Growth, survival, digestive activity and respiratory metabolism of Octopus maya juveniles fed with prepared diets.

The effects of two prepared feeds were tested on growth, survival, enzymatic activity, nutritive reserves in the digestive gland and oxygen consumption of Octopus maya juveniles. For the first time, a semihumid paste (HD, control) and a dry diet, in pelleted form (PD, experimental) with the same formulation were used for this species. The experiment lasted for 42 days. Results indicate that growth rates were similar for both diets (p > 0.05); however, survival (70%) was higher with the PD compared to the HD (48%) (p < 0.05). The performance index was higher for octopuses fed the PD (p < 0.05). No differences in acid proteases activity were observed. However, a higher activity of alkaline proteases in the octopuses fed the PD was observed (p < 0.05). Ingestion rate was higher for octopuses fed the PD. Routine energy inversion was similar in both treatments (p > 0.05). A greater energy inversion was observed in octopuses fed the PD, whose active metabolism was double compared to the octopuses fed the HD. Results showed that the PD promoted similar growth compared to the HD diet but favored survival, and a greater investment in the active metabolism, reflected in the apparent heat increase.

The link between high factor VIII to protein C ratio values and poor liver function after major hepatectomy.

Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P  < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P  < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.

Mapping the literature on the qualitative approach to childhood asthma from 1996 to 2018: a bibliometric analysis / Mapeo de la literatura sobre el enfoque cualitativo del asma infantil desde 1996 hasta 2018: un análisis bibliométrico

Resumo Objectives: to describe the scientific production of qualitative studies in childhood asthma. Methods: bibliometric analysis. Articles were from Web of Science, Scopus, Cochrane, and PubMed (1996-2018), using the search terms asthma, children, qualitative research, qualitative study, qualitative analysis, ethnographic, phenomenology and narrative. Results: 258 articles were retrieved from 143 journals, representing 1.2% of scientific articles on childhood asthma. The growth rate was high. Authorship included 969 authors (85.3% occasional) from 279 institutions. 94.2% were co-authored and 3.5% were international collaborations. The greatest number of articles were from the United States (45.3%), United Kingdom (17.4%) and Canada (7.4%). The categories with the highest number of articles were Nursing & Public, Environmental & Occupational Health (18.2%), Respiratory System (10.1%) and Allergy (7.7%). 99.7% of the articles were in English. Conclusion: these results show a lack of consolidation of the literature based on qualitative studies on childhood asthma with a high percentage of occasional authors and limited international collaboration, indicating a need to strengthen this approach.

Resumen Objetivos: describir la producción científica de los estudios cualitativos sobre el asma infantil. Métodos: análisis bibliométrico. Los artículos procedían de Web of Science, Scopus, Cochrane y PubMed (1996-2018), utilizando los términos de búsqueda asthma, children, qualitative research, qualitative study, qualitative analysis, ethnographic, phenomenology y narrative. Resultados: se recuperaron 258 artículos de 143 revistas, lo que representa el 1,2% de los artículos científicos sobre asma infantil. La tasa de crecimiento fue elevada. La autoría incluyó 969 autores (85,3% ocasionales) de 279 instituciones. El 94,2% fueron coautores y el 3,5% colaboraciones internacionales. El mayor número de artículos procedió de Estados Unidos (45,3%), Reino Unido (17,4%) y Canadá (7,4%). Las categorías con mayor número de artículos fueron Enfermería y Salud Pública, Ambiental y Ocupacional (18,2%), Aparato Respiratorio (10,1%) y Alergia (7,7%). El 99,7% de los artículos estaban en inglés. Conclusión: estos resultados muestran una falta de consolidación de la literatura basada en estudios cualitativos sobre el asma infantil, con un alto porcentaje de autores ocasionales y una limitada colaboración internacional, lo que indica la necesidad de reforzar este enfoque.

