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Challenges in Delivering Gene Therapy
Published in Yashwant Pathak, Gene Delivery, 2022
With the body’s immune response affecting the delivery for gene therapy, there must be strategies to circumvent this immune response. One way of regulating an immune response has been the use of immunosuppressive agents like cyclosporine, tacrolimus, and cyclophosphamide [42]. These immunosuppressive drugs block various pathways that result from antigen presentation all the way to the activation of B and T cells. By using these drugs in conjunction with gene therapy, the immunosuppressive drugs inhibit the synthesis and release of cytokines, while preventing the differentiation of CD4 cells, hence blocking an immune response [43]. This method could hold promising results, such that the suppression of the immune response will allow the vector to unpack the DNA and allow it to integrate the host cell.
Transplants: Experiment or Therapy?
Published in David Lamb, Organ Transplants and Ethics, 2020
There are, however, many residual problems with renal transplants. Many patients reject their grafts and have to return to dialysis, or receive another graft. In the USA 1,500 return to dialysis each year. Complications can occur. Approximately 80 per cent of kidney recipients develop infection at some time after their transplant, and of these for 25 per cent the infection leads to death. The most serious infections involve the lungs. Then there are the risks of side-effects of the immunosuppressive drugs, which include hypertension, hepatitis, and cancer (New York Task Force, 1988:14; also Toledo-Pereyra, 1987; Vincenti, Parfrey, and Briggs, 1986).
Inflammation and immunology
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Christopher Bellamy, Stephen J. Jenkins, Henry J. McSorley, David A. Dorward, Timothy J. Kendall
Immunosuppression may result from specific therapy or may occur as a complication of therapy. To maintain the survival of transplanted organs, drugs and other therapies are administered to suppress the immune response. The main immunosuppressive drugs are designed to suppress specifically the afferent arm of the immune response, blocking the activation of immune cells reactive to the allogeneic (foreign) MHC and other antigens present on the cells of the transplanted organ. Such drugs include tacrolimus, mycophenolate mofetil, and azathioprine. However, if this suppression is overcome and the patient experiences an episode of transplant rejection, the strategy shifts to one targeted at suppressing the effector arm of the response. In these clinical circumstances high-dose corticosteroids are used and, if these are not wholly effective, humanized monoclonal antibody may be used to deplete immunocompetent cells.
Risk factors for fractures following liver transplantation: a population-based cohort study
Published in Annals of Medicine, 2023
Jei-Wen Chang, Hui-Hsin Yang, Niang-Cheng Lin, Fang-Cheng Kuo, Tzu-Ching Lin, Hsin-Lin Tsai
In the patients with fractures, 21.5%, 21.5%, 34.4% and 22.7% were in the 1st (0-1.61 mg/day), 2nd (>1.61-3.78 mg/day), 3rd (>3.78-9.18 mg/day) and 4th (>9.18 mg/day) quartiles of average daily glucocorticoid dose, respectively, compared to 25.3%, 25.3%, 24.1% and 25.2% in the patients without fractures. Overall, 2.1% of the patients received bisphosphonate treatment after transplantation. Calcium and vitamin D supplements were taken by 7.0% and 1.5% of the patients post-transplant, respectively. The most commonly prescribed immunosuppressive drugs were tacrolimus and mycophenolate mofetil/mycophenolic acid. A higher proportion of the recipients with fractures received cyclosporine (12.4% vs. 7.5%) and mycophenolate mofetil/mycophenolic acid (88.8% vs. 83.9%) compared to those without fractures. Conversely, the prescription rates of tacrolimus (93.3% vs. 95.6%) and sirolimus/everolimus (17.7% vs. 29.9%) were lower in the recipients with factures than in those without fractures.
Nutritional Status of Allogeneic Hematopoietic Stem Cell Transplant Recipients and Post-transplant Outcomes
Published in Nutrition and Cancer, 2023
Stephanie Szovati, Caroline F. Morrison, Sarah C. Couch
Calorie intake post-transplant was significantly lower than calorie intake pre-transplant. So et al. found that calorie intake decreased most precipitously from the day before transplant to 1-week post-transplant and was the lowest at 1-week post-transplant (36). Hadjibabaie et al. found that energy intake was lowest 10 day post-transplant (37). Our findings show the distribution of calories post-transplant reflected a higher % of calories from carbohydrate compared to fat, while % of calories from protein remained at pre-transplant intake levels. Since average overall calorie intake decreased significantly post-transplant, the average intake of protein (gm/day) likely was lower as well. Garios et al found that 42% of autologous and allogeneic transplant recipients had protein adequacy levels lower than 60% throughout hospitalization (4), and Hadjibabaie et al found that protein intake was also lowest 10 day post-transplant (38). Studies of HSCT patients have reported that dietary intake post-transplant is greatly impacted by side effects from the conditioning regimen (35) and medications used post-transplant (36, 37). Post-transplant antibiotic treatment may lead to GI mucosal damage resulting in a loss of oral and intestinal microbiota diversity. Additionally, immunosuppressive drugs can increase the risk of GI infection and mucositis is a common side effect of drug toxicity (37). Other GI complications that hinder eating post- transplant reported by HSCT patients include anorexia, dry mouth, altered taste, and nausea (38).
Inducibility or predestination? Queries and concepts around drug-free remission in rheumatoid arthritis
Published in Expert Review of Clinical Immunology, 2023
Bernardo D’Onofrio, Annette van der Helm-van Mil, Tom W.J. Huizinga, Elise van Mulligen
Many studies define the (S)DFR as the best possible achievable condition for RA patients. Being able to successfully stop immunosuppressive drugs could be beneficial for many reasons: 1) to reduce the load of drug’s adverse effects, especially in terms of infections, once the remission is obtained and the damage-benefit ratio of the use of DMARDs is no longer clear; 2) to reduce the load of costs on the health system, especially for biological or targeted-synthetic drugs; 3) to improve patient-reported outcomes; 4) to be able to distinguish between inflammation suppression or ‘true cure’ of RA [1]. Although the rate of DFR varies according to different variables, increasing available data should reassure the clinicians to attempt drug discontinuation once the remission is reached and sustained, in selected patients and in a balanced way.