Organ Systems Research Articles

Grain agriculture and the end of the fossil fuel era

First paragraphs: A great deal of attention is currently focused on how agriculture in highly industrialized coun­tries contributes to greenhouse gas (GHG) emis­sions, and how certain farming innovations might curb the emissions of nitrous oxide and methane and draw down carbon dioxide from the atmos­phere. What is not being discussed is how agricul­ture in general, and grain agriculture in particular, will need to change as society phases out its dependency on fossil fuels in order to achieve carbon (C) neutrality. Over the last century in the U.S., the number of farmers on the land declined by about 66%, in close proportion to the increase in average farm size (U.S. Department of Agriculture Economic Research Service [USDA ERS], n.d.). Integral to these trends has been the simplification of farming systems in which practices like fertility-generating rotations have been replaced with lower-diversity monocultures maintained by applications of fossil fuel–based fertilizers and pesticides (Crews & Peoples, 2004). Between fossil fuel–powered mechanization and fossil fuel–based input intensi­fication, the energy used by farmers to grow maize in the state of Nebraska is 99.7% from fossil fuels and 0.3% human labor (Grassini & Cassman, 2012; Pimentel & Pimentel, 2008). Even organic farming systems often require prodigious fossil fuel inputs with intensive tractor tillage, manure hauling, and mechanical harvesting (Smith et al., 2015). In con­trast to our modern grain-producing agroeecosys­tems, ancestral agroecosystems and natural ecosys­tems of all types—forests, grasslands, deserts, tundra—have remained productive for millennia with no fossil fuel inputs. In this commentary I explore the dependency of grain agriculture on fossil fuel use in the U.S. set in a global context, and approaches for reducing this dependency, including a shift to perennial polycultures that rely on ecological intensification in place of energy-intensive inputs. . . .

Noninvasive assessment of organ-specific and shared pathways in multi-organ fibrosis using T1 mapping.

Fibrotic diseases affect multiple organs and are associated with morbidity and mortality. To examine organ-specific and shared biologic mechanisms that underlie fibrosis in different organs, we developed machine learning models to quantify T1 time, a marker of interstitial fibrosis, in the liver, pancreas, heart and kidney among 43,881 UK Biobank participants who underwent magnetic resonance imaging. In phenome-wide association analyses, we demonstrate the association of increased organ-specific T1 time, reflecting increased interstitial fibrosis, with prevalent diseases across multiple organ systems. In genome-wide association analyses, we identified 27, 18, 11 and 10 independent genetic loci associated with liver, pancreas, myocardial and renal cortex T1 time, respectively. There was a modest genetic correlation between the examined organs. Several loci overlapped across the examined organs implicating genes involved in a myriad of biologic pathways including metal ion transport (SLC39A8, HFE and TMPRSS6), glucose metabolism (PCK2), blood group antigens (ABO and FUT2), immune function (BANK1 and PPP3CA), inflammation (NFKB1) and mitosis (CENPE). Finally, we found that an increasing number of organs with T1 time falling in the top quintile was associated with increased mortality in the population. Individuals with a high burden of fibrosis in ≥3 organs had a 3-fold increase in mortality compared to those with a low burden of fibrosis across all examined organs in multivariable-adjusted analysis (hazard ratio = 3.31, 95% confidence interval 1.77-6.19; P = 1.78 × 10-4). By leveraging machine learning to quantify T1 time across multiple organs at scale, we uncovered new organ-specific and shared biologic pathways underlying fibrosis that may provide therapeutic targets.

The most frequent febrile syndromes and autoinflammatory diseases in adulthood

Autoinflammatory diseases are characterized by inflammatory manifestations in various organ systems, whereby recurrent febrile episodes, musculoskeletal complaints, gastrointestinal and cutaneous symptoms frequently occur accompanied by serological signs of inflammation. Autoinflammatory diseases include rare monogenic entities and multifactorial or polygenic diseases, which can manifest as a variety of symptoms in the course of time. Examples of monogenic autoinflammatory diseases are familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and the recently described VEXAS (vacuoles, E1 enzyme, X‑linked, autoinflammatory and somatic) syndrome. For non-monogenically determined autoinflammatory diseases, the most important representatives in adulthood are adult-onset Still's disease (AOSD) and the Schnitzler syndrome, in which a polygenic susceptibility and epigenetic factors are more likely to play a role.

