Summary Background Systemic lupus erythematosus is a heterogeneous autoimmune disease that is associated with B-cell hyperactivity, autoantibodies, and increased concentrations of B-lymphocyte ...stimulator (BLyS). The efficacy and safety of the fully human monoclonal antibody belimumab (BLyS-specific inhibitor) was assessed in patients with active systemic lupus erythematosus. Methods Patients (aged ≥18 years) who were seropositive with scores of at least 6 on the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) were enrolled in a multicentre phase 3 study, which was done in Latin America, Asia-Pacific, and eastern Europe. Patients were randomly assigned by use of a central interactive voice response system in a 1:1:1 ratio to belimumab 1 mg/kg or 10 mg/kg, or placebo by intravenous infusion in 1 h on days 0, 14, and 28, and then every 28 days until 48 weeks, with standard of care. Patients, investigators, study coordinators, and sponsors were masked to treatment assignment. Primary efficacy endpoint was improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 (reduction ≥4 points in SELENA-SLEDAI score; no new British Isles Lupus Assessment Group BILAG A organ domain score and no more than 1 new B organ domain score; and no worsening <0·3 increase in Physician's Global Assessment PGA score) versus baseline. Method of analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00424476. Findings 867 patients were randomly assigned to belimumab 1 mg/kg (n=289) or 10 mg/kg (n=290), or placebo (n=288). 865 were treated and analysed in the belimumab (1 mg/kg, n=288; 10 mg/kg, n=290) and placebo groups (n=287). Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 51%, odds ratio 1·55 95% CI 1·10–2·19; p=0·0129) and 10 mg/kg (167 58%, 1·83 1·30–2·59; p=0·0006) than with placebo (125 44%) at week 52. More patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 1 mg/kg (153 53%, 1·51 1·07–2·14; p=0·0189) and 10 mg/kg (169 58%, 1·71 1·21–2·41; p=0·0024) than with placebo (132 46%). More patients given belimumab 1 mg/kg (226 78%, 1·38 0·93–2·04; p=0·1064) and 10 mg/kg (236 81%, 1·62 1·09–2·42; p=0·0181) had no new BILAG A or no more than 1 new B flare than did those in the placebo group (210 73%). No worsening in PGA score was noted in more patients with belimumab 1 mg/kg (227 79%, 1·68 1·15–2·47; p=0·0078) and 10 mg/kg (231 80%, 1·74 1·18–2·55; p=0·0048) than with placebo (199 69%). Rates of adverse events were similar in the groups given belimumab 1 mg/kg and 10 mg/kg, and placebo: serious infection was reported in 22 (8%), 13 (4%), and 17 (6%) patients, respectively, and severe or serious hypersensitivity reactions on an infusion day were reported in two (<1%), two (<1%), and no patients, respectively. No malignant diseases were reported. Interpretation Belimumab has the potential to be the first targeted biological treatment that is approved specifically for systemic lupus erythematosus, providing a new option for the management of this important prototypic autoimmune disease. Funding Human Genome Sciences and GlaxoSmithKline.
Abstract Objective To determine the incidence and risk factors for endocarditis and reintervention in patients undergoing placement of right ventricle-to-pulmonary artery valve conduits. Methods All ...right ventricle–to–pulmonary artery valved conduits placed between 1995 and 2014 were included. Freedom from endocarditis, reintervention, and replacement were analyzed using the Kaplan-Meier method and parametric survival regression models. Results A total of 586 patients underwent placement of a total of 792 valved conduits, including 289 (36%) pulmonary homografts, 121 (15%) aortic homografts, 245 (31%) bovine jugular grafts, and 137 (17%) porcine heterografts. There were 474 (60%) primary placements and 318 (40%) replacements. The median duration of conduit follow-up was 7 years; 23 conduits developed endocarditis at a median of 5 years after surgery. The use of bovine jugular grafts was the sole significant risk factor associated with endocarditis (hazard ratio, 9.05; 95% confidence interval, 2.6–31.8 compared with homografts). The hazard was greater for bovine jugular grafts compared with the other conduit types and increased with time; however, bovine jugular grafts were associated with a lower risk for reintervention ( P < .0001) and replacement ( P = .0002). Factors associated with greater risk of both reintervention and replacement were younger age and smaller conduit size. In addition, a diagnosis of truncus arteriosus was associated with a greater risk for replacement ( P = .03). Conclusions Bovine jugular grafts are associated with a significantly greater risk of late endocarditis but with lower reintervention rates compared with other valved conduits. The risk of endocarditis and durability must be balanced during conduit selection. Antibiotic prophylaxis and a high index of suspicion for endocarditis are warranted in patients with bovine jugular grafts.
