TY - JOUR A1 - Genest, F. A1 - Claußen, L. A1 - Rak, D. A1 - Seefried, L. T1 - Bone mineral density and fracture risk in adult patients with hypophosphatasia JF - Osteoporosis International N2 - Summary In adult hypophosphatasia (HPP) patients, elevated lumbar spine dual X-ray absorptiometry (DXA) values are associated with markers of disease severity and disease-specific fracture risk while femoral bone mineral density (BMD), being largely unaffected by the disease severity, may still be useful to monitor other causes of increased fracture risk due to low BMD. Introduction Hypophosphatasia (HPP) is a rare inherited metabolic disorder due to deficient activity of the tissue-nonspecific alkaline phosphatase (TNAP). Clinical manifestation in adult HPP patients is manifold including an increased risk for fractures, but data regarding clinical significance of DXA measurement and associations with fracture risk and disease severity is scarce. Methods Retrospective single-center analysis of DXA scans in patients with confirmed HPP (documented mutation, clinical symptoms, low alkaline phosphatase activity). Further data evaluation included disease-related fractures, laboratory results (alkaline phosphatase, pyridoxalphosphate, phosphoethanolamine), and medical history. Results Analysis included 110 patients (84 female, mean age of 46.2 years) of whom 37.3% (n = 41) were harboring two mutations. Average T-Score level at the lumbar spine was − 0.1 (SD 1.9), and mean total hip T-Score was − 1.07 (SD 0.15). Both lower ALP activity and higher substrate levels (pyridoxalphosphate and phosphoethanolamine) were significantly correlated with increased lumbar spine T-Score levels (p < 0.001) while BMD at the hip was not affected by indicators of disease severity. Increased lumbar spine BMD was significantly associated with an increased risk for HPP-related fractures, prevalent in 22 (20%) patients (p < 0.001) with 21 of them having biallelic mutations. Conclusion BMD in adult HPP patients is not systematically reduced. Conversely, increased lumbar spine BMD appears to be associated with severely compromised mineralization and increased risk for HPP-related fractures while BMD at the hip appears unaffected by indicators of disease severity, suggesting suitability of this anatomic location for assessing and discerning disorders with increased fracture risk owing to reduced BMD like osteoporosis. Trial registration number German register for clinical studies (DRKS00014022) Date of registration 02/10/2018 – retrospectively registered KW - bone mineral density KW - fracture risk KW - hypophosphatasia KW - osteoporosis KW - pseudofracture Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235793 SN - 0937-941X VL - 32 ER - TY - JOUR A1 - Capetian, Philipp A1 - Roessner, Veit A1 - Korte, Caroline A1 - Walitza, Susanne A1 - Riederer, Franz A1 - Taurines, Regina A1 - Gerlach, Manfred A1 - Moser, Andreas T1 - Altered urinary tetrahydroisoquinoline derivatives in patients with Tourette syndrome: reflection of dopaminergic hyperactivity? JF - Journal of Neural Transmission N2 - Tetrahydroisoquinolines (TIQs) such as salsolinol (SAL), norsalsolinol (NSAL) and their methylated derivatives N-methyl-norsalsolinol (NMNSAL) and N-methyl-salsolinol (NMSAL), modulate dopaminergic neurotransmission and metabolism in the central nervous system. Dopaminergic neurotransmission is thought to play an important role in the pathophysiology of chronic tic disorders, such as Tourette syndrome (TS). Therefore, the urinary concentrations of these TIQ derivatives were measured in patients with TS and patients with comorbid attention-deficit/hyperactivity disorder (TS + ADHD) compared with controls. Seventeen patients with TS, 12 with TS and ADHD, and 19 age-matched healthy controls with no medication took part in this study. Free levels of NSAL, NMNSAL, SAL, and NMSAL in urine were measured by a two-phase chromatographic approach. Furthermore, individual