Malignant tumors in tuberous sclerosis complex: a case report and review of the literature

BackgroundTuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the development of benign tumors in any organ system with significant clinical implications in morbidity and mortality. In rare instances, patients with TSC can have malignant tumors, including renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (PNET). It is considered a hereditary renal cancer syndrome despite the low incidence of RCC in TSC patients. TSC is typically diagnosed in prenatal and pediatric patients and frequently associated with neurocognitive disorders and seizures, which are often experienced early in life. However, penetrance and expressivity of TSC mutations are highly variable. Herein, we present a case report, with associated literature, to highlight that there exist undiagnosed adult patients with less penetrant features, whose clinical presentation may contain non-classical signs and symptoms, who have pathogenic TSC mutations.Case presentationA 31-year-old female with past medical history of leiomyomas status post myomectomy presented to the emergency department for a hemorrhagic adnexal cyst. Imaging incidentally identified a renal mass suspicious for RCC. Out of concern for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, the mass was surgically removed and confirmed as RCC. Discussion with medical genetics ascertained a family history of kidney cancer and nephrectomy procedures and a patient history of ungual fibromas on the toes. Genetic testing for hereditary kidney cancer revealed a 5’UTR deletion in the TSC1 gene, leading to a diagnosis of TSC. Following the diagnosis, dermatology found benign skin findings consistent with TSC. About six months after the incidental finding of RCC, a PNET in the pancreatic body/tail was incidentally found on chest CT imaging, which was removed and determined to be a well-differentiated PNET. Later, a brain MRI revealed two small cortical tubers, one in each frontal lobe, that were asymptomatic; the patient’s history and family history did not contain seizures or learning delays. The patient presently shows no evidence of recurrence or metastatic disease, and no additional malignant tumors have been identified.ConclusionsTo our knowledge, this is the first report in the literature of a TSC patient without a history of neurocognitive disorders with RCC and PNET, both independently rare occurrences in TSC. The patient had a strong family history of renal disease, including RCC, and had several other clinical manifestations of TSC, including skin and brain findings. The incidental finding and surgical removal of RCC prompted the genetic evaluation and diagnosis of TSC, leading to a comparably late diagnosis for this patient. Reporting the broad spectrum of disease for TSC, including more malignant phenotypes such as the one seen in our patient, can help healthcare providers better identify patients who need genetic evaluation and additional medical care.

Global modified-Delphi consensus on comorbidities and prognosis of SCN8A-related epilepsy and/or neurodevelopmental disorders.

We aimed to develop consensus on comorbidities (frequency, severity, and prognosis) and overall outcomes in epilepsy, development, and cognition for the five phenotypes of SCN8A-related disorders. A core panel consisting of 13 clinicians, 1 researcher, and 6 caregivers was formed and split into three workgroups. One group focused on comorbidities and prognosis. All groups performed a literature review and developed questions for use in a modified-Delphi process. Twenty-eight clinicians, one researcher, and 13 caregivers from 16 countries participated in three rounds of the modified-Delphi process. Consensus was defined as follows: strong consensus ≥80% fully agree; moderate consensus ≥80% fully or partially agree, <10% disagree; and modest consensus 67%-79% fully or partially agree, <10% disagree. Consensus was reached on the presence of 14 comorbidities in patients with Severe Developmental and Epileptic Encephalopathy (Severe DEE) spanning non-seizure neurological disorders and other organ systems; impacts were mostly severe and unlikely to improve or resolve. Across Mild/Moderate Developmental and Epileptic Encephalopathy (Mild/Moderate DEE), Neurodevelopmental Delay with Generalized Epilepsy (NDDwGE), and NDD without Epilepsy (NDDwoE) phenotypes, cognitive and sleep-related comorbidities as well as fine and gross motor delays may be present but are less severe and more likely to improve compared to Severe DEE. There was no consensus on comorbidities in the SeL(F)IE phenotype but strong conesensus that seizures would largely resolve. Seizure freedom is rare in patients with Severe DEE but may occur in some with Mild/Moderate DEE and NDDwGE. Significant comorbidities are present in most phenotypes of SCN8A-related disorders but are most severe and pervasive in the Severe DEE phenotype. We hope that this work will improve recognition, early intervention, and long-term management for patients with these comorbidities and provide the basis for future evidence-based studies on optimal treatments of SCN8A-related disorders. Identifying the prognosis of patients with SCN8A-related disorders will also improve care and quality-of-life for patients and their caregivers.

