Abnormal Function Research Articles

Long-term safety of lanthanum carbonate in the real word: a 19-year disproportionality analysis from the FDA Adverse Event Reporting System

Background Lanthanum carbonate is widely used to manage serum phosphate and calcium levels in end-stage kidney disease (ESKD) patients, yet comprehensive long-term safety data are lacking. This study leverages the FDA Adverse Event Reporting System (FAERS) to assess the extended safety profile of lanthanum carbonate. Research design and methods We analyzed FAERS data (2004-2022) to study the association between lanthanum carbonate and adverse events (AEs). Using MedDRA v25.0, we identified risk signals through System Organ Classes (SOCs) and Preferred Terms (PTs). Disproportionality analyses quantified lanthanum carbonate-associated AE signals. Results Among 3,284 reports, 2,466 were primary suspected AEs linked to lanthanum carbonate. Males reported AEs more frequently than females. Patients aged over 64 represented the majority. Median onset time for lanthanum carbonate-related AEs was 146 days. Gastrointestinal disorders were prevalent. We identified 16 new signals, including stress, abnormal hepatic function, cholelithiasis, bile duct stone, gastric cancer, and adenocarcinoma gastric. Stress was notable, particularly in male patients over 65 and those with lower weight. Conclusions This study affirms lanthanum carbonate’s long-term safety for reducing elevated blood phosphorus levels. While gastrointestinal disorders were common, attention must focus on emerging AEs, particularly stress, especially in elderly patients.

Investigating the role of rotenone on human blood platelets: Molecular insights into abnormal platelet functions in Parkinson's disease.

Parkinson's disease (PD) is a predominant neuromotor disorder characterized by the selective death of dopaminergic neurons in the midbrain. The majority of PD cases are sporadic or idiopathic, with environmental toxins and pollutants potentially contributing to its development or exacerbation. However, clinical PD patients are often associated with a reduced stroke frequency, where circulating blood platelets are indispensable. Although platelet structural impairment is evident in PD, the platelet functional alterations and their underlying molecular mechanisms are still obscure. Therefore, we investigated rotenone (ROT), an environmental neurotoxin that selectively destroys dopaminergic neurons mimicking PD, on human blood platelets to explore its impact on platelet functions, thus replicating PD conditions in vitro. Our study deciphered that ROT decreased thrombin-induced platelet functions, including adhesion, activation, secretion, and aggregation in human blood platelets. As ROT is primarily responsible for generating intracellular reactive oxygen species (ROS), and ROS is a key player regulating the platelet functional parameters, we went on to check the effect of ROT on platelet ROS production. In our investigation, it became evident that ROT treatment resulted in the stimulation of ROS production in human blood platelets. Additionally, we discovered that ROT induced ROS production by augmenting Ca2+ mobilization from inositol 1,4,5-trisphosphate receptor. Apart from this, the treatment of ROT triggers protein kinase C associated NADPH oxidase-mediated ROS production in platelets. In summary, this research, for the first time, highlights ROT-induced abnormal platelet functions and may provide a mechanistic insight into the altered platelet activities observed in PD patients.

Curcuminoids as cell signaling pathway modulators: A potential strategy for cancer prevention.

Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidences reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoids, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/β-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoids also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoids against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKβ, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology-based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.

Safety and prescribing recommendations for verapamil in newly diagnosed pediatric type 1 diabetes (T1D): The CLVer experience

ObjectivesTo report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D. Research Design and MethodsEighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team. ResultsOverall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event. ConclusionsThe use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034.

What every clinician needs to know about chronic kidney disease: Detection, classification and epidemiology.

