50 results on '"Kremer T"'
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2. A new quantitative method for determining patient risk for reusable medical device categorization based on using and interpreting Kremer's cleaning classification system
- Author
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Kremer, T., Rowan, N.J., and McDonnell, G.
- Published
- 2024
- Full Text
- View/download PDF
3. A review of Spaulding's classification system for effective cleaning, disinfection and sterilization of reusable medical devices: Viewed through a modern-day lens that will inform and enable future sustainability
- Author
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Rowan, N.J., Kremer, T., and McDonnell, G.
- Published
- 2023
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4. Use of real-time immersive digital training and educational technologies to improve patient safety during the processing of reusable medical devices: Quo Vadis?
- Author
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Kremer, T., primary, Murray, N., additional, Buckley, J., additional, and Rowan, N.J., additional
- Published
- 2023
- Full Text
- View/download PDF
5. A review of Spaulding's classification system for effective cleaning, disinfection and sterilization of reusable medical devices: Viewed through a modern-day lens that will addresses future sustainability
- Author
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Rowan, N.J., primary, Kremer, T., additional, and McDonnell, G., additional
- Published
- 2023
- Full Text
- View/download PDF
6. Handinfektionen: Analyse des Einflusses des Glukosemetabolismus und Evaluation des Charlson-Komorbiditätsindexes als prognostisches Hilfsmittel
- Author
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Sorowka, A, Grünewald, T, Kremer, T, Rein, S, Sorowka, A, Grünewald, T, Kremer, T, and Rein, S
- Published
- 2023
7. Dreidimensionelle Analyse der morphologischen Struktur von sensorischen Nervenendigungen in der Pars dorsalis des Ligamentum scapholunatum interosseum
- Author
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Al Meklef, R, Kremer, T, Siemers, F, Rein, S, Al Meklef, R, Kremer, T, Siemers, F, and Rein, S
- Published
- 2023
8. Mikrobiologische Untersuchungen bei Handinfektionen: eine prospektive Studie
- Author
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Sorowka, A, Grünewald, T, Kremer, T, Rein, S, Sorowka, A, Grünewald, T, Kremer, T, and Rein, S
- Published
- 2023
9. Dreidimensionale Korrektur der thorakolumbalen Wirbelsäule nach Resektion eines Sarkoms
- Author
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Keil, H., Kreinest, M., Kneser, U., Kremer, T., Schnetzke, M., Grützner, P., and Matschke, S.
- Abstract
Es wird über den Fall einer hochgradigen Deformität der thorakolumbalen Wirbelsäule nach Resektion eines Sarkoms berichtet. Nach adjuvanter Radiatio bestand ein ausgedehnter Strahlenschaden im Bereich der Haut mit chronischer Fistelung. Es erfolgte die Korrektur über eine Closing-Wedge-Osteotomie von L3 und Verlängerung der vorhandenen dorsalen Instrumentierung (Th10-L4) auf Th8 und das Os ileum. Am Folgetag erfolgte eine Weichteildeckung durch eine freie Latissimus-dorsi-Lappenplastik, welche an eine arterio-venöse Gefäßschleife in der Axilla angeschlossen wurde. Durch dieses interdisziplinäre Vorgehen konnte eine nahezu vollständige Korrektur und eine sichere Weichteildeckung erreicht werden. This article presents the case of a high-grade deformity of the thoraco-lumbar spine. The patient suffered from a sarcoma that was radically resected. Due to adjuvant radiation, the patient suffered from a radiation injury with chronic fistula. In a two-stage approach, the deformity was corrected by a closing-wedge osteotomy of L3 with elongation of the present dorsal spondylodesis (Th10-L4) to Th8 and the iliac bone. Soft-tissue reconstruction was achieved by a free latissimus dorsi flap that was anastomosed to an axillary arterio-venous loop. The presented interdisciplinary approach allowed an almost complete correction of the deformity and stable soft-tissue coverage.
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- 2024
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10. A new passive seismic monitoring strategy for the exploration of natural Hydrogen and Helium occurrences.
- Author
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Kremer, T., primary, Ars, J., additional, Laine, C., additional, Mouquet, P., additional, Peignard, L., additional, Lenir, I., additional, and Voisin, C., additional
- Published
- 2023
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11. Subsurface Fluid Monitoring by Multi-Purposing Microseismic Sensor Arrays
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Gouédard, P., primary, Kremer, T., additional, Ars, J., additional, Renat, Z., additional, Gaubert, T., additional, Voisin, C., additional, Engels, O., additional, Embry, J., additional, and Ferran, J., additional
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- 2023
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12. Integrated Workflow for Natural H2 Exploration
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Rigollet, C., primary, Ars, J., additional, Dupuy, J., additional, Fabre, G., additional, Ferran, J., additional, Kremer, T., additional, Lefeuvre, N., additional, Neumaier, M., additional, Prinzhofer, A., additional, Thomas, E., additional, and Voisin, C., additional
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- 2023
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13. 680 Effects of elexacaftor/tezacaftor/ivacaftor on growth and puberty in children with cystic fibrosis.
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Darukhanavala, A., Kremer, T., Trivedi, M., Dy, F., Onge, I. St., and Longtine, J.
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- *
CYSTIC fibrosis - Published
- 2024
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14. Ist Ausbildung in der ambulanten Handchirurgie zu zeitaufwendig? Vergleich der OP-Zeiten zwischen Weiterbildungsassistenten und Fachärzten
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Graß, C, Rein, S, Pötschke, J, and Kremer, T
- Subjects
ambulante Handchirurgie ,retrospektiv ,ddc: 610 ,Weiterbildung ,Medicine and health ,OP-Zeiten - Abstract
Fragestellung: Ambulante handchirurgische Operationszentren stehen unter einem hohen ökonomischen Druck, sodass möglichst kurze OP-Zeiten angestrebt werden. Für zahlreiche Eingriffe wurde allerdings gezeigt, dass die Durchführung eines operativen Eingriffs durch einen Assistenzarzt [zum vollständigen Text gelangen Sie über die oben angegebene URL]
- Published
- 2022
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15. Patellarekonstruktion durch revaskularisiertes Homograft
- Author
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Schneider, S, Kremer, T, Rein, S, Malmström, N, Böhme, J, Schneider, S, Kremer, T, Rein, S, Malmström, N, and Böhme, J
- Published
- 2022
16. Mott–Hubbard insulating state for the layered van der Waals FePX 3 (X: S, Se) as revealed by NEXAFS and resonant photoelectron spectroscopy
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Jin, Y., Yan, M., Kremer, T., Voloshina, E., Dedkov, Y.
- Published
- 2022
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17. Improved Reconstruction and Coherence Analysis of a Wave-Field Extracted from Ambient Seismic Noise Cross-Correlations.
- Author
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Kremer, T., primary, Mouquet, P., additional, Kasantsev, A., additional, Grauls, A., additional, and Voisin, C., additional
- Published
- 2022
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18. 156: Pre-procedural Sars-CoV-2 testing and pulmonary function testing
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Onge, I. St, primary, Dy, F., additional, Trivedi, M., additional, Longtine, J., additional, Longtine, K., additional, Fish, D., additional, Bielick, C., additional, Schaefer, O., additional, and Kremer, T., additional
- Published
- 2021
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19. 159: Lung function changes following Sars-CoV-2 infection in cystic fibrosis
- Author
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Kremer, T., primary, Onge, I. St, additional, Trivedi, M., additional, Dy, F., additional, Bielick, C., additional, Fish, D., additional, Schaefer, O., additional, Longtine, J., additional, and Longtine, K., additional
- Published
- 2021
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20. A standardized method for evaluating test soils used to demonstrate cleaning efficacy.
