Noninterventional study assessing joint health in persons with hemophilia A after switching to turoctocog alfa pegol: design of pathfinderReal

Factor VIII; Hemofília A; ArticulacióFactor VIII; Hemofilia A; ArticulaciónFactor VIII; Hemophilia A; JointBackground Joint damage affects the quality of life of persons with hemophilia A. The long-term safety and efficacy of turoctocog alfa pegol (N8-GP) prophylaxis in persons with hemophilia A has been investigated in pivotal phase 3 trials in children, adolescents, and adults (pathfinder program). However, there is a lack of data on joint health in adult persons with hemophilia A treated with N8-GP. Objectives To describe the design of the ongoing pathfinderReal study investigating the joint health status in adult persons with hemophilia A after switching to N8-GP. Methods pathfinderReal is a multicountry, noninterventional, single-arm study (NCT05621746) of joint health in adult (≥18 years) male persons with hemophilia A who have switched to N8-GP. Patients enrolled in other interventional studies and those who have previously terminated N8-GP treatment will be excluded. Approximately 124 adults with hemophilia A will be enrolled and followed up for a maximum of 24 months. Data from routine clinical assessments of patients’ joint health will be collected. The primary endpoint is change in Hemophilia Joint Health Score (defined as a change in total score of ≤2) from initiation of N8-GP treatment until the end of the study. Secondary endpoints include number of bleeding episodes, number and resolution of target joints, patient-reported outcomes of problem joint score, pain score, and change in physical function levels. An exploratory endpoint is included to measure the number of patients achieving improved Hemophilia Joint Health Score from the initiation of N8-GP until the end of the study. Conclusion The pathfinderReal study will provide insights regarding the impact of N8-GP on joint health in persons with hemophilia A in a real-world setting.This study is funded by Novo Nordisk AG

Selective removal of α-D-galactose side chains from Rhizobium capsular polysaccharide by guar α-D-galactosidase: Effect on conformational stability and gelation

alpha-D-Galactosidase, isolated from germinating seeds of guar, removed up to 48% of the (1 --> 2)-linked alpha-D-galactose side chains of Rhizobium capsular polysaccharide (CPS), with no loss of the disaccharide side chains (1 --> 6)-linked to the same backbone residues in the hexasaccharide repeating units. Results from differential scanning calorimetry (DSC) and measurements of gel rigidity (G') indicate that removal of alpha-D-galactose side chains facilitates adoption of the "pseudo double-helical" structure proposed from X-ray fibre diffraction analysis (increase in T(m) and reduction in DSC peak width for conformational ordering on cooling), but progressively eliminates the helix-helix aggregation necessary for gel formation (reduction in thermal hysteresis and in G')

Current practice and registration patterns among United Kingdom Haemophilia Centre Doctors' Organisation centers for patients with unclassified bleeding disorders.

BACKGROUND Bleeding of unknown cause (BUC) and unclassified bleeding disorders (UBD) are increasingly recognized. There is no guidance on diagnosis and management. OBJECTIVES To examine UK haemophilia centre registration patterns and current practice for UBD patients. METHODS In a two-step process, the UK National Haemophilia Database (NHD) was reviewed for registration patterns of UBD patients and a survey of UK haemophilia centers was conducted (January/February 2021) to capture current practice for diagnosis and management of patients with UBD. RESULTS/DISCUSSION Overall, registrations with the NHD for UBD patients has sharply risen from 2012 to 2020 and in 2019 accounted for 2.65% of registered patients. For the survey, the response rate was 52/67 (78%). Practice was widely variable; 35/52 (67%) centers register UBD; among these 35 centers, terminology included UBD (28 centers), undiagnosed bleeding disorder (four centers), and BUC (three centers); 34/52 (65%) centers use a formal bleeding assessment tool. For management of dental extraction and high bleeding risk surgery in a fictional UBD patient we found that tranexamic acid was widely used; however, beyond this a variety of hemostatic products were advised including blood products, recombinant factor VIIa/prothrombin complex concentrate, and desmopressin. There was general consensus (≈90%) on avoiding regional anesthesia in pregnancy, but no agreement on the need for fetal precautions to avoid bleeding at delivery (50% would advise these). There was a disparity of opinion on chemical thromboprophylaxis, and management of patients without prior hemostatic challenges and offspring of these patients. CONCLUSION This study provides a snapshot of current practice and real-world data in this area. Future studies need to address the gaps in evidence

Abnormal plasma clot formation and fibrinolysis reveal bleeding tendency in patients with partial factor XI deficiency

Key Points Platelet-poor plasma clotting and fibrinolysis assays detect bleeding tendency in patients with factor XI deficiency. Contact pathway inhibition with corn trypsin inhibitor increases sensitivity of these assays to bleeding tendency.</jats:p

Effect of carrot (Daucus carota) microstructure on carotene bioaccessibility in the upper gastrointestinal tract. 2. in vivo digestions

Nutrient bioaccessibility and subsequent absorption will be directly influenced by changes in food structure during gastrointestinal processing. The accompanying paper (Tydeman et al. J. Agric. Food Chem. 2010, 58, doi: 10.1021/jf101034a) reported results on the effect of carrot processing on the release of carotene into lipid phases during in vitro gastric and small intestinal digestions. This paper describes results from in vivo digestion of two of the types of processed carrot used previously, raw grated carrot and cooked carrot mashed to a pur e. Ileostomy effluents from human volunteers fed meals containing the carrot material were used to study tissue microstructure and carotene release. Raw carrot shreds and intact cells that had survived the pureeing process were identifiable in Heal effluent. The gross tissue structure in the shreds had not changed following digestion. Carotene-containing particles remained encapsulated in intact cells, but were absent from ruptured cells. Microscopy revealed marked changes to the cell walls including swelling and pectin solubilization, which increased in severity with increasing residence time in the upper gut. These observations were entirely consistent with the in vitro observations. It was concluded that a single intact cell wall is sufficient to reduce carotene bioaccessibility from a cell by acting as a physical barrier, which is not broken down during upper gut digestion