Chronic kidney disease (CKD) is a major healthcare challenge, affecting >800 million people worldwide. Implications for population health result from the strong associations of CKD with increased rates of cardiovascular disease, heart failure, progressive CKD leading to kidney failure, acute kidney injury (AKI), and mortality. In addition to a single disease perspective, CKD commonly coexists alongside other long-term conditions, in particular type 2 diabetes and cardiovascular disease. CKD is therefore an important component of multimorbidity that influences individual management and impacts prognosis. CKD is defined by abnormalities of kidney structure or function of any cause with implications for health that are present for longer than 3 months. The diagnosis is usually made on the basis of an abnormal glomerular filtration rate (GFR < 60 mL/min/1.73 m2) and/or the presence of proteinuria (urine albumin to creatinine ratio > 30 mg/g or >3 mg/mmol). GFR is usually estimated from serum creatinine concentration using a variety of validated equations. However, serum creatinine is closely related to muscle mass and may therefore not be an accurate marker of GFR in people with high or low muscle mass (sarcopaenia). Cystatin C is an alternative endogenous marker of GFR that is increasingly being used but also has limitations. An estimate of GFR based on both creatinine and cystatin C is the most accurate. Diagnosis should be followed by classification and risk stratification to guide the development of a risk-based, personalized care plan. Improved detection and widespread implementation of optimal CKD management has the potential to bring major benefits to population health.

Links Between Obstructive Sleep Apnea and Myocardial Blood Flow Changes Impacting Adverse Cardiovascular Disease-related Outcomes.

Recent studies have demonstrated an association between obstructive sleep apnea (OSA) and abnormal myocardial blood flow (MBF), myocardial flow reserve (MFR), and coronary microvascular dysfunction (CMD). Here, we review the evidence and describe the potential underlying mechanisms linking OSA to abnormal MBF. Examining relevant studies, we assess the impact of OSA-specific therapy, such as continuous positive airway pressure (CPAP), on MBF. Recent studies suggest an association between moderate to severe OSA and abnormal MBF/MFR. OSA promotes functional and structural abnormalities of the coronary microcirculation. OSA also promotes the uncoupling of MBF to cardiac work. In a handful of studies with small sample sizes, CPAP therapy improved MBF/MFR. Moderate to severe OSA is associated with abnormal MFR, suggesting an association with CMD. Evidence suggests that CPAP therapy improves MBF. Future studies must determine the clinical impact of improved MBF with CPAP.

Brain structural and functional abnormalities associated with acute post-traumatic headache: iron deposition and functional connectivity

BackgroundThe purpose of this study was to interrogate brain iron accumulation in participants with acute post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI), and to determine if functional connectivity is affected in areas with iron accumulation. We aimed to examine the correlations between iron accumulation and headache frequency, post-concussion symptom severity, number of mTBIs, and time since most recent TBI.MethodsSixty participants with acute PTH and 60 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging including quantitative T2* maps and resting-state functional connectivity imaging. Between group T2* differences were determined using T-tests (p < 0.005, cluster size threshold of 90 voxels). For regions with T2* differences, two analyses were conducted. First, the correlations with clinical variables including headache frequency, number of lifetime mTBIs, time since most recent mTBI, and Sport Concussion Assessment Tool (SCAT) symptom severity scale scores were investigated using linear regression. Second, the functional connectivity of these regions with the rest of the brain was examined (significance of p < 0.05 with family wise error correction for multiple comparisons).ResultsThe acute PTH group consisted of 60 participants (22 male, 38 female) with average age of 42 ± 14 years. The HC group consisted of 60 age-matched controls (17 male, 43 female, average age of 42 ± 13). PTH participants had lower T2* values compared to HC in the left posterior cingulate and the bilateral cuneus. Stronger functional connectivity was observed between bilateral cuneus and right cerebellar areas in PTH compared to HC. Within the PTH group, linear regression showed negative associations of T2* in the left posterior cingulate with SCAT symptom severity score (p = 0.05) and T2* in the left cuneus with headache frequency (p = 0.04).ConclusionsIron accumulation in posterior cingulate and cuneus was observed in those with acute PTH relative to HC; stronger functional connectivity was detected between the bilateral cuneus and the right cerebellum. The correlations of decreased T2* (suggesting higher iron content) with headache frequency and post mTBI symptom severity suggest that the iron accumulation that results from mTBI might reflect the severity of underlying mTBI pathophysiology and associate with post-mTBI symptom severity including PTH.

