Comparison of a Low,Fixed Dose and a High,Weight-Based Dose of Recombinant Factor VIIa in the Treatment of Warfarin-Associated Intracranial Hemorrhage

Background

Recombinant activated Factor VII (rFVIIa) can be used for rapid INR normalization in patients with warfarin-associated intracranial hemorrhage (WA-ICH); however, the optimal dose to normalize INR has not been established.

Methods

This is a retrospective review comparing two rFVIIa hospital protocols for WA-ICH [weight-based dose (80 mcg/kg) or fixed dose (2 mg)]. Primary endpoint was the percentage of patients with INR reversal (INR <1.3) at the next INR draw and the need for further doses of rFVIIa. Secondary endpoints included time to documented INR reversal and sustained INR normalization, morbidity, mortality, change in hematoma size, cost, and adverse drug reactions.

Results

Twenty-nine patients were included in each group. The weight-based group received a mean dose of 78.9 ± 21 mcg/kg versus 26.6 ± 8 mcg/kg in the fixed dose group. More patients in the fixed dose protocol achieved documented INR reversal than those in the weight-based group (92.6 vs 72.4 %, p = 0.19). The weight-based group achieved INR normalization in 229.5 [102, 331] minutes versus 165 [83, 447] minutes in the fixed dose group (p=0.02). Time to sustained INR normalization was similar in both groups. Four patients in the fixed dose group received an additional dose of 1 mg per hospital protocol. With the exception of medication acquisition cost savings of about $4,300 per patient who received fixed dose protocol, all other endpoints were similar between groups.

Conclusions

A low, fixed dose of rFVIIa appears to be as effective as a high, weight-based dose in achieving INR normalization in patients with WA-ICH.     

Tissue-resident T cells,in situ immunity and transplantation

T cells coordinate rejection of transplanted allografts and are key targets for depletion, immunosuppression, and tolerance induction to promote long-term graft survival. Studies in mouse models and humans generally focus on circulating T cells or those from lymphoid sites; however, vast numbers of T cells reside in multiple peripheral tissue sites including lungs, intestines, liver, and skin as non-circulating, tissue-resident memory T cells (Trm cells). In this review, we define the basic properties of Trm cells, the emerging evidence of their importance for protective immunity, and the potential role of resident versus circulating T cells in transplant rejection and in providing protection to prevalent infections posttransplantation. We also discuss potential susceptibilities and/or resistance of protective Trm to immunosuppression therapies, and how consideration of Trm, their compartmentalization, and specificity can enable improved therapies for targeted inhibition of pathogenic and preservation of protective T-cell subsets.     

Differential T-cell responses of semi-immune and susceptible malaria subjects to in silico predicted and synthetic peptides of Plasmodium falciparum

Malaria remains a public health hazard in tropical countries as a consequence of the rise and spread of drug and insecticide resistances; hence the need for a vaccine with widespread application. Protective immunity to malaria is known to be mediated by both antibody and cellular immune responses, though characterization of the latter has been less extensive. The aim of the present investigation was to identify novel T-cell epitopes that may contribute to naturally acquired immune responses against malaria. Using the Microsoft software, Epitome™ T-cell peptide epitopes on 19 Plasmodium falciparum proteins in the Plasmodium Database (www.plasmodb.org.PlasmoDB 9.0) were predicted in-silico. The peptides were synthesized and used to stimulate peripheral blood mononuclear cells (PBMCs) in 14 semi-immune and 21 malaria susceptible subjects for interferon-gamma (IFN-γ) production ex-vivo. The level of IFN-γ production, a marker of T-cell responses, was measured by ELISPOT assay in semi-immune subjects (SIS) and frequently sick subjects (FSS) from an endemic zone with perennial malaria transmission. Of the 19 proteins studied, 17 yielded 27 pools (189 peptides), which were reactive with the subjects’ PBMCs when tested for IFN-γ production, taking a stimulation index (SI) of ≥2 as a cutoff point for a positive response. There were 10 reactive peptide pools (constituting eight protein loci) with an SI of 10 or greater. Of the 19 proteins studied, two were known vaccine candidates (MSP-8 and SSP2/TRAP), which reacted both with SIS and FSS. Similarly the hypothetical proteins (PFF1030w, PFE0795c, PFD0880w, PFC0065c and PF10_0052) also reacted strongly with both SIS and FSS making them attractive for further characterization as mediators of protective immunity and/or pathogenesis.     

