Mariëlle Gelens - Academia.edu (original) (raw)
Papers by Mariëlle Gelens
The Patient - Patient-Centered Outcomes Research, 2017
Background The aim of this study was to develop, together with the Lung Foundation Netherlands an... more Background The aim of this study was to develop, together with the Lung Foundation Netherlands and Dutch Kidney Patients Association, patients and clinicians, a measure to evaluate patient experiences with the orphan drugs pirfenidone (for idiopathic pulmonary fibrosis [IPF]) and eculizumab (for atypical haemolytic uraemic syndrome [aHUS]), as well as a generic measure of patient experiences and satisfaction with medications. Methods Development of the Patient Experiences and Satisfaction with Medications (PESaM) questionnaire consisted of four phases: literature review (phase I); focus groups and individual patient interviews (phase II); item generation (phase III); and face and content validity testing (phase IV). Literature review aimed to identify existing disease-specific and generic patient experience measures to provide guidance on the domains of medication use relevant to patients, the number of items and type of response categories, and to generate an initial pool of items. Subsequent focus groups and patient interviews were conducted to gain insight into the perceived effectiveness of the therapies, the burden of side effects, and how the medication impacted on a patient's daily life. Focus groups and interviews were recorded and transcribed verbatim.
The Netherlands Journal of Medicine, 1999
Background: Calcium acetate (CaAc) is an effective phosphate binder in patients with chronic rena... more Background: Calcium acetate (CaAc) is an effective phosphate binder in patients with chronic renal failure. However, an ® important side effect is gastro-intestinal discomfort. Phos-ex (Cablon, The Netherlands) is the only commercially available non-coated CaAc formulation in our country. We developed two new CaAc formulations: neutral-coated CaAc (NCCaAc) and enteric-coated CaAc (ECCaAc). Methods: In a randomised double-blinded cross-over trial we compared efficacy and tolerance of the three formulations in 19 stable hemodialysis patients, with a mean age of 63 years (range, 36-85), who had been on hemodialysis for 19 months (range, 6-47). Patients were randomised to receive NCCaAc or ECCaAc, with meals, for a period of 10 weeks and after ® cross-over for another 10 weeks. During a third non-blinded period, patients received Phos-ex for 10 weeks. Results: Serum phosphate was significantly higher with ECCaAc compared to NCCaAc (1.8960.07 vs. 1.7060.08 ® mmol / l, P , 0.05). Serum Ca was significantly lower with ECCaAc compared to NCCaAc or Phos-ex (2.3860.04, 2.4760.04 and 2.4860.04 mmol / l, P , 0.05). There were less hypercalcemic and more hyperphosphatemic events in the ECCaAc period, compared to the other periods. The daily CaAc dose and dietary intake of calcium, phosphate, protein and ® calories were comparable in all three periods. With Phos-ex , patients noticed more gastro-intestinal complaints than with to ® NCCaAc and ECCaAc. Two patients stopped taking Phos-ex because of side effects. Conclusions: In hemodialysis patients, phosphate control and tolerance were both influenced by the formulation of CaAc. Although phosphate control was adequate with all three formulations of CaAc, ECCaAc was less effective compared to ® ® NCCaAc or Phos-ex. NCCaAc and ECCaAc were better tolerated than Phos-ex. Regarding efficacy and tolerance, NCCaAc was the best calcium acetate formulation.
Transplantation, Jan 13, 2018
There is no consensus in the literature on the interpretation of single antigen bead (SAB) positi... more There is no consensus in the literature on the interpretation of single antigen bead (SAB) positive for a specific HLA antibody. To inform the debate, we studied the relationship between various SAB positivity algorithms and the impact of resulting donor-specific HLA antibody (DSA) positivity on long-term kidney graft survival in 3237 deceased-donor transplants. First, we showed that the interassay variability can be greatly reduced when working with signal-to-background ratios instead of absolute MFIs. Next, we determined pretransplant DSA using various MFI cut-offs, signal-to-background ratios (STBR) and combinations thereof. The impact of the various cut-offs was studied by comparing the graft survival between the DSA-positive and DSA-negative groups. We did not observe a strong impact of various cut-off levels on 10-year graft survival. A stronger relationship between the cut-off level and 1-year graft survival for DSA-positive transplants was found when using STBR, most pronoun...
