MARISTELA PINHEIRO FREIRE

(Fonte: Lattes)
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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/49 - Laboratório de Protozoologia, Hospital das Clínicas, Faculdade de Medicina
LIM/47 - Laboratório de Hepatologia por Vírus, Hospital das Clínicas, Faculdade de Medicina

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  • article 6 Citação(ões) na Scopus
    Efficacy of ceftazidime-avibactam in solid organ transplant recipients with bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae
    (2023) PEREZ-NADALES, Elena; FERNANDEZ-RUIZ, Mario; NATERA, Alejandra M.; GUTIERREZ-GUTIERREZ, Belen; MULARONI, Alessandra; RUSSELLI, Giovanna; PIERROTTI, Ligia Camera; FREIRE, Maristela Pinheiro; FALCONE, Marco; TISEO, Giusy; TUMBARELLO, Mario; RAFFAELLI, Francesca; ABDALA, Edson; BODRO, Marta; GERVASI, Elena; FARINAS, Maria Carmen; SEMINARI, Elena M.; CASTON, Juan Jose; MARIN-SANZ, Juan Antonio; GALVEZ-SOTO, Victor; RANA, Meenakshi M.; LOECHES, Belen; MARTIN-DAVILA, Pilar; PASCUAL, Alvaro; RODRIGUEZ-BANO, Jesus; AGUADO, Jose Maria; MARTINEZ-MARTINEZ, Luis; TORRE-CISNEROS, Julian; REIPI INCREMENT-SOT Study Grp
    We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL-or Carbapenemaseproducing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study). Outcomes were 14-day and 30-day clinical success (complete resolution of attributable manifestations, adequate source control, and negative follow-up blood cultures) and 30-day all-cause mortality. Multivariable logistic and Cox regression analyses adjusted for the propensity score to receive CAZ-AVI were constructed. Among 210 SOT recipients with CPKP-BSI, 149 received active primary therapy with CAZ-AVI (66/149) or BAT (83/ 149). Patients treated with CAZ-AVI had higher 14-day (80.7% vs 60.6%, P =.011) and 30 day (83.1% vs 60.6%, P = .004) clinical success and lower 30-day mortality (13.25% vs 27.3%, P =.053) than those receiving BAT. In the adjusted analysis, CAZ-AVI increased the probability of 14-day (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.036.84; P = .044) and 30-day clinical success (aOR, 3.14; 95% CI, 1.17-8.40; P = .023). In contrast, CAZ-AVI therapy was not independently associated with 30-day mortality. In the CAZ-AVI group, combination therapy was not associated with better outcomes. In conclusion, CAZ-AVI may be considered a first-line treatment in SOT recipients with CPKP-BSI.
  • article 23 Citação(ões) na Scopus
    Lactated Ringer's Versus 4% Albumin on Lactated Ringer's in Early Sepsis Therapy in Cancer Patients: A Pilot Single-Center Randomized Trial
    (2019) PARK, Clarice Hyesuk Lee; ALMEIDA, Juliano Pinheiro de; OLIVEIRA, Gisele Queiroz de; RIZK, Stephanie Itala; FUKUSHIMA, Julia Tizue; NAKAMURA, Rosana Ely; MOURAO, Matheus Moraes; GALAS, Filomena Regina Barbosa Gomes; ABDALA, Edson; FREIRE, Maristela Pinheiro; KALIL FILHO, Roberto; JR, Jose Otavio Costa Auler; NARDELLI, Pasquale; MARTIN, Greg S.; LANDONI, Giovanni; HAJJAR, Ludhmila Abrahao
    Objective: To investigate the effects of the administration of 4% albumin on lactated Ringer's, when compared with lactated Ringer's alone, in the early phase of sepsis in cancer patients. Design: Single-center, randomized, double-blind, controlled-parallel trial. Setting: A tertiary care university cancer hospital. Patients: Cancer patients with severe sepsis or septic shock. Interventions: Between October 2014 and December 2016, patients were randomly assigned to receive either bolus of albumin in a lactated Ringer's solution or lactated Ringer's solution alone during the first 6 hours of fluid resuscitation after intensive care medicine (ICU) admission. Primary outcome was defined as death from any cause at 7 days. Secondary outcomes were defined as death from any cause within 28 days, change in Sequence Organ Failure Assessment scores from baseline to day 7, days alive and free of mechanical ventilation, days alive and free of vasopressor, renal replacement therapy during ICU stay, and length of ICU and hospital stay. Measurements and Main Results: A total of 360 patients were enrolled in the trial. At 7 days, 46 of 180 patients (26%) died in the albumin group and 40 of 180 (22%) died in the lactated Ringer's group (p = 0.5). At 28 days, 96 of 180 patients (53%) died in the albumin group and 83 of 180 (46%) died in the lactated Ringer's group (p = 0.2). No significant differences in secondary outcomes were observed. Conclusions: Adding albumin to early standard resuscitation with lactated Ringer's in cancer patients with sepsis did not improve 7-day survival.
