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COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3–0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59–1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61–8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation. Coalition COVID-19 Brazil, Bayer SA.

BackgroundMechanical thrombectomy (MT) has become standard for large vessel occlusions, but rates of complete recanalization are suboptimal. Previous reports correlated radiographic signs with clot composition and a better response to specific techniques. Therefore, understanding clot composition may allow improved outcomes.MethodsClinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin-eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of first-pass effect (FPE, modified Thrombolysis in Cerebral Infarction 2c/3) and the number of passes.ResultsA total of 1430 patients of mean±SD age 68.4±13.5 years (median (IQR) baseline National Institutes of Health Stroke Scale score 17.2 (10.5–23), IV-tPA use 36%, stent-retrievers (SR) 27%, contact aspiration (CA) 27%, combined SR+CA 43%) were included. The median (IQR) number of passes was 1 (1–2). FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for red blood cell (RBC)-rich (P<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes than RBC-rich and mixed clots (median 2 and 1.5 vs 1, respectively; P=0.02). CA showed a trend towards a higher number of passes with fibrin-rich clots (2 vs 1; P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots.ConclusionsDespite the lack of correlation between clot histology and FPE, our study adds to the growing evidence supporting the notion that clot composition influences recanalization treatment strategy outcomes.

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

Abstract Background and aims Idiopathic intracranial hypertension (IIH) is increasingly recognized as a venous cerebrovascular disorder, frequently associated with transverse sinus stenosis (TSS). Venous sinus stenting (VSS) has been adopted in selected patients to restore venous outflow; however, its impact on intracranial physiological dynamics remains incompletely understood. Intracranial compliance (IC), reflecting the pressure–volume relationship of the intracranial compartment, may provide insight into cerebrovascular adaptation in venous outflow impairment. We aimed to compare non-invasive IC parameters in IIH patients with TSS treated with best medical therapy (BMT) versus VSS. Methods We conducted a single-center observational study including adults (≥18 years) with IIH and TSS between 2020 and 2022. Patients were managed with BMT or VSS according to clinical indication. IC was assessed using Brain4care®-derived intracranial pressure waveform metrics, including the P2/P1 ratio and time-to-peak (TTP), obtained in supine and seated positions. Continuous variables were expressed as mean ± SD or median (IQR). Statistical analyses were performed using R, with p<0.05 considered significant. Results Among 158 screened patients, 66 were included (49 medical therapy; 17 VSS). The VSS group was older, had lower body mass index, and, as mostly asymptomatic, required lower doses of acetazolamide and topiramate after intervention. No significant differences were observed between groups in P2/P1 ratio or TTP in either body position. Conclusions In IIH associated with TSS, non-invasive assessment revealed similar IC patterns after BMT and VSS. These findings suggest that IC may represent a stable physiological marker of venous cerebrovascular adaptation, complementing clinical outcomes in IIH management. Conflict of interest Lorena Souza Viana, Fabiano Moulin de Moraes, Sandro Luiz de Andrade Matas, Gisele Sampaio Silva: nothing to disclose.

Mead is an alcoholic beverage obtained by fermenting a dilute solution of honey with yeasts. The aim of this study was to develop and evaluate a probiotic mead from the co-fermentation of water kefir and Sacharomyces boulardii . According to the results, the combination of 10 g/L of water kefir grains and 0.75 g/L of S. boulardii , with a fermentation time of 9 days, produced a probiotic mead with a viable cell count of more than 8 Log 10 CFU/mL of S. boulardii and also for lactic acid bacteria, respectively. S. boulardii and lactic acid bacteria showed counts of over 6 Log 10 CFU/mL after gastrointestinal simulation in vitro, with a survival rate of over 70%. Probiotic mead has good luminosity (L*), a tendency to yellow color and the presence of total phenolic compounds and antioxidants. In conclusion, the co-fermentation of water kefir and S. boulardii has potential for the development of probiotic mead.

This study analyzes the eating behavior and factors associated with the presence of disordered eating attitudes in patients undergoing bariatric surgery. It is a cross-sectional, descriptive, and analytical study conducted at a hospital in the Amazon region of Brazil. The Disordered Eating Attitude Scale reduced version (DEAS-s) was used to assess the risk of eating disorders and the Three-Factor Eating Questionnaire (TFEQ-R21) was used to characterize eating behavior. A total of 205 patients participated, with a mean age of 37.5 ± 8.6 years. The majority of participants were female (93.7%; p < 0.001), and the mean BMI was 45.3 ± 6.7 kg/m2. It was found that cognitive restraint had the highest mean (52.6 ± 19.9; p < 0.001). As for the DEAS-s, the question with the highest mean response was “spending one or more days without eating or consuming only liquids to lose weight” (2.80 ± 1.99). Female participants had a higher score for emotional eating (p = 0.016). Disordered eating attitudes showed a correlation with emotional eating and uncontrolled eating. These results suggest that candidates for bariatric surgery may have susceptibility to eating disorders. The importance of a multidisciplinary team conducting monitoring during the preoperative period is highlighted.

