595 results on '"M., Saliba"'
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2. A complex case of young child with ADHD, developmental delay who developed seronegative autoimmune encephalitis exacerbated by stimulants
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M. Saliba, A. Wilton, K. Hagen, and M. Romanowicz
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Seronegative autoimmune encephalitis ,Stimulants ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Autoimmune encephalitis (AE) is a group of disorders characterized by a wide clinical spectrum ranging from the typical limbic encephalitis to more complex neuropsychiatric symptoms including abnormal movements, psychosis, deficits in memory and cognition, dysautonomia, seizures, or coma. Psychiatric symptoms can occur early in the disease progress or manifest during its course. These symptoms are challenging and often slow down the diagnosis of AE. This is a crucial aspect considering that early diagnosis and management of AE are critical for a good outcome. However, there is a lack in studies outlining the exact symptomatology and specific appropriate care that would allow clinicians to achieve an early diagnosis and management. Additionally, AE in children mostly presents with neuropsychiatric symptoms and diagnosis is especially challenging in kids because of their limited capacity in describing their symptoms, the normal childhood behavioral changes and the possibility of a comorbid psychiatric diagnosis. We present a complex case of seronegative AE with comorbid ADHD (Attention Deficit Hyperactivity Disorder) and anxiety in a young six-year-old girl.
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- 2023
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3. SIRPα Mismatch Is Associated With Relapse Protection and Chronic Graft-Versus-Host Disease After Related Hematopoietic Stem Cell Transplantation for Lymphoid Malignancies
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Rima M. Saliba, Samer A. Srour, Uri Greenbaum, Qing Ma, Yudith Carmazzi, Michael Moller, Janet Wood, Stefan O. Ciurea, Piyanuch Kongtim, Gabriela Rondon, Dan Li, Supawee Saengboon, Amin M. Alousi, Katayoun Rezvani, Elizabeth J. Shpall, Kai Cao, Richard E. Champlin, and Jun Zou
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signal regulatory protein alpha ,mismatch ,relapse protection ,cGVHD ,HSCT ,lymphoid malignancies ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematologic malignancies. Alloreactivity after HSCT is known to be mediated by adaptive immune cells expressing rearranging receptors. Recent studies demonstrated that the innate immune system could likewise sense the non-self signals and subsequently enhance the alloimmune response. We recently demonstrated that the donor/recipient mismatch of signal regulatory protein α (SIRPα), an immunoglobulin receptor exclusively expressed on innate cells, is associated with a higher risk of cGVHD and relapse protection in a cohort of acute myeloid leukemia patients who underwent allo-HSCT. Whether these effects also occur in other hematologic malignancies remains unclear. In the present study, we compared outcomes by SIRPα match status in a cohort of 310 patients who received allo-HSCT from an HLA matched-related donor for the treatment of lymphoid malignancies. Multivariable analysis showed that SIRPα mismatch was associated with a significantly higher rate of cGVHD (hazard ratio [HR] 1.8, P= .002), cGVHD requiring systemic immunosuppressive therapy (HR 1.9, P= .005), a lower rate of disease progression (HR 0.5, P= .003) and improved progression-free survival (HR 0.5, P= .001). Notably, the effects of SIRPα mismatch were observed only in the patients who achieved >95% of donor T-cell chimerism. The mismatch in SIRPα is associated with favorable relapse protection and concurrently increased risk of cGVHD in patients who undergo allo-HSCT for lymphoid malignancies, and the optimal donor could be selected based on the finding of the study to mitigate the risk of GVHD and relapse.
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- 2022
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4. Pseudomonas aeruginosa Infection Modulates the Immune Response and Increases Mice Resistance to Cryptococcus gattii
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Eluzia C. Peres-Emidio, Gustavo J. C. Freitas, Marliete C. Costa, Ludmila Gouveia-Eufrasio, Lívia M. V. Silva, Anderson P. N. Santos, Paulo H. F. Carmo, Camila B. Brito, Raquel D. N. Arifa, Rafael W. Bastos, Noelly Q. Ribeiro, Lorena V. N. Oliveira, Monique F. Silva, Tatiane A. Paixão, Alessandra M. Saliba, Caio T. Fagundes, Daniele G. Souza, and Daniel A. Santos
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Cryptococcosis ,coinfection ,Cryptococcus gattii ,Pseudomonas aeruginosa ,iNOS ,Microbiology ,QR1-502 - Abstract
Cryptococcosis is an invasive mycosis caused by Cryptococcus spp. that affects the lungs and the central nervous system (CNS). Due to the severity of the disease, it may occur concomitantly with other pathogens, as a coinfection. Pseudomonas aeruginosa (Pa), an opportunistic pathogen, can also cause pneumonia. In this work, we studied the interaction of C. gattii (Cg) and Pa, both in vitro and in vivo. Pa reduced growth of Cg by the secretion of inhibitory molecules in vitro. Macrophages previously stimulated with Pa presented increased fungicidal activity. In vivo, previous Pa infection reduced morbidity and delayed the lethality due to cryptococcosis. This phenotype was correlated with the decreased fungal burden in the lungs and brain, showing a delay of Cg translocation to the CNS. Also, there was increased production of IL-1β, CXCL-1, and IL-10, together with the influx of iNOS-positive macrophages and neutrophils to the lungs. Altogether, Pa turned the lung into a hostile environment to the growth of a secondary pathogen, making it difficult for the fungus to translocate to the CNS. Further, iNOS inhibition reverted the Pa protective phenotype, suggesting its important role in the coinfection. Altogether, the primary Pa infection leads to balanced pro-inflammatory and anti-inflammatory responses during Cg infection. This response provided better control of cryptococcosis and was decisive for the mild evolution of the disease and prolonged survival of coinfected mice in a mechanism dependent on iNOS.
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- 2022
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5. Enhanced Recovery Stem-Cell Transplantation: Multidisciplinary Efforts to Improve Outcomes in Older Adults Undergoing Hematopoietic Stem-Cell Transplant
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An Ngo-Huang, Rachel Ombres, Rima M. Saliba, Nicholas Szewczyk, LaToya Adekoya, Tacara N. Soones, Jill Ferguson, Rhodora C. Fontillas, Alison M. Gulbis, Chitra Hosing, Partow Kebriaei, Richard Lindsay, David C. Marin, Rohtesh S. Mehta, Amin M. Alousi, Samer Srour, Betul Oran, Amanda L. Olson, Muzaffar H. Qazilbash, Zandra Rivera, Richard E. Champlin, Elizabeth J. Shpall, and Uday R. Popat
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Oncology ,Oncology (nursing) ,Health Policy - Abstract
PURPOSE: Older adults have unique risk factors for poor outcomes after hematopoietic stem-cell transplant (HSCT). We sought to determine the impact of our multidisciplinary supportive care program, Enhanced Recovery after stem-cell transplant (ER-SCT), on survival outcomes in patients age 65 years and older who underwent HSCT. PATIENTS AND METHODS: In this retrospective study, clinicodemographic data, nonrelapse mortality (NRM), overall survival (OS), and relapse were compared between 64 patients age 65 years and older who underwent allogeneic stem-cell transplant during ER-SCT program's first year, October 2017 through September 2018, and 140 historical controls age 65 years and older who underwent allogeneic HSCT, January 2015 through September 2017. RESULTS: In the ER-SCT cohort, 41% (26 of 64) of patients were women, and the median (range) age was 68 (65-74) years; in the control cohort, 38% (53 of 140) of patients were women, and the median (range) age was 67 (65-79) years. Hematopoietic cell transplant comorbidity index and donor type/cell source were similar between cohorts. The ER-SCT cohort had a lower 1-year NRM rate (13% v 26%, P = .03) and higher 1-year OS rate (74% v 53%, P = .007). Relapse rate did not differ significantly between cohorts. In multivariate analyses, ER-SCT was associated with improved 1-year NRM (hazard ratio, 0.4; 95% CI, 0.2 to 0.9; P = .02) and improved 1-year OS (hazard ratio, 0.5; 95% CI, 0.3 to 0.9; P = .03). CONCLUSION: A multidisciplinary supportive care program may improve NRM and OS in older patients undergoing allogeneic HSCT. Randomized studies are warranted to confirm this benefit and explore which program components most contribute to the improved outcomes.
