20 research outputs found

    Differentiating Acute Rejection From Preeclampsia After Kidney Transplantation.

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    OBJECTIVE: To evaluate the clinical and laboratory characteristics in pregnancy that differentiate preeclampsia from acute renal allograft rejection and to investigate the maternal, neonatal, and graft sequelae of these diagnoses. METHODS: We conducted a retrospective case-controlled registry study of data abstracted from Transplant Pregnancy Registry International deliveries between 1968 and 2019. All adult kidney transplant recipients with singleton pregnancies of at least 20 weeks of gestation were included. Acute rejection was biopsy proven and preeclampsia was diagnosed based on contemporary criteria. Variables were compared using χ2, Fisher exact, and Wilcoxon rank sum tests as appropriate. Multivariable linear regression was used to analyze preterm birth. Kaplan-Meier curves with log-rank test and Cox proportional hazards model were used to compare graft loss over time. RESULTS: There were 26 pregnant women with biopsy-confirmed acute rejection who were matched by the year they conceived to 78 pregnant women with preeclampsia. Recipients with acute rejection had elevated peripartum serum creatinine levels (73% vs 14%, P CONCLUSION: In pregnancy, acute rejection is associated with higher creatinine levels, and preeclampsia is associated with increased proteinuria. Acute rejection in pregnancy carries a risk of prematurity and graft loss beyond that of preeclampsia for kidney transplant recipients. FUNDING SOURCE: The Transplant Pregnancy Registry International is supported in part by an educational grant from Veloxis Pharmaceuticals

    Emergent Prelabor Cesarean Birth in Solid Organ Transplant Recipients: Associated Risk Factors and Outcomes.

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    BACKGROUND: Pregnancies after solid-organ transplant are at a higher risk for antepartum admission and pregnancy complications, including cesarean birth. Emergent prelabor cesarean is associated with increased maternal and neonatal morbidity in other high-risk populations, but its incidence and impact in transplant recipients is not well understood OBJECTIVE: To characterize the risk factors and outcomes of emergency prelabor cesarean birth in kidney and liver transplant recipients STUDY DESIGN: Retrospective cohort study of all kidney and liver transplant recipients \u3e20 weeks\u27 gestation enrolled in the Transplant Pregnancy Registry International between 1976 and 2019. Participants admitted antepartum who required an emergency prelabor cesarean were compared to those admitted antepartum who underwent non-emergent birth. Primary outcomes were composite severe maternal morbidity and neonatal composite morbidity. Multivariable logistic regression was conducted for neonatal composite morbidity RESULTS: Of 1,979 births, 181 pregnancies (188 neonates) with an antepartum admission were included. 51 pregnancies (53 neonates, 28%) were delivered by emergent prelabor cesarean birth compared with 130 pregnancies (135 neonates, 72%) admitted antepartum who subsequently did not require emergent delivery. The most common indication for emergent delivery was non-reassuring fetal heart tracing (44 neonates, 86%). Pregnant people who underwent an emergent prelabor cesarean were less likely to birth at a transplant center (37.3% vs 41.5%, p=0.04) and had increased rates of chronic hypertension (33.3% vs 16.2%, p=0.02). There was no significant difference in severe maternal morbidity (3.9% vs 4.6%, p=0.84), though there was an increase in surgical site infection in the emergent prelabor cesarean cohort (3.9% vs 0%, p=0.02). Among those with an emergent prelabor cesarean, there was a significant increase in neonatal composite morbidity (43.4% vs 19.3%,

    Performance of the double multilayer monochromator on the NSLS wiggler beam line X25

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    A tunable, double multilayer x-ray monochromator has recently been implemented on the National Synchrotron Light Source (NSLS) X25 wiggler beam line. It is based on a parallel pair of tungsten-boron-carbide multilayer films grown on silicon substrates and purchased from Osmic, Inc. of Troy, Michigan, USA. It acts as an optional alternative to the conventional double silicon crystal monochromator, and uses the same alignment mechanism. Two other NSLS beam lines also have had this kind of monochromator installed recently, following the lead of the NSLS X20C IBM/MIT beam line which has used a double multilayer monochromator for several years. Owing to the 100 times broader bandwidth of a multilayer x-ray monochromator, compared with a silicon monochromator, the multilayer monochromator has the obvious advantage of delivering 100 times the flux of a silicon monochromator, and thereby makes more efficient use of the continuous synchrotron radiation spectrum, yet preserves the narrow collimation of the incident synchrotron beam. In particular, multilayer x-ray bandwidths, on the order of 1%, are well-matched to x-ray undulator linewidths. Performance results for the X25 multilayer monochromator are presented, comparing it with the silicon monochromator. Of note is its short- and long-term performance as an x-ray monochromator delivering the brightness of the wiggler source in the presence of the high-power white beam. Detailed measurements of its spatial beam profile and wavelength dispersion have been made, and it is shown how its resolution could be improved when desired. Finally, its peculiar, anisotropic resolution function in reciprocal space, and its bearing upon x-ray crystallography and scattering experiments, will be discussed, and highlighted by the results of a protein crystallography experiment. © 1997 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87844/2/71_1.pd

