COVID-19 in the immunocompromised population: data from renal allograft recipients throughout full cycle of the outbreak in Hubei province, China.
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ABSTRACT:
SUBMITTER: Zhang W
PROVIDER: S-EPMC8769129 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND AND OBJECTIVES: Sequential echocardiography is routinely performed in patients with ESRD listed for transplantation. The benefit of this labor- and time-intensive measure, however, remains unclear. Thus, this study elucidated the various obtained routine echocardiography parameters that best predicted mortality and graft survival after renal transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study investigated 553 first renal transplant recipients listed in the Austrian Dialysis and Transplant Registry between 1992 and 2011 who had echocardiographic analysis at transplantation and survived at least 1 year. Cox proportional hazards models with the purposeful selection algorithms for covariables were used to identify predictors of mortality and graft loss. A Fine and Gray model was used to evaluate cause-specific death. RESULTS: During a median follow-up of 7.14 years, 81 patients died, and 59 patients experienced graft loss after the first year. The Kaplan-Meier analysis showed that 85% of patients with a left atrial diameter below the median of 53 mm were alive 10 years after transplantation, whereas only 70% of those patients with a left atrial diameter equal to or above the median had survived (P<0.001). In the multivariable model, left atrial diameter (per millimeter) independently predicted overall mortality (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.08; P<0.001) and cause-specific cardiac death (hazard ratio, 1.04; 95% confidence interval, 1.00 to 1.08; P=0.04). Functional graft loss was predicted by the right atrial diameter (hazard ratio, 1.04; 95% confidence interval, 1.02 to 1.07; P=0.001). CONCLUSION: The left atrial diameter determined at transplantation predicted overall and cardiac mortality. Patients with widely enlarged left atria exhibit a considerably reduced life expectancy. It remains to be determined, however, whether renal transplantation is futile in these patients.
| S-EPMC3848405 | biostudies-other
Project description: Not available
| S-DIXA-D-1152 | biostudies-other
Project description:Steroid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We aimed to gain insight into the mechanisms underlying steroid resistance by identifying novel molecular markers of steroid-refractory acute rejection. Eighty-three kidney transplant recipients (1995-2005), who were treated with methylprednisolone during a first acute rejection episode, were included in this study. Gene expression patterns were investigated in a discovery cohort of 36 acute rejection biopsies, and verified in a validation cohort of 47 acute rejection biopsies. In the discovery set, expression of metallothioneins (MT) was significantly (P<0.000001) associated with decreased response to steroid treatment. Multivariate analysis resulted in a predictive model containing MT-1 as an independent covariate (AUC=0.88, P<0.0000001). In the validation set, MT-1 expression was also significantly associated with steroid resistance (P=0.029). Metallothionein expression was detected in macrophages and tubular epithelial cells. Parallel to the findings in patients, in vitro experiments of peripheral blood mononuclear cells from 11 donors showed that non-response to methylprednisolone treatment is related to highly elevated MT levels. High expression of metallothioneins in renal allografts is associated with resistance to steroid treatment. Metallothioneins regulate intracellular concentrations of zinc, through which they may diminish the zinc-requiring anti-inflammatory effect of the glucocorticoid receptor.
2013-05-21 | GSE47097 | GEO
Project description:BACKGROUND:In 2017, an outbreak of onychomadesis occurred in kindergarten H, Hubei province, China. We investigated the field to learn about the magnitude and reason of the outbreak. METHODS:The case definition was that a child with onychomadesis or transverse ridging (Beau's line) in fingernails and toenails without previous traumatic or systemic disease in kindergarten H from Sep. 1st to Nov. 30th, 2017. A retrospective cohort study was carried out to analyze the epidemiological relationship between onychomadesis and the hand-foot-mouth disease (HFMD) in Primary Class #2, kindergarten H. We also performed a serological survey for neutralizing antibodies against coxsackie virus A6 (CVA6), coxsackie virus A10 (CVA10) among 15 cases and six healthy children in the kindergarten. Meanwhile, some children were carried out with routine blood, fungal microscopic and microelement tests. Indoor environment examinations had been done for all classes. RESULTS:A total of 20 cases were identified in Kindergarten H. Seventy-five percent (15/20) cases occurred in Primary Class #2. Fifty-five percent of the cases (11/20) had suffered from HFMD within two months. The median time between onychomadesis and HFMD was 45?days (ranging from 31 to 58?days). A retrospective cohort study in Primary Class #2 showed the attack rate was 90.0% among 10 children who suffered from HFMD in the past two months compared to 30.0% among 20 children who didn't (Rate Ratio [RR] =3.0, 95% Confidence Interval [CI] =1.5-6.0). The positive rates of neutralizing antibodies were 66.7% for CVA6 and 26.7% for CVA10 in tested cases. The result of routine blood, fungal microscopic, microelements tests were normal in cases. The indicators of environment were within the normal range. CONCLUSION:The results of this study suggested that the outbreak of onychomadesis in Hubei province was probably associated with HFMD epidemic within two months.
