Refining Kidney Survival in 383 Genetically Characterized Patients With Nephronophthisis

Introduction: Nephronophthisis (NPH) comprises a group of rare disorders accounting for up to 10% of end-stage kidney disease (ESKD) in children. Prediction of kidney prognosis poses a major challenge. We assessed differences in kidney survival, impact of variant type, and the association of clinical characteristics with declining kidney function. Methods: Data was obtained from 3 independent sources, namely the network for early onset cystic kidney diseases clinical registry (n = 105), an online survey sent out to the European Reference Network for Rare Kidney Diseases (n = 60), and a literature search (n = 218). Results: A total of 383 individuals were available for analysis: 116 NPHP1, 101 NPHP3, 81 NPHP4 and 85 NPHP11/TMEM67 patients. Kidney survival differed between the 4 cohorts with a highly variable median age at onset of ESKD as follows: NPHP3, 4.0 years (interquartile range 0.3–12.0); NPHP1, 13.5 years (interquartile range 10.5–16.5); NPHP4, 16.0 years (interquartile range 11.0–25.0); and NPHP11/TMEM67, 19.0 years (interquartile range 8.7–28.0). Kidney survival was significantly associated with the underlying variant type for NPHP1, NPHP3, and NPHP4. Multivariate analysis for the NPHP1 cohort revealed growth retardation (hazard ratio 3.5) and angiotensin-converting enzyme inhibitor (ACEI) treatment (hazard ratio 2.8) as 2 independent factors associated with an earlier onset of ESKD, whereas arterial hypertension was linked to an accelerated glomerular filtration rate (GFR) decline. Conclusion: The presented data will enable clinicians to better estimate kidney prognosis of distinct patients with NPH and thereby allow personalized counseling

Entrepreneurial growth and ownership under market socialism in China: a longitudinal case study of small business growth

How firms grow is still a mystery and a definitive explanation remains elusive. This is especially the case for emerging economies, where the development of research into business growth has been notably slow whilst emerging business ventures are developing at hyper speed. Since most empirical studies have focused on the quantitative differences in growth across firms, this paper adopts a longitudinal case study approach to explore the qualitative differences in terms of how various types of firm achieve their growth outcomes in the organisational development process over a prolonged period of time. Through a theoretical lens which focuses on growth process approaches, this study not only demonstrates that entrepreneurial processes take different forms and dimensions in different contexts, but it also provides insights into the interactions of various organisational factors underpinning the strategies and changes that lead to contrasting growth outcomes. Case study findings assert that the ownership factor is a key contingent factor that shapes management structure and resources which, in turn, affect particular entrepreneurial outcomes. Furthermore, a combination of leadership style and the approach to knowledge management also play critical roles in the learning process which, tends to determine the strategy choice of either high or low value added product strategy. The findings of this research are that small firms with a low value product strategy can improve their survival chances and growth through the vertical broadening of a product portfolio in synchrony with increasing production and technology advancement. The case study companies show a tendency to reinforce their industry position by adopting contrasting choices for growth. The paper addresses the challenges and managerial implications for Western company managers in different growth contexts

Weight Gain after Interferon-Free Treatment of Chronic Hepatitis C—Results from the German Hepatitis C-Registry (DHC-R)

Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term weight change of patients receiving interferon-free antiviral treatment for chronic hepatitis C. The German Hepatitis C-registry (DHC-R) is a national multicenter real-world cohort. A total of 5111 patients were followed prospectively after DAA treatment for up to 3 years. Weight change compared to baseline was analyzed at end of treatment and at years 1, 2, and 3 after completion of antiviral therapy. Regression analysis was performed to identify baseline predictors for weight change. While there was no relevant mean weight change (−0.2 kg, SD 4.3 kg) at the end of antiviral treatment, weight started to increase during long-term follow-up reaching +1.7 kg (SD 8.0 kg, p < 0.001) compared to baseline at 3 years (follow-up year 3, FU3) after completion of antiviral therapy. 48%, 31%, and 22% of patients had a weight gain greater than 1, 3, and 5 kg at FU3, respectively. During follow-up, a body mass index (BMI) <30 proved to be the only consistent predictor for weight gain. DAA treatment is followed by a substantial weight gain (+3 kg or more) in one-third of the patients during long-term follow-up. Non-obese patients seemed to be most vulnerable to weight gain. The body compartment involved in weight gain as well as the mechanism of weight gain remain to be elucidated

Supplementary Material for: HCC Immune Surveillance and Antiviral Therapy of Hepatitis C Virus Infection

<b><i>Objective:</i></b> HCV clearance by current antiviral therapies improves clinical outcomes but falls short in eliminating the risk for hepatocellular carcinoma (HCC) emergence. As the HCC immune surveillance establishment is vital for the control of neoplastic development and growth, we investigated its correlation with on-/post-treatment HCC emergence, and further analyzed the influence of viral eradication on this setup in patients with HCV-related liver cirrhosis. <b><i>Design:</i></b> PBMC isolated at baseline and longitudinally during therapy were analyzed for tumor-associated antigen (TAA)-specific CD8+ T cell responses against glypican-3 overlapping peptides in vitro using high-definition flow cytometry. Multianalyte profiling of fifty soluble inflammatory mediators (SIM) in the plasma was also performed using Luminex-based multiplex technology. <b><i>Results:</i></b> Cirrhosis patients were characterized by an altered profile of distinct SIMs at baseline. At this time point, immune-surveilling T cells targeting specific HCC-associated antigens were readily detectable in HCV-free cirrhosis patients whilst being rather weak in such patients who further developed HCC upon virus eradication. Therapy-induced cure of HCV infection analogously reduced the strength of the prevailing HCC immune surveillance machinery, particularly by CD8+ T cells in cirrhosis patients. These results were further validated by T cell reactivities to six immuno-dominant HCC-associated HLA-A2-restricted epi­topes. Further, we demonstrated that this phenomenon was likely orchestrated by alterations in SIMs – with evidence of IL-12 being a major culprit. <b><i>Conclusion:</i></b> Given the relationship between the baseline HCC-specific immune surveilling T cell responses and therapy-associated HCC emergence, and the impact of HCV clearance on its strength and magnitude, we recommend a continued HCC screening in cirrhotic HCV patients despite HCV resolution

For Love of Country? Consumer Ethnocentrism in China, South Korea, and the United States

This cross-cultural comparison aims to understand whether the influence of consumer ethnocentrism (CE) on consumer preference for domestic versus foreign products is product category and country-of-origin dependent. Three countries with dissimilar cultural orientation and economic status-China, South Korea, and the United States-were examined. American consumers were found to be more ethnocentric than Chinese and South Korean consumers. CE was found to significantly and positively predict American and Korean consumers' preference for domestic products across product categories, while Chinese consumers' CE did not translate into their preference for Chinese products. In addition, the relationship between CE and purchase preference varied across product categories as well as countries of origin