We report our experience in ABO incompatible transplantations done in 13 patients since 2009. The transplantations have been across different blood group combinations. The pre conditioning of the patient was done as per the Japanese protocol. Follow up period has been from 4 weeks to 28 months. 2 patients had immediate antibody mediated rejection with loss of graft. The rest 11 patients have normal graft function without any complications. Successful ABO incompatible transplantation is feasible in our country without endangering the life of recipient with reasonable cost control. Further studies are required to modify the protocol to prevent immediate antibody mediated rejections (ABMR).
ABO incompatible living donor kidney transplantation - REVIEW in living donor...Maarten Naesens
- A 60-year old woman with blood type O and end-stage renal disease needed a kidney transplant urgently, but her husband who was willing to donate had blood type A, making them ABO incompatible.
- There were three options for transplantation: waiting 3 years for a deceased donor kidney, entering a paired exchange program, or doing an ABO incompatible transplant.
- Protocols for ABO incompatible transplantation have evolved over time, starting with splenectomy and plasmapheresis, and now typically involving rituximab, non-antigen specific immunoadsorption, and immunosuppression.
- While ABO incompatible transplantation has excellent graft outcomes, it does carry higher risks of complications and infections compared to compatible trans
ABO Incompatible Kidney Transplantation- a review with a perspective from a c...mionresearch
ABO incompatible kidney transplantation is performed all over the world in order to increase the donor pool and reduce the waiting time for kidney transplantation. The success of such transplantation depends on the desensitization at the time of transplantation. Although in the immediate post operative period more antibody mediated rejections are seen. The long term outcome is excellent comparable to the regular kidney transplantation. In a country like India, infections are a major problem related to excessive immunosupression. This article describes the present state of art in ABO incompatible kidney transplantations and the experience of a center from South India where 35 patients have undergone such transplantation.
ABO Incompatible Kidney Transplantation, Michael Casey, MD (W-0007)UF Nephrology
Welcome to the Division of Nephrology, Hypertension, & Renal Transplantation within the Department of Medicine at the University of Florida. The University of Florida is an exciting academic community filled with people passionate in their academic pursuit. The Division of Nephrology, Hypertension, & Renal Transplantation is distinguished by the impact, breadth, and depth of its clinical, training, and research programs. It is the Highest ranked Division of Nephrology within Florida, 13th top program nationally, and is comprised of distinguished faculty, all of whom are involved in patient care, research and education. Our research interests include cutting edge research and collaborations with Departments throughout the University.
For CME Credit, visit our website to register and complete the necessary requirements.
http://nephrology.medicine.ufl.edu
C5 Case Study Session of Three Long-Term Survivors with HIV Disease JayaweeraDSHS
This case study describes a 35-year-old man who presented with end-stage AIDS and liver disease requiring possible liver transplantation. He had HIV for over 10 years, as well as hepatitis B and C. His CD4 count was 69 and viral load was over 100,000. He had severe ascites, high bilirubin, low albumin, and elevated INR. After starting antiretroviral therapy, his viral load decreased and CD4 increased, allowing him to undergo liver transplantation. He had an uneventful recovery and suppression of both HIV and HBV.
Just released to the public domain: Results from use of HepQuant technology in a study of Ledipasvir/Sofosbuvir HCV antivirals.. “Early Improvement in the HepQuant®(HQ)-SHUNT Function Test during Treatment with Ledipasvir/Sofosbuvir in Liver Transplant Recipients with Allograft Fibrosis or Cirrhosis and Patients with Decompensated Cirrhosis who have not undergone Transplantation. O’Leary JG, Burton JR, Helmke SM, Herman A, Cookson MW, Lauriski S, Trotter JF, Denning JM, Pang PS, McHutchison JG, Everson GT. Hepatology 2014;60:1134A.”
Kazunari Tanabe - Japon - - Monday 28 - Alternatives to increase the number ...incucai_isodp
1) ABO-incompatible living donor kidney transplantation (ABOiLKT) has expanded the donor pool by up to 30% by allowing transplantation across ABO blood groups.
2) Recent outcomes of ABOiLKT have been excellent, with low incidence of acute and chronic antibody-mediated rejection seen on protocol biopsies, predicting good long-term outcomes.
3) B cell depleting treatments like rituximab or splenectomy have been effective in reducing acute and chronic rejection in ABOiLKT, leading to improved long-term graft survival comparable to ABO-compatible transplants.
This study compared renal allograft survival in patients with acute humoral rejection (AHR) treated with plasmapheresis and intravenous immunoglobulin to patients with acute cellular rejection (ACR). The study analyzed 286 kidney transplants performed between 1999-2001. 16 patients were diagnosed with AHR based on biopsy findings. These patients were more likely to be female, black, have received a deceased donor kidney, have a positive panel reactive antibody, and have received induction therapy. Most AHR patients were treated with plasmapheresis and intravenous immunoglobulin, while ACR patients received steroids or antilymphocyte therapy. One-year allograft survival was similar between AHR and ACR groups. The study
ABO incompatible living donor kidney transplantation - REVIEW in living donor...Maarten Naesens
- A 60-year old woman with blood type O and end-stage renal disease needed a kidney transplant urgently, but her husband who was willing to donate had blood type A, making them ABO incompatible.
- There were three options for transplantation: waiting 3 years for a deceased donor kidney, entering a paired exchange program, or doing an ABO incompatible transplant.
- Protocols for ABO incompatible transplantation have evolved over time, starting with splenectomy and plasmapheresis, and now typically involving rituximab, non-antigen specific immunoadsorption, and immunosuppression.
- While ABO incompatible transplantation has excellent graft outcomes, it does carry higher risks of complications and infections compared to compatible trans
ABO Incompatible Kidney Transplantation- a review with a perspective from a c...mionresearch
ABO incompatible kidney transplantation is performed all over the world in order to increase the donor pool and reduce the waiting time for kidney transplantation. The success of such transplantation depends on the desensitization at the time of transplantation. Although in the immediate post operative period more antibody mediated rejections are seen. The long term outcome is excellent comparable to the regular kidney transplantation. In a country like India, infections are a major problem related to excessive immunosupression. This article describes the present state of art in ABO incompatible kidney transplantations and the experience of a center from South India where 35 patients have undergone such transplantation.
ABO Incompatible Kidney Transplantation, Michael Casey, MD (W-0007)UF Nephrology
Welcome to the Division of Nephrology, Hypertension, & Renal Transplantation within the Department of Medicine at the University of Florida. The University of Florida is an exciting academic community filled with people passionate in their academic pursuit. The Division of Nephrology, Hypertension, & Renal Transplantation is distinguished by the impact, breadth, and depth of its clinical, training, and research programs. It is the Highest ranked Division of Nephrology within Florida, 13th top program nationally, and is comprised of distinguished faculty, all of whom are involved in patient care, research and education. Our research interests include cutting edge research and collaborations with Departments throughout the University.
For CME Credit, visit our website to register and complete the necessary requirements.
http://nephrology.medicine.ufl.edu
C5 Case Study Session of Three Long-Term Survivors with HIV Disease JayaweeraDSHS
This case study describes a 35-year-old man who presented with end-stage AIDS and liver disease requiring possible liver transplantation. He had HIV for over 10 years, as well as hepatitis B and C. His CD4 count was 69 and viral load was over 100,000. He had severe ascites, high bilirubin, low albumin, and elevated INR. After starting antiretroviral therapy, his viral load decreased and CD4 increased, allowing him to undergo liver transplantation. He had an uneventful recovery and suppression of both HIV and HBV.
