Publications by authors named "M Schmitz"

1,119 Publications

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1,6-Hexanediol, commonly used to dissolve liquid-liquid phase separated condensates, directly impairs kinase and phosphatase activities.

J Biol Chem 2021 Jan 8;296:100260. Epub 2021 Jan 8.

The Institute of Structural Biology, University of Bonn, Bonn, Germany. Electronic address:

The concept of liquid-liquid phase separation (LLPS) has emerged as an intriguing mechanism for the organization of membraneless compartments in cells. The alcohol 1,6-hexanediol is widely used as a control to dissolve LLPS assemblies in phase separation studies in diverse fields. However, little is known about potential side effects of 1,6-hexanediol, which could compromise data interpretation and mislead the scientific debate. To examine this issue, we analyzed the effect of 1,6-hexanediol on the activities of various enzymes in vitro. Already at 1% volume concentration, 1,6-hexanediol strongly impaired kinases and phosphatases and partly blocked DNA polymerases, while it had no effect on DNase activity. At concentrations that are usually used to dissolve LLPS droplets (5-10%), both kinases and phosphatases were virtually inactive. Given the widespread function of protein phosphorylation in cells, our data argue for a careful review of 1,6-hexanediol in phase separation studies.
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http://dx.doi.org/10.1016/j.jbc.2021.100260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948595PMC
January 2021

Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01328 Dresden, Germany.

According to the literature, the autoantigen La is involved in Cap-independent translation. It was proposed that one prerequisite for this function is the formation of a protein dimer. However, structural analyses argue against La protein dimers. Noteworthy to mention, these structural analyses were performed under reducing conditions. Here we describe that La protein can undergo redox-dependent structural changes. The oxidized form of La protein can form dimers, oligomers and even polymers stabilized by disulfide bridges. The primary sequence of La protein contains three cysteine residues. Only after mutation of all three cysteine residues to alanine La protein becomes insensitive to oxidation, indicating that all three cysteines are involved in redox-dependent structural changes. Biophysical analyses of the secondary structure of La protein support the redox-dependent conformational changes. Moreover, we identified monoclonal anti-La antibodies (anti-La mAbs) that react with either the reduced or oxidized form of La protein. Differential reactivities to the reduced and oxidized form of La protein were also found in anti-La sera of autoimmune patients.
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http://dx.doi.org/10.3390/ijms22073377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036718PMC
March 2021

Regulation of Transcription Factor NF-κB in Its Natural Habitat: The Nucleus.

Cells 2021 Mar 29;10(4). Epub 2021 Mar 29.

Institute of Biochemistry, Justus-Liebig-University, D-35392 Giessen, Germany.

Activation of the transcription factor NF-κB elicits an individually tailored transcriptional response in order to meet the particular requirements of specific cell types, tissues, or organs. Control of the induction kinetics, amplitude, and termination of gene expression involves multiple layers of NF-κB regulation in the nucleus. Here we discuss some recent advances in our understanding of the mutual relations between NF-κB and chromatin regulators also in the context of different levels of genome organization. Changes in the 3D folding of the genome, as they occur during senescence or in cancer cells, can causally contribute to sustained increases in NF-κB activity. We also highlight the participation of NF-κB in the formation of hierarchically organized super enhancers, which enable the coordinated expression of co-regulated sets of NF-κB target genes. The identification of mechanisms allowing the specific regulation of NF-κB target gene clusters could potentially enable targeted therapeutic interventions, allowing selective interference with subsets of the NF-κB response without a complete inactivation of this key signaling system.
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http://dx.doi.org/10.3390/cells10040753DOI Listing
March 2021

LAG-3-Expressing Tumor-Infiltrating T Cells Are Associated with Reduced Disease-Free Survival in Pancreatic Cancer.

Cancers (Basel) 2021 Mar 15;13(6). Epub 2021 Mar 15.

Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany.

T cells are the predominant immune cell population in the pancreatic tumor microenvironment. High CD8 and Th1-polarized CD4 T cell infiltration is associated with prolonged survival in human pancreatic ductal adenocarcinoma (PDAC). However, the expression pattern of co-stimulatory and inhibitory receptors by PDAC-infiltrating T cells and their prognostic significance are not well defined. In this study, we employed multiplex immunofluorescence to investigate the intratumoral expression of the co-stimulatory receptor inducible T-cell co-stimulator (ICOS), the inhibitory receptors lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1), and V-domain immunoglobulin suppressor of T cell activation (VISTA) by tumor-infiltrating T cells (CD3) in a cohort of 69 patients with resected PDAC. T cells were enriched particularly within the stromal area and were highly heterogeneous across tumors. Further, T cells were associated with prolonged disease-free survival (DFS). However, LAG-3 expression by PDAC-infiltrating T cells was correlated with reduced DFS. Our study highlights the biological importance of LAG-3 expression by tumor-infiltrating T cells. LAG-3 T cells may represent a novel prognostic marker and a particularly attractive target for immunotherapeutic strategies in PDAC.
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http://dx.doi.org/10.3390/cancers13061297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998134PMC
March 2021

Tumor-infiltrating plasmacytoid dendritic cells are associated with survival in human colon cancer.

J Immunother Cancer 2021 Mar;9(3)

Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany

Background: Plasmacytoid dendritic cells (pDCs) play a key role in the induction and maintenance of antitumor immunity. Conversely, they can act as tolerogenic DCs by inhibiting tumor-directed immune responses. Therefore, pDCs may profoundly influence tumor progression. To gain novel insights into the role of pDCs in colon cancer, we investigated the frequency and clinical relevance of pDCs in primary tumor tissues from patients with colon cancer with different clinicopathological characteristics.

Methods: Immunohistochemical stainings were performed to explore the frequency of tumor-infiltrating BDCA-2 pDCs in patients with colon cancer. Statistical analyses were conducted to determine an association between the pDC density and clinicopathological characteristics of the patients. Furthermore, we used multiplex immunofluorescence stainings to evaluate the localization and phenotype of pDCs in stroma and tertiary lymphoid structures (TLS) of colon cancer tissues.