Colaboración científica de Colombia con países de América Latina y del Caribe sobre la COVID-19 durante 2020 y 2021 / Colombia´s scientific collaboration with Latin American and Caribbean countries on COVID-19 during 2020 and 2021

Introducción: La necesidad de información por desconocimiento del Sars-CoV-2 llevó a los investigadores a generar una gran cantidad de información. Colombia es el segundo país latinoamericano con mayor producción científica sobre el Sars- CoV-2. Objetivo: caracterizar la tendencia de colaboración científica de Colombia con países de Latinoamérica y el Caribe sobre la COVID-19. Materiales y métodos: estudio bibliométrico, los registros se obtuvieron de Scopus (2020 - 2021) con los términos COVID-19, 2019-nCoV, new coronavirus, coronavirus disease 2019 y Sars-CoV-2. Se analizaron indicadores de producción, colaboración y visibilidad. Resultados: se recuperaron 77 registros. La tasa de crecimiento de la producción fue del 65,51 %. El índice de transitoriedad alcanzó el 86,69 %. El autor más productivo fue A.J. Rodríguez Morales de la Fundación Universitaria Autónoma de las Américas y Universidad Tecnológica de Pereira de Colombia (14,28 %). El 96,10 % de las investigaciones procedieron de universidades. La tasa de colaboración inter-latinoamericana alcanzó el 11,66 % con un índice de colaboración de 3,71 ± 3,09. La densidad de la red fue de 0,51. La mayor colaboración se dio con autores de México (n= 27), Perú (n= 26), Chile (n= 25) y Argentina (n= 23). Argentina presentó un mayor outdegree (176) y número de citas (55,03) y Chile un eigenvector superior (0,35). La correlación entre el número de citas y el grado de centralidad fue de 0,9. Conclusión: Colombia tiende a participar en proyectos internacionales y con países de Latinoamérica y el Caribecon mayor capacidad para desarrollar investigaciones.

Introduction: The need for information due to ignorance of Sars-CoV-2 led researchers to write and publish a large amount of information. Colombia is the second within Latin American countries with the highest scientific production on Sars- CoV-2. Objective: to characterize the trend of scientific collaboration between Colombia and Latin American and Caribbean countries on COVID-19. Materials and methods: bibliometric study, the records were acquired from Scopus (2020 - 2021) with the terms COVID-19, 2019-nCoV, new coronavirus, coronavirus disease 2019 and Sars-CoV-2. Indicators of production, collaboration and visibility were analyzed. Results: 77 records were recovered. The production growth rate was 65.51%. The transience index reached 86.69%. The most productive author was A.J. Rodríguez Morales of the Autonomous University Foundation of the Americas and the Technological University of Pereira of Colombia (14.28%). 96.10% of the investigations came from universities. The inter-Latin American collaboration rate reached 11.66% with a collaboration index of 3.71 ± 3.09. The density of the network was 0.51. The greatest collaboration occurred with authors from Mexico (n= 27), Peru (n= 26), Chile (n= 25) and Argentina (n= 23). Argentina presented a higher degree of improvement (176) and number of citations (55.03) and Chile a higher eigenvector (0.35). The connection between the number of citations and the degree of centrality was 0.9. Conclusion: Colombia tends to participate in international projects and with Latin America and the Caribbeancountries with greater capacity to develop research.

Thermal optimality and physiological parameters inferred from experimental studies scale latitudinally with marine species occurrences.