- Author
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Kremer, T A, Bancroft, R, Patel, Z, Owen, M, and McDonnell, G
- Abstract
Background: Cleaning and associated validation requirements are essential for the safe use of reusable devices. In the past, test methods and associated endpoints for cleaning validations have varied worldwide. Recent international standards have updated the requirements to include cleaning endpoints and requirements for the use of test soils for demonstrating cleaning efficacy of washer-disinfectors.Methods: A quantitative comparison of test soils used in cleaning efficacy studies was conducted using a new standardized test method as published in Annexe B ISO 15883-5:2021. Test soils included Artificial Test Soil (ATS 2015), Blood Test Soil (BTS), Coagulated Blood, Defibrinated Blood Soil (DBLSO), Modified Coagulated Blood Soil, Two Component Blood Test Soil and the UK Test Soil (Edinburgh Soil).Conclusion: All the test soils demonstrated acceptable performance in accordance with the standard. [ABSTRACT FROM AUTHOR]- Published
- 2022
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21. Brain expression profiles of two SCN1A antisense RNAs in children and adolescents with epilepsy
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Schneider Marius Frederik, Vogt Miriam, Scheuermann Johanna, Müller Veronika, Fischer-Hentrich Antje H. L., Kremer Thomas, Lugert Sebastian, Metzger Friedrich, Kudernatsch Manfred, Kluger Gerhard, Hartlieb Till, Noachtar Soheyl, Vollmar Christian, Kunz Mathias, Tonn Jörg Christian, Coras Roland, Blümcke Ingmar, Pace Claudia, Heinen Florian, Klein Christoph, Potschka Heidrun, and Borggraefe Ingo
- Subjects
dravet syndrome ,long non coding rna ,regulatory rna ,precision medicine ,epilepsy ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Heterozygous mutations within the voltage-gated sodium channel α subunit (SCN1A) are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of SCN1A are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches.
- Published
- 2024
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22. The use of passive seismic interferometry for the monitoring of subsurface fluids – from shallow groundwater to native or storage gas reservoirs
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Kremer Thomas, Voisin Christophe, Gaubert-Bastide Thomas, Ars Jean-Michel, Mouquet Pascal, Moinet Frédéric, and Ferran Jean-Charles
- Subjects
Environmental sciences ,GE1-350 - Abstract
Passive (ambient noise) seismic interferometry provides multiple ways to gather information about the subsurface seismic properties using recordings of the seismic ambient noise signal. While the first developments and applications of this method showed a useful capacity to either image geological contrasts or monitor the structural properties of the soil, an increasing momentum is observed toward applications related to fluid monitoring of different types (liquid, gas), at all the scales of the subsurface (from meters to kilometers). In this paper we summarize the existing possibilities and technics of seismic interferometry analysis for subsurface fluid detection and characterization and elaborate on their respective deployment in different contexts. We also present a new approach based on estimating and continuously measuring seismic attenuation proxy within interferometric-based surface wavefields, which show a high sensitivity to fluid dynamics and the associated petrophysical variations. The method is illustrated through a field case study related to geological gas storage monitoring, and we elaborate on its potential respective deployment at the industrial scale and for different applications.
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- 2024
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23. [Autologous Breast Reconstruction and Radiotherapy: Consensus Report of the German-Speaking Society for Reconstructive Microsurgery (GSRM)].
- Author
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Heine-Geldern A, Hirche C, Kremer T, Lössl K, Bach AD, Russe E, Fansa H, Beier JP, Harder Y, and Momeni A
- Abstract
Autologous postmastectomy breast reconstruction is associated with favourable long-term clinical outcomes and superior patient-reported outcomes (PROMs) compared with implant-based reconstruction. However, adjuvant radiotherapy has traditionally been considered a relative contraindication to immediate flap-based reconstruction due to its unpredictable effects on the reconstructive outcome. While modern adjuvant postmastectomy radiotherapy (PMRT) has been able to significantly reduce acute and chronic radiation-induced complications, plastic surgeons still hesitate to offer immediate autologous reconstruction to patients expected to undergo adjuvant radiotherapy. More recently, evidence has emerged suggesting a paradigm shift in favour of immediate autologous reconstruction despite subsequent radiotherapy. At the 44
th Annual Meeting of the German-speaking Society for Reconstructive Microsurgery (GSRM) in Bern, Switzerland, a workshop discussed the literature on PMRT and autologous breast reconstruction, aiming to establish consensus among the participants. Several areas of agreement were identified, including the goals of postmastectomy reconstruction, specifically the creation of a soft and sensitive breast symmetrical in shape and size to the unaffected breast via the safest procedure possible. The importance of preserving the maximum amount of native breast skin envelope through skin- and nipple-sparing approaches was emphasised. Finally, a consensus was reached that PMRT should no longer be considered a contraindication to immediate autologous breast reconstruction., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)- Published
- 2024
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24. [Hand Surgery Training Structure in Germany - Evaluation of an Online Questionnaire].
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Rische C, Schmiechen J, Kremer T, and Rein S
- Subjects
- Humans, Germany, Surveys and Questionnaires, Female, Male, Curriculum, Adult, Faculty, Medical statistics & numerical data, Clinical Competence, Internship and Residency, Hand surgery
- Abstract
Background: The duration of the training for hand surgery in Germany was reduced from three to two years in 2020, while other European Countries introduced hand surgery as a separate surgical specialty. Therefore, the structure of hand surgery training in Germany is under intense, ongoing discussion., Objectives: This study aimed to evaluate the current situation of hand surgery training in Germany., Material and Methods: Two separate online questionnaires were developed for self-assessment of residents and teachers in German hand surgery services. The questionnaire contained 29 questions for residents and 24 questions for teachers. Demographic data, educational tools, surgical training parameters and satisfaction were assessed from May to July 2023. The survey was based on the former training time of three years. The online questionnaire was sent to the members and associate members of the German Society for Hand Surgery via email., Results: 148 participants answered the questionnaire, including 54 residents and 94 teachers. Overall, more female residents were assessed, whereas the majority of teachers was male. Hand surgery training is mostly conducted in high-level hospitals (tertiary care p=0.012, quaternary care p<0.001). Residents use digital teaching media significantly more often than teachers do (p<0.001). In contrast, teachers use journals (p=0.006) and clinical visits (p=0.024) significantly more often for their training than residents do. Trainers and trainees mostly agreed about time points of surgical milestones during surgical training that should be performed independently. Both trainers and trainees were largely satisfied with the practical and theoretical training in hand surgery., Conclusions: The importance of digital media in hand surgery training will increase in the near future. Therefore, digital media should be more frequently included in hand surgery training protocols. The study revealed that the majority of residents as well as teachers would appreciate the introduction of an independent hand surgery specialty, which would most likely improve the hand surgery competence in Germany., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
- Published
- 2024
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25. Prospective analysis of glucose metabolism in patients with hand infection.