Transplantation, 2008
MONDAY a mean of 367,000 cells per spheroid. This is in direct contrast to other systems that use... more MONDAY a mean of 367,000 cells per spheroid. This is in direct contrast to other systems that use longer time windows to allow for cell adherence to the scaffolding. Upon, histological examination of the spheroids cultured in the RWV, we found in the H&E and TEM that these spheroids exhibited multicelluar structures, and close cell-cell contact. Upon further characterization of these spheroids we were able to observe that 3 day spheroids retain their undifferentiated stem cell characteristics (ability to differentiate into multiple lineages and expression of stem cell markers). This was evidenced by these spheroids being induced to chondrogenic (collagen II). osteogenic (von Kossa). and adipogenic (oil red staining) differentiation by day 7 after induction, in the presence of lineage specifi c differentiation media respectively. Although preliminary, these results describe a novel model for the utilization of patient derived hMSC as cellular therapy for organ repair. Mesenchymal stem cells are found in abundance in bone marrow and may be easily harvested from bone marrow thereby avoid rejection episodes and the waiting time for a cadaveric donor. These results offer a strong case for exploring the possibilities that hMSCs when harvested from the patients own bone marrow, introduced to the RWV system, and transplanted in to a differentiation inducing media could be a link for in vivo and or in vitro regeneration of organs for transplantation MONDAY-ORAL ABSTRACTS (CONTINUED)
Transplantation, 2006
Morbidity and mortality due to cardiovascular disease are major problems after renal transplantat... more Morbidity and mortality due to cardiovascular disease are major problems after renal transplantation. The effects of three immunosuppressive protocols on cardiovascular end points were investigated in a single-center, randomized, parallel (1-1-1) group. Acute rejection was a secondary safety endpoint. Groups were as follows: group one, tacrolimusϩsirolimus; group two, tacrolimusϩmycophenolate mofetil (MMF); group three, sirolimusϩMMFϩdaclizumab. All groups received two days methylprednisolone only. The Ethical Committee demanded an interim analysis when 50% of the patients were included. In this analysis, 54 patients with a median follow-up of 9.2 months were studied. The Kaplan-Meyer analysis showed a difference in rejection free survival between group one (82%) and group three (34%, Pϭ0.03) and between groups one and two (tacrolimus-based, 76%) and group three (calcineurin-free, 34%, Pϭ0.04). Calcineurin-free immunosuppression with two days of steroids only showed an unacceptable high incidence of acute rejection and re-rejection, and the study had to be stopped.
Nephrology Dialysis Transplantation, 2018
Background Few studies have evaluated the effect of different immunosuppressive strategies on lon... more Background Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients. Methods We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis. Results Three regimes were u...
