Short-term decreased post transplant lymphoproliferative disorder risk after kidney transplantation using two novel regimens.

BACKGROUND: Belatacept is employed alongside calcineurin inhibitor (CNI) therapy to prevent graft rejection in kidney transplant patients who are Epstein-Barr virus (EBV) seropositive. Preliminary data suggested that rates of post-transplant lymphoproliferative disorder (PTLD) were higher in individuals treated with belatacept compared to CNI therapy alone. METHODS: The records of 354 adults who underwent kidney only transplantation from January 2015 through September 2021 at one medical center were evaluated. Patients underwent treatment with either low-doses of mycophenolate, tacrolimus and sirolimus (B0, n = 235) or low-doses of mycophenolate, tacrolimus and belatacept (B1, n = 119). All recipients underwent induction with antithymocyte globulin and a rapid glucocorticosteroid taper. Relevant donor and recipient information were analyzed and endpoints of PTLD were assessed. RESULTS: There were no cases of PTLD in either cohort within the study period. Recipients in the belatacept cohort experienced lower estimated glomerular filtration rates at 12 months (B0: 67.48 vs. B1: 59.10, p = 0.0014). Graft failure at 12 (B0: 1.28% vs. B1: 0.84%, p = 1.0) and 24 months (B0:2.55% vs. B1: 0.84%, p = 0.431) were similar. There was no difference in rejection rates at 12 (B0: 1.27% vs. B1: 2.52%, p = 0.408) or 24 months (B0: 2.12% vs. B1: 2.52%, p = 1.000). Both groups had similar rates of malignancy, mortality and CMV/BK viremia. CONCLUSION: Non-belatacept (MMF, tacrolimus and sirolimus) and belatacept-based (MMF, tacrolimus and belatacept) regimens do not appear to pose any increased risk of early onset PTLD. Both cohorts benefited from low rates of rejection, malignancy, mortality and graft failure. Recipients will continue to be monitored as PTLD can manifest as a long-term complication.

Iatrogenic coronary artery stenosis following coronary stenting.

We present 6-month follow-up of 435 patients undergoing stent deployment. Forty-four patients were referred because of myocardial ischemia related to the stented artery. In six of these patients (14%), the stented vessel revealed a new proximal lesion separated from the stented portion, which warranted further intervention. It is felt that these new lesions are related to the stenting technique as a result of local trauma induced from the guiding catheter.

Atrial septal occlusion improves the accuracy of mitral valve area determination following percutaneous mitral balloon valvotomy.

We investigated the impact of the atrial communication on the mitral valve area calculation after percutaneous mitral balloon valvotomy in 17 patients (15 women, 2 men; mean age 56 +/- 4 years). The hemodynamic measurements and mitral valve area calculations were performed with and without balloon occlusion of the atrial septal puncture site. The mitral valve area determined with balloon occlusion was significantly smaller than the mitral valve area determined without occlusion (1.6 +/- 0.1 vs. 1.9 +/- 0.1 cm2, P less than 0.01), and was similar to the echocardiographically determined valve area (1.6 +/- 0.1 cm2). This decrease in the calculated mitral valve area with occlusion was associated with a decrease in the measured cardiac output, without a change in the mitral valve gradient or the diastolic filling period. Occlusion of the atrial septal puncture site may permit more accurate determination of the mitral valve area and thus provide a better reference point for future comparison should the question or restenosis arise.

Relation between survival and development of coronary artery disease and anti-HLA antibodies after cardiac transplantation.

The importance of chronic humoral rejection in cardiac transplant patients has not been studied extensively. In an attempt to determine whether lymphocytotoxic antibodies are related to heart allograft survival, we evaluated 123 patients whose sera were monitored for cytotoxic antibodies against HLA antigens after transplantation. Patients underwent serial sampling of peripheral blood at the time of right-heart catheterization and endomyocardial biopsy. Patients with three or more sera containing lymphocytotoxic antibodies were considered alloantibody producers (81 of 123 patients). With similar follow-up, mortality was greater for antibody producers (27 of 81 patients) than for nonproducers (three of 42 patients, p less than 0.01). Among antibody producers, the mortality rate was higher when multiple samples obtained during the first 6 months after transplantation contained anti-HLA class I or class II antibodies. Coronary artery disease was documented in 12 of 81 antibody producers and only one of 42 nonproducers (p = 0.05). The presence of anti-HLA antibodies in the serum showed no association with the presence of lymphocytic infiltrates in myocardial biopsies or with hemodynamic abnormalities. However, histologic rejection was present in 14 of 19 antibody producers who died. Thus, the presence of anti-HLA antibodies was associated with increased mortality and the development of coronary artery disease and was a major correlate of the clinical course after cardiac transplantation. High- and low-risk groups can be differentiated within the first 6 months after transplantation.