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Sorowka A, Kremer T, Grünewald T, Hagert E, and Rein S
- Subjects
- Humans, Male, Female, Prospective Studies, Middle Aged, Aged, Adult, Blood Glucose metabolism, Hand surgery, Length of Stay statistics & numerical data, Diabetes Mellitus, Type 2 metabolism, Prediabetic State metabolism, Glycated Hemoglobin metabolism, C-Reactive Protein metabolism, Glucose Tolerance Test
- Abstract
Background: Type-2 diabetes influences the course and severity of hand infections., Methods: We prospectively examined glucose metabolism in 90 patients with hand infection, distinguishing between normal, prediabetic and diabetic states. HbA1c-levels were evaluated prior to surgery. Patients with normal levels took an oral glucose tolerance test and those diagnosed with prediabetes were retested after the infection subsided. Hospital stay, number of surgical interventions and inflammatory markers were examined per group., Results: Sixty-two patients (68.8%) had abnormal glucose metabolism: 17 (18.9%) with history of diabetes and 11 (12.2%) newly diagnosed. Prediabetes was observed in 34 patients (37.8%). At follow-up, prediabetes and diabetes were diagnosed in 7 cases each, and physiological glucose metabolism was observed in 3 patients. For the 11 patients unable to undergo a second oral glucose tolerance test, detailed phone calls confirmed absence of diabetes. C-reactive protein levels were significantly elevated in diabetic patients compared to those with normal glucose metabolism (p = 0.001) or prediabetes (p = 0.034). Patients with history of diabetes were significantly older than those with normal glucose tolerance (p = 0.001) or prediabetes (p = 0.017). There were no significant intergroup differences in thrombocyte count, length of hospital stay, interval from injury to admission or the number surgical interventions., Conclusion: Glucose metabolism should be assessed in patients with hand infections and reassessed after the infection has subsided in prediabetic cases., (Copyright © 2024 SFCM. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
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26. [Acute and post-acute soft tissue reconstruction].
- Author
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Al Meklef R, Rein S, and Kremer T
- Subjects
- Humans, Debridement methods, Surgical Flaps innervation, Male, Burns surgery, Soft Tissue Injuries surgery, Plastic Surgery Procedures methods
- Abstract
Background: The precise analysis of the injured structures requiring reconstruction in complex wound defects is a prerequisite for successful restoration., Objective: The fundamental reconstructive strategies for soft tissue defects of the extremities including injuries to vessels, nerves and burn wounds in the context of the acute and post-acute trauma phases are presented., Material and Methods: The different phases of soft tissue reconstruction are described. Recommendations for action with respect to the reconstruction of the functional structures are described. Two clinical case examples illustrate the approach., Results: The acute reconstruction phase is defined as the period 0-72 h after the traumatic event and includes surgical debridement, primary reconstruction of nerves and vessels using interpositional grafts if necessary and temporary soft tissue reconstruction. Combined thermomechanical trauma requires early debridement combined with internal fixation of open fractures. In the post-acute reconstruction phase, which is generally defined as a period of up to 6 weeks after the traumatic event, definitive soft tissue reconstruction is performed. In the case of long reinnervation distances, nerve transfer or motor replacement plastic surgery is performed in the post-acute phase., Conclusion: The reconstruction of soft tissue after trauma necessitates a stage-dependent approach. In the acute phase procedures aim at the immediate preservation of the limb. In the post-acute phase, definitive soft tissue reconstruction is performed to enable maximum functional preservation. Combined thermomechanical injuries require early surgical treatment in order to prevent infections., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
- Published
- 2024
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27. Where Do They Come From and Where Do They Go? Socioeconomic Patterns in Dog Acquisition and Rehoming.
- Author
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Kremer T and Neal SM
- Abstract
This research examines the ways people acquire dogs in the US as well as the ways the dogs leave the household and the way these differ by income level in seven geographically diverse study communities. A web-based panel survey was distributed and received 6318 responses. Individuals were asked a series of demographic and socioeconomic questions as well as how they acquired their current dogs, how previous dogs left their household, and where they left to. The results indicate that the likelihood of acquiring a dog through friends and family decreased monotonically as income increased, while the opposite was observed for adopting and purchasing a dog. The likelihood of giving a dog away to a friend or family member also decreased as income increased, as opposed to shelter surrender-a person earning over USD 100,000 annually was more than four times likelier to surrender to a shelter than a person earning under USD 15,000. The results suggest a stronger reliance on informal social networks in lower-income communities for both obtaining and placing dogs. As these dogs would otherwise end up in the shelter system, animal shelters may support low-income pet owners to help keep their dogs within their community of care.
- Published
- 2024
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28. Periarticular Proprioception: Analyzing the Three-Dimensional Structure of Corpuscular Mechanosensors in the Dorsal Part of the Scapholunate Ligament.
- Author
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Al Meklef R, Kacza J, Kremer T, and Rein S
- Abstract
Introduction: Sensory nerve endings transmit mechanical stimuli into afferent neural signals and form the basis of proprioception, giving rise to the self-perception of dynamic stability of joints. We aimed to analyze the three-dimensional structure of periarticular corpuscular sensory nerve endings in a carpal ligament to enhance our understanding of their microstructure., Methods: Two dorsal parts of the scapholunate ligament were excised from two human cadaveric wrist specimens. Consecutive cryosections were stained with immunofluorescence markers protein S100B, neurotrophin receptor p75, protein gene product 9.5 (PGP 9.5), and 4',6-diamidino-2-phenylindole. Three-dimensional images of sensory nerve endings were obtained using confocal laser scanning microscopy, and subsequent analysis was performed using Imaris software., Results: Ruffini endings were characterized by a PGP 9.5-positive central axon, with a median diameter of 4.63 μm and a median of 25 cells. The p75-positive capsule had a range in thickness of 0.94 μm and 15.5 μm, consisting of single to three layers of lamellar cells. Ruffini endings were significantly smaller in volume than Pacini corpuscles or Golgi-like endings. The latter contained a median of three intracorpuscular structures. Ruffini endings and Golgi-like endings presented a similar structural composition of their capsule and subscapular space. The central axon of Pacini corpuscles was surrounded by S100-positive cells forming the inner core which was significantly smaller than the outer core, which was immunoreactive for p75 and PGP 9.5., Conclusion: This study reports new data regarding the intricate outer and intracorpuscular three-dimensional morphology of periarticular sensory nerve endings, including the volume, number of cells, and structural composition. These results may form a basis to differ between normal and pathological morphological changes in periarticular sensory nerve endings in future studies., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2024
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29. [Surgical management of burn injury patients : Comments on the guidelines on treatment of thermal injuries in adults].
- Author
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Rennekampff HO and Kremer T
- Subjects
- Adult, Humans, Debridement adverse effects, Skin, Skin Transplantation methods, Quality of Life, Burns surgery
- Abstract
The treatment of burn injury patients is a unique challenge for clinicians. The extent of thermal injuries ranges from very small burns to life-threatening burn injuries. Insufficient treatment can result in a substantial impairment in the quality of life. In order to avoid such sequelae a targeted treatment must be carried out. A precise diagnosis determines the necessary treatment. Superficial second-degree burns (2a) not involving the face, hand or joints with a total body surface area smaller than 10% can usually be treated with modern wound dressings in an outpatient setting. Deep second-degree burns (2b) are an indication for debridement. In addition to the classical surgical procedures with tangential excision, enzymatic debridement can also be employed. Similarly, indeterminate burns (2a/2b) are also considered to be an indication for enzymatic debridement. Third-degree burns are treated with early debridement and skin grafting. These patients can also benefit from special dermal replacement procedures for an improvement of the functional and esthetic results. Due to the long-term visible sequelae of burns, aftercare of these patients is indicated., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
30. Non degradation of chitosan and initial degradation of collagen nerve conduits used for protection of nerve coaptations.
