Long-term Progression Research Articles

Forskolin-induced organoid swelling is associated with long-term cystic fibrosis disease progression.

RationaleCystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC).MethodsWe retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed-effect models and multivariable logistic regression to estimate the association of FIS with long-term forced expiratory volume in 1 s % predicted (FEV1pp) decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC.ResultsFIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95% CI 0.11–0.54%; p=0.004) per 1000-point change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR 0.18, 95% CI 0.07–0.46; p<0.001), CF-related liver disease (adjusted OR 0.18, 95% CI 0.06–0.54; p=0.002) and diabetes (adjusted OR 0.34, 95% CI 0.12–0.97; p=0.044). These associations were absent for SCC.ConclusionThis study exemplifies the prognostic value of a patient-derived organoid-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences.

Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.

The aim of the present study was to investigate serum fetuin-A (Fet-A) levels in patients with Takayasu arteritis (TA) and granulomatous polyangiitis (GPA) and to analyze the relationship between serum Fet-A levels and disease activity scores. Thirty-two TA and 28 GPA patients presented to the rheumatology clinic at Gazi University and met the criteria of American College of Rheumatology 1990 and 2012 International Chapell Hill meeting, respectively, and 20 healthy control subjects were included in the present study. We collected data on serum C-reactive protein (CRP), albumin, calcium, and phosphate levels as well as erythrocyte sedimentation rates. Calcification risk index (CRI) was calculated for each patient. The Birmingham Vasculitis Activity Score (BVAS) and Indian Takayasu Clinical Activity Score (ITAS), were used to assess disease activity in GPA and TA patients respectively. Serum Fet-A levels were significantly lower in the overall vasculitis group compared to control group (p = 0.015). In subgroup analysis, Fet-A levels were significantly lower in those with active disease, compared to control group (p = 0.001, for active TA (n = 18) and GPA (n = 17), respectively). However, there was no significant difference in serum Fet-A levels in inactive cases versus control subjects (p = 0.061, for inactive TA (n = 14) and GPA (n = 11), respectively). Serum Fet-A levels negatively correlated with BVAS (r = - 0.675) and ITAS scores (r = - 0.385), as well as with CRP and CRI. Our results suggest that serum Fet-A level could be a novel biomarker for assessment of activity status in patients with GPA or TA. Key Points • Serum Fetuin-A is negative acute phase protein and systemic calcification inhibitor synthesized in hepatocytes and secreted by various inflammation. • Serum Fetuin-A was negatively correlated with CRP, BVAS, and ITAS scores and significantly decreased in vasculitis patients with high disease activity. • Serum Fetuin-A could be a promising and useful biomarker for the assessment of disease activity for vasculitis, also that it might also be a predictor of long-term cardiovascular progression.

Gender distribution in boards of internal medicine societies and paper authorship: Networking is the key to success

Networking is about building long-term relationships as well as a good reputation over time. Active professional networking is vital to career growth as it involves meeting people who you can support and who can potentially help you in return. Good networking can mean the difference between a “mediocre and a great career”. In several fields, the earlier networking starts, the better it is for the long-term progression of individuals. Sallie Krawcheck has well described this concept when she wrote that “networking is the No. 1 unwritten rule of success”. She was head of Bank of America's Global Wealth and Investment Management division and has been called the most powerful woman on Wall Street. She was also named one of Time's Global Influentials in 2002 and Fortune's Most Influential Person Under the Age of 40 in 2003. Krawcheck left Bank of America in 2011 and is currently the CEO and co-founder of Ellevest, a digital financial advisor for women launched in 2016. Gender gap in authorship: a study of 44,000 articles published in 100 high-impact general medical journalsEuropean Journal of Internal MedicineVol. 97PreviewDear Editor, the profile of the medical profession has changed dramatically in recent decades, with an increasing proportion of women physicians [1]. However, the gender gap in academic medicine continues to be the rule rather than the exception. For example, women are less likely to be promoted to academic leadership positions [2] and receive fewer research grants [3]. Full-Text PDF