Ocean warming is expected to occur due to anthropogenic climate change bringing a spatial shift of marine communities. Experimental data that characterize the aerobic power budget via an aerobic scope, thermal metabolic scope, or thermal preferences have been proposed as tools that can describe species distribution since they characterize species fitness or performance under different temperatures. This study tested the potential relationship between observed occurrences and different physiological studies in the Americas for 11 commercially important species in Mexico. Projections were also developed for Mexico's exclusive economic zone under different climate warming scenarios. The physiological data were fitted from optimum up to pejus temperatures and projected to sea surface temperatures for present (2003-2014) and Representative Concentration Pathway (RCP) scenarios (RCP 2.6, RCP 4.5, RCP 6.0, and RCP 8.5) for the period 2040-2050 and 2090-2100. For species with wide distributions in the Americas, the number of occurrences reported decreases at higher latitudes related to the decrease in species performance calculated from laboratory experiments. In addition, higher species occurrences are usually reported around optimum temperatures. Overall, the results suggest that pejus temperatures likely restrict latitudinal distribution, at least for widely distributed taxons. Regarding Mexican projections, the results varied widely by species. For example, in the Atlantic Ocean, Octopus maya and Panulirus argus are vulnerable to warming scenarios, while Centropomus undecimalis is not. Interestingly, northern Campeche Bank, the Gulf of California, and Western Baja California may act as thermal refugia for marine species indicating they could be assigned as protected areas to support fisheries throughout the Mexican exclusive economic zone. This research adds to the increasing evidence of the relationship between thermal niche and wild population distribution.

Análisis bibliométrico de los 100 artículos más citados publicados en español de Latinoamérica y el Caribe sobre COVID-19

El objetivo del estudio fue identificar los 100 artículos más citados sobre COVID-19 procedentes de Latinoamérica y el Caribe, publicados en español. Los registros se obtuvieron de la Web of Science. Se examinó: número de citas, autoría, cobertura geográfica, colaboración, revista y categorías temáticas. Los 100 artículos se publicaron en 41 revistas. La revista más citada fue Salud Pública de México (10 artículos; 75 citas). México fue el máximo exponente (28 artículos; 201 citas). Los autores más citados fueron: C. Alpuche-Aranda y E. Lazcano-Ponce, afiliados a la institución más citada, el Instituto Nacional de Salud Pública de México (n= 7). La principal categoría de la Web of Science fue Medicine, General & Internal (36 artículos; 173 citas). Epidemiología fue el tema más trabajado. No hubo correlación entre la colaboración internacional y el mayor número de citas (r= 0,15, p= 0,1). El estudio puede ayudar a reconocer la visibilidad de las investigaciones más citadas.

The aim of the study was to identify the 100 most cited articles on COVID-19 from Latin America and the Caribbean, published in Spanish. The records were obtained from the Web of Science. The following were examined: number of citations, authorship, geographic coverage, collaboration, journal and thematic categories. The 100 articles were published in 41 journals. The most cited journal was Salud Pública de México (10 articles; 75 citations). Mexico was the top performer (28 articles; 201 citations). The most cited authors were: C. Alpuche-Aranda and E. Lazcano-Ponce, affiliated with the most cited institution, the National Institute of Public Health of Mexico (n= 7). The main Web of Science category was Medicine, General & Internal (36 articles; 173 citations). Epidemiology was the most worked topic. There was no correlation between international collaboration and the highest number of citations (r= 0.15, p= 0.1). The study may help to recognize the visibility of the most cited research.

Immune Response to Natural and Experimental Infection of Panulirus argus Virus 1 (PaV1) in Juveniles of Caribbean Spiny Lobster.

Experimental infections have been used to better comprehend the immune system of organisms, and to probe for additives that generate greater resistance and help reduce antibiotic use in aquaculture. We compared the immune response of juveniles of the Caribbean spiny lobster, Panulirus argus, infected naturally with Panulirus argus virus 1 (PaV1) versus organisms infected experimentally, to determine the analogy between both infectious processes. The immunological response was measured by hemagglutination activity, hemocyte count, and total phenoloxidase activity in plasma and hemocytes in 211 individuals that were either naturally infected (110), or had been injected with viral inoculum and followed for six months (101). The samples were classified into the following four groups according to the severity of the infection: 0, uninfected; 1, lightly; 2, moderately; and 3, severely infected), which was determined on the basis of PCR and histological criteria. A permutational MANOVA showed that both the origin (natural and experimental), and the severity of the infection contributed significantly to explain the variation in the immune response of lobsters. The lack of significance of the interaction term indicated that the immunological response changed with the severity of the infection in a similar way, regardless of its origin. The results of the present study suggest that the experimental viral infection of PaV1 produces a defense response similar to the natural pathways of contagion, and provides the bases to validate an immunological challenge protocol for the first time in crustaceans. The discussion includes the perspective of the conceptual models of immune response within an ecological context.