Peritoneal Dialysis International, 2015
A 66-year-old peritoneal dialysis (PD) patient presented with new-onset edema, weight gain, hypot... more A 66-year-old peritoneal dialysis (PD) patient presented with new-onset edema, weight gain, hypotension, and oliguria 5 weeks after influenza vaccination (Vaxigrip; Sanofi Pasteur MSD, Gouda, The Netherlands). Her medical history included end-stage renal disease (ESRD) due to IgA nephropathy, and breast cancer treated in 2009 with no evidence of recurrence on mammography 6 weeks before presentation. One year ago, she had similar but milder symptoms 1 week after the same type of influenza vaccination, which responded well to conservative treatment without hospitalization. The patient did well on her PD regimen, which consisted of 3 nocturnal cycles of biocompatible dialysate solution, icodextrin during the day, and an extra manual exchange with amino-acid based solution in the evening. She had a residual diuresis of 1,700 mL per day, and there was zero net ultrafiltration. Hypertension was controlled with telmisartan and lercanidipine. She presented to the dialysis unit with hypotension (blood pressure 80/60 mmHg), complete anuria for the previous 2 days, weight gain of 4 kg, and peripheral edema without elevated jugular venous pressure. Accompanying symptoms were a non-productive cough for 1 week, diffuse myalgia, and loss of appetite. Laboratory analysis revealed hypoalbuminemia, increased hemoglobin, and increased serum creatinine (Table 1). Chest X ray was unremarkable. Apart from flu-like symptoms, there were no clinical signs of infection and/ or sepsis, and C-reactive protein was not elevated (Table 1). Transthoracic echocardiography revealed a marked inspiratory collapse of the inferior vena cava as well as a normal left ventricular ejection fraction. Serology was negative for influenza, parainfluenza, echovirus, Coxsackievirus, respiratory syncytial virus, adenovirus, mycoplasma pneumoniae, chlamydia pneumoniae, legionella pneumophila, and Coxiella burnettii. There
American Journal of Transplantation, 2019
Allocation to highly sensitized patients based on acceptable mismatches results in low rejection ... more Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to non-sensitized patients
Frontiers in Immunology, 2021
CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by s... more CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA ...
American Journal of Transplantation, 2019
Nephrology Dialysis Transplantation, 2018
Frontiers in immunology, 2018
Individual HLA mismatches may differentially impact graft survival after kidney transplantation. ... more Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor-recipient couples that were transplanted between 1995 and 2005. For these donors-recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04-1.23, = 0.003]. When analyzing a subgroup of patients who had their first transpl...
Nephrology Dialysis Transplantation, 2007
Journal of the American Society of Nephrology, 2011
Clinical Journal of the American Society of Nephrology, 2012
BMJ (Clinical research ed.), Jan 24, 2014
To examine risk of malignancy and death in patients with kidney transplant who receive the immuno... more To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus. Systematic review and meta-analysis of individual patient data. Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013. Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival. The search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a ...
Transplantation Journal, 2004
The Patient - Patient-Centered Outcomes Research, 2017
Background The aim of this study was to develop, together with the Lung Foundation Netherlands an... more Background The aim of this study was to develop, together with the Lung Foundation Netherlands and Dutch Kidney Patients Association, patients and clinicians, a measure to evaluate patient experiences with the orphan drugs pirfenidone (for idiopathic pulmonary fibrosis [IPF]) and eculizumab (for atypical haemolytic uraemic syndrome [aHUS]), as well as a generic measure of patient experiences and satisfaction with medications. Methods Development of the Patient Experiences and Satisfaction with Medications (PESaM) questionnaire consisted of four phases: literature review (phase I); focus groups and individual patient interviews (phase II); item generation (phase III); and face and content validity testing (phase IV). Literature review aimed to identify existing disease-specific and generic patient experience measures to provide guidance on the domains of medication use relevant to patients, the number of items and type of response categories, and to generate an initial pool of items. Subsequent focus groups and patient interviews were conducted to gain insight into the perceived effectiveness of the therapies, the burden of side effects, and how the medication impacted on a patient's daily life. Focus groups and interviews were recorded and transcribed verbatim.