Analysis on unidentified cases in which dental information was collected from 2014 to 2019 in Miyagi Prefecture, Japan

This study aimed to summarize the characteristics of unidentified cases in which dental information was collected during 2014–2019 in Miyagi Prefecture and to discuss the challenges and social characteristics of dental identification in routine forensic work. Cases were selected and examined from the database of dental charts collected at Tohoku University and the database of the Miyagi Prefectural Police. The annual percentage of cases with matched dental findings ranged from 19.2 − 37.1%, and 80.6% of the cases were identified within four days using dental information. The most common age group was the 50–70 s. Males were more common in the 20–70 s, whereas females were more frequent in the 80–90 s age group. Utilization of dental information was lower for cases involving young people and those over 90 years of age. The number of unidentified cases and unspecified death cases in the central block was significantly higher than other regions. However, there were no significant differences in sex, age, and season between each region. Spearman’s rank-order analysis of the unspecified deaths showed a strong correlation with the monthly average temperature (ρ = 0.89, p < 0.01).Within the limitations of this study, the results provide valuable information on the long-term progress of routine dental identification work and could be useful as a reference for a statistical survey. Future research must examine the role of dental information in forensic identification by exploring the role of more specific background characteristics among autopsy cases.

Integrated index-based assessment reveals long-term conservation progress in implementation of Convention on Biological Diversity.

The Convention on Biological Diversity (CBD) has launched two long-term, target-based conservation Strategic Plans in the past two decades. We compiled an index-based assessment framework to evaluate target achievements of the CBD using long-term indicators. The CBD Index is steadily increasing, with the Goal Indices for biodiversity mainstreaming, protection, and supporting mechanisms all improving over time. While the State and Pressure Indices continue to deteriorate coupled with human population and economic development, their changing rates have slowed down, most likely because of the constantly growing conservation efforts as revealed by the Response Index. The first quantitative assessment of the CBD’s long-term performance may provide critical science-based evidence for continuing commitments to developing and implementing a new Post-2020 Global Biodiversity Framework. We also call for enhanced efforts to address the emerging challenges in achieving the 2050 Vision for Biodiversity and the adoption of a rapid assessment framework to track future progress.

Evaluation of Brace Treatment Using the Soft Brace Spinaposture: A Four-Years Follow-Up.

The braces of today are constructed to correct the frontal plane deformity of idiopathic adolescent scoliosis (AIS). The Spinaposture brace© (Spinaposture Aps, Copenhagen, Denmark) is a soft-fabric brace for AIS and is designed to enhance rotational axial stability by inducing a sagittal plane kyphotic correction. This prospective observational study evaluated the brace in fifteen patients with AIS. The initial average CA was 16.8° (SD: 2.8). They were followed prospectively every 3 to 6 months during their brace usage until skeletal maturity of 25 months and at long-term follow-up of 44 months. In- and out-of-brace radiographs were performed in six subjects at inclusion. This resulted in an immediate in-brace correction of 25.3 percent in CA (14.3°→10.8°) and induced a kyphotic effect of 14.9 percent (40.8°→47.9°). The average in-brace improvement at first follow-up was 4.5° in CA, and the CA at skeletal maturity was 11° (SD: 7.4°) and long-term 12.0° (SD: 6.8°). In conclusion, the Spinaposture brace© had an immediate in-brace deformity correction and a thoracic kyphotic effect. At skeletal maturity, the deformities improved more than expected when compared to that of the natural history/observation and similar to that of other soft braces. No long-term deformity progression was seen. To substantiate these findings, stronger designed studies with additional subjects are needed.

Knee Strength and Ankle Range of Motion Impacts on Timed Function Tests in Duchenne Muscular Dystrophy: In the Era of Glucocorticoids.