Sex-specific role of the optic gland in octopus maya: A transcriptomic analysis.

The optic glands (OG) of cephalopods are a source of molecules associated with the control of reproductive traits and lifecycle events such as sexual maturation, reproductive behavior, feeding, parental care, and senescence. However, little is known about the role of the optic gland in Octopus maya adults during mating and egg laying. RNA sequencing, de novo transcriptome assembly, ubiquity and differential expression analysis were performed. First, we analyzed the expression patterns of transcripts commonly associated with OG regulatory functions to describe their possible role once the maturation of the gonad is complete. The transcriptomic profiles of the optic gland of both sexes were compared with emphasis on the signaling pathways involved in the dimorphism of reproductive traits. Results suggest that in the OG of males, the reproductive condition (mated or non-mated) did not affect the general expression profile. In contrast, more differentially expressed genes were observed in females. In mated females, the mRNA metabolic process and the response to norepinephrine were enriched, suggesting a high cellular activity in preparation for the laying of the embryos. Whereas in egg-laying females, energetic and metabolic processes were the most represented, including the oxidation-reduction process. Finally, the gene expression patterns in senescence females suggest a physiological response to starvation as well as upregulation of genes involved retrotransposon activity. In conclusion, more substantial fluctuations in gene expression were observed in the optic glands of the fertilized females compared to the males. Such differences might be associated with the regulation of the egg-laying and the onset of senescence.

A Dalbavancin Lock Solution Can Reduce Enterococcal Biofilms After Freezing.

INTRODUCTION: We previously demonstrated the efficacy of a frozen dalbavancin-heparin (DH) lock solution against biofilms of staphylococci. However, as enterococci also commonly cause catheter-related bloodstream infections (C-RBSI), we assessed the bioactivity of frozen dalbavancin (D) and DH against enterococci. METHODS: Over 6 months, we compared the bioactivity of a solution of DH (1 mg/ml) with that of D in terms of cfu counts and metabolic activity against biofilms of Enterococcus faecalis and Enterococcus faecium (four strains each). For each solution, we individually compared results obtained at each time point (months 3 and 6) with baseline (month 0). We also compared the median DH value of each variable at baseline and at months 3 and 6 of freezing with the values obtained for D alone. We used both statistical and clinical criteria when results were within 25% of the reference value. RESULTS: At the end of the experiment (month 6), neither a statistically nor a clinically significant reduction in the bioactivity of D solution was observed in terms of cfu count and metabolic activity against enterococcal biofilms. Regarding the DH solution, we found both statistical and clinical significance in the median percentage reduction in metabolic activity between months 0 and 6 in E. faecalis strains (51.8% vs. 77.8%, P = 0.007). Moreover, after freezing, the DH solution lost significant bioactivity compared with the D solution, especially in E. faecalis. CONCLUSION: A dalbavancin lock solution can be frozen for up to 6 months with no negative effect on its bioactivity against enterococcal biofilms. However, when combined with heparin, its efficacy was reduced. Therefore, we recommend that if lock therapy with frozen dalbavancin is used in the management of enterococcal C-RBSI, heparin should be added simultaneously at the time of catheter lock.

Acquired FXIII Deficiency is Associated with High Morbidity.

BACKGROUND: A factor XIII (FXIII) level >30% is considered necessary to prevent spontaneous bleeding. Bleeding is also a risk in patients with acquired FXIII deficiency, but the hemostatic level of FXIII in this context remains to be determined. METHODS: We retrospectively analyzed all patients diagnosed with acquired FXIII deficiency at a large hospital over 3 years (study ID NCT04416594, http://www.clinicaltrials.gov) and assessed clinical data to identify the best cut-off point for FXIII activity to distinguish between low and high risk of major bleeding in a mixed medical and surgical population. RESULTS: Of the 97 patients who experienced bleeding despite a normal coagulation test, 43.2% had FXIII activity <70%. FXIII activity was significantly lower in surgical patients and patients admitted to the intensive care unit (ICU). Low FXIII activity was significantly associated with long ICU stays and a high incidence of major bleeding. CONCLUSION: Acquired FXIII deficiency is associated with high morbidity. The hemostatic level of FXIII in the setting of acquired FXIII deficiency might be above 30%.

