Conditional Survival of Patients with Limited-Stage Small Cell Lung Cancer After Surgery: A National Real-World Cohort Study.

BACKGROUND: The prognosis of limited-stage small cell lung cancer (LS-SCLC) after surgery usually is estimated at diagnosis, but how the prognosis actually evolves over time for patients who survived for a predefined time is unknown. METHODS: Data on patients with a diagnosis of LS-SCLC after surgery between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year conditional cancer-specific survival (CCSS) and conditional overall survival (COS) were calculated. RESULTS: This study analyzed 997 patients (555 women, 55.7%) with a median age, of 67 years (interquartile range [IQR], 60-73 years). The 5-year CCSS and COS increased from 44.7% and 38.3%, respectively, at diagnosis to 83.7% and 67.9% at 5 years after diagnosis. Although there were large differences with different stages (stages I, II, and III) at diagnosis (respectively 59.5%, 28.4%; 28.1% for CCSS and 50.6%, 24.8%, and 23.6% for COS), the gap decreased with time, and the rates were similar after 5 years (respectively 85.0%, 80.3%, and 79.4% for CCSS; 65.6%, 56.9%, and 61.3% for COS). The 5-year conditional survival for the patients who received lobectomy was better than for those who received sublobectomy or pneumonectomy. Multivariable analyses showed that only age and resection type were independent predictors for CCSS and COS, respectively, throughout the period. CONCLUSION: Conditional survival estimates for LS-SCLC generally increased over time, with the most significant improvement in patients with advanced stage of disease. Resection type and old age represented extremely important determinants of prognosis after a lengthy event-free follow-up period.

The association between histological subtypes and lymph node metastasis and prognosis in early esophageal cancer: a population-based study.

BACKGROUND: There is still a lack of high-level clinical evidence and uniform conclusions on whether there are differences in lymph node metastasis (LNM) and prognosis between early esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). METHODS: Patients with surgically resected, histologically diagnosed, pT1 EAC or ESCC in the Surveillance, Epidemiology and End Results registries database from 2004 to 2015 were included. Multivariable logistic regression, Cox regression, multivariate competing risk model, and propensity score matching were used to analyze association the histology and LNM or prognosis. RESULTS: A total of 570 early esophageal cancer patients were included. The LNM rates were 13.8% and 15.1% for EAC and ESCC ( P  = 0.757), respectively. Multivariate logistic regression analysis showed no significant association between histological type and LNM (odds ratio [OR], 1.209; 95% CI, 0.538-2.715; P  = 0.646). Moreover, the prognosis of early EAC and ESCC was shown to be comparable in both multivariate Cox regression (hazard ratio [HR], 1.483; 95% CI, 0.699-3.150; P  = 0.305) and the multivariate competing risk model (subdistribution HR, 1.451; 95% CI, 0.628-3.354; P  = 0.383). After propensity score matching, there were no significant differences between early EAC and ESCC in terms of LNM (10.6% vs.18.2%, P  = 0.215), 5-year CSS (89.8% [95% CI, 81.0%-98.6%] vs. 79.1% [95% CI, 67.9%-90.3%], P  = 0.102) and 5-year cumulative incidence of CSS (10.2% [95% CI, 1.4%-19.0%] vs. 79.1% [95% CI, 9.7%-32.1%], P  = 0.124). CONCLUSION: The risk of LNM and prognosis of early ESCC and EAC are comparable, so the treatment choice for early esophageal cancer does not depend on the histologic type.

Construction and validation of a risk-scoring model to predict lymph node metastasis in T1b-T2 esophageal cancer.

BACKGROUND: Lymph node status is an important factor in determining preoperative treatment strategies for stage T1b-T2 esophageal cancer (EC). Thus, the aim of this study was to investigate the risk factors for lymph node metastasis (LNM) in T1b-T2 EC and to establish and validate a risk-scoring model to guide the selection of optimal treatment options. METHODS: Patients who underwent upfront surgery for pT1b-T2 EC between January 2016 and December 2022 were analyzed. On the basis of the independent risk factors determined by multivariate logistic regression analysis, a risk-scoring model for the prediction of LNM was constructed and then validated. The area under the receiver operating characteristic curve (AUC) was used to assess the discriminant ability of the model. RESULTS: The incidence of LNM was 33.5% (214/638) in our cohort, 33.4% (169/506) in the primary cohort and 34.1% (45/132) in the validation cohort. Multivariate analysis confirmed that primary site, tumor grade, tumor size, depth, and lymphovascular invasion were independent risk factors for LNM (all P < 0.05), and patients were grouped based on these factors. A 7-point risk-scoring model based on these variables had good predictive accuracy in both the primary cohort (AUC, 0.749; 95% confidence interval 0.709-0.786) and the validation cohort (AUC, 0.738; 95% confidence interval 0.655-0.811). CONCLUSION: A novel risk-scoring model for lymph node metastasis was established to guide the optimal treatment of patients with T1b-T2 EC.

