Pathological classification and prognosis of renal damage caused by antineutrophil cytoplasmic antibody associated vasculitis

Objective To analyze the pathological characteristics and prognostic factors of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods A retrospective analysis of AAV patients with renal biopsy results admitted to Kidney Disease Center of the First Affiliated Hospital from January 2004 to February 2017 was performed. The patients were divided into 4 types according to Berden classification, and their clinical, pathological characteristics and prognosis were compared. The survival curves of each type of patients were plotted by Kaplan-Meier method, and the difference of survival curves was compared using Log-rank test. With entering the maintenance dialysis as the endpoint, Cox regression was used to analyze the prognostic factors. Results A total of 175 patients with AAV, including 59 cases (33.7%) of focal type, 39 cases (22.3%) of crescent type, 32 cases (18.3%) of sclerosis type, 45 cases (25.7%) of mixed type. The basal serum creatinine levels in crescent type group and sclerosis type group were significantly higher than those in the focal type group or mixed type group (all P＜0.05), and loop necrosis rate in sclerosis type group was significantly lower than chat in the focal type group or crescent type group (both P＜0.05). The median follow-up period was 11.8 (0.5-86.7) months. The event-free survival rates were 83.1%, 77.8%, 64.1% and 50.0% in the focal type, mixed type, crescent type and sclerotic type groups (Log-rank χ2=11.537, P=0.009). Cox regression analysis showed higher parathyroid hormone (HR=1.013, 95%CI 1.007-1.019, P＜0.001), glomerular sclerosis ≥50% (HR=10.532, 95%CI 2.903-38.203, P＜0.001) were independent risk factors for AAV patients entering maintenance dialysis, and higher estimated glomerular filtration rate (HR=0.943, 95%CI 0.896-0.993, P=0.025) was protective factor. Conclusion The prognosis of AAV renal damage is worsened according to focal, mixed, crescent and sclerosis types. Lower estimated glomerular filtration rate, higher parathyroid hormone and glomerular sclerosis ≥50% are independent risk factors for AAV patients entering maintenance dialysis.     

Frizzled Receptors in Tumors,Focusing on Signaling,Roles, Modulation Mechanisms,and Targeted Therapies

Wnt molecules play crucial roles in development and adult homeostasis through their receptors Frizzled proteins (Fzds). Fzds mediate canonical β-catenin pathway and various noncanonical β-catenin-independent pathways. Aberrant Fzd signaling is involved in many diseases including cancer. Wnt/β-catenin is a well-established oncogenic pathway involved in almost every aspect of tumor development. However, Fzd-mediated noncanonical Wnt pathways function as both tumor promoters and tumor suppressors depending on cellular context. Fzd-targeted therapies have proven to be effective on cultured tumor cells, tumor cell xenografts, mouse tumor models, and patient-derived xenografts (PDX). Moreover, Fzd-targeted therapies synergize with chemotherapy in preclinical models. However, the occurrence of fragility fractures in patients treated with Fzd-targeted agents such as OMP-54F28 and OMP-18R5 limits the development of this combination. Along with new insights on signaling, roles, and modulation mechanisms of Fzds in human tumors, more Fzd-related therapeutic targets will be developed.Key words: Wnt, Frizzled, β-Catenin, Tumor     

A rare case of monozygotic triplets with Duchenne muscular dystrophy

Twins with Duchenne muscular dystrophy (DMD) have been widely studied. We report the first rare case of monozygotic triplets with DMD who shared consistent phenotypes, including delayed motor and language milestones, muscle wasting and weakness, joint contracture, and lumbar lordosis. Muscle magnetic resonance imaging and biopsy revealed the similar muscle injury characteristics and dystrophin absence. Short tandem repeat analysis confirmed monozygosity. A de novo mutation (exon 49–52 deletion) was found in the triplets but not in their mother. Treatment included prednisone, idebenone, and rehabilitation management. At the 2-year follow-up, motor function had deteriorated, and muscle fatty infiltration was more extensive and severe. Our case offers a unique opportunity for genetic and therapeutic research. Furthermore, it highlights the critical role of genetic factors in DMD phenotypes and provides a potential choice for treatment observations.     

Dual-Energy Computed Tomography Pulmonary Angiography: Comparison of Vessel Enhancement between Linear Blended and Virtual Monoenergetic Reconstruction Techniques

Introduction

Optimal opacification of the pulmonary vasculature is a fundamental factor of a diagnostic quality computed tomography pulmonary angiogram (CTPA). This retrospective study examined the feasibility of utilising a noise-optimised monoenergetic reconstruction of the dual-energy computed tomography pulmonary angiogram (DE-CTPA) as an additional protocol to increase vessel opacification.

