Complications Of Disease Research Articles

Surgical and non-operative treatment of acute complicated diverticulitis in a COVID hospital

Surgical treatment of acute abdomen during the SARS-CoV-2 pandemic was accompanied by an extremely high mortality rate, however, only a few studies have presented the results of acute inflammatory complications of diverticular disease (AICDD).AIM: analysis of treatment of AICDD in a COVID-19 hospital.PATIENTS AND METHODS: the retrospective study included 78 patients with acute diverticulitis (AD) from a COVID hospital, confirmed by CT or intraoperative revision. Assessment of COVID pneumonia, comorbidities, organ dysfunction, CT findings, peritonitis, treatment methods, and in-hospital mortality among patients was performed.RESULTS: organ dysfunction of ≥ 1 point on the qSOFA scale was detected in 59.0% of the patients. According to CT data, abdominal distant gas was detected in 48 (61.5%) patients, and pericolic gas in 14 (17.9%) patients. Segmental colon resection was performed in 60 (76.9%) patients, laparoscopic lavage (LL) of the abdominal cavity — in 3, non-operative treatment (NOT) with drainage of fluid collections — in 6, and only NOT in 10 patients. Most patients with distant or pericolic gas were operated on within an average time of 1 [0; 3.5] hours after admission. Diffuse peritonitis was detected during surgery in 45 (75%) of them. After resection, organ dysfunction of ≥ 2 points on the SOFA scale developed or progressed in 52 (86.7%) patients. The overall mortality rate was 48.7%, and the postoperative mortality was 63.3%. All patients (n = 38) died after segmental colon resection. Successful NOT was achieved in 4 patients with pericolic gas and 3 patients with distant gas.CONCLUSION: surgery for AICDD in patients with COVID-19 is associated with extremely high mortality, therefore, in the absence of obvious signs of diffuse peritonitis, initial non-operative treatment may be life-saving.

Pathologic Analysis of Twenty-one Appendices From Children With Multisystem Inflammatory Syndrome Compared to Specimens of Acute Appendicitis: A Cross-sectional Study.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining the pathomechanism of MIS-C, including the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion. We aimed to examine appendectomy specimens from MIS-C patients and assess their pathologic features, as well as the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histologic evaluation of appendiceal specimens included hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein-1 (PD-1) and SARS-CoV-2 nucleocapsid antigen. Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14% vs. 95%, P < 0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (P = 0.04), as was the proportion of CD4+ to CD8+ (P < 0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients. The appendiceal muscularis of patients with MIS-C lack edema and neutrophilic infiltration typical for AA. SARS-CoV-2 antigens and PD-1 are absent in the appendices of children with MIS-C. These findings argue against the central role of SARS-CoV-2 persistence in the gut and lymphocyte exhaustion as the major triggers of MIS-C.

Predictors of operative management in diabetic foot ulcers.

Surgery plays a key role in the management of complicated diabetic foot disease (DFD). Currently, indications for medical versus surgical management are poorly defined. Prompt identification of patients who require surgery may reduce morbidities and length of hospital stay. This study aims to analyse factors in DFD that necessitate early surgical interventions. All patients admitted under a multi-disciplinary diabetic foot team in a tertiary institution over 2years were included in a retrospective case-control study comparing patients who received medical management and patients who received surgical management. Logistic regression was performed to identify factors associated with surgical management of diabetic foot complications. Three hundred and forty patients were included. 49% of patients required surgical management. Toe ulceration, elevated C-reactive protein (CRP), and the presence of osteomyelitis were associated with surgical management. Multivariate analysis calculated an odds ratio (OR) of 1.01 for CRP (p<0.001), OR 2.19 (p<0.019) favouring surgical management for forefoot ulcers, and OR 2.2 (p<0.019) if osteomyelitis was present. Patients with elevated CRP levels, a forefoot diabetic ulcer and established osteomyelitis were more likely to undergo surgical management. Prompt recognition of these patients has the potential benefit of earlier decision making in definitive surgical interventions.

Review on Diabetes Mellitus: An Insight into the Current Scenarios, the Challenges of Therapy, and Application of Traditional Drugs

Abstract: Diabetes mellitus, an epidemic of the 21st century, is listed as one of the top ten causes of death around the world by the World Health Organization and is a complicated disease to deal with. Medically, a metabolic disorder characterized by elevated blood glucose levels and altered metabolism of biological macromolecules, mainly carbohydrates. Diabetes mellitus has a worldwide prevalence, and populations of all high, middle, as well as low-income countries, are affected by it. More than 400 million persons are currently living with diabetes. Many risk factors, such as lack of exercise, irregular diet, drinking, and smoking habits, as well as genetic factors, also contribute to the increased incidence of diabetes mellitus in the modern era. The conventional therapies for diabetes are based on insulin, insulin analogues, peptides, and oral hypoglycemics. The primary objective is to lower the elevated blood glucose levels and manage the distress to enhance the quality of life of the patient. The management of diabetes is very crucial to avoid complications having serious consequences such as the extra economic burden due to these complications. Conventional drug therapy has its own adverse effects, and its timely availability and cost are still an issue in many low and middle-income countries. Diabetes mellitus has been reported in various ancient kinds of literature along with various natural remedies (plants/herbals) useful in it. These plant-based remedies offer the benefits of lesser or no adverse effects, easy availability due to natural abundance, and low cost. Therefore, extensive research work is carried out in the past few decades to identify and understand the underlying principles of plant-based/herbal medicines to develop new potential lead molecules and a relatively safer, easily available and more economical alternative treatment therapy for diabetes mellitus.