Duchenne Muscular Dystrophy (DMD) is a neuromuscular disorder that presents in childhood and is characterized by slowly progressive proximal weakness and lower extremity contractures that limit ambulatory ability [1, 2]. Contractures develop in the ankles, knees, and hips due to muscle imbalances, fibrotic changes, loss of strength, and static positioning [2, 5]. Currently, standards of care guidelines emphasize the importance of maintaining good musculoskeletal alignment through stretching, bracing, and glucocorticoid (GC) therapy to preserve strength and function. This is a retrospective analysis of prospectively collected data through the CINRG Duchenne Natural history study (DNHS). The objectives of this analysis are to understand the progression of ankle contractures for individuals with DMD and to investigate the relationship between progressive lower limb contractures, knee strength, and Timed Function Tests.A collection of TFTs including supine to stand (STS), 10 meter walk test (10MWT), and timed stair climbing (4SC) have been used to monitor disease progression and are predictive of loss of ambulation in these patients [4]. Multiple factors contribute to loss of ambulation, including progressive loss of strength and contracture development that leads to changing biomechanical demands for ambulation. A better understanding of the changes in strength and range of motion (ROM) that contribute to loss of function is important in a more individualized rehabilitation management plan. In this longitudinal study, we measured strength using quantitative muscle testing (QMT) with the CINRG Quantitative Measurement System (CQMS)), ROM was measuresed with a goniometer and TFTs were measured using a standard stopwatch and methodology. We enrolled 440 participants; mean baseline age was 8.9 (2.1, 28.0) years with 1321 observations used for analysis. GC use was stratified based on duration on drug with 18.7%at < 6 months or naïve; 4.3%<1 year; 58.0%1 < 10 years; and 19.3%between 10-25 years of GC use. Ankle ROM was better for those on GC compared to GC naive but did not significantly influence long-term progression rates. QMT, ROM, age and GCs contribute to speed of TFTs. Knee extension (KE) strength and Dorsiflexion (DF) ROM are significant predictors of speed for all TFTs (p < 0.001). Of the variables used in this analysis, KE strength is the primary predictor of walking speed, estimating that every pound increase in KE results in a 0.042 m/s improvement in 10MWT, and a smaller similar increase of 0.009 m/s with every degree of ankle DF ROM. GC use provides an improvement in strength and ROM but does not affect rate of change. Knee strength has a greater influence on speed of TFTs than DF ROM, although both are statistically significant predictors of speed. Results show that retaining knee strength [1, 2], along with joint flexibility, may be important factors in the ability to perform walking, climbing and supine to stand activities.

A Foreword from the Editor

Low-carbon and intelligent construction are two of the current research hot spots in the Architecture, Engineering, Construction, and Facilities Management (AEC/FM)&nbsp;field.&nbsp;Green building, smart city, AI, BIM, and sustainable development have become high-frequency words in the field[1]. The lack of the adoption of digital technologies (e.g., BIM, AI, digital twin) will lead to project delays, cost inefficiencies, poor quality, and tedious management[2]. Emerging innovations of those digital technologies are bringing a new evolutionary process of engineering applications towards more sustainable and intelligent development[3-4]. In October 2021, the United Nations Environment Programme (UNEP) and Global Alliance for Buildings and Construction (GlobalABC) release the heavyweight report Global Status Report on the Building and Construction Industry 2021[1]. The report states that since the signing of the Paris Agreement&nbsp;in 2015, CO2&nbsp;emissions from the buildings and construction sector have peaked in recent years and subsequently fallen to 2007 levels in 2020. This current decline is due mostly to the COVID-19 pandemic; however, this decline appears to be temporary as emissions pick up again with increasing economic activity. Whereas transformative, long-term progress in sector decarbonizing remains limited[1]. To achieve the Paris Agreement, the global buildings and construction sector must almost completely decarbonize by 2050. Collectively, stakeholders in the sector must seize the opportunity that the COVID-19 economic recovery period offers to foster transformation for decarbonizing the sector. The sector must simultaneously meet a projected near-doubling of global demand for energy services in buildings and at least a doubling of floor space as developing economies continue to respond to the growing demand for building floor space, access to energy services and economic activities. Therefore, to meet the future needs and developments of this fast-growing field, a brand-new journal, Journal of Building Design and Environment (JBDE)&nbsp;has been launched. JBDE is a semi-annual, double-blind peer reviewed, open access journal, dedicated to publishing original research articles/reviews—amongst other submission categories—on the research and application of sustainability and intelligence in the field of construction engineering and design. The scope of JBDE covers (but is not limited to) the following: Civil and Infrastructure Engineering Building and Structural Design Construction Materials Built Environment Construction Engineering and Management Computer Aided-Design and Simulation Energy and Buildings Sustainable Development Urban Planningand Resilience Architectural Aesthetics and Townscape To further encourage research in this area, our publisher, Omniscient Pte. Ltd. has decided to waive article processing charge for the first two issues of the journal’s first volume. Therefore, we strongly welcome all who are interested in building design&nbsp;and environment research to join us authors, reviewers or editorial board members. It is the hope of the entire editorial team of JBDE that this journal will fulfil the needs of those specialising in building design and facilitate discourses and advances in the field.