Results: An increased density of infiltrating pDCs was associated with lower Union for International Cancer Control (UICC) stages. Furthermore, a higher pDC frequency was significantly correlated with increased progression-free and overall survival of patients with colon cancer. Moreover, a lower number of coloncancer-infiltrating pDCs was significantly and independently linked to worse prognosis. In addition, we found that a proportion of pDCs shows a nuclear expression of the transcription factor interferon regulatory factor 7 (IRF7), which is characteristic for an activated phenotype. In various tumor stroma regions, IRF7 pDCs were located in the neighborhood of granzyme B-expressing CD8 T cells. Moreover, pDCs were identified as a novel component of the T cell zone of colon cancer-associated TLS, which are major regulators of adaptive antitumor immunity. A proportion of TLS-associated pDCs displayed a nuclear IRF7 expression and was preferentially located close to CD4 T cells.

Conclusions: These results indicate that higher densities of tumor-infiltrating pDCs are associated with prolonged survival of patients with colon cancer. Moreover, colon cancer-infiltrating pDCs may represent a novel prognostic factor. The colocalization of activated pDCs and T cells in tumor stroma and within TLS may contribute to the correlation between higher pDC densities and better prognosis. In addition, our findings may have implications for the design of novel immunotherapeutic strategies that are based on targeting colon cancer-infiltrating pDCs.
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http://dx.doi.org/10.1136/jitc-2020-001813DOI Listing
March 2021

In-hospital opioid usage following posterior spinal fusion for adolescent idiopathic scoliosis: Does methadone offer an advantage when used with an ERAS pathway?

Spine Deform 2021 Mar 18. Epub 2021 Mar 18.

Department of Pediatric Orthopaedic Surgery, Children's Healthcare of Atlanta, Scottish Rite Campus, Atlanta, GA, USA.

Purpose: Intraoperative methadone has been shown to decrease opioid medication requirement following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). No study to date has investigated the effect of methadone on opioid medication requirement when used in conjunction with an enhanced recovery after surgery (ERAS) protocol following PSF.

Methods: A retrospective cohort study was performed at a single, tertiary care pediatric hospital. Patients with AIS undergoing PSF were consecutively given a single intra-operative methadone dose and matched 1:2 to a AIS control group without methadone. Patients were matched for age, curve magnitude, levels fused, blood loss, and operating time. All children followed a standard ERAS protocol with methadone being the only change in the post-operative regimen. In-hospital data for opioid and non-opioid medication use, surgical, and patient variables were recorded and compared between cohorts.

Results: Twenty-six patients received methadone (average 15.1 ± 1.9 years) and were matched with 52 control patients without methadone (average 14.7 ± 2.2 years). There were no significant differences in total opioid usage at any time-interval prior to hospital discharge or in cumulative opioid usage. Additionally, patients had a similar VAS pain level at discharge (methadone: 4.0 ± 2.3 vs control: 3.8 ± 1.9; P = 0.572). Total opioid usage was correlated with LOS. There were no opioid-related medication complications in either cohort.

Conclusion: There was no decrease of in-hospital opioid usage when methadone was used with an ERAS protocol. Total opioid usage is correlated with hospital LOS following PSF.
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http://dx.doi.org/10.1007/s43390-021-00288-5DOI Listing
March 2021

Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases.

Respir Res 2021 Mar 16;22(1):84. Epub 2021 Mar 16.

McMaster University and St. Joseph's Healthcare, Hamilton, ON, Canada.

Background: In the INBUILD trial in patients with chronic fibrosing interstitial lung diseases (ILDs) and a progressive phenotype, nintedanib reduced the rate of ILD progression with adverse events that were manageable for most patients. We investigated the potential impact of immunomodulatory therapies on the efficacy and safety of nintedanib.

Methods: Subjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had shown progression of ILD within the prior 24 months despite management in clinical practice, were randomized to receive nintedanib or placebo. Certain immunomodulatory therapies were restricted for the first 6 months. We analyzed post-hoc the rate of decline in forced vital capacity (FVC) over 52 weeks in subgroups by glucocorticoid use at baseline and in analyses excluding subjects or FVC measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies.

Results: Of 663 subjects, 361 (54.4%) were taking glucocorticoids at baseline (353 at a dose of ≤ 20 mg/day). In the placebo group, the adjusted rate of decline in FVC (mL/year) over 52 weeks was numerically greater in subjects taking than not taking glucocorticoids at baseline (- 206.4 [SE 20.2] vs - 165.8 [21.9]). The difference between the nintedanib and placebo groups was 133.3 (95% CI 76.6, 190.0) mL/year in subjects taking glucocorticoids at baseline and 76.1 (15.0, 137.2) mL/year in subjects who were not (interaction P = 0.18). The effect of nintedanib on reducing the rate of FVC decline in analyses excluding subjects or measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies was similar to the primary analysis. The adverse event profile of nintedanib was similar between subjects who did and did not use prohibited or restricted therapies at baseline or during treatment with trial drug.

Conclusions: In patients with progressive fibrosing ILDs, the effect of nintedanib on reducing FVC decline was not influenced by the use of immunomodulatory therapies. Nintedanib can be used in combination with immunomodulatory therapies in patients with progressive fibrosing ILDs. Trial registration ClinicalTrials.gov, NCT02999178. Registered 21 December 2016, https://clinicaltrials.gov/ct2/show/NCT02999178.
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http://dx.doi.org/10.1186/s12931-021-01668-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962343PMC
March 2021

Hip Injuries in the Adolescent Athlete.

Clin Sports Med 2021 Apr 5;40(2):385-398. Epub 2021 Feb 5.