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- 2023
6. Interactions of Divers with Reef Biota are More Frequent Among Snorkelers Than Scuba Divers And Increase During Sea Turtle Watching
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Bruna M. Saliba, Lindaa Eggertsen, Thiago C. Mendes, Marina Marconi, Carlosa E.L. Ferreira, and Vinicius J. Giglio
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Tourism, Leisure and Hospitality Management ,Geography, Planning and Development - Abstract
Snorkeling is a popular recreational activity in shallow water of coastal ecosystems. Because snorkeling is commonly assumed to cause comparatively fewer potential impacts to the marine biota than scuba diving, management is generally focused on the latter. We investigated the behavior of snorkelers aiming to quantify their interactions with benthic reef sessile organisms and sea turtles. We also compared the behavior of snorkelers with scuba divers to assess which group of divers is more damaging to the reef biota. Finally, we compared the use of conventional and nonconventional sampling approaches through analysis of social media images to evaluate the reliability of different approaches to investigate the behavior of underwater recreationists. Snorkelers were observed during 5 min; their interactions with benthic organisms were recorded and compared with scuba diver's behavior. Snorkelers'observations were carried out with and without the presence of sea turtles and compared with videos from social media. Videos were extracted from YouTube through a search using keywords and analyzed to quantify the number of interactions of divers with the benthic organisms. Snorkelers caused 33% more contacts and 70% more damage to benthic reef organisms than scuba divers. Most interactions were over the zoanthid Palythoa caribaeorum, which received ~80% of contacts and ~30% of damage. The contact rate of snorkelers with benthic organisms increased 5.5fold when they interacted with sea turtles. Snorkelers sampled through direct observation accounted for more contacts with benthic reef organisms than those observed in social media videos, whereas higher rates of behavioral disturbance to sea turtles were observed in snorkelers sampled in social media videos. As the videos from social media focused on sea turtle watching, they overestimated the amount of snorkelers–sea turtles' interactions but underestimated the amount of contacts with benthic organisms. Our results revealed that snorkeling in shallow waters
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- 2023
7. Characteristics of Graft-Versus-Host Disease (GvHD) After Post-Transplantation Cyclophosphamide Versus Conventional GvHD Prophylaxis
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Rima M. Saliba, Amin M. Alousi, Joseph Pidala, Mukta Arora, Stephen R. Spellman, Michael T. Hemmer, Tao Wang, Camille Abboud, Sairah Ahmed, Joseph H. Antin, Amer Beitinjaneh, David Buchbinder, Michael Byrne, Jean-Yves Cahn, Hannah Choe, Rabi Hanna, Peiman Hematti, Rammurti T. Kamble, Carrie L. Kitko, Mary Laughlin, Lazaros Lekakis, Margaret L. MacMillan, Rodrigo Martino, Parinda A. Mehta, Taiga Nishihori, Sagar S. Patel, Miguel-Angel Perales, Hemalatha G. Rangarajan, Olov Ringdén, Joseph Rosenthal, Bipin N. Savani, Kirk R. Schultz, Sachiko Seo, Takanori Teshima, Marjolein van der Poel, Leo F. Verdonck, Daniel Weisdorf, Baldeep Wirk, Jean A. Yared, Jeffrey Schriber, Richard E. Champlin, and Stefan O. Ciurea
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Male ,Transplantation ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Molecular Medicine ,Immunology and Allergy ,Female ,Cell Biology ,Hematology ,Cyclophosphamide ,Antilymphocyte Serum ,Retrospective Studies - Abstract
Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin (ATG), grade 3-4 aGvHD (28% versus 39%, P = .001), stage 3-4 lower gastrointestinal (GI) tract aGvHD (14% versus 21%, P = .01), and chronic GI GvHD (21% versus 31%, P = .006) were less common after Haplo/PTCy transplantation. In patients with grade 2-4 aGvHD, cGcHD rate after Haplo/PTCY was also lower (hazard ratio [HR] = .4, P < .001) in comparison with MUD/conventional transplantation without ATG in the nonmyeloablative conditioning setting. Irrespective of the use of ATG, non-relapse mortality rate was lower (HR = .6, P = .01) after Haplo/PTCy transplantation, except for transplants that were from a female donor into a male recipient. In patients with cGvHD, irrespective of ATG use, Haplo/PTCy transplantation had lower non-relapse mortality rates (HR = .6, P = .04). Mortality rate was higher (HR = 1.6, P = .03) within, but not after (HR = .9, P = .6) the first 6 months after cGvHD diagnosis. Our results suggest that PTCy-based GvHD prophylaxis mitigates the development of GI GvHD and may translate into lower GvHD-related non-relapse mortality rate.
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- 2022
8. Impact of graft composition on outcomes of haploidentical bone marrow stem cell transplantation
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Rima M. Saliba, Lauren Veltri, Gabriela Rondon, Julianne Chen, Gheath Al-Atrash, Amin Alousi, Charles Martinez, LaJerald Augustine, Chitra M. Hosing, Betul Oran, Katayoun Rezvani, Elisabeth J. Shpall, Partow Kebriaei, Issa F. Khouri, Uday Popat, Richard E. Champlin, and Stefan O. Ciurea
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2020
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9. Organoleptic and physico-chemical evaluation of capretto baladi goats: a value-added meat alternative in an extensive rearing system
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S. Abi Saab, F. Esseily, M. Saliba, and P.Y. Aad
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Capretto ,milk-fed ,value-added meat ,meat properties ,Technology ,Science - Abstract
Abi Saab, S. Esseily, F. Saliba, M. and Aad P. 2017. Organoleptic and physico-chemical evaluation of capretto baladi goats: a value-added meat alternative in an extensive rearing system. Lebanese Science Journal. 18(1): 73-80. The local Baladi breed is considered a common source of fresh meat in Lebanon. Due to the extensive rearing system and the scarcity of pasture, kids resulting from multiple births are not reared, though cultural preference for young meat may valorize these twin kids as an expensive delicacy. Few studies observed growth parameters, physical-chemical and sensory properties of meat in Baladi kids. Therefore, 24 male Baladi kids were fed milk ad libitum post-natally for 24 days, after which 9 were randomly selected and fed pasture grass ad libitum and goat milk (Control), and 15 were fed only milk (Capretto) twice per day. Animals were slaughtered at 4, 6 and 8 weeks of age and body organs compared. Feed intake was measured by weighing kids pre- and post- feeding, and body weight measured twice per week. Meat chemical properties were total ether-extracted fat, kjeldhal protein, and minerals. Meat organoleptic properties were evaluated by consumers for color, taste, odor, richness, juiciness, tenderness and overall appreciation, as cooked by housewives or professionals. Data were analyzed as a CRD using SPSS 10.0 and presented as LSMeans ± SEM. Results showed that Capretto consumed increasing levels of milk from 4 to 8 weeks, with ADG decreasing (P < 0.05) from 4 to 8 weeks. Capretto showed 5% less (P0.05) between Capretto and control, although capretto showed lower (p
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- 2017
10. Efficacy and Safety of Gilteritinib Vs. Sorafenib As Post-Transplant Maintenance in Patients with FLT3-ITD Acute Myeloid Leukemia
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Jason Yeh, Rima M. Saliba, Christopher Wang, Zhou Fang, Bradley Figgins, Sairah Ahmed, Musa Yilmaz, Naval Daver, Rohtesh S. Mehta, Gheath Alatrash, David Marin, Uday R Popat, Richard E Champlin, Elizabeth J Shpall, and Betul Oran
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
11. Pyoderma Gangrenosum and Pregnancy: an Example of Abnormal Inflammation the Importance of Working in a Multidisciplinary Team
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J, Al Hasan, primary, K, Diab, additional, Z, Kalach, additional, M, Saliba, additional, and K, Ghazal, additional
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- 2023
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12. High level of DNA
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Fadi B. Choucair, Eliane G. Rachkidi, Georges C. Raad, Elias M. Saliba, Nina S. Zeidan, Rania A. Jounblat, Imad F. Abou Jaoude, and Mira M. Hazzouri
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Sperm DNA fragmentation ,Sperm chromatin dispersion test ,Male infertility ,Nuclear quality ,Medicine (General) ,R5-920 ,Reproduction ,QH471-489 - Abstract
Assessment of male fertility has been based on routine semen analysis established by the World Health Organization (WHO), evaluating sperm concentration, motility and morphology. Actually, these parameters become less reliable markers to evaluate male fertility potential. Therefore, a search for better markers has led to an increased focus on sperm chromatin integrity testing in fertility work-up and assisted reproductive technologies (ART). In this study, we evaluate sperm DNA fragmentation in 185 Lebanese infertile patients attending fertility clinics all over the country, in comparison with 30 control men of proven fertility, using the sperm chromatin dispersion test (SCD). Our results showed a significantly higher sperm DNA fragmentation in infertile group compared to control group (20.62% vs 12.96%; p
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- 2016
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13. Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation
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Kai Cao, David Marin, Takuye Sekine, Gabriela Rondon, Weicheng Zhao, Nathaniel T. Smith, May Daher, Qing Wang, Li Li, Rima M. Saliba, Ravi Pingali, Uday Popat, Chitra Hosing, Amanda Olson, Betul Oran, Rafet Basar, Rohtesh S. Mehta, Richard Champlin, Elizabeth J. Shpall, and Katayoun Rezvani
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NK cells ,CBT ,NKG2C ,CMV reactivation ,graft selection ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Cytomegalovirus (CMV) remains a major cause of morbidity following allogeneic hematopoietic stem cell transplant. Natural killer cells expressing NKG2C have been shown to play a role in the immune surveillance of human CMV. We studied NKG2C copy number in the donor graft and the risk of CMV reactivation after double umbilical cord blood transplantation (DUCBT) in 100 CMV seropositive DUCBT recipients and their corresponding cord blood (CB) grafts (n = 200). In the setting of DUCBT, the combined graft may contain 0–4 functional copies of NKG2C gene. Sixteen patients received a combined graft with 1 or 2 NKG2C copies and 84 patients were recipients of a combined graft with 3 or 4 NKG2C copies. The 6-month cumulative incidence of CMV reactivation for the two groups was 93.7 and 58.4%, respectively (p = 0.0003). In multivariate analysis, low NKG2C copies in the graft was an independent predictor of CMV reactivation (HR = 2.72, CI = 1.59–4.64; p < 0.0001). Our study points to an important role for donor NKG2C for protection against CMV reactivation after DUCBT. These novel findings may help identify patients at a higher risk of CMV reactivation after DUCBT. Donor NKG2C genotype may be used as a potential criterion in the algorithm for graft selection for DUCBT.