Changes in anthropometric and fitness profile of Italian regional academy rugby union players.

In rugby union, physical characteristics may partially contribute to long-term career progression, especially during adolescence. Therefore, the primary purpose of the study was to evaluate Italian regional rugby union academy players’ (i.e., under-18) anthropometric and physical characteristics during a competitive season. Body mass, height, upper- and lower-body maximal strength, sprint, and high-intensity running ability were assessed in 29 elite players (backs, n = 13, forwards, n = 16). A mixed-design analysis of variance (ANOVA) for repeated measures showed that backs were shorter (ES = 0.59), lighter (ES = 0.94), stronger relative to body mass (bench press; ES = 0.60; deadlift; ES = 0.63; clean ES = 0.63; rowing ES = 0.67), and fitter (shuttle run max; ES = 0.38; shuttle run tot; ES = 0.79) than forwards. However, the forwards achieved greater sprint momentum (initial sprint momentum; ES = 0.97; maximal sprint momentum; ES = 0.98). During the season, players changed in stature, upper-body maximal strength, jumping, and high intensity running (p < 0.05), but not in body weight or lower-body maximal strength (p > 0.05). Maximal strength improved in the first part of the season, whereas jumping and sprinting performances increased in the last part of the season. Therefore, these findings highlight the importance of regularly monitoring the physical development in a long-term perspective, even suggesting that physiological adaptations are heterochronic between positional roles.

Prognostics With Variational Autoencoder by Generative Adversarial Learning

Prognostics predicts the future performance progression and remaining useful life (RUL) of in-service systems based on historical and contemporary data. One of the challenges in prognostics is the development of methods that are capable of handling real-world uncertainties that typically lead to inaccurate predictions. To alleviate the impacts of uncertainties and to achieve accurate degradation trajectory and RUL predictions, a novel sequence-to-sequence predictive model is proposed based on a variational autoencoder that is trained with generative adversarial networks. A long short-term memory network and a Gaussian mixture model are utilized as building blocks so that the model is capable of providing probabilistic predictions. Correlative and monotonic metrics are applied to identify sensitive features in the degradation progress, in order to reduce the uncertainty induced from raw data. Then, the selected features are concatenated with one-hot health state indicators as training data for the model to learn end of life without the need for prior knowledge of failure thresholds. Performance of the proposed model is validated by health monitoring data collected from real-world aeroengines, wind turbines, and lithium-ion batteries. The results demonstrate that significant performance improvement can be achieved in long-term degradation progress and RUL prediction tasks.

