Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features.

Introduction: The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model. Methods: The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained. Results: No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p < 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p < 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p < 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups. Conclusion: Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.

The predictive value of hematological inflammatory markers for acute kidney injury and mortality in adults with hemophagocytic Lymphohistiocytosis: A retrospective analysis of 585 patients.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological hyperactivation-related disease with a high mortality rate. The purpose of this study was to examine the relationship between complete blood count parameters and the occurrence of acute kidney injury (AKI) and mortality in patients with HLH. METHODS: We included 585 adult patients with HLH. Logistic regression models for AKI and 28-day mortality were developed. RESULTS: Multivariate logistic regression models revealed that hemoglobin (HB) ≤ 7.3 g/dl (adjusted OR, 1.651; 95% CI, 1.044-2.612), hemoglobin-to-red blood cell distribution width ratio (HRR) < 0.49 (adjusted OR, 1.692), neutrophil-to-lymphocyte ratio (NLR) ≥ 3.15 (adjusted OR, 1.697), and neutrophil-to-lymphocyte-platelet ratio (NLPR) ≥ 11.0 (adjusted OR, 1.608) were independent risk factors for the development of AKI. Moreover, lower platelet levels (31 × 109/L < platelets < 84 × 109/L, adjusted OR, 2.133; platelets ≤ 31 × 109/L, adjusted OR, 3.545) and higher red blood cell distribution width-to-platelet ratio (RPR) levels (0.20 < RPR < 0.54, adjusted OR, 2.595; RPR ≥ 0.54, adjusted OR, 4.307), lymphocytes ≤ 0.34 × 109/L (adjusted OR, 1.793), NLPR ≥ 11.0 (adjusted OR, 2.898), and the aggregate index of systemic inflammation (AISI) ≤ 7 (adjusted OR,1.778) were also independent risk factors for 28-day mortality. Furthermore, patients with AKI had a worse prognosis than those without AKI (P < 0.05). CONCLUSION: In patients with HLH, hematological parameters are of great value for the early identification of patients at high risk of AKI and 28-day mortality.

Incidence and outcomes of acute kidney disease in patients after type A aortic dissection surgery.

BACKGROUND: Acute kidney injury (AKI), acute kidney disease (AKD) and CKD (chronic kidney disease) were a continuous process. There has been little discussion of risk factors for AKD in the population undergoing surgery for acute type A aortic dissection (AAAD). OBJECTIVE: The main objective of this study was to investigate the risk factors for AKD after surgery for acute type A aortic dissection and the impact of AKD on early and late mortality. DESIGN: AKI was to be defined as an increase in serum creatinine to >0.3 mg/dL or 1.5 times above baseline within 7 days. AKD was defined as the kidney damage within 90 days after AKI. Logistic regression models were performed to identify the risk factors of AKD and the association between AKD and early mortality after AAAD surgery. PARTICIPANTS: Patients with AKI after AAAD surgery admitted in ICU from March 2009 to September 2021 were included. KEY RESULTS: Among the 328 patients who developed AKI after AAAD surgery, 98 patients (29.9%) progressed to AKD. Multivariable analysis revealed that AKI stage 2 (OR, 3.032) and AKI stage 3 (OR, 4.001) have been shown to be independent risk factors for the development of AKD. AKD (OR, 3.175) proved to be an independent risk factor for early mortality, while no significant difference in late mortality was observed between patients in the AKD and non-AKD groups. CONCLUSION: The severity of AKI after surgery of AAAD was independently associated with AKD. The occurrence of AKD had a negative impact on early mortality. CLINICAL TRIAL REGISTRATION: ChiCTR, ChiCTR1900021290. Registered 12 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35795.

Hypoparathyroidism and late-onset hypogonadism in an adult male with familial 22q11.2 deletion syndrome: a case report with 3-year follow-up and review of the literature.

