610 Medizin und Gesundheit
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Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers for several diseases. Here, we profiled the sRNA transcriptomes of AE and CE patients to identify novel biomarkers to aid in medical decisions when current diagnostic procedures are inconclusive. For this, endogenous and parasitic sRNAs were analyzed by sRNA sequencing in serum from disease negative, positive, and treated patients and patients harboring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE, and/or non-parasitic lesion were identified. Our results represent an in-depth characterization of the effect E. multilocularis and E. granulosus s. l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection.
Seltene Erkrankungen (SE) werden durch die im deutschen Gesundheitssystem verwendete Diagnosenklassifikation ICD-10-GM (International Statistical Classification of Diseases and Related Health problems, 10th Revision, German Modification) nur zu einem kleinen Teil eindeutig erfasst. Daher sind Aussagen zur Häufigkeit von SE sowie zum speziellen Versorgungs- und Finanzierungsbedarf nicht möglich, was zu einer lückenhaften Datenlage als Entscheidungsgrundlage für Krankenkassen, Leistungserbringer und Gesundheitspolitik führt. Das Fehlen exakter Informationen behindert auch die wissenschaftliche Arbeit. Daher wird deutschlandweit ab 2023 die Verwendung der Alpha-ID-SE-Datei und der ORPHAcodes für die spezifische Erfassung von SE bei stationären Fällen verpflichtend.
Die Alpha-ID-SE-Datei verknüpft die ICD-10-GM-Kodes mit den international anerkannten ORPHAcodes für die Diagnose von SE. Kommerzielle Anbieter stellen zunehmend die benötigten IT-Tools zur Kodierung von SE zur Verfügung. An mehreren Universitätskliniken mit Zentren für SE wurden Lösungen etabliert, die eine vollständige Kodierung gewährleisten sollen. Hierzu gehören finanzielle Anreize für die kodierenden Bereiche, konkrete Nachfragen nach dem Vorliegen einer SE beim Kodiervorgang und eine semiautomatische Kodierung bei Patient*innen, die schon einmal mit einer SE an der Einrichtung betreut worden waren. Eine Kombination der verschiedenen Ansätze verspricht die höchste Wahrscheinlichkeit einer vollständigen Kodierung.
Für ein umfängliches Bild der SE im Gesundheitssystem und um dem speziellen Versorgungs- und Finanzierungsbedarf besser Rechnung tragen zu können, wäre auch im ambulanten Bereich eine möglichst spezifische und eindeutige Kodierung wünschenswert. Für komplexe SE und bisher undiagnostizierte Patient*innen wird zusätzlich eine strukturierte Erfassung des Phänotyps benötigt.
Diagnosis and therapy of Mycobacterium marinum: a single-center 21-year retrospective analysis
(2022)
Background and Objectives
In Europe, infections with Mycobacterium (M.) marinum are rare. We conducted a retrospective single-center study to assess the clinical spectrum of M. marinum infection and its diagnosis, treatment and outcome under real-world conditions.
Patients and Methods
Eighteen patients presenting with M. marinum infections between 1998 and 2018 were identified in the data warehouse of the University Hospital Würzburg and considered for detailed analysis.
Results
Twelve patients reported aquatic exposure. In 16/18 cases the upper extremities were affected. No invasive infections were detected. Mean time to diagnosis was 15 weeks. Histology revealed granulomatous inflammation in 14 patients while mycobacterial cultures were positive for M. marinum in 16 cases. Most patients received antibiotic monotherapy (14/18) while combination therapy was administered in four cases. Treatment (with a median duration of 10 weeks) was successful in 13 patients. Five patients were lost to follow-up.
Conclusions
Our retrospective analysis of M. marinum infections at a German tertiary referral center revealed a considerable diagnostic delay and the relevance of microbiological culture, PCR and histology for diagnosis. Monotherapy with clarithromycin (rather than doxycycline) appeared as a reasonable treatment option while immunosuppressed or -compromised patients and those with extended disease received combination therapy.
Objective
To evaluate diagnostic accuracy of the corticotropin-releasing hormone (CRH) stimulation test and the overnight 8 mg dexamethasone suppression test (DST) for the differentiation of Cushing’s disease (CD) and ectopic Cushing’s syndrome (ECS).
Methods
Retrospective study in 6 European centers. Inclusion criteria: patients with a) overt adrenocorticotropin (ACTH)-dependent Cushing’s syndrome at the time of dynamic testing, b) histopathological confirmed tumors and/or c) postoperative biochemical remission and/or adrenal insufficiency. Optimal cut-offs were calculated via receiver operating characteristic (ROC) analysis using CD as reference.
Results
469 patients were analyzed [78% females; median age 43 years (IQR 19)]. CRH test and overnight 8 mg DST were performed in 420 [CD, n=394 (94%); ECS, n=26 (6%)] and 237 patients [228 CD (96%), 9 ECS (4%)]. Both tests were performed in 205 patients (44%). The post-CRH %-increase at 30 minutes of both ACTH (cut-off ≥31%, sensitivity 83%, specificity 85%, AUC 0.81) and cortisol (cut-off ≥12%, sensitivity 82%, specificity 89%, AUC 0.86) discriminated best between CD and ECS. A test duration of >60 minutes did not improve diagnostic performance of the CRH test. The optimal cortisol cut-off for the %-suppression during the 8 mg DST was ≥55% (sensitivity 80%, specificity 78%, AUC 0.75).
Conclusion
The CRH test has equivalent sensitivity but higher specificity than the 8 mg DST and is therefore the test of first choice. The diagnostic outcome of ACTH and cortisol is well comparable, however, sampling beyond 60 minutes post-CRH does not provide diagnostic benefits.
