@article{DenglerMaldanerGlaeskeretal.2016,
  author    = {Dengler, Julius and Maldaner, Nicolai and Gl{\"a}sker, Sven and Endres, Matthias and Wagner, Martin and Malzahn, Uwe and Heuschmann, Peter U. and Vajkoczy, Peter},
  title     = {Outcome of Surgical or Endovascular Treatment of Giant Intracranial Aneurysms, with Emphasis on Age, Aneurysm Location, and Unruptured Aneuryms - A Systematic Review and Meta-Analysis},
  series = {Cerebrovascular Diseases},
  volume    = {41},
  journal   = {Cerebrovascular Diseases},
  number    = {3-4},
  organization    = {Giant Intracranial Aneurysm Study Group},
  issn      = {1015-9770},
  doi       = {10.1159/000443485},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196792},
  pages     = {187-198},
  year      = {2016},
  abstract  = {Background: Designing treatment strategies for unruptured giant intracranial aneurysms (GIA) is difficult as evidence of large clinical trials is lacking. We examined the outcome following surgical or endovascular GIA treatment focusing on patient age, GIA location and unruptured GIA. Methods: Medline and Embase were searched for studies reporting on GIA treatment outcome published after January 2000. We calculated the proportion of good outcome (PGO) for all included GIA and for unruptured GIA by meta-analysis using a random effects model. Results: We included 54 studies containing 64 study populations with 1,269 GIA at a median follow-up time (FU-T) of 26.4 months (95\% CI 10.8-42.0). PGO was 80.9\% (77.4-84.4) in the analysis of all GIA compared to 81.2\% (75.3-86.1) in the separate analysis of unruptured GIA. For each year added to patient age, PGO decreased by 0.8\%, both for all GIA and unruptured GIA. For all GIA, surgical treatment resulted in a PGO of 80.3\% (95\% CI 76.0-84.6) compared to 84.2\% (78.5-89.8, p = 0.27) after endovascular treatment. In unruptured GIA, PGO was 79.7\% (95\% CI 71.5-87.8) after surgical treatment and 84.9\% (79.1-90.7, p = 0.54) after endovascular treatment. PGO was lower in high quality studies and in studies presenting aggregate instead of individual patient data. In unruptured GIA, the OR for good treatment outcome was 5.2 (95\% CI 2.0-13.0) at the internal carotid artery compared to 0.1 (0.1-0.3, p < 0.1) in the posterior circulation. Patient sex, FU-T and prevalence of ruptured GIA were not associated with PGO. Conclusions: We found that the chances of good outcome after surgical or endovascular GIA treatment mainly depend on patient age and aneurysm location rather than on the type of treatment conducted. Our analysis may inform future research on GIA.},
  language  = {en}
}
@phdthesis{Wagner2019,
  author    = {Wagner, Martin},
  title     = {Untersuchungen zu den kostimulatorischen Signalwegen PD-1/PD-L1 und CD137/CD137L beim kolorektalen Karzinom},
  doi       = {10.25972/OPUS-18434},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184343},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Kostimulatorische Signalwege spielen beim Zustandekommen einer T-Zell-gebundenen Effektor-Immunantwort eine entscheidende Rolle. In dieser Arbeit wurde die Expression der Signalwege PD-1/PD-L1 und CD137/CD137L im kolorektalen Karzinom untersucht. Hierzu wurde die Expression in den Karzinomen SW480, SW620 und HT-29 mittels qRT-PCR, Western Blot und FACS analysiert. Es konnte gezeigt werden, dass PD-1 und CD137 sowie deren Rezeptoren PD-L1 und CD137L im Kolonkarzinom auf Gen- und Proteinebene exprimiert werden. Zunehmendes Tumorzellwachstum sowie mangelnde N{\"a}hrstoffversorgung f{\"u}hrten zu deutlichen Ver{\"a}nderungen im Expressionsmuster, wobei sich zwischen den Kolonkarzinomen SW480/SW620 und dem Kolonkarzinom HT-29 Unterschiede aufzeigen ließen. Durch die Untersuchungen f{\"u}r diese Arbeit konnten wertvolle Informationen {\"u}ber das Expressionsverhalten der untersuchten kostimulatorischen Signalwege gewonnen werden. Eine m{\"o}gliche Schlussfolgerung ist, dass eine inhibierende PD-1/PD-L1- als auch eine CD137/CD137L-Tumorzell-vermittelte Therapie die Tumorimmunantwort gegen das kolorektale Karzinom st{\"a}rken und damit das {\"U}berleben betroffener Patienten verbessern k{\"o}nnte.},