  • article 12 Citação(ões) na Scopus
    Efficacy of beta-lactam/beta-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project)
    (2021) PIERROTTI, Ligia C.; PEREZ-NADALES, Elena; FERNANDEZ-RUIZ, Mario; GUTIERREZ-GUTIERREZ, Belen; TAN, Ban Hock; CARRATALA, Jordi; ORIOL, Isabel; PAUL, Mical; COHEN-SINAI, Noa; LOPEZ-MEDRANO, Francisco; SAN-JUAN, Rafael; MONTEJO, Miguel; FREIRE, Maristela P.; CORDERO, Elisa; DAVID, Miruna D.; MERINO, Esperanza; STEINKE, Seema Mehta; GROSSI, Paolo A.; CANO, Angela; SEMINARI, Elena M.; VALERIO, Maricela; GUNSEREN, Filiz; RANA, Meenakshi; MULARONI, Alessandra; MARTIN-DAVILA, Pilar; DELDEN, Christian van; DEMIRKAYA, Melike Hamiyet; TUFAN, Zeliha Kocak; LOECHES, Belen; IYER, Ranganathan N.; SOLDANI, Fabio; ERIKSSON, Britt-Marie; PILMIS, Benoit; RIZZI, Marco; COUSSEMENT, Julien; CLEMENTE, Wanessa T.; ROILIDES, Emmanuel; PASCUAL, Alvaro; MARTINEZ-MARTINEZ, Luis; RODRIGUEZ-BANO, Jesus; TORRE-CISNEROS, Julian; AGUADO, Jose Maria
    Background Whether active therapy with beta-lactam/beta-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. Methods We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. Results Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count <= 500 cells/mu L at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. Conclusions Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
  • article 18 Citação(ões) na Scopus
    Impact of pre-transplant carbapenem-resistant Enterobacterales colonization and/or infection on solid organ transplant outcomes
    (2021) TAIMUR, Sarah; POUCH, Stephanie M.; ZUBIZARRETA, Nicole; MAZUMDAR, Madhu; RANA, Meenakshi; PATEL, Gopi; FREIRE, Maristela Pinnheiro; MADAN, Rebecca Pellett; KWAK, Eun Jeong; BLUMBERG, Emily; SATLIN, Michael J.; PISNEY, Larissa; CLEMENTE, Wanessa Trindade; ZERVOS, Marcus J.; HOZ, Ricardo M. La; HUPRIKAR, Shirish
    The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.
