New Surgical Technologies Could Facilitate Surgical Hemostasis in Hemophilic Patients

BACKGROUND: It’s assumed that surgery in haemophilia can be accomplished these days safely.AIM: The aim of this study was to investigate the influence of new surgical technologies in the perioperative management and outcome of surgical procedures in haemophiliacs.METHODS: Two patients with mild haemophilia A underwent surgery (laparoscopic appendectomy and inguinal hernia repair). In both patients, the replacement therapy, with factor VIII, started 30 min before surgery. We used the available surgical technologies and techniques with a proven value in the best clinical practice, to achieve proper and permanent hemostasis. Postoperatively, the replacement therapy and thromboembolic prophylaxis was continued according to the international guidelines for the management of haemophilia.RESULTS: The operative and post-operative periods were uneventful. No significant differences were found in the operation time in our hemophilic patients versus non-hemophilic patients. Significant differences related to the hospital stay duration were found in both patients compared with controls, due to the necessary replacement therapy.CONCLUSION: With new surgical technologies, proper and permanent hemostasis can be achieved, without prolonging the operation time

Real-time prostate motion assessment: image-guidance and the temporal dependence of intra-fraction motion

BACKGROUND: The rapid adoption of image-guidance in prostate intensity-modulated radiotherapy (IMRT) results in longer treatment times, which may result in larger intrafraction motion, thereby negating the advantage of image-guidance. This study aims to qualify and quantify the contribution of image-guidance to the temporal dependence of intrafraction motion during prostate IMRT. METHODS: One-hundred and forty-three patients who underwent conventional IMRT (n=67) or intensity-modulated arc therapy (IMAT/RapidArc, n=76) for localized prostate cancer were evaluated. Intrafraction motion assessment was based on continuous RL (lateral), SI (longitudinal), and AP (vertical) positional detection of electromagnetic transponders at 10 Hz. Daily motion amplitudes were reported as session mean, median, and root-mean-square (RMS) displacements. Temporal effect was evaluated by categorizing treatment sessions into 4 different classes: IMRT(c) (transponder only localization), IMRT(cc) (transponder + CBCT localization), IMAT(c) (transponder only localization), or IMAT(cc) (transponder + CBCT localization). RESULTS: Mean/median session times were 4.15/3.99 min (IMAT(c)), 12.74/12.19 min (IMAT(cc)), 5.99/5.77 min (IMRT(c)), and 12.98/12.39 min (IMRT(cc)), with significant pair-wise difference (p<0.0001) between all category combinations except for IMRT(cc) vs. IMAT(cc) (p>0.05). Median intrafraction motion difference between CBCT and non-CBCT categories strongly correlated with time for RMS (t-value=17.29; p<0.0001), SI (t-value=−4.25; p<0.0001), and AP (t-value=2.76; p<0.0066), with a weak correlation for RL (t-value=1.67; p=0.0971). Treatment time reduction with non-CBCT treatment categories showed reductions in the observed intrafraction motion: systematic error (Σ)<0.6 mm and random error (σ)<1.2 mm compared with ≤0.8 mm and <1.6 mm, respectively, for CBCT-involved treatment categories. CONCLUSIONS: For treatment durations >4-6 minutes, and without any intrafraction motion mitigation protocol in place, patient repositioning is recommended, with at least the acquisition of the lateral component of an orthogonal image pair in the absence of volumetric imaging

Quantifying the influence of bias in reproductive and perinatal epidemiology through simulation

Purpose: The application of simulated data in epidemiological studies enables the illustration and quantification of the magnitude of various types of bias commonly found in observational studies. This was a review of the application of simulation methods to the quantification of bias in reproductive and perinatal epidemiology and an assessment of value gained. Methods: A search of published studies available in English was conducted in August 2020 using PubMed, Medline, Embase, CINAHL, and Scopus. A gray literature search of Google and Google Scholar, and a hand search using the reference lists of included studies was undertaken. Results: Thirty-nine papers were included in this study, covering information (n = 14), selection (n = 14), confounding (n = 9), protection (n = 1), and attenuation bias (n = 1). The methods of simulating data and reporting of results varied, with more recent studies including causal diagrams. Few studies included code for replication. Conclusions: Although there has been an increasing application of simulation in reproductive and perinatal epidemiology since 2015, overall this remains an underexplored area. Further efforts are required to increase knowledge of how the application of simulation can quantify the influence of bias, including improved design, analysis and reporting. This will improve causal interpretation in reproductive and perinatal studies.Jennifer Dunne, Gizachew A Tessema, Milica Ognjenovic, Gavin Pereir

