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BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1â2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.
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OBJECTIVE: Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic. METHODS: Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined. RESULTS: Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944-0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014-1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551-0.852, P = 0.001) were also risk factors for the development of RLS. CONCLUSION: Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.
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Córtex Motor , Síndrome das Pernas Inquietas , Humanos , Síndrome das Pernas Inquietas/epidemiologia , Estudos Transversais , Estudos de Casos e Controles , Diálise Renal/efeitos adversos , Circulação Cerebrovascular/fisiologia , Ferro , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Nephrotoxicity remains the most serious side effect of cisplatin therapy. Cisplatin-induced nephrotoxicity (CIN) limits the use of this drug and affects up to 20% of patients. Several possible interventions such as magnesium supplementation may prevent CIN. This study aimed to review different types of hydration protocols and we conducted a meta-analysis of magnesium supplementation to understand its effect in protecting against CIN. METHODS: A search of the PubMed, Embase, and Cochrane databases was performed. Trials were eligible if they enrolled patients who received cisplatin and different hydration protocols to prevent CIN. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the efficacy of different protocols. RESULTS: We initially identified 1113 different studies and included 33 of them which met the selection criteria. A meta-analysis of 11 retrospective studies that examined magnesium supplementation during hydration showed that this treatment provided significant protection against CIN (OR = 0.22, 95% CI = 0.14 to 0.35). CONCLUSION: There has been uncertainty regarding the best method to prevent CIN. Our results highlight the potentially protective effect of magnesium supplementation during hydration. This study is registered in PROSPERO, CRD42020212682.
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Cisplatino , Insuficiência Renal , Humanos , Cisplatino/efeitos adversos , Hidróxido de Magnésio , Magnésio/uso terapêutico , Estudos Retrospectivos , Insuficiência Renal/induzido quimicamente , Suplementos Nutricionais , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
BACKGROUND: Left ventricular hypertrophy (LVH) and carotid atherosclerosis (CAS) have been identified as factors associated with cognitive impairment (CI) but have not been studied in patients undergoing peritoneal dialysis (PD). This study investigated the relationship between LVH and CAS and cognitive function in patients undergoing PD. METHODS: In this single-center cross-sectional study, the clinically stable patients who were over 18 years of age and had undergone PD for at least 3 months were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), which included seven areas: visuospatial/executive function, naming, attention, language, abstraction, delayed recall, and orientation. LVH was defined as LVMI > 46.7 g/m2.7 in women and LVMI > 49.2 g/m2.7 in men. CAS was defined as carotid intima-media thickness ≥ 1.0 mm and/or the presence of plaque. RESULTS: A total of 207 patients undergoing PD were recruited, with an average age of 52.14 ± 14.93 years and a median PD duration of 8 months (5-19 months). The CI rate was 56%, and the prevalence of CAS was 53.6%. LVH occurred in 110 patients (53.1%). Patients in the LVH group tended to be older, and had a higher body mass index, a higher pulse pressure, a higher male proportion, a lower ejection fraction, a higher prevalence of cardiovascular disease and CI, and a lower MoCA scores.Multivariate logistic regression analysis was conducted to analyze the association between LVH and CI (OR, 10.087; 95% confidence interval, 2.966-34.307). And the association between LVH and CI was still supported after propensity matching scores. CAS was not significantly associated with CI. CONCLUSION: LVH is independently associated with CI in patients undergoing PD, while CAS is not significantly associated with CI.