Side effects of dermato-oncologic therapies

Immune checkpoint inhibitors (ICIs) such as PD(L)1 and CTLA4 antibodies as well as targeted therapies such as BRAF and MEK inhibitors have significantly improved the systemic treatment of skin cancer in adjuvant and advanced therapy settings. All these drugs differ in their spectrum of side effects. The aim of this article is to provide an overview of the spectrum of side effects of dermato-oncological therapies and their management, taking into account the current literature. The most important side effects of ICIs, the CCR4 inhibitor mogamulizumab, the ImmTAC tebentafusp, the BRAF and MEK inhibitors and the multityrosine kinase inhibitor imatinib are considered. Side effects can manifest themselves in all organ systems. Chronic side effects and long-term harm are possible, especially with ICIs, and require close therapy monitoring and patient education. Knowledge of the side effects and the temporal, sometimes delayed course of their occurrence are essential for diagnosis and prompt initiation of therapy.

Suspected Case of Histoplasmosis-Related Immune Reconstitution Inflammatory Syndrome Manifesting as Unilateral Pleural Effusion

Background: Histoplasmosis is a prevalent endemic mycosis that frequently causes opportunistic infections among individuals living with HIV (human immunodeficiency virus), and acquired immunodeficiency syndrome (AIDS). The initiation of antiretroviral therapy (ART) can result in a rare histoplasma-associated immune reconstitution inflammatory syndrome (IRIS) that may be difficult to distinguish between active progressive disease and inflammatory reaction to the medication. Case report: A 35-year-old male with newly diagnosed HIV and cervical biopsy-confirmed histoplasmosis was admitted from the emergency department with disseminated histoplasmosis for HIV antiretroviral treatment and antifungal treatment. Discharged after a 2-week inpatient treatment the patient returned 1 week later with a large left pleural effusion. Two liters of serosanguinous fluid were removed and all fluid cultures and cytology were negative. An extensive work-up remained negative, and given the timeline of presentation in relation to the initiation of ART, it was felt that this isolated left-sided pleural effusion was a manifestation of IRIS. Eventually, corticosteroids were given for IRIS and the patient improved and was discharged on long-term treatment. Conclusions: Immunocompromised subjects are at serious risk for a virulent, aggressive, rapidly advancing histoplasma infection and should be counselled accordingly. Any clinical signs or symptoms of organ system deterioration or compromise should be reported to the provider and a workup for histoplasmosis considered. In patients treated with antiretrovirals, IRIS is particularly confounding since it is difficult to differentiate from active disease. Using corticosteroids in already immunocompromised patients with an established fungal infection requires caution. Compliance with treatment is one of the most important components of care, especially considering the months of protocol.

Nrf2 Signaling Pathway as a Key to Treatment for Diabetic Dyslipidemia and Atherosclerosis.

Diabetes mellitus (DM) is a chronic endocrine disorder that affects more than 20 million people in the United States. DM-related complications affect multiple organ systems and are a significant cause of morbidity and mortality among people with DM. Of the numerous acute and chronic complications, atherosclerosis due to diabetic dyslipidemia is a condition that can lead to many life-threatening diseases, such as stroke, coronary artery disease, and myocardial infarction. The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway is an emerging antioxidative pathway and a promising target for the treatment of DM and its complications. This review aims to explore the Nrf2 pathway's role in combating diabetic dyslipidemia. We will explore risk factors for diabetic dyslipidemia at a cellular level and aim to elucidate how the Nrf2 pathway becomes a potential therapeutic target for DM-related atherosclerosis.

Dynamic hydrogel–metal–organic framework system promotes bone regeneration in periodontitis through controlled drug delivery

Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment’s impact on immune responses. This study explores a novel approach utilizing Metal–Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid's antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel’s synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system's efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis.Graphical

Optimal design on fin-metal foam hybrid structure for melting and solidification phase change storage: An experimental and numerical study

A fin-metal foam composite structure is employed in the phase change energy storage coupled Organic Rankine Cycle system to enhance thermal performance. The 3-D numerical model is validated through an experimental system to analyze the impact of metal foam parameters and fluctuating heat source parameters (amplitude and half-period) on the system's storage-release process during heat source fluctuation. According to the Taguchi method, metal foam porosity significantly influences the total storage-release time. An increase in porosity leads to a continuous increase in the total storage-release time, while an increase in PPI and a decrease in heat source amplitude initially increase and then decrease the total storage-release time. Under constant metal foam PPI (10) and porosity (0.97), Case T (half period = 60 and amplitude = 1.0) demonstrates a 2.04 % increase in average heat transfer rate and a 1.78 % reduction in total storage-release time compared to Case 0 (constant heat source). The average heat release rate sees a 4.23 % increase, while total heat storage and heat release rise by 0.96 % and 1.87 %. The research has specific technical significance for the photothermal application of phase change energy storage technology to the variability and unpredictability of solar energy.

