RESUMO
INTRODUCTION: The incidence of pediatric Wilms' tumor (WT) is high in Africa, though patients abandon treatment after initial diagnosis. We sought to identify factors associated with WT treatment abandonment in Uganda. METHODS: A cohort study of patients < 18 years with WT in a Ugandan national referral hospital examined clinical and treatment outcomes data, comparing children whose families adhered to and abandoned treatment. Abandonment was defined as the inability to complete neoadjuvant chemotherapy and surgery for patients with unilateral WT and definitive chemotherapy for patients with bilateral WT. Patient factors were assessed via bivariate logistic regression. RESULTS: 137 WT patients were included from 2012 to 2017. The mean age was 3.9 years, 71% (n = 98) were stage III or higher. After diagnosis, 86% (n = 118) started neoadjuvant chemotherapy, 59% (n = 82) completed neoadjuvant therapy, and 55% (n = 75) adhered to treatment through surgery. Treatment abandonment was associated with poor chemotherapy response (odds ratio [OR] 4.70, 95% confidence interval [CI] 1.30-17.0) and tumor size > 25 cm (OR 2.67, 95% CI 1.05-6.81). CONCLUSIONS: Children with WT in Uganda frequently abandon care during neoadjuvant therapy, particularly those with large tumors with poor response. Further investigation into the factors that influence treatment abandonment and a deeper understanding of tumor biology are needed to improve treatment adherence of children with WT in Uganda.
Assuntos
Neoplasias Renais , Terapia Neoadjuvante , Tumor de Wilms , Humanos , Uganda , Tumor de Wilms/terapia , Tumor de Wilms/cirurgia , Masculino , Feminino , Neoplasias Renais/terapia , Pré-Escolar , Criança , Terapia Neoadjuvante/estatística & dados numéricos , Lactente , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Estudos Retrospectivos , Encaminhamento e Consulta/estatística & dados numéricos , Estudos de CoortesRESUMO
Breeding animals able to effectively respond to stress could be a long-term, sustainable, and affordable strategy to improve resilience and welfare in livestock systems. In the present study, the concentrations of 29 plasma biomarkers were used as candidate endophenotypes for metabolic stress response in single-SNP, gene- and haplotype-based GWAS using 739 healthy lactating Italian Holstein cows and 88,271 variants. Significant genetic associations were found in all the 3 GWAS approaches for plasma γ-glutamyl transferase concentration on BTA17, for paraoxonase on BTA4, and for alkaline phosphatase and zinc on BTA2. On these chromosomes, single-SNP and gene-based chromosome-wide association studies were performed, confirming GWAS findings. The signals identified for paraoxonase, γ-glutamyl transferase, and alkaline phosphatase were in proximity of the genes coding for them. The heritability of these 4 biomarkers ranged from moderate to high (from 0.39 to 0.54). Plasma biomarkers are known to undergo large changes in concentration during metabolic stress in the transition period, with an inter-individual variability in the rate of change and recovery time. Genetics may account in part for these differences. To assess this, we studied a subset of 139 periparturient cows homozygous at 3 SNPs known to be respectively associated with concentration of plasma ceruloplasmin, paraoxonase and γ-glutamyl transferase. We compared the immune-metabolic profile measured in plasma at -7, +5 and +30 d relative to calving between groups of opposite homozygotes. A significant effect of the genotype was found on paraoxonase and γ-glutamyl transferase plasma concentration at all the 3 time points. No evidence for genotype effect was detected for ceruloplasmin. Understanding the genetic control underlying metabolic stress response may suggest new approaches to foster resilience in dairy cows.