  • article 21 Citação(ões) na Scopus
    Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: The impact of cytomegalovirus disease and lymphopenia
    (2020) PEREZ-NADALES, Elena; GUTIERREZ-GUTIERREZ, Belen; NATERA, Alejandra M.; ABDALA, Edson; MAGALHAES, Maira Reina; MULARONI, Alessandra; MONACO, Francesco; PIERROTTI, Ligia Camera; FREIRE, Maristela Pinheiro; IYER, Ranganathan N.; STEINKE, Seema Mehta; CALVI, Elisa Grazia; TUMBARELLO, Mario; FALCONE, Marco; FERNANDEZ-RUIZ, Mario; COSTA-MATEO, Jose Maria; RANA, Meenakshi M.; STRABELLI, Tania Mara Varejao; PAUL, Mical; FARINAS, Maria Carmen; CLEMENTE, Wanessa Trindade; ROILIDES, Emmanuel; MUNOZ, Patricia; DEWISPELAERE, Laurent; LOECHES, Belen; LOWMAN, Warren; TAN, Ban Hock; ESCUDERO-SANCHEZ, Rosa; BODRO, Marta; GROSSI, Paolo Antonio; SOLDANI, Fabio; GUNSEREN, Filiz; NESTOROVA, Nina; PASCUAL, Alvaro; MARTINEZ-MARTINEZ, Luis; AGUADO, Jose Maria; RODRIGUEZ-BANO, Jesus; TORRE-CISNEROS, Julian; SONG, A. T. Wan; ANDRAUS, W.; D'ALBUQUERQUE, L. A. Carneiro; DAVID-NETO, E.; PAULA, F. Jota de; ROSSI, F.; OSTRANDER, D.; AVERY, R.; RIZZI, M.; LOSITO, A. R.; RAFFAELLI, F.; GIACOMO, P. Del; TISEO, G.; LORA-TAMAYO, J.; SAN-JUAN, R.; GRACIA-AHUFINGER, I; CASTON, J.; RUIZ, Y. A.; ALTMAN, D. R.; V, S. Campos; BAR-SINAI, N.; KOPPEL, F.; ALMAJANO, F. Arnaiz de las Revillas; RICO, C. Gonzalez; MARTINEZ, M. Fernandez; MOURAO, P. H. O.; NEVES, F. A.; FERREIRA, J.; PYRPASOPOULOU, A.; IOSIFIDIS, E.; ROMIOPOULOS, I; V, M. Minero; SANCHEZ-CARRILLO, C.; LARDO, S.; COUSSEMENT, J.; DODEMONT, M.; JIAYUN, K.; MARTIN-DAVILA, P.; FORTUN, J.; ALMELA, M.; MORENO, A.; LINARES, L.; GASPERINA, D. D.; BALSAMO, M. L.; ROVELLI, C.; CONCIA, E.; CHIESI, S.; SALERNO, D. N.; OGUNC, D.; PILMIS, B.; SEMINARI, E. M.; CARRATALA, J.; DOMINGUEZ, A.; CORDERO, E.; LEPE, J. A.; MONTEJO, M.; LUCAS, E. Merino de; ERIKSSON, B. M.; DELDEN, C. van; MANUEL, O.; ARSLAN, H.; TUFAN, Z. Kocak; KAZAK, E.; DAVID, M.; LEASE, E.; CORNAGLIA, G.; AKOVA, M.
    Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
  • article 23 Citação(ões) na Scopus
    Development of a Risk Prediction Model for Carbapenem-resistant Enterobacteriaceae Infection After Liver Transplantation: A Multinational Cohort Study
    (2021) GIANNELLA, Maddalena; FREIRE, Maristela; RINALDI, Matteo; ABDALA, Edson; RUBIN, Arianna; MULARONI, Alessandra; GRUTTADAURIA, Salvatore; GROSSI, Paolo; SHBAKLO, Nour; TANDOI, Francesco; FERRARESE, Alberto; BURRA, Patrizia; FERNANDES, Ruan; CAMARGO, Luis Fernando Aranha; ASENSIO, Angel; ALAGNA, Laura; BANDERA, Alessandra; SIMKINS, Jacques; ABBO, Lilian; HALPERN, Marcia; GIRAO, Evelyne Santana; VALERIO, Maricela; MUNOZ, Patricia; YUNQUERA, Ainhoa Fernandez; STATLENDER, Liran; YAHAV, Dafna; FRANCESCHINI, Erica; GRAZIANO, Elena; MORELLI, Maria Cristina; CESCON, Matteo; VIALE, Pierluigi; LEWIS, Russell
    Background. Patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT), with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies. Methods. Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray subdistribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. Results. A total of 840 LT recipients found to be colonized with CRE before (n = 203) or after (n = 637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (interquartile range [IQR], 9-42) days after LT. Pre- and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical reintervention were retained in the prediction model. Median 30- and 60-day predicted risk was 15% (IQR, 11-24) and 21% (IQR, 15-33), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (area under the curve [AUC], 74.6; Brier index, 16.3) and bootstrapped validation dataset (AUC, 73.9; Brier index, 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/. Conclusions. Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.
