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Background: Ustekinumab and vedolizumab are both effective for treating Crohn's disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi). Methods: Patients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score-weighted cohort. Findings: A total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423). Interpretation: Ustekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients. Funding: National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Key Research Projects of the Sixth Affiliated Hospital, Sun Yat-sen University, the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline.
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Background: In chronic kidney disease (CKD), cognitive impairment is a definite complication. However, the mechanisms of how CKD leads to cognitive impairment are not clearly known. Methods: Cerebral blood flow (CBF) information was collected from 37 patients with CKD (18 in stage 3; 19 in stage 4) and 31 healthy controls (HCs). For CKD patients, we also obtained laboratory results as well as neuropsychological tests. We conducted brain perfusion imaging studies using arterial spin labeling and calculated the relationship between regional CBF changes and various clinical indicators and neuropsychological tests. We also generated receiver operator characteristic (ROC) curves to explore whether CBF value changes in certain brain regions can be used to identify CKD. Results: Compared with HCs, CBF decreased in the right insula and increased in the left hippocampus in the CKD4 group; through partial correlation analysis, we found that CBF in the right insula was negatively correlated with the number connection test A (NCT-A) (r = −0.544, p = 0.024); CBF in the left hippocampus was positively correlated with blood urea nitrogen (r = 0.649, p = 0.005) and negatively correlated with serum calcium level (r = −0.646, p = 0.005). By comparing the ROC curve area, it demonstrated that altered CBF values in the right insula (AUC = 0.861, p < 0.01) and left hippocampus (AUC = 0.862, p < 0.01) have a good ability to identify CKD. Conclusions: Our study found that CBF alterations in the left hippocampus and the right insula brain of adult patients with stage 4 CKD were correlated with disease severity or laboratory indicators. These findings provide further insight into the relationship between altered cerebral perfusion and cognitive impairment in patients with non-end-stage CKD as well as, additional information the underlying neuropathophysiological mechanisms.
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Background: Sunburn is a common problem for outdoor workers and casual outdoor walkers. Carotenoids are important elements in normal function of skin tissue and skin metabolism and are critical in the development of some cancers. However, the possible relationships between sunburn sensitivity, carotenoids and the risk of cancers remain unknown. Objectives: To explore the associations of serum carotenoids with sunburn severity and the risk of cancers. Methods: A cross-sectional study from the National Health and Nutrition Examination Survey from 1999 to 2018 were conducted. The relationship between sunburn and serum carotenoids, cancers were investigated by unconditional or ordinal logistic regression. Mediation analysis was used to explore the effect of carotenoids on the relationship between sunburn and cancers. Results: A total of 25,440 US adults from 1999 to 2018 were enrolled in this study. There were significant differences in sex, race and natural hair color between the sunburn and non-sunburn people. The severity of sunburn was significantly associated with serum trans-ß-carotene, cis-ß-carotene, combined lutein, and vitamin A. The odds ratios of severe reactions were 5.065 (95% CI: 2.266-11.318) in melanoma patients, 5.776 (95% CI: 3.362-9.922) in non-melanoma patients, and 1.880 (95% CI: 1.484-2.380) in non-skin cancers patients. Additionally, serum carotenoids were partially attributable to the effect of sunburn on skin and non-skin cancers. Conclusion: Sunburn severity was associated with cancers, and severer sunburn was related with higher risk of cancers. Serum carotenoids were also associated with sunburn severity. Moreover, the relationship between sunburn and cancers was mediated by some serum carotenoids.