Relationship between gut microbiota and the pathogenesis of gestational diabetes mellitus: a systematic review

IntroductionGestational diabetes mellitus (GDM) is a form of gestational diabetes mellitus characterized by insulin resistance and abnormal function of pancreatic beta cells. In recent years, genomic association studies have revealed risk and susceptibility genes associated with genetic susceptibility to GDM. However, genetic predisposition cannot explain the rising global incidence of GDM, which may be related to the increased influence of environmental factors, especially the gut microbiome. Studies have shown that gut microbiota is closely related to the occurrence and development of GDM. This paper reviews the relationship between gut microbiota and the pathological mechanism of GDM, in order to better understand the role of gut microbiota in GDM, and to provide a theoretical basis for clinical application of gut microbiota in the treatment of related diseases.MethodsThe current research results on the interaction between GDM and gut microbiota were collected and analyzed through literature review. Keywords such as "GDM", "gut microbiota" and "insulin resistance" were used for literature search, and the methodology, findings and potential impact on the pathophysiology of GDM were systematically evaluated.ResultsIt was found that the composition and diversity of gut microbiota were significantly associated with the occurrence and development of GDM. Specifically, the abundance of certain gut bacteria is associated with an increased risk of GDM, while other changes in the microbiome may be associated with improved insulin sensitivity. In addition, alterations in the gut microbiota may affect blood glucose control through a variety of mechanisms, including the production of short-chain fatty acids, activation of inflammatory pathways, and metabolism of the B vitamin group.DiscussionThe results of this paper highlight the importance of gut microbiota in the pathogenesis of GDM. The regulation of the gut microbiota may provide new directions for the treatment of GDM, including improving insulin sensitivity and blood sugar control through the use of probiotics and prebiotics. However, more research is needed to confirm the generality and exact mechanisms of these findings and to explore potential clinical applications of the gut microbiota in the management of gestational diabetes. In addition, future studies should consider the interaction between environmental and genetic factors and how together they affect the risk of GDM.

AT-rich interactive domain-containing protein 1A (ARID1A) expression in placentas with late fetal growth restriction

BACKGROUND: Fetal growth restriction, which is considered as a multifactorial pathology, is a critical problem in obstetrics. The role of mitochondrial dysfunction in the pathogenesis of fetal growth restriction is not yet clear. However, it is known that it leads to oxidative stress, damage to cells and tissues, and dysfunction of key mechanisms for maintaining energy balance, the outcome of which may be the development of placental insufficiency. It is likely that AT-rich interactive domain-containing protein 1A (ARID1A) is involved in the development and function of the human placenta and may be an important marker in the development of fetal growth restriction. AIM: The aim of this study was to evaluate ARID1A protein expression in the placental villous tree in late fetal growth restriction. MATERIALS AND METHODS: This study included 50 placentas from children born at full-term gestation (37–40 weeks). The main study group consisted of placentas with late fetal growth restriction and without major extragenital pathology (n = 35). The control group comprised 15 placentas without fetal growth restriction (n = 15). Histological (n = 50) and immunohistochemical examinations of placentas (15 placentas in the main group and 10 placentas in the control group) using primary monoclonal antibodies to ARID1A were performed. RESULTS: In the study group with fetal growth restriction, chronic placental insufficiency was verified in all cases, dissociated chronic placental insufficiency (25 cases; 71.4%) being predominant, of which 23 cases (92%) were compensated, including 16 cases (69.6%) with moderate circulatory disorders. Hypoplastic chronic placental insufficiency was diagnosed in ten cases (28.6%) and was subcompensated with the presence of pronounced circulatory disorders. In the arteries of the stem villi, the ARID1A protein expression area did not differ between the study groups (p = 0.096), while in the veins in the stem villi with fetal growth restriction, we verified a decrease compared to control (p = 0.05). In the vascular bed of the villi with subcompensated dissociated chronic placental insufficiency, ARID1A protein expression was higher compared to hypoplastic chronic placental insufficiency (p = 0.041). CONCLUSIONS: Chronic placental insufficiency combined with fetal growth restriction is a serious complication of pregnancy with the development of structural and functional abnormalities and dysregulation of placental mechanisms. The ARIDA1A protein expression data obtained, depending on the degree of compensation for chronic placental insufficiency, may indicate the activation of compensatory metabolic mechanisms to maintain the functional activity of the placenta and preserve the viability of the fetus.

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study

IntroductionCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. MethodsParticipants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. DiscussionAusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.

Aerobic exercise improves motor dysfunction in Parkinson's model mice via differential regulation of striatal medium spiny neuron.