Biological profile of secondary hyperparathyroidism in chronic renal failure patients

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease, especially in hemodialysis patients. It is characterized by overproduction of parathyroid hormone in response to chronic deterioration of renal function. The aim of this retrospective study was to determine the average time to develop secondary hyperparathyroidism, analyze the initial phosphocalcic profiles, and evaluate the evolution of these profiles in hemodialysis patients, following the recommendations of the KDOQI 2003 and KDIGO 2009 groups. The study included 134 hemodialysis patients from two private dialysis centers. Data were collected from patients' medical records and analyzed using SPSS software. The results showed that the average time to develop secondary hyperparathyroidism was 3.15 years according to KDOQI recommendations and 4.64 years according to KDIGO recommendations based on parathyroid hormone levels. The initial assessment revealed an imbalance in phosphocalcic metabolism in approximately 20.1% to 22.5% of patients, a proportion that increased to 27.5% during follow-up, according to both sets of recommendations. In conclusion, secondary hyperparathyroidism is an inevitable complication of chronic kidney disease, affecting the vital and functional prognosis of hemodialysis patients. Diagnosis primarily relies on parathyroid hormone levels, associated with phosphocalcemia, vitamin D, and PAL analyses. Treatment aims mainly to maintain blood levels of calcium, phosphorus, and vitamin D within recommended limits and to reduce parathyroid response to phosphocalcic disturbances.

Non-invasive Scores and Serum Biomarkers for Fatty Liver in the Era of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Comprehensive Review From NAFLD to MAFLD and MASLD.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide, making it the leading cause of liver related morbidity and mortality. Currently, liver biopsy is the gold standard for assessing individuals with steatohepatitis and fibrosis. However, its invasiveness, sampling variability, and impracticality for large-scale screening has driven the search for non-invasive methods for early diagnosis and staging. In this review, we comprehensively summarise the evidence on the diagnostic performance and limitations of existing non-invasive serum biomarkers and scores in the diagnosis and evaluation of steatosis, steatohepatitis, and fibrosis. Several non-invasive serum biomarkers and scores have been developed over the last decade, although none has successfully been able to replace liver biopsy. The introduction of new NAFLD terminology, namely metabolic dysfunction-associated fatty liver disease (MAFLD) and more recently metabolic dysfunction-associated steatotic liver disease (MASLD), has initiated a debate on the interchangeability of these terminologies. Indeed, there is a need for more research on the variability of the performance of non-invasive serum biomarkers and scores across the diagnostic entities of NAFLD, MAFLD and MASLD. There remains a significant need for finding valid and reliable non-invasive methods for early diagnosis and assessment of steatohepatitis and fibrosis to facilitate prompt risk stratification and management to prevent disease progression and complications. Further exploration of the landscape of MASLD under the newly defined disease subtypes is warranted, with the need for more robust evidence to support the use of commonly used serum scores against the new MASLD criteria and validation of previously developed scores.

An overview of qualitative and quantitative platelet abnormalities in schistosomiasis.

Schistosomiasis is a neglected tropical disease referring to the infection with blood parasitic trematodes of the genus Schistosoma. It impacts millions of people worldwide, primarily in low-to-middle-income countries. Patients infected with schistosomiasis often exhibit a distinct hematological profile, including anemia, eosinophilia, thrombocytopenia, and coagulopathy. Platelets, essential components of the hemostatic system, play a crucial role in the pathogenesis of schistosomiasis. Schistosomes secrete serine proteases and express ectoenzymes, such as calpain protease, alkaline phosphatase (SmAP), phosphodiesterase (SmNPP5), ATP diphosphohydrolase (SmATPDase1), serine protease Sk1, SmSP2, and Sm22.6, which can interfere with platelet normal functioning. This report provides comprehensive, up-to-date information on platelet abnormalities observed in patients with schistosomiasis, highlighting their importance in the disease progression and complications. It delves into the interactions between platelets and schistosomes, including the impact of platelet dysfunction on hemostasis and immune responses, immune-mediated platelet destruction, and the potential mechanisms by which schistosome tegumental ectoenzymes affect platelets. Furthermore, the report clarifies the relationship between platelet abnormalities and clinical manifestations such as thrombocytopenia, coagulation disorders, and the emergence of portal hypertension and gastrointestinal bleeding. Understanding the complex interplay between platelets and schistosomes is crucial for improving patient management and outcomes in schistosomiasis, particularly for those with platelet alterations. This knowledge contributes to improved diagnostic methods, innovative treatment strategies, and global efforts to control and eliminate schistosomiasis.

