RESUMEN
The diagnostic potential of paramagnetic rim lesions (PRLs) has been previously established; however, the prognostic significance of these lesions has not previously been consistently described. This study aimed to establish the prognostic role of PRLs in MS with respect to the Expanded Disability Status Scale (EDSS) and rates of disability progression. Databases of PubMed, EMBASE, Scopus and reference lists of selected articles were searched up to 29/04/2023. The review was conducted in accordance with PRISMA guidelines and was registered prospectively on PROSPERO (CRD42023422052). 7 studies were included in the final review. All of the eligible studies found that patients with PRLs tend to have higher baseline EDSS scores. Longitudinal assessments revealed greater EDSS progression in patients with PRLs over time in most studies. However, the effect of location of PRLs within the central nervous system were not assessed across the studies. Only one study investigated progression independent of relapse activity (PIRA) and showed that this clinical entity occurred in a greater proportion in patients with PRLs. This review supports PRLs as a predictor of EDSS progression. This measure has widespread applicability, however further multicentre studies are needed. Future research should explore the impact of PRLs on silent disability, PIRA, take into account different MS phenotypes and the topography of PRLs in prognosis.
RESUMEN
BACKGROUND: Transplanted women have high rates of pre-eclampsia. However, determinants of pre-eclampsia and association with graft survival and function remain uncertain. We aimed to determine rates of pre-eclampsia and its association with kidney transplant survival and function. METHODS: Retrospective cohort study analyzing post-kidney transplantation pregnancies (≥20 weeks gestation) from the Australia and New Zealand Dialysis and Transplant Registry (2000-2021). Graft survival was assessed in 3 models accounting for repeated pregnancies and episodes of pre-eclampsia. RESULTS: Pre-eclampsia status was captured in 357/390 pregnancies and occurred in 133 pregnancies (37%). The percentage of pregnancies reported to have pre-eclampsia rose from 27% in 2000-2004, to 48% from 2018-2021. Reported prior exposure to calcineurin inhibitors was high overall, and higher in women who had pre-eclampsia (97% vs 88%, p=0.005). Seventy-two (27%) graft failures were identified after a pregnancy, with median follow-up of 8.08 years. Although women with pre-eclampsia had higher median preconception serum creatinine concentration (1.24 ((IQR) 1.00-1.50) vs. 1.13 (0.99-1.36) mg/dL; p=0.02), in all survival models, pre-eclampsia was not associated with higher death-censored graft failure. In multivariable analysis of maternal factors (age, body mass index, primary kidney disease and transplant-pregnancy interval, preconception serum creatinine concentration, era of birth event and Tacrolimus or Cyclosporin exposure) only era and preconception serum creatinine concentration ≥1.24 mg/dL (odds ratio 2.48, 95% CI 1.19-5.18) was associated with higher pre-eclampsia risk. Both preconception eGFR <45 ml/min/1.73m 2 (adjusted HR 5.55, 95% CI 3.27-9.44, p<0.001) and preconception serum creatinine concentration ≥1.24 mg/dL (adjusted HR 3.06, 95% CI 1.77-5.27, p<0.001) were associated with a higher risk of graft failure even after adjusting for maternal characteristics. CONCLUSIONS: In this large and contemporaneous registry cohort, pre-eclampsia was not associated with worse graft survival or function. Preconception kidney function was the main determinant of graft survival.
RESUMEN
Macromolecular crowding effects arise from steric repulsions and weak, nonspecific, chemical interactions. Steric repulsions stabilize globular proteins, but the effect of chemical interactions depends on their nature. Repulsive interactions such as those between similarly charged species should reinforce the effect of steric repulsions, increasing the equilibrium thermodynamic stability of a test protein. Attractive chemical interactions, on the other hand, counteract the effect of hard-core repulsions, decreasing stability. We tested these ideas by using the anionic proteins from Escherichia coli as crowding agents and assessing the stability of the anionic test protein chymotrypsin inhibitor 2 at pH 7.0. The anionic protein crowders destabilize the test protein despite the similarity of their net charges. Thus, weak, nonspecific, attractive interactions between proteins can overcome the charge-charge repulsion and counterbalance the stabilizing effect of steric repulsion.