TIQ concentrations in TS patients were used in receiver-operating characteristics (ROC) curve analysis to examine the diagnostic value. NSAL concentrations were elevated significantly in TS [434.67 ± 55.4 nmol/l (standard error of mean = S.E.M.), two-way ANOVA, p < 0.0001] and TS + ADHD patients [605.18 ± 170.21 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] compared with controls [107.02 ± 33.18 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] and NSAL levels in TS + ADHD patients were elevated significantly in comparison with TS patients (two-way ANOVA, p = 0.017). NSAL demonstrated an AUC of 0.93 ± 0.046 (S.E.M) the highest diagnostic value of all metabolites for the diagnosis of TS. Our results suggest a dopaminergic hyperactivity underlying the pathophysiology of TS and ADHD. In addition, NSAL concentrations in urine may be a potential diagnostic biomarker of TS. KW - Tourette syndrome KW - ADHD KW - tics KW - biomarkers KW - tetrahydroisoquinoline derivates Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235771 SN - 0300-9564 VL - 128 ER - TY - JOUR A1 - Fehske, Kai A1 - Berninger, Markus T. A1 - Alm, Lena A1 - Hoffmann, Reinhard A1 - Zellner, Johannes A1 - Kösters, Clemens A1 - Barzen, Stefan A1 - Raschke, Michael J. A1 - Izadpanah, Kaywan A1 - Herbst, Elmar A1 - Domnick, Christoph A1 - Schüttrumpf, Jan Philipp A1 - Krause, Matthias T1 - Aktueller Versorgungsstandard von Patellafrakturen in Deutschland JF - Der Unfallchirurg N2 - Hintergrund Die Versorgung von Patellafrakturen ist technisch anspruchsvoll. Auch wenn die radiologischen Ergebnisse zumeist zufriedenstellend sind, deckt sich dies häufig nicht mit der subjektiven Einschätzung der Patienten. Die klassische Versorgung mittels Drahtzuggurtung weist einige Komplikationen auf. Die winkelstabile Plattenosteosynthese hat sich in den letzten Jahren biomechanisch als vorteilhaft erwiesen. Fragestellung Von wem werden Patellafrakturen in Deutschland versorgt? Wie sieht der aktuelle Versorgungsstandard aus? Haben sich „moderne“ Osteosyntheseformen durchgesetzt? Was sind die häufigsten Komplikationen? Material und Methoden Die Mitglieder der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie sowie der Deutschen Kniegesellschaft wurden aufgefordert, an einer Onlinebefragung teilzunehmen. Ergebnisse Insgesamt wurden 511 komplett ausgefüllte Fragebogen ausgewertet. Die Befragten sind zum größten Teil auf Unfallchirurgie spezialisiert (51,5 %) und verfügen über langjährige Berufserfahrung in Traumazentren. Die Hälfte der Operateure versorgt ≤5 Patellafrakturen jährlich. In knapp 40 % der Fälle wird die präoperative Bildgebung um eine Computertomographie ergänzt. Die klassische Zuggurtung ist noch die bevorzugte Osteosyntheseform bei allen Frakturtypen (Querfraktur 52 %, Mehrfragmentfrakturen 40 %). Bei Mehrfragmentfrakturen entscheiden sich 30 % der Operateure für eine winkelstabile Plattenosteosynthese. Bei Beteiligung des kaudalen Pols dient als zusätzliche Sicherung die McLaughlin-Schlinge (60 %). Diskussion Der Versorgungsstandard von Patellafrakturen in Deutschland entspricht weitgehend der aktualisierten S2e-Leitlinie. Nach wie vor wird die klassische Zuggurtungsosteosynthese als Verfahren der Wahl genutzt. Weitere klinische (Langzeit‑)Studien werden benötigt, um die Vorteile der winkelstabilen Plattenosteosynthese zu verifizieren. N2 - Background The treatment of patella fractures is technically demanding. Although the radiological results are mostly satisfactory, this often does not correspond to the subjective assessment of the patients. The classical treatment with tension band wiring with K‑wires has several complications. Fixed-angle plate osteosynthesis seems to be biomechanically advantageous. Objective Who is treating patella fractures in Germany? What is the current standard of treatment? Have modern forms of osteosynthesis become established? What are the most important complications? Material and methods The