scholarly journals A predictive nomogram for choosing tacrolimus or cyclosporine as immunosuppression drugs for pediatric recipients after liver transplantation

2021 ◽  
Author(s):  
Junda Gao ◽  
Tao Zhou ◽  
Zhipeng Zong ◽  
guangxiang gu ◽  
Jianjun Zhang
Keyword(s):  
Calcineurin Inhibitors ◽  
Well Performance ◽  
Post Transplantation ◽  
Discriminative Performance ◽  
Decision Curve Analysis ◽  
Clinical Model ◽  
School Of Medicine ◽  
First Choice ◽  
Application Potential ◽  
Pediatric Recipients

Background: Tacrolimus (TAC) is the first choice of calcineurin inhibitors (CNIs) for recipients after pediatric LT. But there are some special pediatric recipients present an unsatisfied prognosis with the therapy of TAC. We aimed to construct a simple clinical model to predict the effectiveness of TAC in recipients after pediatric LT and help clinicians to choose CsA for an alternative quickly. Methods: Patients who received pediatric LT from 2006 to 2019 at RenJi Hospital, Shanghai Jiaotong University School of Medicine were included in this study. Retrospective data, including demographics, comorbidities, pre-operative lab values, outcome based on post-transplantation events were collected. A nomogram estimating the risk of poor curative effects of those recipients who receive an IS protocol based on TAC was constructed using multivariate logist regression analysis. Results: A total of 2032 recipients were included in this study. Seven parameters (recipient CYP type, cholangitis before LT, GRWR, spleen long diameter, serum albumin, graft volume reduction, donor CYP type) were used to construct the nomogram. The nomogram showed good discriminative performance with the area under receiver operating characteristic (ROC) curve (AUC) of 74.5%, and good calibration. Decision curve analysis demonstrated that the model had a high clinical application potential. Conclusions: A simple clinical model with well performance in predicting the risk of poor curative effects of those recipients who receive an IS protocol based on TAC was constructed. The nomogram can help clinicians quickly choose CsA as an alternative if there are high risks.

scholarly journals Timing of Initiation of Calcineurin Inhibitors in Pediatric Haploidentical Transplantation with Post-Transplantation Cyclophosphamide: Effects on Survival, Relapse, and Cytokine Release Syndrome

2021 ◽  
Author(s):  
Vedat Uygun ◽  
Gülsün Karasu ◽  
Koray Yalçın ◽  
Seda Ozturkmen ◽  
Hayriye Daloğlu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Calcineurin Inhibitors ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Post Transplantation ◽  
Acceptable Alternative ◽  
Haploidentical Transplantation ◽  
Timing Of Initiation ◽  
Overall Survival Analysis ◽  
Matched Donor

Background: The use of unmanipulated haploidentical stem cell transplantations (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) in children has emerged as an acceptable alternative to the patients without a matched donor. However, the timing of calcineurin inhibitors (CNI) used in combination with PTCY is increasingly becoming a topic of controversy. Method: We evaluated 49 children with acute leukemia who underwent unmanipulated haplo-HSCT with PTCY according to the initiation day of CNIs (pre- or post-CY). Results: There were no significant differences in the overall survival analysis between the two groups. The cumulative incidence of relapse at 2 years was 21.2% in the pre-CY group and 38.9% in the post-CY group (p=0.33). Cytokine release syndrome (CRS) was observed more frequently in the post-CY group (p=0.04). The OS and EFS at 2 years in patients with and without CRS in the pre-Cy group were 42.9% vs 87.5% (p=0.04) and 38.1% vs 87.5% (p=0.04), respectively. Conclusion: Our study shows that the argument for starting CNI administration after CY is tenuous, and the rationale for not starting CNI before CY needs to be reconsidered.