RESUMO
Spodoptera frugiperda (J.E. Smith), fall armyworm (FAW), a polyphagous Noctuid pest, was first reported in Uganda in 2016. Farmers were trained to identify and manage the pest, but there was a lack of information on farmer knowledge, perceptions and practices deployed to control it. Therefore, we conducted a survey to assess maize farmers' knowledge, perceptions and management of the pest during the invasion. We interviewed 1,289 maize farmers from 10 maize-growing agro-ecological zones (AEZ) of Uganda using well-structured questionnaires. The data were analyzed using R version 4.2.3. The respondents faced many constraints, including pests, drought, poor soils and labor constraints. Among the pests, FAW was ranked by most (85%) of the respondents as the number one pest problem in maize, and some farmers reported having noticed it way back in 2014. By 2018, more than 90% of the farmers had seen or heard about FAW, and about 80% saw FAW in their fields. The most common FAW symptoms reported by maize farmers were windowing, near tunnel damage, and holes on the cobs. The developmental stages of FAW identified by farmers included eggs (10%), young larvae (78.7%), mature larvae (73.5%) and adult moths (6.7%). Insecticides were the major control tactic, although some farmers used plant extracts, hand-picking, sand, and ash. Farmers sourced information on FAW from various sources, including fellow farmers, radio/TV, extension agents, input dealers, print media, research and NGO extension. There is a need to package clear and uniform information for the farmers and to develop and promote a sustainable solution for FAW management, including harnessing biological control and cultural practices.
RESUMO
Different tests measure text comprehension, including the cloze gap-filling test, often used for language learning. Different studies hypothesized cognitive strategies in this type of test and their relationship with working memory and performance. However, no study investigated the cloze test, working memory, and possible cognitive strategies, while performing the test. Therefore, this study aimed to identify cognitive visual strategies in the cloze test by applying an unsupervised algorithm and to analyze the relationship between these strategies with working memory and performance in the cloze test. Our sample consisted of 51 university students, the largest sample in studies of cognitive strategies with cloze tests. Participants answered an 11-item cloze test in a computer with eye-tracking, a verbal working memory test, and a visuospatial working memory test. Our analysis of participants' scanpath identified two main strategies: one with fewer toggles between text and word bank and fewer fixations than the other one, indicating the existence of a global strategy. Furthermore, a model predicting the efficiency of participants in the cloze test found that item complexity, using a global strategy, and higher scores of working memory were the most significant predictors. These results confirm the hypothesis of a global strategy being related to successfully achieving higher-order reading processes.
Assuntos
Compreensão , Memória de Curto Prazo , Leitura , Humanos , Memória de Curto Prazo/fisiologia , Feminino , Masculino , Adulto Jovem , Adulto , Compreensão/fisiologia , Tecnologia de Rastreamento Ocular , AdolescenteRESUMO
Cyanobacterial blooms present substantial challenges to managers and threaten ecological and public health. Although the majority of cyanobacterial bloom research and management focuses on factors that control bloom initiation, duration, toxicity, and geographical extent, relatively little research focuses on the role of loss processes in blooms and how these processes are regulated. Here, we define a loss process in terms of population dynamics as any process that removes cells from a population, thereby decelerating or reducing the development and extent of blooms. We review abiotic (e.g., hydraulic flushing and oxidative stress/UV light) and biotic factors (e.g., allelopathic compounds, infections, grazing, and resting cells/programmed cell death) known to govern bloom loss. We found that the dominant loss processes depend on several system specific factors including cyanobacterial genera-specific traits, in situ physicochemical conditions, and the microbial, phytoplankton, and consumer community composition. We also address loss processes in the context of bloom management and discuss perspectives and challenges in predicting how a changing climate may directly and indirectly affect loss processes on blooms. A deeper understanding of bloom loss processes and their underlying mechanisms may help to mitigate the negative consequences of cyanobacterial blooms and improve current management strategies.
Assuntos
Cianobactérias , Proliferação Nociva de Algas , Cianobactérias/fisiologiaRESUMO
The cytochrome P450 family of heme metalloenzymes (CYPs) catalyse important biological monooxygenation reactions. Mycobacterium marinum contains a gene encoding a CYP105Q4 enzyme of unknown function. Other members of the CYP105 CYP family have key roles in bacterial metabolism including the synthesis of secondary metabolites. We produced and purified the cytochrome P450 enzyme CYP105Q4 to enable its characterization. Several nitrogen-donor atom-containing ligands were found to bind to CYP105Q4 generating type II changes in the UV-vis absorbance spectrum. Based on the UV-vis absorbance spectra none of the potential substrate ligands we tested with CYP105Q4 were able to displace the sixth distal aqua ligand from the heme, though there was evidence for binding of oleic acid and amphotericin B. The crystal structure of CYP105Q4 in the substrate-free form was determined in an open conformation. A computational structural similarity search (Dali) was used to find the most closely related characterized relatives within the CYP105 family. The structure of CYP105Q4 enzyme was compared to the GfsF CYP enzyme from Streptomyces graminofaciens which is involved in the biosynthesis of a macrolide polyketide. This structural comparison to GfsF revealed conformational changes in the helices and loops near the entrance to the substrate access channel. A disordered B/C loop region, usually involved in substrate recognition, was also observed.