Batch equilibrium experiments and modeling reveal weak temperature dependence of cyclic volatile methylsiloxane sorption in soil/sediment organic carbon-water systems

The organic carbon normalized partition coefficient, KOC, describes the equilibrium distribution of a chemical between water and organic carbon in soil or sediment. It is a key parameter in evaluating chemical persistence, mass distribution, and transport using multimedia fate and transport models. Considerable uncertainty remains about the KOC values of cyclic volatile methylsiloxane (cVMS) compounds, and in particular the dependence of KOC on temperature. In this study, we used a batch equilibrium (BE) method to measure KOC values and their temperature dependence between ∼5 and 25 °C for octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) with soil and sediments. Approximate log KOC values at 25 °C were 4.5–5.0 for D4 and 5.5–6.1 for D5 with different sorbents, and decreased by 0.3 log units or less at 4–5 °C. Enthalpies of sorption, ΔHOC, obtained for the different sorbents ranged from +7.2 to +16 kJ mol−1, with average values of +7.9 and +13 kJ mol−1 for D4 and D5, respectively. These values differ in magnitude and direction from those reported elsewhere based on KOC values determined by a novel dynamic purge-and-trap (PnT) method, but are consistent with predictions based on their solvation properties. A new fugacity-based multimedia model incorporating sorption/desorption kinetics was developed and used to predict concentrations in the phases of BE and PnT systems during desorption of cVMS under different experimental and ideal conditions. Model simulations suggested that KOC values for cVMS compounds derived from the PnT systems could be influenced by sorption disequilibrium between water and solids controlled by desorption rates from the particle phase to water, and subsequent losses due to volatilization and degradation. This has the potential to result in overestimation of KOC values when fitting the experimental data of cVMS mass remaining in a PnT system over time, which could explain the observed differences between the methods.

#1484 Development of a relapse risk score in patients with ANCA-associated vasculitis treated with cyclophosphamide induction

Abstract Background and Aims Cyclophosphamide (CYC), together with rituximab, is the mainstay for induction therapy in ANCA-associated vasculitis (AAV) [1]. The risk factors influencing the likelihood of relapse in individuals undergoing CYC induction are still unclear. This study aims to score the more robust predictors of relapse in these patients, thereby building a clinically useful tool. Method Patients' characteristics were pooled from three cohorts from Italy, Ireland, and Spain. Eligibility criteria were a diagnosis of GPA, MPA, or EGPA, age &amp;gt;18 years, induction treatment with CYC [either as intravenous therapy (IV) and/or oral], and at least 12 months of follow-up. Baseline assessment included clinical data, laboratory testing, and assessment of manifestations of GPA, MPA, and EGPA in each organ system according to the Birmingham Vasculitis Activity Score (BVAS). Relapse was defined as the presence of ≥1 new vasculitis manifestation after a remission lasting at least 3 months; remission was defined as no disease activity (BVAS=0) irrespective of the glucocorticoid use. Time-to-remission and relapse-free survival probabilities were estimated using the Kaplan-Meier method. A multivariate Cox analysis, including the statistically significant factors at a previous univariate analysis, was employed to develop a practical prognostic score, defined as “Relapse Evaluation And Cyclophosphamide Treatment (REACT) score”, in which each independent predictor was assigned a number of weighted points proportional to its β regression coefficient. Results The score development cohort comprised 505 patients. 223 patients (44.2%) had MPA, 217 (43.0%) GPA, and 65 (12.9%) EGPA. 183 patients (36.2%) experienced a relapse, with a median time to relapse of 33 months (IQR: 13-61). A multivariate Cox regression analysis proved that PR3-ANCA (HR: 1, 30, 95% CI 1, 01-1, 87), IV CYC (HR: 1.78, 95% CI 1.31-2.41), cardiovascular involvement (HR: 1.82, 95% CI 1.01-3.25), arthralgias/arthritis (HR: 1.46 95% CI 1.08-1.98) and the absence of rapidly progressive glomerulonephritis (HR: 1.37, 95% CI 1.02-1.85) were all independent risk factors of relapse. These variables were used to build the REACT score, with each item receiving 1 point except for CV involvement and IV CYC, each receiving 2 points. We then identified three risk categories according to the score of each patient (Fig. 1A). We identified 138 (27%) patients with low risk of relapse (score 0-1), 252 (49%) with an intermediate risk (score 2-3), and 115 patients (22%) with a high risk (score 4-7). These three groups showed different relapse probabilities on Kaplan-Meier analysis (pairwise comparisons between the groups were all statistically significant) (Fig. 1B). Conclusion The REACT score can be employed at diagnosis to predict the risk of relapse in patients with AAV treated with cyclophosphamide induction. Its value needs to be confirmed in external cohorts.