Just released to the public domain: Results from use of HepQuant technology in a study of Ledipasvir/Sofosbuvir HCV antivirals.. “Early Improvement in the HepQuant®(HQ)-SHUNT Function Test during Treatment with Ledipasvir/Sofosbuvir in Liver Transplant Recipients with Allograft Fibrosis or Cirrhosis and Patients with Decompensated Cirrhosis who have not undergone Transplantation. O’Leary JG, Burton JR, Helmke SM, Herman A, Cookson MW, Lauriski S, Trotter JF, Denning JM, Pang PS, McHutchison JG, Everson GT. Hepatology 2014;60:1134A.”
Kazunari Tanabe - Japon - - Monday 28 - Alternatives to increase the number ...incucai_isodp
1) ABO-incompatible living donor kidney transplantation (ABOiLKT) has expanded the donor pool by up to 30% by allowing transplantation across ABO blood groups.
2) Recent outcomes of ABOiLKT have been excellent, with low incidence of acute and chronic antibody-mediated rejection seen on protocol biopsies, predicting good long-term outcomes.
3) B cell depleting treatments like rituximab or splenectomy have been effective in reducing acute and chronic rejection in ABOiLKT, leading to improved long-term graft survival comparable to ABO-compatible transplants.
This study compared renal allograft survival in patients with acute humoral rejection (AHR) treated with plasmapheresis and intravenous immunoglobulin to patients with acute cellular rejection (ACR). The study analyzed 286 kidney transplants performed between 1999-2001. 16 patients were diagnosed with AHR based on biopsy findings. These patients were more likely to be female, black, have received a deceased donor kidney, have a positive panel reactive antibody, and have received induction therapy. Most AHR patients were treated with plasmapheresis and intravenous immunoglobulin, while ACR patients received steroids or antilymphocyte therapy. One-year allograft survival was similar between AHR and ACR groups. The study
Crizotinib is a c-MET inhibitor that has demonstrated potent inhibitory activity against ALK fusion cells. The document discusses clinical trials of crizotinib in patients with ALK-positive non-small cell lung cancer (NSCLC). Results from Phase I and II trials showed an objective response rate of 57% and disease control rate of 87% with crizotinib. Current ongoing trials are evaluating crizotinib versus chemotherapy as first-line or second-line treatment in ALK-positive NSCLC.
Thalassemia Transplant Update. Dr. Suradej Hongengspa718
This document summarizes research on treatments for thalassemia, including hematopoietic stem cell transplantation (HSCT) and gene therapy. It discusses outcomes of HSCT using different donor types and conditioning regimens in Thailand. It also presents initial results from a gene therapy clinical trial showing production of gene-modified hemoglobin and polyclonal engraftment without safety issues in the first few treated patients. The research demonstrates favorable outcomes of HSCT for thalassemia and potential for gene therapy to cure patients by adding modified genes to their own blood stem cells.
This document summarizes clinical trial results of the oral ALK inhibitor crizotinib (PF-02341066) in patients with ALK-positive non-small cell lung cancer. The trial showed that crizotinib had significant clinical activity in ALK-positive NSCLC patients, with an objective response rate of 57% and disease control rate of 87%. The median progression-free survival was 10 months for these patients. In contrast, patients with ALK-negative NSCLC did not respond to crizotinib. These results provide evidence that crizotinib is an effective targeted therapy for patients with ALK-positive NSCLC.
The document analyzes antithrombin and protein C levels in 75 pediatric liver transplant patients to determine if low levels predict hepatic artery thrombosis (HAT). It found significantly lower levels of both proteins in patients who developed HAT compared to those who did not. Using cutoff levels, low antithrombin on the day of transplant was predictive of later HAT. Combined deficiencies in antithrombin and protein C may increase thrombosis risk more than individual deficiencies. Early supplementation with both proteins after transplant may help prevent HAT.
Austin Transplantation Sciences is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Transplantation Sciences.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all areas of Transplantation Sciences. Austin Transplantation Sciences accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of Transplantation Sciences.
Austin Transplantation Sciences strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Donor Selection: Unrealted donor transplant. Prof. Richard Champlinspa718
Richard Champlin is a professor and chair of the Department of Stem Cell Transplantation and Cellular Therapy at MD Anderson Cancer Center. He has over 30 years of experience in hematopoietic stem cell transplantation research. In this presentation, he discusses the pros and cons of different stem cell donor sources for transplantation including matched sibling, matched unrelated donor, cord blood, and haploidentical related donors. While matched siblings remain the preferred donor source, innovative strategies are improving outcomes with alternative donor sources like cord blood and haploidentical transplants. Prospective studies are still needed to directly compare outcomes between donor modalities.
This document discusses factors to consider when determining if hematopoietic cell transplantation is appropriate for adult acute lymphoblastic leukemia patients in first remission between ages 35-70 years. It notes that transplantation may be favored for those with high-risk clinical or laboratory features, a sibling donor match available, or residual minimal disease detected after induction. Reduced intensity conditioning may be preferred for older patients or those with comorbidities. Matched unrelated donors are generally favored over umbilical cord blood, unless a center has extensive cord blood transplant experience. The document paradoxically suggests that more intensive new induction regimens may increase the number of older patients eligible for transplantation.
Rituximab is a monoclonal antibody that depletes B cells and has been used to treat various immune-mediated renal diseases and in transplantation. It has shown benefits in refractory lupus nephritis, membranous nephropathy, and cryoglobulinemia in observational studies. However, randomized controlled trials in lupus nephritis did not show a significant benefit of rituximab over standard therapies. Rituximab has also been used successfully in ABO-incompatible and desensitization protocols in renal transplantation to reduce antibody levels, though trials on desensitization showed transient effects. Rituximab may improve outcomes for severe antibody-mediated rejection. Further large randomized trials are still
Rituximab as Induction Immunosuppression in Compatible Kidney Transplantation...Wisit Cheungpasitporn
Rituximab as Induction Therapy After Renal Transplantation: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety. This study evaluated the efficacy and safety of rituximab (RTX) as induction therapy in renal transplant patients. The study randomized 280 patients to receive either a single dose of RTX or placebo before transplantation. The primary outcome was biopsy-proven acute rejection within 6 months. The results showed no difference in rejection rates between the overall RTX and placebo groups. However, among high-immunological risk patients, RTX showed a trend toward lower rejection rates compared to placebo. Patient and graft survival did not differ between groups after
This study examined 4 soldiers with Plasmodium falciparum malaria who had a positive direct antiglobulin test, indicating Coombs'-positive hemolytic disease. In 3 patients, the positive Coombs' tests and hemolytic episodes seemed related to the administration of quinine used to treat relapsed malaria. Two of these patients experienced quinine-related skin reactions. The fourth patient had compensated hemolysis and a positive direct Coombs' test that was unrelated to quinine therapy. Coombs'-positive hemolytic disease is an unusual complication of malaria that clinical evidence suggests may be caused by quinine in some cases, though the mechanism is unknown.
Truvada Randomized Trial of HBIG Withdrawal February 7 2014Dr. Lewis Teperman
This randomized trial evaluated the safety and efficacy of withdrawing hepatitis B immune globulin (HBIG) prophylaxis and replacing it with emtricitabine/tenofovir (FTC/TDF) in liver transplant recipients with chronic hepatitis B infection. Over 2 years, no patients receiving FTC/TDF alone experienced hepatitis B virus recurrence or detectable HBsAg levels. Renal function remained stable or improved, and FTC/TDF was well-tolerated with no evidence of resistance. The results support the use of FTC/TDF without HBIG to prevent post-liver transplant HBV recurrence.