  subject      = {Kolonkarzinom},
  language  = {de}
}
@phdthesis{Wagner2019,
  author    = {Wagner, Martin},
  title     = {Assoziations- und Haplotypenanalyse genetischer Ver{\"a}nderungen der Pannexin-Gengruppe bei Patienten mit schizophrenen Psychosen nach ICD-10 und der Klassifikation von Karl Leonhard},
  doi       = {10.25972/OPUS-18851},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188512},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Bestimmung von genetischen Ver{\"a}nderungen auf PANX 1-3 anhand von Einzelnukleotid Polymorphismen (SNP). Test auf Assoziation von Allelen und Haplotypen mit den schizophrenen Psychosen nach ICD-10 und der Klassifikation von Karl Leonhard in Form einer Fall-Kontroll-Studie mit 1163 Patienten und 479 Kontrollen.},
  subject      = {panx1},
  language  = {de}
}
@article{MagyarWagnerThomasetal.2019,
  author    = {Magyar, Attila and Wagner, Martin and Thomas, Phillip and Malsch, Carolin and Schneider, Reinhard and St{\"o}rk, Stefan and Heuschmann, Peter U and Leyh, Rainer G and Oezkur, Mehmet},
  title     = {HO-1 concentrations 24 hours after cardiac surgery are associated with the incidence of acute kidney injury: a prospective cohort study},
  series = {International Journal of Nephrology and Renovascular Disease},
  volume    = {12},
  journal   = {International Journal of Nephrology and Renovascular Disease},
  doi       = {10.2147/IJNRD.S165308},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177250},
  pages     = {9-18},
  year      = {2019},
  abstract  = {Background: Acute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI. Patients and methods: In the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated. Results: AKI with an incidence of 23.3\% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219). Conclusion: The association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management.},
  language  = {en}
}
@article{WagnerKraemerBlohmetal.2014,
  author    = {Wagner, Martin and Kr{\"a}mer, Johannes and Blohm, Elisabeth and Vergho, Dorothee and Weidemann, Frank and Breunig, Frank and Wanner, Christoph},
  title     = {Kidney function as an underestimated factor for reduced health related quality of life in patients with Fabry disease},
  doi       = {10.1186/1471-2369-15-188},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111159},
  year      = {2014},
  abstract  = {Background: Impairments of health related quality of life (HRQoL) are frequently observed in Fabry disease (FD) and are known to be related to neuropathic pain and cardiovascular events. This study aimed to explore the role of chronic kidney disease (CKD) in a large cohort of patients with FD. Methods: In 96 patients (53\% female; age 40 ± 12 yrs) with genetically proven FD, HRQoL was assessed by the Medical Outcomes Study (SF-36) questionnaire. All patients were na{\"i}ve to enzyme replacement therapy. Three categories for kidney dysfunction were chosen, eGFR ≥/<60 ml/min/1.73 m2 or need of renal replacement therapy (RRT). Minor (e.g. arrhythmia, angina pectoris, etc.) and major (e.g. myocardial infarction, coronary artery bypass, stroke or implantable cardioverter-defibrillator) vascular events as well as pain and pain therapy were considered in linear regression analyses with the dimensions of HRQoL. Results: Ten patients (10\%) had impaired kidney function and a further nine were on RRT (9.4\%). Kidney function and pain emerged as the main factors associated with lower scores on the SF 36, in particular on physical components (PCS beta-coefficients for CKD -6.2, for RRT -11.8, for pain -9.1, p < 0.05, respectively), while controlling for gender, vascular event and pain-therapy. Relationships were found for mental aspects of HRQoL. Age and history of vascular events were not related to HRQoL. Conclusion: Cardiovascular events and pain are important factors related to HRQoL, social functioning and depression. Our study highlights impaired chronic kidney disease, in particular after initiation of RRT, as a strong determinant of reduced HRQoL in FD.},
  language  = {en}
}
@article{OezkurWagnerWeismannetal.2015,
