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Mild or moderate hemophilia is not always a mild or moderate bleeding disorder: back to the clinical phenotype
No full textIn a previous paper, a comprehensive clinicopathologic approach to mild and moderate bleeding disorders (MBD) was proposed by an international working group (IWG) as a part of a project promoted by the European Hematology Association (EHA) on the development of guidelines on the various MBDs. A single pre-diagnosis grade 4 bleeding event according to the ISTH-BAT scale or a comparable event after diagnosis was considered sufficient to classify a patient as affected by a severe bleeding disorder (SBD). In this article, the original IWG integrated by experts and patients' representatives proposed by the European Haemophilia Consortium (EHC) and European Association of Haemophilia and Allied Disorders (EAHAD) applied these criteria to mild and moderate hemophilia A and B to establish the proportion of cases that would be reclassified as SBD taking into account bleeding phenotype, thus improving over the current classification based exclusively on basal factor VIII or IX level. To this aim, publications of unselected cases with bleeding history available from birth to the time of publication were considered to estimate the incidence of a first severe bleeding event. More than 20% of cases with mild or moderate hemophilia met the criteria for SBD by experiencing joint or non-joint severe bleeding events. Furthermore, a significant proportion of patients developed an inhibitor against factor VIII or IX. These results, based on a rigorous methodologic approach, substantiate the criticism of the current classification of hemophilia and argue for the adoption of a new classification that takes into account bleeding phenotype in addition to basal clotting activity
Oncological and survival endpoints in cancer cachexia clinical trials: systematic review 6 of the cachexia endpoints series
No full textBackgroundIn patients receiving anti-cancer treatment, cachexia results in poorer oncological outcomes. However, there is limited understanding and no systematic review of oncological endpoints in cancer cachexia (CC) trials. This review examines oncological endpoints in CC clinical trials.MethodsAn electronic literature search of MEDLINE, Embase and Cochrane databases (1990–2023) was performed. Eligibility criteria comprised participants ≥ 18 years old; controlled design; ≥ 40 participants; and a cachexia intervention for > 14 days. Trials reporting at least one oncological endpoint were selected for analysis. Data extraction was performed using Covidence and followed PRISMA guidelines and the review was registered (PROSPERO CRD42022276710).ResultsFifty-seven trials were eligible, totalling 9743 patients (median: 107, IQR: 173). Twenty-six (46%) trials focussed on a single tumour site: eight in lung, six in pancreatic, six in head and neck and six in GI cancers. Forty-two (74%) studies included patients with Stage III/IV disease, and 41 (70%) included patients receiving palliative anti-cancer treatment. Ten studies (18%) involved patients on curative treatment. Twenty-eight (49%) studies used pharmacological interventions, 29 (50%) used oral nutrition, and two (4%) used enteral or parenteral nutrition. Reported oncological endpoints included overall survival (OS, n = 46 trials), progression-free survival (PFS, n = 7), duration of response (DR, n = 1), response rate (RR, n = 9), completion of treatment (TC, n = 11) and toxicity/adverse events (AE, n = 42). Median OS differed widely from 60 to 3468 days. Of the 46 studies, only three reported a significant positive effect on survival. Seven trials showed a difference in AE, four in TC, one in PFS and one in RR. Reported significances were unreliable due to missing adjustments for extensive multiple testing. Only three of the six trials using OS as the primary endpoint reported pre-trial sample size calculations, but only one recruited the planned number of patients.ConclusionIn CC trials, oncological endpoints were mostly secondary and only few significant findings have been reported. Due to heterogeneity in oncological settings, nutritional and metabolic status and interventions, firm conclusions about CC treatment are not possible. OS and AE are relevant endpoints, but future trials targeting clinically meaningful hazard ratios will required more homogeneous patient cohorts, adequate pre-trial power analyses and adherence to statistical testing standards
Role of the radical character in singlet fission: an ab initio and quantum chemical topology analysis
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Comparison between conventional and artificial intelligence‐assisted setup for digital implant planning: accuracy, time‐efficiency, and user experience
No full textLearning relational categories: benefits of blocking, classification, and subject-specific examples
No full textAntler size decreases with increasing age: evidence of reproductive senescence in male fallow deer (dama dama)
No full textSynthesis and self‐assembly of pore‐forming three‐arm amphiphilic block copolymers
No full textThe synthesis of an amphiphilic three-arm block copolymer (AB)3-BCP, which consists of poly(methyl methacrylate) (PMMA) and poly(butyl methacrylate) (PBMA) in the hydrophobic inner block, is reported. The hydrophilic block segment is based on poly(2-hydroxyethyl methacrylate) (PHEMA) originating from 2-(trimethylsiloxyl)ethyl methacrylate (HEMA-TMS). The preparation is carried out in two steps using a core-first approach. Using atom transfer radical polymerization (ATRP) as a controlled polymerization technique, three (AB)3-BPCs with HEMA contents of 15 to 38 mol−1 % are prepared, applying different reaction conditions. Porous structures are generated from these BCPs by applying a self-assembly and nonsolvent-induced phase separation (SNIPS) protocol. Complex surface structures are observed using scanning electron microscopy (SEM). Bulk morphologies are investigated for a better understanding of the underlying self-assembly. For PHEMA-rich (AB)3-BCPs, non-regular lamellar microphases are observed in transmission electron microscopy (TEM) and confirmed by small-angle X-ray scattering (SAXS). The porous structures and their expected swelling characteristics are analyzed using atomic force microscopy (AFM) in air and water. Time-resolved measurements in water indicate a rapid swelling after immersion into the water bath. The present study paves the way for exciting porous materials based on the herein synthesized amphiphilic three-arm block copolymers useful for applications as absorber materials and coatings
Sustainable and efficient cooling in titanium milling for dental applications: a study on supercritical CO2 + MQL with focus on tool wear and surface topography
No full textPredicting the hamstring graft size for ACL reconstruction using a 3D tendon model in preoperative MRI
No full textBackground: Rupture of the ACL is a common injury among men and women athletes. While planning the surgical ACL reconstruction procedure, the eventual graft’s diameter is extremely important. Many parameters are therefore evaluated pre-surgery to ensure access to reliable data for estimating the graft diameter. Considering this, magnetic resonance imaging (MRI), particularly qualitative analyses of the hamstring tendons, offers a promising approach. Methods: In a retrospective analysis, we carried out 3D segmentation of the gracilis (GT) and semitendinosus tendon (ST) utilizing MRI with varying slice thicknesses and field strengths. The cross-sectional area (CSA) was calculated on different levels (by relying on the models we had thus created) to generate a mean of CSA with six specific segments. We then correlated the mean CSA with the diameter of the graft measured during surgery. Results: A total of 32 patients were included (12 female, 20 male) in this retrospective analysis. We observed the largest CSA in segment 10 mm–0 (16.8 ± 6.1) with differences between men and women. The graft size and tendon diameter correlated significantly in all segments throughout our study cohort. The strongest correlation was apparent in the segment 10 mm–0 (r = 0.552). Conclusions: MRI-based 3D segmentation and the STGT CSA represent a reliable method for estimating preoperatively a quadrupled hamstring graft diameter. The 10 mm–0 mm segment above the joint line showed a strong correlation, making it an ideal reference for graft planning