The pulp plays a key role in the treatment of traumatic dental injuries (TDIs) and is strongly associated with the outcome, particularly in severe cases. A correct pulp diagnosis is essential as it forms the basis for developing the appropriate management strategy. However, many TDIs are complex, and their treatment requires a profound knowledge of the physiological and pathological responses of the affected tissues. This comprehensive review will look at the dentine–pulp complex and its interaction with the surrounding tissues following TDIs. The literature up to 2020 was reviewed based on several searches on PubMed and the Cochrane Library using relevant terms. In addition to the recently revised guidelines of the International Association of Dental Traumatology, this article aims to provide background information with a focus on endodontic aspects and to gather evidence on which a clinician can make decisions on the choice of the appropriate endodontic approach for traumatized permanent teeth.
Background and aims:
Small fiber neuropathy (SFN) is increasingly suspected in patients with pain of uncertain origin, and making the diagnosis remains a challenge lacking a diagnostic gold standard.
Methods:
In this case–control study, we prospectively recruited 86 patients with a medical history and clinical phenotype suggestive of SFN. Patients underwent neurological examination, quantitative sensory testing (QST), and distal and proximal skin punch biopsy, and were tested for pain-associated gene loci. Fifty-five of these patients additionally underwent pain-related evoked potentials (PREP), corneal confocal microscopy (CCM), and a quantitative sudomotor axon reflex test (QSART).
Results:
Abnormal distal intraepidermal nerve fiber density (IENFD) (60/86, 70%) and neurological examination (53/86, 62%) most frequently reflected small fiber disease. Adding CCM and/or PREP further increased the number of patients with small fiber impairment to 47/55 (85%). Genetic testing revealed potentially pathogenic gene variants in 14/86 (16%) index patients. QST, QSART, and proximal IENFD were of lower impact.
Conclusion:
We propose to diagnose SFN primarily based on the results of neurological examination and distal IENFD, with more detailed phenotyping in specialized centers.
Neurodegenerative diseases show an increase in prevalence and incidence, with the most prominent example being Alzheimer's disease. DNA damage has been suggested to play a role in the pathogenesis, but the exact mechanisms remain elusive. We enrolled 425 participants with and without neurodegenerative diseases and analyzed DNA damage in the form of micronuclei in buccal mucosa samples. In addition, other parameters such as binucleated cells, karyolytic cells, and karyorrhectic cells were quantified. No relevant differences in DNA damage and cytotoxicity markers were observed in patients compared to healthy participants. Furthermore, other parameters such as lifestyle factors and diseases were also investigated. Overall, this study could not identify a direct link between changes in buccal cells and neurogenerative diseases, but highlights the influence of lifestyle factors and diseases on the human buccal cytome.
Introduction
We characterized dermal innervation in patients with fibromyalgia syndrome (FMS) as potential contribution to small fiber pathology.
Methods
Skin biopsies of the calf were collected (86 FMS patients, 35 healthy controls). Skin was immunoreacted with antibodies against protein gene product 9.5, calcitonine gene-related peptide, substance P, CD31, and neurofilament 200 for small fiber subtypes. We assessed two skin sections per patient; on each skin section, two dermal areas (150 x 700 mu m each) were investigated for dermal nerve fiber length (DNFL).
Results
In FMS patients we found reduced DNFL of fibers with vessel contact compared to healthy controls (p<0.05). There were no differences for the other nerve fiber subtypes.
Discussion
We found less dermal nerve fibers in contact with blood vessels in FMS patients than in controls. The pathophysiological relevance of this finding is unclear, but we suggest the possibility of a relationship with impaired thermal tolerance commonly reported by FMS patients.
Intra- and interobserver reliability of glenoid fracture classifications by Ideberg, Euler and AO
(2018)
Background:
Representing 3%-5% of shoulder girdle injuries scapula fractures are rare. Furthermore, approximately 1% of scapula fractures are intraarticularfractures of the glenoid fossa. Because of uncertain fracture morphology and limited experience, the treatment of glenoid fossa fractures is difficult. The glenoid fracture classification by Ideberg (1984) and Euler (1996) is still commonly used in literature. In 2013 a new glenoid fracture classification was introduced by the AO. The purpose of this study was to examine the new AO classification in clinical practice in comparison with the classifications by Ideberg and Euler.
Methods:
In total CT images of 84 patients with glenoid fossa fractures from 2005 to 2018 were included. Parasagittal, paracoronary and axial reconstructions were examined according to the classifications of Ideberg, Euler and the AO by 3 investigators (orthopedic surgeon, radiologist, student of medicine) at three individual time settings. Inter- and intraobserver reliability of the three classification systems were ascertained by computing Inter- and Intraclass (ICCs) correlation coefficients using Spearman's rank correlation coefficient, 95%-confidence intervals as well as F-tests for correlation coefficients.
Results:
Inter- and intraobserver reliability for the AO classification showed a perspicuous coherence (R = 0.74 and R = 0.79). Low to moderate intraobserver reliability for Ideberg (R = 0.46) and Euler classification (R = 0.41) was found. Furthermore, data show a low Interobserver reliability for both Ideberg and Euler classification (R < 0.2). Both the Inter- and Intraclass reliability using AO is significantly higher than those using Ideberg and Euler (p < 0.05). Using the new AO classification, it was possible to find a proper class for every glenoid fossa fracture. On average, according to Euler classification 10 of 84 fractures were not classifiable whereas to Ideberg classification 21 of 84 fractures were not classifiable.
Conclusion:
The new AO classification system introduced 2013 facilitates reliable grading of glenoid fossa fractures with high inter- and intraobserver reliability in 84 patients using CT images. It should possibly be applied in order to enable a valid, reliable and consistent academic description of glenoid fossa fractures. The established classifications by Euler and Ideberg are not capable of providing a similar reliability.