| S-EPMC6878681 | biostudies-literature
Project description:At the moment of writing, the future evolution of the COVID-19 epidemic is unclear. Predictions of the further course of the epidemic are decisive to deploy targeted disease control measures. We consider a network-based model to describe the COVID-19 epidemic in the Hubei province. The network is composed of the cities in Hubei and their interactions (e.g., traffic flow). However, the precise interactions between cities is unknown and must be inferred from observing the epidemic. We propose the Network-Inference-Based Prediction Algorithm (NIPA) to forecast the future prevalence of the COVID-19 epidemic in every city. Our results indicate that NIPA is beneficial for an accurate forecast of the epidemic outbreak.
| S-EPMC7341469 | biostudies-literature
Project description:Steroid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We aimed to gain insight into the mechanisms underlying steroid resistance by identifying novel molecular markers of steroid-refractory acute rejection. Eighty-three kidney transplant recipients (1995-2005), who were treated with methylprednisolone during a first acute rejection episode, were included in this study. Gene expression patterns were investigated in a discovery cohort of 36 acute rejection biopsies, and verified in a validation cohort of 47 acute rejection biopsies. In the discovery set, expression of metallothioneins (MT) was significantly (P<0.000001) associated with decreased response to steroid treatment. Multivariate analysis resulted in a predictive model containing MT-1 as an independent covariate (AUC=0.88, P<0.0000001). In the validation set, MT-1 expression was also significantly associated with steroid resistance (P=0.029). Metallothionein expression was detected in macrophages and tubular epithelial cells. Parallel to the findings in patients, in vitro experiments of peripheral blood mononuclear cells from 11 donors showed that non-response to methylprednisolone treatment is related to highly elevated MT levels. High expression of metallothioneins in renal allografts is associated with resistance to steroid treatment. Metallothioneins regulate intracellular concentrations of zinc, through which they may diminish the zinc-requiring anti-inflammatory effect of the glucocorticoid receptor. Transcriptional profiles of 40 renal allograft biopsy samples were analyzed using Illumina HumanRef-8 v3.0 BeadChips (Illumina, San Diego, CA). Expression profiles were investigated in total RNA isolated from biopsy samples of 18 patients with steroid responsive acute rejection and 18 patients with steroid resistant acute rejection. Four biopsies, taken during acute decrease of graft function but with no histomorphologic indication of rejection, were included as controls.
2013-05-21 | E-GEOD-47097 | biostudies-arrayexpress
Project description:Over a follow-up period of 6 years, 4 out of 31 live related renal allograft recipients (12.9%) developed azathioprine induced bone marrow suppression. Presentation in 3 patients was with fever and 2 patients also had associated graft dysfunction. All patients had leucopenia, 2 patients in addition had anaemia and one patient had pancytopenia. Bone marrow suppression developed 9.6 months (3.5-16.0 months) following transplantation and recovery followed over a period of 30 (18-49 days) days after withdrawal of the drug. One patient succumbed during the phase of bicytopenia.
| S-EPMC5530283 | biostudies-other
Project description:Adiponectin (ADPN) prevents the development/recurrence of cardiovascular events via its anti-atherogenic effects. However, few long-term studies have examined the changes in serum ADPN levels and arterial calcification seen in renal allograft recipients.The effects of the serum ADPN level on arterial calcification were examined in 51 Japanese renal allograft recipients. Abdominal aorta calcification was evaluated on computed tomography using the aortic calcification area index (ACAI). The change in the ACAI and serum high-molecular-weight (HMW)-ADPN fractions were studied over an 8-year period. The arterial expression of ADPN, ADPN receptors (AdipoR)1 and 2, and T-cadherin (cadherin-13) were also examined by immunohistochemistry.The change in the ACAI were grouped into quartiles and compared with the alterations in the serum levels of each ADPN fraction over an 8-year period. The change in the ACAI was much lower in the patients with highly elevated HMW-ADPN levels.Multiple regression analysis demonstrated that an advanced age at transplant and a history of cardiovascular complications were associated with an increased change in the ACAI, while higher HMW-ADPN concentrations were associated with improvements in the ACAI. Serum HDL-C level was also identified as a positive factor to increase serum HMW-ADPN level.In immunohistochemical examinations, ADPN was detected on CD31-positive arterial endothelial cells from renal allograft biopsy samples. ADPN co-localized with T-cadherin and AdipoR1, but only partially co-localized with AdipoR2.Both HMW-ADPN and HDL-C might inhibit the progression of vascular calcification by promoting ADPN binding to vascular endothelial cells via T-cadherin and AdipoR in Japanese renal allograft recipients.
