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991.
Giulia Gustinetti Anna Maria Raiola Riccardo Varaldo Federica Galaverna Francesca Gualandi Valerio Del Bono Andrea Bacigalupo Emanuele Angelucci Claudio Viscoli Malgorzata Mikulska 《Biology of blood and marrow transplantation》2018,24(8):1721-1726
To investigate rates and outcomes of antibiotic de-escalation during pre-engraftment neutropenia in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. 110 consecutive HSCTs performed between January 2013 and March 2014 were analyzed. De-escalation was defined as narrowing the spectrum of antibiotic treatment either within (early) or after 96 hours (late) from starting antibiotics. Discontinuation, considered a form of de-escalation, was defined as stopping antibiotics before engraftment. De-escalation failure was defined as restarting/escalating antibiotics within 96 hours after de-escalation. Predictors of de-escalation were analyzed. Among 102 patients who started antibiotics and were included, 68 (67%) received monotherapy (mainly piperacillin-tazobactam, n?=?58), whereas 34 (33%) received combination therapy (mainly meropenem plus glycopeptide, n?=?24). Median duration of neutropenia was 17 days. Bloodstream infections (BSIs) were diagnosed in 28 patients (20%). Early de-escalation rate was 25.5% (n?=?26) and mostly consisted of reducing the spectrum of β-lactams (n?=?11, 42%). In comparison with theoretical scenario of continuing therapy until engraftment, the median savings in terms of antibiotic days were 10 for meropenem, 8 for piperacillin-tazobactam, and 7 for vancomycin. Failure rate of early de-escalation was 15% (4/26). Late de-escalation rate was 30.4% (n?=?31) and failure rate 19% (6/31). The rate of de-escalation any time before engraftment was 55.9% (n?=?57), including discontinuation in 33 patients (32%). Death at day 60 after HSCT occurred in 3 patients who never underwent de-escalation. Acute myeloid disease and BSIs were independent predictors of early de-escalation. De-escalation, including discontinuation, is feasible and safe in pre-engraftment neutropenia after allogeneic HSCT. 相似文献
992.
Yannick Simoni Michael Fehlings Henrik N. Kløverpris Naomi McGovern Si-Lin Koo Chiew Yee Loh Shawn Lim Ayako Kurioka Joannah R. Fergusson Choong-Leong Tang Ming Hian Kam Koh Dennis Tony Kiat Hon Lim Alexander Chung Yaw Fui Chan Weng Hoong Jerry Kok Yen Chan Maria Curotto de Lafaille Sriram Narayanan Evan W. Newell 《Immunity》2018,48(5):1060
993.
Patrizia Chiusolo Gesine Bug Attilio Olivieri Mats Brune Nicola Mordini Paolo Emilio Alessandrino Alida Dominietto Anna Maria Raiola Carmen Di Grazia Francesca Gualandi Maria Teresa Van Lint Felicetto Ferrara Olimpia Finizio Emanuele Angelucci Andrea Bacigalupo 《Biology of blood and marrow transplantation》2018,24(6):1243-1249
We report a modified post-transplant cyclophosphamide (PT-CY) regimen, for unmanipulated haploidentical marrow transplants, in 150 patients with acute myeloid leukemia (AML). All patients received a myeloablative regimen, cyclosporine A (CsA) on day 0, mycophenolate on day +1, and PT-CY 50?mg/kg on days +3 and +5. The median age was 51 (range, 17–74) years, 51 (34%) patients had active disease at transplant, and the median follow-up of surviving patients 903 (range, 150-1955) days. The cumulative incidence (CI) of engraftment, acute graft-versus-host disease (GVHD) grade II to IV, and moderate/severe chronic GVHD was 92%, 17%, and 15%, respectively. The 4-year CI of transplant-related mortality (TRM) and relapse was 20% and 24%, respectively. Four-year survival for remission patients was 72% (74% versus 67% for <60 or ≥60 years of age) and 26% for advanced patients (17% versus 41% for <60 or ≥60 years of age). In a multivariate analysis, active disease at transplant was the only negative predictor of survival, TRM and relapse. The original PT-CY regimen can be modified with CsA on day 0, still providing protection against GVHD, low toxicity, and encouraging low relapse incidence in AML patients, also over 60 years of age. 相似文献
994.
Jacopo Olivieri Federico Mosna Matteo Pelosini Angelo Fama Sara Rattotti Margherita Giannoccaro Giuseppe Carli Maria Chiara Tisi Simone Ferrero Nicola Sgherza Anna Maria Mazzone Dario Marino Teresa Calimeri Giacomo Loseto Francesco Saraceni Gabriella Tomei Simona Sica Giulia Perali Francesco Zaja 《Biology of blood and marrow transplantation》2018,24(9):1814-1822
BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM =?607, FEAM =?431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM?=?2011 versus FEAM?=?2013, P?<?.001), Sorror score ≥3 (BEAM?=?15% versus FEAM?=?10%, P?=?.017), and radiotherapy use (BEAM?=?18% versus FEAM?=?10%, P?<?.001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM?=?31% versus FEAM?=?44%, P?<?.001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM?=?.1 versus FEAM?=?.19, P?<?.001). Response status at day 100 post-ASCT (overall response: BEAM?=?91% versus FEAM?=?88%, P?=?.42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P?=?.04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply. 相似文献
995.