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Doenças das Artérias Carótidas , Disfunção Cognitiva , Diálise Peritoneal , Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Espessura Intima-Media Carotídea , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Estudos Transversais , Diálise Peritoneal/efeitos adversos , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologiaRESUMO
INTRODUCTION: The aim of this study was to investigate the efficacy and safety of limb ischemia preconditioning (LIPC) in the treatment of intradialytic hypotension (IDH) in patients with maintenance hemodialysis (MHD). METHODS: This was a single-center, prospective, and randomized controlled case study. A total of 38 patients with MHD who met the inclusion criteria from September 2021 to August 2022 were selected from the Blood Purification Center of our hospital. They were randomly divided into the LIPC group (n = 19) and the control group (n = 19). For patients in the LIPC group, the femoral artery blood flow was blocked with an LIPC instrument for 5 min (pressurized to 200 mm Hg) before each dialysis, and they were reperfused for 5 min. The cycle was repeated five times, with a total of 50 min for 12 weeks. The control group was pressurized to 20 mm Hg with an LIPC instrument, and the rest was the same as the LIPC group. The blood pressure of 0 h, 1 h, 2 h, 3 h, 4 h, and body weight before and after hemodialysis were measured in the two groups during hemodialysis, the incidence of IDH and the changes of serum troponin I (TNI) and creatine kinase isoenzyme MB (CK-MB) levels before and after the intervention were observed, and the ultrafiltration volume and ultrafiltration rate were recorded. RESULTS: At the 8th and 12th week after intervention, the MAP in the LIPC group was higher than that in the control group (103.28 ± 12.19 mm Hg vs. 93.18 ± 11.11 mm Hg, p = 0.04; 101.81 ± 11.36 mm Hg vs. 91.81 ± 11.92 mm Hg, p = 0.047). The incidence of IDH in the LIPC group was lower than that in the control group (36.5% vs. 43.1%, p = 0.01). The incidence of clinical treatment in IDH patients in the LIPC group was lower than that in the control group (6.3% vs. 12.4%, p = 0.00). The incidence of early termination of hemodialysis in the LIPC group was lower than that in the control group (1.6% vs. 3.8%, p = 0.01). The levels of TNI and CK-MB in the LIPC group after the intervention were lower than those in the control group (322.30 ± 13.72 ng/dL vs. 438.50 ± 24.72 ng/dL, p = 0.00; 159.78 ± 8.48 U/dL vs. 207.00 ± 8.70 U/dL, p = 0.00). The changes of MAP before and after the intervention were negatively correlated with the changes of TNI and CK-MB before and after the intervention (r = -0.473, p = 0.04; r = -0.469, p = 0.04). There were no differences in dry body mass and ultrafiltration rate between the two groups before and after the LIPC intervention (p > 0.05). Multiple linear regression analysis shows that TNI is the main influencing factor of ΔMAP. No LIPC-related adverse events were found during the study period. CONCLUSION: LIPC can effectively reduce the incidence of IDH in patients with MHD and may be associated with the alleviation of myocardial damage.
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Hipotensão , Precondicionamento Isquêmico , Falência Renal Crônica , Humanos , Diálise Renal/efeitos adversos , Estudos Prospectivos , Hipotensão/etiologia , Hipotensão/prevenção & controle , Pressão Sanguínea , Falência Renal Crônica/terapiaRESUMO
INTRODUCTION: Acute kidney injury (AKI) caused by cisplatin is common and has a higher incidence of multiple use, resulting in a poor short- and long-term prognosis for patients. There is currently no good premedication AKI risk assessment tool. The aim of this study was to establish an AKI risk assessment nomogram for patients with multiple cisplatin applications. METHODS: This study was a retrospective analysis of patients who were treated with non-first-time cisplatin chemotherapy regimen at Changzhou Second People's Hospital affiliated to Nanjing Medical University from January 2016 to January 2022. All data from the development group were used to screen the impact factors of AKI via univariate and multivariate analyses. A nomogram was developed based on these impact factors and verified with verification group. The area under the curve (AUC) of receiver operating characteristic (ROC) curve, calibration curves, and decision curve analyses (DCAs) were used to evaluate the nomogram. RESULTS: Among the 256 patients enrolled in 450 cycles of chemotherapy, 282 were in the development cohort (97 AKI), and 168 were in the validation cohort (61 AKI). Multivariate logistic regression revealed that age, hypertension, diabetes, serum cystatin C (sCysC), urinary kidney injury molecule-1 (uKim1), and a single dose of cisplatin were independently associated with AKI. The results showed that our model yielded satisfied diagnostic performance with an AUC value of 0.887 and 0.906 using the development group and on verification group. The calibration plots and DCA showed the superior clinical applicability of the nomogram. These results were verified in the validation cohort. CONCLUSION: A nomogram combining functional (sCysC) and tubular (uKim1) injury biomarkers with conventional clinical factors might assess the risk of AKI after multiple cycles of cisplatin chemotherapy.