Clinical Features and Predictive Nomogram of Acute Kidney Injury in Aging Population Infected with SARS-CoV-2 Omicron Variant.

Background: Since little is known about the acute kidney injury (AKI) in aging population infected with SARS-CoV-2 Omicron variant, we investigated the incidence, clinical features, risk factors and mid-term outcomes of AKI in hospitalized geriatric patients with and without COVID-19 and established a prediction model for mortality. Methods: A real-time data from the Shanghai Ninth People's Hospital information system of inpatients with COVID-19 from 1 April 2022 to 30 June 2022 were extracted. Clinical spectrum, laboratory results, and clinical prognosis were included for the risk analyses. Moreover, Cox and Lasso regression analyses were applied to predict the 90-day death and a nomogram was established. Results: A total of 1607 SARS-CoV-2 infected patients were enrolled; hypertension was the most common comorbidity, followed by chronic cardiovascular disease, diabetes mellitus, and lung disease. Most of the participants were non-vaccinated and the mean age of patients was 82.6 years old (range, 60-103 years). The AKI incidence was higher in relatively older patients (16.29% vs 3.63% in patients older than 80 years and 60 to 80 years, respectively). Linear regression models identified some variables associated with the incidence of AKI, such as older age, clinical spectrum, D-dimer level, number of comorbidities, baseline eGFR, and antibiotic or corticosteroid treatment. In this cohort, 11 patients died in-hospital and 21 patients died at 90-day follow-up. The predictive nomogram of 90-day death achieved a good C-index of 0.823 by using 5 predictor variables: ICU admission, D-dimer, peak of serum creatinine, rate of serum creatinine decline and white blood cell count (WBC). Conclusion: Older age, clinical spectrum, D-dimer level, number of comorbidities, baseline eGFR, and antibiotic or corticosteroid treatment are clinical risk factors for the incidence of AKI in geriatric COVID-19 patients. The prediction nomogram achieved an excellent performance at the prediction of 90-day mortality.

Metabolomic profiling identifies biomarkers and metabolic impacts of surgery for colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors with recurrence and metastasis after surgical resection. This study aimed to identify the physiological changes after surgery and explore metabolites and metabolic pathways with potential prognostic value for CRC. Methods: An ultra-high-performance liquid chromatography Q-exactive mass spectrometry was used to profile serum metabolites from 67 CRC patients and 50 healthy volunteers. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis were used to distinguish the internal characteristics of data in different groups. Multivariate statistics were compiled to screen the significant metabolites and metabolic pathways. Result: A total of 180 metabolites were detected. Under the conditions of variable importance in projection >1 and p-value <0.05, 46 differentially expressed metabolites were screened for further pathway enrichment analysis. Based on the Kyoto Encyclopedia of Genes and Genomes database and Small Molecule Pathway Database, three metabolic pathways-arginine and proline metabolism, ascorbate and aldarate metabolism, and phenylalanine metabolism-were significantly altered after surgical resection and identified as associated with the removal of CRC. Notably, gamma-linolenic acid was upregulated in the CRC preoperative patients compared with those in healthy volunteers but returned to healthy levels after surgery. Conclusion: Through serum-based metabolomics, our study demonstrated the differential metabolic characteristics in CRC patients after surgery compared with those before surgery. Our results suggested that metabonomic analysis may be a powerful method for exploring physiological alterations in CRC patients after surgery as well as a useful tool for identifying candidate biomarkers and monitoring disease recurrence.

Identification of the histone demethylases gene family in Glycyrrhiza inflata reveals genes responding to abiotic stresses.

