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Andrea Ferrari MD Daniel Orbach MD Michela Casanova MD Max M. van Noesel MD Pablo Berlanga MD Bernadette Brennan MD Nadege Corradini MD Reineke A. Schoot MD Gema L. Ramirez-Villar MD Lisa Lyngsie Hjalgrim MD Rita Alaggio MD Gabriela Guillen Burrieza MD Akmal Safwat MD Alison L. Cameron MD Rick R. van Rijn MD Veronique Minard-Colin MD Ilaria Zanetti BSc Gianni Bisogno MD Julia C. Chisholm MD Johannes H. M. Merks MD 《Cancer》2023,129(16):2542-2552
Background
Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined.Methods
This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered.Results
The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2–111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6–25.7) and 34.9% (95% CI, 22.7–47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered.Conclusions
The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge.Plain Language Summary
- Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors.
- Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases.
- This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking.
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Daniel Casanova Gonzalo Gutierrez Monica Gonzalez Noriega Federico Castillo 《World Journal of Transplantation》2020,10(12):381-391
In pancreas transplantation, complications can arise at each step of the process, from the initial selection of donors and recipients through the surgical technique itself and the post-operative period, when lifelong immunosuppression is required. In the early steps, careful retrieval and preservation of the pancreas are crucial for the viability of the organ and ultimate success of the transplant. The pancreas is a low-flow gland, making it highly sensitive to transplantation conditions and presenting risk of pancreatitis due to periods of ischemia. The two groups of donors - after brain death (DBD) or after cardiac arrest (DCD) - require different strategies of retrieval and preservation to avoid or reduce the risk of complications developing during and after the transplantation. For DBD donor transplantation, multiorgan retrieval and cold preservation is the conventional technique. Asystole donor (DCD) transplantation, in contrast, can benefit from the newest technologies, such as hypothermic and especially normothermic preservation machines (referred to as NECMO), to optimize organ preservation. The latter has led to an increase in the pool of donors by facilitating recuperation of organs for transplantation that would have been discarded otherwise. 相似文献
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Kishor Devalaraja-Narashimha Karoline Meagher Yifan Luo Cong Huang Theodore Kaplan Anantharaman Muthuswamy Gabor Halasz Sarah Casanova John OBrien Rebecca Peyser Boiarsky John McWhirter Hans Gartner Yu Bai Scott MacDonnell Chien Liu Ying Hu Adrianna Latuszek Yi Wei Srinivasa Prasad Tammy Huang George Yancopoulos Andrew Murphy William Olson Brian Zambrowicz Lynn Macdonald Lori G. Morton 《Journal of the American Society of Nephrology : JASN》2021,32(1):99
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Gustavo Benaim Paola Casanova Vanessa Hernandez-Rodriguez Sheira Mujica-Gonzalez Nereida Parra-Gimenez Lourdes Plaza-Rojas Juan Luis Concepcion Yi-Liang Liu Eric Oldfield Alberto Paniz-Mondolfi Alirica I. Suarez 《Antimicrobial agents and chemotherapy》2014,58(4):2295-2303
Dronedarone and amiodarone are cationic lipophilic benzofurans used to treat cardiac arrhythmias. They also have activity against the parasitic protozoan Trypanosoma cruzi, the causative agent of Chagas'' disease. They function by disrupting intracellular Ca2+ homeostasis of the parasite and by inhibiting membrane sterol (ergosterol) biosynthesis. Amiodarone also has activity against Leishmania mexicana, suggesting that dronedarone might likewise be active against this organism. This might be of therapeutic interest, since dronedarone is thought to have fewer side effects in humans than does amiodarone. We show here that dronedarone effectively inhibits the growth of L. mexicana promastigotes in culture and, more importantly, has excellent activity against amastigotes inside infected macrophages (the clinically relevant form) without affecting the host cell, with the 50% inhibitory concentrations against amastigotes being 3 orders of magnitude lower than those obtained previously with T. cruzi amastigotes (0.65 nM versus 0.75 μM). As with amiodarone, dronedarone affects intracellular Ca2+ homeostasis in the parasite, inducing an elevation of intracellular Ca2+ levels. This is achieved by rapidly collapsing the mitochondrial membrane potential and inducing an alkalinization of acidocalcisomes at a rate that is faster than that observed with amiodarone. We also show that dronedarone inhibits parasite oxidosqualene cyclase, a key enzyme in ergosterol biosynthesis known to be vital for survival. Overall, our results suggest the possibility of repurposing dronedarone as a treatment for cutaneous, and perhaps other, leishmaniases. 相似文献
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