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- Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 TrialPublication . Al-Batran, SE; Homann, N; Pauligk, C; Illerhaus, G; Martens, UM; Stoehlmacher, J; Schmalenberg, H; Luley, KB; Prasnikar, N; Egger, M; Probst, S; Messmann, H; Moehler, M; Fischbach, W; Hartmann, JT; Mayer, F; Höffkes, HG; Koenigsmann, M; Arnold, D; Kraus, TW; Grimm, K; Berkhoff, S; Post, S; Jäger, E; Bechstein, W; Ronellenfitsch, U; Mönig, S; Hofheinz, RDIMPORTANCE: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. RESULTS: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. CONCLUSIONS AND RELEVANCE: Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00849615.
- Unisensory and multisensory Self-referential stimulation of the lower limb: An exploratory fMRI study on healthy subjectsPublication . Vieira, Ana Isabel; Almeida, Patrícia; Canário, Nádia; Castelo-Branco, Miguel; Nunes, Maria Vânia; Castro-Caldas, AlexandreBackground: The holistic view of the person is the essence of the physiotherapy. Knowledge of approaches that develop the whole person promotes better patient outcomes. Multisensory Selfreferential stimulation, more than a unisensory one, seems to produce a holistic experience of the Self (“Core-Self”). Objectives: (1) To analyze the somatotopic brain activation during unisensory and multisensorial Self-referential stimulus; and (2) to understand if the areas activated by multisensorial Self-referential stimulation are the ones responsible for the “Core-Self.” Methods: An exploratory functional magnetic resonance imaging (fMRI) study was performed with 10 healthy subjects, under the stimulation of the lower limbs with three Self-referential stimuli: unisensory auditory-verbal, unisensory tactile-manual, and multisensory, applying the unisensory stimuli simultaneously. Results: Unisensory stimulation elicits bilateral activations of the temporoparietal junction (TPJ), of the primary somatosensory cortex (S1), of the primary motor cortex (BA4), of the premotor cortex (BA6) and of BA44; multisensory stimulation also elicits activity in TPJ, BA4, and BA6, and when compared with unisensory stimuli, activations were found in: (1) Cortical and subcortical midline structures—BA7 (precuneus), BA9 (medial prefrontal cortex), BA30 (posterior cingulated), superior colliculum and posterior cerebellum; and (2) Posterior lateral cortex—TPJ, posterior BA13 (insula), BA19, and BA37. Bilateral TPJ is the one that showed the biggest activation volume. Conclusion: This specific multisensory stimulation produces a brain activation map in regions that are responsible for multisensory Self-processing and may represent the Core- Self. We recommend the use of this specific multisensory stimulation as a physiotherapy intervention strategy that might promote the Self-reorganization.
- Search for physics beyond the standard model in events with two leptons of same sign, missing transverse momentum, and jets in proton–proton collisions at $\sqrt{s} = 13\,\text {TeV} $Publication . CMS collaboration (2227 authors); Nayak, Aruna; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Calpas, Betty; Di Francesco, Agostino; Faccioli, Pietro; Gallinaro, Michele; Hollar, Jonathan; Leonardo, Nuno; Lloret Iglesias, Lara; Seixas, Joao; Toldaiev, Oleksii; Vadruccio, Daniele; Varela, Joao; Vischia, Pietro; David Tinoco Mendes, Andre; Silva, Pedro; Musella, Pasquale; Pela, JoaoA data sample of events from proton–proton collisions with two isolated same-sign leptons, missing transverse momentum, and jets is studied in a search for signatures of new physics phenomena by the CMS Collaboration at the LHC. The data correspond to an integrated luminosity of 35.9 $\,\text {fb}^{-\text {1}}$ , and a center-of-mass energy of 13 $\,\text {TeV}$ . The properties of the events are consistent with expectations from standard model processes, and no excess yield is observed. Exclusion limits at 95% confidence level are set on cross sections for the pair production of gluinos, squarks, and same-sign top quarks, as well as top-quark associated production of a heavy scalar or pseudoscalar boson decaying to top quarks, and on the standard model production of events with four top quarks. The observed lower mass limits are as high as 1500 $\,\text {GeV}$ for gluinos, 830 $\,\text {GeV}$ for bottom squarks. The excluded mass range for heavy (pseudo)scalar bosons is 350–360 (350–410) $\,\text {GeV}$ . Additionally, model-independent limits in several topological regions are provided, allowing for further interpretations of the results.