Glycyrrhiza inflata Bat. is a type of abiotic-stress-resistant plant with extremely high medicinal value. Histone demethylases (HDMTs) have been known to play crucial roles in the regulation of abiotic stress response. However, the molecular functions of HDMTs has not been studied in G. inflata. Here we identified 34 GiHDMT genes in G. inflata, which could be divided into the 6 groups through phylogenetic analysis. We further found that the gene structure and conserved protein motifs exhibit high conservation in each group of GiHDMT genes. Various abiotic-stress-related elements are detected in GiHDMT promoters, especially for the light-responsive element and abscisic acid-responsive element. Collinearity analysis indicated that segmental duplication contributed to the expansion of the GiHDMT family in licorice. Subcellular localization analysis revealed that green fluorescent protein-tagged GiHDMT2 and GiHDMT18 were predominantly localized in the nucleus, whereas GiHDMT1 were found in both the cytoplasm and nucleus. Real-time quantitative polymerase chain reaction showed that GiHDMTs presented differential expression patterns across different tissues. Moreover, changes in transcription level of GiHDMTs under abiotic stress indicate the potential role of GiHDMTs in the stress response in licorice. Finally, we found the histone methylation levels probably mediated by GiHDMT genes are changed with the treatment of NaCl and Na2 CO3 . Our study will lay the foundation for future research on the regulatory roles of GiHDMT genes in the environmental stress.

The HDA9-HY5 module epigenetically regulates flowering time in Arabidopsis thaliana.

Histone deacetylases (HDACs) play important roles in the repression of gene expression. Our previous study revealed that HISTONE DEACETYLASE 9 (HDA9) interacts with ELONGATED HYPOCOTYL 5 (HY5) and is involved in regulating plant autophagy in response to the light-to-dark transition and nitrogen starvation. In this study, we observed that the hda9-1 and hy5-215 single mutants flowered earlier compared with the wild-type Col-0; in addition, the hda9-1 hy5-215 double mutant flowered earlier than each single mutant. The expression of several positive flowering time genes was upregulated in the hda9-1, hy5-215, and hda9-1 hy5-215 mutants. Chromatin immunoprecipitation analysis demonstrated that HDA9 and HY5 bound directly to the promoter regions of PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) and CONSTANS-LIKE 5 (COL5) and repressed their expression through H3K9 and H3K27 deacetylation. Taken together, our results reveal the epigenetic mechanism explaining how the HDA9-HY5 module functions in controlling flowering time.

A mathematical estimation for quantified calcium supplementation during intermittent hemodialysis using regional citrate anticoagulation.

BACKGROUND: Regional citrate anticoagulation has been recommended as an alternative of anticoagulation for patients at high risk of bleeding undergoing intermittent hemodialysis. Precise calcium supplementation is important for the safety of regional citrate anticoagulation. In this study, we aimed to develop a possible method to optimize calcium supplementation for regional citrate anticoagulation in intermittent hemodialysis. METHODS: The investigation consisted of a pilot study and a validation study. 18 patients undergoing intermittent hemodialysis anticoagulated by citrate, and six types of filters were included in the pilot study. The ionized calcium levels were monitored and maintained in the targeted range. Calcium-free dialysate was used in the study. After linear regression analysis of the clearance of non-protein bound calcium and calculating the ratio of the non-protein bound calcium concentration to total calcium concentration, we developed a mathematical model for estimation of extracorporeal circuit calcium removal. Another 8 maintenance hemodialysis patients (12 sessions) were enrolled in the validation study to validate the new version of the calcium supplementation approach. RESULTS: In the pilot study, positive correlations were found between the clearance of non-protein bound calcium and the hematocrit-adjusted clearance of creatinine and phosphate given in the dialyzer leaflet (R2  = 0.31, p = 0.0165). The ratio of the non-protein bound calcium concentration to total calcium concentration at the pre-filter point after infusion of citrate were constant about 0.75. In the validation study, we found that the systemic ionized calcium levels were stably maintained in the safe range and no filter clotting occurred during the hemodialysis when we used the new model of calcium supplementation. CONCLUSIONS: We developed a possible method to quantify calcium supplementation for intermittent hemodialysis anticoagulated by citrate which may help to avoid negative calcium balance and reduce the incidence of complications.

Metabolomic Profiling Identified Serum Metabolite Biomarkers and Related Metabolic Pathways of Colorectal Cancer.

