Publications by authors named "AH Schmidt"

Importance: Fracture-related infection (FRI) is a serious complication following fracture fixation surgery. Current treatment of FRIs entails debridement and 6 weeks of intravenous (IV) antibiotics. Lab data and retrospective clinical studies support use of oral antibiotics, which are less expensive and may have fewer complications than IV antibiotics.

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On 24 January 2023, Eurotransplant has introduced the virtual crossmatch for kidney and pancreas allocation as a better alternative for the physical Complement Dependent Cytotoxicity (CDC) crossmatches at the donor centre, which were associated with a longer cold ischaemia time and false positive reactions. For the time being, the physical CDC crossmatch at the recipient centre will remain in place as the final histocompatibility check. While Eurotransplant is certainly not the first organ allocation organisation to introduce virtual crossmatching, several novel aspects have been introduced, such as calculation of the virtual panel reactive antibody (vPRA) on 11 loci at the second-field level in addition to the serological broad and split level, electronic HLA typing data transmission using Histoimmunogenetics Markup Language (HML) file format, and the actual virtual crossmatch based on ambiguous, second-field HLA typing of the donor on all 11 loci.

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Biobanking provides benefit for future generations by facilitating medical research and subsequent translation and application of research findings. Long-term storage and research involving biological material and associated data necessitate the proper implementation of ethical and legal standards. A key principle includes recognizing informed consent as a crucial element for legitimizing the collection of biological material and data.

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Purpose Of Review: Stem cell donor registries play an important role in providing stem cell products from unrelated donors to patients with severe blood diseases. In this review, important aspects of donor registry work, current challenges and possible future developments are discussed.

Recent Findings: The current growth in global unrelated stem cell donations is in line with the long-term trend, indicating that donor registries have overcome the COVID-19 pandemic.

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Despite over 41 million registered potential volunteer stem cell donors worldwide, many patients in need of a transplant do not find an HLA-matched unrelated donor or cord blood units, with the respective odds differing significantly between various populations. In this study, we analysed data of 2205 unsuccessful real-life donor searches sent to the DKMS Registry to identify populations in which further donor recruitment would be associated with particularly large patient benefits. For that purpose, we estimated haplotype frequencies of 67 donor populations at various sample sizes and entered them into two different mathematical models.

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Article Synopsis
  • * Currently, about 20% of the combined haplotypes from Europe are represented, but many common and rare haplotypes, particularly those associated with certain diseases, are still lacking from the global sample.
  • * The workshop is now seeking DNA samples from diverse populations, especially non-Europeans, resulting in 537 individuals contributing 294 distinct haplotypes, but still highlighting the need for more representation, particularly from African populations.
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The Immuno Polymorphism Database (IPD) plays a pivotal role for immunogenetics. Due to technical limitations, genotyping often focuses on specific key regions like the antigen recognition domain (ARD) for HLA genotyping, and the databases are populated accordingly. More recently, though, modern next generation sequencing (NGS) assays allow using larger gene segments or even complete genes for genotyping.

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The prerequisite for successful HLA genotyping is the integrity of the large allele reference database IPD-IMGT/HLA. Consequently, it is in the laboratories' best interest that the data quality of submitted novel sequences is high. However, due to its long and variable length, the gene HLA-DRB1 presents the biggest challenge and as of today only 16% of the HLA-DRB1 alleles in the database are characterized in full length.

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Objectives: The goal of this trial was to determine whether coronal plane angulation affects functional and clinical outcomes after the fixation of distal femur fractures.

Design: Multicenter, randomized controlled trial SETTING: 20 academic trauma centers PATIENTS/PARTICIPANTS: 156 patients with distal femur fractures were enrolled. 123 patients were followed 12 months.

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Conscious experience and perception are restricted to a single perspective. Although evidence to suggest differences in phenomenal experience can produce observable differences in behavior, it is not well understood how these differences might influence memory. We used fMRI to scan n = 49 participants while they encoded and performed a recognition memory test for faces and words.

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Optimizing natural killer (NK) cell alloreactivity could further improve outcome after allogeneic hematopoietic cell transplantation (alloHCT). The donor's Killer-cell Immunoglobulin-like Receptor (KIR) genotype may provide important information in this regard. In the past decade, different models have been proposed aiming at maximizing NK cell activation by activating KIR-ligand interactions or minimizing inhibitory KIR-ligand interactions.