  author    = {Oezkur, Mehmet and Wagner, Martin and Weismann, Dirk and Krannich, Jens Holger and Schimmer, Christoph and Riegler, Christoph and R{\"u}cker, Victoria and Leyh, Rainer and Heuschmann, Peter U.},
  title     = {Chronic hyperglycemia is associated with acute kidney injury in patients undergoing CABG surgery - a cohort study},
  series = {BMC Cardiovascular Disorders},
  volume    = {15},
  journal   = {BMC Cardiovascular Disorders},
  number    = {41},
  doi       = {10.1186/s12872-015-0028-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125224},
  year      = {2015},
  abstract  = {Background Chronic hyperglycemia (CHG) with HbA1c as an indicator affects postoperative mortality and morbidity after coronary artery bypass grafting surgery (CABG). Acute kidney injury (AKI) is one of the frequent postoperative complications after CABG impacting short-and long-term outcomes. We investigated the association between CHG and postoperative incidence of AKI in CABG patients with and without history of diabetes mellitus (DM). Methods This cohort study consecutively enrolled patients undergoing CABG in 2009 at the department for cardiovascular surgery. CHG was defined as HbA1c ≥ 6.0 \%. Patients with advanced chronic kidney disease (CKD) were excluded. The incidence of postoperative AKI and its association with CHG was analyzed by univariate and multivariate logistic regression modeling. Results Three-hundred-seven patients were analyzed. The incidence of AKI was 48.2 \%. Patients with CHG (n = 165) were more likely to be female and had greater waist circumference as well as other comorbid conditions, such as smoking, history of DM, CKD, hypertension, pulmonary hypertension, and chronic obstructive pulmonary disease (all p ≤ 0.05). Preoperative eGFR, atrial fibrillation (AF), history of DM and CHG were associated with an increased risk of postoperative AKI in univariate analyses. In multivariate modelling, history of DM as well as preoperative eGFR and AF lost significance, while age, CHG and prolonged OP duration (p < 0.05) were independently associated with postoperative AKI. Conclusions Our results suggest that CHG defined on a single measurement of HbA1c ≥ 6.0 \% was associated with the incidence of AKI after CABG. This finding might implicate that treatment decisions, including the selection of operative strategies, could be based on HbA1c measurement rather than on a recorded history of diabetes.},
  language  = {en}
}
@article{WagnerAshbyKurtzetal.2015,
  author    = {Wagner, Martin and Ashby, Damien R. and Kurtz, Caroline and Alam, Ahsan and Busbridge, Mark and Raff, Ulrike and Zimmermann, Josef and Heuschmann, Peter U. and Wanner, Christoph and Schramm, Lothar},
  title     = {Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {4},
  doi       = {10.1371/journal.pone.0123072},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125514},
  pages     = {e0123072},
  year      = {2015},
  abstract  = {Background Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25—the key hormone of iron-metabolism—on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels. Methods 249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003-2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models. Results Patients (age 67 yrs, 53\% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7\%) and forty (16.1\%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05). Conclusions We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define "high risk" populations in CKD.},
  language  = {en}
}
@article{OezkurGorskiPeltzetal.2014,
  author    = {Oezkur, Mehmet and Gorski, Armin and Peltz, Jennifer and Wagner, Martin and Lazariotou, Maria and Schimmer, Christoph and Heuschmann, Peter U. and Leyh, Rainer G.},
  title     = {Preoperative serum h-FABP concentration is associated with postoperative incidence of acute kidney injury in patients undergoing cardiac surgery},
  doi       = {10.1186/1471-2261-14-117},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110480},
  year      = {2014},