Department of Orthopaedics, San Antonio Military Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234, USA. Electronic address:

This article provides concise and up-to-date information on the most common hip pathologies that affect adolescent athletes. We cover the evaluation and treatment of avulsion injuries, stress fractures, slipped capital femoral epiphysis (SCFE), femoroacetabular impingement, developmental dysplasia of the hip, Legg-Calve-Perthes disease, and coxa saltans focusing on minimizing advanced imaging and using conservative therapy when applicable. Although this is not an all-encompassing list of disorders, it is key to understand these hip pathologies because these injuries occur commonly and can also have detrimental complications if not diagnosed and addressed early, especially SCFE and femoral neck stress fractures.
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http://dx.doi.org/10.1016/j.csm.2020.12.003DOI Listing
April 2021

The active repertoire of Escherichia coli peptidoglycan amidases varies with physiochemical environment.

Mol Microbiol 2021 Mar 5. Epub 2021 Mar 5.

Department of Biology, Washington University in St. Louis, St. Louis, MO, USA.

Nearly all bacteria are encased in peptidoglycan, an extracytoplasmic matrix of polysaccharide strands crosslinked through short peptide stems. In the Gram-negative model organism Escherichia coli, more than 40 synthases and autolysins coordinate the growth and division of the peptidoglycan sacculus in the periplasm. The precise contribution of many of these enzymes to peptidoglycan metabolism remains unclear due to significant apparent redundancy, particularly among the autolysins. E. coli produces three major LytC-type-N-acetylmuramoyl-L-alanine amidases, which share a role in separating the newly formed daughter cells during cytokinesis. Here, we reveal two of the three amidases that exhibit growth medium-dependent changes in activity. Specifically, we report acidic growth conditions stimulate AmiB-and to a lesser extent, AmiC-amidase activity. Combining genetic, biochemical, and computational analyses, we demonstrate that low pH-dependent stimulation of AmiB is mediated through the periplasmic amidase activators NlpD, EnvC, and ActS (formerly known as YgeR). Although NlpD and EnvC promote amidase activity across pH environments, ActS preferentially stimulates AmiB activity in acidic conditions. Altogether, our findings support partially overlapping roles for E. coli amidases and their regulators in cell separation and illuminate the physiochemical environment as an important mediator of cell wall enzyme activity.
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http://dx.doi.org/10.1111/mmi.14711DOI Listing
March 2021

Chronic intercostal neuralgia after placement of right ventricle to pulmonary artery conduit with prosthetic valve.

BMJ Case Rep 2021 Mar 2;14(3). Epub 2021 Mar 2.

Anesthesiology/Pediatric Cardiothoracic Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

Adults with congenital heart disease often have complex medical issues requiring individualised multidisciplinary care for optimising outcomes and quality of life. Chronic pain is an example. We report a rare case of intercostal neuralgia seemingly caused by irritation from a prosthetic valve in a right ventricle to pulmonary artery conduit in a patient with tetralogy of Fallot. Intercostal neuralgia is a painful disorder linked to nerve irritation or injury from trauma, infection or pressure. Although chronic postsurgical pain after cardiac surgery is prevalent, rarely the aetiology relates to valve irritation on a single intercostal nerve. After failing pharmacological therapy for 8 months, the neuralgia completely resolved after an ultrasound-guided neurolytic block with long-term effectiveness and improvement in patient satisfaction.
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http://dx.doi.org/10.1136/bcr-2020-239264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929883PMC
March 2021

Interspecies chimeric conditions affect the developmental rate of human pluripotent stem cells.

PLoS Comput Biol 2021 Mar 1;17(3):e1008778. Epub 2021 Mar 1.

Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Wisconsin, United States of America.

Human pluripotent stem cells hold significant promise for regenerative medicine. However, long differentiation protocols and immature characteristics of stem cell-derived cell types remain challenges to the development of many therapeutic applications. In contrast to the slow differentiation of human stem cells in vitro that mirrors a nine-month gestation period, mouse stem cells develop according to a much faster three-week gestation timeline. Here, we tested if co-differentiation with mouse pluripotent stem cells could accelerate the differentiation speed of human embryonic stem cells. Following a six-week RNA-sequencing time course of neural differentiation, we identified 929 human genes that were upregulated earlier and 535 genes that exhibited earlier peaked expression profiles in chimeric cell cultures than in human cell cultures alone. Genes with accelerated upregulation were significantly enriched in Gene Ontology terms associated with neurogenesis, neuron differentiation and maturation, and synapse signaling. Moreover, chimeric mixed samples correlated with in utero human embryonic samples earlier than human cells alone, and acceleration was dose-dependent on human-mouse co-culture ratios. The altered gene expression patterns and developmental rates described in this report have implications for accelerating human stem cell differentiation and the use of interspecies chimeric embryos in developing human organs for transplantation.
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http://dx.doi.org/10.1371/journal.pcbi.1008778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951976PMC
March 2021

Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update.

Front Cell Dev Biol 2021 9;9:637725. Epub 2021 Feb 9.

Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.

Mesenchymal stromal cells (MSCs) are characterized by an extraordinary capacity to modulate the phenotype and functional properties of various immune cells that play an essential role in the pathogenesis of inflammatory disorders. Thus, MSCs efficiently impair the phagocytic and antigen-presenting capacity of monocytes/macrophages and promote the expression of immunosuppressive molecules such as interleukin (IL)-10 and programmed cell death 1 ligand 1 by these cells. They also effectively inhibit the maturation of dendritic cells and their ability to produce proinflammatory cytokines and to stimulate potent T-cell responses. Furthermore, MSCs inhibit the generation and proinflammatory properties of CD4 T helper (Th)1 and Th17 cells, while they promote the proliferation of regulatory T cells and their inhibitory capabilities. MSCs also impair the expansion, cytokine secretion, and cytotoxic activity of proinflammatory CD8 T cells. Moreover, MSCs inhibit the differentiation, proliferation, and antibody secretion of B cells, and foster the generation of IL-10-producing regulatory B cells. Various cell membrane-associated and soluble molecules essentially contribute to these MSC-mediated effects on important cellular components of innate and adaptive immunity. Due to their immunosuppressive properties, MSCs have emerged as promising tools for the treatment of inflammatory disorders such as acute graft-versus-host disease, graft rejection in patients undergoing organ/cell transplantation, and autoimmune diseases.
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http://dx.doi.org/10.3389/fcell.2021.637725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900158PMC
February 2021

Prion protein oligomers cause neuronal cytoskeletal damage in rapidly progressive Alzheimer's disease.