BACKGROUND: The screening and early detection of colorectal cancer (CRC) still remain a challenge due to the lack of reliable and effective serum biomarkers. Thus, this study is aimed at identifying serum biomarkers of CRC that could be used to distinguish CRC from healthy controls. METHODS: A prospective 1 : 2 individual matching case-control study was performed which included 50 healthy control subjects and 98 CRC patients. Untargeted metabolomic profiling was conducted with liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify CRC-related metabolites and metabolic pathways. RESULTS: In total, 178 metabolites were detected, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish CRC patients from healthy controls. Nine metabolites showed significantly differential serum levels in CRC patients under the conditions of variable importance in projection (VIP) > 1, p < 0.05 using Student's t-test, and fold change (FC) ≥ 1.2 or ≤0.5. The above nine metabolites were 3-hydroxybutyric acid, hexadecanedioic acid, succinic acid semialdehyde, 4-dodecylbenzenesulfonic acid, prostaglandin B2, 2-pyrocatechuic acid, xanthoxylin, 12-hydroxydodecanoic acid, and formylanthranilic acid. Four potential biomarkers were identified to diagnose CRC through ROC curves: hexadecanedioic acid, 4-dodecylbenzenesulfonic acid, 2-pyrocatechuic acid, and formylanthranilic acid. All AUC values of these four serum biomarkers were above 0.70. In addition, the exploratory analysis of metabolic pathways revealed the activated states for the vitamin B metabolic pathway and the alanine, aspartate, and glutamate metabolic pathways associated with CRC. CONCLUSION: The 4 identified potential metabolic biomarkers could discriminate CRC patients from healthy controls, and the 2 metabolic pathways may be activated in the CRC tissues.

An Observational Cohort Study of the 2-Month Use of Regional Citrate Anticoagulation in Maintenance Hemodialysis Patients with Cerebral Hemorrhage.

BACKGROUND Regional citrate anticoagulation (RCA) is a recommended anticoagulation alternative for patients at high risk of bleeding while undergoing intermittent hemodialysis. Previous reports implied the risk of citrate application on bone metabolism. It is unclear whether long-term use of RCA is safe for maintenance hemodialysis patients in terms of bone metabolism. MATERIAL AND METHODS Seven patients with cerebral hemorrhage were included in the study. Blood samples were collected at baseline and 4 and 8 weeks after treatment. Spent dialysate samples were collected during each mid-week dialysis session, using the partial dialysate collection method. All patients were treated with RCA for 4 to 8 weeks, according to their clinical condition. We assessed bone metabolism-associated parameters, bone turnover markers, and magnesium loss at each dialysis session. RESULTS Serum magnesium levels were 1.24±0.13 mmol/L at baseline and significantly decreased to 1.16±0.14 mmol/L after 4 weeks of RCA treatment (P=0.025). Most patients had negative magnesium balance during citrate hemodialysis. Serum total calcium levels did not change significantly after treatment. One bone marker, N-terminal propeptide of type I procollagen (PINP), significantly decreased from 146.07±130.12 mmol/L to 92.42±79.01 mmol/L after citrate treatment (P=0.018). No significant changes were detected in other bone turnover markers. CONCLUSIONS Relatively long-term RCA treatment may decrease serum magnesium levels due to negative magnesium balance. Bone formation marker PINP seemed to decrease after treatment, while other bone turnover markers did not change significantly. Further investigation is needed to verify the effect of RCA on bone remodeling.

Optimized calcium supplementation approach in post-dilution CVVHDF using regional citrate anticoagulation.

BACKGROUND: Regional citrate anticoagulation has been recommended as first choice for anticoagulation of continuous renal replacement therapy. Precise calcium supplementation is important for the safety of regional citrate anticoagulation. In this study we aimed to provide an optimized calcium supplementation approach for regional citrate anticoagulation in post-dilution continuous venous-venous hemodiafiltration. METHODS: Twenty-seven patients receiving post-dilution continuous venous-venous hemodiafiltration anticoagulated by citrate were included in this study. The ionized calcium levels were monitored and maintained in the targeted range. After linear regression analysis of the clearance of non-protein bound calcium and calculating the ratio of the non-protein bound calcium concentration to total calcium concentration, we concluded the mathematical model for calcium supplementation. RESULTS: Positive correlations were found between the clearance of non-protein bound calcium and both dialysate flow rates (r = 0.647, p < 0.001) and ultrafiltration plus substitution fluid flow rates (r = 0.525, p = 0.005). The ratio of the non-protein bound calcium concentration to total calcium concentration values at the pre-filter point after infusion of citrate were constant about 0.83. Based on the clearance and the calcium ratio, the amount of extracorporeal calcium removal can be estimated with a simplified equation. CONCLUSIONS: We provided an optimized calcium supplementation approach for post-dilution continuous venous-venous hemodiafiltration anticoagulated by citrate which may help to estimate the amount of extracorporeal circuit removal of calcium with regard to different dosages of regional citrate anticoagulation.