- Author
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Rein S, Schober R, Poetschke J, and Kremer T
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- Male, Female, Humans, Adolescent, Young Adult, Adult, Middle Aged, Nerve Regeneration physiology, Collagen therapeutic use, Collagen metabolism, Prostheses and Implants, Sciatic Nerve injuries, Chitosan therapeutic use, Chitosan chemistry, Neuroma etiology, Neuroma prevention & control, Neuroma surgery
- Abstract
Background: Nerve conduits are either used to bridge nerve gaps of up to 3 cm or to protect nerve coaptations. Biodegradable nerve conduits, which are currently commercially available, include Chitosan or collagen-based ones. As histological aspects of their degradation are highly relevant for the progress of neuronal regeneration, the aim of this study was to report the histopathological signs of such nerve conduits, which were removed during revision surgery., Materials and Methods: Either Chitosan (n = 2) or collagen (n = 2) nerve conduits were implanted after neuroma resection and nerve grafting (n = 2) or traumatic nerve lesion after cut (n = 1) or crush injury (n = 1) in two females and two men, aged between 17 and 57 years. Revision surgery with removal of the nerve conduits was indicated due to persisting neuropathic pain and sensorimotor deficits, limited joint motion, or neurolysis with hardware removal at a median time of 17 months (range: 5.5-48 months). Histopathological analyses of all removed nerve conduits were performed., Results: A scar neuroma was diagnosed in one out of four patients. Mechanical complication occurred in one patient after nerve conduit implantation bridged over finger joints. Intraoperatively no or only initial signs of degradation of the nerve conduits were observed. Chitosan conduits revealed largely unchanged shape and structure of chitosan, and coating of the conduit by a vascularized fibrous membrane. The latter contained deposits taken up by macrophages, most likely representing dissolved chitosan. Characteristic histopathologic features of the degradation of collagen conduits were a disintegration of the compact collagen into separate fine circular strands, No foreign body reaction was observed in all removed nerve conduits., Conclusions: Both Chitosan nerve conduits have not been degraded. The collagen nerve conduits showed a beginning degradation process. Furthermore, wrapping the repaired nerve with a nerve conduit did neither prevent adhesions nor improved nerve gliding. Therefore, biodegradation in time should be particularly addressed in further developments of nerve conduits., (© 2023 Wiley Periodicals LLC.)
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- 2024
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31. Conjoined Free Fibula Transplantation and First Carpometacarpal Joint Prosthesis for Functional Thumb Reconstruction-A Case Report.
- Author
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Rein S, Geister D, and Kremer T
- Subjects
- Female, Humans, Middle Aged, Thumb surgery, Fibula surgery, Activities of Daily Living, Carpometacarpal Joints surgery, Plastic Surgery Procedures
- Abstract
Background: Giant cell tumors grow locally invasive with osseous and soft tissue destruction, requiring wide resection to avoid recurrence. Stable reconstruction of the first carpometacarpal (CMC-1) joint remains a challenge due to its high range of mobility. The latter is of paramount for the functionality of the hand., Purpose: Therefore, the aim of this study was to report our approach for a combined reconstruction of the first metacarpal and the CMC-1 joint., Methods: A 58-year-old woman underwent wide resection of a benign giant cell tumor at the base and shaft of the first metacarpal of the left thumb. Because of the loss of the CMC-1 joint and the instability of the thumb, an osseous reconstruction using a vascularized fibular graft combined with a TOUCH Dual Mobility CMC-1 prosthesis was performed to reconstruct the CMC-1 joint., Results: Osseous healing was observed after 3 months. No tumor recurrence and good joint function were documented at the follow-up investigation after 1 year. The patient reported only minor restrictions during activities of daily living. Thumb opposition was possible with a Kapandji score of 8/10. A slight pain while walking remained as a donor-side morbidity at the right lower leg., Conclusion: Metacarpal reconstruction with vascularized fibula bone grafts allowed a combined joint reconstruction with a commercially available prosthesis, which is an approach to restore the complex range of motion of the thumb., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
32. [Surgical management of burn injury patients : Comments on the guidelines on treatment of thermal injuries in adults].
- Author
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Rennekampff HO and Kremer T
- Subjects
- Humans, Adult, Debridement adverse effects, Debridement methods, Skin, Outpatients, Quality of Life, Burns surgery, Burns etiology
- Abstract
The treatment of burn injury patients is a unique challenge for clinicians. The extent of thermal injuries ranges from very small burns to life-threatening burn injuries. Insufficient treatment can result in a substantial impairment in the quality of life. In order to avoid such sequelae a targeted treatment must be carried out. A precise diagnosis determines the necessary treatment. Superficial second-degree burns (2a) not involving the face, hand or joints with a total body surface area smaller than 10% can usually be treated with modern wound dressings in an outpatient setting. Deep second-degree burns (2b) are an indication for debridement. In addition to the classical surgical procedures with tangential excision, enzymatic debridement can also be employed. Similarly, indeterminate burns (2a/2b) are also considered to be an indication for enzymatic debridement. Third-degree burns are treated with early debridement and skin grafting. These patients can also benefit from special dermal replacement procedures for an improvement of the functional and esthetic results. Due to the long-term visible sequelae of burns, aftercare of these patients is indicated., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
33. [Evaluation of the Charlson Comorbidity Index as a prognostic tool for assessing the severity of hand infections]
- Author
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Sorowka A, Grünewald T, Kremer T, and Rein S
- Subjects
- Humans, Prognosis, Length of Stay, Hand, Upper Extremity
- Abstract
Background: The Charlson Comorbidity Index (CCI) is used for the prognostic analysis of comorbidities. Comorbidities, especially diabetes mellitus, are a decisive factor for the development and course of hand infections. This study aimed to determine the CCI in patients with hand infections in order to examine how comorbidities influence the course and severity of hand infections., Material and Methods: Ninety patients with hand infections requiring surgery but without previous antibiotic treatment were studied prospectively. The respective CCI was determined on admission to hospital. A total score of zero points was defined as "low", a score of one to three as "medium" and a score of four to nine points as a "high" index. Age, CRP level, duration of inpatient stay and the number of performed surgeries were documented and statistically evaluated., Results: The median CCI was 0,5 points with a range of 0-9 points. The most common comorbidity was diabetes mellitus without end-organ damage, followed by heart failure and chronic lung disease. Patients with a low total score (median 51 years) were significantly younger than those with a medium score (median 60 years; p=0,018) or a high score (median 66,5 years; p=0,018). In addition, patients with a low or medium score had a shorter hospital stay (median 6 vs. 11,5 days; plow=0,003; pmean=0,005), required fewer surgeries (median 1 vs. 3 surgeries; plow=0,002; pmean=0,003) and had a lower CRP level (median 8,3 mg/l vs. 7,1 mg/l vs. 86,25 mg/l; plow=pmean=0,001) than those with a high index. A significant positive correlation was found between the CCI and patient age (Spearman's ρ=0,367; p<0,001) as well as the length of hospital stay (Spearman's ρ=0,261; p=0,013), the number of surgeries (Spearman's ρ=0,219; p=0,038) and the CRP level (Spearman's ρ=0,212; p=0,045)., Conclusions: The CCI is an appropriate questionnaire for the prognostic assessment of the course and severity of hand infections, particularly with regard to the length of hospital stay, the number of surgeries and the CRP level., Competing Interests: Susanne Rein: Firma Mediwound, und DIZG Berlin, aber nicht im Zusammenhang mit diesem Manuskript, sondern im Rahmen anderer Forschungsprojekte., (Thieme. All rights reserved.)
- Published
- 2023
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34. Microbiologic Analysis of Hand Infections: A Prospective Study.