The striatum plays a crucial role in providing input to the basal ganglia circuit and is implicated in the pathological process of Parkinson's disease (PD). Disruption of the dynamic equilibrium in the basal ganglia loop can be attributed to the abnormal functioning of the medium spiny neurons (MSNs) within the striatum, potentially acting as a trigger for PD. Exercise has been shown to mitigate striatal neuronal dysfunction through neuroprotective and neurorestorative effects and to improve behavioral deficits in PD model mice. In addition, this effect is offset by the activation of MSNs expressing dopamine D2 receptors (D2-MSNs). In the current study, we investigated the underlying neurobiological mechanisms of this effect. Our findings indicated that exercise reduces the power spectral density of the beta-band in the striatum and decreases the overall firing frequency of MSNs, particularly in the case of striatal D2-MSNs. These observations were consistent with the results of molecular biology experiments, which revealed that aerobic training specifically enhanced the expression of striatal dopamineD2 receptors (D2R). Taken together, our results suggest that aerobic training aimed at upregulating striatal D2R expression to inhibit the functional activity of D2-MSNs represents a potential therapeutic strategy for the amelioration of motor dysfunction in PD.

HPSC-Derived Astrocytes at the Forefront of Translational Applications in Neurological Disorders

Astrocytes, the most abundant glial cell type in the brain, play crucial roles in maintaining homeostasis within the central nervous system (CNS). Impairment or abnormalities of typical astrocyte functions in the CNS serve as a causative or contributing factor in numerous neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. Currently, disease-modeling and drug-screening approaches, primarily focused on human astrocytes, rely on human pluripotent stem cell (hPSC)-derived astrocytes. However, it is important to acknowledge that these hPSC-derived astrocytes exhibit notable differences across studies and when compared to their in vivo counterparts. These differences may potentially compromise translational outcomes if not carefully accounted for. This review aims to explore state-of-the-art in vitro models of human astrocyte development, focusing on the developmental processes, functional maturity, and technical aspects of various hPSC-derived astrocyte differentiation protocols. Additionally, it summarizes their successful application in modeling neurological disorders. The discussion extends to recent advancements in the large-scale production of human astrocytes and their application in developing high-throughput assays conducive to therapeutic drug discovery.

IL-37 ameliorates myocardial fibrosis by regulating mtDNA-enriched vesicle release in diabetic cardiomyopathy mice

BackgroundDiabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities of the heart and ultimately evolves to heart failure. IL-37 exerts a substantial influence on the regulation of inflammation and metabolism. Whether IL-37 is involved in DCM is unknown.MethodsThe plasma samples were collected from healthy controls, diabetic patients and DCM patients, and the level of IL-37 and its relationship with heart function were observed. The changes in cardiac function, myocardial fibrosis and mitochondrial injury in DCM mice with or without IL-37 intervention were investigated in vivo. By an in vitro co-culture approach involving HG challenge of cardiomyocytes and fibroblasts, the interaction carried out by cardiomyocytes on fibroblast profibrotic activation was studied. Finally, the possible interactive mediator between cardiomyocytes and fibroblasts was explored, and the intervention role of IL-37 and its relevant molecular mechanisms.ResultsWe showed that the level of plasma IL-37 in DCM patients was upregulated compared to that in healthy controls and diabetic patients. Both recombinant IL-37 administration or inducing IL-37 expression alleviated cardiac dysfunction and myocardial fibrosis in DCM mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling and the cGAS-STING pathway to initiate pro-fibrotic process and adverse remodeling. However, the presence of IL-37 ameliorated mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, resulting in a reduction in release of mtDNA-enriched vesicle and ultimately attenuating the progression of DCM.ConclusionsCollectively, our study demonstrates a protective role of IL-37 in DCM, offering a promising therapeutic agent for this disease.Graphical abstractHyperglycemia aggravates mitochondrial injury through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA in DCM mice. Fibroblasts then engulf these mtDNA-enriched vesicles, activating TLR9 signaling and the cGAS-STING pathway to initiate profibrotic process and adverse remodeling. However, both exogenous and endogenous IL-37 ameliorate mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, and reducing the release of mtDNA-enriched vesicles, which attenuates the progression of DCM

Structural and Functional Characteristics of the Dorsolateral Prefrontal Cortex in Schizophrenia Spectrum Disorders and Their Associations with Onset Age