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- 2018
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14. Toll-Like Receptor 3 (TLR3) Is Engaged in the Intracellular Survival of the Protozoan Parasite
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Carolina T, Rath, Áislan C, Vivarini, José Vitorino, Dos Santos, Jorge M, Medina, Alessandra M, Saliba, Jeremy C, Mottram, Ana Paula C A, Lima, Teresa Cristina, Calegari-Silva, Renata M, Pereira, and Ulisses G, Lopes
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Mice ,Leishmania mexicana ,Animals ,Parasites ,Fungal and Parasitic Infections ,Interleukin-12 ,Leishmaniasis ,Protein Kinases ,Interleukin-10 ,Toll-Like Receptor 3 - Abstract
The protozoan parasite Leishmania (L.) amazonensis infects and replicates inside host macrophages due to subversion of the innate host cell response. In the present study, we demonstrate that TLR3 is required for the intracellular growth of L. (L.) amazonensis. We observed restricted intracellular infection of TLR3(−/−) mouse macrophages, reduced levels of IFN1β and IL-10, and increased levels of IL-12 upon L. (L.) amazonensis infection, compared with their wild-type counterparts. Accordingly, in vivo infection of TLR3(−/−) mice with L. (L.) amazonensis displayed a significant reduction in lesion size. Leishmania (L.) amazonensis infection induced TLR3 proteolytic cleavage, which is a process required for TLR3 signaling. The chemical inhibition of TLR3 cleavage or infection by CPB-deficient mutant L. (L.) mexicana resulted in reduced parasite load and restricted the expression of IFN1β and IL-10. Furthermore, we show that the dsRNA sensor molecule PKR (dsRNA-activated protein kinase) cooperates with TLR3 signaling to potentiate the expression of IL-10 and IFN1β and parasite survival. Altogether, our results show that TLR3 signaling is engaged during L. (L.) amazonensis infection and this component of innate immunity modulates the host cell response.
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- 2023
15. Deep Reinforcement Learning with Uncertain Data for Real-Time Stormwater System Control and Flood Mitigation
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Sami M. Saliba, Benjamin D. Bowes, Stephen Adams, Peter A. Beling, and Jonathan L. Goodall
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real-time control ,reinforcement learning ,smart stormwater systems ,urban flooding ,Hydraulic engineering ,TC1-978 ,Water supply for domestic and industrial purposes ,TD201-500 - Abstract
Flooding in many areas is becoming more prevalent due to factors such as urbanization and climate change, requiring modernization of stormwater infrastructure. Retrofitting standard passive systems with controllable valves/pumps is promising, but requires real-time control (RTC). One method of automating RTC is reinforcement learning (RL), a general technique for sequential optimization and control in uncertain environments. The notion is that an RL algorithm can use inputs of real-time flood data and rainfall forecasts to learn a policy for controlling the stormwater infrastructure to minimize measures of flooding. In real-world conditions, rainfall forecasts and other state information are subject to noise and uncertainty. To account for these characteristics of the problem data, we implemented Deep Deterministic Policy Gradient (DDPG), an RL algorithm that is distinguished by its capability to handle noise in the input data. DDPG implementations were trained and tested against a passive flood control policy. Three primary cases were studied: (i) perfect data, (ii) imperfect rainfall forecasts, and (iii) imperfect water level and forecast data. Rainfall episodes (100) that caused flooding in the passive system were selected from 10 years of observations in Norfolk, Virginia, USA; 85 randomly selected episodes were used for training and the remaining 15 unseen episodes served as test cases. Compared to the passive system, all RL implementations reduced flooding volume by 70.5% on average, and performed within a range of 5%. This suggests that DDPG is robust to noisy input data, which is essential knowledge to advance the real-world applicability of RL for stormwater RTC.
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- 2020
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16. Gridded global surface ozone metrics for atmospheric chemistry model evaluation
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E. D. Sofen, D. Bowdalo, M. J. Evans, F. Apadula, P. Bonasoni, M. Cupeiro, R. Ellul, I. E. Galbally, R. Girgzdiene, S. Luppo, M. Mimouni, A. C. Nahas, M. Saliba, and K. Tørseth
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Environmental sciences ,GE1-350 ,Geology ,QE1-996.5 - Abstract
The concentration of ozone at the Earth's surface is measured at many locations across the globe for the purposes of air quality monitoring and atmospheric chemistry research. We have brought together all publicly available surface ozone observations from online databases from the modern era to build a consistent data set for the evaluation of chemical transport and chemistry-climate (Earth System) models for projects such as the Chemistry-Climate Model Initiative and Aer-Chem-MIP. From a total data set of approximately 6600 sites and 500 million hourly observations from 1971–2015, approximately 2200 sites and 200 million hourly observations pass screening as high-quality sites in regionally representative locations that are appropriate for use in global model evaluation. There is generally good data volume since the start of air quality monitoring networks in 1990 through 2013. Ozone observations are biased heavily toward North America and Europe with sparse coverage over the rest of the globe. This data set is made available for the purposes of model evaluation as a set of gridded metrics intended to describe the distribution of ozone concentrations on monthly and annual timescales. Metrics include the moments of the distribution, percentiles, maximum daily 8-hour average (MDA8), sum of means over 35 ppb (daily maximum 8-h; SOMO35), accumulated ozone exposure above a threshold of 40 ppbv (AOT40), and metrics related to air quality regulatory thresholds. Gridded data sets are stored as netCDF-4 files and are available to download from the British Atmospheric Data Centre (doi:10.5285/08fbe63d-fa6d-4a7a-b952-5932e3ab0452). We provide recommendations to the ozone measurement community regarding improving metadata reporting to simplify ongoing and future efforts in working with ozone data from disparate networks in a consistent manner.
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- 2016
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17. Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era
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Laura K. Whited, Jose Banchs, Richard E. Champlin, Uday R. Popat, Elizabeth J. Shpall, Gabriela Rondon, Rima M. Saliba, and Jason Yeh
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medicine.medical_specialty ,Cyclophosphamide ,Ischemia ,Graft vs Host Disease ,Gastroenterology ,Internal medicine ,Diabetes mellitus ,Humans ,Medicine ,Myocardial infarction ,Retrospective Studies ,Transplantation ,Hematopoietic cell ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Cardiotoxicity ,Heart failure ,cardiovascular system ,business ,medicine.drug - Abstract
Key Points The incidence of acute cardiac toxicity remains low and manageable after matched allo-HCT in the era of PTCy prophylaxis.Older age, hypertension, arrhythmia, diabetes, and cardiac comorbidities increase this risk of cardiac toxicity but PTCy did not., Visual Abstract, Graft-versus-host disease (GVHD) is one of the leading causes of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). Posttransplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicity, and few studies have evaluated the cardiac toxicities that arise after PTCy. We completed a retrospective analysis of patients who underwent matched-donor allo-HCT at our institution and who received PTCy- or non-PTCy–based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after allo-HCT. We included 585 patients in our analysis and found that 38 (6.5%) experienced cardiac toxicity after allo-HCT. The toxicities included arrhythmias (n = 21), heart failure (n = 14), pericardial effusion (n = 10), and myocardial infarction or ischemia (n = 7). Patients who received PTCy had a 7.4% incidence of cardiac toxicity, whereas non-PTCy recipients had an incidence of 5.8% (P = .4). We found that age >55 years (P = .02) and a history of hypertension (P = .01), arrhythmia (P = .003), diabetes (P = .04), and cardiac comorbidities (P < .001) were significant predictors of cardiac toxicity, whereas none of the preparative and GVHD prophylaxis regimens were predictive. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity after allo-HCT. We found that a higher score correlated with an incidence of cardiac toxicity. Furthermore, the development of cardiac toxicity was associated with worse 1-year overall survival (OS) and NRM. The use of PTCy was associated with improvements in 1-year OS and NRM rates.