Crimson Publishers: Interferon-Free Therapy for Hepatits C in Brazil and Sust...CrimsonGastroenterology
Introduction: Hepatitis C has been treated with interferon and ribavirin for over a decade with described global sustained virological response rates of 33% to 56%. Direct acting antiviral drugs available since 2013 in USA and 2015 in Brazil are changing this reality.
Purpose: Analyze the real-life efficacy and safety of interferon-free therapy.
Methods: Repot six cases of different treatments guided by north-american and european guildelines.
Results: Every reported patient achieved sustained virological response. The only adverse event was anemia in one patient.
Conclusion: Direct-acting antiviral drugs will dramatically change the population which can be treated and increase sustained virological response rates.
Jose Maria Morales - Spain - Tuesday 29 - HLA for Renal Allocationincucai_isodp
1. The document discusses the benefits of HLA matching in renal transplantation and how HLA matching is essential for retransplantation and sensitized patients.
2. It presents data showing improved graft and patient survival with better HLA matching and with newer immunosuppressive drugs.
3. The use of older donors and recipients is discussed, along with strategies like "old for old" transplantation, to better utilize available donor organs while maintaining patient outcomes.
A case of severe autoimmune haemolytic anaemia due to clinically significant ...Apollo Hospitals
Anti N antibody belongs to the MNS blood group system. Usually, anti N antibodies are naturally occurring, cold agglutinins. Clinically significant anti N antibodies have also been reported. We report here a case of autoantibody with anti N specificity presenting with severe autoimmune haemolytic anaemia.
This document contains 120 clinical cases presented by Dr. Juan Carlos Díaz Torre, a pediatric neonatologist. Each case presents a patient scenario or medical issue and asks the reader to choose the most appropriate response from a list of options. The cases cover a wide range of topics in pediatrics, obstetrics/gynecology, family medicine and internal medicine.
The slides for my talk on 'Toxicological Myths and Half-Truths' that was given at the CICM ASM 2013 in Wellington, New Zealand. The theme of the conference was "Down with Dogma: Challenging the Fundamentals of Critical Care"
This document summarizes three patient cases involving liver failure:
1. A 40-year-old woman presented with abdominal pain and fatigue due to alcohol abuse and acetaminophen overdose. Her condition deteriorated rapidly and she underwent successful liver transplantation.
2. A 62-year-old man with cirrhosis presented with recurrent variceal bleeding and developed hepatorenal syndrome while awaiting transplantation. He was treated with TIPS and CRRT and ultimately received a liver.
3. A 52-year-old woman with autoimmune cirrhosis presented with symptoms of heart failure and was found to have pulmonary hypertension on echocardiogram. She was evaluated for liver transplantation.
Robert Orlowski is a professor of myeloma/lymphoma at MD Anderson Cancer Center who has published extensively on cancer therapy. His research focuses on translating promising laboratory findings into clinical trials for hematologic malignancies. The document summarizes several of his presentations and studies on new treatments for multiple myeloma and other plasma cell dyscrasias, including studies on carfilzomib, lenalidomide, and other novel agents alone and in combination for newly diagnosed, relapsed/refractory, and amyloidosis patients. It discusses efficacy and safety results and the changing treatment landscape in these diseases.
Membranous nephropathy (MN) is a glomerular disease characterized by subepithelial immune deposits causing nephrotic syndrome in many cases. It can be primary or secondary. Evaluation of secondary causes includes screening for autoimmune diseases, viral infections, malignancies and other underlying conditions. Treatment involves treating any identified secondary cause. For primary MN, supportive care is initially recommended, with immunosuppressive therapy considered for persistent high-risk disease. Treatment options include steroids, calcineurin inhibitors and alkylating agents. Close monitoring of response is important to guide management.
Development and Validation of a Two-Site Immunoradiometric assay for Glypican...Premier Publishers
This study aimed to develop and validate an immunoradiometric assay (IRMA) to measure glypican-3 (GPC3) levels in plasma samples and evaluate its diagnostic potential for hepatocellular carcinoma (HCC). The researchers established an IRMA to measure GPC3 and compared its performance to a commercial ELISA kit using plasma samples from 150 HCC patients, 150 hepatitis C patients, and 150 healthy controls. The IRMA showed better diagnostic accuracy than the ELISA kit for distinguishing HCC patients from controls and hepatitis C patients based on receiver operating characteristic analysis. Using the optimized IRMA, the study found that GPC3 levels could help discriminate HCC from hepatitis C with high sensitivity and specificity and was a
This document provides an overview of organ transplantation, including:
1. A brief history of transplantation from early experiments to modern developments in immunosuppression.
2. Definitions of different types of transplants including autotransplants, allotransplants, and xenotransplants.
3. A discussion of transplant immunobiology including allorecognition and the mechanisms of rejection.
4. Descriptions of different types of clinical rejection such as hyperacute, acute, and chronic rejection.
5. An overview of commonly used immunosuppressive drugs including corticosteroids, cyclosporine, and monoclonal antibodies.
Renal transplantation is the preferred treatment for end-stage renal disease as it offers better quality of life and longevity than long-term dialysis. Diabetic nephropathy accounts for 40% of diseases resulting in renal transplantation and patients with this condition are more prone to post-transplant complications. The transplantation process involves coordinating with transplant teams early, evaluating potential donors for conditions like HIV or malignancy, and managing physiological changes after brain death to preserve organ perfusion until transplantation. After transplantation, the kidney is placed in the lower abdomen and connected to blood vessels and the bladder, with acute rejection potentially occurring within the first three post-transplant months.
Crizotinib is a c-MET inhibitor that has demonstrated potent inhibitory activity against ALK fusion cells. The document discusses clinical trials of crizotinib in patients with ALK-positive non-small cell lung cancer (NSCLC). Results from Phase I and II trials showed an objective response rate of 57% and disease control rate of 87% with crizotinib. Current ongoing trials are evaluating crizotinib versus chemotherapy as first-line or second-line treatment in ALK-positive NSCLC.
Thalassemia Transplant Update. Dr. Suradej Hongengspa718
This document summarizes research on treatments for thalassemia, including hematopoietic stem cell transplantation (HSCT) and gene therapy. It discusses outcomes of HSCT using different donor types and conditioning regimens in Thailand. It also presents initial results from a gene therapy clinical trial showing production of gene-modified hemoglobin and polyclonal engraftment without safety issues in the first few treated patients. The research demonstrates favorable outcomes of HSCT for thalassemia and potential for gene therapy to cure patients by adding modified genes to their own blood stem cells.
This document summarizes clinical trial results of the oral ALK inhibitor crizotinib (PF-02341066) in patients with ALK-positive non-small cell lung cancer. The trial showed that crizotinib had significant clinical activity in ALK-positive NSCLC patients, with an objective response rate of 57% and disease control rate of 87%. The median progression-free survival was 10 months for these patients. In contrast, patients with ALK-negative NSCLC did not respond to crizotinib. These results provide evidence that crizotinib is an effective targeted therapy for patients with ALK-positive NSCLC.
The document analyzes antithrombin and protein C levels in 75 pediatric liver transplant patients to determine if low levels predict hepatic artery thrombosis (HAT). It found significantly lower levels of both proteins in patients who developed HAT compared to those who did not. Using cutoff levels, low antithrombin on the day of transplant was predictive of later HAT. Combined deficiencies in antithrombin and protein C may increase thrombosis risk more than individual deficiencies. Early supplementation with both proteins after transplant may help prevent HAT.
