An inquiry into the treatment of sepsis using plasma exchange therapy: A systematic review and meta-analysis.

Sepsis is a potentially lethal condition that occurs when the body's response to infection damages tissue and organs. The production of inflammatory mediators typically assists in defending the body against infection; however, an overreaction to inflammation can cause coagulation problems, vascular endothelial damage, and organ hypoperfusion. Blood purification methods, such as plasmapheresis, can effectively remove inflammatory mediators from plasma. The purpose of this meta-analysis was to explore the efficacy of plasma exchange for sepsis treatment as noted in recent studies. The authors searched the Pubmed (Medline), Cochrane Central Register of Controlled Trials (The Cochrane Library), Embase (Ovid), and Scopus databases and included controlled clinical studies that compared plasmapheresis or plasma filtration with conventional treatment in patients with severe sepsis. The Newcastle-Ottawa Scale literature quality assessment tool was used to assess the risk of bias. The primary study outcome was all-cause mortality. The random effects model was adopted for conducting the meta-analysis. Among the 1013 records found, the study included 5 trials, all of which carried a low risk of bias. The use of plasmapheresis was associated with a longer stay in the intensive care unit (odds ratio [OR], 0.85, 95% confidence interval [CI], 0.39-1.32, heterogeneity [I2 ] = 0%), a significant reduction in all-cause mortality (OR, 0.54, 95% CI, 0.33-0.89, I2  = 70%), and reduced mortality (OR, 0.29, 95% CI, 0.13-0.67, I2  = 0%) in adults; the results for children differed from this (OR, 0.79, 95% CI, 0.36-1.72, I2  = 89%). Four trials reported no adverse events; one trial reported an adverse event related to plasma exchange, including an instance of hypotension in one patient. Plasmapheresis appeared to be an effective treatment for patients suffering from sepsis. A large number of additional randomised controlled trials are needed to confirm this finding.

Development of a Multivariable Prediction Model for Citrate Accumulation in Liver Transplant Patients Undergoing Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation.

INTRODUCTION: Patients with impaired citrate metabolism may experience citrate accumulation (CA), which causes life-threatening metabolic acidosis and hypocalcemia. CA poses a challenge for clinicians when deciding on the use of regional citrate anticoagulation (RCA) for patients with liver dysfunction. This study aimed to develop a prediction model integrating multiple clinical variables to assess the risk of CA in liver transplant patients. METHODS: This single-center prospective cohort study included postoperative liver transplant patients who underwent continuous renal replacement therapy (CRRT) with RCA. The study end point was CA. A prediction model was developed using a generalized linear mixed-effect model based on the Akaike information criterion. The predictive values were assessed using the receiver operating characteristic curve and bootstrap resampling (times = 500) to estimate the area under the curve (AUC) and the corresponding 95% confidence interval (CI). A nomogram was used to visualize the model. RESULTS: This study included 32 patients who underwent 133 CRRT sessions with RCA. CA occurred in 46 CRRT sessions. The model included lactate, norepinephrine >0.1 µg/kg/min, alanine aminotransferase, total bilirubin, and standard bicarbonate, which were tested before starting each CRRT session and body mass index, diabetes mellitus, and chronic kidney disease as predictors. The AUC of the model was 0.867 (95% CI 0.786-0.921), which was significantly higher than that of the single predictor (p < 0.05). A nomogram visualized the prediction model. CONCLUSIONS: The prediction model integrating multiple clinical variables showed a good predictive value for CA. A nomogram visualized the model for easy application in clinical practice.

Derivation and validation of plasma endostatin for predicting renal recovery from acute kidney injury: a prospective validation study.