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- 2021
18. Prognostic significance of <scp>measurable residual disease</scp> in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation in second or later complete remission
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Oren Pasvolsky, Rima M. Saliba, Celina Ledesma, Uday R. Popat, Amin Alousi, Amanda Olson, Betul Oran, Chitra Hosing, Qaiser Bashir, Muzaffar H. Qazilbash, Nicholas J. Short, Farhad Ravandi, Richard Champlin, Elizabeth J. Shpall, and Partow Kebriaei
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Hematology - Published
- 2022
19. HLA Factors versus Non-HLA Factors for Haploidentical Donor Selection
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Rohtesh S. Mehta, Kai Cao, Rima M. Saliba, Gheath Al-Atrash, Amin M. Alousi, Konstantinos Lontos, Curtis Marcoux, Yudith Carmazzi, Gabriela Rondon, Qaiser Bashir, Chitra M. Hosing, Partow Kebriaei, Issa Khouri, David Marin, Yago Nieto, Betul Oran, Uday R. Popat, Muzaffar H. Qazilbash, Jeremy Ramdial, Katayoun Rezvani, Richard E. Champlin, and Elizabeth J. Shpall
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Abstract
When multiple haploidentical donors are available for transplantation, those of younger generations are generally selected over those of older generations. However, it is unclear who is the optimal donor when selecting candidates from within a generation, such as father versus mother, son versus daughter, or brother versus sister. Although traditionally male donors are favored over female donors, particularly for male recipients, and significant associations of individual HLA mis(matches) on outcomes are being increasingly recognized, the hierarchy of factors for donor selection is indeterminate. To assess whether HLA factors take precedence over non-HLA factors and to isolate the influence of specific characteristics on outcomes, we analyzed 412 patients stratified by donor relationship: child donor (son [n = 202] versus daughter [n = 96]), parent (father [n = 28] versus mother [n = 29]), and sibling (noninherited maternal [NIMA; n = 29] versus paternal [NIPA; n = 28] mismatched). Among siblings, NIMA mismatch was associated with a lower risk of acute graft-versus-host disease (aGVHD); B-leader mismatch was associated with high nonrelapse mortality (NRM), poor progression-free survival, and a trend toward poor overall survival (OS), whereas A-mismatch was associated with lower aGVHD. Among parent donors, the relationship did not impact any outcome; B-leader mismatch was associated with higher NRM and a trend toward poor OS, whereas A-mismatch was associated with lower NRM and improved progression-free survival and OS. Among child donors, no individual HLA mismatch was predictive of any outcome, and daughter donors were not associated with any adverse outcomes in multivariate analyses. Our data suggest that certain HLA factors may be more significant in some cases and should be given priority over simply selecting a donor based on relationship/sex.
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- 2022
20. Impact of Gender on Outcomes of Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplant
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Oren Pasvolsky, Rima M. Saliba, Adeel Masood, Ali H. Mohamedi, Mark R. Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Jeremy Ramdial, Yago Nieto, Hans C. Lee, Krina K. Patel, Partow Kebriaei, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski, Elizabeth J. Shpall, Richard E. Champlin, and Muzaffar H. Qazilbash
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
21. Long-Term Follow-up Outcomes of Patients That Underwent Allogeneic or Autologous Hematopoietic Transplant Shortly after a COVID-19 Infection
- Author
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Alejandro Marinos, Jeremy L Ramdial, Rima M. Saliba, Fareed Khawaja, Amin M. Alousi, Gabriela Rondon, Julianne Chen, Celina Ledesma, Dr. Roy F. Chemaly, Richard E. Champlin, David Marin, May Daher, Katayoun Rezvani, and Elizabeth J. Shpall
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
22. Myeloablative Fractionated Busulfan Regimens in Matched Donor Transplantation
- Author
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Uday R. Popat, Rima M. Saliba, Rohtesh S. Mehta, Amin M. Alousi, Gheath Al-Atrash, Qaiser Bashir, Julianne Chen, Alison M. Gulbis, Chitra M. Hosing, Jin S. Im, Partow Kebriaei, Issa F. Khouri, Jitesh D. Kawedia, David Marin, Yago Nieto, Amanda Olson, Betul Oran, Jeremy Ramdial, Neeraj Y. Saini, Samer A. Srour, Katayoun Rezvani, Muzaffar H. Qazilbash, Hagop Kantarjian, Borje S. Andersson, Richard E. Champlin, and Elizabeth J. Shpall
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
23. Mismatch in SIRPα, a regulatory protein in innate immunity, is associated with chronic GVHD in hematopoietic stem cell transplantation
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Janet Wood, Rima M. Saliba, Liang Li, Gabriela Rondon, Michael B. Møller, Samer A. Srour, Katayoun Rezvani, David Partlow, Stefan O. Ciurea, Daniel Li, Richard E. Champlin, Qing Ma, Jun Zou, Yudith Carmazzi, Elizabeth J. Shpall, Piyanuch Kongtim, Betul Oran, Kai Cao, and Uri Greenbaum
- Subjects
Myeloid ,Hematopoiesis and Stem Cells ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Acute ,Regenerative Medicine ,Rare Diseases ,Clinical Research ,Stem Cell Research - Nonembryonic - Human ,Genetics ,medicine ,Humans ,Innate ,2.1 Biological and endogenous factors ,Aetiology ,Allorecognition ,Cancer ,Transplantation ,Leukemia ,Donor selection ,business.industry ,Inflammatory and immune system ,Hematopoietic Stem Cell Transplantation ,Immunity ,Myeloid leukemia ,Hematology ,Stem Cell Research ,medicine.disease ,Acquired immune system ,Immunity, Innate ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,medicine.anatomical_structure ,Graft-versus-host disease ,Myelodysplastic Syndromes ,Immunology ,business - Abstract
Recent compelling evidence showed that innate immune effector cells could recognize allogeneic grafts and prime an adaptive immune response. Signal regulatory protein α (SIRPα) is an immunoglobulin superfamily receptor that is expressed on myeloid cells; the interaction between SIRPα and its ubiquitously expressed ligand CD47 elicits an inhibitory signal that suppresses macrophage phagocytic function. Additional studies showed that donor-recipient mismatch in SIRPα variants might activate monocytic allorecognition, possibly as the result of non-self SIRPα-CD47 interaction. However, the frequency of SIRPα variation and its role in hematopoietic stem cell transplantation (HSCT) remains unexplored. We studied 350 patients with acute myeloid leukemia/myelodysplastic syndrome who underwent HLA-matched related HSCT and found that SIRPα allelic mismatches were present in 39% of transplantation pairs. SIRPα variant mismatch was associated with a significantly higher rate of chronic graft-versus-host disease (GVHD; hazard ratio [HR], 1.5; P = .03), especially de novo chronic GVHD (HR, 2.0; P = .01), after adjusting for other predictors. Those with mismatched SIRPα had a lower relapse rate (HR, 0.6; P = .05) and significantly longer relapse-free survival (RFS; HR, 0.6; P = .04). Notably, the effect of SIRPα variant mismatch on relapse protection was most pronounced early after HSCT and in patients who were not in remission at HSCT (cumulative incidence, 73% vs 54%; HR, 0.5; P = .01). These findings show that SIRPα variant mismatch is associated with HSCT outcomes, possibly owing to innate allorecognition. SIRPα variant matching could provide valuable information for donor selection and risk stratification in HSCT.
- Published
- 2021
24. Outcomes of Second Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Myeloid Leukemia
- Author
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Richard E. Champlin, Amanda Olson, Uri Greenbaum, Gheath Alatrash, Rohtesh S. Mehta, Rima M. Saliba, Katayoun Rezvani, Jeremy Ramdial, Jacinth Joseph, Muzaffar H. Qazilbash, Amin M. Alousi, Fevzi Firat Yalniz, David Marin, Jin Im, Betul Oran, Elizabeth J. Shpall, Partow Kebriaei, Gabriela Rondon, Uday R. Popat, Rashmi Kanagal-Shamanna, and Chitra Hosing
- Subjects
Adult ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Graft vs Host Disease ,Gastroenterology ,Young Adult ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,In patient ,Aged ,Retrospective Studies ,Transplantation ,Hematopoietic cell ,Adult patients ,business.industry ,Medical record ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Cell Biology ,Hematology ,Middle Aged ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,Cord blood ,Remission duration ,Molecular Medicine ,business - Abstract
Relapse after allogeneic hematopoietic cell transplantation (HCT) leads to poor survival in patients with acute myeloid leukemia (AML). A second HCT (HCT2) may achieve durable remission. To determine the outcomes of patients who received an HCT2 for relapsed AML and to evaluate the predictors of overall survival (OS) and progression-free survival (PFS). We retrospectively reviewed medical records of adult patients who underwent an HCT2 for relapsed AML at our institution during 2000 to 2019. Ninety-one patients were identified with a median age of 44 years (range 18-73) at HCT2. Donor types were HLA-identical sibling (n = 37 [41%]), HLA-matched–unrelated (n = 34 [37%]), haploidentical (n = 19 [21%]), and cord blood (n=1 [1%]). Donors were different at HCT2 in 53% of patients. The majority of patients received reduced intensity conditioning (n = 71 [78%]) and were in remission (n = 56 [61%]) at HCT2. The median remission duration after HCT1 was 8.4 months (range 1-70) and the median time between transplants was 14 months (range 3-73). The median follow-up of surviving patients after HCT2 was 66 months (range 2-171), with 32% alive at time of analysis. The most common cause of death was disease recurrence (n = 45 [73%]). At 2 years, the rates of OS, PFS, progression, and nonrelapse mortality were 36%, 27%, 42%, and 18%, respectively. The development of chronic graft-versus-host disease (GVHD) after first HCT and HCT comorbidity index (HCT-CI) ≥2 at HCT2 were associated with inferior PFS and OS after HCT2. A second HCT is feasible in selected patients with AML who have relapsed after HCT1. Long-term survival benefit is possible in patients without chronic GVHD after HCT1 and HCT-CI
- Published
- 2021
25. Toll-Like Receptor 3 (TLR3) Is Engaged in the Intracellular Survival of the Protozoan Parasite Leishmania (Leishmania) amazonensis
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Carolina T. Rath, Áislan C. Vivarini, José Vitorino dos Santos, Jorge M. Medina, Alessandra M. Saliba, Jeremy C. Mottram, Ana Paula C. A. Lima, Teresa Cristina Calegari-Silva, Renata M. Pereira, and Ulisses G. Lopes
- Subjects
Infectious Diseases ,Immunology ,Parasitology ,Microbiology - Abstract
The protozoan parasite Leishmania (L.) amazonensis infects and replicates inside host macrophages due to subversion of the innate host cell response. In the present study, we demonstrate that TLR3 is required for the intracellular growth of L. (L.) amazonensis .
