Atomoxetine: toxicological aspects of a new treatment for Attention Deficit Hyperactivity Disorder in Brazil.

Atomoxetine is a drug widely used for the treatment of the attention deficit hyperactivity disorder (ADHD) with reduced risk of adverse motor reactions and chemical dependence. However, the pharmacokinetics characteristics as well as the toxicological risk of atomoxetine deserves further investigation to comprehensively analyze the therapeutic and safety aspects of this drug. This study aimed to predict the physicochemical profile and medicinal chemistry characteristics of atomoxetine, alongside its pharmacokinetic properties-namely absorption, distribution, metabolism, and excretion-as well as its toxicology (ADMET) potential through the utilization of web-based in silico tools. This research emphasizes predicted physicochemical, medicinal chemistry, and absorption parameters of atomoxetine that could influence the efficacy and safety of this drug for ADHD treatment. Additionally, atomoxetine also presents noteworthy predicted risks of hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, respiratory system toxicity, skin toxicity, and carcinogenicity. These findings underscore the necessity for further assessments of atomoxetine's safety profile, particularly considering different patient populations and durations of drug treatment. The data reported here from in silico predictions suggest that closer monitoring is warranted when atomoxetine is administered to patients with ADHD. Moreover, controlled studies detailing reliable protocols for personalized dosing, considering the multifactorial variability in metabolism efficiency and toxicological potential, would enable a more comprehensive assessment of atomoxetine's safety profile.

Phylogeographic patterns of Cyphocharax from trans-Andean rivers and northward expansion to lower Central America (Teleostei, Curimatidae).

Phylogenetic analyses of mitochondrial and nuclear data of 31 specimens of Cyphocharax from trans-Andean rivers support the presence of one lineage of Cyphocharax aspilos in Lago Maracaibo and three cryptic lineages of Cyphocharax magdalenae: (1) Cauca-Magdalena and Ranchería, (2) León and Atrato, and (3) Chucunaque-Tuira, Santa María, and Chiriquí basins of Central America. Results suggest that the Serranía del Perijá facilitated Late Miocene cladogenetic events, whereas post-Isthmian C. magdalenae expansion was enabled by gene flow across the lower Magdalena valley and Central American lowlands. Time-calibrated phylogenetics indicate that the C. magdalenae colonized lower Central America in the Pliocene (3.7 MYA; Ma), the divergence Atrato-Magdalena occurred in Late Pliocene (3.0 Ma) and the split Ranchería-Magdalena during the Middle Pleistocene (1.3 Ma). Updated geographic distribution data support the hypothesis that the Cordillera de Talamanca functions as a barrier to northward expansion of C. magdalenae in Central America.

Respiratory muscle strength can improve the prognostic assessment in COPD.

Impaired lung function, respiratory muscle weakness and exercise intolerance are present in COPD and contribute to poor prognosis. However, the contribution of the combination of these manifestations to define prognosis in COPD is still unknown. This study aimed to define cut-off points for both inspiratory and expiratory muscle strength (MIP and MEP, respectively) for mortality prediction over 42-months in patients with COPD, and to investigate its combination with other noninvasive established prognostic measures (FEV1, V̇O2peak and 6MWD) to improve risk identification. Patients with COPD performed pulmonary function, respiratory muscle strength, six-minute walk and cardiopulmonary exercise tests, and were followed over 42 months to analyze all-cause mortality. A total of 79 patients were included. The sample was mostly (91.1%) comprised of severe (n = 37) and very severe (n = 34) COPD, and 43 (54%) patients died during the follow-up period. Cut-points of ≤ 55 and ≤ 80 cmH2O for MIP and MEP, respectively, were associated with increased risk of death (log-rank p = 0.0001 for both MIP and MEP) in 42 months. Furthermore, MIP and MEP substantially improved the mortality risk assessment when combined with FEV1 (log-ranks p = 0.006 for MIP and p < 0.001 for MEP), V̇O2peak (log-rank: p < 0.001 for both MIP and MEP) and 6MWD (log-ranks: p = 0.005 for MIP; p = 0.015 for MEP). Thus, patients severely affected by COPD presenting MIP ≤ 55 and/or MEP ≤ 80 cmH2O are at increased risk of mortality. Furthermore, MIP and MEP substantially improve the mortality risk assessment when combined with FEV1, V̇O2peak and 6MWD in patients with COPD.

Computational antigenic insights into the novel NADC-34-like Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) isolate YC-2020.