Background: the dorsolateral prefrontal cortex (DLPFC) is one of the latest brain structures to mature during the ontogeny, and its structural and functional abnormalities play an important role in the pathogenesis of schizophrenia. As schizophrenia spectrum disorders usually start before the complete brain maturation and their earlier onset is coupled with worse prognosis, we suggested that earlier illness onset is related to more pronounced aberrations of the DLPFC. The aim of study was to analyze the associations of the onset age of schizophrenia spectrum disorders with structural and functional characteristics of the DLPFC that differentiated patients with schizophrenia spectrum disorders from healthy controls. Patients and methods: male patients with a diagnosis of schizophrenia spectrum disorders (n = 82) and healthy controls (n = 86) underwent structural MRI and functional resting-state fMRI. Cortical thickness and whole-brain functional connectivity of the DLPFC as well as local coherence and amplitude of low-frequency fluctuations of haemodynamic signal in the DLPFC were analyzed. Results: patients demonstrated a decreased gray matter thickness in the DLPFC bilaterally along with aberrant (predominantly decreased) functional connectivity of the DLPFC with other brain structures in each hemisphere. These measures were not associated with the age of illness onset. Conclusions: structural and functional abnormalities revealed in this study coincide with conventional view on the DLPFC as one of the key regions in schizophrenia spectrum disorders pathogenesis, however, these aberrations were not related to the age of psychosis onset. Possible interpretations of our results and limitations of the study are discussed in the article.

#607 Pre- and post-hemodialysis differences in heart failure diagnosis by current heart failure guidelines in patients with end-stage renal disease

Abstract Background and Aims Patients with end-stage renal disease (ESRD) who are on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF). Dialysis patients experience a volume change of ∼3–4 kg before and after HD, which can affect hemodynamic indicators, some of which are highly influenced by a patient's volume status. Therefore, depending on when echocardiography is performed, there may be differences in hemodynamic parameters. However, it is not easy to perform echocardiography in the euvolemic state in the clinical setting. This study estimated pre- and post-HD in ESRD HF diagnosis prevalence using the current guidelines. Method We prospectively investigated ESRD patients on HD using echocardiography between pre and post HD. We used structural or functional abnormality criteria of 2021 ESC guideline. Results A total of 54 patients were enrolled. The mean age was 62.6 years and 40.1% were male. Forty-five patients (83.3%) had hypertension, 28 (51.9%) had diabetes, 20 (37.0%) had ischemic heart disease. Mean NT-pro BNP level was 11959.9pg/dL. The mean ideal body weight was 59.3 kg, mean hemodialysis time was 237.4 minutes, and mean real filtration was 2.8 kg. The mean LVEF was 62.4% and mean LVEDD was 52.0 mm in pre-HD. Post-HD echocardiography showed significantly lower LAVI (33.3 ± 15.9 vs. 40.6 ± 17.1, p = 0.030), TR jet V (2.5 ± 0.4 vs. 2.8 ± 0.4 m/s, p &amp;lt; 0.001), and RVSP (32.1 ± 10.3 vs. 38.4 ± 11.6, p = 0.005) compared with pre-HD. There was no difference in LVEF, E/E’ ratio, or LV GLS. A total of 88.9% for pre-HD and 66.7% for post-HD had at least structural or functional abnormalities in echocardiographic parameters according to recent HF guidelines, p = 0.007). Conclusion Our data showed that the majority of patients undergoing hemodialysis satisfy the diagnostic criteria for HF according to current HF guidelines, and the difference of prevalence of HF was 22.2% between pre- and post- HD.