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BACKGROUND: Cognitive impairment is a well-defined complication of chronic kidney disease (CKD), but the neural mechanisms are largely unknown. OBJECTIVES: The study aimed to assess white matter (WM) microstructure changes and their relationship with cognitive impairment development during CKD progression. METHODS: Diffusion tensor imaging (DTI) datasets were acquired from 38 patients with CKD (19 patients were at stage 3; 19 patients were at stage 4) and 22 healthy controls (HCs). Tract-based spatial statistics (TBSS) was implemented to assess the differences in WM integrity among the three groups. The associations between abnormal WM integrity and clinical indicators (digit symbol test scores, the type A number connection test scores, hemoglobin, serum urea, serum creatinine, serum calcium, and serum potassium levels) were also computed. RESULTS: Compared with patients with CKD at stage 3 and HCs, patients with CKD at stage 4 showed significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the corpus callosum (CC), anterior thalamic radiation, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. Correlation analysis showed that the MD in the genu of CC was negatively associated with the digit symbol test scores (r = -0.61, p = 0.01), and the FA in the left anterior thalamic radiation was positively associated with the level of serum calcium (r = 0.58, p = 0.01). CONCLUSION: Patients with non-end-stage CKD have multiple abnormalities in WM regions. DTI metrics change with the progression of CKD and are primarily associated with cognitive impairment. The reduced integrity of WM tracts may be related to a low level of blood calcium.
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OBJECTIVE: To compare the estimated glomerular filtration rates (eGFR) by five formulas based on serum creatinine (SCr), and to explore the diagnostic efficacy of full age spectrum (FAS) equation based on SCr for renal insufficiency in patients with chronic kidney disease (CKD). METHODS: 2 219 patients with CKD admitted to department of nephrology of Guangdong Provincial Second People's Hospital from December 2015 to January 2018 were enrolled. According to the diagnostic criteria of kidney disease outcomes quality initiative (K/DOQI), patients were divided into CKD 1-5 stages. In all patients, Tc-GFR was measured by clearance rate of 99mTc-diethylene triaminepen taacetic acid (99mTc-DTPA) within 1 month, and SCr was determined. The eGFR was calculated by Cockcrofi-Gault (C-G) formula bases on SCr, Chinese modified modification of diet in renal disease (cMDRD) equation, Chronic Kidney Disease Epidemiology Collaboration Group (CKD-EPI) equation, measure and calculation (MC) equation and FAS equation, respectively, and body surface area (BSA) was used for correction of eGFR. The differences of Tc-GFR and eGFR calculated by different formulas were compared, and the correlations between eGFR calculated by different formulas and Tc-GFR were analyzed by Spearman correlation analysis. Tc-GFR was used as a reference standard to evaluate the bias, precision and accuracy of eGFR formulas, and the receiver operating characteristics (ROC) curve of each eGFR formula was plotted to evaluate its diagnostic efficacy for renal insufficiency in patients with CKD. RESULTS: According to the inclusion and exclusion criteria, 382 patients with CKD were enrolled in the final analysis. There were 31, 69, 92, 75 and 115 patients with CKD 1-5 stages, respectively. In all patients, the differences between Tc-GFR and eGFR calculated by different formulas were statistically significant, and eGFR was positively correlated with Tc-GFR. The best correlation coefficient was between eGFR of cMDRD formula and Tc-GFR (r = 0.883, P = 0.000), and the lowest was of MC formula (r = 0.848, P = 0.000). The best correlation between the eGFR calculated by FAS formula and the Tc-GFR was in CKD 2 stage (r = 0.538, P = 0.000), and the lowest correlation was found in CKD 5 stage (r = 0.229, P = 0.014). Compared with Tc-GFR (the reference equation), the FAS formula showed the smallest bias [the difference between Tc-GFR and eGFR = 8.64, 95% confidence interval (95%CI) = 7.04-10.19], and the best accuracy [the percentage of eGFR falling into the range of Tc-GFR ±30% (P30) = 42.67%, 95%CI = 37.69-47.65]; CKD-EPI equation showed the best precision (QR of the difference between Tc-GFR and eGFR = 17.43, 95%CI = 15.33-21.28). ROC curve analysis showed that the area under the curve (AUC) of cMDRD formula was the largest (0.944), and the specificity was the highest (87.23%); the sensitivity of CKD-EPI formula was the highest (94.00%); and the AUC of MC formula was the smallest (0.918). The AUC of FAS formula was 0.940 (95%CI = 0.917-0.964, P = 0.000), it was higher than that of MC formula, but there was no significant difference between FAS formula and other formulas. When the cut-off value of eGFR calculated by FAS formula was 32.62 mL×min-1×1.73 m-2, the sensitivity, specificity, positive predictive value, negative predictive value was 93.00%, 81.56%, 83.64%, 11.54%, respectively. CONCLUSIONS: Compared with C-G formula, cMDRD formula, CKD-EPI formula and MC formula, FAS formula showed smaller bias and higher accuracy, and had higher specificity and sensitivity in the diagnosis of renal insufficiency in patients with CKD, which could be applied to the determination of GFR in early stage of CKD. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017727.