- Published
- 2022
26. One note on an infinity
- Author
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H. M. Saliba
- Subjects
General Mathematics - Published
- 2022
27. Donor clonal hematopoiesis increases risk of acute graft versus host disease after matched sibling transplantation
- Author
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Guillermo Garcia-Manero, Betul Oran, Amin M. Alousi, Andy Futreal, Uday R. Popat, Rima M. Saliba, Koichi Takahash, Feng Wang, Hagop M. Kantarjian, Richard E. Champlin, Tomoyuki Tanaka, Gheath Alatrash, Rohtesh S. Mehta, Kai Cao, and Elizabeth J. Shpall
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Myeloid ,Population ,Context (language use) ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,education ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Hematology ,Confidence interval ,Transplantation ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Stem cell ,business - Abstract
Clonal hematopoiesis (CH) is associated with older age and an increased risk of myeloid malignancies and cardiovascular complications. We analyzed donor DNA samples in patients with AML/MDS who underwent first allogeneic stem cell transplant (SCT) to investigate the association between donor CH and transplant outcomes. We performed targeted deep sequencing of 300 genes on donor blood samples and identified CH with the minimum variant allele frequency of 2%. Among 363 donors, 65 (18%) had CH. The most frequently mutated genes were DNMT3A (31 of 65; 48%), TET2 (16 of 65; 25%), PPM1D (5 of 65, 8%), and ASXL1 (7 of 65; 11%). Transplant outcomes: time to neutrophil and platelet recovery, relapse incidence, transplant-related mortality and progression-free survival, were comparable by donor CH. However, risk of grade II-IV and III-IV acute graft versus host disease (aGvHD) at 6 months after transplant was higher with donor CH vs. without donor CH (hazard ratio (HR) = 2.4, 95% Confidence Interval (CI) = 1.6-3.6, p < 0.001 and HR = 3.8, 95% CI = 1.6-8.9, p = 0.003). In this homogenous population of AML/MDS patients, donor CH was associated with increased risk of grade II-IV and III-IV aGvHD. Further studies to investigate the mechanisms of increased aGvHD and therapeutic interventions to improve aGvHD in the context of donor CH are warranted.
- Published
- 2021
28. Acute graft-versus-host disease is the foremost cause of late nonrelapse mortality
- Author
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Muzaffar H. Qazilbash, Samer A. Srour, Borje S. Andersson, Jeremy Ramdial, Betul Oran, Rohtesh S. Mehta, Uday R. Popat, Partow Kebriaei, Chitra Hosing, Amanda Olson, Richard E. Champlin, Rima M. Saliba, Qaiser Bashir, and Amin M. Alousi
- Subjects
Transplantation ,medicine.medical_specialty ,business.industry ,Hazard ratio ,Retrospective cohort study ,Hematology ,Confidence interval ,Fludarabine ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,business ,Survival analysis ,Busulfan ,030215 immunology ,medicine.drug ,Cause of death - Abstract
Despite low nonrelapse mortality (NRM) at day 100 after allogeneic hematopoietic cell transplantation (HCT), NRM at 1 year remains substantial. In this study, we retrospectively analyzed 199 patients who were treated on a phase II clinical trial assessing safety and efficacy of myeloablative fractionated busulfan and fludarabine conditioning regimen for hematologic malignancies. The goal of the study was to identify factors associated with NRM occurring between days 101 and 365 post-HCT and generate a hypothesis for future studies to reduce the risk of NRM at 1 year. We found that a vast majority (83%) of patients who experienced NRM between days 101 and 365 had prior grade II-IV acute graft-versus-host disease (GVHD), which was the leading cause of death either by itself (33.3%) or complicated by infections (37.5%). In multivariate analysis, grade II-IV acute GVHD (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.3–6.6, p = 0.01) was the only significant predictor of NRM between days 101 and 365. Measures to reduce the risk of acute GVHD could lower the risk of NRM at 1 year and improve overall survival.
- Published
- 2021
29. Allogeneic stem cell transplant for patients with myeloproliferative neoplasms in blast phase: improving outcomes in the recent era
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Rohtesh S. Mehta, Lucia Masarova, Rima M. Saliba, Amanda Olson, Naval Daver, Qaiser Bashir, Samer A. Srour, Amin M. Alousi, Stefan O. Ciurea, Ankur Varma, Prithviraj Bose, Richard E. Champlin, Uday R. Popat, Naveen Pemmaraju, Mithun Vinod Shah, Srdan Verstovsek, and Betul Oran
- Subjects
Male ,Myeloproliferative Disorders ,business.industry ,medicine.medical_treatment ,Hematopoietic Stem Cell Transplantation ,Hematology ,Hematopoietic stem cell transplantation ,Allografts ,Blast Phase ,Disease-Free Survival ,Survival Rate ,Cancer research ,Humans ,Medicine ,Female ,Stem cell ,Blast Crisis ,business ,Retrospective Studies - Published
- 2021
30. Efficacy of Azacitidine Post-Transplant Maintenance for FLT3-Negative Acute Myeloid Leukemia and Myelodysplastic Syndrome
- Author
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Oren Pasvolsky, Rima M. Saliba, Uday R Popat, Amin M Alousi, Rohtesh S. Mehta, Jason Yeh, Gheath Alatrash, Adeel Masood, Jeremy L. Ramdial, Gabriela Rondon, Partow Kebriaei, Richard E Champlin, Elizabeth J Shpall, and Betul Oran
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
31. Son Vs Daughter Haploidentical Donor for T Cell-Replete HCT with Ptcy Prophylaxis
- Author
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Rohtesh S. Mehta, Rima M. Saliba, Amin M Alousi, Gheath Alatrash, Qaiser Bashir, Chitra Hosing, Partow Kebriaei, Issa F. Khouri, Yago Nieto, Betul Oran, Uday R Popat, Muzaffar H Qazilbash, Jeremy L. Ramdial, Gabriela Rondon, Samer A Srour, Katy Rezvani, Richard E Champlin, Elizabeth J Shpall, and Kai Cao
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
32. HLA B-Leader Mismatch Is Associated with Poor Outcomes in NIMA/NIPA Mismatched Haploidentical Sibling Donor HCT
- Author
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Rohtesh S. Mehta, Rima M. Saliba, Amin M. Alousi, Gheath Alatrash, Qaiser Bashir, Chitra Hosing, Partow Kebriaei, Issa F. Khouri, Yago Nieto, Betul Oran, Uday R. Popat, Muzaffar H. Qazilbash, Jeremy L. Ramdial, Gabriela Rondon, Samer A. Srour, Katy Rezvani, Richard E. Champlin, Elizabeth J. Shpall, and Kai Cao
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
33. Prognostic Significance of Measurable Residual Disease for Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Stem Cell Transplant in Second Complete Remission and Beyond
- Author
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Oren Pasvolsky, Rima M. Saliba, Celina Ledesma, Uday R Popat, Amin M Alousi, Amanda L. Olson, Betul Oran, Chitra Hosing, Qaiser Bashir, Muzaffar H Qazilbash, Nicholas Short, Farhad Ravandi, Richard E Champlin, Elizabeth J Shpall, and Partow Kebriaei
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
34. Mother Vs Father Haploidentical Donor for T Cell-Replete HCT with Ptcy Prophylaxis
- Author
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Rohtesh S. Mehta, Rima M. Saliba, Amin M Alousi, Gheath Alatrash, Qaiser Bashir, Partow Kebriaei, Issa F. Khouri, Yago Nieto, Betul Oran, Uday R Popat, Muzaffar H Qazilbash, Jeremy L. Ramdial, Gabriela Rondon, Samer A Srour, Katy Rezvani, Richard E Champlin, Elizabeth J Shpall, and Kai Cao
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
35. Post-Transplantation Cyclophosphamide Versus Tacrolimus and Methotrexate Graft-Versus-Host Disease Prophylaxis for HLA-Matched Donor Transplantation
- Author
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Rohtesh S. Mehta, Rima M. Saliba, Gabriela Rondon, Gheath Al-Atrash, Qaiser Bashir, Chitra M. Hosing, Partow Kebriaei, Issa Khouri, Yago Nieto, Betul Oran, Uday R. Popat, Muzaffar H. Qazilbash, Jeremy Ramdial, Samer A. Srour, Richard E. Champlin, Katayoun Rezvani, Elizabeth J. Shpall, and Amin M. Alousi
- Subjects
Transplantation ,Methotrexate ,Molecular Medicine ,Immunology and Allergy ,Graft vs Host Disease ,Humans ,Cell Biology ,Hematology ,Neoplasm Recurrence, Local ,Cyclophosphamide ,Tacrolimus ,Retrospective Studies - Abstract
The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is increasing in patients undergoing HLA-matched sibling (MSD) or unrelated (MUD) donor hematopoietic cell transplantation (HCT), but data about its comparative efficacy against the traditional GVHD prophylaxis are scarce. Two broad questions assessed in this study were (a) comparison of PTCy-based GVHD prophylaxis versus Tac/MTX (without ATG) in the MSD and (b) comparison of PTCy-based GVHD prophylaxis versus Tac/MTX (with ATG) in the MUD group. This retrospective single-center study analyzed the outcomes of 964 patients who received Tac/MTX (n = 578) versus PTCy-based (n = 386) GVHD prophylaxis. All MUD recipients in the Tac/MTX group also received ATG; thus separate analyses were conducted for MSD (n = 412) and MUD (n = 552) cohorts. In the MUD cohort, 306 patients received Tac/MTX/ATG and 246 received PTCy-based GVHD prophylaxis. In the MSD cohort, 272 received Tac/MTX and 140 received PTCy-based prophylaxis. Both PTCy groups included somewhat older patients than the Tac/MTX groups and more patients had myeloid malignancy (85%-90% versus 59%-64%, respectively). A majority of patients in all groups received myeloablative conditioning and peripheral blood graft. Both PTCy groups had a significantly delayed neutrophil engraftment, higher risk of hemorrhagic cystitis, and higher risk of bacterial infections than the Tac/MTX groups. The risks of viral infections and related deaths were significantly higher in Tac/MTX group in the MUD cohort. In multivariate analysis, the risk of grade III-IV acute GVHD was similar in PTCy and Tac/MTX groups in both MSD and MUD cohorts, but the risk of chronic GVHD was significantly lower with PTCy in the MSD cohort. PTCy was associated with a significantly lower risk of non-relapse mortality and better progression-free survival in the MUD. PTCy was associated with improved GVHD-free relapse-free survival in both MSD and MUD groups. Our data suggest a benefit of using PTCy-based GVHD prophylaxis in both MSD (versus Tac/MTX) and MUD (versus Tac/MTX/ATG) HCT.