#1437 Renal expression pattern of the relaxin receptor, RXFP1, and effects of the RXFP1 agonist, AZD5462, on renin in non-human primates and humans

Abstract Background and Aims RXFP1 is a G protein-coupled receptor (GPCR) for the pregnancy hormone, relaxin. While preclinical studies, performed primarily in rodent, describe beneficial effects of this pleiotropic peptide across several organ systems, there has been a disappointing lack of success in translating these observations into clinical benefit. To provide a potential pharmacological explanation accounting for this translational gap, the aim of this study was thus to thoroughly evaluate RXFP1 expression across species and tissues as well as to evaluate the renal-intrinsic effects of the RXFP1 agonist, AZD5462. Method Unbiased bioinformatic analysis of several gene expression databases was used as a first approach to compare RXFP1 tissue-level expression between rodent and human. Experimental validation was subsequently performed using scRNAseq, RNAscope and immunohistochemistry on mouse, rat, non-human primate (NHP) and human kidney. The putative renal target engagement effects of RXFP1 agonism were assessed by determining the acute and chronic effects of the RXFP1-selective small molecule agonist, AZD5462, on plasma renin concentrations in both NHPs and in a Phase 1 randomized, single-blind, placebo-controlled study in healthy humans. Results RXFP1 was identified as one of the most highly expressed GPCRs in human and NHP kidney glomeruli. Specifically, by multiple assays, we identified glomerular endothelial cells as the principal cell type expressing RXFP1. This observation is in stark contrast to mouse and rat kidney, where RXFP1 was not readily detected. AZD5462 administered orally to NHPs and healthy human participants elicited an early and sustained dose-dependent increase in plasma renin concentration, and in humans an additional decline in serum creatinine. Conclusion Human RXFP1 kidney glomerular expression is conserved with NHPs but not rodent, thus highlighting the translational and pharmacological challenges in studying RXFP1/relaxin biology across species. The concordant ability of AZD5462 to induce elevations in renin and reduction in serum creatinine, together with relaxin's reported renal-hemodynamic activity in humans, may underlie a previously unappreciated renal-intrinsic RXFP1 target engagement mechanism driving its hemodynamic and renal effects. The potential therapeutic benefits of RXFP1 agonism are the subject of on-going clinical trials in heart failure patients.

The Scope of Mendelian Cardiomyopaties Genes

The review is devoted to the analysis of the scope of the genes of Mendelian cardiomyopathies (CM), specifically hypertrophic, dilatational, arrhythmogenic, and restrictive cardiomyopathy. According to Simple ClinVar, pathogenic/probably pathogenic variants of 75 genes lead to the development of one or more types of CM. At the same time, these genes are characterized by their expression in various tissues and organs (not only in the heart and blood vessels, but also in various parts of the brain, gastrointestinal tract, etc.), as well as by their involvement in a variety of metabolic pathways and biological processes. These data are generally consistent with the results of genome-wide association studies (GWAS). Polymorphisms of the CM genes are associated with various types of CM and other cardiovascular diseases, as well as obesity, various diseases of the musculoskeletal and nervous systems, mental, oncological, infectious diseases, and others. In addition to pathological conditions, common variants of the CM genes contributed to the variability of a wide range of quantitative traits, including pathogenetically significant for various multifactorial diseases. The non-randomness of the identified associations of CM genes with a wide range of diseases is evidenced by: comorbidity of CM with GWAS-associated diseases or the involvement of the latter as a symptom, a risk factor for the development of myocardial pathology, a modifier of the clinical presentation; overlapping of the affected organ systems and the spectrum of pathologies associated with common variants (according to GWAS) and to which rare pathogenic variants (according to OMIM) of the CM genes lead; confirmation of the involvement of CM genes in the pathogenesis of pathologies of other organ systems at the molecular level. Thus, the data presented in the review indicate the wide scope of the genes of primary CM, which goes beyond the cardiovascular system. That indicates the relevance of conducting comprehensive studies aimed at determining the cause-and-effect relationships between the CM and pathologies of other organs, including with the involvement of molecular genetic data.