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Rein S, Sorowka A, Grünewald T, and Kremer T
- Subjects
- Animals, Prospective Studies, RNA, Ribosomal, 16S genetics, Hand, Bacteremia, Bites and Stings
- Abstract
Background: Hand infections are a common problem in emergency departments. Staphylococcus aureus is the main pathogen of both hand and blood stream infections. Therefore, the aim of the present study was to evaluate the frequency and impact of bacteremia in patients with hand infections to improve the microbiologic diagnostics. Patients and Methods: A prospective study of 90 patients with acute hand infections without antimicrobial pre-treatment was performed. Blood cultures were taken pre-operatively. If positive, transesophageal echocardiography was performed to rule out infectious endocarditis. Tissue samples were microbiologically processed using standardized culture media. If negative, a broad-spectrum bacterial 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) was applied. The etiology and location of the infection, the length of hospital stay, the number of surgical interventions, and the inflammatory parameters were obtained. Results: Six patients with bacteremia (6.6%) were diagnosed, after animal bites (n = 3) and intra-articular empyema (n = 3). Pathogens included Staphylococcus pettenkoferi , Pasteurella multocida , Staphylococcus epidermidis , Staphylococcus aureus , and Bacteroides pyogenes . No case of infective endocarditis was detected. Patients with bacteremia required more surgical interventions (p = 0.002), had a longer hospital stay (p < 0.001), higher plasma C-reactive protein (CRP; p = 0.016), and a higher age (p = 0.002) compared with those without bacteremia. In 14 cases (15.6%) no pathogen was detected by culture, whereas the subsequent broad-spectrum PCR diagnosed three cases (21.4%). Conclusions: Pre-operative blood cultures in patients with hand infections are important to detect bacteremia as an essential marker of clinical severity. Those blood cultures are indicated after deep animal bites and joint empyema. A precise identification of pathogens is fundamental for an effective treatment of hand infections, for which a 16S rRNA gene PCR can contribute in culture-negative tissue samples.
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- 2023
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35. Immunofluorescence analysis of sensory nerve endings in the periarticular tissue of the human elbow joint.
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Rein S, Esplugas M, Garcia-Elias M, Kremer T, Siemers F, and Lühmann P
- Subjects
- Humans, Carbonic Anhydrase II, Choline O-Acetyltransferase, Sensory Receptor Cells, Fluorescent Antibody Technique, Elbow Joint
- Abstract
Introduction: To investigate the dynamic aspects of elbow stability, we aimed to analyze sensory nerve endings in the ligaments and the capsule of elbow joints., Materials and Methods: The capsule with its anterior (AJC) and posterior (PJC) parts, the radial collateral ligament (RCL), the annular ligament (AL), and the ulnar collateral ligament with its posterior (PUCL), transverse (TUCL) and anterior parts (AUCL) were dissected from eleven human cadaver elbow joints. Sensory nerve endings were analyzed in two levels per specimen as total cell amount/ cm
2 after immunofluorescence staining with low-affinity neurotrophin receptor p75, protein gene product 9.5, S-100 protein and 4',6-Diamidin-2-phenylindol, Carbonic anhydrase II and choline acetyltransferase on an Apotome microscope according to Freeman and Wyke's classification., Results: Free nerve endings were the predominant mechanoreceptor in all seven structures followed by Ruffini, unclassifiable, Golgi-like, and Pacini corpuscles (p ≤ 0.00001, respectively). Free nerve endings were observed significant more often in the AJC than in the RCL (p < 0.00002). A higher density of Ruffini endings than Golgi-like endings was observed in the PJC (p = 0.004). The RCL contained significant more Ruffini endings than Pacini corpuscles (p = 0.004). Carbonic anhydrase II was significantly more frequently positively immunoreactive than choline acetyltransferase in all sensory nerve endings (p < 0.05). Sensory nerve endings were significant more often epifascicular distributed in all structures (p < 0.006, respectively) except for the AJC, which had a pronounced equal distribution (p < 0.00005)., Conclusion: The high density of free nerve endings in the joint capsule indicates that it has pronounced nociceptive functions. Joint position sense is mainly detected by the RCL, AUCL, PUCL, and the PJC. Proprioceptive control of the elbow joint is mainly monitored by the joint capsule and the UCL, respectively. However, the extreme range of motion is primarily controlled by the RCL mediated by Golgi-like endings., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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36. Breast Implant-Associated Tumors.
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von Fritschen U, Kremer T, Prantl L, and Fricke A
- Abstract
In addition to anaplastic large T-cell lymphomas (BIA-ALCL), other implant-related tumors have been described for some years. Squamous cell carcinoma (SSC) and B-cell lymphomas occurred in very rare cases. The unexplained pathogenesis as well as the unclear individual risk profile is an ongoing source of uncertainty for patients and physicians. The pathogenesis of the tumors is still largely not understood. While BIA-ALCL occurs more frequently with textured breast implants, other tumors were also observed with smooth implants and at other implant sites. Multiple potential mechanisms are discussed. It is suspected that the etiology of a chronic inflammatory response and subsequently immunostimulation is multifactorial and appears to play a key role in the malignant transformation. Since there are currently no sufficiently valid data for a specific risk assessment, this must be done with caution. This article presents the incidence, pathogenesis, as well as the level of evidence according to the current state of knowledge, and evaluates and discusses the current literature., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)
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- 2023
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37. Three-dimensional distribution of sensory nerve endings in the dorsal part of the scapholunate ligament.
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Rein S, Kremer T, and Meklef RA
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- Humans, Wrist Joint physiology, Ligaments, Articular physiology, Sensory Receptor Cells, Lunate Bone diagnostic imaging, Lunate Bone physiology, Scaphoid Bone physiology
- Published
- 2023
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38. "Studying cognitive reappraisal as an antidote to the effect of negative emotions on medical residents' learning: a randomized experiment".
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Kremer T, Mamede S, do Nunes MPT, van den Broek WW, and Schmidt HG
- Subjects
- Humans, Cognition physiology, Emotions physiology, Learning, Antidotes, Internship and Residency
- Abstract
Background: Medical trainees often encounter situations that trigger emotional reactions which may hinder learning. Evidence of this effect on medical trainees is scarce and whether it could be counteracted is unclear. This study investigated the effect of negative emotions on medical residents' learning and whether cognitive reappraisal counteracts it., Methods: Ninety-nine medical residents participated in a three-phase experiment consisting of: (1) watching a video, either a neutral or an emotion-induction version, the latter either followed by cognitive reappraisal or not (2) learning: all participants studied the same medical text; study-time and cognitive engagement were measured; (3) test: a recall-test measured learning. Data was analysed using Chi-square test and one-way ANOVA., Results: Study time significantly varied between conditions (p = 0.002). The two emotional conditions spent similar time, both significantly less than the neutral condition. The difference in test scores failed to reach significance level (p = 0.053). While the emotional conditions performed similarly, their scores tended to be lower than those of the neutral condition., Conclusion: Negative emotions can adversely affect medical residents' learning. The effect of emotions was not counteracted by cognitive reappraisal, which has been successfully employed to regulate emotions in other domains. Further research to examine emotion regulation strategies appropriate for medical education is much needed., (© 2023. The Author(s).)
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- 2023
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39. Soft Tissue Reconstruction of Complex Infrainguinal Wounds Following Revisionary Vascular Surgery.