Assuntos
Mycobacterium marinum , Mycobacterium marinum/genética , Mycobacterium marinum/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Estrutura Secundária de Proteína , Macrolídeos/química , Macrolídeos/metabolismo , Heme/química , Cristalografia por Raios XRESUMO
BACKGROUND: Rhipicephalus (Boophilus) microplus (Canestrini, 1888), the Asian blue tick, is a highly invasive and adaptable ectoparasite. This tick species has successfully established itself in most regions of the world, with movement of cattle being a major driver for its spread. In the recent past, R. microplus ticks have been reported in three districts of Uganda. Information on its spread and distribution are vital in deepening our understanding of the ecological scenarios that lead to tick persistence and in the formulation of control strategies. This is especially important in the cattle-dense districts. METHODS: We randomly collected tick specimens from 1,461cattle spread across seven cattle dense districts located in the Central, Karamoja and West Nile regions of Uganda from January to September 2020. The ticks were identified using standard morpho-taxonomic keys and the R. microplus tick species identities were confirmed by sequencing of the ITS2 region, 12S rRNA and 16S rRNA genes and phylogenetic analyses. RESULTS: Adult ticks (n = 13,019) were collected from 1,461 cattle. Seventeen tick species were identified based on morpho-taxonomic keys and the majority (47.4%; n=6184) of these were R. appendiculatus. In total, 257 R. microplus ticks were found infesting cattle in 18 study sites in the districts of Amudat, Kaabong, Napak (Karamoja region) and Arua (West Nile region). The identity of R. microplus was confirmed using molecular technics. No R. microplus tick was recorded in the districts of Lyantonde and Nakaseke (Central region). Arua district accounted for 82.1% (n=211) of the R. microplus ticks recorded followed by Napak district at 16.3% (n=42), while Amudat and Kaabong districts accounted for 1.5% (n=4). Rhipicephalus microplus and R. decoloratus co-existed in 6 of the 13 study sites in Arua district, while in another 6 study sites, no R. decoloratus was recorded. In the Karamoja region districts R. decoloratus co-existed with R.microplus. Of the total 618 ticks belonging to four species of the subgenus Boophilus recorded in this study, R. decoloratus accounted for 50.04% (n=334), followed by R. microplus at 41.58% (n=257), R. geigyi at 2.75% (n=17) and R. annulatus at 1.61% (n=10). In the districts of Amudat, Kaabong and Napak, R. decoloratus was more dominant (76.1%; n=179) of the three Rhipicephalus (Boophilus) tick species recorded, followed by R. microplus (19.5%; n=46) and R. geigyi (4.2%; n=10). Contrariwise, R. microplus was more dominant (84%; n=211) in Arua district followed by R. decoloratus (10.7%; n=27), R. annulatus (3.9%; n=10) and R. geigyi (1.1%; n=3). Phylogenetic analyses of the ITS2 region, 12S rRNA and 16S rRNA genes revealed subgrouping of the obtained sequences with the previously published R. microplus sequences from other parts of the world. CONCLUSION: Rhipicephalus microplus ticks were found infesting cattle in four districts of Uganda. The inability to find R. decoloratus, an indigenous tick, from six sites in the district of Arua is suggestive of its replacement by R. microplus. Rhipicephalus microplus negatively affects livestock production, and therefore, there is a need to determine its distribution and to deepen the understanding of the ecological factors that lead to its spread and persistence in an area.