Co-administration of probiotics and vitamin D reduced disease severity and complications in patients with Parkinson's disease: a randomized controlled clinical trial.

Probiotics have beneficial effects on the nervous system by modulating the gut-brain axis. Additionally, vitamin D supplementation presents a potential way for ameliorating neuropsychological disorders, particularly in regions with a high prevalence of vitamin D deficiency. The current clinical trial aimed to investigate the role of co-administered supplementation of probiotics and Vitamin D on the different inflammatory aspects of patients with Parkinson's disease. Forty-six patients with PD were recruited From the Functional Neurosurgery Research Center, Tehran, Iran. These patients were randomly allocated to one of the two treatment groups: Group A, who received probiotic/vitamin D supplements (n = 23), and Group B who received placebo capsules (n = 23) for 12 weeks. As primary outcomes, Interferon-Gamma (IFN-γ), interleukin 1 beta (IL-1β), IL-6, IL-10, Tumor Necrosis Factor-Alpha (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in serum were evaluated at the baseline and the end of the trial. Moreover, Additional questionnaire-based factors including gastrointestinal symptom rating scale (GSRS), Beck Anxiety Inventory (BAI), and Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated. Our findings demonstrated that the consumption of probiotic/vitamin D supplements leads to a significant decrease in IL-1β, INF-γ, IL-6, and MDA levels, while showing a significant increase in IL-10 and TAC levels compared to the placebo group (P < 0.05). Additionally, it leads to a significant decrease in the disease severity, anxiety, and gastrointestinal problems in PD patients in comparison to the placebo group (P < 0.05). Given the acknowledged role of inflammation in the pathogenesis of Parkinson's disease on one hand, and the recognized anti-inflammatory and antioxidant effects associated with probiotics and vitamin D on the other hand, the concurrent administration of probiotics and vitamin D supplements emerges as a promising and potentially effective treatment option for individuals with PD.

Single-nucleus analysis reveals microenvironment-specific neuron and glial cell enrichment in Alzheimer’s disease

BackgroundAlzheimer’s disease (AD) is a complicated neurodegenerative disease. Neuron-glial cell interactions are an important but not fully understood process in the progression of AD. We used bioinformatic methods to analyze single-nucleus RNA sequencing (snRNA-seq) data to investigate the cellular and molecular biological processes of AD.MethodsnRNA-seq data were downloaded from Gene Expression Omnibus (GEO) datasets and reprocessed to identify 240,804 single nuclei from healthy controls and patients with AD. The cellular composition of AD was further explored using Uniform Manifold Approximation and Projection (UMAP). Enrichment analysis for the functions of the DEGs was conducted and cell development trajectory analyses were used to reveal underlying cell fate decisions. iTALK was performed to identify ligand-receptor pairs among various cell types in the pathological ecological microenvironment of AD.ResultsSix cell types and multiple subclusters were identified based on the snRNA-seq data. A subcluster of neuron and glial cells co-expressing lncRNA-SNHG14, myocardin-related transcription factor A (MRTFA), and MRTFB was found to be more abundant in the AD group. This subcluster was enriched in mitogen-activated protein kinase (MAPK)-, immune-, and apoptosis-related pathways. Through molecular docking, we found that lncRNA-SNHG14 may bind MRTFA and MRTFB, resulting in an interaction between neurons and glial cells.ConclusionsThe findings of this study describe a regulatory relationship between lncRNA-SNHG14, MRTFA, and MRTFB in the six main cell types of AD. This relationship may contribute to microenvironment remodeling in AD and provide a theoretical basis for a more in-depth analysis of AD.

Expert consensus on the clinical application of oral small-molecule antiviral drugs against COVID-19

Although COVID-19 no longer constitutes a "public health emergency of international concern", which still has being spreading around the world at a low level. Small molecule drugs are the main antiviral treatment for novel coronavirus recommended in China. Although a variety of small-molecule antiviral drugs against COVID-19 have been listed in China, there is no specific drug recommendation for special populations. Society of Bacterial Infection and Resistance of Chinese Medical Association, together with the National Clinical Research Center for Respiratory Disease, and the National Center for Respiratory Medicine, organized domestic experts in various fields such as respiratory, virology, infection, critical care, emergency medicine and pharmacy to release Expert Consensus on the Clinical Application of Oral Small-Molecule Antiviral Drugs against COVID-19. The main content of this consensus includes the introduction of seven small-molecule antiviral drugs against COVID-19, focusing on the drug recommendations for 14 special groups such as the elderly, patients with complicated chronic diseases, tumor patients, pregnant women, and children, and providing suggestions for clinicians to standardize drug use.

Rescue splenic artery embolization in an adult patient of sickle cell disease presented with acute splenic sequestration crisis.