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality in surgical patients. Nonrecovery from AKI may increase mortality and early risk stratification seems key to improving clinical outcomes. The aim of the current study was to explore and validate the value of endostatin for predicting failure to recover from AKI. METHODS: We conducted a prospective cohort study of 198 patients without known chronic kidney disease who underwent noncardiac major surgery and developed new-onset AKI in the first 48 h after admission to the ICU. The biomarkers of plasma endostatin, neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were detected immediately after AKI diagnosis. The primary endpoint was nonrecovery from AKI (within 7 days). Cutoff values of the biomarkers for predicting nonrecovery were determined in a derivation cohort (105 AKI patients). Predictive accuracy was then analyzed in a validation cohort (93 AKI patients). RESULTS: Seventy-six of 198 (38.4%) patients failed to recover from AKI onset, with 41 in the derivation cohort and 35 in the validation cohort. Compared with NGAL and cystatin C, endostatin showed a better prediction for nonrecovery, with an area under the receiver operating characteristic curve (AUC) of 0.776 (95% confidence interval (CI) 0.654-0.892, p < 0.001) and an optimal cutoff value of 63.7 ng/ml. The predictive ability for nonrecovery was greatly improved by the prediction model combining endostatin with clinical risk factors of Sequential Organ Failure Assessment (SOFA) score and AKI classification, with an AUC of 0.887 (95% CI 0.766-0.958, p < 0.001). The value of the endostatin-clinical risk prediction model was superior to the NGAL-clinical risk and cystatin C-clinical risk prediction models in predicting failure to recover from AKI, which was supported by net reclassification improvement and integrated discrimination improvement. Further, the endostatin-clinical risk prediction model achieved sensitivity and specificity of 94.6% (76.8-99.1) and 72.7% (57.2-85.0), respectively, when validated in the validation cohort. CONCLUSION: Plasma endostatin shows a useful value for predicting failure to recover from AKI. The predictive ability can be greatly improved when endostatin is combined with the SOFA score and AKI classification.

Nutritional status and nutritional intervention of older inpatients in China.

BACKGROUND: Malnutrition is a critical issue among older inpatients, yet limited large-scale research related to this issue has been conducted in China. This study aimed to examine the nutritional status and support of older inpatients in China, assess the associations between disease categories and malnutrition on admission, and explore effective nutritional intervention. METHODS: A total of 24,139 older participants from the China Nutrition Fundamental Data 2020 Project were included. Malnutrition was measured by the Global Leadership Initiative on Malnutrition criteria. Adjusted odds ratios (aORs) were calculated using logistic analysis. RESULTS: The overall frequency of malnutrition on admission was 18.9%. Participants with infections were more likely to have malnutrition (aOR = 1.929, 95% CI 1.486-2.504). Risks that were also noted for malnutrition included neoplasms (aOR = 1.822, 95% CI 1.697-1.957), hemic and lymphatic diseases (aOR = 1.671, 95% CI 1.361-2.051), nervous system diseases (aOR = 1.222, 95% CI 1.126-1.326), respiratory diseases (aOR = 1.613, 95% CI 1.490-1.746), and digestive system diseases (aOR = 1.462, 95% CI 1.357-1.577). Further, 32.26% inpatients with malnutrition during hospitalization didn't receive nutritional support. Oral nutrition supplements, enteral tube feeding, and parenteral nutrition were associated with stable or improved nutritional status. CONCLUSIONS: Older inpatients were at a high risk for malnutrition but did not receive adequate nutritional intervention. More resources and attention need to be devoted to the nutritional status of older inpatients and targeted nutritional support.

Predictive Value of Perioperative Cardiac Troponin I in Patients Undergone Liver Transplantation: A Retrospective Cohort Study.

Objective: To examine the change rule and clinical significance of cardiac troponin I (cTnI) in the perioperative period of liver transplantation in adults, as well as its association with 28-day mortality. Methods: This was a retrospective cohort study: patients who underwent elective orthotopic liver transplantation (OLT) in Beijing Chao-Yang Hospital between June 2015 and June 2020 were selected, and plasma cTnI values were collected through the electronic medical record system within 7 days after surgery. Furthermore, the baseline clinical data of these patients were collected, and the change curve of cTnI values following liver transplantation was plotted. Using univariate and multivariate logistic regression models, the relationship between the level of postoperative cTnI and short-term mortality was investigated. The primary study endpoint was mortality within 28 days after surgery. Results: We included 414 patients who had undergone liver transplantation in this study, 48 of whom died within 28 days after surgery. cTnI, a specific marker of myocardial injury, could predict that the postoperative cardiovascular complications were higher in the death group and significantly affect the short-term prognosis of patients; however, its prognostic cut-off value was approximately 0.545 ng/mL (13×URL), indicating that a minor elevation of cTnI after liver transplantation did not significantly affect the prognosis. Moreover, a comparison of the baseline data and postoperative ICU management scores of the two groups revealed that diabetes, maximum value of cTnI >0.545 ng/mL within 7 days, and the need for postoperative renal replacement therapy (RRT) were independent prognostic factors of death within 28 days after liver transplantation. Conclusion: Within 7 days after surgery, an increase in cTnI to the maximum value of 0.545 ng/mL (13×URL) could have a significant impact on the short-term prognosis of patients. Diabetes and postoperative RRT were two independent prognostic factors for liver transplantation perioperative mortality.