    The Effects of Helminth Removal on Coccidia Superspreaders in a Wild Peromyscus Population

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    Most living organisms are coinfected with multiple parasites that interact with each other and the host in complex, dynamic relationships. One way to explore these types of coinfected ecosystems is to selectively remove a dominant parasite from a host. This study explored the consequences of intestinal nematode removal on coccidia populations residing in the gut of wild Peromyscus mice in order to better understand macroparasite-microparasite relationships. It specifically focused on treatment effects in superspreaders of coccidia. These superspreaders were found to be sub-adult reproductive male mice (+10 log eggs/g, p = 2e-5). Hosts with characteristics of these superspreaders responded best to treatment: there was a significant decrease in coccidia burden and increase in parasite aggregation for males (-4.23 log eggs/g, p = 0.01; k < 0.10, p = 0.04) and sub-adults (-4.84 log eggs/g, p = 0.02; k < 0.17, p = 0.07). Furthermore, females showed a bipolar response to treatment, with 76% segregating into either a high infection category (38%; log 3-4 eggs/g) or a low infection category (38%; log 0-1 eggs/g). These categories are hypothesized to represent normal and pregnant female mice, respectively. Lastly, there was a trend towards decreasing prevalence of coccidia in the treated population (p = 0.11). These findings reveal notable heterogeneity in population responses to treatment and support a direct, immune-mediated interaction between nematodes and coccidia. It also highlights the benefits of targeting superspreaders to halt coccidia transmission, as these mice showed most pronounced decrease in coccidia burden and increase in parasite aggregation, predictive of more probable disease extinction within a population. The treatment outcomes described here are also applicable to human health, as deworming is a widely used practice in developing countries. Relationships drawn between the response of immune compromised mice to anthelmintics and the response of HIV positive patients to these drugs can be useful in predicting the outcome of health interventions and in informing global health policy

    Differentiating Acute Rejection From Preeclampsia After Kidney Transplantation

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    OBJECTIVE: To evaluate the clinical and laboratory characteristics in pregnancy that differentiate preeclampsia from acute renal allograft rejection and to investigate the maternal, neonatal, and graft sequelae of these diagnoses. METHODS: We conducted a retrospective case-controlled registry study of data abstracted from Transplant Pregnancy Registry International deliveries between 1968 and 2019. All adult kidney transplant recipients with singleton pregnancies of at least 20 weeks of gestation were included. Acute rejection was biopsy proven and preeclampsia was diagnosed based on contemporary criteria. Variables were compared using χ2, Fisher exact, and Wilcoxon rank sum tests as appropriate. Multivariable linear regression was used to analyze preterm birth. Kaplan-Meier curves with log-rank test and Cox proportional hazards model were used to compare graft loss over time. RESULTS: There were 26 pregnant women with biopsy-confirmed acute rejection who were matched by the year they conceived to 78 pregnant women with preeclampsia. Recipients with acute rejection had elevated peripartum serum creatinine levels (73% vs 14%, P\u3c.001), with median intrapartum creatinine of 3.90 compared with 1.15 mg/dL (P\u3c.001). Conversely, only patients with preeclampsia had a significant increase in proteinuria from baseline. Although there were no significant differences in maternal outcomes, graft loss within 2 years postpartum (42% vs 10%) and long-term graft loss (73% vs 35%) were significantly increased in recipients who experienced acute rejection (P\u3c.001 for both). The frequency of delivery before 32 weeks of gestation was 53% with acute rejection and 20% with preeclampsia. After controlling for hypertension and immunosuppressant use, acute rejection was associated with higher frequency of delivery at less than 32 weeks of gestation (adjusted odds ratio 4.04, 95% CI 1.10-15.2). CONCLUSION: In pregnancy, acute rejection is associated with higher creatinine levels, and preeclampsia is associated with increased proteinuria. Acute rejection in pregnancy carries a risk of prematurity and graft loss beyond that of preeclampsia for kidney transplant recipients. FUNDING SOURCE: The Transplant Pregnancy Registry International is supported in part by an educational grant from Veloxis Pharmaceuticals

    Discordant congenital heart defects in monochorionic twins: Risk factors and proposed pathophysiology.