BACKGROUND: 22q11.2 deletion syndrome (DiGeorge syndrome) is associated with multiple organ dysfunctions such as cardiac defects, immunodeficiency, and hypoplasia of parathyroid glands. Moreover, the phenotype of 22q11.2 DS has clinical variability and heterogeneity. CASE PRESENTATION: In this report, we present the case of a 35-year-old patient with a past medical history that included recurrent infections, mild learning difficulties in childhood, pediatric obesity, and cataract. He was admitted to the endocrinology department for the management of hypogonadism and hypocalcemia. During the 3-year follow-up, the patient gradually developed primary hypoparathyroidism, hypogonadism, chronic renal failure, and heart failure, and his medical condition deteriorated. Meanwhile, in order to improve clinicians' awareness of the endocrine manifestations of adult 22q11.2 DS and reduce missed diagnoses, we reviewed 28 case reports of adult 22q11.2 DS to analyze the clinical characteristics. DISCUSSION: Here, we report the case of a young man diagnosed with 22q11.2 DS presented a rare combination of multiple endocrine disorders. This is the first time that a patient with 22q11.2DS had late-onset hypogonadism caused by primary testicular failure combined with decreased pituitary gonadotropin reserve in a patient with 22q11.2DS.

A prediction model for acute kidney injury in adult patients with hemophagocytic lymphohistiocytosis.

Background and aims: Hemophagocytic lymphohistiocytosis is a clinical syndrome resulting from abnormally active immune cells and a cytokine storm, with the accompanying phagocytosis of blood cells. Patients with hemophagocytic lymphohistiocytosis often suffer acute kidney injury during hospitalization, which usually signifies poor prognosis. We would like to establish a prediction model for the occurrence of acute kidney injury in adult patients with hemophagocytic lymphohistiocytosis for risk stratification. Method: We extracted the electronic medical records of patients diagnosed with hemophagocytic lymphohistiocytosis during hospitalization from January 2009 to July 2019. The observation indicator is the occurrence of acute kidney injury within 28 days of hospitalization. LASSO regression was used to screen variables and modeling was performed by COX regression. Results: In the present study, 136 (22.7%) patients suffered from acute kidney injury within 28 days of hospitalization. The prediction model consisted of 11 variables, including vasopressor, mechanical ventilation, disseminated intravascular coagulation, admission heart rate, hemoglobin, baseline cystatin C, phosphorus, total bilirubin, lactic dehydrogenase, prothrombin time, and procalcitonin. The risk of acute kidney injury can be assessed by the sum of the scores of each parameter on the nomogram. For the development and validation groups, the area under the receiver operating characteristic curve was 0.760 and 0.820, and the C-index was 0.743 and 0.810, respectively. Conclusion: We performed a risk prediction model for the development of acute kidney injury in patients with hemophagocytic lymphohistiocytosis, which may help physicians to evaluate the risk of acute kidney injury and prevent its occurrence.

Procalcitonin, Interleukin-6 and C-reactive Protein Levels Predict Renal Adverse Outcomes and Mortality in Patients with Acute Type A Aortic Dissection.

Background: Acute type A aortic coarctation (AAAD) is a highly deadly and serious life-threatening disease. The purpose of this study was to estimate the predictive value of peak procalcitonin, interleukin-6, and C-reactive protein levels on adverse renal outcomes and mortality in patients undergoing surgery for AAAD. Methods: Perioperative peak PCT, CRP, and IL-6 levels were retrospectively collected in 331 patients hospitalized with AAAD from 2009 to 2021. The primary endpoints were AKI stage 2-3 and mortality. The receiver operating characteristic (ROC) curves were used to compare the predictive values of peak PCT, CRP, and IL-6 for different clinical outcomes. Multivariable logistic regression analysis was used to find risk factors for AKI and 30-day mortality. Results: The incidence of AKI stage 2-3 following AAAD was 50.8% (168/331). The 30-day and overall mortality were significantly greater in the AKI 2-3 group than in the AKI 0-1 group (P = 0.000). ROC curve analysis showed that peak PCT, with an area under the ROC curve (AUC) of 0.712, was a more accurate predictor of adverse renal outcomes than peak IL-6 and CRP. Multivariable logistic regression analysis revealed that PCT > 0.39 ng/mL was an independent risk factor for AKI stage 2-3. Peak IL-6 > 259 pg/mL was found to be an independent risk factor for 30-day mortality. Conclusion: In patients with surgery for AAAD, peak PCT provides a well-predictive indicator of AKI stage 2-3 and peak IL-6 indicates a favorable predictor of 30-day mortality.

Clinical features and prognostic factors of acute kidney injury caused by adult secondary hemophagocytic lymphohistiocytosis.