Mol Neurodegener 2021 02 22;16(1):11. Epub 2021 Feb 22.

Department of Neurology, University Medicine Goettingen and German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany.

Background: High-density oligomers of the prion protein (HDPs) have previously been identified in brain tissues of patients with rapidly progressive Alzheimer's disease (rpAD). The current investigation aims at identifying interacting partners of HDPs in the rpAD brains to unravel the pathological involvement of HDPs in the rapid progression.

Methods: HDPs from the frontal cortex tissues of rpAD brains were isolated using sucrose density gradient centrifugation. Proteins interacting with HDPs were identified by co-immunoprecipitation coupled with mass spectrometry. Further verifications were carried out using proteomic tools, immunoblotting, and confocal laser scanning microscopy.

Results: We identified rpAD-specific HDP-interactors, including the growth arrest specific 2-like 2 protein (G2L2). Intriguingly, rpAD-specific disturbances were found in the localization of G2L2 and its associated proteins i.e., the end binding protein 1, α-tubulin, and β-actin.

Discussion: The results show the involvement of HDPs in the destabilization of the neuronal actin/tubulin infrastructure. We consider this disturbance to be a contributing factor for the rapid progression in rpAD.
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http://dx.doi.org/10.1186/s13024-021-00422-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898440PMC
February 2021

Particle Filtration Efficiency Testing of Sterilization Wrap Masks.

J Prev Med Public Health 2021 Jan 22;54(1):31-36. Epub 2020 Dec 22.

Department of Anesthesiology, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Objectives: Non-traditional materials are used for mask construction to address personal protective equipment shortages during the coronavirus disease 2019 (COVID-19) pandemic. Reusable masks made from surgical sterilization wrap represent such an innovative approach with social media frequently referring to them as "N95 alternatives." This material was tested for particle filtration efficiency and breathability to clarify what role they might have in infection prevention and control.

Methods: A heavyweight, double layer sterilization wrap was tested when new and after 2, 4, 6, and 10 autoclave sterilizing cycles and compared with an approved N95 respirator and a surgical mask via testing procedures using a sodium chloride aerosol for N95 efficiency testing similar to 42 CFR 84.181. Pressure testing to indicate breathability was also conducted.

Results: The particle filtration efficiency for the sterilization wrap ranged between 58% to 66%, with similar performance when new and after sterilizing cycles. The N95 respirator and surgical mask performed at 95% and 68% respectively. Pressure drops for the sterilization wrap, N95 and surgical mask were 10.4 mmH2O, 5.9 mmH2O, and 5.1 mmH2O, respectively, well below the National Institute for Occupational Safety and Health limits of 35 mmH2O during initial inhalation and 25 mmH2O during initial exhalation.

Conclusions: The sterilization wrap's particle filtration efficiency is much lower than a N95 respirator, but falls within the range of a surgical mask, with acceptable breathability. Performance testing of non-traditional mask materials is crucial to determine potential protection efficacy and for correcting misinterpretation propagated through popular media.
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http://dx.doi.org/10.3961/jpmph.20.394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939758PMC
January 2021

Inhibition of Glucose Metabolism Abrogates the Effector Phase of Bullous Pemphigoid-Like Epidermolysis Bullosa Acquisita.

J Invest Dermatol 2021 Feb 18. Epub 2021 Feb 18.

Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany; Center for Research on Inflammation of the Skin (CRIS), University of Lübeck, Lübeck, Germany. Electronic address:

Bullous pemphigoid-like epidermolysis bullosa acquisita (EBA) is an autoantibody-driven, granulocyte-mediated skin disease. The role of cellular metabolism and its potential as a therapeutic target in EBA are unknown. We investigated the effect of 2-deoxy-D-glucose and metformin in the antibody transfer model of EBA. Both metformin and 2-deoxy-D-glucose attenuated disease in this model. Subsequently, we demonstrate that the stimulation of neutrophils by immune complexes increases the rate of aerobic glycolysis and that this increase is required to induce the release of leukotriene B4 and ROS critical for EBA. Accordingly, 2-deoxy-D-glucose as an inhibitor of the glycolytic enzymes hexokinase and phosphoglucose isomerase and heptelidic acid, an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, blunted this neutrophil response. Decreasing oxidative phosphorylation, metformin also inhibited this neutrophil response but only when applied in suprapharmacological doses, rendering a direct effect of metformin on neutrophils in vivo unlikely. Considering that the oxidative phosphorylation inhibitor oligomycin likewise inhibits these neutrophil responses and that immune complex stimulation does not alter the rate of oxidative phosphorylation, these results, however, suggest that intact mitochondria are necessary for neutrophil responses. Collectively, we highlight 2-deoxy-D-glucose and metformin as potential drugs and both glycolysis and oxidative phosphorylation in neutrophils as promising therapeutic targets in EBA.
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http://dx.doi.org/10.1016/j.jid.2021.01.014DOI Listing
February 2021

Bioactive Electrospun Fibers: Fabrication Strategies and a Critical Review of Surface-Sensitive Characterization and Quantification.

Chem Rev 2021 Feb 19. Epub 2021 Feb 19.

Department of Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, 97070 Würzburg, Germany.