Expanded hemodialysis: Is anticoagulation of the dialysis circuit different from online hemodiafiltration and high-flux hemodialysis?

Expanded hemodialysis (HDx) has a high capacity for removing medium and medium-large molecules; however, there are no specific recommendations during HDx for anticoagulation of the dialysis circuit. We aimed to evaluate the differences in the efficacy of anticoagulation procedures using the venous port and 40 mg enoxaparin in HDx compared to high-flux hemodialysis (HF-HD) and postdilution online hemodiafiltration (HDF). We compared anticoagulant activity in 11 patients in HDx, HF-HD, and HDF under similar dialysis conditions. In the 33 dialysis sessions, 40 mg enoxaparin was administered through the venous port, and pre- and postdialysis antifactor Xa activity (aXa) and activated partial thromboplastin time (APTT), postdialysis clotting time of the vascular access, visual clotting score of the dialyzer, and any complications with the extracorporeal circuit or bleeding were registered. APTT postdialysis in HDx was not significantly different from that in HF-HD and HDF. Postdialysis aXa in HDx was not significantly different from that in HF-HD and HDF. We found no significant differences in visual clotting score of the dialyzer. Enoxaparin administered through the venous port was sufficient for anticoagulation within the extracorporeal circuit in HDx, HF-HD, and HDF. There were no differences in postdialysis aXa or APTT, most likely because when low molecular-weight heparin is applied through venous port, lesser enoxaparin concentration reaches the dialyzer. Thus, we conclude that the dose of enoxaparin administered through the venous port should not be adjusted according to dialysis technique.

Mortality in acquired thrombotic thrombocytopenic purpura in the pre-caplacizumab era.

Despite the effectiveness of plasma exchange (PEX) and immunosuppressants in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP), a number of patients still die as a result of the disease. Whether caplacizumab could rescue these patients remains still unsettled. The objective of this study was to characterise mortality patterns and prognostic factors in the first episode of aTTP.We queried the Spanish TTP Registry for patients with a diagnosis of aTTP in their presenting episode who fulfilled complete clinical and follow-up data (n = 102). The patients were diagnosed between 2004 and 2018, and all were treated with daily PEX and corticosteroids. Clinical and laboratory data were analysed at diagnosis and during the treatment course.Eight patients (7.7%) died between 12 h and 36 days after presentation, and could be classified into three patterns: death before treatment, early death driven by acute cardiac or neurologic events, and late death due to unremitted aTTP. Stupor or coma at diagnosis and platelet count < 20 × 109 /L by the 6th treatment day were independently associated with increased risk of death.Stupor or coma at diagnosis and lack of response to PEX by the 6th day in patients experiencing the first episode of aTTP are strong predictors of mortality. These patients could be rescued by novel agents aimed at halting the microvascular thrombosis until adequate immunosuppression is achieved.

Geographical distribution and international collaboration of Latin American and Caribbean scientific publications on tuberculosis in Pubmed. / Distribución geográfica y colaboración internacional de las publicaciones científicas latinoamericanas y del Caribe sobre tuberculosis en PubMed.