  • article 40 Citação(ões) na Scopus
    Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center
    (2021) THOMAZ, Danilo Y.; ALMEIDA, Joao N. de; SEJAS, Odeli N. E.; NEGRO, Gilda M. B. Del; CARVALHO, Gabrielle O. M. H.; GIMENES, Viviane M. F.; SOUZA, Maria Emilia B. de; ARASTEHFAR, Amir; CAMARGO, Carlos H.; MOTTA, Adriana L.; ROSSI, Flavia; PERLIN, David S.; FREIRE, Maristela P.; ABDALA, Edson; BENARD, Gil
    Clonal outbreaks due to azole-resistant Candida parapsilosis (ARCP) isolates have been reported in numerous studies, but the environmental niche of such isolates has yet to be defined. Herein, we aimed to identify the environmental niche of ARCP isolates causing unremitting clonal outbreaks in an adult ICU from a Brazilian cancer referral center. C. parapsilosis sensu stricto isolates recovered from blood cultures, pericatheter skins, healthcare workers (HCW), and nosocomial surfaces were genotyped by multilocus microsatellite typing (MLMT). Antifungal susceptibility testing was performed by the EUCAST (European Committee for Antimicrobial Susceptibility Testing) broth microdilution reference method and ERG11 was sequenced to determine the azole resistance mechanism. Approximately 68% of isolates were fluconazole-resistant (76/112), including pericatheter skins (3/3, 100%), blood cultures (63/70, 90%), nosocomial surfaces (6/11, 54.5%), and HCW's hands (4/28, 14.2%). MLMT revealed five clusters: the major cluster contained 88.2% of ARCP isolates (67/76) collected from blood (57/70), bed (2/2), pericatheter skin (2/3), from carts (3/7), and HCW's hands (3/27). ARCP isolates were associated with a higher 30 day crude mortality rate (63.8%) than non-ARCP ones (20%, p = 0.008), and resisted two environmental decontamination attempts using quaternary ammonium. This study for the first time identified ARCP isolates harboring the Erg11-Y132F mutation from nosocomial surfaces and HCW's hands, which were genetically identical to ARCP blood isolates. Therefore, it is likely that persisting clonal outbreak due to ARCP isolates was fueled by environmental sources. The resistance of Y132F ARCP isolates to disinfectants, and their potential association with a high mortality rate, warrant vigilant source control using effective environmental decontamination.
  • article 3 Citação(ões) na Scopus
    Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection
    (2023) RINALDI, Matteo; BONAZZETTI, Cecilia; GALLO, Mena; FERRARO, Giuseppe; FREIRE, Maristela; TERRABUIO, Debora Raquel Benedita; TANDOI, Francesco; ROMAGNOLI, Renato; ROSA, Francesco Giuseppe De; MULARONI, Alessandra; FERRARESE, Alberto; BURRA, Patrizia; HALPERN, Marcia; BALBI, Elizabeth; SIMKINS, Jacques; ABBO, Lilian; MORRAS, Ignacio; CANTERO, Mireia; ALAGNA, Laura; BANDERA, Alessandra; CLEMENTE, Wanessa Trinidade; VALERIO, Maricela; FERNANDEZ, Ainhoa; MUNOZ, Patricia; STATLENDER, Liran; YAHAV, Dafna; CAMARGO, Luis Fernando Aranha; GIRAO, Evelyne Santana; GROSSI, Paolo; VIALE, Pierluigi; CURTI, Stefania; GIANNELLA, Maddalena
    Background: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking.Methods: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out.Results: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score >= 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE >= 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score >= 11 and SOFA score >= 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective.Conclusions: Both INCREMENT-SOT-CPE >= 11 and SOFA >= 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.
  • conferenceObject
    Prior Infection or Colonization with Carbapenem-Resistant Enterobacteriaceae Is Not an Absolute Contraindication for Solid Organ Transplantation
    (2016) HUPRIKAR, S.; CASNER, L.; POUCH, S.; FREIRE, M. Pinheiro; MADAN, R.; KWAK, E.; SATLIN, M.; HARTMAN, P.; PISNEY, L.; MOURAO, P. Henrique; HOZ, R. La; PATEL, G.