y el antibiótico más utilizado fue amoxcilina clavulánico. 125 pacientes eran subsidiarios de recibir tratamiento corticoideo sistémico (43,9%), de los cuales 75 (26,3%) lo recibieron y 50 (17,5%) no lo recibieron. Conclusión: La mortalidad en nuestro medio es similar a la de otros centros y se da fundamentalmente en pacientes mayores. En cuanto a la realización de pruebas diagnósticas complementarias utilizadas con el fin de determinar el agente microbiológico, es un recurso infrautilizado y de baja rentabilidad en nuestro ámbito hospitalario. Existe una escasa adherencia a la guía de tratamiento antibiótico empírico de nuestro hospital. Como conclusión, debemos incrementar los esfuerzos dirigidos a optimizar el diagnóstico etiológico y la adherencia a las guías terapéuticas locales<br /

The Importance of a Multidisciplinary Approach in the Management of a Patient with Type I Gaucher Disease

Managing the multisystemic symptoms of type I Gaucher Disease (GD) requires a multidisciplinary team approach that includes disease-specific treatments, as well as supportive care. This involves a range of medical specialists, general practitioners, supportive care providers, and patients. Phenotype classification and the setting of treatment goals are important for optimizing the management of type I GD, and for providing personalized care. The ability to classify disease severity using validated measurement tools allows the standardization of patient monitoring, and the measurement of disease progression and treatment response. Defining treatment goals is useful to provide a benchmark for assessing treatment response and managing the expectations of patients and their families. Although treatment goals will vary depending on disease severity, they include the stabilization, improvement or reversal (if possible) of clinical manifestations. Enzyme replacement therapy (ERT) is the standard care for patients with type I GD, but a novel substrate reduction therapy (SRT), Eliglustat, has demonstrated safety and efficacy in selected patients. To ensure that treatment goals are being achieved, regular and comprehensive follow up are necessary

The multifaceted function of granzymes in sepsis: some facts and a lot to discover

1 figure, 1 tableSepsis is a serious global health problem. In addition to a high incidence, this syndrome has a high mortality and is responsible for huge health expenditure. The pathophysiology of sepsis is very complex and it is not well-understood yet. However, it is widely accepted that the initial phase of sepsis is characterized by a hyperinflammatory response while the late phase is characterized by immunosuppression and immune anergy, increasing the risk of secondary infections. Granzymes (Gzms) are a family of serine proteases classified according to their cleavage specificity. Traditionally, it was assumed that all Gzms acted as cytotoxic proteases. However, recent evidence suggests that GzmB is the one with the greatest cytotoxic capacity, while the cytotoxicity of others such as GzmA and GzmK is not clear. Recent studies have found that GzmA, GzmB, GzmK, and GzmM act as pro-inflammatory mediators. Specially, solid evidences show that GzmA and GzmK function as extracellular proteases that regulate the inflammatory response irrespectively of its ability to induce cell death. Indeed, studies in animal models indicate that GzmA is involved in the cytokine release syndrome characteristic of sepsis. Moreover, the GZM family also could regulate other biological processes involved in sepsis pathophysiology like the coagulation cascade, platelet function, endothelial barrier permeability, and, in addition, could be involved in the immunosuppressive stage of sepsis. In this review, we provide a comprehensive overview on the contribution of these novel functions of Gzms to sepsis and the new therapeutic opportunities emerging from targeting these proteases for the treatment of this serious health problem.This work was supported in part by FEDER/Gobierno de Aragón (group B29), Ministerio de Economia y Competitividad [SAF2014-54763-C2-1 and SAF2017-83120-C2-1-R (JP-P), SAF2014-54763-C2-2-R (EG)] and Instituto de Salud Carlos III (PI16-00526, LM-L; PI18/00527, JP-P). Predoctoral grants/contracts from Fundacion Santander/Universidad de Zaragoza (LS and MA), Ministerio de Ciencia, Innovación y Universidades (MG-T). MA has a Juan de la Cierva Contract (Ministerio de Ciencia, Innovación y Universidades) and JS-M a Rio Hortega Contract (Instituto de Salud Carlos III). JP was supported by Fundación Aragon I+D (ARAID).Peer reviewe

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective

Measurement of the lifetime and Λ separation energy of 3ΛH

The most precise measurements to date of the 3ΛH lifetime τ and Λ separation energy BΛ are obtained using the data sample of Pb-Pb collisions at √= 5.02 TeV collected by ALICE at the LHC. The 3ΛH is reconsNN structed via its charged two-body mesonic decay channel (3ΛH→ 3He + π− and the charge-conjugate process). The measured values τ=[253±11 (stat.)±6 (syst.)] ps and BΛ=[102±63 (stat.)±67 (syst.)] keV are compatible with predictions from effective field theories and confirm that the 3ΛH structure is consistent with a weakly-bound system

Measurement of ψ (2S) production as a function of charged-particle pseudorapidity density in pp collisions at √s = 13 TeV and p–Pb collisions at √sNN = 8.16 TeV with ALICE at the LHC

Production of inclusive charmonia in pp collisions at center-of-mass energy of √s = 13 TeV and p–Pb collisions at center-of-mass energy per nucleon pair of √sNN = 8.16 TeV is studied as a function of charged-particle pseudorapidity density with ALICE. Ground and excited charmonium states (J/ψ, ψ(2S)) are measured from their dimuon decays in the interval of rapidity in the center-of-mass frame 2.5 < ycms < 4.0 for pp collisions, and 2.03 < ycms < 3.53 and −4.46 < ycms < −2.96 for p–Pb collisions. The charged-particle pseudorapidity density is measured around midrapidity (|η| < 1.0). In pp collisions, the measured charged-particle multiplicity extends to about six times the average value, while in p-Pb collisions at forward (backward) rapidity a multiplicity corresponding to about three (four) times the average is reached. The ψ(2S) yield increases with the charged-particle pseudorapidity density. The ratio of ψ(2S) over J/ψ yield does not show a significant multiplicity dependence in either colliding system, suggesting a similar behavior of J/ψ and ψ(2S) yields with respect to charged-particle pseudorapidity density. Results for the ψ(2S) yield and its ratio with respect to J/ψ agree with available model calculations

Investigation of K+K− interactions via femtoscopy in Pb-Pb collisions at √sNN = 2.76 TeV at the CERN Large Hadron Collider

Femtoscopic correlations of non-identical charged kaons (K+K−) are studied in Pb−Pb collisions at a center-of-mass energy per nucleon−nucleon collision sNN−−−√=2.76 TeV by ALICE at the LHC. One-dimensional K+K− correlation functions are analyzed in three centrality classes and eight intervals of particle-pair transverse momentum. The Lednický and Luboshitz interaction model used in the K+K− analysis includes the final-state Coulomb interactions between kaons and the final-state interaction through a0(980) and f0(980) resonances. The mass of f0(980) and coupling were extracted from the fit to K+K− correlation functions using the femtoscopic technique for the first time. The measured mass and width of the f0(980) resonance are consistent with other published measurements. The height of the ϕ(1020) meson peak present in the K+K− correlation function rapidly decreases with increasing source radius, qualitatively in agreement with an inverse volume dependence. A phenomenological fit to this trend suggests that the ϕ(1020) meson yield is dominated by particles produced directly from the hadronization of the system. The small fraction subsequently produced by FSI could not be precisely quantified with data presented in this paper and will be assessed in future work