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Sumeet S Teotia

Publications and source records attributed to Sumeet S Teotia.

7 recordsLinked to original sources
PubMed2006

Increased immunosuppression, not anticoagulation, extends cardiac xenograft survival.

BACKGROUND: Cardiac xenograft function is lost due to delayed xenograft rejection (DXR) characterized by microvascular thrombosis and myocardial necrosis. The cause of DXR is unknown but may result from thrombosis induced by antibody-mediated activation of endothelial cells and/or by incompatibilities in thromboregulatory interactions. METHODS: To examine these issues, a series (Groups 1-6) of previous transgenic CD46 pig-to-baboon heterotopic cardiac transplants were reanalyzed for baseline immunosuppressive levels, graft survival and infectious complications with and without systemic anticoagulation. Groups 1-4 received low dose tacrolimus and sirolimus maintenance therapy, with splenectomy, anti-CD20 and daily alpha-Gal polymer. Group 1 recipients received no anticoagulation. Groups 2-4 were anticoagulated with aspirin and Plavix, Lovenox, or Coumadin, respectively. Group 5 was treated with Lovenox and high dose tacrolimus and sirolimus maintenance therapy. Group 6 recipients received no postoperative anticoagulation but the same immunosuppression as group 5. RESULTS: Median survival (15-22 days) within groups 1-4 was not significantly different. At rejection all tissues exhibited microvascular thrombosis, coagulative necrosis and similar levels of platelet and fibrin deposition. Groups 5 and 6 median survival (76 days) was significantly increased compared to groups 1-4. There was no significant difference in median survival between Lovenox treated recipients (68 days) and anticoagulant free recipients (96 days). Rejected tissues showed vascular antibody deposition, microvascular thrombosis, and myocyte necrosis. CONCLUSION: Significant prolongation in xenograft survival is achieved by improved immunosuppression. These results suggest that ongoing immune responses remain the major stimulus for DXR.

Animals↗
PubMed2006

Do progressive tension sutures really decrease complications in abdominoplasty?

The purpose of this study is to evaluate the efficacy of progressive tension sutures (PTS) in preventing or reducing seroma formation and local wound complications in patients undergoing abdominoplasty. Forty-nine patients who underwent abdominoplasty procedures with the use of PTS were retrospectively compared with a historical control group of 54 patients who underwent standard abdominoplasty. Primary outcomes measured were seroma formation and local wound complications, including hypertrophic scar formation, umbilical distortion, and wound necrosis. Secondary outcomes were all other complications and time to drain removal. Overall complication rates and local wound complication rates were significantly reduced with the addition of PTS to abdominoplasty. Seroma formation and the time to drain removal were reduced in the PTS group, but the findings were not statistically significant.

Abdomen↗
PubMed2005

Cardiac xenotransplantation: recent preclinical progress with 3-month median survival.

OBJECTIVES: Transplantation is limited by a lack of human organ donors. Organs derived from animals, most likely the pig, represent a potential solution to this problem. For the heart, 90-day median graft survival of life-supporting pig hearts transplanted to nonhuman primates has been considered a reasonable standard for entry into the clinical arena. Overcoming the immune barrier to successful cardiac xenotransplantation is most appropriately first explored with the non-life-supporting heterotopic model. METHODS: We performed a series of 7 heterotopic heart transplantations from CD46 transgenic pigs to baboons using a combination of therapeutic agents largely targeted at controlling the synthesis of anti-pig antibodies. Rituximab (anti-CD20) and Thymoglobulin (rabbit antithymocyte globulin [ATG]; SangStat Medical Corp, Fremont, Calif) were used as induction therapy. Baseline immunosuppression consisted of splenectomy, tacrolimus, sirolimus, steroids, and TPC (an anti-Gal antibody therapeutic). Rejection events were not treated. RESULTS: By using Kaplan-Meier analysis, median graft survival was 96 days (range, 15-137 days; 95% confidence interval, 38-99 days). Only 2 grafts were lost as a result of rejection, as defined by cessation of graft palpation. There was no evidence of a consumptive coagulopathy, infectious complications were treatable, and no posttransplantation lymphoproliferative disorders occurred. No cellular infiltration was observed. CONCLUSIONS: This study reports the longest median survival to date (96 days) of pig hearts transplanted heterotopically into baboons. Duplication of these results in the orthotopic life-supporting position could bring cardiac xenotransplantation to the threshold of clinical application.

Animals↗
PubMed2005

Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival.