Austin Transplantation Sciences is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Transplantation Sciences.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all areas of Transplantation Sciences. Austin Transplantation Sciences accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of Transplantation Sciences.
Austin Transplantation Sciences strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Donor Selection: Unrealted donor transplant. Prof. Richard Champlinspa718
Richard Champlin is a professor and chair of the Department of Stem Cell Transplantation and Cellular Therapy at MD Anderson Cancer Center. He has over 30 years of experience in hematopoietic stem cell transplantation research. In this presentation, he discusses the pros and cons of different stem cell donor sources for transplantation including matched sibling, matched unrelated donor, cord blood, and haploidentical related donors. While matched siblings remain the preferred donor source, innovative strategies are improving outcomes with alternative donor sources like cord blood and haploidentical transplants. Prospective studies are still needed to directly compare outcomes between donor modalities.
This document discusses factors to consider when determining if hematopoietic cell transplantation is appropriate for adult acute lymphoblastic leukemia patients in first remission between ages 35-70 years. It notes that transplantation may be favored for those with high-risk clinical or laboratory features, a sibling donor match available, or residual minimal disease detected after induction. Reduced intensity conditioning may be preferred for older patients or those with comorbidities. Matched unrelated donors are generally favored over umbilical cord blood, unless a center has extensive cord blood transplant experience. The document paradoxically suggests that more intensive new induction regimens may increase the number of older patients eligible for transplantation.
Rituximab is a monoclonal antibody that depletes B cells and has been used to treat various immune-mediated renal diseases and in transplantation. It has shown benefits in refractory lupus nephritis, membranous nephropathy, and cryoglobulinemia in observational studies. However, randomized controlled trials in lupus nephritis did not show a significant benefit of rituximab over standard therapies. Rituximab has also been used successfully in ABO-incompatible and desensitization protocols in renal transplantation to reduce antibody levels, though trials on desensitization showed transient effects. Rituximab may improve outcomes for severe antibody-mediated rejection. Further large randomized trials are still
Rituximab as Induction Immunosuppression in Compatible Kidney Transplantation...Wisit Cheungpasitporn
Rituximab as Induction Therapy After Renal Transplantation: A Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety. This study evaluated the efficacy and safety of rituximab (RTX) as induction therapy in renal transplant patients. The study randomized 280 patients to receive either a single dose of RTX or placebo before transplantation. The primary outcome was biopsy-proven acute rejection within 6 months. The results showed no difference in rejection rates between the overall RTX and placebo groups. However, among high-immunological risk patients, RTX showed a trend toward lower rejection rates compared to placebo. Patient and graft survival did not differ between groups after
This study examined 4 soldiers with Plasmodium falciparum malaria who had a positive direct antiglobulin test, indicating Coombs'-positive hemolytic disease. In 3 patients, the positive Coombs' tests and hemolytic episodes seemed related to the administration of quinine used to treat relapsed malaria. Two of these patients experienced quinine-related skin reactions. The fourth patient had compensated hemolysis and a positive direct Coombs' test that was unrelated to quinine therapy. Coombs'-positive hemolytic disease is an unusual complication of malaria that clinical evidence suggests may be caused by quinine in some cases, though the mechanism is unknown.
Truvada Randomized Trial of HBIG Withdrawal February 7 2014Dr. Lewis Teperman
This randomized trial evaluated the safety and efficacy of withdrawing hepatitis B immune globulin (HBIG) prophylaxis and replacing it with emtricitabine/tenofovir (FTC/TDF) in liver transplant recipients with chronic hepatitis B infection. Over 2 years, no patients receiving FTC/TDF alone experienced hepatitis B virus recurrence or detectable HBsAg levels. Renal function remained stable or improved, and FTC/TDF was well-tolerated with no evidence of resistance. The results support the use of FTC/TDF without HBIG to prevent post-liver transplant HBV recurrence.
Crimson Publishers: Interferon-Free Therapy for Hepatits C in Brazil and Sust...CrimsonGastroenterology
Introduction: Hepatitis C has been treated with interferon and ribavirin for over a decade with described global sustained virological response rates of 33% to 56%. Direct acting antiviral drugs available since 2013 in USA and 2015 in Brazil are changing this reality.
Purpose: Analyze the real-life efficacy and safety of interferon-free therapy.
Methods: Repot six cases of different treatments guided by north-american and european guildelines.
Results: Every reported patient achieved sustained virological response. The only adverse event was anemia in one patient.
Conclusion: Direct-acting antiviral drugs will dramatically change the population which can be treated and increase sustained virological response rates.
Jose Maria Morales - Spain - Tuesday 29 - HLA for Renal Allocationincucai_isodp
1. The document discusses the benefits of HLA matching in renal transplantation and how HLA matching is essential for retransplantation and sensitized patients.
2. It presents data showing improved graft and patient survival with better HLA matching and with newer immunosuppressive drugs.
3. The use of older donors and recipients is discussed, along with strategies like "old for old" transplantation, to better utilize available donor organs while maintaining patient outcomes.
A case of severe autoimmune haemolytic anaemia due to clinically significant ...Apollo Hospitals
Anti N antibody belongs to the MNS blood group system. Usually, anti N antibodies are naturally occurring, cold agglutinins. Clinically significant anti N antibodies have also been reported. We report here a case of autoantibody with anti N specificity presenting with severe autoimmune haemolytic anaemia.
This document contains 120 clinical cases presented by Dr. Juan Carlos Díaz Torre, a pediatric neonatologist. Each case presents a patient scenario or medical issue and asks the reader to choose the most appropriate response from a list of options. The cases cover a wide range of topics in pediatrics, obstetrics/gynecology, family medicine and internal medicine.
The slides for my talk on 'Toxicological Myths and Half-Truths' that was given at the CICM ASM 2013 in Wellington, New Zealand. The theme of the conference was "Down with Dogma: Challenging the Fundamentals of Critical Care"
This document summarizes three patient cases involving liver failure:
1. A 40-year-old woman presented with abdominal pain and fatigue due to alcohol abuse and acetaminophen overdose. Her condition deteriorated rapidly and she underwent successful liver transplantation.
2. A 62-year-old man with cirrhosis presented with recurrent variceal bleeding and developed hepatorenal syndrome while awaiting transplantation. He was treated with TIPS and CRRT and ultimately received a liver.
3. A 52-year-old woman with autoimmune cirrhosis presented with symptoms of heart failure and was found to have pulmonary hypertension on echocardiogram. She was evaluated for liver transplantation.
Robert Orlowski is a professor of myeloma/lymphoma at MD Anderson Cancer Center who has published extensively on cancer therapy. His research focuses on translating promising laboratory findings into clinical trials for hematologic malignancies. The document summarizes several of his presentations and studies on new treatments for multiple myeloma and other plasma cell dyscrasias, including studies on carfilzomib, lenalidomide, and other novel agents alone and in combination for newly diagnosed, relapsed/refractory, and amyloidosis patients. It discusses efficacy and safety results and the changing treatment landscape in these diseases.
Membranous nephropathy (MN) is a glomerular disease characterized by subepithelial immune deposits causing nephrotic syndrome in many cases. It can be primary or secondary. Evaluation of secondary causes includes screening for autoimmune diseases, viral infections, malignancies and other underlying conditions. Treatment involves treating any identified secondary cause. For primary MN, supportive care is initially recommended, with immunosuppressive therapy considered for persistent high-risk disease. Treatment options include steroids, calcineurin inhibitors and alkylating agents. Close monitoring of response is important to guide management.