In this computational study, we advanced the understanding of the antigenic properties of the NADC-34-like isolate of the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), named YC-2020, relevant in veterinary pathology. We utilized sequence comparison analyses of the M and N proteins, comparing them with those of NADC34, identifying substantial amino acid homology that allowed us to highlight conserved epitopes and crucial variants. Through the application of Clustal Omega for multiple sequence alignment and platforms like Vaxijen and AllerTOP for predicting antigenic and allergenic potential, our analyses revealed important insights into the conservation and variation of epitopes essential for the development of effective diagnostic tools and vaccines. Our findings, aligned with initial experimental studies, underscore the importance of these epitopes in the development of targeted immunodiagnostic platforms and significantly contribute to the management and control of PRRSV. However, further studies are required to validate the computational predictions of antigenicity for this new viral isolate. This approach underscores the potential of computational models to enable ongoing monitoring and control of PRRSV evolution in swine. While this study provides valuable insights into the antigenic properties of the novel PRRSV isolate YC-2020 through computational analysis, it is important to acknowledge the limitations inherent to in silico predictions, specifically, the absence of laboratory validation.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Validation of enzyme immunoassays for quantifying sex steroid hormones in tropical screech owls (Megascops choliba).

Androgens and estrogens are steroid hormones that regulate reproductive processes in both males and females. Monitoring plasma levels of these steroids or their metabolites present in feces, offers diagnostic support for assessing the reproductive status of animals. Immunoassays are commonly used methods for quantifying these hormones, but their protocols require species-specific validation to ensure reliability. The objective of this study was to perform analytically and biologically validation of enzyme immunoassay (EIA) kits for measuring testosterone (T), estradiol (E2), faecal androgen metabolites (fAM), and faecal estrogenic metabolites (fEM) in the tropical screech owl (Megascops choliba). Serum and fecal samples were collected from six adult females and six males both before and during breeding season, with males' gonadal activity assessed using electroejaculation (EE). The parallelism test confirmed the immunogenic similarity of the antigens in the estradiol and testosterone standards and the antigens in the serum samples and fecal extracts of M. choliba. Additionally, the EIA kits displayed nearly 100% recovery rates, and showed coefficients of variation ranging from 8% to 14% at the intra-assay level and from 10% to 16% at the inter-assay level, underscoring result reliability and consistency. In males, the highest serum T and fAM levels were recorded concurrently with the presence of spermatozoa in samples collected via EE. Although females did not exhibit oviposition events, significantly higher E2 and fEM levels were observed in August compared to May, suggesting potential seasonal variations in estrogenic hormone production. Fecal androgen and estrogen levels were significantly different between sexes in August, with males having higher fAM and females having higher fEM levels. Overall, the immunoassays validated in this study were found to be efficient in diagnosing reproductive activity in owls.

Additional effects using progestins in mares on levels of thyroid hormones and steroids in neonates.

The risk of pregnancy loss in mares leads to the use of exogenous hormones to help pregnancy maintenance. The objective was to evaluate the proportion of thyroid hormones and steroids in neonates, in the following postpartum period, born to mares fed with synthetic progesterone and to verify the existence of a correlation between the level of progesterone between mother and neonate. Twenty-seven mares and their foals were used. The animals were divided into 5 experimental groups: group 1 (control, without hormonal supplementation), group 2 (random samples fed to 120 days of pregnancy with long-term progesterone), group 3 (mares fed with short-term progesterone as of 280.º day of pregnancy), group 4 (mares fed with long-term progesterone as of 280.º day of pregnancy) and group 5 (mares fed with synthetic hormone [altrenogest] as of 280.º day of pregnancy). The animal's blood collection took place immediately after parturition for the hormonal measurement. The hormones measured in neonates were total T3, free T4, TSH, progesterone and cortisone. In mares, only levels of progesterone. The groups of neonates showed no difference on levels of total T3, free T4, TSH and progesterone. There was no difference on levels of progesterone in mares among the groups. Neonates from groups 4 and 5 had higher and lower cortisone levels, respectively. No neonate showed clinical change. There was also no correlation between levels of progesterone in mares and foals. Thus, hormonal supplementation with long-term progesterone as of 280 days of pregnancy leds to an increase in the neonate's cortisone levels, in the meantime, supplementation with altrenogest as of 280 days of pregnancy caused a decrease on cortisone levels in foals, despite clinical signs have not been observed on these animals.

Energy levels and lysine, calcium and phosphorus adjustments on broiler nutrient digestibility and performance.