Carlo Marani Anna Maria Raiola Silvia Morbelli Alida Dominietto Giulia Ferrarazzo Daniele Avenoso Livia Giannoni Riccardo Varaldo Francesca Gualandi Di Grazia Teresa Lamparelli Stefania Bregante Maria Teresa Van Lint Adalberto Ibatici Francesca Bovis Roberto Massimo Lemoli Marco Gobbi Andrea Bacigalupo Emanuele Angelucci 《Biology of blood and marrow transplantation》2018,24(12):2501-2508
Disease relapse remains an unmet medical need for patients with Hodgkin lymphoma (HL) receiving an allogeneic hematopoietic cell transplantation (HCT). With the aim of identifying patients at high risk for post-transplant relapse, we retrospectively reviewed 41 HL patients who had received haploidentical (haplo) nonmyeloablative (NMA) HCT with high dose post-transplant cyclophosphamide (PT-Cy) for graft-versus-host (GVHD) prophylaxis. Primary refractory disease, relapse within 6 months from autologous stem cell transplantation, age, pretransplant chemotherapy, HCT comorbidity index (HCT-CI), sex mismatch, tumor burden and pretransplant fluorodeoxyglucose positron emission tomography (FDG-PET) status, assessed by Deauville score, were analyzed as variables influencing outcomes. All but 1 patient engrafted: median time to neutrophil and platelet recovery was 15 (interquartile range, 13 to 23) days and 19 (interquartile range, 12 to 28) days, respectively. Cumulative incidence of severe (grade III to IV) acute graft-versus-host disease (GVHD) and 3-year moderate-severe chronic GVHD was 2.4% and 11.8%, respectively. The 3-year overall (OS), progression free (PFS), and graft relapse-free survival (GRFS) were 75.6%, 43.9%, and 39%, respectively. On multivariate analysis, 3-year OS was significantly worse in patients with HCT-CI ≥3 (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1 to 21.8; P?=?.03). Three-year relapse rate, 3-year PFS, and 3-year GRFS were significantly worse in patients with HCT-CI ≥3 (HR, 3.5; 95% CI, 1.3 to 9.3; P = .01; HR, 3.3; 95% CI, 1.2 to 9.0; P?=?.02; and HR, 4.2; 95% CI, 1.7 to 9.9; P?=?.001, respectively) and in patients with a Deauville score ≥4 on pretransplant FDG-PET (HR, 4.4; 95% CI, 1.6-12.4; P?=?.005, HR, 3.8; 95% CI, 1.5 to 9.7; P?=?.005; and 3.2; 95% CI, 1.3 to 7.9; P?=?.01, respectively). On univariate analysis, 3-year NRM was significantly worse only in patients with a HCT-CI ≥3 (HR, 17.6; 95% CI, 1.4 to 221.0). Among relapsed or refractory HL patients undergoing haplo NMA HCT with PT-Cy, pretransplant FDG-PET with a Deauville score ≥4 and HCT-CI ≥3 identified patients at high risk of relapse. Moreover, an HCT-CI ≥3 was associated with higher NRM and lower OS. 相似文献
996.
Francesca Bonifazi Jacopo Olivieri Mariarosaria Sessa Elisa Dan Barbara Sinigaglia Simonetta Rizzi Maria Rosa Motta Andrea Bontadini Francesca Ulbar Valeria Giudice Cristina Papayannidis Antonio Curti Angela Chiereghin Tiziana Lazzarotto Michele Cavo Mario Arpinati 《Biology of blood and marrow transplantation》2018,24(12):2450-2458
Chronic graft-versus-host disease (cGVHD) is a major complication after stem cell transplantation (HSCT). Several randomized studies already demonstrated that anti-T lymphoglobulin (ATLG) is effective in preventing GVHD after myeloablative unrelated and HLA-identical sibling transplants. However, the issue of doses and the potential increase of relapses still remain unsolved. Here we report data on 190 patients with acute leukemia and myelodysplastic syndrome who underwent an unrelated HSCT with low-dose ATLG (15 to 30 mg/kg) given at an earlier timing (days –6 to –2). HSCT was performed from HLA 10/10 (n?=?62, 33%), 9/10 (n?=?91, 48%), 8/10 (n?=?30, 16%), and <8/10 (n?=?7, 4%) identical unrelated donor. Peripheral blood was the stem cell source in 42% (n?=?80). Median follow-up was 51 months. Grades II to IV and III to IV acute GVHD were 26% and 9%, respectively, and 2-year overall and moderate to severe cGVHD were 23% and 14%, respectively. The 3-year incidences of relapse and nonrelapse mortality were 26% and 18%, respectively. The rates of 3-year overall survival (OS), disease-free survival (DFS), and GVHD-free and relapse-free survival (GRFS) were 60%, 56% and 44%, respectively. Factors such as younger donor, good performance status, and early disease were associated with better outcome in terms of OS, DFS, and GRFS. Our data indicate that doses of ATLG lower that those used in randomized clinical trials can be used for GVHD prevention, even in the adult setting, without clear increases in relapse and infections; these findings need to be further validated by a prospective randomized study. 相似文献
997.