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Creatinina/sangue , Insuficiência Renal Crônica/diagnóstico , Taxa de Filtração Glomerular/fisiologia , Humanos , Valor Preditivo dos Testes , Insuficiência Renal Crônica/fisiopatologia , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To probe the clinical value of estimated glomerular filtration rate (GFR) formulas for adults Chinese based on the serum cystatin C(SCys C, SCysCAC). METHODS: GFRs for 96 cases of patient in hospital suffering from the kidney diseases without dialysis from January to December in 2011 were measured using clearance rate of (99m) Tc-diethylene triamine pentaacetic acid ((99m) Tc- DTPA, Tc-GFR) by prospective control study method. Based on the renal function, 96 patients were sorted into renal function insufficient group (RFI, n=54) and renal function normal group (RFN, n=42). The SCys C, serum creatinine (SCr) and blood urea nitrogen (BUN) were measured at the same day for calculating GFRs simultaneously by nine formulas such as SCysCAC, Arnal-Dade, Grubb, Filler, Grubb, Hojs, Larsson, Macisaac, Rule etc. The comparison were performed for the estimated GFRs (eGFRs) of renal insufficiency patients and those with normal renal function and the correlation analysis were done between the calculations and Tc-GFR respectively. RESULTS: eGFRs calculated by SCysCAC, Arnal-Dade, Larsson and Rule formulae always were close to those of Tc-GFR and that were 37.96±32.65 ml×min(-1)×1.73 m(-2), 33.69±25.24 ml×min(-1)×1.73 m(-2), 34.16±33.65 ml×min(-1)×1.73 m(-2), 33.02±30.88 ml×min(-1)×1.73 m(-2) vs. 36.21±31.16 ml×min(-1)×1.73 m(-2) in RFI group, 112.99±39.26 ml×min(-1)×1.73 m(-2), 101.86±72.29 ml×min(-1)×1.73 m(-2), 102.69±71.78 ml×min(-1)×1.73 m(-2), 99.12±69.54 ml×min(-1)×1.73 m(-2) vs. 110.54±48.98 ml×min(-1)×1.73 m(-2) in RFN group (all P>0.05). The absolute value difference between eGFR by SCysCAC, Larsson and Arnal-Dade formulae and Tc-GFR in RFN or RFI group showed no significant change and the absolute value of the value difference between SCysCAC-eGFR and Tc-GFR was the least among the three absolute values and showed that eGFRs from the three formulas could all reflect the GFR accurately and the SCysCAC formula was the best. The correlation analysis showed the eGFRs from every formula could all to some extent reflect the glomerular function or GFR accurately. CONCLUSION: The SCysCAC formula was a quickly and accurate method for estimating GFR and may apply clinically.