Association of malnutrition with all-cause mortality in the elderly population: A 6-year cohort study

Background and aimsFew studies have explored the association between malnutrition, defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality, particularly in the Chinese population. This study aimed to investigate the association between the GNRI and all-cause mortality in the elderly population.Methods and resultsParticipants aged ≥60 years were eligible for this study and were divided into three groups by the GNRI: An adequate nutrition group, participants with a GNRI ≥98; mild malnutrition group, participants with a GNRI ≥82 but <98; and a severe malnutrition group, participants with a GNRI <82. The results implied that there was a positive association between severe malnutrition and all-cause mortality in the total population (hazard ratio (HR): 2.591 and 95% confidence interval (CI): 1.729–3.884), male subjects (HR: 2.903 and 95% CI: 1.718–4.906), and female subjects (HR: 2.081 and 95% CI: 1.071–4.046). Similar associations between severe malnutrition and all-cause mortality were observed in both the 60–69 and 70–79 years age groups (HR: 2.863 and 2.600, 95% CI: 1.444–5.678 and 1.394–4.849, respectively). However, no significant association was observed between mild malnutrition and all-cause mortality.ConclusionsSevere malnutrition could increase all-cause mortality in the 60- to 79-year-old population. However, there was no association of mild malnutrition with all-cause mortality.     

Assessment of fluid and nutritional status using bioelectrical impedance methods in acute kidney injury patients requiring continuous renal replacement therapy

Objective To investigate the predictive value of nutritional and fluid status measured by bioelectrical impedance methods for the prognosis of acute kidney injury (AKI) patients undergoing continuous renal replacement therapy (CRRT). Methods Patients with severe AKI received CRRT in the First Affiliated Hospital of Nanjing Medical University from September 2016 to September 2018 were enrolled, and divided into death group and survival group according to 28-day survival. Cox regression was used to analyze the association between 28-day survival and lean tissue index (LTI), fat tissue index (FTI), the ratio of extracellular water (ECW) and body cell mass (BCM) (ECW/BCM), and overhydration (OH), respectively. Results A total of 156 patients were included, including 101 males and 55 females. The age was (62.7±15.4) years, with sequential organ failure assessment (SOFA) score of 9.9±3.9. The 28-day mortality rate was 46.2%. The pre-CRRT OH values in the 28-day survival group and death group were 2.95(1.80, 5.50) L and 4.20(2.95, 5.70) L(P=0.016), and ECW/BCM values were 1.00(0.76, 1.18) and 1.07(0.88, 1.25) (P=0.033), respectively. Univariate Cox regression analysis showed that pre-CRRT high OH values (HR=1.08, 95%CI 1.00-1.17, P=0.040) and high ECW/BCM values (HR=3.02, 95%CI 1.46-6.22, P=0.003) were associated with 28-day death. The changes of OH values (HR=0.83, 95%CI 0.72-0.95, P=0.008) and ECW/BCM values (HR=6.79, 95%CI 1.72-26.82, P=0.006) between pre-CRRT and the 7th day after CRRT initiation were significantly associated with 28-day mortality in patients who survived 7 days after CRRT initiation. After adjusting for age, gender, and SOFA scores, multivariate Cox regression analysis showed that the high OH value (HR=1.16, 95%CI 1.06-1.27, P=0.002) and the high ECW/BCM value (HR=2.80, 95%CI 1.30-6.06, P=0.003) before CRRT, the change of OH value (HR=0.82, 95%CI 0.72-0.95, P=0.008) and ECW/BCM value (HR=2.79, 95%CI 1.30-5.98, P=0.009) between the 7th day after CRRT initiation and pre-CRRT, were independently associated with 28-day death, while LTI (HR=0.93, 95%CI 0.86-1.02, P=0.113) and FTI (HR=0.98, 95%CI 0.92-1.04, P=0.475) before CRRT were uncorrelated with 28-day death. Conclusions In bioelectrical impedance analysis, the high OH value and high ECW/BCM value before CRRT are associated with 28-day mortality in patients with AKI, while the nutritional indicators LTI and FTI before CRRT are not significantly related. The correction of fluid overload by CRRT within 7 days may reduce the risk of 28-day mortality.     

Longitudinal blood pressure patterns and cardiovascular disease risk

Abstract

Observational and interventional studies have unequivocally demonstrated that “present”, i.e. single-occasion, blood pressure is one of the key determinants of cardiovascular disease risk. Over the past two decades, however, numerous publications have suggested that longitudinal blood pressure data and assessment of long-term blood pressure exposure provide incremental prognostic value over present blood pressure. These studies have used several different indices to quantify the overall exposure to blood pressure, such as time-averaged blood pressure, cumulative blood pressure, blood pressure trajectory patterns, and age of hypertension onset. This review summarises existing research on the association between these indices and hard cardiovascular outcomes, outlines the strengths and weaknesses of these indices, and provides an overview of how longitudinal blood pressure changes can be measured and used to improve cardiovascular disease risk prediction.

• KEY MESSAGES

• Numerous recent publications have examined the relation between cardiovascular disease and long-term blood pressure (BP) exposure, quantified using indices such as time-averaged BP, cumulative BP, BP trajectory patterns, and age of hypertension onset.

• This review summarises existing research on the association between these indices and hard cardiovascular outcomes, outlines the strengths and weaknesses of these indices, and provides an overview of how longitudinal BP changes can be measured and used to improve cardiovascular disease risk prediction.

• Although longitudinal BP indices seem to predict cardiovascular outcomes better than present BP, there are considerable differences in the clinical feasibility of these indices along with a limited number of prospective data.