BACKGROUND AND AIMS: Hemophagocytic lymphohistiocytosis is a clinical syndrome caused by a cytokine storm and phagocytosis of blood cells. Acute kidney injury is typically associated with a poor prognosis in hemophagocytic lymphohistiocytosis. In the present study, a retrospective analysis of patient data was performed to identify risk factors associated with acute kidney injury in hemophagocytic lymphohistiocytosis. METHODS: All patients included  in the study were diagnosed with hemophagocytic lymphohistiocytosis between January 2009 and July 2019. Acute kidney injury was diagnosed according to the Kidney Disease Improving Global Outcomes guidelines, according to the 2012 update. We collected the general information of the patients, clinical manifestations, treatments, as well as laboratory data from the electronic medical records. RESULTS: We analyzed 600 patients with hemophagocytic lymphohistiocytosis. Serum phosphorus, need for vasopressors, heart failure, gastrointestinal symptoms, disseminated intravascular coagulation, high heart rate at admission, total bilirubin and albumin levels were independently associated with an increased risk of developing acute kidney injury. Independent risk factors for in-hospital mortality were administration of vasopressors, acute kidney injury stage III, baseline Cystatin-C, total bilirubin, number of days of glucocorticoid therapy, fibrinogen level and presence of multi-organ failure. CONCLUSION: Patients with hemophagocytic lymphohistiocytosis usually exhibit high hospital mortality, particularly in the presence of acute kidney injury. The risk factors for the occurrence of acute kidney injury and increased mortality identified in the study may assist clinicians in the prevention of acute kidney injury, and in its timely treatment in patients affected by hemophagocytic lymphohistiocytosis, to ultimately improve prognosis.

Incidence- and In-hospital Mortality-Related Risk Factors of Acute Kidney Injury Requiring Continuous Renal Replacement Therapy in Patients Undergoing Surgery for Acute Type a Aortic Dissection.

Background: Few studies on the risk factors for postoperative continuous renal replacement therapy (CRRT) in a homogeneous population of patients with acute type A aortic dissection (AAAD). This retrospective analysis aimed to investigate the risk factors for CRRT and in-hospital mortality in the patients undergoing AAAD surgery and to discuss the perioperative comorbidities and short-term outcomes. Methods: The study collected electronic medical records and laboratory data from 432 patients undergoing surgery for AAAD between March 2009 and June 2021. All the patients were divided into CRRT and non-CRRT groups; those in the CRRT group were divided into the survivor and non-survivor groups. The univariable and multivariable analyses were used to identify the independent risk factors for CRRT and in-hospital mortality. Results: The proportion of requiring CRRT and in-hospital mortality in the patients with CRRT was 14.6 and 46.0%, respectively. Baseline serum creatinine (SCr) [odds ratio (OR), 1.006], cystatin C (OR, 1.438), lung infection (OR, 2.292), second thoracotomy (OR, 5.185), diabetes mellitus (OR, 6.868), AKI stage 2-3 (OR, 22.901) were the independent risk factors for receiving CRRT. In-hospital mortality in the CRRT group (46%) was 4.6 times higher than in the non-CRRT group (10%). In the non-survivor (n = 29) and survivor (n = 34) groups, New York Heart Association (NYHA) class III-IV (OR, 10.272, P = 0.019), lactic acidosis (OR, 10.224, P = 0.019) were the independent risk factors for in-hospital mortality in patients receiving CRRT. Conclusion: There was a high rate of CRRT requirement and high in-hospital mortality after AAAD surgery. The risk factors for CRRT and in-hospital mortality in the patients undergoing AAAD surgery were determined to help identify the high-risk patients and make appropriate clinical decisions. Further randomized controlled studies are urgently needed to establish the risk factors for CRRT and in-hospital mortality.

Risk Factors for Acute Kidney Injury in Adult Patients With COVID-19: A Systematic Review and Meta-Analysis.