MicroRNA-7 regulates the proliferation and metastasis of human papillary carcinoma cells by targeting Bcl-2.

Papillary carcinoma is the most common type of thyroid cancer responsible for significant number of mortalities across the globe. This study was conducted to investigate the role and therapeutic implications of microRNA-7 in human papillary carcinoma. Gene expression analysis was carried out through quantitative real time PCR method. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to determine the cell proliferation. Clonogenic assay was used to assess the colony forming ability of cancer cells. Cell apoptosis was analyzed by 4',6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB) and annexin V/PI staining assays. Migration of cancer cells was estimated through scratch heal assay and cell invasion was determined by transwell assay method. Western blotting was done to examine the protein expression. Xenografted mice models were employed to examine the effects of miR-7 overexpression in vivo. Results showed miR-7 to be significantly (P < 0.05) repressed in papillary carcinoma. Cancer cell proliferation was inhibited by miR-7 through induction of apoptotic cell death as revealed by DAPI, AO/EB and annexin V/PI staining assays. The colony forming potential of cancer cells also decreased under miR-7 overexpression. miR-7 overexpression also inhibited the migration and invasion of cancer cells. Bcl-2 was identified as the intracellular target of miR-7 and regulatory effects of miR-7 were seen to be exerted through translation repression of Bcl-2. The results of xenograft study revealed miR-7 overexpression significantly (P < 0.05) suppressed the growth of the tumor in vivo. The results point towards the therapeutic implications of miR-7 in the management of papillary carcinoma.

Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization.

PURPOSE: Recent evidence has shown that CD4+ T helper (Th) cells are involved in renal inflammation and fibrosis. However, whether renal fibrosis can be alleviated by intervening in the polarization of CD4+ T cells remains unknown. Our research investigated the effects of intravenously administered placenta mesenchymal stromal cells (PMSCs) or treatment with extracellular EVs (EVs) derived from PMSCs (PMSC-EVs) on the polarization of CD4+ T cells in rats with unilateral ureteral obstruction (UUO). We further verified how PMSCs affect inflammatory factor secretion and the levels of regulatory T (Treg) and Th17 CD4+ T cells in vitro. MATERIALS AND METHODS: We evaluated renal interstitial inflammation and fibrosis by pathological section staining, tested the polarization of CD4+ T cells (Th17 and Treg phenotypes) by flow cytometry (FCM) and immunohistochemistry, and detected the cytokines secreted by CD4+ T cells by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with that of control rats, the renal tissue of PMSC-treated rats exhibited lower renal Masson scores and more Foxp3+ cell infiltration, with a significantly decreased IL17A+CD4+ T cell/CD4+ T cell ratio and a significantly elevated anti-inflammatory cytokine (IL-10) level. When CD4+ T cells were cocultured with PMSCs, CD4+IL17A+ cell percentages were decreased in a UUO model after 7 days of coculture with PMSCs. The secretion of TGF-ß and IL-10 was significantly increased (P < 0.05), while the secretion of IFN-γ, IL-17, and IL-6 was significantly decreased (P < 0.05) in the PMSC coculture group. Moreover, after treatment with PMSC-EVs, tubulointerstitial fibrosis was alleviated, and Foxp3+/IL-17+ cell infiltration was increased in the kidneys of UUO model animals on day 7. CONCLUSIONS: PMSCs can convert the inflammatory environment into an anti-inflammatory environment by affecting the polarization of CD4+ T cells and macrophages, inhibiting the inflammatory factors IFN-γ and IL-17, and upregulating the expression of the anti-inflammatory factors TGF-ß and IL-10, ultimately leading to renal protection. Such functions may be mediated by the paracrine activity of PMSC-EVs.

A case report of a post-polypectomy syndrome with severe sepsis and organ dysfunction.