Chicken broilers digestibility and performance fed with different ME levels, with and without adjustments of digestible lysine, calcium, and available phosphorus, were evaluated. For digestibility, 210 male Cobb 500 chicken broilers were used and distributed into a 3x2+1 factorial arrangement, with three ME levels (3050; 3125 and 3200 kcal/kg) with and without nutrient adjustment, plus one control treatment (2975 kcal ME/kg), totaling seven treatments including six repetitions with five birds into each repetition. For initial performance, 1120 birds were distributed randomly with eight replications within treatments and 20 birds for each replication. For final performance, 1008 chickens were distributed with eight replications and 18 birds for each replication. The DCDM and DCCP were improved (P<0.05) according to the increase of ME and the adjustment in dietary nutrients, as well as GE digestibility. The final performance showed no interaction (P>0.05) between energy and nutrient adjustment, but the increase in energy levels improved the feed conversion ratio (FCR=1.370). Increasing energy density with nutrient adjustment improves both nutrient utilization and bird performance.

Integrating Genomic and Chromosomal Data: A Cytogenetic Study of Transancistrus santarosensis (Loricariidae: Hypostominae) with Characterization of a ZZ/ZW Sex Chromosome System.

The plecos (Loricariidae) fish represent a great model for cytogenetic investigations due to their variety of karyotypes, including diploid and polyploid genomes, and different types of sex chromosomes. In this study we investigate Transancistrus santarosensis a rare loricariid endemic to Ecuador, integrating cytogenetic methods with specimens' molecular identification by mtDNA, to describe the the species karyotype. We aim to verify whether sex chromosomes are cytologically identifiable and if they are associated with the accumulation of repetitive sequences present in other species of the family. The analysis of the karyotype (2n = 54 chromosomes) excludes recent centric fusion and pericentromeric inversion and suggests the presence of a ZZ/ZW sex chromosome system at an early stage of differentiation: the W chromosome is degenerated but is not characterized by the presence of differential sex-specific repetitive DNAs. Data indicate that although T. santarosensis has retained the ancestral diploid number of Loricariidae, it accumulated heterochromatin and shows non-syntenic ribosomal genes localization, chromosomal traits considered apomorphic in the family.

Intramacrophage lipid accumulation compromises T cell responses and is associated with impaired drug therapy against visceral leishmaniasis.

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first-line anti-leishmanial drugs. Despite being pro-inflammatory, the in vitro generated uninfected lipid-laden macrophages (LLMs) or adipose-tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL-10 and lower IL-12p70 cytokines, inhibiting CD4+ T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti-leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high-fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4+ Th1 and CD8+ T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80+ CD11b+ CD11c+ macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first-line anti-leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host-protective immune response and reducing the efficacy of antiparasitic drug therapies.

Quantitative proteomic profile analysis of thyroid dysfunction effects on seminal vesicles and repercussions on male fertility.

Hypothyroidism and thyrotoxicosis are associated with male reproductive disorders, but little is known about the influence of the thyroid hormone milieu on seminal vesicle (SV) function and metabolism. In this sense, we investigated the effects of hypothyroidism and thyrotoxicosis induced in adulthood Wistar male rats on SV function and identified new thyroid hormone targets on male reproduction regulation using novel proteomic approaches. Hypothyroidism reduces SV size and seminal fluid volume, which are directly associated with low testosterone and estradiol levels, while thyrotoxicosis increases Esr2 and Dio1 expression in the SV. We found 116 differentially expressed proteins. Hypothyroidism reduces the expression of molecular protein markers related to sperm viability, capacitation and fertilization, protection against oxidative stress and energetic metabolism in SV, while it increases the expression of proteins related to tissue damage. In conclusion, thyroid dysfunction in the adult phase impairs several morphological, molecular and functional characteristics of SV.

Erratum: Evaluation of the characteristics of infection prevention and control programs and infection control committees in Brazilian hospitals: A countrywide cross-sectional study - CORRIGENDUM.

[This corrects the article DOI: 10.1017/ash.2023.136.].

Taxonomic revision of the Ophidion holbrookii Putnam, 1874 (Ophidiiformes: Ophidiidae) species complex, with description of a new species from Brazil.