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Injúria Renal Aguda , Nomogramas , Humanos , Cisplatino/efeitos adversos , Estudos Retrospectivos , Injúria Renal Aguda/diagnóstico , Medição de RiscoRESUMO
OBJECTIVE: The brain neuromechanism in maintenance hemodialysis patients (MHD) with cognitive impairment (CI) remains unclear. The study aimed to probe the relationship between spontaneous brain activity and CI by using resting-state functional magnetic resonance imaging (rs-fMRI) data. METHODS: Here, 55 MHD patients with CI and 28 healthy controls were recruited. For baseline data, qualitative data were compared between groups using the χ2 test; quantitative data were compared between groups using the independent samples t-test, ANOVA test, Mann-Whitney U-test, or Kruskal-Wallis test. Comparisons of ALFF/fALFF/ReHo values among the three groups were calculated by using the DPABI toolbox, and then analyzing the correlation with clinical variables. p < .05 was considered a statistically significant difference. Furthermore, back propagation neural network (BPNN) was utilized to predict cognitive function. RESULTS: Compared with the MHD-NCI group, the patients with MHD-CI had more severe anemia and higher urea nitrogen levels, lower mALFF values in the left postcentral gyrus, lower mfALFF values in the left inferior temporal gyrus, and greater mALFF values in the right caudate nucleus (p < .05). The above-altered indicators were correlated with MOCA scores. BPNN prediction models indicated that the diagnostic efficacy of the model which inputs were hemoglobin, urea nitrogen, and mALFF value in the left central posterior gyrus was optimal (R2 = 0.8054), validation cohort (R2 = 0.7328). CONCLUSION: The rs-fMRI can reveal the neurophysiological mechanism of cognitive impairment in MHD patients. In addition, it can serve as a neuroimaging marker for diagnosing and evaluating cognitive impairment in MHD patients.
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Mapeamento Encefálico , Disfunção Cognitiva , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Diálise Renal/efeitos adversos , UreiaRESUMO
OBJECTIVE: This study evaluated the efficacy and safety of limb ischemic preconditioning (LIPC) in treating restless leg syndrome (RLS) in maintenance hemodialysis (MHD) patients. METHODS: A total number of 45 patients participated in the study. They were randomly divided into LIPC group and control group. The LIPC was performed by inflating the limb ischemic preconditioning training device in the patient's thigh to 200 mmHg to create transient ischemia, whereas control group inflated the device to 20 mmHg. International Restless Legs Syndrome (IRLS), Clinical Global Impression Scale (CGI-S), and Medical Outputs Study Sleep Scale were employed to evaluate LIPC effectiveness. The primary endpoint was the 'rate of clinical improvement in RLS severity', defined as the percentage of patients who had an IRLS score decrease of ≥5 points in each group. RESULTS: After intervention, the rate of clinical improvement in RLS severity was 56.5% in the LIPC group and 13.6% in the control group (13 (56.5) vs 3 (13.6), p = 0.003). In addition, the LIPC group's IRLS, CGI-S scores, the sleep disturbance and somnolence scores showed a significant downward trend compared to the control group (-5.5 ± 5.3 vs - 1.0 ± 3.8, p = 0.002; -1.7 ± 1.2 vs - 0.5 ± 1.4, p = 0.003; -15.5 ± 17.8 vs 3.7 ± 12.0, p < 0.001; -9.9 ± 18.8 vs - 2.4 ± 8.6, p = 0.003). During the study, there were no serious adverse event in any of the patients. CONCLUSIONS: LIPC could be employed to effectively and safely alleviate the RLS symptoms in MHD patients.