Assuntos
Doenças dos Bovinos , Rhipicephalus , Infestações por Carrapato , Bovinos , Animais , RNA Ribossômico 16S/genética , Infestações por Carrapato/epidemiologia , Infestações por Carrapato/veterinária , Uganda/epidemiologia , Filogenia , Controle de Ácaros e Carrapatos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/parasitologiaRESUMO
The Mediterranean fruit fly (medfly) (Ceratitis capitata, Diptera: Tephritidae), is an extremely polyphagous pest that threatens the fruit production and trading industry worldwide. Monitoring C. capitata populations and analysing its dynamics and phenology is considered of outmost importance for designing and implementing sound management approaches. The aim of this study was to investigate the factors regulating the population dynamics of the C. capitata in a coastal and semi-mountainous area. We focused on effects of topography (e.g. elevation), host presence and seasonal patterns of ripening on the phenological patterns considering data collected in 2008. The experimental area is characterized by mixed fruit orchards, and Mediterranean climate with mild winters. Two trap types were used for population monitoring. The female targeted McPhail type and the male targeted Jackson type. Traps were placed in farms located at different elevations and landscape morphology (coastal and semi-mountainous areas). The main crops included citrus, apples, peaches, plums, pears, figs, quinces and apricots. Adult captures were first recorded in May, peaked in mid-summer and mid-autumn and almost ceased at the end of the season (January 2008). Captures in the coastal areas preceded that of highlands by 15 days. Most of the adults detected during the fruit ripening of late stone fruit cultivars (first peak) and citrus (second peak). The probability of capturing the first adults preceded almost three weeks the peak of adult captures either considering the elevation or host focus analyses. The results provide valuable information on the seasonal population trend of C. capitata in mixed fruit Mediterranean orchards and can support the set-up of IPM systems in areas with various landscapes and different hosts throughout the fruit growing season.
Assuntos
Ceratitis capitata , Citrus , Malus , Tephritidae , Feminino , Masculino , Animais , Ceratitis capitata/fisiologia , Estações do Ano , ClimaRESUMO
Shallow lake ecosystems are particularly prone to disturbances such as pulsed dissolved organic matter (allochthonous-DOM; hereafter allo-DOM) loadings from catchments. However, the effects of allo-DOM with contrasting quality (in addition to quantity) on the planktonic communities of microbial loop are poorly understood. To determine the impact of different qualities of pulsed allo-DOM disturbance on the coupling between bacteria and ciliates, we conducted a mesocosm experiment with two different allo-DOM sources added to mesocosms in a single-pulse disturbance event: Alder tree leaf extract, a more labile (L) source and HuminFeed® (HF), a more recalcitrant source. Allo-DOM sources were used as separate treatments and in combination (HFL) relative to the control without allo-DOM additions (C). Our results indicate that the quality of allo-DOM was a major regulator of planktonic microbial community biomass and/or composition through which both bottom-up and top-down forces were involved. Bacteria biomass showed significant nonlinear responses in L and HFL with initial increases followed by decreases to pre-pulse conditions. Ciliate biomass was significantly higher in L compared to all other treatments. In terms of composition, bacterivore ciliate abundance was significantly higher in both L and HFL treatments, mainly driven by the bacterial biomass increase in the same treatments. GAMM models showed negative interaction between metazoan zooplankton biomass and ciliates, but only in the L treatment, indicating top-down control on ciliates. Ecosystem stability analyses revealed overperformance, high resilience and full recovery of bacteria in the HFL and L treatments, while ciliates showed significant shift in compositional stability in HFL and L with incomplete taxonomic recovery. Our study highlights the importance of allo-DOM quality shaping the response within the microbial loop not only through triggering different scenarios in biomass, but also the community composition, stability, and species interactions (top-down and bottom-up) in bacteria and plankton.
Assuntos
Ecossistema , Lagos , Animais , Lagos/microbiologia , Matéria Orgânica Dissolvida , Bactérias , Biomassa , PlânctonRESUMO
BACKGROUND: Gastroschisis causes near complete mortality in low-income countries (LICs). This study seeks to understand the impact of bedside bowel reduction and silo placement, and protocolized resuscitation on gastroschisis outcomes in LICs. METHODS: We conducted a retrospective cohort study of gastroschisis patients at a tertiary referral center in Kampala, Uganda. Multiple approaches for bedside application of bowel coverage devices and delayed closure were used: sutured urine bags (2017-2018), improvised silos using wound protectors (2020-2021), and spring-loaded silos (2022). Total parental nutrition (TPN) was not available; however, with the use of improvised silos, a protocol was implemented to include protocolized resuscitation and early enteral feeding. Risk ratios (RR) for mortality were calculated in comparison to historic controls from 2014. RESULTS: 368 patients were included: 42 historic controls, 7 primary closures, 81 sutured urine bags, 133 improvised silos and 105 spring-loaded silos. No differences were found in sex (p = 0.31), days to presentation (p = 0.84), and distance traveled to the tertiary hospital (p = 0.16). Following the introduction of bowel coverage methods, the proportion of infants that survived to discharge increased from 2% to 16-29%. In comparison to historic controls, the risk of mortality significantly decreased: sutured urine bags 0.65 (95%CI: 0.52-0.80), improvised silo 0.76 (0.66-0.87), and spring-loaded silo 0.65 (0.56-0.76). CONCLUSION: Bedside application of bowel coverage and protocolization decreases the risk of death for infants with gastroschisis, even in the absence of TPN. Further efforts to expand supply of low-cost silos in LICs would significantly decrease the mortality associated with gastroschisis in this setting. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: III (Retrospective Comparative Study).
