Evaluating the role of pathogenic dementia variants in posterior cortical atrophy

Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to “posterior Alzheimer's disease (AD)” pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against ∼4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE ε4 association, and demonstrate the utility of NeuroX

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Periton Diyalizi Hastalarında Uygulanan Özyönetim Programının Hastaların Bazı Laboratuvar Bulguları, Sodyum ve Fosfor Tüketimi Davranışlarına Etkisi

Amaç: Bu çalışmanın amacı, periton diyalizi (PD) hastalarında uygulanan öz-yönetim programının hastaların bazı laboratuvar bulguları, sodyum ve fosfor tüketimi davranışlarına etkisini açıklamaktır. Gereç ve yöntem: Çalışmanın evrenini, Ocak-Mart 2020 tarihleri arasında Türkiye’nin batısında yer alan bir ildeki Üniversite Hastanesi Periton Diyalizi ünitesine ayaktan gelen 30 PD hastası oluşturmuştur. Bu çalışmada, ön test-son test deseni kullanılmıştır. Hastaların bazı laboratuvar bulguları, diyette sodyum ve fosfor alımı konusunda olumlu davranış değişikliği sağlamalarına yönelik öz yönetim programı uygulanmıştır. Çalışmada kullanılan anket formu iki bölümden oluşmuştur; 1. bölümde sosyo-demografik ve hastalığa ilişkin veriler, 2. bölümde ise sodyum ve fosfor alımına yönelik sorular yer almıştır. Çalışma verileri değerlendirilirken tanımlayıcı istatistiksel yöntemlerin yanında, ön test-son test puan ortalamaları arasındaki farkı saptamaya yönelik olarak, paired simple t testi ve Mc Namer testi uygulanmıştır. Bulgular: Periton diyalizi hastalarında, girişim öncesi ve sonrası bazı laboratuvar bulguları (plazma sodyum, idrar sodyum, diyalizat sodyum, plazma fosfor, idrar fosfor, plazma kalsiyum) puan ortalaması arasında istatistiksel olarak anlamlı fark bulunmamıştır (p>0,05). Periton diyalizi hastalarında girişim öncesi ve sonrası sodyum ve fosfor alımına yönelik sorulara verilen yanıtlara bakıldığında; ön test-son test puanları arasında istatistiksel olarak anlamlı fark saptanmamıştır (p>0,05). Sonuç: Periton diyalizi hastalarıyla yürütülen bu çalışma sonuçları, öz yönetim programının hastalarda bazı laboratuvar değerleri ve sodyum ve fosfor alımına yönelik olumlu değişimler yaratmadığını ortaya koymaktadır. Hastalarla daha uzun süre zaman geçirmeleri nedeniyle davranış değişikliği kazandırmada düzeyini artırmada hemşirelere önemli sorumluluklar düşmektedir.Objective: The aim of this study is to explain the effect of the self-management program applied in peritoneal dialysis (PD) patients on some laboratory findings, sodium and phosphorus consumption behaviors of the patients. Materials and Methods: The population of the study consisted of 30 PD patients who came to the peritoneal dialysis unit of the University Hospital in a province in the west of Turkey between January-March 2020. In this study, pretest-posttest design was used. A self-management program was applied for patients to provide positive behavioral changes regarding some laboratory findings and dietary sodium and phosphorus intake. Questionnaire form to be used in the study consisted of two parts; in the first part, socio-demographic and disease related data, and in the second part, questions about sodium and phosphorus intake were included. While evaluating the study data, in addition to descriptive statistical methods, paired simple t test and Mc Namer test were applied to determine the difference between the pretest-posttest mean scores. Results: There was no statistically significant difference between the mean scores of some laboratory findings (plasma sodium, urine sodium, dialysate sodium, plasma phosphorus, urine phosphorus, plasma calcium) in PD patients before and after the intervention (p>0.05). Considering the answers given to the questions about sodium and phosphorus intake before and after the intervention in PD patients; no statistically significant difference was found between pretest-posttest scores (p>0.05). Conclusion: The results of this study conducted with PD patients reveal that the self-management program did not create positive changes in some laboratory values and sodium and phosphorus intake in patients. Nurses have important responsibilities in increasing their level of gaining behavior change because they spend longer time with patients

IgA nephropathy: association of C4d with clinical and histopathological findings and possible role of IgM

Background: In patients with IgA nephropathy (IgAN) lectin and alternative pathways of the complement can be activated. Our aim was to analyze the association of glomerular and extraglomerular C4d stainingthe representative of lectin pathwaywith demographic, clinical and histopathological findings in primary IgAN patients. Design: Seventy-three patients were enrolled and after re-evaluation 37 of them were included in this study. Biopsies were analyzed for staining with anti-C4d primary monoclonal antibody by immunohistochemistry. Patients were classified as positive and negative groups based on their glomerular C4d deposition. Groups were compared for their baseline clinical and histopathological findings. Results: Sixteen (43.2%) of 37 patients were C4d-positive. Glomerular C4d-staining was associated with more severe proteinuria (2906mg/day vs. 1091mg/day; p=0.002), lower GFR (54.87mL/min vs. 95mL/min; p=0.023), higher blood pressure (p=0.022), more severe endocapillary hypercellularity (p<0.001) and more severe tubular atrophy (p<0.01). Mesangial IgM deposition was found to be associated with glomerular C4d staining and nephrotic range proteinuria. Conclusions: Glomerular C4d deposition was found to be associated with more unfavorable histopathological and clinical findings at the time of diagnosis. Association of mesangial IgM deposition with the activation of lectin pathway is a novel finding. Mesangial IgM deposition in our patients may reflect the genetic heterology of IgAN between diverse populations. However, since these data are about association, a cause-and-effect about IgM and IgAN cannot be proven solely with these findings

Association of Presence and Quantity of C4d with the Severity of Kidney Injury in Primary Membranous Nephropathy

OBJECTIVE: The aim of this study was to evaluate the correlation between glomerular C4d staining and the demographic, clinical and histopathological findings in patients with primary membranous nephropathy (MN)

Quantification of Immune Deposits in Renal Diseases

In this series of renal diseases, in addition to semiquantitative scoring of direct immunofluorescein images, the immune deposits were quantified by image analysis. The aim of this study was to evaluate quantitative measurements for diagnosis and prognosis of renal immune complex diseases. Immunoglobulin A (IgA) nephropathy (n = 27, 54%), membranous nephropathy (n = 8, 16%), membranoproliferative glomerulonephritis (n = 8, 16%), and systemic lupus erithematosus nephritis cases (n = 7, 14%) were evaluated by semiquantitative scores (SS) for IgG, IgA, IgM, C3, C1q, lambda, and kappa. The quantitative measures, intensity, mean and total optical density (MOD and TOD) were determined by image analysis software. There was positive correlation between SS; and intensity as well as TOD for 199 positive stained images, but not between SS and MOD. TOD was important for determining SS by linear regression. When all of the cases were considered, creatinin at the time of biopsy was only slightly correlated with intensity and TOD of IgM. Intensity and TOD, but not SS of IgA was significantly increased in IgA nephropathy cases with adverse histopathologic prognostic features. In 4 cases (8%) only TOD allowed identification of the predominantly deposited antibody. TOD and intensity seems to have better correlation with prognostic histopathologic features than SS. TOD may be useful for determining predominant immune deposit, a feature important for diagnosis