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Precondicionamento Isquêmico , Síndrome das Pernas Inquietas , Transtornos do Sono-Vigília , Humanos , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/terapia , Síndrome das Pernas Inquietas/diagnóstico , Método Duplo-Cego , Diálise Renal , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
AIMS: Many previous studies have examined the effect of different hydration strategies on prevention of contrast-induced acute kidney injury (CI-AKI), but the optimal strategy is unknown. We performed a network meta-analysis (NWM) of these previous studies to identify the optimal strategy. METHODS AND RESULTS: Web of Science, PubMed, OVID Medline, and Cochrane Library were searched from their inception dates to September 30, 2018. Randomized controlled trials (RCTs) were selected based on strict inclusion criteria, and a Bayesian NWM was performed using WinBUGS V.1.4.3. We finally analyzed 60 eligible RCTs, which examined 21,293 patients and 2232 CI-AKI events. Compared to intravenous 0.9% sodium chloride (reference), intravenous sodium bicarbonate (OR [95% CI]: 0.74 [0.57, 0.93]), hemodynamic guided hydration (0.41 [0.18, 0.93]), and RenalGuard guided hydration (0.32 [0.14, 0.70]) significantly reduced the occurrence of CI-AKI. Oral hydration and intravenous 0.9% sodium chloride were each noninferior to no hydration in preventing CI-AKI. Intravenous 0.9% sodium chloride, sodium bicarbonate, and hemodynamic guided hydration were each noninferior to oral hydration in preventing CI-AKI. Based on surface under the cumulative ranking curve values, the RenalGuard system was best (0.974) and hemodynamic guided hydration was second best (0.849). CONCLUSION: There was substantial evidence to support the use of RenalGuard or hemodynamic guided hydration for preventing CI-AKI in high-risk patients, especially those with chronic kidney disease or cardiac dysfunction.
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Injúria Renal Aguda , Meios de Contraste/efeitos adversos , Hidratação/métodos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Humanos , Metanálise em Rede , Risco Ajustado/métodosRESUMO
AIMS: To investigate the impacts of combinatorial atorvastatin (Ator) perioperative administration and mesenchymal stem cell (MSC) implantation on therapeutic effects in the rat experimental acute kidney injury. METHODS: The model of renal ischemia-reperfusion (I/R) injury was induced by the release of bilateral renal pedicle clamps following 45 min of occlusion. Immediately after reperfusion, CM-Dil-labeled MSCs (1 × 10(6) cells) or vehicles only were administered through the carotid artery of the animals pretreated with or without Ator. RESULTS: The combined treatment with Ator and MSCs (Ator+MSCs) markedly reduced the elevated levels of serum creatinine and blood urea nitrogen, as well as the severity of renal damage 24 h after I/R injury. In addition, we also observed inhibition of renal tubular cell apoptosis and promotion of proliferation in the Ator+MSCs group compared with the other groups. Consistent with the improvement in renal function and morphology, Ator pretreatment significantly ameliorated oxidative stress, inhibited inflammation response, and increased the viability of implanted MSCs. With regard to the further mechanism, we found that the expression of Toll-like receptor 4 (TLR4) and high-mobility group box 1, potential mediators of innate immunity, was significantly decreased in the Ator-treated groups. CONCLUSION: Ator treatment may protect the kidney undergoing I/R injury through suppression of TLR4 signaling, creating a better environment for the survival of grafted MSCs. The extra benefit of the Ator+MSCs combined therapy may result from the Ator-mediated inhibition of oxidative stress and inflammation in the ischemic kidney.
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Injúria Renal Aguda/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Rim/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Pirróis/farmacologia , Traumatismo por Reperfusão/metabolismo , Animais , Atorvastatina , Proteína HMGB1/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Inflamação/metabolismo , Rim/irrigação sanguínea , Estresse Oxidativo/efeitos dos fármacos , Ratos , Receptor 4 Toll-Like/efeitos dos fármacosRESUMO
The function and structure of brain networks (BN) may undergo changes in patients with end-stage renal disease (ESRD), particularly in those accompanied by mild cognitive impairment (ESRDaMCI). Many existing methods for fusing BN focus on extracting interaction features between pairs of network nodes from each mode and combining them. This approach overlooks the correlation between different modal features during feature extraction and the potentially valuable information that may exist between more than two brain regions. To address this issue, we propose a model using a multi-head self-attention mechanism to fuse brain functional networks, white matter structural networks, and gray matter structural networks, which results in the construction of brain fusion networks (FBN). Initially, three networks are constructed: the brain function network, the white matter structure network, and the individual-based gray matter structure network. The multi-head self-attention mechanism is then applied to fuse the three types of networks, generating attention weights that are transformed into an optimized model. The optimized model introduces hypergraph popular regular term and L1 norm regular term, leading to the formation of FBN. Finally, FBN is employed in the diagnosis and prediction of ESRDaMCI to evaluate its classification performance and investigate the correlation between discriminative brain regions and cognitive dysfunction. Experimental results demonstrate that the optimal classification accuracy achieved is 92.80%, which is at least 3.63% higher than the accuracy attained using other methods. This outcome confirms the effectiveness of our proposed method. Additionally, the identification of brain regions significantly associated with scores on the Montreal cognitive assessment scale may shed light on the underlying pathogenesis of ESRDaMCI.