Post-transplantation growth among pediatric recipients of liver transplantation

2005 ◽  
Vol 9 (4) ◽  
pp. 480-485 ◽  
Author(s):  
Idris V.R. Evans ◽  
Steven H. Belle ◽  
Yuling Wei ◽  
Carol Penovich ◽  
Kris Ruppert ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Post Transplantation ◽  
Pediatric Recipients

scholarly journals Timing of Initiation of Calcineurin Inhibitors in Pediatric Haploidentical Transplantation with Post-Transplantation Cyclophosphamide: Effects on Survival, Relapse, and Cytokine Release Syndrome

2021 ◽  
Author(s):  
Vedat Uygun ◽  
Gulsun Karasu ◽  
Koray Yalçın ◽  
Seda Öztürkmen ◽  
Hayriye Daloglu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Calcineurin Inhibitors ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Post Transplantation ◽  
Acceptable Alternative ◽  
Haploidentical Transplantation ◽  
Timing Of Initiation ◽  
Overall Survival Analysis ◽  
Matched Donor

Abstract The use of unmanipulated haploidentical stem cell transplantations (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) in children has emerged as an acceptable alternative to the patients without a matched donor. However, the timing of calcineurin inhibitors (CNI) used in combination with PTCY is increasingly becoming a topic of controversy. We evaluated 49 children with acute leukemia who underwent unmanipulated haplo-HSCT with PTCY according to the initiation day of CNIs (pre- or post-CY). There were no significant differences in the overall survival analysis between the two groups. The cumulative incidence of relapse at 2 years was 21.2% in the pre-CY group and 38.9% in the post-CY group (p = 0.33). Cytokine release syndrome (CRS) was observed more frequently in the post-CY group. Our study shows that the argument for starting CNI administration after CY is tenuous, and the rationale for not starting CNI before CY needs to be reconsidered.

scholarly journals Specialty Career Preferences among Final Year Medical Students at the School of Medicine, Makerere University College of Health Sciences, Uganda

2020 ◽  
Author(s):  
Job Kuteesa ◽  
Victor Musiime ◽  
Ian G. Munabi ◽  
Aloysius G. Mubuuke ◽  
Robert Opoka ◽  
...  
Keyword(s):  
Medical Students ◽  
Career Guidance ◽  
Health Sciences ◽  
Focus Group Discussions ◽  
Group Discussions ◽  
Makerere University ◽  
School Of Medicine ◽  
Factors Influencing ◽  
First Choice ◽  
Career Preferences

Abstract Background : Uganda has an imbalanced distribution of the health workforce, which may be influenced by the specialty career preferences of medical students. In spite of this, there is inadequate literature concerning the factors influencing specialty career preferences in our setting. We aimed to determine the specialty career preferences and the factors influencing the preferences among final year medical students in the School of Medicine, Makerere University College of Health Sciences (MakCHS). Methods: A sequential explanatory mixed methods study design with a descriptive cross-sectional study followed by a qualitative study was used. A total of 135 final year medical students in MakCHS were recruited using consecutive sampling. Self-administered questionnaires and three focus group discussions were conducted. Quantitative data was analysed in STATA version 13 (StataCorp, College Station, Tx, USA) using descriptive statistics, chi-square tests and logistic regression. Qualitative data was analysed in NVIVO version 12 (QRS International, Cambridge, MA) using content analysis. Results: Of 135 students 91 (67.4%) were male and their median age was 24 years (IQR: 24, 26). As a first choice, the most preferred specialty career was obstetrics and gynecology (34/135, 25.2%), followed by surgery (27/135, 20.0%), pediatrics (18/135, 13.3%) and internal medicine (17/135, 12.6%). Non-established specialties such as anesthesia and Ear Nose and Throat (ENT) were not selected as a first choice by any student. Female students had 63% less odds of selecting surgical related specialties compared to males (aOR=0.37, 95%CI: 0.17-0.84) . The focus group discussions highlighted controlled lifestyle, assurance of a good life through better financial remuneration and inspirational specialists as facilitators for specialty preference. Bad experience during the clinical rotations, lack of career guidance plus perceived poor and miserable specialists were highlighted as barriers to specialty preference. Conclusion. Obstetrics and Gynecology, Surgery, Pediatrics and Internal Medicine are well-established disciplines, which were dominantly preferred. Females were less likely to select surgical disciplines given the perceived effects on lifestyle by these disciplines for example interruption of family life. Therefore, a need to formulate career guidance and mentorship programs is required, to attract students to the neglected disciplines.