Fabricating a porous scaffold with high surface area has been a major strategy in the tissue engineering field. Among the many fabrication methods, electrospinning has become one of the cornerstone techniques due to its enabling the fabrication of highly porous fibrous scaffolds that are of natural or synthetic origin. Apart from the basic requirements of mechanical stability and biocompatibility, scaffolds are further expected to embody functional cues that drive cellular functions such as adhesion, spreading, proliferation, migration, and differentiation. There are abundant distinct approaches to introducing bioactive molecules to have a control over cellular functions. However, the lack of a thorough understanding of cell behavior with respect to the availability and spatial distribution of the bioactive molecules in 3D fibrous scaffolds is yet to be addressed. The rational selection of proper sets of characterization techniques would essentially impact the interpretation of the cell-scaffold interactions. In this timely Review, we summarize the most popular methods to introduce functional compounds to electrospun fibers. Thereafter, the strength and limitations of the conventional characterization methods are highlighted. Finally, the potential and applicability of emerging characterization techniques such as high-resolution/correlative microscopy approaches are further discussed.
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http://dx.doi.org/10.1021/acs.chemrev.0c00816DOI Listing
February 2021

Altered mRNA and Protein Expression of Monocarboxylate Transporter MCT1 in the Cerebral Cortex and Cerebellum of Prion Protein Knockout Mice.

Int J Mol Sci 2021 Feb 4;22(4). Epub 2021 Feb 4.

Département de Physiologie, Université de Lausanne, 1005 Lausanne, Switzerland.

The effect of a cellular prion protein (PrP) deficiency on neuroenergetics was primarily analyzed via surveying the expression of genes specifically involved in lactate/pyruvate metabolism, such as monocarboxylate transporters (, , ). The aim of the present study was to elucidate a potential involvement of PrP in the regulation of energy metabolism in different brain regions. By using quantitative real-time polymerase chain reaction (qRT-PCR), we observed a marked reduction in MCT1 mRNA expression in the cortex of symptomatic Zürich I mice, as compared to their wild-type (WT) counterparts. MCT1 downregulation in the cortex was accompanied with significantly decreased expression of the MCT1 functional interplayer, the Na/K ATPase α2 subunit. Conversely, the MCT1 mRNA level was significantly raised in the cerebellum of vs. WT control group, without a substantial change in the Na/K ATPase α2 subunit expression. To validate the observed mRNA findings, we confirmed the observed change in MCT1 mRNA expression level in the cortex at the protein level. MCT4, highly expressed in tissues that rely on glycolysis as an energy source, exhibited a significant reduction in the hippocampus of vs. WT mice. The present study demonstrates that a lack of PrP leads to altered MCT1 and MCT4 mRNA/protein expression in different brain regions of vs. WT mice. Our findings provide evidence that PrP might affect the monocarboxylate intercellular transport, which needs to be confirmed in further studies.
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http://dx.doi.org/10.3390/ijms22041566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913939PMC
February 2021

T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation.

Int J Mol Sci 2021 Jan 26;22(3). Epub 2021 Jan 26.

Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 03128 Dresden, Germany.

Since the first description of nuclear autoantigens in the late 1960s and early 1970s, researchers, including ourselves, have found it difficult to establish monoclonal antibodies (mabs) against nuclear antigens, including the La/SS-B (Sjögrens' syndrome associated antigen B) autoantigen. To date, only a few anti-La mabs have been derived by conventional hybridoma technology; however, those anti-La mabs were not bona fide autoantibodies as they recognize either human La specific, cryptic, or post-translationally modified epitopes which are not accessible on native mouse La protein. Herein, we present a series of novel murine anti-La mabs including truly autoreactive ones. These mabs were elicited from a human La transgenic animal through adoptive transfer of T cells from non-transgenic mice immunized with human La antigen. Detailed epitope and paratope analyses experimentally confirm the hypothesis that somatic hypermutations that occur during T cell dependent maturation can lead to autoreactivity to the nuclear La/SS-B autoantigen.
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http://dx.doi.org/10.3390/ijms22031198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865296PMC
January 2021

Generating the American Shoulder and Elbow Surgeons Score Using Multivariable Predictive Models and Computer Adaptive Testing to Reduce Survey Burden.

Am J Sports Med 2021 03 1;49(3):764-772. Epub 2021 Feb 1.

Investigation performed at the Defense Health Agency, Military Health System for the US Military, Rosslyn, Virginia, USA.

Background: The preferred patient-reported outcome measure for the assessment of shoulder conditions continues to evolve. Previous studies correlating the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CATs) to the American Shoulder and Elbow Surgeons (ASES) score have focused on a singular domain (pain or physical function) but have not evaluated the combined domains of pain and physical function that compose the ASES score. Additionally, previous studies have not provided a multivariable prediction tool to convert PROMIS scores to more familiar legacy scores.

Purpose: To establish a valid predictive model of ASES scores using a nonlinear combination of PROMIS domains for physical function and pain.

Study Design: Cohort study (Diagnosis); Level of evidence, 3.

Methods: The Military Orthopaedics Tracking Injuries and Outcomes Network (MOTION) database is a prospectively collected repository of patient-reported outcomes and intraoperative variables. Patients in MOTION research who underwent shoulder surgery and completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at varying time points were included in the present analysis. Nonlinear multivariable predictive models were created to establish an ASES index score and then validated using "leave 1 out" techniques and minimal clinically important difference /substantial clinical benefit (MCID/SCB) analysis.

Results: A total of 909 patients completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at presurgery, 6 weeks, 6 months, and 1 year after surgery, providing 1502 complete observations. The PROMIS CAT predictive model was strongly validated to predict the ASES (Pearson coefficient = 0.76-0.78; = 0.57-0.62; root mean square error = 13.3-14.1). The MCID/SCB for the ASES was 21.7, and the best ASES index MCID/SCB was 19.4, suggesting that the derived ASES index is effective and can reliably re-create ASES scores.