Structural changes and allergenic properties of ß-lactoglobulin upon exposure to high-intensity ultrasound

Scope The aim of this work was to investigate the effects of high-intensity ultrasound (sonication), on the structure and allergenicity of the major cow's milk allergen, beta-lactoglobulin (BLG). Methods and results Structural changes upon sonication of BLG were monitored by circular dichroism spectroscopy, tryptophan emission fluorescence, hydrophobic dye and retinol binding, as well as digestibility and phenol-oxidase cross-linking capacity. Allergenicity was monitored in individual patients sera, basophil activation test, and skin prick testing in 41 cow's milk allergy patients. Uncontrolled local temperature changes induced modifications in BLG secondary structure accompanied by formation of dimers, trimers, and oligomers of BLG that were more digestible by pepsin and had reduced retinol binding. Controlled temperature conditions induced changes in secondary structure of BLG without causing formation of oligomers, or changing protein's capacity to bind retinol. Both sonicated forms of BLG had more exposed hydrophobic surfaces than native BLG and underwent facilitated cross-linking reaction with phenol-oxidase. Sonication had a minor effect on IgE-binding properties of BLG. Conclusion Sonication-induced structural changes in major whey allergen were not clinically significant in cow's milk allergy patients. Ultrasound can be a safe procedure for dairy processing as it maintains the nutritional value and does not increase allergenic potential of BLG

The current role for clinical and renal histological findings as predictor for outcome in Australian patients with lupus nephritis

© The Author(s) 2018. Objectives: To investigate the current demographic, clinical and histological characteristics of patients with lupus nephritis (LN) in Western Australia (WA) with regards to their predictive value for patient and renal outcome. Methods: Retrospective study of adult systemic lupus erythematosus (SLE) patients with a first renal biopsy demonstrating LN between 1997 and 2017 at a metropolitan tertiary hospital in WA. Clinical data were collected at baseline and last follow-up with renal biopsy findings classified by International Society of Nephrology (ISN) criteria. Annual incidence rates (AIRs)/100,000, Kaplan–Meyer curves and Cox regression hazard ratio for independent predictors for patient and renal survival were applied. Results: The AIR was 3.3, 3.1 and 0.4 for Asian (n = 29), Indigenous Australian (IA) (n = 11) and Caucasian (n = 43) patients, respectively (p &lt; 0.01). There was no significant subgroup difference regarding ISN class (proliferative 66%, membranous 19%, mesangial 15%), levels of proteinuria (median PCR 300 mg/mmol) or frequency of raised creatinine (31%), anti-dsDNA antibody (89%) or hypocomplementaemia (88%). Treatment included corticosteroids (91%), cyclophosphamide (30%), mycophenolate (67%) and antihypertensive drugs (67%). Five- (81%) and 10-year (70%) survival was lower for IAs than for Caucasians and Asians (95% each at both time points) (p = 0.016). Five- and 10-year renal survival (endpoint renal replacement therapy (RRT)) was 86% and 64% for IA vs 100% for Asian, 100% and 96% for Caucasian patients (p = 0.02). IA background was the only independent predictor for poor patient survival and together with male gender also for renal survival. Only 25% of all patients remained free of any organ damage with non-renal damage observed in 53% of survivors. Conclusions: LN incidence in WA was 0.75/100,000 with the lowest rate observed in Caucasians. While Asian patients have the same favourable outlook as Caucasians, the outcome is much bleaker for IA patients. Other clinical and histological findings did not predict outcomes, and importantly more than half of all surviving patients accrued non-renal damage

Destabilizing NF1 variants act in a dominant negative manner through neurofibromin dimerization.

The majority of pathogenic mutations in the neurofibromatosis type I (NF1) gene reduce total neurofibromin protein expression through premature truncation or microdeletion, but it is less well understood how loss-of-function missense variants drive NF1 disease. We have found that patient variants in codons 844 to 848, which correlate with a severe phenotype, cause protein instability and exert an additional dominant-negative action whereby wild-type neurofibromin also becomes destabilized through protein dimerization. We have used our neurofibromin cryogenic electron microscopy structure to predict and validate other patient variants that act through a similar mechanism. This provides a foundation for understanding genotype-phenotype correlations and has important implications for patient counseling, disease management, and therapeutics

French and Spanish-speaking children use different visual and motor units during spelling acquisition

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