Splenic sequestration crisis is a potentially fatal complication of sickle cell disease, mainly seen in young children. Only a few case series describe the acute splenic sequestration crisis in adults and its management, which primarily consists of supportive care and, in some cases, splenectomy. Splenic artery embolization has seldom been described in sickle cell disease. This is probably the first case in which an adult with sickle cell disease presented with an acute splenic sequestration crisis was managed successfully through splenic artery embolization. This 22-year-old female, a known case of sickle cell disease, presented with severe pain in the abdomen and low-grade intermittent fever for two days, secondary to an acute splenic sequestration crisis. The diagnosis of acute splenic sequestration was made based on clinical and blood parameters, ultrasonography, and computed tomography. Even with adequate supportive care and blood transfusions, the patient's condition worsened with a rapid fall in the hemoglobin and total platelet count. Considering splenectomy to be a high-risk procedure for this patient, a decision of rescue splenic artery embolization was taken, which was successful. Splenic artery embolization may be considered a lifesaving procedure in patients with acute splenic sequestration, where the risk of splenectomy can be high. Adequate post-procedure supportive care is vital for preventing complications.

Family Support and Type 2 Diabetes Self-management Behaviors in Underserved Latino/a/x Patients.

Latino/a/x families experience persistent Type 2 diabetes mellitus (T2DM) disparities, including higher rates of diagnosis and mortality due to disease complications than their non-Hispanic White counterparts. Though greater social support is associated with improved disease outcomes for Latino/a/x patients with diabetes, research has yet to identify the specific pathways through which social support, and specifically family support, influences self-management. This study tested a theoretical model highlighting the mechanisms and pathways linking social support and physical health. Specifically, self-efficacy and depression were tested as psychological pathways connecting family support to diabetes self-management behaviors and diabetes morbidity in Latino/a/x patients with T2DM. Data from 177 patients were analyzed using structural equation modeling. Measures included diabetes-specific family support needed and received, depressive symptoms, self-efficacy in diabetes management, diabetes self-management behaviors, health appraisal, and hemoglobin A1c. Greater diabetes-specific family support was significantly associated with more frequent engagement in diabetes self-management behaviors, both directly (p < .001) and through diabetes self-efficacy's partial mediation of this relationship (p = .013). Depression was not significantly associated with either family support (support received, p = .281; support needed, p = .428) or self-management behaviors (p = .349). Family support and diabetes self-efficacy may be important modifiable psychosocial factors to target via integrated care interventions aimed at supporting Latino/a/x patients with T2DM. Future research is needed to test empirically based, culturally adapted interventions to reduce T2DM-related health disparities in this population.

Factors associated with risk analysis for asymptomatic left ventricular diastolic dysfunction in nondialysis patients with chronic kidney disease

Heart failure (HF) constitutes a major determinant of outcome in chronic kidney disease (CKD) patients. The main pattern of HF in CKD patients is preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD) is a frequent pathophysiological mechanism and specific preclinical manifestation of HFpEF. Therefore, exploring and intervention of the factors associated with risk for LVDD is of great importance in reducing the morbidity and mortality of cardiovascular disease (CVD) complications in CKD patients. We designed this retrospective cross-sectional study to collect clinical and echocardiographic data from 339 nondialysis CKD patients without obvious symptoms of HF to analyze the proportion of asymptomatic left ventricular diastolic dysfunction (ALVDD) and its related factors associated with risk by multivariate logistic regression analysis. Among the 339 nondialysis CKD patients, 92.04% had ALVDD. With the progression of CKD stage, the proportion of ALVDD gradually increased. The multivariate logistic regression analysis revealed that increased age (OR 1.237; 95% confidence interval (CI) 1.108–1.381, per year), diabetic nephropathy (DN) and hypertensive nephropathy (HTN) (OR 25.000; 95% CI 1.355–48.645, DN and HTN vs chronic interstitial nephritis), progression of CKD stage (OR 2.785; 95% CI 1.228–6.315, per stage), increased mean arterial pressure (OR 1.154; 95% CI 1.051–1.268, per mmHg), increased urinary protein (OR 2.825; 95% CI 1.484–5.405, per g/24 h), and low blood calcium (OR 0.072; 95% CI 0.006–0.859, per mmol/L) were factors associated with risk for ALVDD in nondialysis CKD patients after adjusting for other confounding factors. Therefore, dynamic monitoring of these factors associated with risk, timely diagnosis and treatment of ALVDD can delay the progression to symptomatic HF, which is of great importance for reducing CVD mortality, and improving the prognosis and quality of life in CKD patients.

Wearable self-powered ballistic signal detectors with ferroelectric composites arrays for cardiovascular and diabetic complication