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Algoritmos , Cistatina C/sangue , Taxa de Filtração Glomerular , Testes de Função Renal , Adulto , Idoso , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: To discuss the clinical application value of determining glomerular filtration rate(GFR) with the new intelligent determination and analysis system for GFR (B&G System). METHODS: GFR of 216 hospitalized patients suffering from the different diseases was determined accurately by clearance rate of (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) (Tc-GFR), and the serum creatinine (SCr) and blood urea nitrogen (BUN) were also determined. At the same time GFR was determined by B&G system and Robert formula (B&G-GFR, Robert-GFR), and creatinine clearance rate (CCr) and GFR were calculated by Cockcroft/Gault formula(CG-CCr-GFR). All the results were compared, and correlation analysis was done for the three groups of data. RESULTS: Among 216 patients, B&G-GFR and Tc-GFR in 106 patients with renal insufficiency and 110 patients with normal renal function showed no significant difference (ml · min(-1)· 1.73 m(-2): 29.13 ± 18.96 vs. 32.28 ± 25.03, 121.13 ± 49.79 vs. 118.48 ± 43.25, both P >0.05), while Robert-GFR (ml · min(-1) · 1.73 m(-2): 21.45 ± 15.67, 93.54 ± 30.01) and CG-CCr-GFR (ml · min(-1) · 1.73 m(-2): 11.87 ± 8.69, 86.27 ± 21.44)were significantly lower than Tc-GFR (P<0.05 or P <0.01 ). The values of B&G-GFR, Robert-GFR, CG-CCr-GFR and Tc-GFR in renal insufficiency group (ml · min(-1) · 1.73 m(-2) :6.15 ± 14.07, 13.83 ± 11.36, 23.41 ± 24.34) were respectively significantly lower than that of normal renal function group (ml · min(-1) · 1.73 m(-2):7.65 ± 6.54, 24.94 ± 13.24, 32.21 ± 21.81, all P <0.05). B&G-GFR, Robert-GFR, and CG-CCr-GFR of both groups were positively correlated with Tc-GFR (P<0.05 or P <0.01), but negatively correlated with SCr (P<0.05 or P <0.01). CONCLUSION: B&G-GFR, Robert-GFR and CG-CCr-GFR , to a certain extent, do accurately reflect GFR. However, B&G-GFR is more accurate than others, and it can take the place of Tc-GFR clinically. B&G system has the advantage of accuracy, simplicity, speed, safety and low-price compared with other methods for the determination of GFR, and it warrants popularization.
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Inteligência Artificial , Taxa de Filtração Glomerular , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Processamento de Sinais Assistido por Computador , Adulto JovemRESUMO
OBJECTIVE: To prepare an intelligent determination and analysis system for renal glomerular filtration rate(GFRBMAS), and to explore its value in clinical setting. METHODS: GFRBMAS was prepared by programming with VB 6.0 software. GFR of 79 inpatients suffering from the different diseases was determined accurately by using clearance rate of (99)Tc(m)-diethylene triamine pentaacetic acid (DTPA) (Tc-GFR). The serum creatinine (SCr), blood urea nitrogen (BUN), serum uric acid (Uric), serum calcium (Ca) and serum phosphorus (P) were determined with both GFRBMAS and 7170S automatic biochemistry determination apparatus (ititachi), and the result of GFR was compared with that determined by using GFRBMAS and 7170S automatic biochemical determination apparatus. At the same time GFR was determined by using Robert formula (GFRBMAS-GFR, Robert-GFR), and creatinine clearance rate was calculated with Cockcroft/Gault formula (CG-CCr). All the results were compared and analyzed. RESULTS: No significant difference of SCr, BUN, Uric, Ca and P values determined by two methods. Robert-GFR and CG-CCr values were significantly lower than Tc-GFR value in the normal renal function group and the renal insufficiency group (P<0.01) and that of GFRBMAS-GFR was close to that of Tc-GFR and relative analysis showed that the values of GFRBMAS-GFR, Robert-GFR, CG-CCr showed significantly positive correlation with that of Tc-GFR, but negative correlation with values of SCr and BUN (P<0.05 or P<0.01). CONCLUSION: GFRBMAS-GFR, Robert-GFR and CG-CCr could all reflect GFR with accuracy to certain extent and GFRBMAS-GFR can take the place of Tc-GFR in clinical setting.