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Encéfalo , Disfunção Cognitiva , Falência Renal Crônica , Humanos , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/patologia , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Substância Cinzenta/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiopatologia , Rede Nervosa/fisiopatologia , Rede Nervosa/patologia , Substância Branca/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia , Imageamento por Ressonância MagnéticaRESUMO
Brain functional networks derived from functional magnetic resonance imaging (fMRI) provide a promising approach to understanding cognitive processes and predicting cognitive abilities. The topological attribute parameters of global networks are taken as the features from the overall perspective. It is constrained to comprehend the subtleties and variances of brain functional networks, which fell short of thoroughly examining the complex relationships and information transfer mechanisms among various regions. To address this issue, we proposed a framework to predict the cognitive function status in the patients with end-stage renal disease (ESRD) at a functional subnetwork scale (CFSFSS). The nodes from different network indicators were combined to form the functional subnetworks. The area under the curve (AUC) of the topological attribute parameters of functional subnetworks were extracted as features, which were selected by the minimal Redundancy Maximum Relevance (mRMR). The parameter combination with improved fitness was searched by the enhanced whale optimization algorithm (E-WOA), so as to optimize the parameters of support vector regression (SVR) and solve the global optimization problem of the predictive model. Experimental results indicated that CFSFSS achieved superior predictive performance compared to other methods, by which the mean absolute error (MAE), mean absolute percentage error (MAPE), and root mean square error (RMSE) were up to 0.5951, 0.0281 and 0.9994, respectively. The functional subnetwork effectively identified the active brain regions associated with the cognitive function status, which offered more precise features. It not only helps to more accurately predict the cognitive function status, but also provides more references for clinical decision-making and intervention of cognitive impairment in ESRD patients.
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Cognição , Falência Renal Crônica , Animais , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Algoritmos , Baleias , Falência Renal Crônica/diagnóstico por imagemRESUMO
PURPOSE: To assess changes in neurovascular coupling (NVC) by evaluating the relationship between cerebral perfusion and brain connectivity in patients with end-stage renal disease (ESRD) undergoing hemodialysis versus in healthy control participants. And by exploring brain regions with abnormal NVC associated with cognitive deficits in patients, we aim to provide new insights into potential preventive and therapeutic interventions. MATERIALS AND METHODS: A total of 45 patients and 40 matched healthy controls were prospectively enrolled in our study. Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Arterial spin labeling (ASL) was used to calculate cerebral blood flow (CBF), and graph theory-based analysis of results from resting-state functional magnetic resonance imaging (rs-fMRI) was used to calculate brain network topological parameters (node betweenness centrality [BC], node efficiency [Ne], and node degree centrality [DC]). Three NVC biomarkers (CBF-BC, CBF-Ne, and CBF-DC coefficients) at the whole brain level and 3 NVC biomarkers (CBF/BC, CBF/Ne, and CBF/DC ratios) at the local brain region level were used to assess NVC. Mann-Whitney U tests were used to compare the intergroup differences in NVC parameters. Spearman's correlation analysis was used to evaluate the relationship among NVC dysfunctional pattern, cognitive impairment, and clinical characteristics multiple comparisons were corrected using a voxel-wise false-discovery rate (FDR) method (p < .05). RESULTS: Patients showed significantly reduced global coupling coefficients for CBF-Ne (p = .023) and CBF-BC (p = .035) compared to healthy controls. Coupling ratios at the local brain region level were significantly higher in patients in 33 brain regions (all p values < .05). Coupling ratio changes alone or accompanied by changes in CBF, node properties, or both CBF and node properties were identified. In patients, negative correlations were seen between coupling ratios and MoCA scores in many brain regions, including the left dorsolateral superior frontal gyrus, the bilateral median cingulate and paracingulate gyri, and the right superior parietal gyrus. The correlations remained even after adjusting for hemoglobin and hematocrit levels. CONCLUSION: Disrupted NVC may be one mechanism underlying cognitive impairment in dialysis patients.
