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1.
Qingyang Xiao Yitian Zhou Stefan Winter Florian Büttner Elke Schaeffeler Matthias Schwab Volker M. Lauschke 《International journal of cancer. Journal international du cancer》2020,146(9):2475-2487
Multidrug resistance due to facilitated drug efflux mediated by ATP-binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease-specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug-specific for subgroups treated with the MRP1 substrates cyclophosphamide (log-rank p = 0.0011) and doxorubicin (log-rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log-rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine. 相似文献
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Nuno Rui Paulino Pereira Paul T. Ogink Olivier Q. Groot Marco L. Ferrone Francis J. Hornicek C.N. van Dijk J.A.M. Bramer Joseph H. Schwab 《The spine journal》2019,19(1):144-156
Background Context
Postoperative morbidity may offset the potential benefits of surgical treatment for spine metastatic disease; hence, risk factors for postoperative complications and reoperations should be taken into considerations during surgical decision-making. In addition, it remains unknown whether complications and reoperations shorten these patients' survival.Purpose
We aimed to describe and identify factors associated with having a complication within 30 days of index surgery as well as factors associated with having a subsequent reoperation. Furthermore, we assessed the effect of 30-day complications and reoperations on the patients' postoperative survival, as well as described neurologic changes after surgery.Study Design
Retrospective cohort study.Patient Sample
We included 647 patients 18 years and older who had surgery for metastatic disease in the spine between January 2002 and January 2014 in one of two affiliated tertiary care centers.Outcome Measures
Our primary outcomes were complications within 30 days after surgery and reoperations until final follow-up or death.Methods
We used multivariate logistic regression to identify risk factors for 30-day complications and reoperations. We used the Cox regression analysis to assess the effect of postoperative complications and reoperations on survival.Results
From 647 included patients, 205 (32%) had a complication within 30 days. The following variables were independently associated with 30-day complications: lower albumin levels (odds ratio [OR]: 0.69, 95% confidence interval [CI]=0.49–0.96, p=.021), additional comorbidities (OR=1.42, 95% CI=1.00–2.01, p=.048), pathologic fracture (OR=1.41, 95% CI=0.97–2.05, p=.031), three or more spine levels operated upon (OR=1.64, 95% CI=1.02–2.64, p=.027), and combined surgical approach (OR=2.44, 95% CI=1.06–5.60, p=.036). One hundred and fifteen patients (18%) had at least one reoperation after the initial surgery; prior radiotherapy (OR=1.56, 95% CI=1.07–2.29, p=.021) to the spinal tumor was independently associated with reoperation. 30-day complications were associated with worse survival (hazard ratio [HR]=1.40, 95% CI=1.17–1.68, p<.001), and reoperation was not significantly associated with worse survival (HR=0.80, 95% CI=0.09–1.00, p=.054). Neurologic status worsened in 42 (6.7%), remained stable in 445 (71%), and improved in 140 (22%) patients after surgery.Conclusions
Three or more spine levels operated upon and prior radiotherapy should prompt consideration of a preoperative plastic surgery consultation regarding soft tissue coverage. Furthermore, if time allows, aggressive nutritional supplementation should be considered for patient with low preoperative serum albumin levels. Surgeons should be aware of the increase in complications in patients presenting with pathologic fracture, undergoing a combined approach, and with any additional preoperative comorbidities. Importantly, 30-day complications were associated with worsened survival. 相似文献5.
Testing association of rare genetic variants with resistance to three common antiseizure medications
Stefan Wolking Claudia Moreau Anne T. Nies Elke Schaeffeler Mark McCormack Pauls Auce Andreja Avbersek Felicitas Becker Martin Krenn Rikke S. Møller Marina Nikanorova Yvonne G. Weber Sarah Weckhuysen Gianpiero L. Cavalleri Norman Delanty Chantal Depondt Michael R. Johnson Bobby P.C. Koeleman Wolfram S. Kunz Anthony G. Marson Josemir W. Sander Graeme J. Sills Pasquale Striano Federico Zara Fritz Zimprich Matthias Schwab Roland Krause Sanjay M. Sisodiya Patrick Cossette Simon L. Girard Holger Lerche EpiPGX Consortium 《Epilepsia》2020,61(4):657-666
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Stoll Svenja Macha Kosmas Marsch Armin Gerner Stefan T. Siedler Gabriela Fröhlich Kilian Volbers Bastian Strasser Erwin F. Schwab Stefan Kallmünzer Bernd 《Journal of neurology》2020,267(7):2007-2012
Journal of Neurology - Oral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation require dose adjustment based on certain clinical criteria, but the off-label use of the reduced... 相似文献
10.
David J. Seiffge MD Gian Marco De Marchis MD Masatoshi Koga MD PhD Maurizio Paciaroni MD Duncan Wilson PhD Manuel Cappellari MD Kosmas Macha MD Georgios Tsivgoulis MD Gareth Ambler PhD Shoji Arihiro MD Leo H. Bonati MD Bruno Bonetti MD Bernd Kallmünzer MD Keith W. Muir MD PhD Paolo Bovi MD Henrik Gensicke MD Manabu Inoue MD Stefan Schwab MD Shadi Yaghi MD Martin M. Brown MD PhD FRCP Philippe Lyrer MD Masahito Takagi MD PhD Monica Acciarrese MD Hans Rolf Jager MD FRCP Alexandros A. Polymeris MD Kazunori Toyoda MD PhD Michele Venti MD Christopher Traenka MD Hiroshi Yamagami MD PhD Andrea Alberti MD Sohei Yoshimura MD PhD Valeria Caso MD Stefan T. Engelter MD David J. Werring MD PhD FRCP the RAF RAF-DOAC CROMIS- SAMURAI NOACISP Erlangen and Verona registry collaborators 《Annals of neurology》2020,87(5):677-687