Background Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that plays a crucial role in modulating the inflammatory response and activating the complement system. Additionally, plasma PTX3 has emerged as a potential biomarker for various infectious diseases. The aim of this study was to evaluate the association of PTX3 gene polymorphisms and PTX3 plasma levels with susceptibility to leprosy and clinical characteristics. Methods Patients with leprosy from a hyperendemic area in the Northeast Region of Brazil were included. Healthy household contacts and healthy blood donors from the same geographical area were recruited as a control group. The rs1840680 and rs2305619 polymorphisms of PTX3 were determined by real-time PCR. Plasma levels of PTX3 were determined by ELISA. Results A total of 512 individuals were included. Of these, 273 were patients diagnosed with leprosy; 53 were household contacts, and 186 were healthy blood donors. No association was observed between PTX3 polymorphisms and susceptibility to leprosy or development of leprosy reaction or physical disability. On the other hand, plasma levels of PTX3 were significantly higher in patients with leprosy when compared to household contacts ( p  = 0.003) or blood donors ( p  = 0.04). It was also observed that PTX3 levels drop significantly after multidrug therapy ( p  < 0.0001). Conclusions Our results suggest that PTX3 may play an important role in the pathogenesis of leprosy and point to the potential use of this molecule as an infection marker.

This study examined the effects of cottonseed processing form and the inclusion of calcium lignosulfonate in high-concentrate diets for feedlot cull ewes on carcass traits and non-carcass components. Thirty Santa Inês cull ewes with an average body weight of 44.2 ± 5.2 kg and an average age of 50 months were distributed into collective stalls in a completely randomized design. The treatments consisted of diets including whole cottonseed, crushed cottonseed, whole cottonseed treated with lignosulfonate (100 g/kg, as fed), crushed cottonseed treated with lignosulfonate (100 g/kg, as fed), and a control diet without cottonseed. The experimental diets did not influence (P>0.05) average daily weight gain (0.195 kg/day), slaughter weight (51.74 kg), or in vivo biometric and on-carcass measurements. There was no difference (P>0.05) in loin-eye area or subcutaneous fat thickness as evaluated in vivo by ultrasound. There was no diet effect on hot carcass weight and yield (24.8 kg and 47.8 %), cold carcass weight and yield (24.2 kg and 46.8 %), or chilling loss (2.1 %). Non-carcass components did not differ in response to the diets (P>0.05). Dietary inclusion of calcium lignosulfonate increases the proportions of udder and liver relative to empty body weight (P<0.05). Neither the cottonseed processing method nor the inclusion of calcium lignosulfonate in high-concentrate diets for cull ewes affects their performance, biometric or morphometric measurements, non-carcass components, or qualitative traits of their carcass.

Given the changes in the digestive tract post-bariatric surgery, adapting to a new pattern of eating behavior becomes crucial, with special attention to the specifics of chewing mechanics. This study aimed to investigate the association between self-perception of chewing, chewing behavior, and the presence of gastrointestinal symptoms in preoperative patients undergoing bariatric surgery. Sixty adult candidates for bariatric surgery at a public hospital in Belém (Brazil) were analyzed. Participants predominantly exhibited unilateral chewing patterns (91.6%), a fast chewing rhythm (73.3%), a large food bolus (80%), liquid intake during meals (36.7%), and 41.7% reported that chewing could cause some issue. Significant associations were found between the perception of causing problems and chewing scarcity (p = 0.006), diarrhea (p = 0.004), absence of slow chewing (p = 0.048), and frequent cutting of food with front teeth (p = 0.034). These findings reveal a relationship between the perception of chewing problems and chewing scarcity, presence of diarrhea, and fast chewing.

Background and aims Brazilian Cerrado soils have low phosphorus content, leading many farmers to frequently apply fertilizers. With respect to this, Trichoderma are fungi with traits that can improve the fertility and health of the soil and promote plant growth. In this study, native strains of Trichoderma ( T. viride GT-8, T. reesei GT-31, and T. longibrachiatum GT-32) from the Brazilian Cerrado were characterized. The impact of their inoculation on soybean growth and grain yield was also assessed under two phosphate fertilization conditions: 400 and 200 kg ha −1 of simple superphosphate (SPP). Two independent field experiments were conducted with the cultivars Nidera NS6601 IPRO and DM 69IX60RSF 12X RR2PRO. Leaf and rhizospheric soil samples were collected for biochemical analyses. Results The strains showed phosphate solubilization from fertilizers and exhibited other PGP traits. Inoculation of GT-32 on cv. Nidera NS6601 resulted in a 4.5% increase in grain yield under 200 kg ha −1 of SPP. For the second cultivar, the use of GT-31 and GT-32 at 200 kg ha −1 of SSP resulted in grain yield increases of 22.7% and 18.6%, respectively. Inoculated plants showed higher shoot dry weight, chlorophyll content, phenolic compounds, and antioxidant responses under both fertilization conditions. Furthermore, enzymatic activities were higher in the rhizospheric soil of plants inoculated with GT-31 and GT-32 strains. Conclusion These findings demonstrated the potential of the GT-31 and GT-32 strains to improve soybean growth and yield with reduced fertilizer use. Additionally, their use could offer a sustainable strategy for enhancing soil health and fertility in Brazilian Cerrado soils. Graphical Abstract