Background and Objective: Since December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Studies found that the incidence of acute kidney injury (AKI) in COVID-19 patients was more than double the incidence of AKI in non-COVID-19 patients. Some findings confirmed that AKI is a strong independent risk factor for mortality in patients with COVID-19 and is associated with a three-fold increase in the odds of in-hospital mortality. However, little information is available about AKI in COVID-19 patients. This study aimed to analyse the risk factors for AKI in adult patients with COVID-19. Methods: A systematic literature search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Library, CNKI, VIP and WanFang Data from 1 December 2019 to 30 January 2021. We extracted data from eligible studies to compare the effects of age, sex, chronic diseases and potential risk factors for AKI on the prognosis of adult patients with COVID-19. Results: In total, 38 studies with 42,779 patients were included in this analysis. The meta-analysis showed that male sex (OR = 1.37), older age (MD = 5.63), smoking (OR = 1.23), obesity (OR = 1.12), hypertension (OR=1.85), diabetes (OR=1.71), pneumopathy (OR = 1.36), cardiovascular disease (OR = 1.98), cancer (OR = 1.26), chronic kidney disease (CKD) (OR = 4.56), mechanical ventilation (OR = 8.61) and the use of vasopressors (OR = 8.33) were significant risk factors for AKI (P < 0.05). Conclusions: AKI is a common and serious complication of COVID-19. Overall, male sex, age, smoking, obesity, hypertension, diabetes, pneumopathy, cardiovascular disease, cancer, CKD, mechanical ventilation and the use of vasopressors were independent risk factors for AKI in adult patients with COVID-19. Clinicians need to be aware of these risk factors to reduce the incidence of AKI. System Review Registration: PROSPERO, identifier [CRD42021282233].

Erythropoietin Attenuates Experimental Contrast-Induced Nephrology: A Role for the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling Pathway.

The aim of the present study was to investigate the effect of erythropoietin (EPO) on contrast-induced nephrology (CIN) in vivo and in vitro. Male C57BL/6J mice were divided into four groups: control, CIN (iohexol 6.0 g/kg), EPO (3,000 IU/kg), and CIN+EPO. Hematoxylin and eosin (H&E) staining and biochemical index analyses were performed to evaluate renal injury. The cellular proliferation rate was detected using the Cell Counting Kit-8 (CCK-8) assay. In addition, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometric assay were used to assess the apoptosis of tissue and cells, respectively. Renal protein expression associated with apoptosis, pyroptosis, and signaling pathways was determined by Western blot (WB) assays for tissues and cells. The results showed that EPO significantly decreased serum creatinine, blood urea nitrogen, and cystatin C levels and alleviated renal histological changes in vivo. The protein levels of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway components were overexpressed in the EPO treatment group. Furthermore, EPO suppressed the cell apoptosis and pyroptosis; decreased the protein levels of cleaved caspase-3, Bax, gasdermin D (GSDMD), and caspase-1; and enhanced the expression of Bcl-2. In summary, EPO could exert renoprotective effect by activating the JAK2/STAT3 signaling pathway, which may be a novel potential therapy for the treatment of CIN in the clinic.

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04-2.60; score 2: HR 2.48, 95% CI 1.40-4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55-4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.

Different techniques for peritoneal dialysis catheter implantation: A systematic review and network meta-analysis.

The current consensus recommended the peritoneal dialysis catheter (PDC) techniques based on the patients' anesthesia situation and previous abdominal surgery. However, the research comparing of all the existing PDC techniques is lacking. The objective was to compare the efficacy and safety of PDC techniques by network meta-analysis (NMA). A systematic review of databases was conducted to identify eligible studies. NMA was used to estimate the ranking for endpoints. Our NMA included 41 studies (9 randomized controlled trials (RCTs) and 32 observational trials) and enrolled 3902 patients, comparing three techniques: the laparoscopic catheterization (LC), open surgery catheterization (OSC), and percutaneous catheterization (PC). NMA in RCTs showed OSC had the highest incidence of catheter mechanical dysfunction, PC and LC were very similar, but this result had no statistical difference. NMA in observational studies showed that LC had the highest 1-year catheter survival but without statistical difference (LC vs. OSC: odds ratio (OR) 1.75, 95% credible intervals (CrIs) 0.90-3.40; PC vs. OSC: OR 1.55, 95% CrIs 0.80-2.97; PC vs. LC: OR 0.88, 95% CrIs 0.54-1.44). OSC had the lowest incidence for bleeding. The complications of leakage, peritonitis, and exit/tunnel infection were inconclusive due to the inconsistent results between RCTs and observational studies. Our NMA revealed LC may have the best 1-year catheter survival. PC and LC might be efficacious in lowering the mechanical dysfunction. OSC had the lowest incidence for bleeding. More RCTs with larger scale and higher quality are needed in order to obtain more credible evidence.

Risk factors for severe acute kidney injury among patients with rhabdomyolysis.