Abstract Background Flexible and wearable electronic devices with lightweight are needed to monitor and guide treatment in patients with cardiovascular disease and diabetic complication. We aimed to develop self-powered wearable bio-signal sensing arrays for cardiovascular and diabetic complication diagnosis and continuous monitoring. Methods Ferroelectric composites were designed to have piezoelectric property and high flexibility. Detection of arterial pulse as ballistogram (BCG) was simultaneously compared with electrocardiogram (ECG) in 20 controls. Heart rate and components of ECG was compared with those of BCG. Then, 9 ferroelectric BCG sensors as a square type array with self-power generation were fabricated to attachable thin film. Pressure distribution with BCG sensor array attached to socks were compared between 20 controls and 20 patients with diabetic neuropathy or vasculopathy during standing and ambulation for gait pressure distribution. Pressure distribution pattern was compared to neuropathy and vasculopathy parameters. Results Heart rate between BCG and ECG was significantly correlated (interclass correlation coefficient, ICC 0.99, 95% CI 0.98-0.99, p&amp;lt;0.001). QRS and T wave in ECG were correlated to second and third wave in BCG. Radial artery augmentation index by blood pressure monitoring was significantly correlated to BCG pressure (ICC 0.76, 95% CI 0.38-0.90, p=0.002). Analysis of foot pressure distribution demonstrated the highest pressure point at the anterolateral plantar area below a little tow. However, pressure gradient between anterolateral and anteromedial plantar area in diabetic patients was greater than that in controls (42.3±10.2 mV vs. 31.2±8.5 mV, p=0.024). Pressure gradient in diabetic patients was correlated to ankle-brachial index (ICC 0.62, 95% CI 0.32-0.90, p=0.036), but not to neuropathy parameters. Conclusion Wearable BCG sensor could accurately detect heart rate, blood pressure index and significantly correlated to ABI. Pressure distribution pattern and gradient analysis in diabetic patients by wearable BCG sensor arrays might predict diabetic complications. Gait remedial training guided by wearable BCG sensor arrays might aid to prevent diabetic complications.

#1814 Infection associated pancreatitis in peritoneal dialysis, a case report

Abstract Background and Aims Peritoneal dialysis (PD) patients seem to have a higher incidence of acute alithiasic pancreatitis. Though rare and with some suggested triggers described in the literature, this is still a poorly understood and potentially life-threatening complication. We present a 60 years old woman concluding antimicrobial therapy with an icodextrin night-dwell regimen for peritonitis presenting with epigastric pain. This work reviews our approach to cloudy effluent from non-infectious causes during an infection while managing acute pancreatitis in the PD setting. We report diagnostic difficulties and treatment considerations with a positive outcome. Method We present a 60 years old woman on PD for one year presenting to the emergency room in November of 2023 with severe epigastric pain, nausea and emesis. She suffered from stage 5 chronic kidney disease due to autosomal dominant polycystic kidney disease and had disease complications as anemia and secondary hyperthyroidism controlled within targets. She was on automated PD (APD) with glucose based solutions. She was on the 17th of 21 days antibiogram guided treatment (ceftazidime) for a Enterobacter ludwigii PD-related peritonitis with good clinical evolution and peritoneal effluent (PE) leukocyte count per μl from 1258 to 91 in 5 days. In the previous 3 months she had had 2 other infectious episodes. A bacteremic urinary tract infection to E. coli associated with peritonitis treated with antibiogram guided therapy (ceftazidime) followed by C. difficile colitis treated with oral vancomycin. During each infection period she transitioned from APD to continuous ambulatory peritoneal dialysis with an icodextrin night dwell. On admission she presented with normal vital signs, no fever, and abdominal distention with severe epigastric tenderness to palpation without muscular guarding. Her dwell exchange showed blood-tinged cloudy PE. She had hemoglobin of 11.3 g/dl, otherwise normal blood cell counts, and raised amylase (213 UI/l) and lipase (1467 UI/l). There was no elevation of transaminases, cholestatic enzymes, C-reactive protein or procalcitonin and lipidemia or hyperbilirubinemia were normal. PE cell count showed 213/μl leukocytes and 202/μl erythrocytes. Abdominal ultrasound showed no evidence of an obstructive cause. She was admitted in the surgical care unit for a conservative and watchful approach. Results On presentation we accounted for the peritonitis still under treatment, acute pancreatitis, drug therapy and recently introduced icodextrin solution. The acute alithiasic pancreatitis diagnosis was established but there was still a possible causative role of icodextrin or infection and refractory peritonitis could also not be promptly excluded. The literature suggests icodextrin and other drugs as causes for acute pancreatitis in some patients but also mentions the possibility of cloudy or hemorrhagic effluent due to abdominal inflammation processes. Considering the clinical stability, the multiple possible contributing causative agents and the differential diagnosis of refractory peritonitis we closely monitored PE cell count evolution keeping the icodextrin dwell and ceftazidime prescriptions and collected samples for bacterial and fungal culture. The cultures were negative and stability of leukocyte count and mononuclear cell predominance (Fig. 1) helped us exclude the peritonitis hypothesis and attribute the PE changes to the pancreatitis process. Conclusion Inpatient monitoring and identifying all possible causes are essential to ensure good outcomes in PD patients suffering from acute pancreatitis. Full anamnesis, physical examination and close attention to laboratory findings were key in allowing adequate antibiotic therapy and resolution of the abdominal inflammatory process at hand while maintaining an adequate PD prescription.