Post-polypectomy syndrome (PPS) results from electrocoagulation injury to the bowel wall that induces a transmural burn and localized peritonitis. It has a good prognosis; however, there are exceptions when complications are observed. We here report a case of a 50-year-old man who developed lumbosacral pain and high fever with chills four days after colonoscopy, during which polypectomy was performed by endoscopic mucosal resection (EMR) and argon plasma coagulation (APC). Both the plain abdominal film and abdominal CT scan showed no free air, and lumbar CT showed no apparent lesions, which satisfied the diagnosis of PPS. However, the patient was in a critical condition as he developed septic shock caused by bacteremia. Following active treatment, the patient's condition rapidly improved. Therefore, we suggest that clinicians should consider the severity of PPS with sepsis and colon transmural burn. Patients with a diagnosis of PPS should be admitted to the hospital for observation and treatment to avoid adverse consequences.

Histone tales: lysine methylation, a protagonist in Arabidopsis development.

Histone methylation plays a fundamental role in the epigenetic regulation of gene expression driven by developmental and environmental cues in plants, including Arabidopsis. Histone methyltransferases and demethylases act as 'writers' and 'erasers' of methylation at lysine and/or arginine residues of core histones, respectively. A third group of proteins, the 'readers', recognize and interpret the methylation marks. Emerging evidence confirms the crucial roles of histone methylation in multiple biological processes throughout the plant life cycle. In this review, we summarize the regulatory mechanisms of lysine methylation, especially at histone H3 tails, and focus on the recent advances regarding the roles of lysine methylation in Arabidopsis development, from seed performance to reproductive development, and in callus formation.

The possibility of using effluent ionized calcium to assess regional citrate anticoagulation in continuous renal replacement therapy.

AIM: This study aimed to investigate whether effluent ionized calcium was an appropriate indicator to assess anticoagulant effect in continuous renal replacement therapy with regional citrate anticoagulation instead of post-filter ionized calcium. METHODS: In total, 48 paired samples of effluent fluid and post-filter blood were obtained from critically ill patients who required continuous renal replacement therapy. All samples were taken for ionized calcium measurements and were assessed by point-of-care analyzer. Correlations and agreements between two methods were performed by Pearson linear analysis and Bland-Altman analysis accordingly. RESULTS: The mean post-filter ionized calcium was 0.42 ± 0.12 mmol/L, and mean ionized calcium level of effluent fluid was 0.39 ± 0.11 mmol/L. The ionized calcium level of effluent fluid was significantly correlated with post-filter ionized calcium in all continuous renal replacement therapy patients. Bland-Altman analysis showed that the mean difference of ionized calcium between two sampling sites in all continuous renal replacement therapy patients was -0.02 mmol/L with 95% confidence interval ranging from -0.09 to 0.04 mmol/L. The significant correlations and agreements were also demonstrated in continuous veno-venous hemofiltration, continuous veno-venous hemodialysis, and continuous veno-venous hemodiafiltration modalities separately. CONCLUSION: The effluent ionized calcium could be a considerable substitute for post-filter ionized calcium to monitor the validity of regional citrate anticoagulation in continuous renal replacement therapy with less blood loss.

Bisphenol A analogs in patients with chronic kidney disease and dialysis therapy.

Bisphenol A (BPA) accumulates in patients with chronic kidney disease (CKD), and hemodialysis filters may contribute to bisphenol burden in patients on hemodialysis (HD). The serum levels of BPA and three BPA analogs, namely, bisphenol B (BPB), bisphenol S (BPS), and bisphenol F (BPF), in 58 patients with CKD, 66 patients on dialysis therapy and 30 healthy control were investigated. The content of four bisphenols (BPs) was also examined in three types of dialysis filters, followed by an in vitro elution experiment to test the release of BPs from the dialysis filters. The serum levels of BPA (r = -0.746, p < 0.05) and BPS (r = -0.433, p < 0.05) in 58 CKD patients and 30 healthy control were correlated with the decrease in estimated glomerular filtration rate. The serum levels of BPs in the HD patients were higher than those in the peritoneal dialysis patients (p < 0.05). In the in vitro study on the BP contents in dialysis filters, BPA was the main form of the BPs in the polysulfone membrane (20.86 ±â€¯1.18 ng/mg) and in the polyamide membrane (18.70 ±â€¯2.88 ng/mg), and a modicum of BPS (0.01 ±â€¯0.01 ng/mg) was detected in the polyethersulfone membrane. The results of the elution experiment were in accordance with the results of BPs content in the dialysis filters. Insufficient renal function may lead to BPs accumulation in patients with CKD, and BPs in dialysis products may cause BPs burden in patients on HD.