Development and Validation of a Two-Site Immunoradiometric assay for Glypican...Premier Publishers
This study aimed to develop and validate an immunoradiometric assay (IRMA) to measure glypican-3 (GPC3) levels in plasma samples and evaluate its diagnostic potential for hepatocellular carcinoma (HCC). The researchers established an IRMA to measure GPC3 and compared its performance to a commercial ELISA kit using plasma samples from 150 HCC patients, 150 hepatitis C patients, and 150 healthy controls. The IRMA showed better diagnostic accuracy than the ELISA kit for distinguishing HCC patients from controls and hepatitis C patients based on receiver operating characteristic analysis. Using the optimized IRMA, the study found that GPC3 levels could help discriminate HCC from hepatitis C with high sensitivity and specificity and was a
This document provides an overview of organ transplantation, including:
1. A brief history of transplantation from early experiments to modern developments in immunosuppression.
2. Definitions of different types of transplants including autotransplants, allotransplants, and xenotransplants.
3. A discussion of transplant immunobiology including allorecognition and the mechanisms of rejection.
4. Descriptions of different types of clinical rejection such as hyperacute, acute, and chronic rejection.
5. An overview of commonly used immunosuppressive drugs including corticosteroids, cyclosporine, and monoclonal antibodies.
Renal transplantation is the preferred treatment for end-stage renal disease as it offers better quality of life and longevity than long-term dialysis. Diabetic nephropathy accounts for 40% of diseases resulting in renal transplantation and patients with this condition are more prone to post-transplant complications. The transplantation process involves coordinating with transplant teams early, evaluating potential donors for conditions like HIV or malignancy, and managing physiological changes after brain death to preserve organ perfusion until transplantation. After transplantation, the kidney is placed in the lower abdomen and connected to blood vessels and the bladder, with acute rejection potentially occurring within the first three post-transplant months.
Kidney transplantation involves transplanting a kidney from a living or deceased donor into a patient with end-stage renal disease. There are several indications for kidney transplantation including chronic kidney failure, diabetes, and genetic disorders. Compatibility between donor and recipient is based on blood type and human leukocyte antigens. After transplantation, patients take immunosuppressant drugs to prevent rejection and have improved quality of life compared to dialysis. While transplantation carries risks of infection, rejection and side effects, it provides longer survival than remaining on dialysis.
Kidney transplantation is the most effective therapy for end-stage renal disease. It involves transplanting a kidney from a living or deceased donor. Immunosuppressive medications are used to prevent rejection and include corticosteroids, calcineurin inhibitors like cyclosporine and tacrolimus, mTOR inhibitors like sirolimus, and antimetabolites. Common post-transplant complications include infection from viruses like CMV and BK virus, acute rejection, chronic allograft dysfunction, and malignancy. Long-term management requires monitoring for these complications and adjusting immunosuppression.
Replication allows data from a MySQL master database to be synchronized with one or more slave databases. The master records all data changes in its binary log. Slave databases connect to the master and receive the binary log transactions, which they then apply locally to stay synchronized with the master database. Replication can be used for load balancing reads across multiple slave servers or for high availability by failing over to a slave if the master fails.
Longterm follow up of abo incompatible kidney transplantation-a study from indiamionresearch
Background: There is a need to do ABO incompatible kidney transplantation in a country like India where deceased donor transplantation is not common. More than 90% transplantations are
done with living donors. Although short term results have been reported from 4 centers, there is
paucity of data on long term follow-up of such patients. Methods: The data of 18 patients who had
undergone ABO incompatible transplantation exceeding a follow-up of 12 months up to 66 months
were analyzed. It was compared with the data of compatible kidney transplantation during the
same period. Results: In both the groups, there was a similar incidence of urinary tract infection
and gastroenteritis with complete recovery. Tuberculosis was successfully treated in 2 patients
who had undergone ABO incompatible transplantation. The graft function was excellent with an
average follow-up period of 38.2 months. There was no patient mortality during the follow-up period. Conclusion: The long term outcome of ABO incompatible kidney transplantation is similar to
compatible kidney transplantation despite the increased incidence of short term complications.
Newer Chemotherapy agents and renal toxicitykdj200
1. The document discusses various chemotherapy agents that can cause kidney toxicity, including cisplatin, methotrexate, gemcitabine, calcineurin inhibitors, and tyrosine kinase inhibitors.
2. It presents five case studies of patients who developed acute kidney injury following treatment with specific chemotherapy agents: ifosfamide, clofarabine, carfilzomib, temsirolimus, and anthracyclines.
3. For each case, it analyzes the likely offending agent and possible mechanisms of nephrotoxicity based on previous literature and known renal side effect profiles of the drugs.
Anaesthesia for Living Donor Combined Liver Kidney TransplantationApollo Hospitals
Orthotopic liver transplantation is now the best therapeutic option for patients with chronic liver failure [1]. Liver transplant is now a routine surgery performed in numerous medical centers throughout the world. Till now about 600 liver transplants have been performed in the Indraprastha Apollo Hospital, New Delhi. Combined liver kidney transplantation (CKLT) is the treatment for end-stage liver and kidney diseases. Combined liver kidney transplantation from living donors is performed in very few centers. Not many cases of Living donor combined Liver Kidney transplantation has been described in the literature. Here we report the clinical experience of our first living donor combined liver kidney transplantation (kidney after liver) in patient with end-stage liver disease (ESLD) and end stage renal failure (ESRD). Liver and kidney graft has been harvested from two living related donors.
Role of Plasma Exchange in ABO-incompatible Kidney TransplantationApollo Hospitals
In the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However,
multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection.
outh Africa has one of the highest incidences of human immunodeficiency virus (HIV) infection in Africa. The rollout of antiretroviral therapy (ART) in South Africa has been tremendously successful in extending the lives of HIV-infected persons. Consequently, more patients who would have died before the availability of ART are now receiving a diagnosis of HIV-associated nephropathy.1
The rates of disease progression and death in the population of HIV-positive patients with chronic kidney disease can be modified by ART, which reduces the risk of advanced chronic kidney disease among patients with HIV-associated nephropathy by approximately 60%.2,3 It has been estimated that the prevalence of chronic kidney disease among HIV-infected patients receiving treatment is between 8% and 22%4-7; among untreated patients, it is estimated to be between 20% and 27%.8,9 Confronted with a high burden of HIV disease and limited resources, South Africa faces considerable challenges in providing renal-replacement therapy for the large numbers of HIV-infected persons in whom chronic kidney disease will develop during their lifetime.
According to the Texas Department of State Health Services, there ar.pdfakashitproduct
According to the Texas Department of State Health Services, there are approximately 17.7
million adults (age 18+) living in Texas, of which 1.47 million have diabetes. In 2010, 341,430
adult Texans were diagnosed with diabetes for the first time.
What is the incidence of diabetes in Texas? Express your answer in units of per 1000 persons
per year.