#1090 POCUS for diagnosis of congestive kidney due to severe acidemia

Abstract Background and Aims Point-of-Care Ultrasonography (POCUS) is a novel approach where the treating physician directly performs ultrasonography at the bedside, enabling rapid understanding of the patient's condition, diagnosis, and immediate connection to treatment. Venous Excess Ultrasound (VExUS), one method in POCUS, can swiftly identify structural or functional abnormalities in internal organs, allowing for more accurate assessment of congestion in organs. Here, we report a typical case which illustrates the usefulness of VExUS in correct diagnosis and appropriate management of congestive kidney failure. Method A case report. Results A 51-year-old woman with mitochondrial myopathy with chronic heart failure was admitted due to loss of appetite and failure to thrive. She presented with acute kidney injury (AKI) and severe acidemia. Given her medical history and physical examination, prerenal causes (hypovolemia/hypotension) of AKI were considered most likely. However, with a significantly elevated NT-proBNP level of 14700, congestive kidney was also considered. Bedside echocardiography showed no evidence of low output syndrome, whereas VExUS (Venous Excess Ultrasound) Score indicated assessed as Grade 2 (moderate congestion). In addition to administering fluids for the suspected prerenal causes (hypovolemia/hypotension), sodium bicarbonate was administered suspecting a negative impact of severe acidemia on cardiac function. With the improvement of acidemia and only a small volume of fluid therapy, there was a rapid improvement in AKI with normalization of VExUS score. This suggested that the main cause of AKI was congestive kidney. Conclusion This case demonstrated the significant contribution of VExUS in accurate diagnosis and treatment.

#2810 Exploring non-renal vasculature: therapeutic implications of proton pump inhibitor and anthelmintic treatment in PCK rat model

Abstract Background and Aims Cystic kidney diseases represent ciliopathies that can cause vascular damage through renal hypertension. Additionally, there is growing experimental evidence of endothelial cell abnormalities associated with ciliary protein deficiencies. PCK rats, a strain derived from Sprague-Dawley (SD) rats that develops both polycystic kidney disease (PKD) and liver disease, serve as a model for recessive PKD. The PCK rat model also presents abnormalities in non-renal vascular function. Another study from our group suggests a potential therapeutic benefit of repurposed therapy with a proton pump inhibitor (PPi) and an anthelmintic agent in attenuating the progression of PKD in a PCK rat model. Here, we investigated whether these drugs can also improve endothelial function. Method The compounds were administered to 3-week-old male and female PCK rats (n = 5-6) for a total of 10 weeks. Untreated PCK rats and age-matched SD rats (n = 5-6) served as controls. After perfusion fixation, the aorta was harvested and its thoracic rings were used to evaluate the contraction/relaxation responses ex vivo by organ bath experiments. Additional rings were preserved for histological and molecular biological analyses. Results Male PCK rats exhibited impaired endothelial function compared to healthy controls. Endothelium-dependent relaxation to acetylcholine was improved by 10% after treatment with PPi, while the anthelmintic administration had no protective effect. PKD also impaired endothelial function in female PCK rats compared to healthy SD controls. There was an improvement in endothelium-dependent relaxation to acetylcholine after treatment with PPi by 5.5%, while administration of the anthelmintic agent further impaired endothelial function. Conclusion 13-week-old PCK rats show endothelial dysfunction in non-renal vasculature. Treatment with a proton pump inhibitor improved endothelial function in male PCK rats to the level of healthy SD controls. By contrast, in a parallel study, the anthelmintic had a positive effect on renal function but a detrimental impact on endothelial function. These intricate relationships underscore the need for further exploration to understand the underlying mechanisms and broader implications of our findings, illustrating the challenges and potential avenues for the development of effective treatments for PKD.

#1259 Relationship between renal dysfunction, non-obstructive ACS and in-hospital prognosis: findings from the CCC-ACS project