#664 Childhood Takayasu arteritis: a multicentre retrospective study

Abstract Background and Aims Takayasu arteritis (TA) is a rare, large vessel vasculitis affecting mainly the aorta and its major branches. Data on paediatric TA (pTA) is very scarce. The aim of this study was to characterize clinical presentation, therapy and outcome of pTA in a global study population. Method We conducted an international multicentre retrospective observational study of children diagnosed with pTA. Inclusion criteria were an age of less than 18 years at initial presentation in the year 2000 or more recently. Clinical data were collected from patients’ charts by the treating paediatric rheumatologist or nephrologist; data were fully anonymised for analysis purposes. Follow-up data was collected up to 2 years after diagnosis. Results 198 patients from 20 countries were included (76% female). The median age at disease onset was 12 years. Arterial hypertension (67%), a difference in pulses between limbs (65%) and fatigue (66%) were the most common symptoms at presentation. The gastrointestinal system was the second most affected organ system. The median eGFR (estimated glomerular filtration rate) at baseline was 105 ml/min/1.73 m2. Renal artery stenosis was documented in 58% of all patients and in 37% there was need for an invasive renovascular procedure. In 25 of 32 (78%) patients who had either a positron emission tomography–magnetic resonance imaging (PET-MRI) or PET-computed tomography (CT) there was evidence of active inflammation mainly of the aorta. 67% of all patients showed thickened wall abnormalities and 31% had arterial dilatations in a major vessel on any one or more anatomical imaging modality such as ultrasound, CT or MRI. Immunosuppressive treatment was primarily steroids, cyclophosphamide and methotrexate, 37% of all patients were treated with monoclonal antibodies of which 65% received an anti-tumor necrosis factor (TNF) antibody, 31% an anti-Interleukin 6 (IL-6) antibody and 4% an anti-B-cell antibody. Dialysis was necessary in 7% and one patient underwent kidney transplantation. Seven patient deaths (4%) were documented at the most recent follow-up. The renal function after two years was median eGFR 102 ml/min/1.73 m2, with 67% showing normal function, 31% presenting with chronic kidney disease (CKD) stage 1, 1% with stage 2, 1% with stage 3 and no patients showed stages 4 and 5. A quarter of the patients (27%) were still symptomatic at the 2-year follow-up. The median systolic blood pressure was 117 (interquartile range 107–125) mmHg. 64% of all patients still had antihypertensive treatment, and 87% were still on immunosuppressive therapy. Conclusion Our study represents the largest paediatric cohort of children diagnosed with Takayasu arteritis. Several organ systems were involved at onset and the clinical spectrum was highly variable. We will in our further analyses in more detail describe the outcome in relation to presenting symptoms and treatment.

#990 Association between frailty and chronic kidney disease: findings from CHARLS

Abstract Background and Aims Frailty is a complex age-related clinical condition characterized by a decline in physiological capacity of several organ systems, with a resultant increased susceptibility to stressors. Little is known about the association between frailty and chronic kidney disease (CKD) among Chinese adults. The present study sought to investigate the relationship between frailty and CKD based on a large, nationally representative survey. Method The participants were 4231 adults aged ≥50 years from the China Health and Retirement Longitudinal Study (CHARLS). Based on the FRAIL scale, frailty and prefrailty were defined. CKD was defined as eGFR less than 60 mL/min/1.73 m2, calculated according to the CKD Epidemiology Collaboration (CKD-EPI) equation, or self-reported CKD. Logistic regression models were conducted to analyze the cross-sectional relationship between frailty and CKD. Cox proportional hazards regression models were used to examine the effect of frail status and frail components on CKD. Results We found that prevalence of frailty in CKD individuals was 13.9% while in patients without CKD was 8.4%. The prevalence of CKD in robust group was 6.0%, in prefrail group was 10.1% and in frail group was 14.0%. In frail status, after adjusted, the incidence of CKD was 1.713 (95% CI 1.109-2.646) in the frail group compared with robust group (P = 0.015). While there was no statistical difference in the incidence of CKD among the prefrail group and robust group. In frail components, after adjusted, weight loss was associated with higher risk of CKD [HR (95% CI): 1.617 (1.170-2.235)]. Conclusion We found that the prevalence of frailty was relatively high in the population. In frail status, both prefrail and frail were associated with a higher risk of CKD. In frail components, weight loss was associated with an increase incidence of CKD. Frailty is reversible, so early identification of frailty may reduce the incidence of CKD and improve the adverse consequences associated with CKD.