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Encéfalo , Disfunção Cognitiva , Falência Renal Crônica , Imageamento por Ressonância Magnética , Acoplamento Neurovascular , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Acoplamento Neurovascular/fisiologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Falência Renal Crônica/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Adulto , Circulação Cerebrovascular/fisiologia , Diálise Renal , Neuroimagem/métodos , Idoso , Estudos Prospectivos , Testes de Estado Mental e Demência , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologiaRESUMO
OBJECTIVE: The objective of this meta-analysis was to compare the efficacy and safety between glucocorticoids combined with mycophenolate mofetil (MMF) versus glucocorticoids combined with cyclophosphamide (CTX) for henoch schonlein purpura nephritis (HSPN) in children. METHODS: Databases including PubMed, EMbase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched from the inception to April 5th, 2024. Eligible studies comparing glucocorticoids combined with MMF versus glucocorticoids combined with CTX for HSPN in children were included. Data were analyzed using Review Manager Version 5.3. RESULTS: Ten studies were included in the meta-analysis. Six randomized controlled trials (RCTs) and 4 non-randomized studies involving 675 patients were identified. Compared with CTX therapeutic schedule, MMF therapeutic schedule had a higher complete remission (CR) within the 6 months (OR 1.61, 95%CI 1.16-2.22, Pâ =â .004) and CR within the 12 months (OR 1.73, 95%CI 1.00-2.97, Pâ =â .05). However, there was no significant difference between MMF and CTX therapeutic schedule concerning total remission (TR) within the 6 months (OR 1.54, 95%CI 0.82-2.92, Pâ =â .18) and TR within the 12 months (OR 2.08, 95%CI 0.86-5.01, Pâ =â .10). In addition, incidences of gastrointestinal discomfort (OR 0.33, 95%CI 0.19-0.56, Pâ <â .0001), liver function injury (OR 0.28, 95%CI 0.09-0.87, Pâ =â .03), myelosuppression (OR 0.15, 95%CI 0.06-0.41, Pâ =â .0001), alopecia (OR 0.25, 95%CI 0.07-0.91, Pâ =â .03) in MMF therapeutic schedule were all lower than CTX therapeutic schedule. There was no statistically significant difference between the 2 therapeutic schedules concerning infection (OR 0.90, 95%CI 0.50-1.61, Pâ =â .72), rash (OR 0.38, 95%CI 0.07-2.04, Pâ =â .26). CONCLUSION: Glucocorticoids combined with MMF had a higher CR and lower incidence of adverse effects compared with glucocorticoids combined with CTX in the treatment of HSPN in children.
Assuntos
Ciclofosfamida , Quimioterapia Combinada , Vasculite por IgA , Imunossupressores , Ácido Micofenólico , Nefrite , Humanos , Vasculite por IgA/tratamento farmacológico , Vasculite por IgA/complicações , Ciclofosfamida/uso terapêutico , Ciclofosfamida/efeitos adversos , Ácido Micofenólico/uso terapêutico , Ácido Micofenólico/efeitos adversos , Criança , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem , Nefrite/tratamento farmacológico , Glucocorticoides/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Pré-EscolarRESUMO
RATIONALE AND OBJECTIVES: To assess changes in the central executive network (CEN) of patients with mild cognitive impairment (MCI) associated with end-stage renal disease (ESRD). METHODS: A total of 121 patients with ESRD and 66 healthy controls (HCs) were enrolled. Patients were divided into an MCI group (n = 67) and a cognitively unimpaired group (n = 54). All participants underwent resting-state functional magnetic resonance imaging and were evaluated using the Montreal Cognitive Assessment (MoCA). The functional attributes of the CEN were calculated using three methods of functional connectivity (FC) analysis. Relationships among imaging features, cognitive scale scores, and clinical data were assessed, and a model was constructed to diagnose MCI in patients with ESRD. RESULTS: The comparison of the three groups showed that there were significant differences in the FC values of five connection pairs within the CEN, and the CEN demonstrated significant differences in connectivity to ten brain regions. In patients with MCI associated with ESRD, the information transmission efficiency of the CEN was reduced, which demonstrates the characteristics of a random network to some extent. Significant correlations were observed among imaging parameters, cognitive scale scores, and clinical data. The diagnostic model constructed based on these results demonstrated excellent discrimination and calibration. CONCLUSION: Alterations in the function of the CEN provide relevant bases for revealing the neuropathological mechanism of MCI in patients with ESRD. The diagnostic model developed in this study may help to establish more reliable imaging markers for detecting early cognitive impairment in this patient population.