Cell cycle arrest biomarkers for predicting renal recovery from acute kidney injury: a prospective validation study.

BACKGROUND: Acute kidney injury (AKI) is a common disease in the intensive care unit (ICU). AKI patients with nonrecovery of renal function have a markedly increased risk of death compared with patients with recovery. The current study aimed to explore and validate the utility of urinary cell cycle arrest biomarkers for predicting nonrecovery in patients who developed AKI after ICU admission. METHODS: We prospectively and consecutively enrolled 379 critically ill patients who developed AKI after admission to the ICU, which were divided into a derivation cohort (194 AKI patients) and a validation cohort (185 AKI patients). The biomarkers of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were detected at inclusion immediately after AKI diagnosis (day 0) and 24 h later (day 1). The optimal cut-off values of these biomarkers for predicting nonrecovery were estimated in the derivation cohort, and their predictive accuracy was assessed in the validation cohort. The primary endpoint was nonrecovery from AKI (within 7 days). RESULTS: Of 379 patients, 159 (41.9%) patients failed to recover from AKI onset, with 79 in the derivation cohort and 80 in the validation cohort. Urinary [TIMP-2]*[IGFBP7] on day 0 showed a better prediction ability for nonrecovery than TIMP-2 and IGFBP7 alone, with an area under the reciever operating characteristic curve (AUC) of 0.751 [95% confidence interval (CI) 0.701-0.852, p < 0.001] and an optimal cut-off value of 1.05 ((ng/mL)2/1000). When [TIMP-2]*[IGFBP7] was combined with the clinical factors of AKI diagnosed by the urine output (UO) criteria, AKI stage 2-3 and nonrenal SOFA score for predicting nonrecovery, the AUC was significantly improved to 0.852 (95% CI 0.750-0.891, p < 0.001), which achieved a sensitivity and specificity of 88.8% (72.9, 98.7) and 92.6% (80.8, 100.0), respectively. However, urine [TIMP-2]*[IGFBP7], TIMP-2 alone, and IGFBP7 alone on day 1 performed poorly for predicting AKI recovery. CONCLUSION: Urinary [TIMP-2]*[IGFBP7] on day 0 showed a fair performance for predicting nonrecovery from AKI. The predictive accuracy can be improved when urinary [TIMP-2]*[IGFBP7] is combined with the clinical factors of AKI diagnosed by the UO criteria, AKI stage 2-3 and nonrenal SOFA score.

Prognostic value of dynamic plasma endostatin for the prediction of mortality in acute kidney injury: A prospective cohort study.

OBJECTIVE: The aim of the current study was to evaluate the value of plasma endostatin for predicting 30-day mortality of patients with acute kidney injury (AKI). METHODS: Patients who underwent non-cardiac major surgery and developed AKI in the first 48 hours after admission to the intensive care unit were consecutively included. Concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys C), and endostatin were measured at three time points: 0, 24, and 48 hours after the AKI diagnosis. Clinical patient characteristics were recorded after AKI was diagnosed. RESULTS: A total of 256 new-onset AKI patients were enrolled. Of these, 48 (18.7%) patients died within 30 days. The difference in plasma endostatin values between 0 and 24 hours (ΔEndostatin-24h) yielded the best area under the curve (AUC) of 0.747 for predicting 30-day mortality in AKI patients; NGAL and Cys C achieved AUC of 0.672 and 0.647, respectively. The predictive AUC increased to 0.833 when ΔEndostatin-24h was combined with sequential organ failure assessment score and AKI classification. CONCLUSION: Dynamic plasma endostatin is useful for predicting 30-day mortality in AKI patients. The predictive power of dynamic plasma endostatin can be significantly improved when it is combined with clinical patient data.