Lanthanide-Containing Polyoxometalate Crystallized with Bolaamphiphile Surfactants as Inorganic–Organic Hybrid Phosphors

Lanthanide elements such as europium exhibit distinctive emissions due to the transitions of inner-shell 4f electrons. Inorganic materials containing lanthanide elements have been widely used as phosphors in conventional displays. The hybridization of lanthanide ions with organic components enables to control of the material’s shapes and properties and broadens the possibility of lanthanide compounds as inorganic–organic materials. Lanthanide ion-containing polyoxometalate anions (Ln-POM) are a promising category as an inorganic component to design and synthesize inorganic–organic hybrids. Several inorganic–organic Ln-POM systems have been reported by hybridizing with cationic surfactants as luminescent materials. However, single-crystalline ordering has not been achieved in most cases. Here, we report syntheses and structures of inorganic–organic hybrid crystals of lanthanide-based POM and bolaamphiphile surfactants with two hydrophilic heads in one molecule. An emissive decatungstoeuropate ([EuW10O36]9−, EuW10) anion was employed as a lanthanide source. The bolaamphiphile counterparts are 1,8-octamethylenediammonium ([H3N(CH2)8NH3]2+, C8N2) and 1,10-decamethylenediammonium ([H3N(CH2)10NH3]2+, C10N2). Both hybrid crystals of C8N2-EuW10 and C10N2-EuW10 were successfully obtained as single crystals, and their crystal structures were unambiguously determined using X-ray diffraction measurements. The photoluminescence properties of C8N2-EuW10 and C10N2-EuW10 were investigated by means of steady-state and time-resolved spectroscopy. The characteristic emission derived from the EuW10 anion was retained after the hybridization process.

#1623 Risk factors for end-stage kidney disease and death in ANCA-associated vasculitis with glomerulonephritis

Abstract Background and Aims ANCA-associated vasculitis (AAV) with glomerulonephritis (AAV-GN) still carries poor prognosis despite treatment improvement over the last years. Currently, improving assessment of disease activity and severity and defining risk factors for ESKD pose challenges. In this study we aim to determine and characterize risk factors associated with progression to ESKD or death in patients with AAV-GN. Method We retrospectively analysed all AAV-GN cases of our Center. ESKD was considered as a composite outcome of eGFR&amp;lt;15 or dialysis dependency. Biopsies were classified according to Berden's classification (BC), Brix's renal risk score (RRS), Mayo Clinic Chronicity Score (MCCS) and AAV-GN combined score (AAV-GN-CS). Categorical variables were analysed by non-parametric chi-square or fisher's exact test; and continuous variables by Mann-Whitney U test. Cox regression models were applied for death and Kaplan-Meier estimator. Significance value α = 0.05 was considered. Results A total of 74 patients, 56.8% male, 69 years-old median age were included. Of them, 81.2% were MPO, 11.6% PR3 and 7.2% negative. At presentation, 35.3% had alveolar haemorrhage, 13.4% GI and 66.7% constitutional manifestations. At diagnosis, median eGFR was 7.5 mL/min/1.73 m2 (5.0-13.0), proteinuria 2.2g/g (0.45-4.17) and all patients had haematuria. Initial median ANCA titer (ATi) was 100 UI/mL (51-134) and at last follow-up 44 (15-101). 64.2% of all patients required dialysis at presentation. Of these, 14.0% recovered until discharge. We also analyzed biopsies of 57 patients. According to BC, 15.8% were focal, 40.4% crescentic, 26.3% mixed, and 17.5% focal. ESKD risk was medium in 28.3% and high in 69.8%, as determined by RRS; whereas low in 31%, intermediate in 42.3% and high in 19% as per AAV-GN-CS. Induction treatment (IT) used was cyclophosphamide (CYC) in 46.3%, CYC plus rituximab (RTX) in 18.3% and RTX in 3.3%. Only 17 patients (26.2%) were added plasmapheresis (PLEX). Only 28% achieved kidney remission (KRm), 7% relapsed and 68.7% developed ESKD. Of them, 95.5% had eGFR&amp;lt;15 at diagnosis, 30% low C3, 37.5% crescentic pattern, 28.1% mixed and 28.1% sclerotic. 87% of ESKD patients had &amp;lt;25% normal glomeruli (NG), and 87.1% high ESKD risk (RRS). Progression to ESKD was associated with lower eGFR (p &amp;lt; 0.001) and low C3 at diagnosis (p = 0.026), lower %NG (p = 0.004), higher %CG (p = 0.004), higher %IFTA (p = 0.011), worse BC (p = 0.012), higher RRS (p &amp;lt; 0.001) and MCCS categories (p = 0.010), but not with AAV-GN-CS. ATi reduction seems to determine better renal outcome (p = 0.042). No significant differences were seen with IT or maintenance treatment, nor with PLEX addition. No patient treated with RTX, or combined treatment developed ESKD. Mortality was 32.8% and the best predictive model includes age, GI manifestations and KRm (p &amp;lt; 0.001). Age (p = 0.004), lower eGFR at diagnosis (p = 0.016) and GI manifestations (p = 0.003) were predictive of death, while achieving KRm improved survival (p = 0.009). Conclusion Our results reveal that AAV-GN patients have poor kidney outcome when presenting with severe kidney dysfunction, high ANCA titers and low C3 levels. Worse histological scoring is determinant of ESKD. The prediction power of AAV-GN-CS must be demonstrated in large cohorts. RTX effectivity on kidney survival must be further supported. Patient survival is related with younger age at diagnosis, organ systems involved at clinical presentation, and achievement of kidney remission.