#1346 Inpatient and outpatient service review of a Greek reference centre for glomerular diseases

Abstract Background and Aims The glomerulonephritis (GN) is a rare and complicated disease with high demand of hospital resources while the chronic kidney disease and end-stage renal disease present increased prevalence in these patients. Method We retrospectively assessed the inpatient and outpatient service of a Greek reference centre for glomerular diseases during the pre-Covid-19 period 2018-2020. Results 267 patients (38% female, median age 65 ± 23 years) included. All patients underwent a kidney biopsy by the nephrologist without complications. ANCA associated GN (18%), Focal Segmental Glomerulosclerosis/Minimal Change Disease (17.5%), IgA nephropathy (17%), Membranous Nephropathy (12.6%), Lupus Nephritis (5%), Membranoproliferative GN (3%), Fibrillary GN (3%), Monoclonal Gammopathy of Renal Significance (3.3%) and IgG4-related disease (2%.) are encompassed. We reported median 75 new patients per year. Regarding the inpatient service, we observed an increasing trend to the hospitalizations during this period (274, 452, 461 hospitalizations in 2018, 2019, 2020 respectively). The AAGN was the most common disease of hospitalizations through this period (53% in 2018, 33% in 2019, 39% in 2020), whereas the second most common was the FSGS/MCD (28% in 2018, 13% in 2019, 23.8% in 2020). The outpatient's service review also revealed an increasing number of visits per person per year (279, 456 and 464 total visits in 2018, 2019 and 2020 respectively). The disease with the highest number of visits per person was reported the AAV (median 3.25 visits per patient per year). All the patients were managed in adherence to the latest guidelines for GN in collaboration with a multidisciplinary team, consisting of nephrologist, rheumatologist, cardiologist, and pathologist. Finally, we reported complete response at 76% of the patients and in terms of renal improvement, 46% presented eGFR≥60 ml/min/1.73 m2, 45% eGFR&amp;lt;60 ml/min/1.73 m2 and only 9% progressed to ESRD after the first year of treatment. Conclusion Patients with GN present an increased need for hospitalization and regular outpatient visits. Addressing these diseases necessitates the expertise of a multidisciplinary team to provide comprehensive care that maximizes the potential for sustained positive long-term outcomes.

#571 Vitamin D receptor from VSMCs regulates vascular calcification during CKD: a potential role for miR-145a

Abstract Background and Aims Vascular calcification (VC) is a highly prevalent complication of chronic kidney disease (CKD) and is associated with the higher morbidity-mortality of patients with CKD. Vitamin D receptor (VDR) has been proposed to play a role in the osteoblastic differentiation of vascular smooth muscle cells (VSMCs), but the involvement of vitamin D (1, 25D) in VC associated to CKD is controversial. Accumulating evidence points to microRNAs as important players in the process of VC and recent studies show that miR-145a expression decreases in VSMCs during VC. In addition, VDR has been considered as a potent regulator of these small molecules, while miR-145a was identified as a target for 1, 25D. Our aim was to determine the role of local vitamin D signalling in VSMCs during CKD-induced VC and the involvement of miR-145a in this process. Method We used epigastric arteries from CKD-affected patients and from individuals with normal renal function. In vivo, we employed an experimental model of CKD-induced VC in mice with conditional deletion of VDR in VSMC (Myh11-CreERT2+ VDRlox/lox), while in vitro, we used mouse VSMC with (VDRwt) or without VDR (VDRko) incubated in calcification media. Transfection experiments with mmu-miR-145a-5p mimic or mmu-miR-145a-5p inhibitor were carried out in mouse VDRwt VSMCs. Results CKD-affected patients showed an increase in VC, alongside an increased arterial expression of VDR compared with controls with normal renal function. Conditional gene silencing of VDR in arterial VSMCs led to a significant decrease of VC in the mouse model of CKD, despite similar levels of renal impairment and serum calcium and phosphate levels. This was accompanied by lower arterial expression of osteopontin (OPN) and lamin A, and a higher expression of sclerostin (SOST). Runx2 was increased in arteries of both CKD groups independently of the presence of VDR in VSMCs. Furthermore, CKD-affected mice showed a reduction of miR-145a expression in calcified arteries, which was significantly recovered in animals with deletion of VDR in VSMCs. In vitro, the absence of VDR prevented VC, inhibited the increase of OPN, and re-established the expression of miR-145a. Forced expression of miR-145a in vitro in VDRwt VSMCs blunted VC and decreased OPN levels. Mir-145a levels markedly decreased both in human and mouse VDRwt VSMCs incubated in calcification media and 1, 25D. Overexpression of miR-145a suppressed the levels of OPN induced by 1, 25D, while the inhibition of mir-145a led to a significant increase in OPN levels, even higher than in cells treated solely with 1, 25D. A predicted miR-145a-binding site was detected at the 3’UTR of OPN mRNA transcript, through the extended seed region of the miRNA, pointing to OPN as a possible target of mir-145a during VC in CKD. There were no significant differences in Runx2 levels in 1, 25D-treated cells after transfection with mir-145a mimic or inhibitor. Conclusion VDR is induced in calcified VSMCs during CKD where it can modulate the expression of promoters and inhibitors of VSMC transdifferentiation, as well as small noncoding RNA molecules such as mir-145a that modulate VC. The regulation of these pathways by VDR seems to be essential for the settings of CKD-induced VC, as deletion of VDR from VSMCs prevented it.