Solution
191 Patients with hepatocellular carcinoma (HCC) within Milan criteria receive
priority on the liver transplant(LT) waiting list(WL) and compete with non-HCC candidates. We
compared dropout from the WL using a competing risks approach to assess the relative access to
transplant for these two groups. The cohort consists of all candidates listed 4/14/04 - 12/31/2007
with HCC candidates identifi ed via initial exception application. Status 1 and pediatric patients
were excluded. Dropouts included removals for candidate death, too sick, and for other. A
multivariable waiting list analysis was performed using a Cox model of time to dropout and
competing risks model. Results: Non-HCC patients had a signifi cantly higher dropout rate from
the WL compared with HCC patients over one year after listing/exception. This was reproducible
across all regions. Ablation had little infl uence on HCC dropout. Larger tumor size, higher
MELD score and/or AFP were associated with increased dropout. Multivariable analysis with
competing risks showed that MELD, log AFP, max tumor size were of signifi cance in predicting
dropout for HCC patients. % dropout Days after Listing 30 60 90 180 365 Non-HCC All MELD
6.5 9 10.6 13.9 17.9 No Ablation 2.2 4 6 9.2 11.8 Ablation 1.4 3.1 4.7 8 11.2 Non-HCC MELD
<21 1.4 2.9 4.4 8.1 13.1 HCC + MELD < 8 0.6 1.4 1.9 4 6.6 HCC + MELD 8-11 0.9 2.4 3.7 6.1
8.5 HCC + MELD 11-14 1 2.8 4.3 7.8 10.3 HCC + MELD >14 3.9 6.6 9.4 13.9 17.7 Tumor < 2
cm 0.9 2.6 4.9 8.2 11.2 2-2.6 1.8 3.4 5.1 8 10.4 2.6-3.3 2.3 3.8 5.2 8.4 11.1 > 3.3 2 4.4 6.3 10
13.4 AFP < 500 1.7 3.2 4.8 7.5 10.2 500-1000 2.8 6.4 9.2 15.3 18.2 >1000 4 8.3 13 21.8 27.8
Conclusions: HCC patients appear to be advantaged in the current allocation scheme as shown
by lower dropout rates. This advantage is consistent through the UNOS regions. A continuous
score incorporating MELD, AFP and tumor size would help prioritize HCC with non-HCC
patients to help equate dropout rates and equalize the allocation scheme. Abstract# 4 Primary
Outcomes from a Randomized, Phase III Study of Belatacept vs Cyclosporine in Kidney
Transplant Recipients (BENEFIT Study). F. Vincenti,1 J. M. Grinyo,2 B. Charpentier,3 J. D.
Medina-Pestana,4 L. Rostaing,5 Y. Vanrenterghem,6 G. B. Di Russo,7 P. Garg,7 C.-S. Lin,7 C.
Larsen.8 1UCSF; 2Univ Hospital of Bellvitge; 3Hopital Bicetre; 4Hospital do Rim e Hipertensao
Unifesp; 5CHU Ranguell; 6Univ Hospital Kuleuven; 7Bristol-Myers Squibb; 8Emory Univ
School of Medicine. Introduction: Belatacept, a co-stimulation blocker, is being developed as an
immunosuppressant for kidney transplant recipients to avoid the renal and.
This document discusses HIV and its effects on the kidney. It begins by outlining how HIV medications and the virus itself can impact renal function. It then discusses how monitoring renal function in HIV patients requires looking beyond creatinine and eGFR, as proximal tubule damage is common. Studies mentioned show increasing rates of chronic kidney disease in HIV populations and risk factors like tenofovir use and older age. Biopsy results from local patients demonstrate frequent tenofovir toxicity and the value of the urine APR test. Ongoing research aims to better estimate glomerular filtration rate and understand discrepancies with estimated values.
This document presents the case of a 28-year-old woman who received a kidney transplant in 2019 due to end-stage renal disease caused by focal segmental glomerulosclerosis (FSGS). Her kidney function and proteinuria were stable after transplant until November 2019 when a biopsy showed recurrent FSGS. She received plasma exchange and rituximab treatment. Over the following year her kidney function remained stable with decreasing proteinuria in response to ongoing plasma exchange and rituximab.
This document provides information about kidney transplantation, including the pre-transplant, transplant, and post-transplant processes. It discusses patient assessment, investigations, immunization, donor selection, admission for transplant surgery, complications, immunosuppressive drugs used, and drug-drug interactions that can affect immunosuppressive levels. The pre-transplant phase involves evaluating patient eligibility and matching them with a donor. During transplant, the kidney is surgically implanted. Post-transplant care requires lifelong immunosuppression to prevent rejection while managing any issues.
myPlatelet article PCI patients Ind Heart Journal April 2015Jugnu Jain
This study evaluated 200 patients undergoing percutaneous coronary intervention (PCI) who were prescribed antiplatelet medications like clopidogrel, prasugrel, or ticagrelor. The patients underwent testing to detect mutations in the CYP2C19 gene, which impacts clopidogrel metabolism, and a platelet reactivity assay to assess drug effectiveness. Based on the results, some patients had their antiplatelet therapy modified, such as increasing the clopidogrel dose or switching to prasugrel or ticagrelor for those with CYP2C19 mutations on clopidogrel. The study found 16.5% of patients had clopidogrel resistance due to CYP2C19 mutations
Transfusion Medicine support in live related combined liver and kidney transp...Apollo Hospitals
Combined liver and kidney transplantation (CLKT) is the procedure of choice for patients with dual-organ failure. Transfusion Medicine support in live related combined liver and kidney transplantation (CLKT) not only involves the provision of safest possible blood and histocompatibility testing (HLA typing & CDC Crossmatch) but also ensures better patient care due to availability of various advance immunohematological techniques in a time bound frame. A fully equipped functional and sophisticated blood bank and HLA lab is a must in the hospitals where such surgeries are done.
This document discusses considerations for liver transplantation including:
1. Evaluating a patient's need, safety, ability to comply, and quality of life for transplant eligibility.
2. Assessing donor liver fitness including medical history, lab tests, and biopsy.
3. Managing a patient's care while waiting for transplant including preventing complications.
4. Evaluating potential causes for graft dysfunction after transplant such as rejection or other issues.
02 withdrawal of immunosuppressants in pediatric liver transplantFanny Yeh
This study aimed to minimize the dose of tacrolimus (CNI) in pediatric patients after liver transplantation. Sixteen patients were recruited and had their tacrolimus dose gradually reduced over time. Six patients were able to be weaned off tacrolimus completely and remained off it for over two years. Those with metabolic liver disease and who were recruited earlier after transplantation were more likely to be weaned off. Some patients experienced low-grade fibrosis or rejection when being weaned off tacrolimus, showing the importance of monitoring during the process. The study concluded that tacrolimus withdrawal is feasible in select pediatric patients and long-term monitoring is suggested.
1) A study compared the efficacy and safety of Roxadustat versus erythropoiesis-stimulating agents for treating anemia in chronic kidney disease patients. A meta-analysis found that Roxadustat significantly increased hemoglobin and improved iron metabolism but had a higher risk of serious adverse events.
2) Another study compared splenectomy versus eltrombopag as second-line treatments for immune thrombocytopenic purpura and found that while splenectomy had a faster response time, the overall response rates were similar between the two treatments after 2 years.
3) A meta-analysis on treatments for aplastic anemia found that rabbit antithymocyte globulin and horse antithym
1) The study evaluated converting 210 stable liver transplant recipients from twice-daily tacrolimus to a once-daily prolonged-release formulation on a 1 mg to 1 mg basis.
2) Seven patients (3.3%) withdrew from the conversion due to side effects. Liver enzymes increased mildly in some patients but renal function and uric acid levels improved.
3) Seven additional patients (3.4%) experienced suspected acute rejection after converting, though three cases were attributed to non-adherence. Most patients reported more social/travel flexibility with once-daily dosing.