The Netherlands Journal of Medicine, 1999
Background: Calcium acetate (CaAc) is an effective phosphate binder in patients with chronic rena... more Background: Calcium acetate (CaAc) is an effective phosphate binder in patients with chronic renal failure. However, an ® important side effect is gastro-intestinal discomfort. Phos-ex (Cablon, The Netherlands) is the only commercially available non-coated CaAc formulation in our country. We developed two new CaAc formulations: neutral-coated CaAc (NCCaAc) and enteric-coated CaAc (ECCaAc). Methods: In a randomised double-blinded cross-over trial we compared efficacy and tolerance of the three formulations in 19 stable hemodialysis patients, with a mean age of 63 years (range, 36-85), who had been on hemodialysis for 19 months (range, 6-47). Patients were randomised to receive NCCaAc or ECCaAc, with meals, for a period of 10 weeks and after ® cross-over for another 10 weeks. During a third non-blinded period, patients received Phos-ex for 10 weeks. Results: Serum phosphate was significantly higher with ECCaAc compared to NCCaAc (1.8960.07 vs. 1.7060.08 ® mmol / l, P , 0.05). Serum Ca was significantly lower with ECCaAc compared to NCCaAc or Phos-ex (2.3860.04, 2.4760.04 and 2.4860.04 mmol / l, P , 0.05). There were less hypercalcemic and more hyperphosphatemic events in the ECCaAc period, compared to the other periods. The daily CaAc dose and dietary intake of calcium, phosphate, protein and ® calories were comparable in all three periods. With Phos-ex , patients noticed more gastro-intestinal complaints than with to ® NCCaAc and ECCaAc. Two patients stopped taking Phos-ex because of side effects. Conclusions: In hemodialysis patients, phosphate control and tolerance were both influenced by the formulation of CaAc. Although phosphate control was adequate with all three formulations of CaAc, ECCaAc was less effective compared to ® ® NCCaAc or Phos-ex. NCCaAc and ECCaAc were better tolerated than Phos-ex. Regarding efficacy and tolerance, NCCaAc was the best calcium acetate formulation.
Transplantation, Jan 13, 2018
There is no consensus in the literature on the interpretation of single antigen bead (SAB) positi... more There is no consensus in the literature on the interpretation of single antigen bead (SAB) positive for a specific HLA antibody. To inform the debate, we studied the relationship between various SAB positivity algorithms and the impact of resulting donor-specific HLA antibody (DSA) positivity on long-term kidney graft survival in 3237 deceased-donor transplants. First, we showed that the interassay variability can be greatly reduced when working with signal-to-background ratios instead of absolute MFIs. Next, we determined pretransplant DSA using various MFI cut-offs, signal-to-background ratios (STBR) and combinations thereof. The impact of the various cut-offs was studied by comparing the graft survival between the DSA-positive and DSA-negative groups. We did not observe a strong impact of various cut-off levels on 10-year graft survival. A stronger relationship between the cut-off level and 1-year graft survival for DSA-positive transplants was found when using STBR, most pronoun...
Transplantation, 2008
MONDAY a mean of 367,000 cells per spheroid. This is in direct contrast to other systems that use... more MONDAY a mean of 367,000 cells per spheroid. This is in direct contrast to other systems that use longer time windows to allow for cell adherence to the scaffolding. Upon, histological examination of the spheroids cultured in the RWV, we found in the H&E and TEM that these spheroids exhibited multicelluar structures, and close cell-cell contact. Upon further characterization of these spheroids we were able to observe that 3 day spheroids retain their undifferentiated stem cell characteristics (ability to differentiate into multiple lineages and expression of stem cell markers). This was evidenced by these spheroids being induced to chondrogenic (collagen II). osteogenic (von Kossa). and adipogenic (oil red staining) differentiation by day 7 after induction, in the presence of lineage specifi c differentiation media respectively. Although preliminary, these results describe a novel model for the utilization of patient derived hMSC as cellular therapy for organ repair. Mesenchymal stem cells are found in abundance in bone marrow and may be easily harvested from bone marrow thereby avoid rejection episodes and the waiting time for a cadaveric donor. These results offer a strong case for exploring the possibilities that hMSCs when harvested from the patients own bone marrow, introduced to the RWV system, and transplanted in to a differentiation inducing media could be a link for in vivo and or in vitro regeneration of organs for transplantation MONDAY-ORAL ABSTRACTS (CONTINUED)
Transplantation, 2006
Morbidity and mortality due to cardiovascular disease are major problems after renal transplantat... more Morbidity and mortality due to cardiovascular disease are major problems after renal transplantation. The effects of three immunosuppressive protocols on cardiovascular end points were investigated in a single-center, randomized, parallel (1-1-1) group. Acute rejection was a secondary safety endpoint. Groups were as follows: group one, tacrolimusϩsirolimus; group two, tacrolimusϩmycophenolate mofetil (MMF); group three, sirolimusϩMMFϩdaclizumab. All groups received two days methylprednisolone only. The Ethical Committee demanded an interim analysis when 50% of the patients were included. In this analysis, 54 patients with a median follow-up of 9.2 months were studied. The Kaplan-Meyer analysis showed a difference in rejection free survival between group one (82%) and group three (34%, Pϭ0.03) and between groups one and two (tacrolimus-based, 76%) and group three (calcineurin-free, 34%, Pϭ0.04). Calcineurin-free immunosuppression with two days of steroids only showed an unacceptable high incidence of acute rejection and re-rejection, and the study had to be stopped.