scholarly journals Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort

2020 ◽  
Vol 9 (11) ◽  
pp. 3479 ◽  
Author(s):  
Dominique Bertrand ◽  
Florian Terrec ◽  
Isabelle Etienne ◽  
Nathalie Chavarot ◽  
Rebecca Sberro ◽  
...  
Keyword(s):  
Opportunistic Infections ◽  
Real Life ◽  
Calcineurin Inhibitors ◽  
Pneumocystis Pneumonia ◽  
Post Transplantation ◽  
Infectious Risk ◽  
Real Life Setting ◽  
Cmv Disease ◽  
Cmv Dnaemia

Conversion from calcineurin-inhibitors (CNIs) to belatacept can help kidney-transplant (KT) recipients avoid CNI-related nephrotoxicity. The risk of associated opportunistic infections (OPIs) is ill-defined. We conducted a multicentric cohort study across 15 French KT-centers in a real-life setting. Between 07-2010 and 07-2019, 453 KT recipients were converted from CNI- to belatacept-based therapy at 19 [0.13–431] months post-transplantation. Most patients, i.e., 332 (79.3%), were converted after 6-months post-transplantation. Follow-up time after conversion was 20.1 +/− 13 months. OPIs developed in 42(9.3%) patients after 14 +/− 12 months post-conversion. Eight patients (19%) had two OPI episodes during follow-up. Incidences of CMV DNAemia and CMV disease were significantly higher in patients converted before 6-months post-KT compared to those converted later (i.e., 31.6% vs. 11.5%; p < 0.001; and 11.6% vs. 2.4%, p < 0.001, respectively). Cumulative incidence of OPIs was 6.5 OPIs/100 person–years. Incidence of CMV disease was 2.8/100 person–years, of pneumocystis pneumonia 1.6/100 person–years, and of aspergillosis 0.2/100 person–years. Multivariate analyses showed that estimated glomerular filtration (eGFR) < 25 mL/min/1.73 m2 at conversion was independently associated with OPIs (HR = 4.7 (2.2 − 10.3), p < 0.001). The incidence of EBV DNAemia was 17.3 events /100 person–years. At 1-year post-conversion, mean eGFR had significantly increased from 32.0 +/− 18 mL/min/1.73 m2 to 42.2 +/− 18 mL/min/1.73 m2 (p < 0.0001). Conversion to belatacept is an effective strategy with a low infectious risk.

Concomitant Thrombotic Microangiopathy and Rejection in a Recent Kidney Transplant: A Case Study

2020 ◽  
pp. 1-4
Author(s):  
Muhammad A. Bukhari ◽  
Abdulaziz Al-Thumali ◽  
El-Sadig Yousif ◽  
Muhammad A. Bukhari ◽  
Najla K Almalki ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Thrombotic Microangiopathy ◽  
De Novo ◽  
Kidney Transplant Recipient ◽  
Calcineurin Inhibitors ◽  
Armed Forces ◽  
Post Transplantation ◽  
Medical Interventions ◽  
Antibody Mediated Rejection ◽  
Life Threatening

Thrombotic microangiopathy (TMA) is an uncommon, life-threatening complication that adversely affects kidney transplant recipient and allograft survival. Post-transplantation TMA can occur as recurrence of the primary TMA or as a de novo condition. The latter can be triggered by numerous factors post-transplantation including calcineurin inhibitors, certain infections and antibody-mediated rejection. Rejection-associated TMAs carry a significantly lower graft survival rate compared with post-transplant TMAs that are not associated with rejection. In this case report, we present a rare case of rejection-associated TMA in a recently transplanted renal allograft that was managed in Al-Hada Armed Forces Hospital. Despite the poor expected outcome of this condition; the patient was successfully treated after early initiation of medical interventions. Transplantation teams may face many challenges managing such a combination of medical conditions, which may halt pursuing appropriate diagnostic and therapeutic measures in a timely fashion. This article highlights some of these challenges for better understanding of such a complex condition.