Abstract Background and Aims Acute coronary syndrome (ACS) is an acute and critical condition of coronary heart disease (CHD) with high mortality and poor prognosis. The prevalence of non-obstructive ACS is about 5% ∼ 15%. Among patients with non-obstructive ACS, which patients are more prone to poor prognosis is a concern. Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease, and due to its special pathophysiological mechanism, non-obstructive ACS may not be uncommon in CKD patients. Therefore, the aim of this study was to investigate the relationship between renal function, the occurrence and prognosis of non-obstructive ACS. Method Improving Care for Cardiovascular Disease in China - Acute Coronary Syndrome (CCC-ACS), a hospital-based medical quality improvement project, is a hospital-based medical quality improvement project to improve the compliance of ACS guidelines in China and improve the prognosis of patients. It was jointly sponsored by the American Heart Association (AHA) and the Chinese Society of Cardiology (CSC) in 2014, with 240 hospitals participating, representing different levels of ACS management in Chinese hospitals. We analyzed patients who underwent coronary angiography from November 2014 to July 2019 in CCC-ACS. Patients were divided into eGFR &amp;lt;60 ml/min·1.73 m² and eGFR≥60 ml/min·1.73 m² groups according to estimated glomerular filtration rate (eGFR) calculated by the EPI formula. According to the results of coronary angiography, the patients were divided into obstructive ACS group and non-obstructive ACS group (obstructive ACS group was defined as at least one coronary artery stenosis ≥ 50%; the others were non-obstructive ACS group). Outcome was defined as in-hospital all-cause mortality and in-hospital MACEs. Results A total of 77 586 patients were included, including 2 292 patients (3.0%) with non-obstructive ACS and 75 294 patients (97.0%) with obstructive ACS. After adjusting for confounding factors using a multivariate logistic regression model, patients with eGFR&amp;lt;60 ml/min·1.73 m² had an approximately 20% increased risk of non-obstructive ACS compared with patients with eGFR≥60 ml/min·1.73 m². The comparison of in-hospital outcomes between the patients with non-obstructive ACS and obstructive ACS is shown in Fig. 1. In-hospital outcomes showed that although the obstructive ACS group had a worse in-hospital prognosis than the non-obstructive ACS group, and the eGFR&amp;lt;60 ml/min·1.73 m² group had a worse in-hospital prognosis than the eGFR≥60 ml/min·1.73 m² group, further grouping of patients showed that the non-obstructive ACS group with eGFR&amp;lt;60 ml/min·1.73 m² had a worse prognosis than the obstructive ACS group with eGFR≥60 ml/min·1.73 m². Confounding factors adjusted for non-obstructive ACS showed that lower eGFR was associated with a higher risk of in-hospital MACEs. After analyzing the in-hospital medication and discharge medication of patients, it was found that the standardized cardiovascular drug therapy was inadequate in patients with non-obstructive ACS. Conclusion Patients with non-obstructive ACS have worse renal function than patients with obstructive ACS, and the proportion of patients with eGFR&amp;lt;60 ml/min·1.73 m² is higher. In patients with non-obstructive ACS, the risk of in-hospital MACEs significantly increased as eGFR decreased. This suggests that we may consider giving standardized cardiovascular drug therapy to patients with non-obstructive ACS, especially those with non-obstructive ACS combined with abnormal renal function, in order to improve the prognosis of patients. This needs to be confirmed by more randomized controlled trial results.

Groove pancreatitis presenting with upper gastrointestinal obstruction and abnormal renal function: A case report and literature review

Groove pancreatitis presenting with upper gastrointestinal obstruction and abnormal renal function: A case report and literature review

Relationship Between Hand Strength and Function in Duchenne Muscular Dystrophy and Spinal Muscular Atrophy: Implications for Clinical Trials.

Measurement of muscle strength and motor function is recommended in clinical trials of neuromuscular diseases, but the loss of hand strength at which motor function is impacted is not documented. To establish the relationship between hand strength and function, and to determine the strength threshold that differentiates normal and abnormal hand function in individuals with Duchenne Muscular Dystrophy (DMD) or Spinal Muscular Atrophy (SMA). Maximal handgrip and key pinch strength were measured with the MyoGrip and MyoPinch dynamometers, respectively. Hand function was assessed using the MoviPlate, the Motor Function Measure items for distal upper limb (MFM-D3-UL) and the Cochin Hand Function Scale (CHFS). Data from 168 participants (91 DMD and 77 SMA, age 6-31 years) were analyzed. Relationships between strength and function were significant (P < 0.001). Hand function was generally preserved when strength was above the strength threshold determined by Receiver-Operating Characteristic (ROC) analysis: For MFM-D3-UL, the calculated handgrip strength thresholds were 41 and 13% of the predicted strength for a healthy subject (% pred) and the key pinch strength thresholds were 42 and 26% pred for DMD and SMA, respectively. For the MoviPlate, handgrip strength thresholds were 11 and 8% pred and key pinch strength thresholds were 21 and 11% pred for DMD and SMA, respectively. For participants with sub-threshold strength, hand function scores decreased with decreasing strength. At equal % pred strength, individuals with SMA had better functional scores than those with DMD. Hand function is strength-dependent for most motor tasks. It declines only when strength falls below a disease-specific threshold. Therefore, therapies capable of maintaining strength above this threshold should preserve hand function.