Extension's role in improving livestock production: information needs, institutions and opportunities

This research looked into In Nigeria, livestock production intelligence is often prioritized by centralized extension services. National agricultural extension services are primarily designed to spread knowledge on crop production, whereas livestock institutions and sectors are driven by veterinarians who are concerned about animal health. In many developing nations, however, the possibility of raising livestock production through the supply of knowledge is growing. The context of such growth is described in this paper, as well as some of the differences between livestock extension services and institutions. Livestock production is a major part of any country&#39;s economy and is essential for guaranteeing food and nutritional security. For centuries, livestock has been known to supply man&#39;s animal nutritional needs, as well as give numerous additional benefits to farmers and the national economy. Nigeria&#39;s population is rapidly increasing quicker than the increase of animal protein in a population of nearly of 402 million people by 2050, there will be a million people. Interactions between livestock and the surroundings in developing countries can be both positive and negative. On the one hand, herbivore composted manure can be a valuable resource. In more industrial operations, and where there are huge densities of animals, it is a nutrient for micro crops, but in more industrial systems, or where there are large concentrations of animals, it is a dietary staple for large-scale crops. They have the potential to contaminate waterways. On the other hand, ruminant systems in developing countries can be considered relatively inefficient use of resources. Because most of these production systems have large yield variability, boosting the effectiveness of the process is critical. Through appropriate development strategies, the cattle industry presents a tremendous opportunity for research and innovation can contribute to the development of more long-term solutions Future progress in this field must be based on existing institutions while also aiming to respond flexibly and fairly to the needs of livestock farmers.

Association between Dietary Pattern, Nutritional Status, Metabolic Factors, and Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) can be harmful to the body to varying degrees, and over a prolonged period, patients may develop steatotic cirrhosis or even develop liver cancer based on cirrhosis. Moreover, its harms are related to its severity. Patients with severe steatosis develop hepatocyte destruction, transaminase abnormalities, and long-term progression to steatotic cirrhosis, or even liver cancer, which should be treated aggressively. In order to provide theoretical basis for the prevention and early intervention of NAFLD, we analysis the relationship between nonalcoholic fatty liver disease(NAFLD) and dietary pattern, nutritional status, metabolic factor A total of 517 participants (200 males and 317 females) recruited in this study were gained from the health check center of The Ningbo Seventh Hospital, Ningbo, China, from September 2018 to August 2019. Patients diagnosed with NAFLD were selected as the study subjects. The data on the dietary pattern, nutritional status, and metabolic factors were collected for further analysis. A total of 517 eligible participants (317 females and 200 males) were involved in this study, with a mean age of 54.7 ± 16.7 years. Dessert and fruit diet, healthy dietary pattern, animal food dietary pattern, high salt diet mode, triglyceride, uric acid, adiponectin, and waist-hip ratio were significantly different between the two groups (P < 0.05). Dietary patterns, nutritional status, metabolic factors, and NAFLD are correlated. Furthermore, applying this correlation law can better manage NAFLD patients.

Molecular Signature Predictive of Long-Term Liver Fibrosis Progression to Inform Antifibrotic Drug Development

There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression. A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n= 421) and was validated in an independent NAFLD cohort (n= 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic exvivo cultures of clinical fibrotic liver tissues (n= 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n= 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n= 122). A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic exvivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in exvivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients. The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development.

The Expansion of Lignocellulose Biomass Conversion Into Bioenergy via Nanobiotechnology

Lignocellulosic biomass has arisen as a solution to our energy and environmental challenges because it is rich in feedstock that can be converted to biofuels. Converting lignocellulosic biomass to sugar is a complicated system involved in the bioconversion process. There are indeed a variety of techniques that have been utilized in the bioconversion process consisting of physical, chemical, and biological approaches. However, most of them have drawbacks when used on a large scale, which include the high cost of processing, the development of harmful inhibitors, and the detoxification of the inhibitors that have been produced. These constraints, taken together, hinder the effectiveness of current solutions and demand for the invention of a new, productive, cost-effective, and environmentally sustainable technique for LB processing. In this context, the approach of nanotechnology utilizing various nanomaterials and nanoparticles in treating lignocellulose biomass and bioenergy conversion has achieved increased interest and has been explored greatly in recent times. This mini review delves into the application of nanotechnological techniques in the bioconversion of lignocellulose biomass into bioenergy. This review on nanotechnological application in biomass conversion provides insights and development tools for the expansion of new sectors, resulting in excellent value and productivity, contributing to the long-term economic progress.