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Hernekamp JF, Lauer H, Goertz O, Weigang E, Kneser U, and Kremer T
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- Male, Humans, Female, Middle Aged, Aged, Aged, 80 and over, Retrospective Studies, Treatment Outcome, Thigh, Postoperative Complications etiology, Postoperative Complications surgery, Vascular Surgical Procedures adverse effects, Free Tissue Flaps surgery, Free Tissue Flaps transplantation, Plastic Surgery Procedures adverse effects
- Abstract
Background: Large, full-thickness infrainguinal wounds following revision revascularization procedures of the lower extremity are a challenging complication for reconstructive surgery. Frequently, these patients present with various comorbidities and after several previous reconstructive attempts. Therefore no straightforward soft tissue reconstruction is likely., Methods: Patients who presented with large, complex inguinal wounds for soft tissue reconstruction were analyzed retrospectively in terms of flap choice, outcome, and complication rates. A focus was set on the reconstructive technique and a subgroup analysis was assessed., Results: Nineteen patients (11 men, 8 women) who received 19 flaps (17 pedicled, 2 free flaps) were included in this retrospective study. Average patient age was 73.3 years (range: 53-88). Ten fasciocutaneous flaps (anterolateral thigh [ALT], 52.6%) and 9 muscle flaps (47.4%) were applied. Among muscle flaps, 3 pedicled gracilis flaps, 4 pedicled rectus abdominis flaps, and 2 free latissimus dorsi flaps were used. No flap losses were observed except 1 case of limited distal flap necrosis (gracilis group). Body mass index ranged from 19 to 37, mean 26.8. Mean surgery time in all patients was 165.9 min (range: 105-373). Revision surgery due to local wound healing problems averaged 1.6 in all patients. In all cases sufficient soft tissue reconstruction was achieved and bypasses were preserved. Lengths of stay averaged 27.2 days (range: 14-59). Mortality was considerably (10.5%) due to systemic complications (one patient died due to a heart attack 4 weeks postoperatively, another patient died due to an extensive pulmonary embolism 2 weeks postoperatively)., Conclusions: Soft tissue reconstruction of complex inguinal wounds after revision vascular surgery is challenging and wound healing problems are expectable. In addition to the rectus abdominis flap the pedicled ALT flap is feasible in a broad variety of medium to large wounds. Free flap reconstruction is recommended for very large defects. A structured interdisciplinary approach is required for the management of complex wounds after vascular surgery to prevent and to deal with complications and perioperative morbidity., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2023
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40. Reduced Real-life Affective Well-being and Amygdala Habituation in Unmedicated Community Individuals at Risk for Depression and Anxiety.
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Berhe O, Höflich A, Moessnang C, Reichert M, Kremer T, Gan G, Ma R, Braun U, Reininghaus U, Ebner-Priemer U, Meyer-Lindenberg A, and Tost H
- Subjects
- Young Adult, Humans, Anxiety, Anxiety Disorders, Amygdala, Depression, Habituation, Psychophysiologic
- Abstract
Background: Early identification of risk for depression and anxiety disorders is important for prevention, but real-life affective well-being and its biological underpinnings in the population remain understudied. Here, we combined methods from epidemiology, psychology, ecological momentary assessment, and functional magnetic resonance imaging to study real-life and neural affective functions in individuals with subclinical anxiety and depression from a population-based cohort of young adults., Methods: We examined psychological measures, real-life affective valence, functional magnetic resonance imaging amygdala habituation to negative affective stimuli, and the relevance of neural readouts for daily-life affective function in 132 non-help-seeking community individuals. We compared psychological and ecological momentary assessment measures of 61 unmedicated individuals at clinical risk for depression and anxiety (operationalized as subthreshold depression and anxiety symptoms or a former mood or anxiety disorder) with those of 48 nonrisk individuals and 23 persons with a mood or anxiety disorder. We studied risk-associated functional magnetic resonance imaging signals in subsamples with balanced sociodemographic and image quality parameters (26 nonrisk, 26 at-risk persons)., Results: Compared with nonrisk persons, at-risk individuals showed significantly decreased real-life affective valence (p = .038), reduced amygdala habituation (familywise error-corrected p = .024, region of interest corrected), and an intermediate psychological risk profile. Amygdala habituation predicted real-life affective valence in control subjects but not in participants at risk (familywise error-corrected p = .005, region of interest corrected)., Conclusions: Our data suggest real-life and neural markers for affective alterations in unmedicated community individuals at risk for depression and anxiety and highlight the significance of amygdala habituation measures for the momentary affective experience in real-world environments., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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41. Comparative histomorphological analysis of elbow ligaments and capsule.
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Lühmann P, Kremer T, Siemers F, and Rein S
- Subjects
- Biomechanical Phenomena, Cadaver, Elbow, Eosine Yellowish-(YS), Hematoxylin, Humans, Ligaments, Rubber, Collateral Ligaments anatomy & histology, Elbow Joint anatomy & histology
- Abstract
This study aimed to compare the histomorphology of the elbow capsule and its ligaments to gain a better understanding of the clinically relevant biomechanical stabilization. Eleven human elbows were dissected including the joint capsule with its anterior (AJC) and posterior (PJC) parts, the annular ligament (AL), the radial collateral ligament (RCL) and the ulnar collateral ligament with its anterior (AUCL), posterior (PUCL) and transverse (TUCL) parts. Hematoxylin-Eosin and Elastica van Gieson as conventional histology stainings were applied to determine collagenous and elastic fiber arrangements in transmission and polarization light microscopy. The radial collateral ligament and the anterior part of the ulnar collateral ligament showed significantly more densely packed parallel fiber arrangement than the anterior joint capsule, the posterior joint capsule, and the posterior part of the ulnar collateral ligament (p < 0.02, respectively). The PUCL had significantly more mixed tight and loose parallel arrangements than the PJC, the annular ligament, the RCL, the AUCL and the transverse part of the ulnar collateral ligamentp < 0.02, respectively), while the PJC showed significantly more interlaced mixed tight and loose fiber arrangement than the AL, the RCL and the AUCL (p < 0.003, respectively). The AJC had a significantly higher amount of elastic fibers as compared to the AL, the RCL, the AUCL and the TUCL in fascicular regions (p < 0.04, respectively), while the AUCL had significantly lesser elastic fibers than the AJC and the PJC (p < 0.004, respectively). The densely packed parallel fiber arrangement and few elastic fibers of the AUCL, RCL, and AL indicate a strong biomechanically stabilizing function. The fiber arrangement of the PUCL and the TUCL with few elastic fibers support the medial elbow stabilization. Crimping and elastic fibers provide the viscoelasticity of the joint capsule., (© 2022 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)
- Published
- 2022
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42. [Reconstruction of Soft Tissue Defects of the Achilles Tendon Region: a Literature Review].
- Author
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Rein S and Kremer T
- Subjects
- Humans, Treatment Outcome, Achilles Tendon surgery, Achilles Tendon injuries, Soft Tissue Injuries surgery, Free Tissue Flaps surgery, Plastic Surgery Procedures
- Abstract
Background: Soft tissue defects in the achilles tendon region occur after trauma, but also as a complication after open recon- struction of the tendon with subsequent infection., Objectives: Recommendations for the treatment of soft tissue injuries involving the Achilles tendon are presented., Materials and Methods: A search of the German, French and English literature on reconstruction of soft tissue defects of the Achilles tendon region was performed, which were differentiated into singular and combined tendocutaneous defects. Combined defects were further subdivided into three reconstructive principles: a simple soft tissue reconstruction without tendon repair or a combined reconstruction of the soft tissue as well as the tendon using either a vascularized tendon transplant or an avascular tendon graft., Results: Local and distally-based pedicled flaps include a relatively high risk or perioperative morbidity, whereas free flaps are described with significantly lower complications rates. Therefore, the authors prefer free flaps for reconstruction. Potential donor sites are the Medial Sural Artery (MSAP-) flap for smaller defects or free fasciocutaneous or muscle flaps in patients with large defects. The standard for tendocutaneousreconstructions is the free anterolateral thigh flap including vascularized fascia. Non-vascularized tendon grafts are frequently applied from the flexor hallucis longus- or peroneus brevis tendon., Conclusions: Reconstructions over the Achilles tendon require thin and stable reconstructions that additionally allow slippage of soft tissues. Moreover, the use of normal shoes should be possible. The postoperative strength and range of motion of the ankle joint show comparable functional results after vascularized and non-vascularized tendon reconstruction., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
- Published
- 2022
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43. Multi-platform quantitation of alpha-synuclein human brain proteoforms suggests disease-specific biochemical profiles of synucleinopathies.