Smoking Habits of Black South African Patients with Diabetes Mellitus

Cigarette smoking is a major arteriosclerotic risk factor, and this is enhanced by the presence of diabetes mellitus. Although smoking rates are increasing in many African countries, they have been little studied. We have critically assessed smoking among black diabetic and general medical patients at Baragwanath Hospital in Soweto, South Africa. As well as direct questioning of patients, we also used urinary cotinine:creatinine ratio as an objective marker. The admitted smoking rate was 16 % in 118 diabetic patients, compared with 22 % in 105 medical patients. Using a validated biochemical index of smoking (urinary cotinine:creatinine >1.0 μg mg⁻¹) the rates were 37 % and 33 %, respectively. Most of the excess however was due to women who took snuff, and when excluded, the estimated real rates were 20 % (diabetic) and 24 % (medical). Amongst diabetic smokers mean cotinine:creatinine ratio was higher than in medical smokers (4.7 ± 6.0 v 1.8 ± 2.0 μg mg⁻¹) despite admitted similar smoking consumption. A separate control group of British smokers had a mean level of 3.6 ± 1.3 though their consumption was twice that of the South African groups. We conclude that smoking is common among South African black diabetic patients (20 %), though it is less than reported figures for the black general population (28 %), and British diabetic patients (35 %). Questionnaire studies may seriously underestimate smoking rates, though this effect is considerably less in African compared with British smokers. Urinary cotinine also allows quantification of the ‘smoking load’, which is rarely reflected by admitted cigarette consumption.     

Influence of Heating during Cooking on Trans Fatty Acid Content of Edible Oils: A Systematic Review and Meta-Analysis

Consumption of trans fatty acids (TFA) is associated with adverse health outcomes and is a considerable burden on morbidity and mortality globally. TFA may be generated by common cooking practices and hence contribute to daily dietary intake. We performed a systematic review and meta-analysis to investigate the relationship between heating edible oils and change in their TFA content. A systematic search of experimental studies investigating the effect of various methods of heating on TFA content of edible oils was conducted in Medline and Embase since their inception up to 1 October 2020 without language restrictions. Comparable data were analysed using mixed multilevel linear models taking into account individual study variation. Thirty-three studies encompassing twenty-one different oils were included in this review. Overall, heating to temperatures <200 °C had no appreciable impact on different TFA levels. Between 200 and 240 °C, levels of C18:2 t (0.05% increase per 10 °C rise in temperature, 95% CI: 0.02 to 0.05%), C18:3t (0.18%, 95% CI: 0.14 to 0.21%), and total TFA (0.38%, 95% CI: 0.20 to 0.55%) increased with temperature. A further increase in total TFA was observed with prolonged heating between 200 and 240 °C. Our findings suggest that heating edible oils to common cooking temperatures (≤200 °C) has minimal effect on TFA generation whereas heating to higher temperatures can increase TFA level. This provides further evidence in favour of public health advice that heating oils to very high temperatures and prolonged heating of oils should be avoided.     

Chagas disease reactivation in rheumatologic patients: association with immunosuppressive therapy and humoral response

Clinical Rheumatology - Evidence for Chagas disease reactivation (CDR) in rheumatologic patients under rheumatologic treatments (RTs) is scarce. To screen and follow-up patients with rheumatic...     

Optimal Design of Double-Walled Corrugated Board Packaging

Designing corrugated board packaging is a real challenge, especially when the packaging material comes from multiple recycling. Recycling itself is a pro-ecological and absolutely necessary process, but the mechanical properties of materials that are processed many times deteriorate with the number of cycles. Manufacturers are trying to use unprecedented design methods to preserve the load-bearing capacity of packaging, even when the material itself is of deteriorating quality. An additional obstacle in the process of designing the structure of paper packaging is the progressive systematic reduction of the grammage (the so-called lightweight process) of corrugated cardboard. Therefore, this research presents a critical look at the process of optimal selection of corrugated cardboard for packaging structures, depending on the paper used. The study utilizes analytical, simplified formulas to estimate the strength of cardboard itself as well as the strength of packaging, which are then analyzed to determine their sensitivity to changes in cardboard components, such as the types of paper of individual layers. In the performed sensitivity analysis, numerical homogenization was used, and the influence of initial imperfections on the packaging mechanics was determined. The paper presents a simple algorithm for the optimal selection of the composition of corrugated cardboard depending on the material used and the geometry of the packaging, which allows for a more conscious production of corrugated cardboard from materials derived, e.g., from multiple recycling.