- Published
- 2022
36. Outcomes in patients with CRLF2 overexpressed acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation
- Author
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Rohtesh S. Mehta, Issa F. Khouri, Paul Koller, Muzaffar H. Qazilbash, Partow Kebriaei, Elias Jabbour, Betul Oran, Chitra Hosing, Jeffrey L. Jorgensen, Stefan O. Ciurea, Marina Konopleva, Richard E. Champlin, Elizabeth J. Shpall, Nitin Jain, Amanda Olson, Hagop M. Kantarjian, Uday R. Popat, Sa Wang, Gabriela Rondon, Celina Ledesma, Rima M. Saliba, and Amin M. Alousi
- Subjects
Oncology ,Transplantation ,medicine.medical_specialty ,Hematopoietic cell ,business.industry ,Lymphoblastic Leukemia ,Hematopoietic Stem Cell Transplantation ,MEDLINE ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Text mining ,Internal medicine ,medicine ,Humans ,In patient ,Receptors, Cytokine ,business - Published
- 2021
37. Fractionated busulfan myeloablative conditioning improves survival in older patients with acute myeloid leukemia and myelodysplastic syndrome
- Author
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Betul Oran, Ben C. Valdez, Partow Kebriaei, Rohtesh S. Mehta, Katy Rezvani, David Marin, Julianne Chen, Elizabeth J. Shpall, Amin M. Alousi, Uday R. Popat, Richard E. Champlin, Qaiser Bashir, Rima M. Saliba, Amanda Olson, Stefan O. Ciurea, Borje S. Andersson, and Chitra Hosing
- Subjects
Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,Busulfan ,Aged ,business.industry ,Hazard ratio ,Area under the curve ,Myeloid leukemia ,Myeloablative Agonists ,Survival Analysis ,Fludarabine ,Leukemia, Myeloid, Acute ,Regimen ,Treatment Outcome ,Oncology ,Myelodysplastic Syndromes ,030220 oncology & carcinogenesis ,Methotrexate ,business ,medicine.drug - Abstract
Background A myeloablative conditioning regimen can be safely given to older patients and those with comorbidities without increasing nonrelapse mortality (NRM) by fractionating the dose of intravenous busulfan. How this approach compares in efficacy with traditional, nonfractionated, lower dose regimens is unknown. Methods Outcomes were compared in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome who received either myeloablative, fractionated busulfan (f-Bu) dosed to achieve an area under the curve of 20,000 μmol per minute (f-Bu20K) over 2 weeks (n = 84) or a standard, nonfractionated, lower busulfan dose regimen of 16,000 μmol per minute (Bu16K) over 4 days (n = 78). Both groups also received fludarabine 40 mg/m2 intravenously for 4 days. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Patients in the Bu16K group who had unrelated donors also received antithymocyte globulin. The primary endpoint was progression-free survival. Results Roughly one-half of the patients were aged >65 years, approximately 40% had poor-risk cytogenetics, approximately 40% of those with AML were not in complete remission, and approximately 40% had a comorbidity index >3. At 2 years, progression-free survival was significantly improved in the f-Bu20K group compared with the Bu16K group (45% vs 24%, respectively; hazard ratio [HR], 0.6; 95% CI, 0.4-0.8; P = .004). This was because of a significant reduction in progression (34% vs 59%, respectively; HR, 0.5; 95% CI, 0.3-0.8; P = .003) without any increase in NRM (21% vs 15%, respectively; HR, 1.4; 95% CI, 0.7-3; P = .3), which resulted in improved overall survival (51% vs 31%, respectively; HR, 0.6; 95% CI, 0.3-0.9; P = .01). Conclusions A myeloablative, fractionated busulfan regimen reduces relapse and improves survival without increasing NRM in older patients with AML and myelodysplastic syndrome.
- Published
- 2021
38. Myeloablative Fractionated Busulfan Fludarabine and Thiotepa Regimen for Haploidentical Donor Transplantation
- Author
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Uday R. Popat, Rima M. Saliba, Rohtesh S. Mehta, Amin M. Alousi, Gheath Al-Atrash, Qaiser Bashir, Chitra M. Hosing, Alison M. Gulbis, Jin S. Im, Partow Kebriaei, Issa F. Khouri, Jitesh D. Kawedia, David Marin, Yago Nieto, Amanda Olson, Betul Oran, Jeremy Ramdial, Neeraj Y. Saini, Terri Lynn Shigle, Samer A. Srour, Katayoun Rezvani, Muzaffar H. Qazilbash, Borje S. Andersson, Elizabeth J. Shpall, and Richard E. Champlin
- Subjects
Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2023
39. Azithromycin may increase hematologic relapse rates in matched unrelated donor hematopoietic cell transplant recipients who receive anti-thymocyte globulin, but not in most other recipients
- Author
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Ajay Sheshadri, Muhammad H. Arain, Gabriela Rondon, Amin M. Alousi, Chitra Hosing, Richard E. Champlin, Lara Bashoura, Rohtesh S. Mehta, Badar Patel, Rima M. Saliba, Uday R. Popat, Burton F. Dickey, Luis C. Bueno, and Tahreem Ahmed
- Subjects
hematopoietic cell transplant ,Transplantation Conditioning ,matched unrelated donor ,Graft vs Host Disease ,Azithromycin ,Article ,Text mining ,anti-thymocyte globulin ,Recurrence ,Hematologic relapse ,medicine ,Humans ,Antilymphocyte Serum ,azithromycin ,Transplantation ,Hematopoietic cell ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Matched Unrelated Donor ,Transplant Recipients ,Anti-thymocyte globulin ,Hematologic Neoplasms ,Immunology ,business ,Unrelated Donors ,medicine.drug - Published
- 2020
40. 'Eu acho que eu existo, então por que eu não me vejo?': uma análise da dominação masculina através das lentes do cinema
- Author
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A. M. SALIBA
- Published
- 2022
41. Endothelial Activation and Stress Index (EASIX) at Admission Predicts Fluid Overload in Recipients of Allogeneic Stem Cell Transplantation
- Author
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Celina Ledesma, Gabriela Rondon, Ankur Varma, Rima M. Saliba, Stefan O. Ciurea, Richard E. Champlin, Julianne Chen, and Samer A. Srour
- Subjects
medicine.medical_specialty ,Graft vs Host Disease ,Cohort Studies ,chemistry.chemical_compound ,Interquartile range ,Internal medicine ,Humans ,Transplantation, Homologous ,Medicine ,Cumulative incidence ,Aged ,Proportional Hazards Models ,Transplantation ,Univariate analysis ,Creatinine ,Receiver operating characteristic ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Tissue Donors ,chemistry ,Cohort ,business - Abstract
Fluid overload (FO) grade ≥2 (more than 10% weight gain from baseline) has recently been recognized as an important toxicity associated with a high rate of nonrelapse mortality in recipients of allogeneic hematopoietic cell transplantation (AHCT). The causes for FO remain unclear. We hypothesized that endothelial damage, possibly due to treatments received prior to AHCT, may be associated with this toxicity and sought to determine whether the Endothelial Activation and Stress Index (EASIX) (defined as lactate dehydrogenase [U/L] × creatinine [mg/dL]/platelets [109 cells/L]) correlates with grade ≥2 FO in 2 cohorts of recipients of AHCT at our institution. We tested our hypothesis in a cohort of 145 consecutive recipients (study cohort) of AHCT transplant from HLA-haploidentical donors and validated the findings in a cohort of 449 (validation cohort) recipients of AHCT from HLA-matched donors who underwent transplantation between 2010 and 2015. Predictors of grade ≥2 FO were evaluated using competing risks regression in univariate analysis and classification and regression tree (CART) analysis in multivariate analysis. The cumulative incidence of grade ≥2 FO was estimated considering death as a competing risk. EASIX scores were evaluated based on log2-transformed values. Optimal predictive EASIX cutoff values were determined based on receiver operating characteristics curve analysis. Grade ≥2 FO occurred in 21% and 6% of the study and validation cohorts, respectively, with the majority of these cases being diagnosed before the day of AHCT. Median log2 EASIX score at admission was 2.4 (interquartile range [IQR], 1.3, 3.7) and 2.5 (IQR, 1.4, 3.9) in the 2 respective cohorts. In univariate analysis, high EASIX at admission was a significant predictor of grade ≥2 FO in the study (cutoff: 4.4, hazard ratio [HR] = 4.8, P 60 years (HR = 9.6, P = .04) in the validation cohort. At admission, the prevalence of EASIX score of >4.3 (18% versus 17%, P = .9) was not different between the diabetics and nondiabetics. EASIX score at admission is a significant predictor of grade ≥2 FO in recipients of AHCT from HLA-haploidentical or HLA-matched donors. Independently of EASIX, older patients with low weight were associated with increased risk of grade ≥2 FO for recipients of HLA-haploidentical transplants. For the HLA-matched cohort, diabetes and older age were associated with increased FO risk. These findings require validation in external cohorts.