Pep-3D-Search: a method for B-cell epitope prediction based on mimotope analysis.

BACKGROUND: The prediction of conformational B-cell epitopes is one of the most important goals in immunoinformatics. The solution to this problem, even if approximate, would help in designing experiments to precisely map the residues of interaction between an antigen and an antibody. Consequently, this area of research has received considerable attention from immunologists, structural biologists and computational biologists. Phage-displayed random peptide libraries are powerful tools used to obtain mimotopes that are selected by binding to a given monoclonal antibody (mAb) in a similar way to the native epitope. These mimotopes can be considered as functional epitope mimics. Mimotope analysis based methods can predict not only linear but also conformational epitopes and this has been the focus of much research in recent years. Though some algorithms based on mimotope analysis have been proposed, the precise localization of the interaction site mimicked by the mimotopes is still a challenging task. RESULTS: In this study, we propose a method for B-cell epitope prediction based on mimotope analysis called Pep-3D-Search. Given the 3D structure of an antigen and a set of mimotopes (or a motif sequence derived from the set of mimotopes), Pep-3D-Search can be used in two modes: mimotope or motif. To evaluate the performance of Pep-3D-Search to predict epitopes from a set of mimotopes, 10 epitopes defined by crystallography were compared with the predicted results from a Pep-3D-Search: the average Matthews correlation coefficient (MCC), sensitivity and precision were 0.1758, 0.3642 and 0.6948. Compared with other available prediction algorithms, Pep-3D-Search showed comparable MCC, specificity and precision, and could provide novel, rational results. To verify the capability of Pep-3D-Search to align a motif sequence to a 3D structure for predicting epitopes, 6 test cases were used. The predictive performance of Pep-3D-Search was demonstrated to be superior to that of other similar programs. Furthermore, a set of test cases with different lengths of sequences was constructed to examine Pep-3D-Search's capability in searching sequences on a 3D structure. The experimental results demonstrated the excellent search capability of Pep-3D-Search, especially when the length of the query sequence becomes longer; the iteration numbers of Pep-3D-Search to precisely localize the target paths did not obviously increase. This means that Pep-3D-Search has the potential to quickly localize the epitope regions mimicked by longer mimotopes. CONCLUSION: Our Pep-3D-Search provides a powerful approach for localizing the surface region mimicked by the mimotopes. As a publicly available tool, Pep-3D-Search can be utilized and conveniently evaluated, and it can also be used to complement other existing tools. The data sets and open source code used to obtain the results in this paper are available on-line and as supplementary material. More detailed materials may be accessed at (http://kyc.nenu.edu.cn/Pep3DSearch/).

[The formation of BPDE-DNA adduct in rat and its determination by high performance liquid chromatography].

OBJECTIVE: To study the benzo (a) pyrene (BaP) induced DNA adduct in rat and establish a method to measure the DNA adduct in blood by high performance liquid chromatography (HPLC). METHODS: The SD rats were treated with 100 mg/kg of BaP-DMSO (cosolvent: 1% sodium carboxymethyl cellulose) once by i.p., and the blood of femoral vein was collected 5 hours later. The blood DNA was extracted by kit and confirmed by agarose gel electrophoresis. After extraction, the DNA adducts were hydrolyzed in 0.1 nmol/L HCl at 90 degrees C for 4 hours. The acid-hydrolysis products (BP-tetrols) of DNA adducts were extracted by ethyl acetate and measured by HPLC, and finally confirmed by HPLC-MS. RESULTS: In chromatogram there were new peaks to occur for rats treated by BaP, with compared to control. By HPLC-MS, one of the new peaks was confirmed to be BP-tetrol. CONCLUSION: The rats ingesting BaP in the way described in this experiment can form DNA adducts, and the adducts in blood can be detected by HPLC.