17 february lupus nephritis prof ashraf foudaFarragBahbah
This document discusses key points about lupus nephritis. It notes that 35% of adults with SLE have clinical evidence of nephritis at diagnosis, and 50-60% develop nephritis within 10 years. Lupus nephritis reduces survival at 10 years to 88% compared to 92% for SLE alone. Renal biopsy is recommended for confirmed proteinuria over 0.5 g/24h or active urine sediment. Repeat biopsy may be considered for worsening renal function or unexplained changes. Treatment typically involves steroids like prednisone combined with immunosuppressants like MMF or cyclophosphamide. While initial response rates are similar, steroids alone is associated with more relapses. Long term
The document discusses several cases of glomerular disease:
1) A 27-year-old male with nephrotic syndrome and a kidney biopsy showing IgG and C3 deposits along the glomerular basement membrane consistent with membranous nephropathy.
2) A 78-year-old female admitted with nephrotic syndrome after a history of NSAID use, with a biopsy showing focal segmental glomerulosclerosis.
3) A 26-year-old male with nephrotic syndrome and renal impairment, whose biopsy demonstrated membranoproliferative glomerulonephritis with C3 deposition and subendothelial electron dense deposits. Follow up showed elevated
Case #1.
Azathioprine에 의한 심한 골수부전 환자를 소개 하였습니다.
실제로 소개드린 첫번째 문헌(GUT)에 의하면 골수 억제의 부작용은 초기 치료 기간에 집중되어 있지만 전 치료 기간에 발생될 수 있는 것으로 되어 있습니다. 문헌들에 의하면 TPMT 활성이 저하된 환자에게 많이 발생하고 투여 전 TPMT 활성을 검사 한 후 치료를 시작 하여야 한다는 내용들이 많습니다. 그러나 TPMT 검사는 고가에 오랜 검사기간이 걸리는 검사입니다(비보험 225,750원, 20일). 또한 슬라이드에 소개드린 두번째 문헌(DDS)에는 스크리닝 검사의 효용성에 대하여 회의적인 결과를 보고 하였습니다.
면역 억제제 투여시 첫 약물로써 가장 간단하게 투여할 수 있는 이뮤란(Azathioprine)이라는 이름의 약물 역시도 주의하며 투여 해야 할 약물 이라 생각 됩니다. 심각한 혈액학적 합병증의 발생률은 약 6% 정도로 보고되고 있으며, 류마티스질환 치료 하시는 분들 역시도 오랜 치료기간 한두번의 경험을 할 수 있는 정도라고 합니다. 사용을 안할 수 없는 약물인 만큼 투여 전 환자와 보호자에게 발생 가능한 부작용에 대한 충분한 설명이 필요 하다고 생각 합니다.
Case #2.
Hepatic enz. elevation 주소로 오신 분이고, non-A, non-B hepatitis로써 ANA 검사상 high titer 소견을 보였습니다. 그런데 ANA 보고시 간과할 수 있는 ANA pattern이 'Discrete speckled' 로 보고되고 Anti Centromere Ab. 양성소견 이었습니다. 다시 병력 청취 하였더니 Raynaud disease가 의심 되었던 case 입니다. ANA 검사 결과를 볼때 titer 뿐 아니라 pattern도 챙겨 보아야 한다는 교훈을 얻었던 case 입니다.
Journal club multitarget therapy lupus nephritis maintenance chaken CHAKEN MANIYAN
Multitarget therapy of tacrolimus, mycophenolate mofetil and steroids achieved a 45.9% complete remission rate in induction treatment of lupus nephritis. This study assessed the efficacy of continuing multitarget therapy versus switching to azathioprine as maintenance treatment over 18 months. The cumulative renal relapse rate was lower in the multitarget group at 5.47% compared to 7.62% in the azathioprine group. More patients in the multitarget group maintained complete remission during maintenance treatment with no significant differences in safety profiles between the groups.
Similar to Abo incompatible kidney transplantion - A single center experience (20)
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Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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2. The following preconditioning protocol was used:
d Minus 7 days.
d Rituximab 200 mg infusion.
d Oral immunosuppressive drugs e prednisolone 10 mg,
mycophenolate mofetil 360/540 mg twice a day, tacroli-
mus 0.1 mg per kilogram body weight.
d Plasma exchange on alternate day after dialysis so as to
lower the anti A/anti B titer to 1 in 4 with a maximum of
4 exchanges. Two liters of plasma exchange was carried
out in adults and in children 40 ml per kilogram body
weight. The replacement was done with 5% albumin.
The last exchange was carried out on the day of kidney
transplantation. After the 8th transplant, the protocol was
changed to mandatory 4 plasma exchanges and IvIg low
dose 5 g after the 3rd exchange.
d DSA and cross match were repeated on the day of
kidney transplantation. The surgery was performed
only if both of them were negative.
d Basiliximab 20 mg Iv infusion on Day 1 and Day 4 of
transplantation.
Post transplantation protocol:
d Methyl prednisolone 500 mg e Day 1, 250 mg e Day 2
& Day 3.
d Prednisolone 20 mg from Day 4, tapered to 10 mg by 2
weeks.
d Mycophenolate mofetil 360 mg twice a day if patient
weight less than 60 kg. 540 mg twice a day if weight
more or equal to 60 kg.
d Tacrolimus to maintain level between 8 and 10 ng/mL.
d Prophylaxis with valganciclovir and cotrimoxazole.
RESULTS
Thirteen patients underwent ABO incompatible kidney
transplantation since 2009 (Table 1). One was done in
2009, 1 in 2010, 3 in 2011 and rest in 2012. Out of the
13 recipients 9 were male and 4 female. Age was between
13 and 57 years. Ten patients had haplo match and 3
patients had mismatch on HLA typing. Three were chil-
dren. Two of the children had reflux nephropathy as their
native disease. Prior nephrectomy was not done in them.
Out of the other recipients 2 had diabetic nephropathy, 1
failed graft with re-transplantation, 1 focal segmental glo-
merulosclerosis (FSGS), 2 IgA nephropathy and rest the
cause unknown. A to O was done in 5 patients, B to O in
3 patients, B to A in 2 patients and A to B in 3 patients.
The immediate pre-operative titers were 1 in 2 in 4 patients,
1 in 4 in 8 patients, 1 in 8 in 1 patient. One patient under-
went 2 plasma exchanges, 5 underwent 3 exchanges and 7
underwent 4 exchanges. Two patients (Sr. no. 1 and 7) had
hyperacute rejection. In both of them the titers were 1 in 2
pre-operative. Hence after the 8th transplantation, the
protocol was changed to mandatory 4 plasma exchanges
with IvIg to ensure adequate immunosuppression. In the
11 patients with functioning graft, the follow-up period
has been between 4 weeks and 28 months. All of them
have normal renal function without any proteinuria. One
patient (Sr. no. 6) had urinary tract infection (UTI) and
cytomegalovirus (CMV) infection for which she received
successful treatment and her immunosuppressants has
been reduced to 2 drugs (steroids þ tacrolimus). One
patient (Sr. no. 8) had acute tubular necrosis (ATN)
Table 1 Showing the results of ABO incompatible kidney transplantations.