members of the German Society for Orthopedics and Trauma Surgery and the German Knee Society were asked to participate in an online survey. Results A total of 511 completed questionnaires were evaluated. Most of the respondents are specialized in trauma surgery (51.5%), have many years of professional experience and work in trauma centers. Of the surgeons 50% treat ≤5 patella fractures annually. In almost 40% of the cases preoperative imaging is supplemented by computed tomography. The classical tension band wiring with K‑wires is still the preferred form of osteosynthesis for all types of fractures (transverse fractures 52%, comminuted fractures 40%). In the case of comminuted fractures 30% of the surgeons choose fixed-angle plate osteosynthesis. If the inferior pole is involved a McLaughlin cerclage is used for additional protection in 60% of the cases. Discussion The standard of care for patella fractures in Germany largely corresponds to the updated S2e guidelines. Tension band wiring is still the treatment of choice. Further (long-term) clinical studies are needed to verify the advantages of fixed-angle plates. T2 - Current treatment standard for patella fractures in Germany KW - Kniegelenk KW - Winkelstabile Platte KW - Klassische Zuggurtung KW - Versorgungsstrategien KW - Umfrage KW - knee joint KW - fixed-angle plate KW - tension band wiring KW - treatment strategy KW - survey Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235047 SN - 0177-5537 VL - 124 ER - TY - JOUR A1 - Brodehl, Andreas A1 - Milting, Hendrik A1 - Gerull, Brenda T1 - Special Issue “Cardiovascular Genetics” JF - Genes N2 - No abstract available KW - cardiovascular genetics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234229 SN - 2073-4425 VL - 12 IS - 4 ER - TY - JOUR A1 - Brand, Markus A1 - Reimer, Stanislaus A1 - Reibetanz, Joachim A1 - Flemming, Sven A1 - Kornmann, Marko A1 - Meining, Alexander T1 - Endoscopic full thickness resection vs. transanal endoscopic microsurgery for local treatment of rectal neuroendocrine tumors - a retrospective analysis JF - International Journal of Colorectal Disease N2 - 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. KW - rectum KW - neuroendocrine tumor (NET) KW - transanal endoscopic microsurgery (TEM) KW - endoscopic full thickness resection (eFTR) KW - full-thickness resection device (FTRD) Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234833 SN - 0179-1958 VL - 36 ER - TY - JOUR A1 - Riemer, Manuel A1 - Kranke, Peter A1 - Helf, Antonia A1 - Mayer, Debora A1 - Popp, Maria A1 - Schlesinger, Tobias A1 - Meybohm, Patrick A1 - Weibel, Stephanie T1 - Trial registration and selective outcome reporting in 585 clinical trials investigating drugs for prevention of postoperative nausea and vomiting JF - BMC Anesthesiology N2 - Background: Selective outcome reporting in clinical trials introduces bias in the body of evidence distorting clinical decision making. Trial registration aims to prevent this bias and is suggested by the International Committee of Medical Journal Editors (ICMJE) since 2004. Methods: The 585 randomized controlled trials (RCTs) published between 1965 and 2017 that were included in a recently published Cochrane review on antiemetic drugs for prevention of postoperative nausea and vomiting were selected. In a retrospective study, we assessed trial registration and selective outcome reporting by comparing study publications with their registered protocols according to the ‘Cochrane Risk of bias’ assessment tool 1.0. Results: In the Cochrane review, the first study which referred to a registered trial protocol was published in 2004. Of all 585 trials included in the Cochrane review, 334 RCTs were published in 2004 or later, of which only 22% (75/334) were registered. Among the registered trials, 36% (27/75) were pro- and 64% (48/75) were retrospectively registered. 