610 Medizin und Gesundheit
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- Klinik und Poliklinik für Anästhesiologie (ab 2004) (32)
Schriftenreihe
Sonstige beteiligte Institutionen
- Klinikum Fulda (2)
- Apotheke, Universitätsklinikum Würzburg (1)
- Clinical Trial Center (CTC) / Zentrale für Klinische Studien Würzburg (ZKSW) (1)
- Fraunhofer (1)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (1)
- Interdisciplinary Bank of Biological Material and Data Würzburg (IBDW) (1)
- Klinikum Main-Spessart Lohr (1)
- Krankenhaushygiene und Antimicrobial Stewardship (1)
- Krankenhaushygiene und Antimicrobial Stewardship, Universitätsklinikum Würzburg (1)
- Lehrkrankenhaus II. Medizinische Klinik Klinikum Coburg (1)
Objectives
Trauma evaluation of extremities can be challenging in conventional radiography. A multi-use x-ray system with cone-beam CT (CBCT) option facilitates ancillary 3-D imaging without repositioning. We assessed the clinical value of CBCT scans by analyzing the influence of additional findings on therapy.
Methods
Ninety-two patients underwent radiography and subsequent CBCT imaging with the twin robotic scanner (76 wrist/hand/finger and 16 ankle/foot/toe trauma scans). Reports by on-call radiologists before and after CBCT were compared regarding fracture detection, joint affliction, comminuted injuries, and diagnostic confidence. An orthopedic surgeon recommended therapy based on reported findings. Surgical reports (N = 52) and clinical follow-up (N = 85) were used as reference standard.
Results
CBCT detected more fractures (83/64 of 85), joint involvements (69/53 of 71), and multi-fragment situations (68/50 of 70) than radiography (all p < 0.001). Six fractures suspected in radiographs were ruled out by CBCT. Treatment changes based on additional information from CBCT were recommended in 29 patients (31.5%). While agreement between advised therapy before CBCT and actual treatment was moderate (κ = 0.41 [95% confidence interval 0.35–0.47]; p < 0.001), agreement after CBCT was almost perfect (κ = 0.88 [0.83–0.93]; p < 0.001). Diagnostic confidence increased considerably for CBCT studies (p < 0.001). Median effective dose for CBCT was 4.3 μSv [3.3–5.3 μSv] compared to 0.2 μSv [0.1–0.2 μSv] for radiography.
Conclusions
CBCT provides advantages for the evaluation of acute small bone and joint trauma by detecting and excluding extremity fractures and fracture-related findings more reliably than radiographs. Additional findings induced therapy change in one third of patients, suggesting substantial clinical impact.
Purpose
We used exact matching for a highly balanced comparison of ab interno trabeculectomy (AIT) with the trabectome to trabeculectomy with mitomycin C (TRAB).
Methods
A total of 5485 patients who underwent AIT were exact-matched to 196 TRAB patients by baseline intraocular pressure (IOP), number of glaucoma medications, and glaucoma type. Nearest-neighbor–matching was applied to age. Success was defined as a final IOP of less than 21 mmHg, IOP reduction of at least 20% reduction from baseline, and no secondary surgical interventions. Outcomes were measured at 1, 3, 6, 12, 18, and 24 months.
Results
A total of 165 AIT could be matched to 165 TRAB. The mean baseline IOP was 22.3 ± 5.6 mmHg, and the baseline number of glaucoma medications was 2.7 ± 1.1 in both groups. At 24 months, IOP was reduced to 15.8 ± 5.2 mmHg in AIT and 12.4 ± 4.7 mmHg in TRAB. IOP was lower than baseline at all visits (p < 0.01) and lower in TRAB than AIT (p < 0.01). Glaucoma medications were reduced to 2.1 ± 1.3 in AIT and 0.2 ± 0.8 in TRAB. Compared to baseline, patients used fewer drops postoperatively (p < 0.01) and more infrequently in TRAB than in AIT (p > 0.01). Secondary surgical interventions had the highest impact on success and became necessary in 15 AIT and 59 TRAB patients. Thirty-two challenging events occurred in TRAB and none in AIT.