  abstract  = {Background Fatty acid binding protein (FABP) is an intracellular transport protein associated with myocardial damage size in patients undergoing cardiac surgery. Furthermore, elevated FABP serum concentrations are related to a number of common comorbidities, such as heart failure, chronic kidney disease, diabetes mellitus, and metabolic syndrome, which represent important risk factors for postoperative acute kidney injury (AKI). Data are lacking on the association between preoperative FABP serum level and postoperative incidence of AKI. Methods This prospective cohort study investigated the association between preoperative h-FABP serum concentrations and postoperative incidence of AKI, hospitalization time and length of ICU treatment. Blood samples were collected according to a predefined schedule. The AKI Network definition of AKI was used as primary endpoint. All associations were analysed using descriptive and univariate analyses. Results Between 05/2009 and 09/2009, 70 patients undergoing cardiac surgery were investigated. AKI was observed in 45 patients (64\%). Preoperative median (IQR) h-FABP differed between the AKI group (2.9 [1.7-4.1] ng/ml) and patients without AKI (1.7 [1.1-3.3] ng/ml; p = 0.04), respectively. Patients with AKI were significantly older. No statistically significant differences were found for gender, type of surgery, operation duration, CPB-, or X-Clamp time, preoperative cardiac enzymes, HbA1c, or CRP between the two groups. Preoperative h-FABP was also correlated with the length of ICU stay (rs = 0.32, p = 0.007). Conclusions We found a correlation between preoperative serum h-FABP and the postoperative incidence of AKI. Our results suggest a potential role for h-FABP as a biomarker for AKI in cardiac surgery.},
  language  = {en}
}
@phdthesis{Wagner2005,
  author    = {Wagner, Martin},
  title     = {Proliferationsverhalten kultivierter Mesangialzellen und glatter Gef{\"a}ßmuskelzellen nach Stimulation mit Angiotensin II und atherogenen Lipoproteinen : Rezeptorbeteiligung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-15589},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {Hintergrund: Atherogene Lipoproteine und Angiotensin II sind an der Entstehung von Athe-rosklerose und Glomerulosklerose maßgeblich beteiligt. Sowohl klinische Studien als auch experimentelle Beobachtungen weisen auf eine Interaktion beider Substanzen im Sinne ei-ner Potenzierung ihrer Einzeleffekte hin. Die vorliegende Arbeit untersuchte die Auswirkun-gen von Angiotensin II und nativen und oxidierten Low Density Lipoproteinen (natLDL bzw. oxLDL) auf den Zellzyklus von kultivierten vaskul{\"a}ren Gef{\"a}ßmuskelzellen (BSMC) und Me-sangiumzellen (NHMC) im Sinne einer Proliferations{\"a}nderung unter anderem durch eine Beeinflussung der beteiligten Rezeptoren. Ebenso wurde die Interaktion von oxidierten LDL mit der Zelle sowohl qualitativ als auch quantitativ bestimmt. Methoden: Die Proliferation wurde sowohl mittels radioaktiv markiertem 3H-Thymidin-Einbau als auch durch den MTT-Assay, der auf der photometrisch messbaren Umwandlung von 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl Tetrazoliumbromid beruht, quantifiziert. Die Rezepto-ren wurden auf Proteinebene durch Western Blot Analysen nachgewiesen. Zum Nachweis der Interaktion von oxidierten LDL mit den inkubierten Zellen wurden die oxidierten LDL mit-tels 3,3'-Dioctadecyclindocarbocyanin (DiI) fluoreszenzmarkiert. Visualisiert werden konnte die Interaktion in der Histochemie, die quantitative Bestimmung der DiI-oxLDL-Aufnahme erfolgte durch fluorometische Messung. Ergebnisse: Sowohl native als auch oxidierte LDL steigerten die Proliferation in BSMC und NHMC. In Myozyten lag das Maximum im Tritiumeinbau bei ca. 450\% bezogen auf die Kon-trollzellen bei 10 µg/ml natLDL, und bei ca. 350\% bei 20 µg/ml oxLDL. In NHMC fiel der An-stieg der Proliferation weniger stark aus, ca. 150\% bei 30 µg/ml natLDL und ca. 180\% bei 3 µg/ml oxLDL. Im MTT-Assay konnten signifikante Dosis-Wirkungs-Beziehungen erstellt wer-den, die absolute Proliferationssteigerung war jedoch geringer: BSMC 120\%, NHMC 140\%. Fluoreszenzmarkierte oxLDL wurden {\"u}ber Endozytose in einem