Conclusion: The PROMIS CAT predictive models are able to approximate the ASES score within 13 to 14 points, which is 7 points more accurate than the ASES MCID/SCB derived from the sample. Our ASES index algorithm, which is freely available online (https://osf.io/ctmnd/), has a lower MCID/SCB than the ASES itself. This algorithm can be used to decrease patient survey burden by 11 questions and provide a reliable ASES analog to clinicians.
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http://dx.doi.org/10.1177/0363546520987240DOI Listing
March 2021

Disentangling multiple chemical and non-chemical stressors in a lotic ecosystem using a longitudinal approach.

Sci Total Environ 2021 May 25;769:144324. Epub 2020 Dec 25.

Helmholtz Centre for Environmental Research - UFZ, Department River Ecology, Brückstr. 3a, 39114 Magdeburg, Germany.

Meeting ecological and water quality standards in lotic ecosystems is often failed due to multiple stressors. However, disentangling stressor effects and identifying relevant stressor-effect-relationships in complex environmental settings remain major challenges. By combining state-of-the-art methods from ecotoxicology and aquatic ecosystem analysis, we aimed here to disentangle the effects of multiple chemical and non-chemical stressors along a longitudinal land use gradient in a third-order river in Germany. We distinguished and evaluated four dominant stressor categories along this gradient: (1) Hydromorphological alterations: Flow diversity and substrate diversity correlated with the EU-Water Framework Directive based indicators for the quality element macroinvertebrates, which deteriorated at the transition from near-natural reference sites to urban sites. (2) Elevated nutrient levels and eutrophication: Low to moderate nutrient concentrations together with complete canopy cover at the reference sites correlated with low densities of benthic algae (biofilms). We found no more systematic relation of algal density with nutrient concentrations at the downstream sites, suggesting that limiting concentrations are exceeded already at moderate nutrient concentrations and reduced shading by riparian vegetation. (3) Elevated organic matter levels: Wastewater treatment plants (WWTP) and stormwater drainage systems were the primary sources of bioavailable dissolved organic carbon. Consequently, planktonic bacterial production and especially extracellular enzyme activity increased downstream of those effluents showing local peaks. (4) Micropollutants and toxicity-related stress: WWTPs were the predominant source of toxic stress, resulting in a rapid increase of the toxicity for invertebrates and algae with only one order of magnitude below the acute toxic levels. This toxicity correlates negatively with the contribution of invertebrate species being sensitive towards pesticides (SPEAR index), probably contributing to the loss of biodiversity recorded in response to WWTP effluents. Our longitudinal approach highlights the potential of coordinated community efforts in supplementing established monitoring methods to tackle the complex phenomenon of multiple stress.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144324DOI Listing
May 2021

Short term outcomes of an enhanced recovery after surgery (ERAS) pathway versus a traditional discharge pathway after posterior spinal fusion for adolescent idiopathic scoliosis.

Spine Deform 2021 Jan 18. Epub 2021 Jan 18.

British Columbia Children's Hospital, Vancouver, BC, USA.

Purpose: Enhanced Recovery after Surgery (ERAS) pathways have been shown to decrease length of stay (LOS) after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). The aim of this study was to compare immediate post-operative outcomes following an ERAS pathway with a traditional pathway for AIS.

Methods: A prospective dual-center study of patients treated using an ERAS pathway (203 patients) or a traditional discharge (TD) pathway (73 patients) was performed with focus on pain at discharge, quality of life at one month, and return to school/work.

Results: LOS was 55% less in the ERAS group (4.8 days TD vs. 2.2 days ERAS, p < 0.001). Length of surgery (4.8 h TD vs. 2.8 h, p < 0.001) and EBL (500 cc vs. 240 cc, p < 0.001) were greater in the TD group, likely related to larger curve magnitudes ((62.0° TD vs. 54.0° ERAS, p < 0.001), a higher percentage of patients undergoing osteotomies (94% vs. 46%, p < 0.001) and more levels fused (11.4 ± 1.6 vs. 10.1 ± 2.6, p < 0.001) in the TD group. Regression analysis showed no difference in Visual Analog Score (VAS) score at discharge or quality of recovery using the QOR9 instrument between groups at follow up. There was no difference in return to school (p = 0.43) and parents' return to work (p = 0.61) between the groups.

Conclusion: Patients managed with an ERAS pathway had similar pain scores at discharge than those managed with a TD pathway. Both groups showed evidence of rapid return to normalcy by the first follow up visit.
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http://dx.doi.org/10.1007/s43390-020-00282-3DOI Listing
January 2021

A cross-industry collaboration to assess if acute oral toxicity (Q)SAR models are fit-for-purpose for GHS classification and labelling.

Regul Toxicol Pharmacol 2021 Mar 17;120:104843. Epub 2020 Dec 17.

Leadscope (an Instem company), 1393 Dublin Rd, Columbus, OH, 43215, USA. Electronic address:

This study assesses whether currently available acute oral toxicity (AOT) in silico models, provided by the widely employed Leadscope software, are fit-for-purpose for categorization and labelling of chemicals. As part of this study, a large data set of proprietary and marketed compounds from multiple companies (pharmaceutical, plant protection products, and other chemical industries) was assembled to assess the models' performance. The absolute percentage of correct or more conservative predictions, based on a comparison of experimental and predicted GHS categories, was approximately 95%, after excluding a small percentage of inconclusive (indeterminate or out of domain) predictions. Since the frequency distribution across the experimental categories is skewed towards low toxicity chemicals, a balanced assessment was also performed. Across all compounds which could be assigned to a well-defined experimental category, the average percentage of correct or more conservative predictions was around 80%. These results indicate the potential for reliable and broad application of these models across different industrial sectors. This manuscript describes the evaluation of these models, highlights the importance of an expert review, and provides guidance on the use of AOT models to fulfill testing requirements, GHS classification/labelling, and transportation needs.
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http://dx.doi.org/10.1016/j.yrtph.2020.104843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005249PMC
March 2021

Integrative public data-mining pipeline for the validation of novel independent prognostic biomarkers for lung adenocarcinoma.