This study integrates morphological and molecular data to redefine the taxonomic limits of Ophidion holbrookii, as well as its geographic ranges, with the description of a new species from the eastern and southeastern coast of Brazil, South America. Ophidion zavalai n. sp. is described based on variations related to ontogeny and sexual development of swim bladder and sonic apparatus, which are likely important traits for species recognition. The description of O. zavalai n. sp. and the redefinition of distribution limits of O. holbrookii corroborate the existence of different complex species in the western Atlantic, revealing important gaps of knowledge regarding morphological variation and species habits. Ophidion zavalai n. sp. is the first species of Ophidion described from the southwestern Atlantic Ocean and contributes to evidence of a distinct coastal fauna in Brazil and surrounding areas of Argentina province.

Hospital at Home: A New Model of Home Care in Brazil / Hospitalización a domicilio: un nuevo modelo de atención domiciliaria en Brasil

Introducción: Home Care (HC) es directamente responsable por la reducción de la demanda de camas hospitalarias en Brasil. El modelo brasileño de hospitalización domiciliaria en el sector privado se basó en la atención continua de enfermería durante los últimos 30 años sin revisión adicional. Objetivos: Descubrir si el modelo brasileño de hospitalización domiciliaria se alinea con los diferentes modelos HC vigen-tes en todo el mundo, analizar sus limitaciones y desafíos y proponer un nuevo modelo rentable de atención domiciliaria en Brasil llamado Hospital at Home (HaH). Método: Revisión de artículos publicados en bases de datos, actas de congresos, guías de práctica clínica y regulaciones guberna-mentales entre 2006-2022. Se analizaron 920 pacientes atendidos en la modalidad de Hospitalización Domiciliaria por una empresa privada de HC en Brasil en noviembre de 2022. Resultados: Los modelos de HC europeos y norteamericanos no se basan en cuidados de enfermería continuos. Si analizó la elegibilidad de 920 pacientes atendidos en la modalidad de Hospitalización Domiciliaria por una empresa privada de HC en Brasil en noviembre de 2022 para inclusión en el nuevo modelo HaH, propuesto con 10 pilares basados en evidencia donde un equipo multidisciplinario es ayudado por enfoque de participación del socio de atención y una estrategia de gestión clínica basada en análisis de datos apoyados en recursos digitales de salud. Conclusiones: Creemos que el modelo HaH remodelará la hospitalización domiciliaria en Brasil, establecerá las bases para la atención domiciliaria basada en el valor y contribuirá a la sostenibilidad de la HC brasileña. (AU)

Introduction: Home Care (HC) is directly responsible for reducing the demand for hospital beds in Brazil. Brazilian Home Hospitalization model in the private sector was built on continuous nursing care for the last 30-years without further review. Objectives: Find if Brazilian Home Hospitalization model aligns with the different HC models in effect around the world, evaluate its limitations and challenges and propose a new cost-effective model of domiciliary care in Brazil called Hospital at Home (HaH). Method: Review of articles published in data bases, conference proceedings, clinical practice guidelines, and government regulations between 2006-2022. 920 patients receiving care in the Home Hospitalization modality by a private HC company in Brazil were analyzed in November 2022. Results: European and North American HC models are not built on continuous nursing care. 920 patients receiving care in the Home Hospitalization modality by a private HC company in Brazil had their eligibility assessed in November 2022 to be included in the new HaH model, proposed with 10 evidence-based pillars where a multidisciplinary team is aided by a care partner engagement approach and a clinical management strategy based on data analysis supported by digital health resources. Conclusions: We believe the HaH model will reshape home hospitalization in Brazil, set up the groundwork for value-based Home Care and contribute to the sustainability of Brazilian HC. (AU)

Phylogenomics, evolution of trophic traits and divergence times of hemiodontid fishes (Ostariophysi: Characiformes).