- Published
- 2020
42. Impact of graft composition on outcomes of haploidentical bone marrow stem cell transplantation
- Author
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Chitra Hosing, Richard E. Champlin, Julianne Chen, Amin M. Alousi, Issa F. Khouri, Betul Oran, Uday R. Popat, Gabriela Rondon, Gheath Alatrash, Partow Kebriaei, Charles Martinez, Stefan O. Ciurea, Rima M. Saliba, Lauren Westfall Veltri, Elizabeth J. Shpall, La Jerald Augustine, and Katayoun Rezvani
- Subjects
Pathology ,medicine.medical_specialty ,Transplantation Conditioning ,Bone marrow transplantation ,Cyclophosphamide ,Extramural ,business.industry ,medicine.medical_treatment ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Hematology ,Hematopoietic stem cell transplantation ,Bone Marrow Stem Cell Transplantation ,medicine.anatomical_structure ,Bone Marrow ,medicine ,Humans ,Bone marrow ,Letters to the Editor ,business ,Bone Marrow Transplantation ,Stem Cell Transplantation ,medicine.drug - Published
- 2020
43. Better allele-level matching improves transplant-related mortality after double cord blood transplantation
- Author
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Betül Oran, Kai Cao, Rima M. Saliba, Katayoun Rezvani, Marcos de Lima, Sairah Ahmed, Chitra M. Hosing, Uday R. Popat, Yudith Carmazzi, Partow Kebriaei, Yago Nieto, Gabriela Rondon, Dana Willis, Nina Shah, Simrit Parmar, Amanda Olson, Brandt Moore, David Marin, Rohtesh Mehta, Marcelo Fernández-Viña, Richard E. Champlin, and Elizabeth J. Shpall
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Cord blood transplant requires less stringent human leukocyte antigen matching than unrelated donors. In 133 patients with hematologic malignancies who engrafted after double cord blood transplantation with a dominant unit, we studied the effect of high resolution testing at 4 loci (-A, -B, -C, -DRB1) for its impact on 2-year transplant-related mortality. Ten percent of the dominant cord blood units were matched at 7–8/8 alleles using HLA-A, -B, -C, and -DRB1; 25% were matched at 6/8, 40% at 5/8, and 25% at 4/8 or less allele. High resolution typing at 4 loci showed that there was no 2-year transplant-related mortality in 7–8/8 matched patients. Patients with 5–6/8 matched dominant cord blood units had 2-year transplant-related mortality of 39% while patients with 4/8 or less matched units had 60%. Multivariate regression analyses confirmed the independent effect of high resolution typing on the outcome when adjusted for age, diagnosis, CD34+ cell dose infused, graft manipulation and cord to cord matching. The worst prognostic group included patients aged over 32 years with 4/8 or less matched cord blood units compared with patients who were either younger than 32 years old independent of allele-level matching, or aged over 32 years but with 5–6/8 matched cord blood units (Hazard Ratio 2.2; 95% confidence interval: 1.3–3.7; P
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- 2015
- Full Text
- View/download PDF
44. History of tailings dam failure: Impacts on access to safe water and influence on the legislative framework
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Roberta N, Guimarães, Victor R, Moreira, Joyce R A, Cruz, Aloysio P M, Saliba, and Míriam C S, Amaral
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Environmental Engineering ,Rivers ,Water Supply ,Water Quality ,Humans ,Environmental Chemistry ,Environment ,Pollution ,Waste Management and Disposal - Abstract
Tailings dams have been built since 3000 BCE and despite the advancement of construction methods, mainly in the second half of the 21st century, their ruptures were still recorded. The main direct impacts are related to the loss of human lives, impairment of physical structures and changes in water quality. In this review, different dam failure events were critically analyzed considering their social and environmental impacts, besides the gaps in current regulations framework to appropriately charge the companies involved. These aspects differ the current review paper from those currently available, which also present advancements in the discussion of actions taken after the ruptures, the impacts on water quality, and the challenges related to the water supply. It has been noticed a lack of studies and methodologies capable to predict the water quality under scenarios of tailings contamination. Studies covering that aspect would be an important tool for planning emergency responses by stakeholders. With that in mind, the article discloses the pathway toward an effective strategy in scenarios of tailing dam failure that would mitigate the impacts on water quality and guarantee access to safe water.
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- 2022
45. Nickel electrodeposition in LEU metal foil annular targets to produce Mo-99
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Ricardo F. Ianelli, Adonis M. Saliba-Silva, Eriki M. Takara, José Garcia Neto, José A.B. Souza, Elita F. Urano de Carvalho, and Michelangelo Durazzo
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General Materials Science ,Condensed Matter Physics - Published
- 2022
46. Mycophenolate Mofetil: A Friend or a Foe with Post-Transplantation Cyclophosphamide and Tacrolimus Prophylaxis in HLA-Matched Donors?
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Rohtesh S. Mehta, Rima M. Saliba, Eiko Hayase, Robert R. Jenq, Susan Abraham, Asif Rashid, Gabriela Rondon, Gheath Al-Atrash, Qaiser Bashir, Chitra M. Hosing, Partow Kebriaei, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Betul Oran, Uday R. Popat, Muzaffar H. Qazilbash, Jeremy Ramdial, Samer Srour, Richard E. Champlin, Katayoun Rezvani, Elizabeth J. Shpall, and Amin M. Alousi
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Transplantation ,Graft vs Host Disease ,Humans ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology ,Mycophenolic Acid ,Neoplasm Recurrence, Local ,Cyclophosphamide ,Tacrolimus - Abstract
Adapted from the haploidentical hematopoietic stem cell transplantation (HCT) literature, post-transplantation cyclophosphamide (PTCy) is being used increasingly with HLA-matched donors, generally with a calcineurin inhibitor, such as tacrolimus (Tac), and with or without mycophenolate mofetil (MMF). Owing to its immunosuppressive and potentially antitumor and antimicrobial properties, MMF is an attractive drug; the benefit gained when it is used with PTCy/Tac remains unclear, however. To assess this, we compared PTCy/Tac (n = 242) and PTCy/Tac/MMF (n = 144) regimens in recipients of HLA-matched donor transplantation. In multivariate analysis, the PTCy/Tac/MMF group had a significantly higher risk of grade II-IV acute graft-versus-host disease (aGVHD) (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.6 to 2.8; P.001), and steroid-refractory/dependent aGVHD (HR, 4.8; 95% CI, 2.4 to 9.6; P.001), yet a significantly lower risk of relapse (HR, .5; 95% CI, .3 to .9; P = .009) and better progression-free survival (PFS) (HR, .7; 95% CI, .5 to .9; P = .04). There were no differences in the risk of grade III-IV aGVHD, chronic graft-versus-host disease (cGVHD), nonrelapse mortality, or overall survival. MMF was associated with prolonged neutrophil engraftment by 2 days and an elevated risk of bacterial infection. In an exploratory stool microbiome analysis (n = 16), we noted a higher relative abundance of β-glucuronidase-producing bacteria in the MMF group, which may have a role in the pathogenesis of MMF-related GVHD. Our data suggest that the addition of MMF to PTCy/Tac for HLA-matched donor HCT does not provide any advantage for GVHD prevention. Further studies are needed to decipher this mechanism and understand its role with PTCy-based prophylaxis.