Assuntos
Gastrosquise , Lactente , Humanos , Gastrosquise/cirurgia , Estudos Retrospectivos , Uganda/epidemiologia , Resultado do Tratamento , IntestinosRESUMO
A common pathological denominator of various neurodegenerative diseases is the accumulation of protein aggregates. Neurotoxic effects are caused by a loss of the physiological activity of the aggregating protein and/or a gain of toxic function of the misfolded protein conformers. In transmissible spongiform encephalopathies or prion diseases, neurodegeneration is caused by aberrantly folded isoforms of the prion protein (PrP). However, it is poorly understood how pathogenic PrP conformers interfere with neuronal viability. Employing in vitro approaches, cell culture, animal models and patients' brain samples, we show that misfolded PrP can induce aggregation and inactivation of TAR DNA-binding protein-43 (TDP-43). Purified PrP aggregates interact with TDP-43 in vitro and in cells and induce the conversion of soluble TDP-43 into non-dynamic protein assemblies. Similarly, mislocalized PrP conformers in the cytosol bind to and sequester TDP-43 in cytosolic aggregates. As a consequence, TDP-43-dependent splicing activity in the nucleus is significantly decreased, leading to altered protein expression in cells with cytosolic PrP aggregates. Finally, we present evidence for cytosolic TDP-43 aggregates in neurons of transgenic flies expressing mammalian PrP and Creutzfeldt-Jakob disease patients. Our study identified a novel mechanism of how aberrant PrP conformers impair physiological pathways by cross-seeding.
Assuntos
Síndrome de Creutzfeldt-Jakob , Doenças Priônicas , Príons , Animais , Humanos , Proteínas de Ligação a DNA , Mamíferos/metabolismo , Doenças Priônicas/metabolismo , Proteínas Priônicas , Príons/metabolismoRESUMO
Lakes worldwide are affected by multiple stressors, including climate change. This includes massive loading of both nutrients and humic substances to lakes during extreme weather events, which also may disrupt thermal stratification. Since multi-stressor effects vary widely in space and time, their combined ecological impacts remain difficult to predict. Therefore, we combined two consecutive large enclosure experiments with a comprehensive time-series and a broad-scale field survey to unravel the combined effects of storm-induced lake browning, nutrient enrichment and deep mixing on phytoplankton communities, focusing particularly on potentially toxic cyanobacterial blooms. The experimental results revealed that browning counteracted the stimulating effect of nutrients on phytoplankton and caused a shift from phototrophic cyanobacteria and chlorophytes to mixotrophic cryptophytes. Light limitation by browning was identified as the likely mechanism underlying this response. Deep-mixing increased microcystin concentrations in clear nutrient-enriched enclosures, caused by upwelling of a metalimnetic Planktothrix rubescens population. Monitoring data from a 25-year time-series of a eutrophic lake and from 588 northern European lakes corroborate the experimental results: Browning suppresses cyanobacteria in terms of both biovolume and proportion of the total phytoplankton biovolume. Both the experimental and observational results indicated a lower total phosphorus threshold for cyanobacterial bloom development in clearwater lakes (10-20 µg P L-1 ) than in humic lakes (20-30 µg P L-1 ). This finding provides management guidance for lakes receiving more nutrients and humic substances due to more frequent extreme weather events.