Feng Liu Shuibing Wang Zhigang Lu Yumei Sun Chaogang Yang Qiongwei Zhou Shaoli Hong Shengxiang Wang Bin Xiong Kan Liu Nangang Zhang 《Biomedical microdevices》2018,20(4):83
Isolation and detection of circulating tumor cells (CTCs) has showed a great clinical impact for tumor diagnosis and treatment monitoring. Despite significant progresses of the existing technologies, feasible and cost-effective CTC isolation techniques are more desirable. In this study, a novel method was developed for highly efficient isolation of CTCs from breast cancer patients based on biophysical properties using a pyramid-shaped microchamber. Through optimization tests, the outlet height of 6 μm and the flow rate of 200 μL/min were chosen as the optimal conditions. The capture efficiencies of more than 85% were achieved for cancer cell lines (SKBR3, BGC823, PC3, and H1975) spiked in DMEM and healthy blood samples without clogging issue. In clinic assay, the platform identified CTCs in 13 of 20 breast cancer patients (65%) with an average of 4.25?±?4.96 CTCs/2 mL, whereas only one cell was recognized as CTC in 1 of 15 healthy blood samples. The statistical analyses results demonstrated that both CTC positive rate and CTC counts were positive correlated with TNM stage (p < 0.001; p?=?0.02, respectively). This microfluidic platform successfully demonstrated the clinical feasibility of CTC isolation and would hold great potential of clinical application in predicting and monitoring the prognosis of cancer patients. 相似文献
998.
Minimally invasive vascular interventional surgery is widely used and remote-controlled vascular interventional surgery robots (RVIRs) are being developed to reduce the occupational risk of the intervening physician in minimally invasive vascular interventional surgeries. Skilled surgeon performs surgeries mainly depending on the detection of collisions. Inaccurate force feedback will be difficult for surgeons to perform surgeries or even results in medical accidents. In addition, the surgeon cannot quickly and easily distinguish whether the proximal force exceeds the safety threshold of blood vessels or not, and thus it results in damage to the blood vessels. In this paper, we present a novel method comprising compensatory force measurement and multimodal force feedback (MFF). Calibration experiments and performance evaluation experiments were carried out. Experimental results demonstrated that the proposed method can measure the proximal force of catheter/guidewire accurately and assist surgeons to distinguish the change of proximal force more easily. This novel method is suitable for use in actual surgical operations. 相似文献
999.
In the ever advancing field of minimally invasive surgery, flexible instruments with local degrees of freedom are needed to navigate through the intricate topologies of the human body. Although cable or concentric tube driven solutions have proven their merits in this field, they are inadequate for realizing small bending radii and suffer from friction, which is detrimental when automation is envisioned. Soft robotic actuators with locally actuated degrees of freedom are foreseen to fill in this void, where elastic inflatable actuators are very promising due to their S3-principle, being Small, Soft and Safe. This paper reports on the characterization of a chip-on-tip endoscope, consisting out of a soft robotic pneumatic bending microactuator equipped with a 1.1?×?1.1 mm2 CMOS camera. As such, the total diameter of the endoscope measures 1.66 mm. To show the feasibility of using this system in a surgical environment, a preliminary test on an eye mock-up is conducted. 相似文献
1000.
In this paper, we present an ultrasonically controlled switching system that can save the battery power for implantable devices by turning the system on and off, on-demand. Ultrasonic control is employed to reduce the device size, increase the penetration depth, and reduce misalignment sensitivity associated with alternative techniques using permanent magnet and RF signal. As a proof-of-concept demonstration, a 665 kHz ultrasonic signal is used to activate a piezoelectric receiver which in turn switches a battery-powered RF system on-and-off. In-vitro tests show a reliable switching functionality at distances of up to 8 cm while consuming 43.5 nW (14.5 nA current consumption with 3 V power supply) when the system is in off-state, a factor of 10–100 times lower than the sleep-mode power consumption of typical RF SoC systems. The dimension of fabricated prototype is 6.3?×?16.7?×?2? mm3 allowing it to be easily incorporated into many existing implantable devices. 相似文献