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- 2022
47. Haploidentical versus Matched Unrelated versus Matched Sibling Donor Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide
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Rohtesh S. Mehta, Rima M. Saliba, Sassine Ghanem, Amin M. Alousi, Gabriela Rondon, Paolo Anderlini, Gheath Al-Atrash, Qaiser Bashir, Chitra M. Hosing, Jin S. Im, Partow Kebriaei, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Betul Oran, Uday R. Popat, Muzaffar H. Qazilbash, Jeremy Ramdial, Neeraj Saini, Samer A. Srour, Richard E. Champlin, Katayoun Rezvani, and Elizabeth J. Shpall
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2022
48. Impact of Induction Therapy on the Outcome of Immunoglobulin Light Chain Amyloidosis after Autologous Hematopoietic Stem Cell Transplantation
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Amir Hamdi, Chitra Hosing, Medhavi Honhar, Uday R. Popat, Richard E. Champlin, Donna M. Weber, Gabriela Rondon, Muzaffar H. Qazilbash, Rima M. Saliba, Sheeba K. Thomas, Robert Z. Orlowski, Qaiser Bashir, A. Megan Cornelison, Aimaz Afrough, Ankur Varma, Nina Shah, and Simrit Parmar
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Adult ,Male ,Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,AL amyloidosis ,Humans ,Medicine ,Immunoglobulin Light-chain Amyloidosis ,Aged ,Lenalidomide ,Transplantation ,Chemotherapy ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Induction Chemotherapy ,Hematology ,Middle Aged ,medicine.disease ,Hematologic Response ,Thalidomide ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,business ,030215 immunology ,medicine.drug - Abstract
With the availability of immunomodulatory imide drugs (IMiDs) and proteasome inhibitors (PI), most patients with immunoglobulin light chain amyloidosis (AL) receive induction therapy before autologous hematopoietic stem cell transplantation (auto-HCT). In this study we evaluated the type of induction therapy and its impact on the outcome of auto-HCT in AL. We identified 128 patients with AL who underwent high-dose chemotherapy and auto-HCT at our institution between 1997 and 2013. Patients were divided into 3 groups: no induction, conventional chemotherapy (CC)-based induction (melphalan, steroids), and IMiD/PI-based induction (thalidomide, lenalidomide, or bortezomib). The hematologic response (HR) and organ response were defined according to the established criteria. Median age at auto-HCT was 58 years (range, 35 to 75). Twenty patients (15.5%) received no induction, 25 (19.5%) received CC, and 83 (65%) received IMiDs/PIs. One, 2, or 3 or more organs were involved in 90 (70%), 20 (16%), and 18 (14%) patients, respectively. After auto-HCT 12 of 20 (60%), 15 of 24 (62%), and 72 of 83 (87%) assessable patients achieved HR at 100 days in no induction, CC, and IMiD/PI groups, respectively (P = .001). Organ response at 1 year after auto-HCT was seen in 7 of 18 (39%), 14 of 24 (58%), and 37 of 79 (47%) assessable patients in no induction, CC, and IMiD/PI groups, respectively (P = .3). Achieving a hematologic complete response was associated with a significantly higher probability of achieving an organ response (P = .02). After a median follow-up of 26 months, rates of 2-year progression-free survival were 67%, 56%, and 73% in no induction, CC, and IMiD/PI groups, respectively (P = .07; hazard ratio, .5; 95% confidence interval [CI], .3 to 1.1). Rates of 2-year overall survival were 73%, 76%, and 87% in no induction, CC, and IMiD/PI groups, respectively (P = .05; hazard ratio, .4; 95% CI, .2 to .9). On multivariate analysis a low β2-microglobulin (P = .01; hazard ratio, .3; 95% CI, .1 to .7) and induction therapy with IMiD/PI (P = .01; hazard ratio, .3; 95% CI, .1 to .7) were associated with a better overall survival. Induction therapy with either CC or IMiDs/PIs is safe and feasible in selected patients with AL. IMiD/PI-based induction is associated with a longer overall survival compared with patients who received no induction or CC before auto-HCT.
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- 2018
49. Pilot study using post-transplant cyclophosphamide (PTCy), tacrolimus and mycophenolate GVHD prophylaxis for older patients receiving 10/10 HLA-matched unrelated donor hematopoietic stem cell transplantation
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Rima M. Saliba, Amin M. Alousi, Uday R. Popat, Muzaffar H. Qazilbash, Simrit Parmar, Stefan O. Ciurea, Chitra Hosing, Gabriela Rondon, Mithun Vinod Shah, Partow Kebriaei, Betul Oran, Ioana Rus, Richard E. Champlin, Issa F. Khouri, Doris Soebbing, and Julianne Chen
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Male ,Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,Myeloid ,Cyclophosphamide ,medicine.medical_treatment ,Graft vs Host Disease ,Pilot Projects ,Hematopoietic stem cell transplantation ,Mycophenolate ,Gastroenterology ,Tacrolimus ,Article ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Leukemia, Myeloid, Acute ,Leukemia ,surgical procedures, operative ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Unrelated Donors ,business ,030215 immunology ,medicine.drug - Abstract
Allogeneic SCT for older patients remains challenging at least in part due to graft-versus-host disease (GVHD) and higher treatment-related mortality (TRM). We conducted a prospective pilot study primarily for older patients undergoing matched unrelated donor (MUD) SCT using a reduced-intensity (RIC) melphalan-based conditioning and post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis with tacrolimus and mycophenolate mofetil. Twenty-two patients (median age 64) underwent RIC MUD SCT for high-risk hematological malignancies including AML/MDS (73%), CML/MPD (18%), and other (10%). Two (9%) patients had early death; the rest (100%) engrafted. After a median follow-up of 17 months, 11 patients were alive and disease-free with an estimated 2-year progression-free (PFS) and overall (OS) survival of 48%. The cumulative incidences of grades 2-4 and 3-4 acute GVHD (aGVHD) at day +100 and 2-years post-SCT were 32% and 4%, and 59% and 24%, respectively. No cases of chronic GVHD (cGVHD) were noted. However, late acute GVHD was observed in 6 (27%) patients. In conclusion, RIC MUD SCT with melphalan-based conditioning and PTCy-based GVHD-based prophylaxis for older patients appears effective in controlling relapse. While cGVHD was not seen and early aGVHD appears controllable, a significant proportion developed late aGVHD responsible for higher TRM seen in these patients.
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- 2018
50. Prediction of Knee Joint Contact Forces From External Measures Using Principal Component Prediction and Reconstruction
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Michael J. Rainbow, Allison L. Clouthier, Kevin J. Deluzio, Christopher M. Saliba, and Scott C.E. Brandon
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Adult ,Male ,musculoskeletal diseases ,Motion analysis ,medicine.medical_specialty ,Knee Joint ,Computer science ,0206 medical engineering ,Population ,Biophysics ,02 engineering and technology ,Osteoarthritis ,Contact force ,03 medical and health sciences ,0302 clinical medicine ,Gait (human) ,Physical medicine and rehabilitation ,Predictive Value of Tests ,Linear regression ,medicine ,Humans ,Orthopedics and Sports Medicine ,education ,Gait ,Aged ,030203 arthritis & rheumatology ,Principal Component Analysis ,education.field_of_study ,Rehabilitation ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,020601 biomedical engineering ,Biomechanical Phenomena ,Case-Control Studies ,Gait analysis ,Female ,human activities - Abstract
Abnormal loading of the knee joint contributes to the pathogenesis of knee osteoarthritis. Gait retraining is a noninvasive intervention that aims to reduce knee loads by providing audible, visual, or haptic feedback of gait parameters. The computational expense of joint contact force prediction has limited real-time feedback to surrogate measures of the contact force, such as the knee adduction moment. We developed a method to predict knee joint contact forces using motion analysis and a statistical regression model that can be implemented in near real-time. Gait waveform variables were deconstructed using principal component analysis, and a linear regression was used to predict the principal component scores of the contact force waveforms. Knee joint contact force waveforms were reconstructed using the predicted scores. We tested our method using a heterogenous population of asymptomatic controls and subjects with knee osteoarthritis. The reconstructed contact force waveforms had mean (SD) root mean square differences of 0.17 (0.05) bodyweight compared with the contact forces predicted by a musculoskeletal model. Our method successfully predicted subject-specific shape features of contact force waveforms and is a potentially powerful tool in biofeedback and clinical gait analysis.
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- 2018
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