OBJECTIVE: The objective of the study was to describe the geographical coverage of Latin American and Caribbean scientific publications on tuberculosis and its international collaboration. MATERIALS AND METHODS: The records were retrieved from the PubMed database (2009-2018), limiting the search to Latin American and Caribbean countries. Articles were analyzed in several categories, such as the total number, countries, institutions, authors, collaborations, and citations. The software UCINET and VOSviewer were used. RESULTS: 2,495 items were recovered, 4.2% of world production. More than half of the research came from Brazil (52.5%), Mexico (16.6%) and Peru (10.5%). 97.6% of the production is co-authored, with a rate of international collaboration of 24.5%. The countries with the highest production in international collaboration are Brazil (39.1%), Peru (26.8%) and Mexico (16%); they are also the countries with the best OutDegree, OutCloseness and Betweenness. The United States (11.9%), United Kingdom (5.8%), France (2.1%), Spain and Switzerland (1.7%), South Africa (1.7%) and Italy (1.6%) are the main collaborators with Latin America. CONCLUSION: Brazil, together with Peru and Mexico, is the undisputed leader in Latin American and Caribbean tuberculosis production, due to the volume of articles and its position in the collaborative network. The eradication of tuberculosis requires continuing research in international collaboration, to carry out more effective health policies on tuberculosis.

OBJETIVO: Describir la cobertura geográfica de las publicaciones científicas de América Latina y el Caribe sobre tuberculosis y su colaboración internacional. MATERIALES Y MÉTODOS: Los registros fueron recuperados de la base de datos bibliográfica PubMed (2009-2018), limitando la búsqueda a países latinoamericanos y del Caribe. Los artículos se analizaron en varias categorías, como número total, países participantes, instituciones, autores, colaboraciones y citas. Se utilizó el software UCINET y VOSviewer para representar las redes de colaboración. RESULTADOS: Se recuperaron 2495 artículos, 4,2% de la producción mundial. Más de la mitad de las investigaciones proceden de Brasil (52,5%), México (16,6%) y Perú (10,5%). El 97,6% de la producción presenta coautoría, con una tasa de colaboración internacional del 24,5%. Los países con mayor producción en colaboración internacional son Brasil (39,1%), Perú (26,8%) y México (16%), además son los que presentan mejor centralidad, cercanía e intermediación. Estados Unidos (11,9%), Reino Unido (5,8%), Francia (2,1%), España y Suiza (1,7%), Sudáfrica (1,7%) e Italia (1,6%), son los principales colaboradores con Latinoamérica. CONCLUSIÓN: Brasil, junto a Perú y México, es líder de la producción científica sobre tuberculosis en Latinoamérica y el Caribe, por el volumen de artículos y su posición en la red de colaboración. La erradicación de la tuberculosis pasa por continuar investigando en colaboración internacional, y así llevar a cabo políticas de salud más efectivas en tuberculosis.

Incidence and clinical profile of venous thromboembolism in hospitalized COVID-19 patients from Madrid region.

BACKGROUND: COVID-19 related in-hospital venous thromboembolism (VTE) incidence is high but data reported vary significantly. Some studies show that up to half of the events are diagnosed early after admission. OBJECTIVES: To study symptomatic VTE incidence in acute COVID-19 hospitalized patients and to describe timing of VTE diagnosis. METHODS: Multicenter cohort of 5966 patients hospitalized with acute COVID-19. Multicenter Registry of 844 hospitalized patients with acute COVID-19 and associated acute VTE. RESULTS: By the time of cohort data collection, 68 patients (1.14%) were still hospitalized, 19.8% had died, and 5.4% required ICU. During a median follow-up of 6 days (IQR, 4-12), 183 patients (3.07%; 95% CI, 2.64-3.55) presented a symptomatic VTE event. The cumulative incidences of VTE at 7, 14 and 21 days in wards [2.3% (95% CI, 1.9-2.7), 3.6% (95% CI, 3.0-4.3), and 4.3% (95% CI, 3.5-5.1)] were similar to the ones reported in ICU [2.2% (95% CI, 1.0-4.4), 2.9% (95% CI, 1.5-5.3), and 4.1% (95% CI, 2.2-6.8)], but at 30 and 60 days were higher in ICU [6.9% (95% CI, 4.2-10.5), and 12.8% (95% CI, 8.1-18.5)] than in wards. Eighty-eight VTE events (48%) were diagnosed early, within 48 h of admission. VTE was not associated with death (HR, 0.79; 95% CI, 0.55-1.12). CONCLUSIONS: Incidence of symptomatic VTE in our COVID-19 cohort is consistent with that of other real-life studies recently published. Early VTE events are, along with COVID-19, the reason for admission rather than an in-hospital complication.