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Diagnóstico por Computador , Taxa de Filtração Glomerular , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To investigate the relationship between insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene and uncompensated cirrhosis of liver with hepatorenal syndrome (HRS). METHODS: ACE I/D polymorphism was detected by polymerase chain reaction amplification of DNA fragment in 56 patients of uncompensated liver cirrhosis with HRS, and 60 healthy individuals served as the controls. At the same time, alanine aminotransferase, aspartate transaminase, serum creatinine (SCr), blood urea nitrogen (BUN) and glomerular filtration rate (GFR) etc. were measured in all the subjects, and the difference between these variables among different genotypes was noted. RESULTS: There was no significant difference in genotypes and allele frequency between the HRS group and controls(all P>0.05). The I allele frequency was higher than the D allele in all the subjects (all P<0.01). But in the control group, there was no significant difference in the genotype frequency among three genomic groups, while the II genotype frequency was higher than the one of ID and DD (all P<0.05). SCr and BUN of the II genotype were higher in the HRS group than that of ID and DD(both P<0.05) and GFR of the II genotype was lower than the one of ID and DD in the HRS group(P<0.05). CONCLUSION: There is relationship between ACE gene polymorphism and the incidence of uncompensated liver cirrhosis with HRS. II genotype may be the genetic factor of vulnerability to HRS patients with uncompensated cirrhosis of liver. The degree of kidney failure in II genotype population is more serious than in ID and DD individuals with uncompensated liver cirrhosis complicated by HRS.
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Síndrome Hepatorrenal/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Feminino , Deleção de Genes , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutagênese InsercionalRESUMO
OBJECTIVE: To investigate the relationship between glomerular filtration rate(GFR) and possible involved clinical factors and to offer an basis for building measurement GFR by the calculation method. METHODS: GFR from 46 cases of normal renal function group and 52 cases of renal insufficient group were determined by using clearance of 99mTc-DTPA, serum creatinine(SCr), urea nitrogen, uric, potassium, sodium, calcium and hemoglobin were determined. Simultaneously, heart rate, urine specific gravity, 24 hours urine protein quantum, average artery pressure, weight index and body surface area were determined. Age, isotope dose for determining GFR were recorded. The simple correlation analysis between GFR in every group and the difference primitive diseases and clinical factors mentioned above were performed and the multiple correlation analysis between every clinical factors mentioned above that had significantly correlation between GFR and GFR were performed as well. RESULTS: GFR in normal renal function group, insufficient group and the difference primitive diseases had significantly negative correlation with SCr, while the correlations between GFR and other clinical factors were different. CONCLUSION: SCr is the ideal index for GFR for renal insufficient patients due to different primitive diseases and patients with normal renal function.
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Taxa de Filtração Glomerular , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Creatinina/sangue , Feminino , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pentetato de Tecnécio Tc 99m/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
BACKGROUND/OBJECTIVE: To investigate the therapeutics of heparin-free hemodialysis (HD) with the inside of hollow fibers in a dialyzer coated with human albumins (HFHd-A1). METHODS: Clinical contrast study between HFHd-A1 and heparin-free HD with hollow fibers in dialyzer by normal saline flush (HFHd-NS) was performed by adopting the cross-over design method. The dialysis effect, the effect on life signs, blood platelet functions, change of dialyzer fiber-bundle volume, appearance image, and image of scanning electron microscopy of the inside of hollow fibers in dialyzer after dialysis and the biocompatibility of dialyzer of two HD methods were compared. RESULTS: HFHd-A1 could overcome all shortcomings of HFHd-NS and had more merits and increased expenses for HFHd-A1 were not high. CONCLUSION: HFHd-A1 was an effective and feasible method which could salvage patients with bleeding diseases or bleeding tendency and who need HD.