| S-EPMC5931493 | biostudies-literature
Project description:BACKGROUND:Cardiovascular disease (CVD) due to atherosclerosis is a major cause of death in renal allograft recipients. Recently, C1q/TNF-? related protein-9 (CTRP9), which is a paralog of adiponectin (ADPN), has been suggested to be related to the prevention of atherosclerosis and the occurrence of CVD, but this relationship has not been confirmed in renal allograft recipients. SUBJECTS AND METHODS:The relationships among the serum CTRP9 concentration, serum ADPN concentration, and vascular calcification were investigated in 50 kidney transplantation recipients at our hospital. Calcification of the abdominal aorta was evaluated according to the aortic calcification area index (ACAI) calculated from CT images. Changes in the serum CTRP9 and ADPN fractions and ACAI were examined for 8 years. In addition, the expression of CTRP9 and ADPN and their respective receptors AdipoR1 and R2 in muscular arteries of the kidney was examined by immunofluorescence. RESULTS:In renal allograft recipients, the serum CTRP9 concentration at the start of the observation was not significant correlated with eGFR or serum high-molecular-weight (HMW)-ADPN concentration (rS = -0.009, p = 0.950; rS = -0.226, p = 0.114, respectively). However, the change in the serum CTRP9 concentration was positively correlated with the change in the serum HMW-ADPN concentration (rS = 0.315, p = 0.026) and negatively correlated with the change in ACAI (rS = -0.367, p = 0.009). Multiple regression analysis revealed that the serum HMW-ADPN concentration was a significant positive factor for the change in the serum CTRP9 concentration. Moreover, for ACAI, an increase in the serum CTRP9 concentration was an improving factor, but aging was an exacerbating factor. Furthermore, colocalization of CTRP9 and AdipoR1 was noted in the luminal side of intra-renal arterial intima. CONCLUSION:In renal allograft recipients, both CTRP9 and HMW-ADPN were suggested to prevent the progression of aortic calcification through AdipoR1.
| S-EPMC6964899 | biostudies-literature
Project description:BackgroundMycophenolic acid (MPA) is widely used as part of immunosuppressive regimens following allograft transplantation. The large pharmacokinetic (PK) and pharmacodynamic (PD) variability and narrow therapeutic range of MPA provide a potential for therapeutic drug monitoring. The objective of this pilot study was to investigate the MPA PK and PD relation in combination with belatacept (2nd generation CTLA4-Ig) or cyclosporine (CsA).MethodsSeven renal allograft recipients were randomized to either belatacept (n = 4) or cyclosporine (n = 3) based immunosuppression. Samples for MPA PK and PD evaluations were collected predose and at 1, 2 and 13 weeks posttransplant. Plasma concentrations of MPA were determined by HPLC-UV. Activity of inosine monophosphate dehydrogenase (IMPDH) and the expressions of two IMPDH isoforms were measured in CD4+ cells by HPLC-UV and real-time reverse-transcription PCR, respectively. Subsets of T cells were characterized by flow cytometry.ResultsThe MPA exposure tended to be higher among belatacept patients than in CsA patients at week 1 (P = 0.057). Further, MPA concentrations (AUC0-9 h and C0) increased with time in both groups and were higher at week 13 than at week 2 (P = 0.031, n = 6). In contrast to the postdose reductions of IMPDH activity observed early posttransplant, IMPDH activity within both treatment groups was elevated throughout the dosing interval at week 13. Transient postdose increments were also observed for IMPDH1 expression, starting at week 1. Higher MPA exposure was associated with larger elevations of IMPDH1 (r = 0.81, P = 0.023, n = 7 for MPA and IMPDH1 AUC0-9 h at week 1). The maximum IMPDH1 expression was 52 (13-177)% higher at week 13 compared to week 1 (P = 0.031, n = 6). One patient showed lower MPA exposure with time and did neither display elevations of IMPDH activity nor IMPDH1 expression. No difference was observed in T cell subsets between treatment groups.ConclusionThe significant influence of MPA on IMPDH1 expression, possibly mediated through reduced guanine nucleotide levels, could explain the elevations of IMPDH activity within dosing intervals at week 13. The present regulation of IMPDH in CD4+ cells should be considered when interpreting measurements of IMPDH inhibition.
| S-EPMC2724496 | biostudies-literature