konzentrations- und zeitab-h{\"a}ngigen Prozess mit einer S{\"a}ttigung nach ca. 14 Stunden in die Zellen aufgenommen. Der oxLDL-spezifische LOX-1-Rezeptor konnte jederzeit nachgewiesen werden. Durch Angiotensin II alleine und in Co-Inkubation mit atherogenen Lipoproteinen konnte kei-ne Proliferations{\"a}nderung gezeigt werden. Die spezifische Hemmung des AT1-Rezeptors mit Losartan bewirkte ebenfalls keine signifikanten {\"A}nderungen. Auch die Inkubation der Zellen mit Agenzien, die die AT1-Rezeptordichte erh{\"o}hen sollten, erbrachte im Western Blot keine Ver{\"a}nderungen. Im Vergleich unterschiedlich alter Zellpopulationen ließ sich in h{\"o}heren Passagen der proliferationsvermittelnde AT1-Rezeptor kaum nachweisen, jedoch war in die-sen Zellpopulationen der antagonistisch wirkende AT2-Rezeptor stark exprimiert. Zusammenfassung: Atherogene Lipoproteine beeinflussen zeit- und konzentrationsabh{\"a}ngig m{\"o}glicherweise {\"u}ber eine LOX-1 vermittelte Endozytose den Zellzyklus von kultivierten glat-ten Muskelzellen und Mesangiumzellen im Sinne einer Proliferationssteigerung. Die uneinheitlichen Effekte von Angiotensin II auf die Proliferationsrate k{\"o}nnen durch die starken Expressionsschwankungen der antagonistisch wirkenden Angiotensin II-Rezeptor-Subtypen (AT1 und AT2) vor allem in unterschiedlich alten Zellpopulationen erkl{\"a}rt werden. Wodurch diese Expressionsver{\"a}nderungen verursacht sind, ist gegenw{\"a}rtig noch unklar, ebenso, ob diese Effekte im atherosklerotischen Plaque in vivo nachweisbar und pathophy-siologisch bedeutsam.},
  language  = {de}
}
@article{WalterGrussNeidlingeretal.2020,
  author    = {Walter, Steffen and Gruss, Sascha and Neidlinger, Jana and Stross, Isabelle and Hann, Alexander and Wagner, Martin and Seufferlein, Thomas and Walter, Benjamin},
  title     = {Evaluation of an Objective Measurement Tool for Stress Level Reduction by Individually Chosen Music During Colonoscopy—Results From the Study "ColoRelaxTone"},
  series = {Frontiers in Medicine},
  volume    = {7},
  journal   = {Frontiers in Medicine},
  doi       = {10.3389/fmed.2020.00525},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212337},
  year      = {2020},
  abstract  = {Background and Aims: Colonoscopy as standard procedure in endoscopy is often perceived as uncomfortable for patients. Patient's anxiety is therefore a significant issue, which often lead to avoidance of participation of relevant examinations as CRC-screening. Non-pharmacological anxiety management interventions such as music might contribute to relaxation in the phase prior and during endoscopy. Although music's anxiolytic effects have been reported previously, no objective measurement of stress level reduction has been reported yet. Focus of this study was to evaluate the objective measurement of the state of relaxation in patients undergoing colonoscopy. Methods: Prospective study (n = 196) performed at one endoscopic high-volume center. Standard colonoscopy was performed in control group. Interventional group received additionally self-chosen music over earphones. Facial Electromyography (fEMG) activity was obtained. Clinician Satisfaction with Sedation Instrument (CSSI) and Patients Satisfaction with Sedation Instrument (PSSI) was answered by colonoscopists and patients, respectively. Overall satisfaction with music accompanied colonoscopy was obtained if applicable. Results: Mean difference measured by fEMG via musculus zygomaticus major indicated a significantly lower stress level in the music group [7.700(±5.560) μV vs. 4.820(±3.330) μV; p = 0.001]. Clinician satisfaction was significantly higher with patients listening to music [82.69(±15.04) vs. 87.3(±15.02) pts.; p = 0.001]. Patient's satisfaction was higher but did not differ significantly. Conclusions: We conclude that self-chosen music contributes objectively to a reduced stress level for patients and therefore subjectively perceived satisfaction for endoscopists. Therefore, music should be considered as a non-pharmacological treatment method of distress reduction especially in the beginning of endoscopic procedures.},
  language  = {en}
}