41% (11/27) of the prospectively registered trials were free of selective outcome reporting bias, 22% (6/27) were incompletely registered and assessed as unclear risk, and 37% (10/27) were assessed as high risk. Major outcome discrepancies between registered and published high risk trials were a change from the registered primary to a published secondary outcome (32%), a new primary outcome (26%), and different outcome assessment times (26%). Among trials with high risk of selective outcome reporting 80% favoured at least one statistically significant result. Registered trials were assessed more often as ‘overall low risk of bias’ compared to non-registered trials (64% vs 28%). Conclusions: In 2017, 13 years after the ICMJE declared prospective protocol registration a necessity for reliable clinical studies, the frequency and quality of trial registration in the field of PONV is very poor. Selective outcome reporting reduces trustworthiness in findings of clinical trials. Investigators and clinicians should be aware that only following a properly registered protocol and transparently reporting of predefined outcomes, regardless of the direction and significance of the result, will ultimately strengthen the body of evidence in the field of PONV research in the future. KW - clinical trial KW - postoperative nausea and vomiting KW - selective outcome reporting KW - systematic review KW - trial registration Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265518 VL - 21 ER - TY - JOUR A1 - Herrmann, Johannes A1 - Notz, Quirin A1 - Schlesinger, Tobias A1 - Stumpner, Jan A1 - Kredel, Markus A1 - Sitter, Magdalena A1 - Schmid, Benedikt A1 - Kranke, Peter A1 - Schulze, Harald A1 - Meybohm, Patrick A1 - Lotz, Christopher T1 - Point of care diagnostic of hypercoagulability and platelet function in COVID-19 induced acute respiratory distress syndrome: a retrospective observational study JF - Thrombosis Journal N2 - Background Coronavirus disease 2019 (COVID-19) associated coagulopathy (CAC) leads to thromboembolic events in a high number of critically ill COVID-19 patients. However, specific diagnostic or therapeutic algorithms for CAC have not been established. In the current study, we analyzed coagulation abnormalities with point-of-care testing (POCT) and their relation to hemostatic complications in patients suffering from COVID-19 induced Acute Respiratory Distress Syndrome (ARDS). Our hypothesis was that specific diagnostic patterns can be identified in patients with COVID-19 induced ARDS at risk of thromboembolic complications utilizing POCT. Methods This is a single-center, retrospective observational study. Longitudinal data from 247 rotational thromboelastometries (Rotem®) and 165 impedance aggregometries (Multiplate®) were analysed in 18 patients consecutively admitted to the ICU with a COVID-19 induced ARDS between March 12th to June 30th, 2020. Results Median age was 61 years (IQR: 51–69). Median PaO2/FiO2 on admission was 122 mmHg (IQR: 87–189), indicating moderate to severe ARDS. Any form of hemostatic complication occurred in 78 % of the patients with deep vein/arm thrombosis in 39 %, pulmonary embolism in 22 %, and major bleeding in 17 %. In Rotem® elevated A10 and maximum clot firmness (MCF) indicated higher clot strength. The delta between EXTEM A10 minus FIBTEM A10 (ΔA10) > 30 mm, depicting the sole platelet-part of clot firmness, was associated with a higher risk of thromboembolic events (OD: 3.7; 95 %CI 1.3–10.3; p = 0.02). Multiplate® aggregometry showed hypoactive platelet function. There was no correlation between single Rotem® and Multiplate® parameters at intensive care unit (ICU) admission and thromboembolic or bleeding complications. Conclusions Rotem® and Multiplate® results indicate hypercoagulability and hypoactive platelet dysfunction in COVID-19 induced ARDS but were all in all poorly related to hemostatic complications.. KW - COVID-19 KW - acute Respiratory Distress Syndrome KW - point of care testing KW - thromboelastometry KW - impedance aggregometry; WHOLE-BLOOD