Effect of Baicalin-Aluminum Complexes on Fecal Microbiome in Piglets.

The gut microbiome has important effects on gastrointestinal diseases. Diarrhea attenuation functions of baicalin (BA) is not clear. Baicalin-aluminum complexes (BBA) were synthesized from BA, but the BBA's efficacy on the diarrhea of piglets and the gut microbiomes have not been explored and the mechanism remains unclear. This study has explored whether BBA could modulate the composition of the gut microbiomes of piglets during diarrhea. The results showed that the diarrhea rate reduced significantly after treatment with BBA. BBA altered the overall structure of the gut microbiomes. In addition, the Gene Ontology (GO) enrichment analysis indicated that the functional differentially expressed genes, which were involved in the top 30 GO enrichments, were associated with hydrogenase (acceptor) activity, nicotinamide-nucleotide adenylyltransferase activity, and isocitrate lyase activity, belong to the molecular function. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that flagellar assembly, bacterial chemotaxis, lipopolysaccharide biosynthesis, ATP-binding cassette transporters (ABC) transporters, biosynthesis of amino acids, and phosphotransferase system (PTS) were the most enriched during BBA treatment process. Taken together, our results first demonstrated that BBA treatment could modulate the gut microbiomes composition of piglets with diarrhea, which may provide new potential insights on the mechanisms of gut microbiomes associated underlying the antimicrobial efficacy of BBA.

Solutes removal characteristics at various effluent rates during different continuous renal replacement therapy modalities.

BACKGROUND: Some studies suggest the effluent as a surrogate solute removal indicator in continuous hemodialysis or hemofiltration, but the delivered clearance is frequently smaller than prescribed. This study aims at testing whether the effluent, represented by mL/kg/h, could measure solute clearance and whether increasing effluent increases clearance proportionately in continuous hemodialysis or hemofiltration. METHODS: Patients treated with continuous renal replacement therapy for various diagnoses were included. The range of dialysate flow rate or substitution fluid flow rate was 1-5 L/h; solutes in the effluent and in the plasma entering the filter were measured, and the ratio of solutes in the effluent and in the plasma entering the filter and the clearance of blood urea nitrogen, creatinine, phosphate, and ß2-microglobulin were calculated. RESULTS: The ratio of solutes in the effluent and in the plasma entering the filter showed a decreasing trend with increased dialysate flow rate or substitution fluid flow rate (p < 0.05), but solute clearance showed an increasing trend. The increase in solute clearance was less than expected from the increased effluent (p < 0.01), and actual delivered clearance was always below the corresponding prescribed clearance (p < 0.001). CONCLUSION: With increasing prescribed clearance of continuous renal replacement therapy, effluent rate overestimated the delivered clearance.

Calcium supplementation in CVVH using regional citrate anticoagulation.

INTRODUCTION: Calcium supplementation is one of the most important factors in maintaining the safety and efficacy of regional citrate anticoagulation (RCA) during continuous renal replacement therapy (CRRT). The aims of this study were to assess the determinants of calcium requirements in RCA-CVVH and to simplify the calcium supplementation approach. METHODS: Our study consisted of two parts. The first part was a discovery phase to determine the key factors of calcium supplementation. Twenty critically ill patients who required RCA-CVVH were enrolled in this part. Systemic citrate, total calcium, protein-bound calcium, and ionized calcium concentrations were serially measured using the traditional RCA protocol. A two-phase calcium supplementation protocol was then proposed, and algorithms were developed for calcium supplementation. The second part of the study was the validation phase. Another 97 critically ill patients were enrolled and were treated with RCA-CVVH using the new version of the calcium supplementation protocol. FINDINGS: The loss of calcium flux in the extracorporeal circuit and the increase in citrate-calcium complexes in vivo were the main determinants of the required calcium supplementation. In the CVVH mode, the rate of calcium infusion had to be reduced after systemic citrate level reached a steady state. With the aid of mathematical models, systemic calcium levels could be stably maintained in the normal range, and the frequencies of calcium monitoring were reduced. DISCUSSION: Calcium supplementation during RCA-CVVH undergoes two phases. We propose mathematical models to quantify the need for calcium supplementation, which enable individualization of the RCA prescription and simplify the management of RCA in the CVVH mode.