The Economic Burden of Post-transplant Events in Renal Transplant Recipients

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Gihan Hamdy Elsisi
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Real Life ◽  
Calcineurin Inhibitors ◽  
Therapeutic Index ◽  
Medical Community ◽  
Blood Levels ◽  
Renal Transplant Recipients ◽  
Post Transplantation ◽  
Stage Renal Disease

Kidney transplantation (KT) is considered the optimum treatment choice for end stage renal disease (ESRD) both from a clinical and economic perspective. The incidence of acute rejection (AR) from KD could differ according to different patient and donor characteristic, as well as, the type of immunosuppressant agent allocated. Thus, it is crucial to carefully examine the costs associated with the type of immunosuppressant agents as they directly affect the clinical outcomes of recipients. Tacrolimus which is one of the Calcineurin inhibitors (CI) have proven a huge success in kidney transplantation and are considered the cornerstone therapy post transplantation. Since the expiry of its patent in 2008, generic versions have been introduced in the market. While it has been widely accepted in the medical community to switch from brand to generic drug products provided that they have proven therapeutic bioequivalence, the switch has been documents to be sensitive case with particular products which are characterized by a narrow therapeutic index (NTI). Their concern is that most of the bioequivalence studies are conducted in health volunteers’ whom do not suffer any comorbidity which is not the case in real life settings. González et al., 2017 note that this conversion affected its dose and blood levels which lead to the occurrence of acute rejection episodes due to under immunosuppression and report that infectious adverse events occurred as a result of over immunosuppression. Another important observation that there was a post serum creatinine increase after the formulation conversion and also patients experienced greater incidence of magnesium wasting, and more episodes of rejection which led to greater institutional costs of care. These findings highlight that cost containment policies need to be revisited especially with NTI drugs as their extra monitoring costs might actually off-set the savings of the generic product in the short term.

scholarly journals Radiomics for the Prediction of Epilepsy in Patients With Frontal Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ankang Gao ◽  
Hongxi Yang ◽  
Yida Wang ◽  
Guohua Zhao ◽  
Chenglong Wang ◽  
...  
Keyword(s):  
Cross Validation ◽  
Pearson Correlation ◽  
Characteristic Curve ◽  
Tumor Grade ◽  
Support Vector ◽  
Discriminative Performance ◽  
Adequate Treatment ◽  
Clinical Model ◽  
First Order ◽  
Texture Model

ObjectiveThis study was conducted in order to investigate the association between radiomics features and frontal glioma-associated epilepsy (GAE) and propose a reliable radiomics-based model to predict frontal GAE.MethodsThis retrospective study consecutively enrolled 166 adult patients with frontal glioma (111 in the training cohort and 55 in the testing cohort). A total 1,130 features were extracted from T2 fluid-attenuated inversion recovery images, including first-order statistics, 3D shape, texture, and wavelet features. Regions of interest, including the entire tumor and peritumoral edema, were drawn manually. Pearson correlation coefficient, 10-fold cross-validation, area under curve (AUC) analysis, and support vector machine were adopted to select the most relevant features to build a clinical model, a radiomics model, and a clinical–radiomics model for GAE. The receiver operating characteristic curve (ROC) and AUC were used to evaluate the classification performance of the models in each cohort, and DeLong’s test was used to compare the performance of the models. A two-sided t-test and Fisher’s exact test were used to compare the clinical variables. Statistical analysis was performed using SPSS software (version 22.0; IBM, Armonk, New York), and p &lt;0.05 was set as the threshold for significance.ResultsThe classification accuracy of seven scout models, except the wavelet first-order model (0.793) and the wavelet texture model (0.784), was &lt;0.75 in cross-validation. The clinical–radiomics model, including 17 magnetic resonance imaging-based features selected among the 1,130 radiomics features and two clinical features (patient age and tumor grade), achieved better discriminative performance for GAE prediction in both the training [AUC = 0.886, 95% confidence interval (CI) = 0.819–0.940] and testing cohorts (AUC = 0.836, 95% CI = 0.707–0.937) than the radiomics model (p = 0.008) with 82.0% and 78.2% accuracy, respectively.ConclusionRadiomics analysis can non-invasively predict GAE, thus allowing adequate treatment of frontal glioma. The clinical–radiomics model may enable a more precise prediction of frontal GAE. Furthermore, age and pathology grade are important risk factors for GAE.