Nephrology Dialysis Transplantation, 2018
Background Few studies have evaluated the effect of different immunosuppressive strategies on lon... more Background Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients. Methods We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis. Results Three regimes were u...
Peritoneal Dialysis International, 2015
A 66-year-old peritoneal dialysis (PD) patient presented with new-onset edema, weight gain, hypot... more A 66-year-old peritoneal dialysis (PD) patient presented with new-onset edema, weight gain, hypotension, and oliguria 5 weeks after influenza vaccination (Vaxigrip; Sanofi Pasteur MSD, Gouda, The Netherlands). Her medical history included end-stage renal disease (ESRD) due to IgA nephropathy, and breast cancer treated in 2009 with no evidence of recurrence on mammography 6 weeks before presentation. One year ago, she had similar but milder symptoms 1 week after the same type of influenza vaccination, which responded well to conservative treatment without hospitalization. The patient did well on her PD regimen, which consisted of 3 nocturnal cycles of biocompatible dialysate solution, icodextrin during the day, and an extra manual exchange with amino-acid based solution in the evening. She had a residual diuresis of 1,700 mL per day, and there was zero net ultrafiltration. Hypertension was controlled with telmisartan and lercanidipine. She presented to the dialysis unit with hypotension (blood pressure 80/60 mmHg), complete anuria for the previous 2 days, weight gain of 4 kg, and peripheral edema without elevated jugular venous pressure. Accompanying symptoms were a non-productive cough for 1 week, diffuse myalgia, and loss of appetite. Laboratory analysis revealed hypoalbuminemia, increased hemoglobin, and increased serum creatinine (Table 1). Chest X ray was unremarkable. Apart from flu-like symptoms, there were no clinical signs of infection and/ or sepsis, and C-reactive protein was not elevated (Table 1). Transthoracic echocardiography revealed a marked inspiratory collapse of the inferior vena cava as well as a normal left ventricular ejection fraction. Serology was negative for influenza, parainfluenza, echovirus, Coxsackievirus, respiratory syncytial virus, adenovirus, mycoplasma pneumoniae, chlamydia pneumoniae, legionella pneumophila, and Coxiella burnettii. There
American Journal of Transplantation, 2019
Allocation to highly sensitized patients based on acceptable mismatches results in low rejection ... more Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to non-sensitized patients
Frontiers in Immunology, 2021
CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by s... more CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA ...
American Journal of Transplantation, 2019
Nephrology Dialysis Transplantation, 2018
Frontiers in immunology, 2018
Individual HLA mismatches may differentially impact graft survival after kidney transplantation. ... more Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor-recipient couples that were transplanted between 1995 and 2005. For these donors-recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04-1.23, = 0.003]. When analyzing a subgroup of patients who had their first transpl...
Nephrology Dialysis Transplantation, 2007
Journal of the American Society of Nephrology, 2011
Clinical Journal of the American Society of Nephrology, 2012
BMJ (Clinical research ed.), Jan 24, 2014
To examine risk of malignancy and death in patients with kidney transplant who receive the immuno... more To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus. Systematic review and meta-analysis of individual patient data. Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013. Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival. The search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a ...
Transplantation Journal, 2004