#2070 Associations of fecal and plasma levels of SCFAs with gut microbiota and clinical characteristics in non-dialysis renal anemia patients

Abstract Background and Aims Renal anemia is one of the most common complications of Chronic Kidney Disease (CKD). The gut-kidney axis hypothesis has led to numerous studies showing that patients with CKD have a distinct gut microbiota structure compared with controls and that changes in gut microbiota correlate with disease severity and progression. The short-chain fatty acids (SCFAs) are speculated to be pivotal in the gut-kidney crosstalk. However, the role of SCFAs in renal anemia has not been elucidated. This study aimed to explore and compare the fecal and plasma levels of SCFAs in non-dialysis renal anemia patients and healthy controls to reveal the potential interactions among SCFAs, gut microbiota, and clinical features of renal anemia, which may provide new light on further studies. Method A cohort of 30 non-dialysis renal anemia patients and 20 healthy controls were recruited from the First Affiliated Hospital of Zhengzhou University. Gut microbiota was analyzed using 16S rRNA gene amplification sequencing. Fecal and plasma concentrations of SCFAs were measured using GC-MS/MS platform. The clinical characteristics of patients with renal anemia and controls were evaluated. Results Renal anemia patients displayed altered microbiota composition compared to healthy subjects. The relative abundance of Enterobacterales, Enterobacteriaceae, Escherichia-Shigella, and Escherichia-coli were higher in patients with renal anemia, and the Lachnospiraceae family decreased in renal anemia patients. In contrast, the relative abundance of Lachnospirales, Lachnospiraceae, and Bacteroides vulgatus was higher in the control group. Patients with renal anemia had higher fecal and plasma concentrations of SCFAs compared to controls. The fecal and plasma concentrations of SCFAs were significantly different not only between the patients with renal anemia and controls but also in the different severity of renal anemia. Moreover, different types of SCFAs are intimately associated with clinical characteristics. The applications of medications may exert effects on the fecal and plasma SCFAs. A positive correlation was obtained between Lachnospirales and the plasma SCFAs. The levels of acetic acid and caproic acid in fecal and the levels of acetic acid, propionic acid, and butyric acid in plasma were all positively correlated with the abundance of Cyanobacteria. Conclusion The gut metabolites SCFAs are tightly linked to the alterations of gut microbiota and clinical characteristics of renal anemia. Further studies are warranted to elucidate the relationships more in-depth.

#289 Lipocalin-2 promotes cardiovascular calcification in chronic kidney disease by upregulating STAT3/NCOA4-mediated ferritinophagy and ferroptosis

Abstract Background and Aims Cardiovascular calcification (CVC) is a common complication of chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality without any effective therapies. To date, the underlying mechanism of CKD-CVC has not been elucidated. Recent studies suggest that ferroptosis is a novel programmed cell death that may play a role in the process of CKD-CVC, but the mechanism is largely unclear. Ferritinophagy is an important inducer of ferroptosis that is regulated by nuclear receptor coactivator 4 (NCOA4). However, the relationship between ferritinophagy and CKD-CVC has not been explored. Lipocalin-2 (LCN2) is an iron-trafficking protein that has been associated with both osteogenesis and ferroptosis, but the exact role and molecular mechanism of LCN2 in CKD-CVC needs to be explored. Method A cross-sectional clinical study was utilized to examine the association between LCN2 expression and CKD-CVC in serum and calcified radial arteries of CKD patients. LCN2 knockout mice, their wild type littermates and mice infected with VSMCs-targeted adeno-associated virus encoding LCN2 gene or negative control gene were all fed by the high adenine and phosphate diet to induce CKD-CVC.VSMCs transfected with LCN2-overexpressing lentivirus, LCN2-shRNA lentivirus or LCN2 siRNA and recombinant LCN2 stimulated VSMCs were treated under the condition of calcifying medium to investigate the role of LCN2 in CKD-CVC in vitro. Cardiovascular calcification was evaluated by Von-kossa staining and tissue calcium content assay. VSMCs calcification were checked by the Alizarin Red Staining and cellular calcium content assay. Cellular reactive oxygen species (ROS) were measured by the DCFDA assay. Lipid peroxidation was measured by the fluorescence of the fatty acid analog C11-BODIPY581/591 probe. Intracellular labile ferrous iron levels were measured by fluorescence of Phen Green SK probe and ferro-orange probe. Transmission electron microscopy was also used to examine mitochondrial change of ferroptosis. Results The cross-sectional study identified that LCN2 levels in serum and radial arteries were significantly increased as the severity of CKD-CVC increased. High adenine and phosphate diet intake provokes renal fibrosis and cardiovascular calcification in vivo. In vitro, five-days high phosphate sodium stimulation induced calcium deposition and osteoblastic trans differentiation of VSMCs. Meanwhile, high phosphate also increased the levels of ferroptosis in VSMCs as evidenced by decreased cell viability, iron and ROS accumulation, upregulated PTGS2 and MDA levels, reduced glutathione peroxidase 4 (GPX4) levels and significantly mitochondrial damage in VSMCs. Intriguingly, calcium deposition in VSMCs could be reversed by the ferroptosis inhibitor ferrostatin-1. LCN2 expression was significantly upregulated both in the aorta of mice and calcified VSMCs. Compared with WT mice, deletion of LCN2 inhibited cardiovascular calcification whereas VSMC-targeted LCN2 overexpression aggravated CKD-CVC. Consistently, LCN2 knockdown also alleviated calcium deposition of VSMCs. Meanwhile, inhibition of ferroptosis were observed after LCN2 silencing as evidenced by decreased ferrous and lipid oxidation while increased levels of GPX4. Mechanically, we demonstrated high phosphate increased the protein level of NCOA4 and downregulated FTH1, which was reversed by depletion of LCN2. Knockdown of NCOA4 partly alleviated the ferritin reduction, ferroptosis, and calcification in VSMCs, indicating that NCOA4-mediated ferritinophagy was required for VSMCs calcification. Furthermore, we found that the recombinant LCN2 treatment significantly upregulated phosphorylated STAT3. STAT3 signaling inhibitor abolished the recombinant LCN2 induced NCOA4 upregulation and calcification in VSMCs. Conclusion Our findings indicate that the pro-calcific effect of high phosphate is due to VSMCs ferroptosis mediated by LCN2 upregulation. LCN2 silencing alleviates CKD-CVC by suppressing the STAT3/ NCOA4/FTH1 signaling mediated ferritinophagy. LCN2 could serve as a candidate therapeutic strategy for CKD-CVC.