Clinical Drug Trials: The Path to the Patient.

The aim of this chapter is to describe and give an overview of the steps from the conception of an idea in the lab to reaching the market. Starting from the early discovery in the lab environment (including reverse and classical pharmacology), and briefly going over the different phases of clinical trials: Phase I, first tests in humans; Phase II, safety and efficacy; Phase III, efficacy confirmation; and Phase IV, post-authorization, in which the investigation would focus on long-term effects, completion of technical and safety sheet. Finally, a short conclusion in regard to the continuous overview and revision of drugs in the market.

Efficacy of enoxaparin in preventing coagulation during high-flux haemodialysis, expanded haemodialysis and haemodiafiltration.

BACKGROUND: Low-molecular-weight heparins (LMWHs) are easily dialysable with high-flow membranes; however, it is not clear whether the LMWH dose should be adjusted according to the membrane type and dialysis technique. This study aimed to evaluate the influence of the dialyser on anticoagulation of the extracorporeal dialysis circuit. METHODS: Thirteen patients received the same dose of LMWH through the arterial port via three dialysis techniques: high-flux haemodialysis (HF-HD), online haemodiafiltration (HDF) and expanded haemodialysis (HDx). All dialysis was performed under similar conditions: duration, 4 h; blood flow, 400 mL/min; and dialysate flow, 500 mL/min. Antifactor Xa (aXa) activity and activated partial thromboplastin time (APTT) were measured before and after the dialysis. Clotting time of the vascular access site after haemodialysis, visual clotting score of the dialyser and any complications with the extracorporeal circuit or bleeding were registered. RESULTS: Post-dialysis aXa activity in HF-HD (0.26 ± 0.02 U/mL) was significantly different from that in HDF (0.21 ± 0.02 U/mL, P = 0.024), and there was a trend in HDx (0.22 ± 0.01 U/mL, P = 0.05). APTT post-dialysis in HF-HD (30.5 ± 0.7 s) was significantly different from that in HDx (28.2 ± 0.64 s, P = 0.009) and HDF (28.8 ± 0.73 s, P = 0.009). CONCLUSIONS: AXa activity in HDF was significantly lower than that in HF-HD, possibly because of more losses of LMWH through the dialyser. Given the higher anticoagulant loss in HDF and probably in HDx than in HF-HD, the enoxaparin dose administered may be adjusted according to the dialysis technique.

Ruxolitinib for steroid-refractory graft versus host disease in pediatric HSCT: high response rate and manageable toxicity.

Ruxolitinib, a selective Janus Kinase (JAK) 1/2 inhibitor, is a promising treatment for the steroid-refractory graft-vs-host disease (GvHD) after hematopoietic stem cell transplantation (HSCT). Most studies have been performed in the adult population showing efficacy against GvHD. In this retrospective study, we evaluated the outcomes of 19 children who received ruxolitinib for refractory acute or chronic GvHD (cGvHD) after HSCT from two Pediatric Hemato-Oncology Departments in Spain between March 2017 and December 2018. Patients received a median number of 4 (IQR 2) previous lines of treatment before starting ruxolitinib. The overall response rate in acute GvHD (aGvHD) and cGvHD was 87% and 91%, respectively. Complete response (CR) was observed in 37% of aGvHD and 8.3% of cGvHD. Remarkably, 43% and 40% of patients with steroid-refractory gastrointestinal aGvHD and lung cGvHD achieved CR. During ruxolitinib treatment, there were 36%, 31%, and 10% infections caused by viruses, bacteria, and fungi, respectively. Overall, four patients interrupted ruxolitinib due to infectious complications, hematological, and liver toxicity. The 2-year overall survival was 71.9% (CI 95% 58.6-85.2). Our experience supports the use of ruxolitinib as an effective treatment for steroid-refractory acute and cGvHD in children with a moderate toxicity profile.