The South American characiform family Hemiodontidae comprises five genera and 34 species. The family lacks comprehensive phylogenetic hypotheses resolving its species relationships. The studies that addressed these questions exhibited a narrow taxon sampling or used single-locus markers. Herein we surveyed hundreds of ultraconserved elements (UCEs) loci to provide the first molecular phylogenetic hypothesis and divergence time estimates for hemiodontids encompassing all its genera and most species (27 of the 34 valid species). We also tracked the history of the protractile upper jaw in the genera Argonectes and Bivibranchia across the recovered phylogenies through ancestral state reconstruction. Our results corroborate the monophyly of Hemiodontidae and the genera Argonectes and Bivibranchia in all phylogenetic methods with maximum clade support. The genera Anodus and Hemiodus were not monophyletic because Anodus elongatus was sister to the monotypic Micromischodus instead of A. orinocensis, and H. immaculatus did not form a clade with its other congeners, but instead was sister to the clade including Anodus and Micromischodus. All remaining species of Hemiodus were placed together into a monophyletic group, where they were arranged into four major subclades. The relationship in the family is summarised as: (Bivibranchia, (Argonectes, ((H. immaculatus, (Anodus, Micromischodus)), Hemiodus clade))), in discordance with the morphological phylogeny that placed all genera monophyletic and resolved the family as: ((Anodus, Micromischodus), (Hemiodus, (Argonectes, Bivibranchia))). The origin of Hemiodontidae was estimated from the Late Cretaceous to the Middle Paleogene, with the mean age in the Paleocene, while the origin of most hemiodontid genera except Bivibranchia occurred in the Miocene. Unordered parsimony and likelihood reconstruction indicates that Argonectes and Bivibranchia developed their protractile upper jaw independently.

Haemodynamic support for paediatric septic shock: a global perspective.

Septic shock is a leading cause of hospitalisation, morbidity, and mortality for children worldwide. In 2020, the paediatric Surviving Sepsis Campaign (SSC) issued evidence-based recommendations for clinicians caring for children with septic shock and sepsis-associated organ dysfunction based on the evidence available at the time. There are now more trials from multiple settings, including low-income and middle-income countries (LMICs), addressing optimal fluid choice and amount, selection and timing of vasoactive infusions, and optimal monitoring and therapeutic endpoints. In response to developments in adult critical care to trial personalised haemodynamic management algorithms, it is timely to critically reassess the current state of applying SSC guidelines in LMIC settings. In this Viewpoint, we briefly outline the challenges to improve sepsis care in LMICs and then discuss three key concepts that are relevant to management of children with septic shock around the world, especially in LMICs. These concepts include uncertainties surrounding the early recognition of paediatric septic shock, choices for initial haemodynamic support, and titration of ongoing resuscitation to therapeutic endpoints. Specifically, given the evolving understanding of clinical phenotypes, we focus on the controversies surrounding the concepts of early fluid resuscitation and vasoactive agent use, including insights gained from experience in LMICs and high-income countries. We outline the key components of sepsis management that are both globally relevant and translatable to low-resource settings, with a view to open the conversation to the large variety of treatment pathways, especially in LMICs. We emphasise the role of simple and easily available monitoring tools to apply the SSC guidelines and to tailor individualised support to the patient's cardiovascular physiology.

Predictors of cardiopulmonary exercise testing in COPD patients according to the Weber classification.

BACKGROUND: Weber classification stratifies cardiac patients based on peak oxygen consumption (V̇O2), the gold-standard measure of exercise capacity. OBJECTIVE: To determine if Weber classification is a useful tool to discriminate clinical phenotypes in COPD patients and to evaluate if disease severity and other clinical measures can predict V̇O2peak. METHODS: Three hundred and six COPD patients underwent cardiopulmonary exercise testing (CPX) and were divided according to Weber class: 1) Weber A (n = 34); 2) Weber B (n = 88); 3) Weber C (n = 138); and 4) Weber D (n = 46). RESULTS: Weber class D patients demonstrated a reduced V̇O2 peak, heart rate (HR), minute ventilation (V̇E), oxygen (O2) pulse, circulatory power (CP), oxygen uptake efficiency slope (OUES), oxygen saturation (SpO2%), delta (Δ)HR and ΔSpO2 when compared to Weber A and B (p<0.05). Moreover, Dyspnea and the V̇E/carbon dioxide production (V̇CO2) slope were higher in Weber D compared with Weber C and A (p<0.001). Hierarchical regression analysis demonstrated significant predictors of V̇O2peak (R2= 0.131; Adj R 2 = 1.25), including HR (ß=0.5757; t = 5.7; P<0.001) and forced expiratory volume in one second (FEV1) (ß=0.119; t = 2.16; P<0.03). Among the Weber C + D groups, predictors of V̇O2peak (R = 0.78; R2= 0.60; Adj R2 =0.59), dyspnea (ß=0.076; t = 1.111; P<0.27) and maximal voluntary ventilation (MVV) (ß=0.75; t = 1.14; P<0.00). CONCLUSION: Weber classification may be a useful tool to stratify cardiorespiratory fitness in COPD patients. Other clinical measures may be useful in predicting peak V̇O2 in mild-to-severe COPD, moreover different phenotypes may be important tool to improve physical capacity of chronic disease patients.