1.Personalized medicine in non-small cell lung cancer: a review from a pharmacogenomics perspective.
Wenxiao JIANG ; Guiqing CAI ; Peter C HU ; Yue WANG
Acta Pharmaceutica Sinica B 2018;8(4):530-538
Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to modern medicine. While generalized medicine with traditional chemotherapy yielded comparatively poor response rates and treatment results, the cornerstone of personalized medicine using genetic profiling to direct treatment has exalted the successes seen in the field and raised the standard for patient treatment in lung and other cancers. Here, we discuss the current state and advances in the field of personalized medicine for lung cancer, reviewing several of the mutation-targeting strategies that are approved for clinical use and how they are guided by patient genetic information. These classes include inhibitors of tyrosine kinase (TKI), anaplastic lymphoma kinase (ALK), and monoclonal antibodies. Selecting from these treatment plans and determining the optimal dosage requires in-depth genetic guidance with consideration towards not only the underlying target genes but also other factors such as individual metabolic capability and presence of resistance-conferring mutations both directly on the target gene and along its cascade(s). Finally, we provide our viewpoints on the future of personalized medicine in lung cancer, including target-based drug combination, mutation-guided drug design and the necessity for data of population genetics, to provide rough guidance on treating patients who are unable to get genetic testing.
3.Endovascular Thrombectomy Versus Intravenous Thrombolysis of Posterior Cerebral Artery Occlusion Stroke
Silja RÄTY ; Thanh N. NGUYEN ; Simon NAGEL ; Davide STRAMBO ; Patrik MICHEL ; Christian HERWEH ; Muhammad M. QURESHI ; Mohamad ABDALKADER ; Pekka VIRTANEN ; Marta OLIVE-GADEA ; Marc RIBO ; Marios PSYCHOGIOS ; Anh NGUYEN ; Joji B. KURAMATSU ; David HAUPENTHAL ; Martin KÖHRMANN ; Cornelius DEUSCHL ; Jordi Kühne ESCOLÀ ; Jelle DEMEESTERE ; Robin LEMMENS ; Lieselotte VANDEWALLE ; Shadi YAGHI ; Liqi SHU ; Volker PUETZ ; Daniel P.O. KAISER ; Johannes KAESMACHER ; Adnan MUJANOVIC ; Dominique Cornelius MARTERSTOC ; Tobias ENGELHORN ; Anne BERBERICH ; Piers KLEIN ; Diogo C. HAUSSEN ; Mahmoud H. MOHAMMADEN ; Hend ABDELHAMID ; Isabel FRAGATA ; Bruno CUNHA ; Michele ROMOLI ; Wei HU ; Jianlon SONG ; Johanna T. FIFI ; Stavros MATSOUKAS ; Sunil A. SHETH ; Sergio A. SALAZAR-MARIONI ; João Pedro MARTO ; João Nuno RAMOS ; Milena MISZCZUK ; Christoph RIEGLER ; Sven POLI ; Khouloud POLI ; Ashutosh P. JADHAV ; Shashvat DESAI ; Volker MAUS ; Maximilian KAEDER ; Adnan H. SIDDIQUI ; Andre MONTEIRO ; Tatu KOKKONEN ; Francesco DIANA ; Hesham E. MASOUD ; Neil SURYADAREVA ; Maxim MOKIN ; Shail THANKI ; Pauli YLIKOTILA ; Kemal ALPAY ; James E. SIEGLER ; Italo LINFANTE ; Guilherme DABUS ; Dileep YAVAGHAL ; Vasu SAINI ; Christian H. NOLTE ; Eberhart SIEBERT ; Markus A. MÖHLENBRUCH ; Peter A. RINGLEB ; Raul G. NOGUEIRA ; Uta HANNING ; Lukas MEYER ; Urs FISCHER ; Daniel STRBIAN
Journal of Stroke 2024;26(2):290-299
Background:
and Purpose Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone.
Methods:
From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0–1) and independent outcome (mRS 0–2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment.
Results:
Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3–P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79–1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05–2.12), sICH (aOR 2.87, 95% CI 1.23–6.72), and mortality (aOR 1.77, 95% CI 1.07–2.95).
Conclusion
Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.