BACKGROUND: We analyzed bacterial and fungal infectious complications in a cohort of 16 consecutive experiments with the longest surviving cardiac xenografts to date. METHODS: Transgenic, porcine-to-baboon, heterotopic (abdomen) cardiac xenotransplantation was performed in 16 consecutive experiments, using rapamycin, tacrolimus, corticosteroids, anti-CD20 monoclonal antibody, and an alpha-Gal-PEG polymer, as immunosuppression. Prophylactic anti-microbials included i.v. trimethoprim/sulfamethoxazole, oral ganciclovir/valganciclovir, and oral itraconazole. An episode of bacterial infection was defined as a positive blood and/or wound culture with: leukocytosis, fever >101.5 degrees F, and/or clinical deterioration. RESULTS: Mean graft survival was 71 +/- 29 days; the longest was 113 days. There were 23 episodes of bacterial infection; 14 resolved with treatment. The mean time to the first episode of infection was 44 +/- 21 days (n=12). Eight of 16 deaths were due to infection: two bacterial-only, two cytomegalovirus (CMV) only, four both bacterial and CMV, and none fungal. The frequency of infection was 1, 2.8, and 1.8 episodes/100 survival days, respectively, for animals whose grafts survived for 30 to 59, 60 to 89, and >90 days. CMV infection (reviewed in detail in a separate communications) was due to baboon CMV, and was associated with low serum levels of ganciclovir. CONCLUSION: In a cardiac xenograft model that achieved prolonged (>3 months) survival, bacteremia was common, but usually reversible, and fungal infection was prevented with prophylaxis. The level of immunosuppression required to achieve clinically meaningful xenograft survival is associated with a level of bacterial and fungal infectious complications that is manageable and similar to the early clinical experiences in human transplantation. Further research will determine if the viral infectious complications observed in these experiments can be reduced by optimizing blood levels of anti-viral prophylaxis and monitoring viral polymerase chain reaction levels.

Animals↗
PubMed2005

Warfarin or low-molecular-weight heparin therapy does not prolong pig-to-primate cardiac xenograft function.

Microvascular thrombosis is a prominent feature in cardiac delayed xenograft rejection (DXR). We investigated the impact of warfarin or low-molecular-weight heparin (LMWH) anti-coagulation on xenograft function using a heterotopic pig-to-primate model. Donor hearts were from CD46 transgenic pigs and baboon immunosuppression included tacrolimus, sirolimus, anti-CD20 and TPC, an alpha-galactosyl-polyethylene glycol conjugate. Three groups of animals were studied. Group 1 (n = 9) was treated with warfarin, Group 2 (n = 13) with LMWH and Group 3, received no anti-coagulant drugs. The median duration of xenograft function was 20 days (range 3-62 days), 18 days (range 5-109 days) and 15 days (range 4-53 days) in Groups 1 to 3 respectively. Anti-coagulation achieved the targeted international normalized prothrombin ratio (INR) and anti-factor Xa levels consistent with effective in vivo therapy yet, no significant impact on median xenograft function was observed. At rejection, a similar histology of thrombosis and ischemia was apparent in each group and the levels of fibrin deposition and platelet thrombi in rejected tissue was the same. Anti-coagulation with warfarin or LMWH did not have a significant impact on the onset of DXR and microvascular thrombosis. However, a role for specific anti-coagulant strategies to achieve long-term xenograft function cannot be excluded.

Animals↗
PubMed2004

Cardiac xenotransplantation: progress toward the clinic.

BACKGROUND: Animal organs could satisfy the demand for solid organ transplants, which currently exceeds the limited human donor supply. Hyperacute rejection, the initial immune barrier to successful xenotransplantation, has been overcome with pig donors transgenic for human complement regulatory proteins. Delayed xenograft rejection, thought to be mediated by anti-pig antibodies predominantly to Gal antigens, is currently regarded as the major barrier to successful xenotransplantation. A median graft survival of 90 days in the life-supporting position is considered a reasonable initial standard for consideration of entry to the clinic. METHODS: A series of 10 heterotopic heart transplants from CD46 transgenic pigs to baboons was completed. Immunosuppression consisted of splenectomy, Rituximab (Anti-CD20), tacrolimus, sirolimus, corticosteroids, and TPC. Thymoglobulin (Rabbit Anti-Thymocyte Globulin) was used to treat putative rejection episodes. RESULTS: Median graft survival was 76 days (range 56-113 days, n = 9). Only three grafts were lost to rejection. The remaining grafts lost were due to recipient mortality with baboon cytomegalovirus (BCMV) being the major cause (n = 4). No cellular infiltrates were present as a manifestation of rejection. Three hearts showed chronic graft vasculopathy. CONCLUSIONS: The median survival of 76 days in this group of heterotopic porcine-to-baboon cardiac xenografts represents a major advance over the median 27-day survival reported in the literature. Cellular rejection may not constitute a direct major barrier to xenotransplantation. A median survival of 90 days may be achievable with better control of BCMV infection. If further studies in the orthotopic position replicate these outcomes, criteria considered appropriate for clinical application of cardiac xenotransplantation would be approached.

Animals↗