Syngeneic and Allogeneic Hematopoietic Stem Cell Transplantation In Mice With Myelodysplastic Syndrome

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1515-1515
Author(s):  
Yang Jo Chung ◽  
Terry J Fry ◽  
Peter D Aplan
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Relapse Rate ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Clinical Model ◽  
Allogeneic Hsct ◽  
Relapse Rates

Abstract The myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies characterized by dysplasia, ineffective hematopoiesis and a propensity for progression to acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative therapy for the majority of patients. However, overall survival (OS) of patients with MDS following allogeneic HSCT is only about 40%, due to both relapse and non-relapse mortality (NRM) including graft versus host disease (GVHD). Available data suggests that long-term survival following HSCT for MDS is due both to myeloablative therapy and a graft versus tumor (GVT) effect. Mice that express a NUP98-HOXD13 (NHD13) transgene develop MDS with virtually 100% penetrance. In order to develop a pre-clinical model for the study of MDS HSCT, we transplanted NHD13 mice, which are bred on a C57 Bl6 background, with bone marrow harvested from syngeneic C57Bl6 donors. Sub lethally irradiated (650 rad) recipient NHD13 mice transplanted with syngeneic donor cells relapsed early, with no therapeutic benefit in terms of hematologic parameters in peripheral blood or survival. However, lethally irradiated (1000 rad) recipient mice that were transplanted with syngeneic donor bone marrow (BM) showed complete normalization of peripheral blood counts significantly enhanced survival (median survival of 15 months) compared with non-transplanted NHD13 mice (median survival 10 months). Although there were no detectable MDS cells for up to 38 weeks post-transplant, all mice eventually relapsed and died. In order to determine if a GVT effect could enhance survival, we performed 3 types of allogeneic HSCT with donor BM that was mismatched at minor histocompatibility antigen loci (C3H.SW x C57Bl6 donors); donor BM only, donor BM with donor splenocytes (6 x 10E06 CD3+ T cells), and donor BM with donor regulatory T cells (Treg). None of these forms of allogeneic HSCT let to enhanced survival compared to that achieved with syngeneic HSCT. The early relapse rate for allogeneic HSCT with donor BM only was decreased compared to the syngeneic HSCT group (8.3% vs 28% at post-transplantation week 6 and 17% vs 43% at post-transplantation week 16); however, the relapse rate at 38 weeks was similar between the two groups (83.3% vs 85.7%). Adding donor splenocytes, containing reactive T-cells, dramatically decreased the relapse rate, such that the relapse rate was only 20% at post-transplantation week 38, suggesting a GVT effect. This GVT effect was accompanied by a severe GVH effect, and OS was not different between the allogeneic BM + splenocyte and the syngeneic HSCT groups. In an attempt to induce a GVT effect without a severe GVHD, we transplanted allogeneic Treg cells along with allogeneic BM, however, survival and relapse rates were similar to those with allogeneic BM only. Taken together, these findings suggest that a lethal dose of ionizing radiation (1000 rads) is insufficient to eradicate the MDS initiating cell, and that transplantation of donor CD3+ splenocytes leads to decreased relapse rates, but at the cost of severe GVHD. We suggest that the NHD13 mice are a feasible pre-clinical model for the study of HSCT for MDS. Disclosures: No relevant conflicts of interest to declare.

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