Cancer is one of the main causes of mortality worldwide. Common therapy schemes are always based on chemotherapy, radiotherapy and/or surgery. Among chemotherapeutics, vanadium compounds have ...recently emerged as non-platinum antitumor agents. In this sense, Metvan (V
IV
O(Me
2
phen)
2
(SO
4
)) was identified as one of the most promising vanadium anticancer complexes. In this work, the Metvan compound was encapsulated into well designed and developed nanostructured lipid carriers (NLCs) with the aim of improving its biopharmaceutical profile with regards to bioavailability, degradation, solubility and cell up-take. A quality by design approach was followed to find the optimal nanoparticle formulation for Metvan delivery. Results exhibited that the ideal formulation was obtained by using myristyl myristate as the lipid matrix and Pluronic F128 as the stabilizing agent with a mean nanoparticle size of 230.8 ± 3.1 nm and a mean surface charge of −7.9 ± 0.8 mV. The formulation showed an encapsulation efficiency of approximately 80% with a sustained drug release for more than 60 h. The kinetic release mechanism of Metvan from the nanoparticles fitted the Korsmeyer-Peppas model, indicating the Fickian diffusion of Metvan from the nanoparticles. On the other hand, the results showed that the nanoparticle-Metvan system is more effective to decrease cell viability on human osteosarcoma cells (MG-63) compared to the free drug, suggesting a possible different cell internalization mechanism and intracellular effect.
A new Metvan-NLC compound was developed to improve Metvan's biopharmaceutical profile and antitumor efficacy.
•A vortex assisted MSPD method for ibuprofen enantiomer extraction from breast milk.•Factorial design with desirability functions was used for optimization of extraction.•Experimental conditions to ...keep enantiomeric fraction and resolution were achieved.•Enantiomeric fractions between 0.3 and 0.5 were estimated in breast milk samples.
A mixture of β-cyclodextrin (β-CD) and primary and secondary amine (PSA) sorbents was employed for the extraction and quantification of ibuprofen enantiomers from human breast milk, combining a vortex-assisted matrix solid-phase dispersion method (MSPD) and direct chiral liquid chromatography (CLC) with ultraviolet detection (UV). The MSPD sample preparation procedure was optimized focusing on both the type and amount of dispersion/sorption sorbents and the nature of the elution solvent, in order to obtain acceptable recoveries and avoiding enantiomer conversion. These MSPD parameters were optimized with the aid of an experimental design approach. Hence, a factorial design was used for identification of the main variables affecting the extraction process of ibuprofen enantiomers. Under optimum selected conditions, MSPD combined with direct CLC-UV was successfully applied for ibuprofen enantiomeric determination in breast milk at enantiomer levels between 0.15 and 6.0μgg−1. The proposed analytical method also provided good repeatability, with relative standard deviations of 6.4% and 8.3% for the intra-day and inter-day precision, respectively.
Introduction
Up to 50% of patients with brain tumors experience psychiatric symptoms, and rates up to 80% have been reported in malignant neoplasms such as glioblastoma multiforme (GBM). Still, ...clinical presentation as mania-like syndromes is a rare phenomenon, mainly occurring when frontal structures are compromised.
We present the case of a 42-year-old woman who was admitted to our hospital due to manic symptoms coinciding with a recurrence of a bifrontal GBM, for which she underwent surgery 5 months prior.
Objectives
1) To describe the clinical particularities of this case, focusing on the differential diagnosis.
2) To review the association between manic symptoms and frontal dysfunction caused by brain tumors, with special interest on GBM.
Methods
A review of the patient’s clinical history and complementary tests performed was carried out. Likewise, we reviewed the available literature in relation to manic symptoms related to brain tumors.
Results
The patient’s GBM recurrence presented with late onset symptoms of mania, including euphoric mood, increased spending, ideas of grandiosity and hyper-religiosity. She had no previous psychiatric history but, interestingly, she had an extensive affective burden in her family, with 4 consummated suicides. However, she also presented other clinical signs, such as disorientation, perseveration, mild memory impairment and stereotyped motor behaviors, that pointed to relevant frontal lobe dysfunction, suggesting Moria as a possible contribution for the symptoms described.