INFLUENCE MECHANISMS OF INNOVATION-BASED ACTIVITY OF SMALL AND MEDIUM ENTERPRISES IN THE FORMATION OF A COMPETITIVE ECONOMY

Topicality. The topicality is that innovative actions are critical for demonstrating resilience in an increasingly competitive global economy. As a result, market participants must constantly adapt and upgrade their products, services, and manufacturing methods to take advantage of the most recent scientific and technological advances. It is critical to investigate, develop, and implement innovative ideas, methods, and products that will improve the economy and society.&#x0D; Aim and tasks. The analysis and study of mechanisms for increasing competitiveness and increasing the share of the international market in economic competition and development, identifying the economic contribution of innovative entrepreneurship, is the development of small and medium enterprises in a rapidly globalizing world.Research results. The prospects for the development of small and medium businesses in industrialized countries were examined, and recommendations for the actions were made. The establishment of a socioeconomic system that will assure long-term economic progress is critical for modern society's well-being. Development and competitive advantages are determined by science, innovation, and technology. All three of these criteria are necessary for long-term economic growth and sustainable productivity increase. In highly developed industrial societies, small and medium enterprises (SMEs), which play an important role in technological growth, form the foundation of the economic structure. As a result, it's critical to foster a technical innovation culture in SMEs, encourage creative thinking in the development of new products, processes, and services, improve knowledge management skills, and encourage risk-taking.&#x0D; Conclusion. Materials and findings in the study can be utilized to establish complicated and systematic measures, as well as conceptual approaches to problem solving, in order to create a competitive economy of innovative small and medium businesses in modern times.

Affect regulation in psychoanalytic treatments of patients with a borderline personality disorder-psychoanalysis and psychodynamic psychotherapy-a comparison.

BACKGROUNDA recent meta-analysis has confirmed that the effects of psychotherapy on patients with borderline personality disorders (BPD) are still insufficiently understood. Evidence of differences between different types of therapies has been questioned.AIMTo study repetitive interaction patterns in patients with BPD undergoing either psychoanalysis or psychodynamic therapy. METHODSPsychoanalysis (PSA) or psychodynamic psychotherapy (PDT) was administered to 10 patients each, the two groups were matched. Therapy regimens were applied according to care as usual/manualized including quality control and supervision as usual. Randomization to one of the groups was done after baseline assessment. During classical PSA (n = 10) and PDT (n = 10), semiannually, recordings (audio or video) of five consecutive therapy sessions were taken over three years for an ex-post analysis. The patients' characteristics, such as affect parameters [Affect regulation and experience Q-sort (AREQ)], quality of object relations (quality of object relations scale) and personality traits [Shedler-Westen Assessment Procedure (SWAP-200)] were analyzed retrospectively by independent raters. Therapeutic action (psychotherapy process Q-sort) and affective (re)actions of the patients (AREQ) were then analyzed in relation to changes found in the patients' characteristics. RESULTSDuring the first year of therapy (PSA: n = 10; PDT: n = 9), the therapeutic method PSA was associated with significant improvements in the variable "SWAP Borderline", while in PDT change was not significantly different to baseline (PSA: P = 0.04; PDT: P = 0.33). Long-term results and follow up was available for seven participants in PSA and for five in PDT after three years; change in SWAP borderline for the whole sample was not significant at this time point when confronting to baseline (P = 0.545). However, differences between PSA and PDT were significant when analyzing the “mean change” in the SWAP Borderline variable after one year of therapy (P = 0.024): PSA led to slightly increased BPD symptoms, while PDT to a decrease; for the long run, variance of observed change was higher in PSA than in PDT (SDPSA ± 9.29 vs SDPDT ± 7.94). Our assumption that transference interpretations, closely followed by affective changes in the patient, could be useful modes of interaction was reproducible in our findings, especially when looking at the descriptive findings in the long-term data. The analysis of repetitive interaction structures demonstrated a very specific "time-lag" between therapeutic intervention and a corresponding increase in positive affect in successful therapy cases.CONCLUSIONExploring the change processes in the patients' characteristics and linking these changes to specific treatment strategies is of clinical importance when starting treatment and for its long-term progress.