Humoral immune responses after cardiac transplantation: correlation with fatal rejection and graft atherosclerosis.

Although the advent of cyclosporine has allowed dramatic improvement in survival rates after heart transplantation, long-term outcome remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic cardiac transplants despite cyclosporine administration. The hypothesis of our study is that human heart transplant recipients given treatment with cyclosporine are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 118 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with positive sera on at least three separate samplings at minimal intervals of 1 week were considered to be antibody producers (Ab+), and those with less than three positive sera samplings were considered nonproducers (Ab-). Donor lymphocytes were not available for most recipients for the assessment of the specificity of antibodies produced. Seventy-six of 118 patients (64%) were Ab+. One-year, 3-year, and 5-year actuarial survival rates were 81%, 70%, and 53%, respectively, for Ab+ patients compared with corresponding rates of 93%, 90%, and 90%, respectively, in Ab- patients (p less than 0.01). Graft atherosclerosis confirmed by coronary angiography or autopsy developed in 12 Ab+ patients (16%), compared with 1 of 42 Ab- patients (2.3%) (p less than 0.05). These data show that almost two thirds of heart transplant recipients produce anti-HLA antibodies after grafting that correlate strongly with adverse outcome. Immunotherapies directed at control of deleterious humoral immune responses need to be developed.

Synthesis of angiotensinogen by renin-containing neuroblastomas.

Angiotensinogen in plasma is of hepatic origin, but many organs possess the ability to synthesize this protein because messenger RNA for angiotensinogen is widely distributed in the body. The cell types responsible for the extrahepatic synthesis of angiotensinogen remain to be identified. To examine whether renin-containing cells synthesize angiotensinogen, we have utilized a polyclonal antibody to angiotensinogen and immunoprecipitated metabolically labeled cells of two neuroblastomas known to contain renin. The results indicate that the cell line Neuro 2a synthesizes and releases a protein with a molecular mass of 57 kDa that is specifically recognized by the angiotensinogen antibody, indicating that Neuro 2a synthesizes angiotensinogen. Similarly, the cell line NB41A3 was also found to synthesize a protein specifically recognized by the antibody to angiotensinogen.

The underreporting of disease and physicians' knowledge of reporting requirements.

Previous studies of underreporting of disease have mainly addressed the attitudes of physicians toward reporting of communicable disease to public health agencies and have not examined adequately the physicians' knowledge of the reporting system as a cause of underreporting. To investigate, the authors designed a questionnaire and distributed it to 345 physicians at two hospitals. One hundred and sixty-nine questionnaires, which examined knowledge of reporting requirements and reasons for not complying with those requirements during 1978-81, were returned (a 49 percent response rate). Most of the respondents knew that reporting is required, but their knowledge in specific areas, such as which diseases are reportable, varied greatly. The number of physicians who knew which diseases they are required to report ranged from a low of 63 physicians (37 percent) for trachoma to 163 (96 percent) for syphilis. Of the 169 physicians, only 50 believed they knew how to report reportable diseases, and only 40 of them knew the correct procedures. Thirty-six percent of the 169 physicians indicated that they had not reported any cases at all during 1978-81. On the average, physicians recalled reporting 28 percent of their reportable cases. When they indicated why they had not complied with reporting requirements, the physicians chose reasons that reflected a lack of knowledge of the reporting system. The most common reasons were "did not know how to report" and "did not know it was a reportable disease." The results suggest that a major factor in physician underreporting is a lack of knowledge of the morbidity reporting system.