Manic symptoms in the context of brain tumors appear in 7-15% of patients with psychiatric symptoms, usually associated with right frontal dysfunction (75% of cases). Bifrontal affectation, such as this patient, is only described in 6% of cases. Although fast growing, malignant tumors have been associated with higher rates of psychiatric symptoms, no correlation has been described between these and brain tumor histology.
Conclusions
- The presence of atypical manic symptoms, such as those presented in this case, should raise clinical concern for secondary mania.
- Moria shares similarities with mania, including mood elevation, tendency to hilarity or hyper-sexuality, that may hinder diagnosis of patients with frontal dysfunction.
- This case outlines the difficulties in making a differential diagnosis in patient with both manic and neurological signs, and highlights the implication of frontal structures in the development of manic symptoms.
Disclosure of Interest
None Declared
ABSTRACTInverted depth perception in satellite images is a well-known phenomenon. It has been previously verified that the illusion is prevalent in Northern Hemisphere (NH) images, while it is ...observed in Southern Hemisphere (SH) images to a much smaller extent. However, the equatorial zone has not been examined despite its interesting geometric position in relation to the Sun and satellite orbits. We present a user study (n = 313) in which participants were asked to identify landforms on 16 satellite images from the equatorial region. Our main findings are: (a) surprisingly, on the equatorial line and roughly ±1° of it in either direction, the results are consistent with the NH images; (b) instead, the expected variation/ambiguity occurs with the images 2–5° south of the Equator. These outcomes imply that based on illumination alone, the ‘middle’ (i.e. the Equator) might be somewhat more south from the perspective of the studied illusion. The observed effect surpasses various individual and group differences such as biological sex, expertise and education levels. Landcover cues such as snow, vegetation etc. do not appear to moderate the observed effect either. Our observations contribute towards a better understanding of the causes and prevalence of the relief inversion illusion.
Abstract
Background
Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2–infected patients. Vitamin K activates both hepatic coagulation factors and ...extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease.
Methods
A total of 135 hospitalized COVID-19 patients were compared with 184 historic controls. Inactive vitamin K–dependent MGP (desphospho-uncarboxylated dp-uc MGP) and prothrombin (PIVKA-II) were measured inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed using computed tomography.
Results
dp-ucMGP was elevated in COVID-19 patients compared with controls (P < .001), with even higher dp-ucMGP in patients with poor outcomes (P < .001). PIVKA-II was normal in 82.1% of patients. dp-ucMGP was correlated with desmosine (P < .001) and with coronary artery (P = .002) and thoracic aortic (P < .001) calcification scores.
Conclusions
dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome; hepatic procoagulant factor II remained unaffected. These data suggest pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively.
Indirectly quantified extrahepatic vitamin K status is severely reduced in COVID-19. Data suggest pneumonia-induced vitamin K depletion leading to elastic fiber damage and thrombosis due to impaired vitamin K–dependent activation of matrix Gla protein and endothelial protein S, respectively.
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•Effective decontamination of N95 facemasks contaminated with SARS-COV-2.•Ozone degradation of polypropylene fibers used in facemasks.•The mechanical properties of elastic bands were ...affected after 120 min of O3 exposure,•The propylene fibers of the N95 show signs of degradation after 120 min of O3 exposure.
COVID-19 pandemic created a global shortage of medical protective equipment. Here, we considered ozone (O3) a disinfectant alternative due to its potent oxidative activity against biological macromolecules. The O3 decontamination assays were done using SARS-CoV-2 obtained from patients to produce artificial contamination of N95 masks and biosecurity gowns. The quantification of SARS-CoV-2 was performed before and after exposing the samples to different ozone gas concentrations for times between 5 and 30 min. Viral loads as a function of the O3 exposure time were estimated from the data obtained by the RT-PCR technique. The genetic material of the virus was no longer detected for any tested concentrations after 15 min of O3 exposure, which means a disinfection Concentration-Time above 144 ppm min. Vibrational spectroscopies were used to follow the modifications of the polymeric fibers after the O3 treatment. The results indicate that the N95 masks could be safely reused after decontamination with treatments of 15 min at the established O3 doses for a maximum of 6 cycles.
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