Conclusion
Both AIT and TRAB reduced IOP and medications. This reduction was more significant in TRAB but at the expense of four times as many secondary interventions.
Purpose
Local treatment of small well-differentiated rectal neuroendocrine tumors (NETs) is recommended by current guidelines. However, although several endoscopic methods have been established, the highest R0 rate is achieved by transanal endoscopic microsurgery (TEM). Since a recently published study about endoscopic full thickness resection (eFTR) showed a R0 resection rate of 100%, the aim of this study was to evaluate both methods (eFTR vs. TEM).
Methods
We retrospectively analyzed all patients with rectal NET treated either by TEM (1999–2018) or eFTR (2016–2019) in two tertiary centers (University Hospital Wuerzburg and Ulm). We analyzed clinical, procedural, and histopathological outcomes in both groups.
Results
Twenty-eight patients with rectal NET received local treatment (TEM: 13; eFTR: 15). Most tumors were at stage T1a and grade G1 or G2 (in the TEM group two G3 NETs were staged T2 after neoadjuvant chemotherapy). In both groups, similar outcomes for en bloc resection rate, R0 resection rate, tumor size, or specimen size were found. No procedural adverse events were noted. Mean procedure time in the TEM group was 48.9 min and 19.2 min in the eFTR group.
Conclusion
eFTR is a convincing method for local treatment of small rectal NETs combining high safety and efficacy with short interventional time.
In peripheral nervous system (PNS), the blood-nerve barrier (BNB) and myelin barrier (MB) are important physiological fences for maintaining the environment for axons, Schwann cells and other associated cells within peripheral nerves. The perineurium surrounding the nerves and endoneurial vessels nourishing the nerves compose the BNB. Schwann cells wrapping around neurons form the MB. Destruction or malfunction of the barriers has been postulated as an initial step in the development of pathologic conditions concerning human peripheral nerves, such as traumatic neuropathy and the disease of chronic inflammatory demyelination polyneuropathy (CIDP).
Tight junction proteins (TJPs) are intercellular junctions building the microstructure of barriers. They play a key role in tightly connecting adjacent cells, controlling the passage of ions, water and other molecules via the paracellular pathway, and maintaining the cell polarity. Among the family of TJPs, claudins are the major structural components which form the backbone of TJs. Certain key TJPs [e.g. claudins (claudin-1, -5, -19, occludin, zona occludens (ZO-1)] have been identified in neural barriers and explored for therapeutic targets. The expression of Cldn12 gene has been documented in human/rodent tibial nerves, spinal cord and DRG. However, the role of claudin-12 in PNS is unknown.
In the present study, we firstly found a loss of claudin-12 immunoreactivity (IR) in male or postmenopausal female patients with painful CIDP or non-inflammatory polyneuropathy (PNP). Then, we utilized male and female Cldn12-KO mice and the chronic constriction injury (CCI) model. Cldn12 mRNA and IR were reduced in WT mice after nerve injury. Deletion of Cldn12 via general knockout (KO) induced mechanical allodynia at baseline level and after CCI in time-dependent manner in male mice. KO of Cldn12 in males resulted in loss of small axons, perineurial barrier and MB breakdown, as well as TJP complex disruption with claudin-1, -19 and Pmp22 reduction. Moreover, local Cldn12 siRNA application mimicked mechanical allodynia and MB breakdown.
In conclusion, claudin-12 deficiency is associated with painful CIDP/non-inflammatory PNP. Claudin-12 is a regulatory TJP crucial for mechanical nociception, perineurial barrier and MB integrity, and proper TJP composition in mice. Therefore, further investigating the functions of claudin-12 and its mechanism is important to prompt the development of new therapeutic approaches for painful neuropathies.
Objectives
The present investigation aimed to evaluate the subjective perception of deformational cranial asymmetries by different observer groups and to compare these subjective perceptions with objective parameters.