RESUMO
The structure and function of brain networks (BN) may be altered in patients with end-stage renal disease (ESRD). However, there are relatively few attentions on ESRD associated with mild cognitive impairment (ESRDaMCI). Most studies focus on the pairwise relationships between brain regions, without taking into account the complementary information of functional connectivity (FC) and structural connectivity (SC). To address the problem, a hypergraph representation method is proposed to construct a multimodal BN for ESRDaMCI. First, the activity of nodes is determined by connection features extracted from functional magnetic resonance imaging (fMRI) (i.e., FC), and the presence of edges is determined by physical connections of nerve fibers extracted from diffusion kurtosis imaging (DKI) (i.e., SC). Then, the connection features are generated through bilinear pooling and transformed into an optimization model. Next, a hypergraph is constructed according to the generated node representation and connection features, and the node degree and edge degree of the hypergraph are calculated to obtain the hypergraph manifold regularization (HMR) term. The HMR and L1 norm regularization terms are introduced into the optimization model to achieve the final hypergraph representation of multimodal BN (HRMBN). Experimental results show that the classification performance of HRMBN is significantly better than that of several state-of-the-art multimodal BN construction methods. Its best classification accuracy is 91.0891%, at least 4.3452% higher than that of other methods, verifying the effectiveness of our method. The HRMBN not only achieves better results in ESRDaMCI classification, but also identifies the discriminative brain regions of ESRDaMCI, which provides a reference for the auxiliary diagnosis of ESRD.
Assuntos
Disfunção Cognitiva , Falência Renal Crônica , Humanos , Encéfalo/fisiologia , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/patologiaRESUMO
Septic acute kidney injury (SAKI) is one of the most common and life-threatening complications of sepsis. Patients with SAKI have increased mortality. However, the underlying pathogenesis is unclear, and the treatment targeting SAKI is unsatisfactory. Thus, identifying optimal biomarkers for SAKI diagnosis and treatment is an urgent requisite. Accumulating evidence indicates that noncoding RNAs (ncRNAs) are involved in the occurrence and progression of SAKI. In the present review, we summarized the studies of ncRNAs in SAKI, including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs). The ncRNAs are divided into protective and damage factors according to their role in SAKI, and their expression patterns, functions, and molecular mechanisms were elaborated. Next, we proposed that ncRNAs have the potential to be diagnostic and prognostic biomarkers for SAKI and as new therapeutic targets. This review aimed to provide a comprehensive overview of ncRNAs in SKAI and explored the clinical value of ncRNAs as ideal biomarkers of SAKI.