THROMBOELASTOMETRY; DEFINITION; DISEASE Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260739 VL - 19 IS - 1 ER - TY - JOUR A1 - Notz, Quirin A1 - Lotz, Christopher A1 - Herrmann, Johannes A1 - Vogt, Marius A1 - Schlesinger, Tobias A1 - Kredel, Markus A1 - Muellges, Wolfgang A1 - Weismann, Dirk A1 - Westermaier, Thomas A1 - Meybohm, Patrick A1 - Kranke, Peter T1 - Severe neurological complications in critically ill COVID‑19 patients JF - Journal of Neurology N2 - No abstract available. KW - COVID-19 KW - neurological complications Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232429 SN - 0340-5354 ER - TY - JOUR A1 - Schmid, Benedikt A1 - Kredel, Markus A1 - Ullrich, Roman A1 - Krenn, Katharina A1 - Lucas, Rudolf A1 - Markstaller, Klaus A1 - Fischer, Bernhard A1 - Kranke, Peter A1 - Meybohm, Patrick A1 - Zwißler, Bernhard A1 - Frank, Sandra T1 - Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS - a randomized, placebo-controlled, double-blind trial JF - Trials N2 - Background Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients. Methods This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days. Discussion The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion. Trial registration This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47. KW - acute respiratory distress syndrome KW - solnatide KW - extravascular lung water KW - pulmonary edema KW - critical care Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258783 VL - 22 IS - 1 ER - TY - JOUR A1 - Schrader, Nikolas A1 - Riese, Thorsten A1 - Kurlbaum, Max A1 - Meybohm, Patrick A1 - Kredel, Markus A1 - Surat, Güzin A1 - Scherf-Clavel, Oliver A1 - Strate, Alexander A1 - Pospiech, Andreas A1 - Hoppe, Kerstin T1 - Personalized antibiotic therapy for the critically ill: Implementation strategies and effects on clinical outcome of piperacillin therapeutic drug monitoring — a descriptive retrospective analysis JF - Antibiotics N2 - Therapeutic drug monitoring (TDM) is increasingly relevant for an individualized antibiotic therapy and subsequently a necessary tool to reduce multidrug-resistant pathogens, especially in light of diminishing antimicrobial capabilities. Critical illness is associated with profound pharmacokinetic and pharmacodynamic alterations, which challenge dose finding and the application of particularly hydrophilic drugs such as β-lactam antibiotics. Methods: Implementation strategy, potential benefit, and practicability of the developed standard operating procedures were retrospectively analyzed from January to December 2020. Furthermore, the efficacy of the proposed dosing target of piperacillin in critically ill patients was evaluated. Results: In total, 160 patients received piperacillin/tazobactam therapy and were subsequently included in the study. Of them, 114 patients received piperacillin/tazobactam by continuous infusion and had at least one measurement of piperacillin serum level according to the standard operating procedure. In total, 271 measurements were performed with an average level of 79.0 ± 46.0 mg/L. Seventy-one piperacillin levels exceeded 100 mg/L and six levels were lower than 22.5 mg/L. The high-level and the low-level group differed significantly in infection laboratory parameters (CRP (mg/dL) 20.18 ± 11.71 vs. 5.75 ± 5.33) and renal function [glomerular filtration rate (mL/min/1.75 m2) 40.85 ± 26.74 vs. 120.50 ± 70.48]. Conclusions: Piperacillin levels are unpredictable in critically ill patients. TDM during piperacillin/tazobactam therapy is highly recommended for all patients. Although our implementation strategy was effective, further strategies implemented into the daily clinical workflow might support the health care staff and increase the clinicians' alertness. KW - therapeutic drug monitoring KW - piperacillin/tazobactam KW - personalized antimicrobial therapy KW - antimicrobial stewardship Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250052 SN - 2079-6382 VL - 10 IS - 12 ER -