Assuntos
Cianobactérias , Fitoplâncton , Lagos/microbiologia , Substâncias Húmicas , Eutrofização , Nutrientes , Fósforo/análise , ChinaRESUMO
Irritant diaper dermatitis is a common dermatologic problem among infants and young children. Severe erosive presentations, although uncommon, are diagnostically challenging and can mimic non-accidental trauma (NAT). Diagnosing inflicted injury and NAT where it does not exist can cause parental distress, yet failing to diagnose inflicted injury and NAT can result in re-injury. We describe three cases of severe erosive diaper dermatitis in pediatric patients aged 2-6 years that were initially concerning for inflicted scald burn or neglect.
Assuntos
Queimaduras , Maus-Tratos Infantis , Dermatite das Fraldas , Lactente , Humanos , Criança , Pré-Escolar , Dermatite das Fraldas/diagnóstico , Dermatite das Fraldas/etiologia , Queimaduras/complicações , Maus-Tratos Infantis/diagnóstico , Diagnóstico Diferencial , PaisRESUMO
In recent years, there has been a growing demand for minimally processed foods that offer health benefits and premium sensory characteristics. This trend has led to increased consumption of virgin (VOs) and cold-pressed (CPOs) oils, which are rich sources of bioactive substances. To meet consumer needs for new oil products conferring multi-functional properties over a longer storage period, the scientific community has been revisiting traditional enrichment practices while exploring novel fortification technologies. In the last four years, the interest has been growing faster; an ascending number of annually published studies are about the addition of different plant materials, agri-food by-products, or wastes (intact or extracts) to VOs and CPOs using traditional or innovative fortification processes. Considering this trend, the present review aims to provide an overview and summarize the key findings from relevant papers that were retrieved from extensively searched databases. Our meta-analysis focuses on exposing the most recent trends regarding the exploitation of VOs and CPOs as substrates, the fortification agents and their form of use, as well as the fortification technologies employed. The review critically discusses possible health claim and labeling issues and highlights some chemical and microbial safety concerns along with authenticity issues and gaps in quality specifications that manufacturers have yet to address. All these aspects are examined from the perspective of developing new oil products with well-balanced techno-, senso- and bio-functional characteristics.
Assuntos
Óleos de Plantas , Verduras , Óleos de Plantas/química , Manipulação de Alimentos , Oxirredução , Estresse OxidativoRESUMO
One-third of newly diagnosed adult acute myeloid leukaemia (AML) carry FLT3 mutations, which frequently occur together with nucleophosmin (NPM1) mutations and are associated with worse prognosis. FLT3 inhibitors are widely used in clinics with limitations due to drug resistance. AML cells carrying FLT3 mutations in both mouse models and patients present low expression of GATA1, a gene involved in haematopoietic changes preceding AML. Here, we show that FLT3 inhibition induces cellular responses and restores the GATA1 pathway and functions in NPM1/FLT3-ITD mutated AML, thus providing a new mechanism of action for this drug.
RESUMO
Background: Autoimmune gastritis (AIG), characterized with the presence of anti-parietal-cell antibodies (APCA), is a risk factor for gastric cancer. However, AIG may go underdiagnosed, especially in the case of H. pylori infection and the presence of gastric precancerous lesions (GPL), due to the ambiguous pathology and delayed symptom onset. Aim: Investigate the prevalence and characteristics of AIG in GPL patients. Methods: Prevalence of AIG was determined with the presence of APCA in patients with GPL (n = 256) and the control group (n = 70). Pathological characteristics and levels of gastrin 17 (G17), pepsinogen (PG) I and II and anti-Helicobacter pylori IgG were assessed in GPL cases, and the severity of intestinal metaplasia and gastric atrophy was scored by expert pathologists. Results: APCA positivity was observed in 18% of cases vs. 7% of controls (p = 0.033). Only 3/256 patients were previously diagnosed with AIG. The presence of APCA was associated with corpus-limited and extended GPL. A receiver operating curve analysis demonstrated that the G17 and PGI/II ratio could identify APCA-positive patients within GPL cases (AUC: 0.884). Conclusions: The prevalence of AIG is higher in patients with GPL but goes undiagnosed. Using G17 and PG I/II as diagnostic markers can help to identify patients with AIG and improve surveillance programs for patients with GPL.
RESUMO
BACKGROUND: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.