Magnetic resonance elastography for prediction of long-term progression and outcome in chronic liver disease: A retrospective study.

Although magnetic resonance elastography (MRE) has been well-established for detecting and staging liver fibrosis, its prognostic role in determining outcomes of chronic liver disease (CLD) is mostly unknown. This retrospective study consisted of 1269subjects who underwent MRE between 2007 and 2009 and followed up until death or last known clinical encounter or end of study period. Charts were reviewed for cirrhosis development, decompensation, and transplant or death. The cohort was split into baseline noncirrhosis (group 1), compensated cirrhosis (group 2), and decompensated cirrhosis (group 3). Cox-regression analysis with age, sex, splenomegaly, CLD etiology, Child-Pugh Score (CPS), Fibrosis-4 Index(FIB-4) score, and Model for End-Stage Liver Disease (MELD)-adjusted HR for every 1-kPa increase in liver stiffness measurement (LSM) were used to assess the predictive performance of MRE on outcomes. Group 1(n=821) had baseline median LSM of 2.8kPa, and cirrhosis developed in 72 (8.8%) subjects with an overall rate of about 1% cirrhosis/year. Baseline LSM predicted the future cirrhosis with multivariable adjusted HR of 2.38 (p<0.0001) (concordance, 0.84). Ingroup 2(n=277) with baseline median LSM of 5.7kPa, 83 (30%) subjects developed decompensation. Baseline LSM predicted the future decompensation in cirrhosis with FIB-4 and MELD-adjusted HR of 1.22 (p<0.0001) (concordance, 0.75). Ingroup 3(n=171) with median baseline LSM of 6.8kPa (5.2, 8.4), 113 (66%) subjects had either death or transplant. Baseline LSM predicted the future transplant or death with HR of 1.11 (p=0.013) (concordance 0.53) but not in CPS and MELD-adjusted models (p=0.08). MRE-based LSM is independently predictive of development of future cirrhosis and decompensation, and has predictive value in future transplant/death in patients with CLD.

Accelerated Long-Term Hearing Loss Progression After Recovery From Idiopathic Sudden Sensorineural Hearing Loss.

Background and Introduction: Idiopathic sudden sensorineural hearing loss (ISSNHL) is characterized by rapid onset, typically unilateral presentation, and variable recovery. This case-control observational study aimed to improve patient counseling by objectively characterizing long-term hearing loss progression following ISSNHL, using sequential audiometry in the largest-to-date cohort of patients with ISSNHL.Methods: Patients diagnosed with ISSNHL at a tertiary referral hospital from 1994 through 2018 with sequential audiometry were studied. Case controls with sensorineural hearing loss (SNHL) were matched by age, sex, baseline hearing status, and frequency of sequential audiometry. Hearing loss progression was quantified using Kaplan–Meier (K–M) analysis to account for variable follow-up duration. A subgroup analysis was performed by age, sex, preexisting comorbidities, ISSNHL-associated symptoms, ISSNHL treatment, and degree of post-ISSNHL hearing recovery.Results: A total of 660 patients were identified with ISSNHL. In patients with post-ISSNHL recovery to good hearing [pure tone average (PTA) <30 dB and word recognition score (WRS) > 70%], median time to progression to non-serviceable (PTA > 50 dB or WRS <50%) SNHL was 16.4 years. In patients with incomplete post-ISSNHL hearing recovery, contralateral ears were also at significantly higher risk of SNHL progression over the following 12-year period. Male sex was associated with increased risk of SNHL progression [odds ratio (OR) 3.45 male vs. female] at 5-year follow up. No other subgroup factors influenced the likelihood of SNHL progression.Discussion and Conclusion: Patients should be counseled on continued risk to long-term hearing after stabilization of hearing post-ISSNHL, with particular emphasis on greater risk to the contralateral ear in those with incomplete ipsilateral recovery.