Assuntos
Injúria Renal Aguda , MicroRNAs , RNA Longo não Codificante , Humanos , RNA não Traduzido/genética , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/genética , RNA Longo não Codificante/genética , BiomarcadoresRESUMO
Effectively selecting discriminative brain regions in multi-modal neuroimages is one of the effective means to reveal the neuropathological mechanism of end-stage renal disease associated with mild cognitive impairment (ESRDaMCI). Existing multi-modal feature selection methods usually depend on the Euclidean distance to measure the similarity between data, which tends to ignore the implied data manifold. A self-expression topological manifold based multi-modal feature selection method (SETMFS) is proposed to address this issue employing self-expression topological manifold. First, a dynamic brain functional network is established using functional magnetic resonance imaging (fMRI), after which the betweenness centrality is extracted. The feature matrix of fMRI is constructed based on this centrality measure. Second, the feature matrix of arterial spin labeling (ASL) is constructed by extracting the cerebral blood flow (CBF). Then, the topological relationship matrices are constructed by calculating the topological relationship between each data point in the two feature matrices to measure the intrinsic similarity between the features, respectively. Subsequently, the graph regularization is utilized to embed the self-expression model into topological manifold learning to identify the linear self-expression of the features. Finally, the selected well-represented feature vectors are fed into a multicore support vector machine (MKSVM) for classification. The experimental results show that the classification performance of SETMFS is significantly superior to several state-of-the-art feature selection methods, especially its classification accuracy reaches 86.10%, which is at least 4.34% higher than other comparable methods. This method fully considers the topological correlation between the multi-modal features and provides a reference for ESRDaMCI auxiliary diagnosis.
Assuntos
Disfunção Cognitiva , Falência Renal Crônica , Humanos , Falência Renal Crônica/diagnóstico por imagem , Artérias , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Disfunção Cognitiva/diagnóstico por imagemRESUMO
RATIONALE AND OBJECTIVES: The goal of this study was to investigate the relationship between altered brain micro-structure and function, and cognitive function in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis. Specially, diffusion kurtosis imaging (DKI), the resting-state functional connectivity (FC) algorithm, and the least squares support vector regression machine (LSSVRM) were utilized to conduct our study. MATERIALS AND METHODS: A total of 50 patients and 36 matched healthy controls were prospectively enrolled in our study. All subjects completed the Montreal cognitive assessment scale (MoCA) test. DKI and resting-state functional magnetic resonance imaging were measured. Relationship between DKI parameters, FC, and MoCA scores was evaluated. LSSVRM combined with the whale optimization algorithm (WOA) was used to predict cognitive function scores. RESULTS: In ESRD patients, altered DKI metrics were identified in 12 brain regions. Furthermore, we observed changes in FC values based on regions of interest (ROIs) in nine brain regions, involved in default mode network (DMN), frontoparietal network (FPN), and the limbic system. Significant correlations among DKI values, FC values, and MoCA scores were found. To some extent, altered FC showed significant correlations with changed DKI parameters. Furthermore, optimized prediction models were applied to more accurately predict the cognitive function associated with ESRD patients. CONCLUSION: Micro-structural and functional brain changes were found in ESRD patients, which may account for the onset of cognitive impairment in affected patients. These quantitative parameters combined with our optimized prediction model may be helpful to establish more reliable imaging markers to detect and monitor cognitive impairment associated with ESRD.
Assuntos
Disfunção Cognitiva , Falência Renal Crônica , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologia , Cognição , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Mapeamento Encefálico/métodosRESUMO
Continuous vertical air temperature (AT) from in-situ observation is of crucial importance for understanding the atmospheric environment, but the satellite data that have complete spatial coverage lacked vertical in-situ observation data, and the vertical dropsonde data from in-situ observations only were single-point observations. Therefore, this article introduced machine learning algorithms for fusing in-situ observation and multi-satellite data to achieve spatial continuity of vertical data on a large scale. Specially, random forest (RF), support vector regression (SVR), artificial neural network (ANN) and recurrent neural network (RNN) were employed to capture the non-linear relationships between the variables and estimated AT. The pre-training process and fine-tuning process ensured the prediction of AT spatiotemporal distribution. The four models were implemented for three-dimensional AT estimating across China. Additionally, we used the radiosonde observation data to evaluate the accuracy of estimated AT data under conventional weather and typhoon conditions. Our results revealed that the RF model performed the best with the R of 0.9992, the MAE of 0.70 °C, and the RMSE of 1.04 °C at the national scale, followed by the SVR and ANN models. The RNN model exhibited promising results under typhoon conditions, which will be valuable insights for further research on the applicability of machine learning models under different weather conditions. Besides, having a larger sample size does not necessarily result in reduced errors. For instance, the MAE value for SVR in the pressure height range of 100-200 hPa was larger than that in the pressure height range of 300-400 hPa, but the former sample size was 16,324, which was 7433 higher than the latter.