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Article Synopsis
  • The study investigates if high-dose cytarabine-based salvage chemotherapy before allogeneic stem-cell transplantation improves survival in patients with acute myeloid leukaemia who haven't responded well to previous treatments.
  • 281 patients aged 18 to 75 were randomly assigned to either receive chemotherapy or immediate stem-cell transplantation; the main goal was to measure treatment success as complete remission by day 56 after HSCT.
  • Results showed that 83% of patients in the chemotherapy group achieved treatment success, suggesting that prior chemotherapy could be an effective approach before transplantation in these patients.
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Allogeneic hematopoietic stem cell (HSC) transplantation is a curative therapy for many severe blood diseases. As many patients have no suitable family donor, large unrelated donor registries and donor centers have been established in many countries, along with an international system for the provision of unrelated donor HSC products. As an essential part of this system, DKMS operates donor centers in 7 countries with a total of 12.

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Children's body odours are effective chemical cues in the parent-child relationship. Mothers can recognize the odour of their child and prefer this odour over that of unfamiliar children. This effect is mediated by genetic similarity and developmental stage and is therefore suited to promote parental care at pre-pubertal stage, while facilitating incest avoidance at (post-)pubertal stage.

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The proposed ICH Q14 guideline "Analytical procedure development" describes science and risk-based approaches for development and maintenance of analytical procedures suitable for the assessment of the quality of drug substances and drug products. As a case study, the systematic development and validation of a supercritical fluid chromatography (SFC)-based purity method for carbamazepine is presented. Systematic analytical quality by design (AQbD) principles were applied using the software package Fusion QbD to the method development approach.

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Article Synopsis
  • MICA is a stress-induced ligand that activates NK and T cell responses, playing a crucial role in anti-tumor immunity.
  • The study found high frequencies of duplications (1%) and deletions (0.4%) of the MICA gene across over two million individuals, with significant variations among different ethnic groups, reaching up to 9.2% in Mexico.
  • The findings suggest that these copy number variations result from independent recombination events and highlight the need for more research on their potential links to diseases, particularly in cancer studies.
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Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed worldwide to treat blood cancer and other life-threatening blood disorders. As successful transplantation requires an HLA-compatible donor, unrelated donor centers and registries have been established worldwide to identify donors for patients without a family match. Ethnic minorities are underrepresented in large donor registries.

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The purity analysis of therapeutic peptides can often be challenging, demanding the application of more than a single analytical technique. Supercritical fluid chromatography nowadays is a promising alternative to reversed-phase liquid chromatography, providing orthogonal and complementary information. This study investigated its applicability for the separation of human insulin, its analogs and degradation products.

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Background: Bone marrow (BM) transplantation is a life-saving therapy for hematological diseases, and the BM harbors also highly useful (progenitor) cell types for novel cell therapies manufacture. Yet, the BM collection technique is not standardized.

Methods: Benchmarking our collection efficiency to BM collections worldwide (N = 1248), we noted a great variability of total nucleated cell (TNC) yields in BM products (HPC-M) with superior performance of our center, where we have implemented a small volume aspirate policy.

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Objective: Acute compartment syndrome (ACS) is a true emergency. Even with urgent fasciotomy, there is often muscle damage and need for further surgery. Although ACS is not uncommon, no validated classification system exists to aid in efficient and clear communication.

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Background & Aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated.

Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764).

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Patients in need of hematopoietic stem cell transplantation often rely on unrelated stem cell donors matched in certain human leukocyte antigen (HLA) genes. Donor search is complicated by the extensive allelic variability of the HLA system. Therefore, large registries of potential donors are maintained in many countries worldwide.

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The Genotype List (GL) String grammar for reporting HLA and Killer-cell Immunoglobulin-like Receptor (KIR) genotypes in a text string was described in 2013. Since this initial description, GL Strings have been used to describe HLA and KIR genotypes for more than 40 million subjects, allowing these data to be recorded, stored and transmitted in an easily parsed, text-based format. After a decade of working with HLA and KIR data in GL String format, with advances in HLA and KIR genotyping technologies that have fostered the generation of full-gene sequence data, the need for an extension of the GL String system has become clear.

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