Biomark Med 2020 12;14(17):1651-1662

Division of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

We aimed to develop a candidate-based integrative public data mining strategy for validation of novel prognostic markers in lung adenocarcinoma. An approach integrating meta-analyses of publicly available clinical information linked RNA expression, gene copy number and mutation datasets combined with independent immunohistochemistry and survival datasets. After validation of pipeline integrity utilizing data from the well-characterized prognostic factor Ki-67, prognostic impact of the calcium- and integrin-binding protein, CIB1, was analyzed. CIB1 was overexpressed in lung adenocarcinoma which correlated with pathological tumor and pathological lymph node status and impaired overall/progression-free survival. In multivariate analyses, CIB1 emerged as UICC stage-independent risk factor for impaired survival. Our pipeline holds promise to facilitate further identification and validation of novel lung cancer-associated prognostic markers.
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http://dx.doi.org/10.2217/bmm-2020-0405DOI Listing
December 2020

Optimization of the Real-Time Quaking-Induced Conversion Assay for Prion Disease Diagnosis.

Front Bioeng Biotechnol 2020 19;8:586890. Epub 2020 Nov 19.

Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University Medical Center Göttingen, Göttingen, Germany.

The real-time quaking-induced conversion (RT-QuIC) assay is a highly reproducible and robust methodology exhibiting an excellent pre-mortem diagnostic accuracy for prion diseases. However, the protocols might be time-consuming and improvement of the detection technology is needed. In the present study, we investigated the influence of a pre-analytical cerebrospinal fluid (CSF) treatment with proteinase K (PK) on the kinetic of the RT-QuIC signal response. For this purpose, we added PK at different concentrations in RT-QuIC reactions seeded with Creutzfeldt-Jakob disease (sCJD) CSF. We observed that a mild pre-analytical PK treatment of CSF samples resulted in an increased seeding efficiency of the RT-QuIC reaction. Quantitative seeding parameters, such as a higher area under the curve (AUC) value or a shorter lag phase indicated a higher conversion efficiency after treatment. The diagnostic accuracy resulting from 2 μg/ml PK treatment was analyzed in a retrospective study, where we obtained a sensitivity of 89%. Additionally, we analyzed the agreement with the previously established standard RT-QuIC protocol without PK treatment in a prospective study. Here, we found an overall agreement of 94% to 96%. A Cohen's kappa of 0.9036 (95% CI: 0.8114-0.9958) indicates an almost perfect agreement between both protocols. In conclusion, the outcome of our study can be used for a further optimization of the RT-QuIC assay in particular for a reduction of the testing time.
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http://dx.doi.org/10.3389/fbioe.2020.586890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710546PMC
November 2020

The Military Orthopedics Tracking Injuries and Outcomes Network: A Solution for Improving Musculoskeletal Care in the Military Health System.

Mil Med 2020 Nov 26. Epub 2020 Nov 26.

Department of Orthopaedics, Walter Reed National Military Medical Center, Bethesda, MD 20889.

Introduction: Musculoskeletal injuries are an endemic amongst U.S. Military Service Members and significantly strain the Department of Defense's Military Health System. The Military Health System aims to provide Service Members, military retirees, and their families the right care at the right time. The Military Orthopedics Tracking Injuries and Outcomes Network (MOTION) captures the data that can optimize musculoskeletal care within the Military Health System. This report provides MOTION structural framework and highlights how it can be used to optimize musculoskeletal care.

Materials And Methods: MOTION established an internet-based data capture system, the MOTION Musculoskeletal Data Portal. All adult Military Health System patients who undergo orthopedic surgery are eligible for entry into the database. All data are collected as routine standard of care, with patients and orthopedic surgeons inputting validated global and condition-specific patient reported outcomes and operative case data, respectively. Patients have the option to consent to allow their standard of care data to be utilized within an institutional review board approved observational research study. MOTION data can be merged with other existing data systems (e.g., electronic medical record) to develop a comprehensive dataset of relevant information. In pursuit of enhancing musculoskeletal injury patient outcomes MOTION aims to: (1) identify factors which predict favorable outcomes; (2) develop models which inform the surgeon and military commanders if patients are behind, on, or ahead of schedule for their targeted return-to-duty/activity; and (3) develop predictive models to better inform patients and surgeons of the likelihood of a positive outcome for various treatment options to enhance patient counseling and expectation management.

Results: This is a protocol article describing the intent and methodology for MOTION; thus, to date, there are no results to report.

Conclusions: MOTION was established to capture the data that are necessary to improve military medical readiness and optimize medical resource utilization through the systematic evaluation of short- and long-term musculoskeletal injury patient outcomes. The systematic enhancement of musculoskeletal injury care through data analyses aligns with the National Defense Authorization Act (2017) and Defense Health Agency's Quadruple Aim, which emphasizes optimizing healthcare delivery and Service Member medical readiness. This transformative approach to musculoskeletal care can be applied across disciplines within the Military Health System.
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http://dx.doi.org/10.1093/milmed/usaa304DOI Listing
November 2020

Pharmacokinetics and Optimal Dose Selection of Cefazolin for Surgical Prophylaxis of Pediatric Patients.

J Clin Pharmacol 2021 May 9;61(5):666-676. Epub 2020 Dec 9.

B. Braun Medical Inc., Allentown, Pennsylvania, USA.

Cefazolin is an antibiotic frequently used for perioperative prophylaxis. Data from healthy adults and pediatric surgery patients were pooled to refine a previously developed population pharmacokinetic (PK) model and to determine the optimal body weight cutoff for selecting fixed doses of either 1 or 2 g cefazolin to produce exposures in pediatric surgery patients similar to a single 2-g dose in adults. Regardless of dose used, cefazolin was well tolerated in pediatric patients. A total of 1102 plasma samples from 62 patients from 3 studies were available to assess the previous model. The pooled data set allowed for simplification of the model such that allometrically scaled clearance and volume parameters were found to provide a robust fit while removing unnecessary covariate relationships. Monte Carlo simulations using the final cefazolin population PK model suggested an optimal weight cutoff of 50 kg, in contrast to the previously suggested 60 kg for a single 2-g dose. Patients at or above this 50-kg cutoff would receive a 2-g dose of cefazolin, and those below 50 kg but ≥25 kg would receive a 1-g dose of cefazolin.
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http://dx.doi.org/10.1002/jcph.1785DOI Listing
May 2021

Triage of hrHPV-positive women: comparison of two commercial methylation-specific PCR assays.