- Author
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Moors TE, Mona D, Luehe S, Duran-Pacheco G, Spycher L, Mundigl O, Kaluza K, Huber S, Hug MN, Kremer T, Ritter M, Dziadek S, Dernick G, van de Berg WDJ, and Britschgi M
- Subjects
- Aged, Brain pathology, Detergents, Humans, alpha-Synuclein metabolism, Lewy Body Disease pathology, Multiple System Atrophy pathology, Synucleinopathies
- Abstract
Based on immunostainings and biochemical analyses, certain post-translationally modified alpha-synuclein (aSyn) variants, including C-terminally truncated (CTT) and Serine-129 phosphorylated (pSer129) aSyn, are proposed to be involved in the pathogenesis of synucleinopathies such as Parkinson's disease with (PDD) and without dementia (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, quantitative information about aSyn proteoforms in the human brain in physiological and different pathological conditions is still limited. To address this, we generated sequential biochemical extracts of the substantia nigra, putamen and hippocampus from 28 donors diagnosed and neuropathologically-confirmed with different synucleinopathies (PD/PDD/DLB/MSA), as well as Alzheimer's disease, progressive supranuclear palsy, and aged normal subjects. The tissue extracts were used to build a reverse phase array including 65 aSyn antibodies for detection. In this multiplex approach, we observed increased immunoreactivity in donors with synucleinopathies compared to controls in detergent-insoluble fractions, mainly for antibodies against CT aSyn and pSer129 aSyn. In addition, despite of the restricted sample size, clustering analysis suggested disease-specific immunoreactivity signatures in patient groups with different synucleinopathies. We aimed to validate and quantify these findings using newly developed immunoassays towards total, 119 and 122 CTT, and pSer129 aSyn. In line with previous studies, we found that synucleinopathies shared an enrichment of post-translationally modified aSyn in detergent-insoluble fractions compared to the other analyzed groups. Our measurements allowed for a quantitative separation of PDD/DLB patients from other synucleinopathies based on higher detergent-insoluble pSer129 aSyn concentrations in the hippocampus. In addition, we found that MSA stood out due to enrichment of CTT and pSer129 aSyn also in the detergent-soluble fraction of the SN and putamen. Together, our results achieved by multiplexed and quantitative immunoassay-based approaches in human brain extracts of a limited sample set point to disease-specific biochemical aSyn proteoform profiles in distinct neurodegenerative disorders., (© 2022. The Author(s).)
- Published
- 2022
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44. A cross-species spatiotemporal proteomic analysis identifies UBE3A-dependent signaling pathways and targets.
- Author
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Pandya NJ, Meier S, Tyanova S, Terrigno M, Wang C, Punt AM, Mientjes EJ, Vautheny A, Distel B, Kremer T, Elgersma Y, and Jagasia R
- Subjects
- Animals, Disease Models, Animal, Mice, Proteome, Rats, Signal Transduction, Ubiquitin-Protein Ligases genetics, Angelman Syndrome drug therapy, Angelman Syndrome genetics, Angelman Syndrome metabolism, Proteomics
- Abstract
Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal E3 ligase UBE3A. Restoring UBE3A levels is a potential disease-modifying therapy for AS and has recently entered clinical trials. There is paucity of data regarding the molecular changes downstream of UBE3A hampering elucidation of disease therapeutics and biomarkers. Notably, UBE3A plays an important role in the nucleus but its targets have yet to be elucidated. Using proteomics, we assessed changes during postnatal cortical development in an AS mouse model. Pathway analysis revealed dysregulation of proteasomal and tRNA synthetase pathways at all postnatal brain developmental stages, while synaptic proteins were altered in adults. We confirmed pathway alterations in an adult AS rat model across multiple brain regions and highlighted region-specific differences. UBE3A reinstatement in AS model mice resulted in near complete and partial rescue of the proteome alterations in adolescence and adults, respectively, supporting the notion that restoration of UBE3A expression provides a promising therapeutic option. We show that the nuclear enriched transketolase (TKT), one of the most abundantly altered proteins, is a novel direct UBE3A substrate and is elevated in the neuronal nucleus of rat brains and human iPSC-derived neurons. Taken together, our study provides a comprehensive map of UBE3A-driven proteome remodeling in AS across development and species, and corroborates an early UBE3A reinstatement as a viable therapeutic option. To support future disease and biomarker research, we present an accessible large-scale multi-species proteomic resource for the AS community ( https://www.angelman-proteome-project.org/ )., (© 2022. The Author(s).)
- Published
- 2022
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45. AntimiR targeting of microRNA-134 reduces seizures in a mouse model of Angelman syndrome.
- Author
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Campbell A, Morris G, Sanfeliu A, Augusto J, Langa E, Kesavan JC, Nguyen NT, Conroy RM, Worm J, Kielpinski L, Jensen MA, Miller MT, Kremer T, Reschke CR, and Henshall DC
- Abstract
Angelman syndrome (AS) is a severe neurodevelopmental disorder featuring ataxia, cognitive impairment, and drug-resistant epilepsy. AS is caused by mutations or deletion of the maternal copy of the paternally imprinted UBE3A gene, with current precision therapy approaches focusing on re-expression of UBE3A . Certain phenotypes, however, are difficult to rescue beyond early development. Notably, a cluster of microRNA binding sites was reported in the untranslated Ube3a1 transcript, including for miR-134, suggesting that AS may be associated with microRNA dysregulation. Here, we report levels of miR-134 and key targets are normal in the hippocampus of mice carrying a maternal deletion of Ube3a ( Ube3a
m-/p+ ). Nevertheless, intracerebroventricular injection of an antimiR oligonucleotide inhibitor of miR-134 (Ant-134) reduced audiogenic seizure severity over multiple trials in 21- and 42-day-old AS mice. Interestingly, Ant-134 also improved distance traveled and center crossings of AS mice in the open-field test. Finally, we show that silencing miR-134 can upregulate targets of miR-134 in neurons differentiated from Angelman patient-derived induced pluripotent stem cells. These findings indicate that silencing miR-134 and possibly other microRNAs could be useful to treat clinically relevant phenotypes with a later developmental window in AS., Competing Interests: The Royal College of Surgeons in Ireland (D.C.H.) holds a patent for the inhibition of microRNA-134 for the treatment of seizure-related disorders and other neurologic injuries (US 9,803,200 B2). J.W., M.A.J., and M.T.M. are employees of F Hoffman-La Roche Ltd. All other authors have no competing interests., (© 2022 The Author(s).)- Published
- 2022
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46. Case-based dynamic learning of the NEPPC asthma and anosmia: Typical presentation in an atypical age.
- Author
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Muise ED, Boyer D, Simoneau T, Laidlaw TM, Lee EY, Kremer T, and Nelson BA
- Subjects
- Anosmia, Anti-Inflammatory Agents, Non-Steroidal, Humans, Asthma complications, Asthma diagnosis, Rhinitis, Sinusitis
- Published
- 2022
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47. Does recorded oximetry utilizing a consensus-based algorithm compare to polysomnography in discontinuing home oxygen therapy in premature infants?