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    A six-fold increase in congenital heart defects (CHD) exists among monochorionic (MC) twins compared to singleton or dichorionic twin pregnancies. Though MC twins share an identical genotype, discordant phenotypes related to CHD and other malformations have been described, with reported rates of concordance for various congenital anomalies at less than 20%. Our objective was to characterize the frequency and spectrum of CHD in a contemporary cohort of MC twins, coupled with genetic and clinical variables to provide insight into risk factors and pathophysiology of discordant CHD in MC twins. Retrospective analysis of all twins receiving prenatal fetal echocardiography at a single institution from January 2010 -March 2020 (N = 163) yielded 23 MC twin pairs (46 neonates) with CHD (n = 5 concordant CHD, n = 18 discordant CHD). The most common lesions were septal defects (60% and 45.5% in concordant and discordant cohorts, respectively) and right heart lesions (40% and 18.2% in concordant and discordant cohorts, respectively). Diagnostic genetic testing was abnormal for 20% of the concordant and 5.6% of the discordant pairs, with no difference in rate of abnormal genetic results between the groups (p = 0.395). No significant association was found between clinical risk factors and development of discordant CHD (p>0.05). This data demonstrates the possibility of environmental and epigenetic influences versus genotypic factors in the development of discordant CHD in monochorionic twins

    Mode of Obstetric Delivery in Kidney and Liver Transplant Recipients and Associated Maternal, Neonatal, and Graft Morbidity During 5 Decades of Clinical Practice

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    Importance: Rates of cesarean delivery (CD) are increased among transplant recipients. There is a need to define the indications for CD and associated outcomes among transplant recipients to determine the safest mode of obstetric delivery. Objective: To evaluate the association of mode of obstetrical delivery with maternal and neonatal morbidity among pregnant women who have received a kidney or liver transplant. Design, Setting, and Participants: This registry-based retrospective cohort study used data from the Transplant Pregnancy Registry International, which has recruited participants since 1991 from 289 diverse academic and community settings, mainly in North America. Eligible participants were recipients of a kidney or liver transplant who were aged 18 years or older at the time of a live birth at or later than 20 weeks\u27 gestational age and who delivered between 1968 and 2019. The data were analyzed from April 30, 2020, to April 16, 2021. Exposures: Scheduled CD, a trial of labor resulting in CD (TOL-CD), or a TOL resulting in vaginal delivery (TOL-VD). Main Outcomes and Measures: The primary outcomes were severe maternal morbidity and neonatal composite morbidity. Multivariate regression was conducted to calculate odds ratios (ORs) or β values and 95% CIs with adjustment for differences in maternal comorbidities and gestational age at delivery. Nonmedical indications for CD are those not associated with decreased morbidity or mortality in the obstetric literature. Results: This study included 1865 women, of whom 1435 were kidney transplant recipients and 430 were liver transplant recipients. The age range of the participants was 18 to 48 years; the median body mass index among the participants was in the normal range, and the median transplant-to-conception interval was more than 2 years. Compared with a scheduled CD, a TOL was not associated with increased severe maternal morbidity among kidney transplant recipients (TOL-CD: adjusted odds ratio [aOR], 1.80 [95% CI, 0.77-4.22]; TOL-VD: aOR, 1.22 [95% CI, 0.57-2.62]) (for liver transplant recipients, the numbers were too small for multivariate modeling). In the adjusted model, a TOL was associated with a decrease in neonatal composite morbidity among kidney transplant recipients who underwent TOL-CD (aOR, 0.52; 95% CI, 0.32-0.82) and TOL-VD (aOR, 0.36; 95% CI, 0.24-0.53) and liver transplant recipients who underwent TOL-VD (aOR, 0.41; 95% CI, 0.19-0.87) but not for TOL-CD (aOR, 0.58; 95% CI, 0.21-1.61). The main factors associated with CD after labor were placental abruption (aOR, 12.96; 95% CI, 2.85-59.07) and pregestational diabetes (aOR 5.44; 95% CI, 2.54-11.68). The rate of CD was 51.6% (741 of 1435) among kidney transplant recipients and 41.4% (178 of 430) among liver transplant recipients. In total, 229 of 459 kidney transplant recipients (49.9%) and 50 of 105 liver transplant recipients (47.6%) had scheduled CDs performed for either a nonmedical indication or a repeated indication, although women with these indications are candidates for a TOL. Conclusions and Relevance: In this cohort study, TOL vs a scheduled CD was associated with improved neonatal outcomes among kidney and transplant recipients and not with increased severe maternal morbidity among kidney transplant recipients. These findings may be used to facilitate multidisciplinary decisions regarding the mode of obstetrical delivery
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