Clin Epigenetics 2020 11 11;12(1):171. Epub 2020 Nov 11.

Klinik und Poliklinik für Frauenheilkunde und Fortpflanzungsmedizin, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Germany.

Aim: High-risk human papillomavirus (hrHPV)-based screening is becoming increasingly important, either by supplementing or replacing the traditional cytology-based cervical Pap smear. However, hrHPV screening lacks specificity, because it cannot differentiate between transient virus infection and clinically relevant hrHPV-induced disease. Therefore, reliable triage methods are needed for the identification of HPV-positive women with cervical intraepithelial neoplasia (CIN) in need of treatment. Promising tools discussed for the triage of these patients are molecular diagnostic tests based on epigenetic markers. Here, we compare the performance of two commercially available DNA methylation-based diagnostic assays-GynTect® and the QIAsure Methylation Test-in physician-taken cervical scrapes from 195 subjects.

Findings: Both GynTect® and the QIAsure Methylation Test detected all cervical carcinoma and carcinoma in situ (CIS). The differences observed in the detection rates between both assays for the different grades of cervical lesions (QIAsure Methylation Test: CIN1 26.7%, CIN2 27.8% and CIN3 74.3%; GynTect®: CIN1 13.3%, CIN2 33.3% and CIN3 60%) were not significant. Concerning the false-positive rates, significant differences were evident. For the healthy (NILM) hrHPV-positive group, the false-positive rates were 5.7% for GynTect® and 26.4% for QIAsure Methylation Test (p = 0.003) and for the NILM hrHPV-negative group 2.2% vs. 23.9% (p = 0.006), respectively. When considering hrHPV-positive samples only for comparison (n = 149), GynTect® delivered significantly higher specificity compared to the QIAsure Methylation Test for CIN2 + (87.6% vs. 67.4% (p < 0.001)) and CIN3 + (84.1% vs. 68.2% (p = 0.002)). Overall our findings suggest that DNA methylation-based tests are suitable for the triage of hrHPV-positive women. With the goal to provide a triage test that complements the limited specificity of HPV testing in HPV-based screening, GynTect® may be preferable, due to its higher specificity for CIN2+ or CIN3+ .
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http://dx.doi.org/10.1186/s13148-020-00963-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661165PMC
November 2020

Current Practice Patterns in Anterior Cruciate Ligament Reconstruction Among Fellowship-Trained Military Orthopaedic Surgeons.

Arthrosc Sports Med Rehabil 2020 Oct 14;2(5):e523-e529. Epub 2020 Oct 14.

San Antonio Military Medical Center, Fort Sam Houston, Texas, U.S.A.

Purpose: To evaluate current practice patterns in anterior cruciate ligament reconstruction (ACLR) surgery among fellowship-trained military surgeons.

Methods: The MOTION database is a prospectively collected dataset of intraoperative variables across the Military Health System. This database was queried using Current Procedural Terminology code 29888 for ACLR among active-duty service members between October 2016 and December 2019. The intraoperative data pertaining to ACLR involving both isolated primary ACLRs and primary ACLRs combined with meniscal or chondral injuries were extracted with patient age, sex, and rank.

Results: Two hundred sixty-six primary ACLRs performed by 21 fellowship-trained orthopaedic surgeons at 9 MTFs were identified. The mean age of patients undergoing ACLR was 27.2 ± 7.7 years. Bone-patellar tendon-bone autograft was the most commonly used graft source (137 of 266 [51.5%] cases.) Meniscal injuries were treated with an isolated debridement in 53 of 156 (34.0%) tears, whereas meniscal repair was performed in 86 of 156 (55.1%) tears. Concomitant chondral pathology was noted in 43 of 266 cases (16.2%) and most commonly addressed with chondroplasty (25 of 49 [51.0%] chondral lesions).

Conclusions: Bone-patellar tendon-bone autograft was the most commonly used graft type in ACLR among fellowship-trained surgeons treating active-duty service members. Concomitant meniscal pathology was encountered at rates comparable with what has been previously reported, and meniscal repair was favored over meniscal debridement in more than 50% cases.

Level Of Evidence: Level IV: Therapeutic case series.
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http://dx.doi.org/10.1016/j.asmr.2020.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588646PMC
October 2020

Retrospective analysis of free temporoparietal fascial flap for defect reconstruction of the hand and the distal upper extremity.

Arch Orthop Trauma Surg 2021 Jan 1;141(1):165-171. Epub 2020 Nov 1.

Department of Plastic and Hand Surgery of the Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstr. 12, 91054, Erlangen, Germany.

Introduction: Soft tissue reconstruction of the hand and distal upper extremity is challenging to preserve the function of the hand as good as possible. Therefore, a thin flap has been shown to be useful. In this retrospective study, we aimed to show the use of the free temporoparietal fascial flap in soft tissue reconstruction of the hand and distal upper extremity.

Methods: We analysed the outcome of free temporoparietal fascial flaps that were used between the years 2007and 2016 at our institution. Major and minor complications, defect location and donor site morbidity were the main fields of interest.

Results: 14 patients received a free temporoparietal fascial flap for soft tissue reconstruction of the distal upper extremity. Minor complications were noted in three patients and major complications in two patients. Total flap necrosis occurred in one patient.

Conclusion: The free temporoparietal fascial flap is a useful tool in reconstructive surgery of the hand and the distal upper extremity with a low donor site morbidity and moderate rates of major and minor complications.
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http://dx.doi.org/10.1007/s00402-020-03635-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815614PMC
January 2021