Materials and methods
The 3D datasets of ten infants with different severities of deformational plagiocephaly (DP) were presented to 203 observers, who had been subdivided into five different groups (specialists, pediatricians, medical doctors (not pediatricians), parents of infants with DP, and laypersons). The observers rated their subjective perception of the infants’ cranial asymmetries using a 4-point Likert-type scale. The ratings from the observer groups were compared with one another using a multilevel modelling linear regression analysis and were correlated with four commonly used parameters to objectively quantify the cranial asymmetries.
Results
No significant differences were found between the ratings of the specialists and those of the parents of infants with DP, but both groups provided significantly more asymmetric ratings than did pediatricians, medical doctors, or laypersons. Moreover, the subjective perception of cranial asymmetries correlated significantly with commonly used parameters for objectively quantifying cranial asymmetries.
Conclusions
Our results demonstrate that different observer groups perceive the severity of cranial asymmetries differently. Pediatricians’ more moderate perception of cranial asymmetries may reduce the likelihood of parents to seek therapeutic interventions for their infants. Moreover, we identified some objective symmetry-related parameters that correlated strongly with the observers’ subjective perceptions.
Clinical relevance
Knowledge about these findings is important for clinicians when educating parents of infants with DP about the deformity.
Das Ziel dieser Studie war es, die Pathomechanismen der Enzepahlopathie, welche während einer akuten Nierenschädigung beobachtet werden kann, zu untersuchen. Wir konzipierten ein Zellkulturmodell, welches aus der cerebralen Endothelzelllinie cEND und der Nierentubuluszelllinie HK-2 bestant. Die Nierenzellen wurden einem Sauerstoff-Glukose-Entzug zugeführt, um eine akute Nierenschädigung zu simulieren. Nach weiterer Behandlung mit zwei urmämischen Toxinen (Indoxylsulfate und Indolessigsäure) und gemeinsamer Inkubation beider Zelllinien für insgesamt 48 Stunden wurden die cEND-Zellen geerntet und die Expression von Tight junction-Proteinen und Glukosetransportern untersucht.
Cell death is an essential aspect of life that plays an important role for successful development and tissue remodeling as well as for diseases. There are several different types of cell death that differ from each other in morphological, functional and biochemical ways. Regulated cell death that occurs in physiological processes is generally equated with programmed cell death (PCD), whereby apoptosis is the most studied form of PCD. Ferroptosis is a form of regulated cell death and unique in its requirements for iron and lipid peroxidation. It is linked to numerous biological processes, such as amino acid metabolism, phospholipid metabolism and sterol synthesis. Cholesterol biosynthesis is a complex pathway with a large number of enzymes and substrates that are potential target points for cellular dysfunctions. Motivated by the results from a CRISPR-based genetic screening in this thesis, we focused on 7-dehydrocholesterol reductase (DHCR7), the enzyme responsible for conversion of 7-dehydrocholesterol (7-DHC) to cholesterol. In this work we focused on the ferroptosis sensitive cell line HT1080 and generated a series of models to address the importance of DHCR7 in ferroptosis. Using CRISPR/Cas9, HT1080 DHCR7_KO and DHCR7/SC5D_KO cell lines were generated and used to validate their sensitivity against ferroptosis inducers and sterol consumption. We could show that 7-DHC is a strong antiferroptotic agent that could prevent cell death in genetic models as well as when supplemented directly to cells. Importantly, all the results obtained were subsequently confirmed in isogenic reconstituted pairs from the HT1080 DHCR7/SC5D_KO. Moreover, we demonstrate that this protective effect is not due to an inherent and unspecific resistance as the sensitivity to non-ferroptotic stimuli was equally effective in killing the HT1080 DHCR7_KO and DHCR7/SC5D_KO cell lines. We could also show that selenium present in the media has a strong impact on the activity of 7-DHC and this is because in its absence the effective concentration is rapidly decreased. Surprisingly we also demonstrate that removing sterol from cell culture triggers ferroptosis in cells unable to synthesize 7-DHC, suggestive that this could be used as a novel mechanism to trigger ferroptosis. Ultimately, in the present work we could show that unlike previously reported, 7-DHC is not only a toxic intermediate of the cholesterol biosynthesis pathway but under specific circumstances it has a strong pro-survival effect.