- Author
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White H, Sobelman C, Kremer T, Lee A, and Rhein LM
- Subjects
- Algorithms, Consensus, Humans, Infant, Infant, Newborn, Oxygen, Polysomnography methods, Infant, Premature, Oximetry methods
- Abstract
Background: Approximately a third of all extremely preterm infants diagnosed with bronchopulmonary dysplasia will require home oxygen therapy (HOT). Lack of consensus-based guidelines has led to significant variability in outpatient HOT management in the United States. A common assessment performed before discontinuing oxygen is a formal polysomnogram (PSG). PSGs are potentially undesirable due to cost, lack of convenient access, and parental stress, so alternative testing to determine the optimal timing of safe oxygen discontinuation are needed., Methods: We compared nocturnal recorded home oximetry (RHO) with PSG data in a cohort of patients from the RHO trial for patients who had recordings performed simultaneously to or within 24 h of their PSG. The RHO trial was a randomized, unblinded, multi-center trial comparing two oxygen management strategies. Parameters of oxygenation were compared between PSG and RHO, and nonoximegtry findings from the PSG that changed clinical management were identified., Results: A total of 53 infants randomized to obtain a PSG as part of the RHO trial (55%) completed a PSG, and of those, 32 (64%) completed both a PSG with comparison RHO. There were more white infants in both groups than other races and ethnicities. Bland-Altman analysis showed a strong agreement of oxygen saturation time below 90% SpO
2 between PSG and RHO results (slope = 1.014, p = 0.24). Results agreed in 96% of cases., Conclusion: RHO is a safe and effective alternative to PSG to assist in determination of discontinuing HOT in infants with BPD without other risks for sleep-disordered breathing., (© 2021 Wiley Periodicals LLC.)- Published
- 2022
- Full Text
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48. Teaching Microsurgical Breast Reconstruction-A Retrospective Cohort Study.
- Author
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Fischer S, Diehm YF, Kotsougiani-Fischer D, Gazyakan E, Radu CA, Kremer T, Hirche C, and Kneser U
- Abstract
Microsurgical breast reconstruction demands the highest level of expertise in both reconstructive and aesthetic plastic surgery. Implementation of such a complex surgical procedure is generally associated with a learning curve defined by higher complication rates at the beginning. The aim of this study was to present an approach for teaching deep inferior epigastric artery perforator (DIEP) and transverse upper gracilis (TUG) flap breast reconstruction, which can diminish complications and provide satisfying outcomes from the beginning. DIEP and TUG flap procedures for breast reconstruction were either performed by a senior surgeon (>200 DIEP/TUG, " no-training group "), or taught to one of five trainees (>80 breast surgeries; >50 free flaps) in a step-wise approach. The latter were either performed by the senior surgeon, and a trainee was assisting the surgery (" passive training "); by the trainee, and a senior surgeon was supervising (" active training "); or by the trainee without a senior surgeon (" after training "). Surgeries of each group were analyzed regarding OR-time, complications, and refinement procedures. A total of 95 DIEP and 93 TUG flaps were included into this study. Before the first DIEP/TUG flap without supervision, each trainee underwent a mean of 6.8 DIEP and 7.3 TUG training surgeries ( p > 0.05). Outcome measures did not reveal any statistically significant differences (passive training/active training/after training/no-training: OR-time (min): DIEP: 331/351/338/304 ( p > 0.05); TUG: 229/214/239/217 ( p > 0.05); complications (n): DIEP: 6/13/16/11 ( p > 0.05); TUG: 6/19/23/11 ( p > 0.05); refinement procedures (n): DIEP:71/63/49/44 ( p > 0.05); TUG: 65/41/36/56 ( p > 0.05)), indicating safe and secure implementation of this step-wise training approach for microsurgical breast reconstruction in both aesthetic and reconstructive measures. Of note, despite being a perforator flap, DIEP flap required no more training than TUG flap, highlighting the importance of flap inset at the recipient site.
- Published
- 2021
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49. Systematic Assessment of 10 Biomarker Candidates Focusing on α-Synuclein-Related Disorders.
- Author
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Schulz I, Kruse N, Gera RG, Kremer T, Cedarbaum J, Barbour R, Zago W, Schade S, Otte B, Bartl M, Hutten SJ, Trenkwalder C, and Mollenhauer B
- Subjects
- Biomarkers cerebrospinal fluid, Humans, alpha-Synuclein cerebrospinal fluid, tau Proteins cerebrospinal fluid, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Multiple System Atrophy diagnosis
- Abstract
Background: Objective diagnostic biomarkers are needed to support a clinical diagnosis., Objectives: To analyze markers in various neurodegenerative disorders to identify diagnostic biomarker candidates for mainly α-synuclein (aSyn)-related disorders (ASRD) in serum and/or cerebrospinal fluid (CSF)., Methods: Upon initial testing of commercially available kits or published protocols for the quantification of the candidate markers, assays for the following were selected: total and phosphorylated aSyn (pS129aSyn), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), tau protein (tau), ubiquitin C-terminal hydrolase L1 (UCHL-1), glial fibrillary acidic protein (GFAP), calcium-binding protein B (S100B), soluble triggering receptor expressed on myeloid cells 2 (sTREM-2), and chitinase-3-like protein 1 (YKL-40). The cohort comprised participants with Parkinson's disease (PD, n = 151), multiple system atrophy (MSA, n = 17), dementia with Lewy bodies (DLB, n = 45), tau protein-related neurodegenerative disorders (n = 80, comprising patients with progressive supranuclear palsy (PSP, n = 38), corticobasal syndrome (CBS, n = 16), Alzheimer's disease (AD, n = 11), and frontotemporal degeneration/amyotrophic lateral sclerosis (FTD/ALS, n = 15), as well as healthy controls (HC, n = 20). Receiver operating curves (ROC) with area under the curves (AUC) are given for each marker., Results: CSF total aSyn was decreased. NfL, pNfH, UCHL-1, GFAP, S100B, and sTREM-2 were increased in patients with neurodegenerative disease versus HC (P < 0.05). As expected, some of the markers were highest in AD (i.e., UCHL-1, GFAP, S100B, sTREM-2, YKL-40). Within ASRD, CSF NfL levels were higher in MSA than PD and DLB (P < 0.05). Comparing PD to HC, interesting serum markers were S100B (AUC: 0.86), sTREM2 (AUC: 0.87), and NfL (AUC: 0.78). CSF S100B and serum GFAP were highest in DLB., Conclusions: Levels of most marker candidates tested in serum and CSF significantly differed between disease groups and HC. In the stratification of PD versus other tau- or aSyn-related conditions, CSF NfL levels best discriminated PD and MSA. CSF S100B and serum GFAP best discriminated PD and DLB. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.)
- Published
- 2021
- Full Text
- View/download PDF
50. [The free serratus carpaccio flap: indications and technique].
- Author
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Rein S, Gazyakan E, Kneser U, and Kremer T
- Subjects
- Fascia, Humans, Reproducibility of Results, Skin Transplantation, Free Tissue Flaps surgery, Hand Injuries surgery, Plastic Surgery Procedures, Soft Tissue Injuries surgery
- Abstract
Purpose: Soft tissue reconstructions of the hand require a thin and resistant flap palmarly as well as sliding abilities between the extensor tendons and the flap on the dorsum of the hand. Elasticity is required to maintain the normal wrist range of motion. One option in these cases is the free serratus fascia flap that sometimes shows limitations regarding resistance as well as reliability. Here, we describe an easy modification including a thin muscle cuff in the serratus fascia flap - the serratus carpaccio flap - that improves the ease of flap harvest and morbidity rates., Methods: The indications for the serratus carpaccio flap, the technique of flap harvest and contouring as well as flap inset are described in detail. Clinical examples are given., Results: The main advantage of the serratus carpaccio flap is the ability of the surgeon to adapt the flap thickness to the recipient site requirements. This allows excellent results regarding contour and function. Split thickness skin grafting fromthe instep region of the foot additionally allows optimal results for palmar as well as plantar defect reconstruction. Eighteen flaps for soft tissue defects of the hand (n = 5), foot (n = 10), and lower leg (n = 3) were performed. Complications included one flap loss, one venous re-anastomosis, two partial wound dehiscences and one postoperative hematoma at the donor site. Seventeen flaps survived completely. Secondary thinning procedures were not required., Conclusions: The serratus carpaccio flap is an excellent option for the reconstruction of medium-sized skin and soft tissue defects of the dorsum of the hand or foot, the palm, and the distal forearm., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
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