#1351 Assessment of safety and efficacy of expanded hemodialysis in comparison to HDF

Abstract Background and Aims In end-stage kidney disease, solutes with a wide spectrum of molecular weight, called uremic toxins, are retained due to impaired kidney cleansing capacity. Particularly, the retention of toxins in the middle molecular weight range 15–45 kDa might negatively affects multiple organ systems and metabolic pathways. The removal of such large uraemic toxins is still a challenge. HDF has produced some results although large convective volume, optimal vascular access to increase the blood flow rate and strict water quality management are required. Medium Cut-Off, high Retention Onset membrane have been recently developed introducing the concept therapy called “expanded haemodialysis” (HDx). Furthermore, vitamin E-coated membrane has potential beneficial effects on inflammation and oxidative stress. Method A prospective longitudinal single-center study was conducted for 3 months among 18 chronic haemodialysis patients. Patients were randomly assigned into either HDF with high flux membrane or HDx with Theranova or ViE-X membrane. The primary goal was to assess albumin loss among the three types of dialyzers. Secondary goals included assessment of depurative efficacy for uraemic toxins and clinical outcomes. Throughout the treatment, a proportional part of the dialysis fluid was collected to quantify albumin loss. Blood samples were taken before and after dialysis session in order to calculate the Removal Ratio and at two different intradialytic timepoints from arterial and venous line of the circuit in order to calculate instantaneous clearance. Results Mean albumin loss was significantly higher in patients undergoing HDx with Theranova membrane (ANOVA, p&amp;lt;0.001) without any difference in serum albumin concentration among the three groups. Instantaneous clearance of small and middle molecules was significantly higher in patients undergoing HDF, but we didn't find differences in removal ratio. Reduction of Erythropoietin resistance index was observed in patients treated with ViE-X membrane but it was related to their lower dialysis vintage. Conclusion HDx with Theranova membrane was associated with higher albumin loss without any effect on pre-dialysis serum albumin. Moreover, patients treated Theranova membrane, in the presence lower Qb, lower convective dose and lower instantaneous clearance reached same dialysis efficacy compared to HDF.

Systematic histology and evidence for the male reproductive activity of Amphibalanus amphitrite (Darwin, 1854)

AbstractThe striped acorn barnacle, Amphibalanus amphitrite, a taxon of Balanidae, is commonly found along Thailand's coastline. In this study, we used histological methods to describe the microscopic anatomy of A. amphitrite. All samples (n = 30) were obtained from the seagrass beds of Libong Island, Thailand, in the Andaman Sea. Histological observation of various longitudinal sections from specimens of A. amphitrite provides clear insights into the organization of organ systems in the species. The digestive tract was observed to be mainly divided into four subregions, including the cuticle‐lined mouth and esophagus, which is characterized by a high columnar epithelium, the stomach, and the intestine. The accessory organ, including the digestive gland, exhibited lobulated structures and was covered with low columnar epithelial cells on a thin layer of smooth muscle. Furthermore, we examined the reproductive system, including both the ovary and testes, as well as the process of gametogenesis. Testicular development was predominantly observed during active breeding seasons throughout the observation.