Sr. no. Sex Age Blood group Tissue
typing
Titer on
the day
of Tx
Plasma
exchange
Outcome Follow-up Remarks
Recipient Donor
1 M 54 O þve A Haplo 1 in 2 3 Hyperacute rejection e On hemodialysis
2 M 26 O þve B Àve Haplo 1 in 4 2 Serum creatinine e 1.5 mg/dL 28 months No proteinuria
DM/UTI
3 M 48 A þve B þve Mis-match 1 in 4 3 Serum creatinine e 1.1 mg/dL 15 months Scorpion bite
4 M 47 B þve A þve Mis-match 1 in 2 3 Serum creatinine e 1.2 mg/dL 10 months
5 M 13 O Àve B þve Haplo 1 in 2 3 Serum creatinine e 0.8 mg/dL 10 months
6 F 21 O þve A þve Haplo 1 in 8 4 Serum creatinine e 0.8 mg/dL 5 months CMV infection, UTI
7 M 13 O þve A þve Haplo 1 in 2 3 Hyperacute rejection e On hemodialysis
8 F 45 O þve B þve Haplo 1 in 4 4 þ IvIg Serum creatinine e 1.3 mg/dL 2.5 months ATN, bleed
9 F 30 B þve A þve Haplo 1 in 4 4 þ IvIg Serum creatinine e 1.4 mg/dL 2 months Tacro toxicity
10 F 33 O þ ve A þve Haplo 1 in 4 4 þ IvIg Serum creatinine e 1.2 mg/dL 1.5 months
11 M 57 O þve A þve Mis-match 1 in 4 4 þ IvIg Serum creatinine e 1 mg/dL 1.5 months
12 M 27 A þve B þve Haplo 1 in 4 4 þ IvIg Serum creatinine e 1 mg/dL 1 month
13 M 14 B þve A þve Haplo 1 in 4 4 þ IvIg Serum creatinine e 0.6 mg/dL 1 month
2 Indian Journal of Transplantation 2012 -; Vol. -, No. - Ravichandran et al.
Please cite this article in press as: Ravichandran R, et al., ABO incompatible kidney transplantation e A single center experience, Indian
Journal of Transplantation (2012), http://dx.doi.org/10.1016/j.ijt.2012.10.002
3. following hypotension due to post-operative bleed on the
second day which settled conservatively with blood transfu-
sion. The coagulation parameters were normal. The ATN
was confirmed by renal biopsy and the dose of tacrolimus
was reduced. The renal function returned to normal after
3 days. One patient (Sr. no. 9) had Tacrolimus toxicity
which was proved on biopsy and elevated level of tacroli-
mus. The drug was withdrawn and serum creatinine came
down to 1.4 mg/dL from 2.7 mg/dL. She continues to be
on 2 drugs (steroids þ mycophenolate) with stable renal
function. Patient Sr. no. 3 has the longest follow-up of 28
months with serum creatinine of 1.5 mg/dL without protein-
uria. His donor was 64 year at the time of transplantation.
None of these patients had any episode of rejection. In
both patients who had biopsy, C4d was found positive.
The renal function returned to normal without any anti
rejection treatment. Post-operative anti A, anti B titers
were measured for 1 week. The values continued to be
the same as the pre-operative state in all recipients. The
hospital stay was between 7 days and 14 days. The cost
involved was a package of Rs 6.5 lakhs including all the
treatment for donor and recipient.
DISCUSSION
ABO incompatible kidney transplantation is gaining popu-
larity all over the world.7
More than a thousand transplan-
tations have been done in Japan.4
Other centers from
USA,8
Europe,9e11
Australia12
and UK13
have also re-
ported several such transplantations. The increasing
demand for kidney transplantation and the shortage of
cadaveric kidneys makes it important that we start such
a program in India. The problem of ABO incompatible
transplantation could be 2-fold e (a) aggressive pre-opera-
tive immunosuppressive protocols which can increase
patient mortality and (b) cost of such therapy, which would
deter this treatment in our country. For a successful ABO
incompatible transplantation it is essential to lower the
anti A and anti B titers and adequately immunosuppress
the patient prior to transplantation. This is called pre-condi-
tioning of the patient. Several protocols have been used all
over the world.7
Splenectomy, which was performed in the
early days is not necessary with the present protocols.14
Since splenectomy carried a high mortality in dialysis
patients, it was a deterrent for us to start our incompatible
transplant program until 2009. The various protocols
involved a standard or low dose IvIg, rituximab, triple
immunosuppressive drugs, interleukin receptor blockers
and antibody depletion by plasmapheresis or immunoad-
sorption. The Japanese protocol of Tanabe4
suited us
most with the use of 1 dose rituximab 1 week prior to
the transplantation and the combination of tacrolimus,
MMF, prednisolone, plasmapheresis and basiliximab.
This has the advantage of less cost and less immunosup-
pression compared to the American and European proto-
cols. The antibody titers were measured using the
conventional tube test (CTT) with the addition of DTT
which helps to separate the IgG antibodies.15
CTT is
commonly used in Japan.4,16
The cutoff for the anti A
and anti B antibody titers also varies from center to center.
It could be as low as 1 in 4 or as high as 1 in 32.7
There
is of course, some difference in the values by the 2 methods
e the microcolumn gel card (MG) test and CTT. Accord-
ing to Cheng and Hao who compared the 2 methods in
288 serum samples, the MG card test was more sensitive
than CTT in detection of both anti A and anti B. IgG
with the MG results being approximately 2-fold higher
than those for CTT. When we started the program we
took 1 in 4 as the cutoff point for our first 8 transplants.
Therefore, the number of plasma exchanges varied from
2 to 3 to achieve this target. However, in 2 patients we
had ABMR confirming the inadequacy of pre-conditioning.
Hence, after the eighth transplant we decided to make 4
plasmapheresis mandatory for all patients and included
a low dose of IvIg after the third plasmapheresis. We
changed our protocol since a low antibody titer alone did
not ensure the prevention of ABMR. Recent studies have
reported ABMR occurring in 17.9e30% of ABO incom-
patible kidney transplants.17,18
The greatest incidence of
acute ABMR occurs 2e7 days after the transplant. The first
2 weeks is a critical period during which accommodation is
usually induced and established.5
The other eleven patients
who had a functioning graft have been followed up from 4
weeks to 28 months. They have been on conventional triple
immunosuppressive drugs like the other regular transplant
recipients and have not had any serious complications. In
2 patients biopsy had to be done for deterioration of renal
function e one had ATN due to hypotension which
improved well with correction of the volume status and
the other due to tacrolimus toxicity which also improved
on withdrawing the drug. Both the biopsies showed the
presence of C4D in the peritubular capillaries. It has been
shown in ABO incompatible transplants that the mere pres-
ence of C4D does not necessarily indicate an ABMR.1,19
Two of our patients had diabetes, 2 had reflux nephropathy
with bladder dysfunction and one was a re-transplant after
a failed graft. In spite of the additional morbid conditions
they have done well till today. The 2 patients who lost their
grafts are back on dialysis. In other 11 patients, the renal
function has been excellent with no significant proteinuria.
The cost for the ABO renal transplantation is of concern
since the protocols could use immunoadsorption columns
which are expensive and standard dose IvIg which is
ABO incompatible kidney transplantation Original Article 3
Please cite this article in press as: Ravichandran R, et al., ABO incompatible kidney transplantation e A single center experience, Indian
Journal of Transplantation (2012), http://dx.doi.org/10.1016/j.ijt.2012.10.002
4. equally expensive. With our protocol we have been able to
do these transplants for a package of Rs 6.5 lakhs which
includes the pre-conditioning and post-op treatment for
10 days. ABO incompatible kidney transplantation is
feasible in our country without undue risk to the life of
recipient and at reasonable cost. It is essential that we
achieve an immunosuppressive protocol which would
prevent graft loss also.
CONFLICTS OF INTEREST
All authors have none to declare.
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4 Indian Journal of Transplantation 2012 -; Vol. -, No. - Ravichandran et al.
Please cite this article in press as: Ravichandran R, et al., ABO incompatible kidney transplantation e A single center experience, Indian
Journal of Transplantation (2012), http://dx.doi.org/10.1016/j.ijt.2012.10.002