#2938 The association between serum iron biomarkers and health-related quality of life in patients undergoing dialysis

Abstract Background and Aims Anemia is a very common complication of chronic kidney disease, affecting most patients undergoing dialysis. Iron deficiency, one of the causes of anemia, is generally a second consideration in the management of anemia. Nephrologists mainly focus on the correction of hemoglobin, often prescribing iron therapy for this indication only. However, iron has important physiological functions besides erythropoiesis. Conversely, iron overload can lead to oxidative stress and cellular damage. Therefore, nephrologists have been cautious to prescribe iron therapy to patients with already high serum iron levels. This caution has been underscored by studies linking higher levels of iron to increased mortality. Unfortunately, evidence is lacking regarding the impact of iron on important patient-reported outcomes like health-related quality of life (HRQoL). Therefore, the aim of this study is to explore the association between serum iron biomarkers, health-related quality of life (HRQoL) and the presence of anemia-related symptoms over a one-year period in patients undergoing dialysis. Method Data were obtained from the multicenter, prospective, observational Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). Adult patients new to dialysis were included, and had a baseline and follow-up assessments at 3, 6 and 12 months, with measurements of serum iron biomarkers ferritin and transferrin saturation (TSAT). HRQoL, encompassing physical and mental HRQoL, was measured using the validated 12-item Short Form Health Survey (SF12, summary scores ranging from 0 to 100). The presence of anemia-related symptoms: fatigue, shortness of breath, restless legs and muscle cramps were assessed using the Dialysis Symptom Index. Patients were categorized into 4 groups depending on their ferritin levels (μg/L): &amp;lt;200, 200–500 (reference), &amp;gt;500–700 and &amp;gt;700, and into 3 groups depending on their TSAT levels (%) at baseline: &amp;lt;20, 20–39 (reference), and ≥40. Longitudinal analyses were conducted using sequential conditional mean models to adjust for time-independent and time-varying confounding. All analyses captured the overall association over a one-year follow-up. Results We included 1069 patients, of whom 76% started hemodialysis, the median age was 68, 66% were male, and 32% were receiving iron therapy. Over a one-year follow-up, patients with ferritin &amp;lt;200 μg/L had similar physical HRQoL (MD=0.5 ; 95% CI –2.4 to 3.3 ) and mental HRQoL (MD=0.04 ; 95% CI -2.0 - 2.0) compared to the reference group with ferritin between 200–500 μg/L. Patients with ferritin between 501–700 μg/L also had a similar physical and mental HRQoL mental HRQoL compared to those with ferritin between 200-500 μg/L. This was also found for patients with ferritin above 700 μg/L (Fig. 1). Similarly, patients with TSAT levels below 20% and patients with TSAT levels ≥40% had comparable physical and mental HRQoL compared the reference group of patients with a TSAT between 20-39% (Fig. 2). For the secondary objectives, we found no significant differences in the anemia-related symptoms fatigue, shortness of breath, restless legs, or muscle cramps between patients with various levels of ferritin nor between the various TSAT groups. Conclusion We found that dialysis patients with higher or lower levels of ferritin or TSAT did not have a significantly different physical or mental HRQoL over a one year-follow up after starting dialysis. Similarly, no significant differences were found in the presence of fatigue, shortness of breath, restless legs, and muscle cramps between patients with these higher or lower levels of serum iron markers. And although iron levels do have impact on clinical outcomes such as mortality, these results suggest that they do not influence patient reported outcomes such as physical and mental HRQoL.