359 Transient vs. persistent improved ejection fraction in non-ischaemic dilated cardiomyopathy

Abstract Aims The recent definition of heart failure with improved ejection fraction (HFimpEF) outlined the importance of the longitudinal assessment of left ventricular ejection fraction (LVEF). However, long-term progression and outcomes of this subgroup are poorly explored. We sought to assess the LVEF trajectories and the correlations with outcome in non-ischaemic dilated cardiomyopathy (NICM) with improved ejection fraction (impEF). Methods and results Consecutive NICM patients with baseline LVEF ≤40% enrolled in the Trieste Heart Muscle Disease Registry with ≥1 LVEF assessment after baseline were included. ImpEF was defined as a baseline LVEF ≤40%, a ≥ 10 point increase from baseline LVEF, and a second measurement of LVEF &amp;gt;40%. Transient impEF was defined by the documentation of recurrent LVEF ≤40% during follow-up. The primary endpoint was a composite of all-cause death, heart transplantation and left ventricular assist device (D/HT/LVAD). Among 800 patients, 460 (57%) had impEF (median time to improvement 13 months). Higher heart rate, smaller left atrium, absence of severe mitral regurgitation and shorter duration of disease were associated with impEF. ImpEF was independently associated with lower risk of D/HT/LVAD (HR: 0.36; 95% CI: 0.27–0.48; P &amp;lt; 0.001). Transient impEF was observed in 189 patients (41% of the overall impEF group) and was associated with higher risk of D/HT/LVAD compared with persistent impEF at multivariable analysis (HR: 2.54; 95% CI: 1.60–4.04). Conclusions In NICM, we observed a 57% rate of impEF. However, recurrent decline in LVEF was observed in ≈40% of impEF patients and it was associated with an increased risk of D/HT/LVAD.

Association of Genetic Variants of Klotho with BP Responses to Dietary Sodium or Potassium Intervention and Long-Term BP Progression

Objectives: Klotho (KL) plays pivotal roles in the progression of salt-sensitive hypertension. Salt-sensitive hypertension was associated with KL genotypes. We aimed to explore the association of common genetic variants of KL with individual blood pressure (BP) responses to sodium and potassium through a dietary intervention study as well as long-term BP progression. Methods: We conducted family-based dietary interventions among 344 participants from 126 families in rural villages of northern China in 2004. Subjects sequentially underwent a baseline diet, a low-salt diet (51.3 mmol/day Na), a high-salt diet (307.8 mmol/day Na), and a high-salt + potassium supplementation diet (307.8 mmol/day Na + 60 mmol/day K). After dietary intervention, we followed up with these participants in 2009 and 2012. The associations between 6 single-nucleotide polymorphisms (SNPs) of KL and phenotypes were analyzed through a linear mixed-effects model. Results: SNPs rs211247 and rs1207568 were positively correlated with the BP response to high-salt diet in the dominant model after adjusting for confounders (β = 1.670 and 2.163, p = 0.032 and 0.005, respectively). BPs rs526906 and rs525014 were in a haplotype block. Block rs526906-rs525014 was positively correlated with diastolic BP response to potassium and potassium sensitivity in the additive model (β = 0.845, p = 0.032). In addition, regression analysis indicated that rs211247 was associated with long-term systolic BP alterations after 8 years of follow-up in the recessive model (β = 20.47, p = 0.032). Conclusions: Common variants of the KL gene might modify individual BP sensitivity to sodium or potassium and influence the long-term progression of BP, suggesting a potential role in the development of salt-sensitive hypertension. Thus, KL may be a new early intervention target for salt-sensitive hypertension.