Eine Prognoseeinschätzung bei Patienten mit hypoxischer Enzephalopathie (HIE) nach Reanimation wird frühestens 72 Stunden nach Reanimation empfohlen. Bis zu diesem Zeitpunkt besteht eine für Ärzte und Angehörige belastende prognostische Lücke. Und auch nach 72 Stunden bestehen nur ungenaue Angaben zum weiteren Vorgehen, sodass eine fundierte Prognoseeinschätzung aktuell eine deutliche Herausforderung im Alltag klinisch tätiger Ärzte darstellt.
Der Nervus opticus ist als Bestandteil des zentralen Nervensystems mit dem Liquorsystem verbunden. Intrazerebrale Druckerhöhungen wirken sich daher unmittelbar auf die ihn ummantelnde Nervenscheide und deren Durchmesser aus, sodass sich die Bestimmung des Optikusnervenscheidendurchmessers (ONSD) mittels transorbitaler Sonographie in der Diagnostik unterschiedlicher intrakranieller Erkrankungen bereits bewährt hat. Das Krankheitsbild der HIE wurde als weiteres mögliches Einsatzgebiet des ONSD jedoch bisher nicht untersucht.
Ziel dieser Dissertation war es daher, den ONSD grundsätzlich auf seine Verlässlichkeit als Prognoseparameter bei HIE nach Reanimation zu überprüfen. Besonderes Augenmerk lag hierbei auf der Ermöglichung einer frühzeitigen Prognoseeinschätzung innerhalb von 24 Stunden sowie auf der Definition eines prognostischen Cut-Off-Wertes als klare Entscheidungshilfe für weitere therapeutische Strategien.
24, 48 und 72 Stunden nach Reanimation werden signifikant unterschiedliche ONSD unter überlebenden und verstorbenen Patienten nachgewiesen. Letztere weisen dabei im Vergleich sowohl höhere als auch im zeitlichen Verlauf signifikant ansteigende ONSD-Werte auf. Als prognostischer Cut-Off-Wert konnte eine Grenze bei 5,75mm festgelegt werden.
Zusammenfassend stellt die sonographische Bestimmung des ONSD eine sinnvolle Zusatzdiagnostik in der Prognoseeinschätzung bei Patienten mit HIE nach Reanimation dar.
Brustkrebs ist die häufigste maligne Erkrankung der Frau. Die Therapie setzt sich in der Regel individuell aus den Bausteinen der chirurgischen Tumorexzision, der Bestrahlung und der systemischen Therapie zusammen. Daneben gewinnt die ketogene Diät als supportiver Therapieansatz immer mehr an Aufmerksamkeit und Forschungsinteresse. Diese Ernährungsform imitiert durch starke Restriktion der Kohlenhydratzufuhr den Fastenstoffwechsel, da Blutzucker- und konsekutiv auch Insulinspitzen im Blut vermieden werden. Eine tragende Rolle kommt dabei der Bildung von Ketonkörpern, allen voran Betahydroxybutyrat, zu, die sowohl in den Tumorstoffwechsel als auch in immunologische Prozesse eingreifen können. In dieser Arbeit wurde ausgewählten Brustkrebszellen 3 mM Betahydroxybutyrat zugesetzt und ihr Wachstumsverhalten, ihre Chemo- und Radiosensitivität im Vergleich zu Kontrollzellen erfasst. Die Kontrollzellen wurden identisch behandelt, jedoch wurde Ihnen kein Betahydroxybutyrat zugefügt. Es zeigte sich dabei kein statistisch signifikanter Unterschied zwischen den beiden Zellgruppen.