BACKGROUND: Acute kidney injury (AKI) is a life-threatening complication of rhabdomyolysis (RM). The aim of the present study was to assess patients at high risk for the occurrence of severe AKI defined as stage II or III of KDIGO classification and in-hospital mortality of AKI following RM. METHODS: We performed a retrospective study of patients with creatine kinase levels > 1000 U/L, who were admitted to the West China Hospital of Sichuan University between January 2011 and March 2019. The sociodemographic, clinical and laboratory data of these patients were obtained from an electronic medical records database, and univariate and multivariate regression analyses were subsequently conducted. RESULTS: For the 329 patients included in our study, the incidence of AKI was 61.4% and the proportion of stage I, stage II, stage III were 18.8, 14.9 and 66.3%, respectively. The overall mortality rate was 19.8%; furthermore, patients with AKI tended to have higher mortality rates than those without AKI (24.8% vs. 11.8%; P < 0.01). The clinical conditions most frequently associated with RM were trauma (28.3%), sepsis (14.6%), bee sting (12.8%), thoracic and abdominal surgery (11.2%) and exercise (7.0%). Furthermore, patients with RM resulting from sepsis, bee sting and acute alcoholism were more susceptible to severe AKI. The risk factors for the occurrence of stage II-III AKI among RM patients included hypertension (OR = 2.702), high levels of white blood cell count (OR = 1.054), increased triglycerides (OR = 1.260), low level of high-density lipoprotein cholesterol (OR = 0.318), elevated serum phosphorus (OR = 5.727), 500010,000 U/L (OR = 8.093). Age ≥ 60 years (OR = 2.946), sepsis (OR = 3.206) and elevated prothrombin time (OR = 1.079) were independent risk factors for in-hospital mortality in RM patients with AKI. CONCLUSIONS: AKI is independently associated with mortality in patients with RM, and several risk factors were found to be associated with the occurrence of severe AKI and in-hospital mortality. These findings suggest that, to improve the quality of medical care, the early prevention of AKI should focus on high-risk patients and more effective management.

Role of TLR4/MyD88/NF-κB signaling in the contrast-induced injury of renal tubular epithelial cells.

The aim of the present study was to explore the role of toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling in the contrast-induced injury of renal tubular epithelial cells, and to investigate the potential mechanisms. HK-2 cells cultured in vitro were randomly divided into six groups as follows: i) The blank group; ii) the iohexol group; iii) the NF-κB RNAi group (NF-κB siRNA + iohexol); iv) the TLR4 RNAi group (TLR4 siRNA + iohexol); v) the NF-κB blocker group (PDTC + iohexol); and vi) the TLR4 blocker group (CLI-095 + iohexol). The expression of the TLR4/MyD88/NF-κB signaling pathway proteins was detected by reverse transcription-quantitative (RT-q)PCR and western blot analysis, and the cellular proliferation rate was determined using the Cell Counting Kit-8 assay. The mRNA expression levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were also detected using RT-qPCR, and apoptosis was assessed by flow cytometry and western blotting to detect apoptosis-associated proteins (caspase-3, caspase-9 and cleaved caspase-9). Compared with the blank group, the apoptotic rates and the expression levels of TLR4, MyD88, NF-κB, caspase-3, cleaved caspase-9, TNF-α, IL-1ß and IL-6 were upregulated in the iohexol group (P<0.001). However, when TLR4 or NF-κB were blocked or silenced, these effects were reversed (P<0.001). Collectively, the results of the present study indicated that TLR4/MyD88/NF-κB signaling is involved in the contrast-induced injury of renal tubular epithelial cells by inducing inflammation and apoptosis.

[Risk Factors for Sepsis Associated-Acute Kidney Injury in Intensive Care Unit Patients].

OBJECTIVE: To explore the risk factors of acute kidney injury (AKI) in patients with sepsis in intensive care unit (ICU). METHODS: The medical records of patients diagnosed with sepsis in ICU of West China Hospital of Sichuan University from March 2009 to June 2016 were retrospectively analyzed. Differences between AKI group and Non-AKI group in general data, background disease, ICU entry and exit dates, complications, laboratory data and other related data were analyzed through univariate and multivariate statistical methods. RESULTS: A total of 2331 patients with sepsis were included in the study, including 626 patients in the AKI group and 1695 patients in the Non-AKI group. The multivariate logistic regression analysis revealed that age >40 yr. (odds ratio (OR) =2.752), diabetes (OR=2.563), hypertension/coronary heart disease (OR=1.851), chronic kidney disease (OR=15.876), heart failure (OR=2.295), acute respiratory distress syndrome (OR=2.067), severe acute pancreatitis (OR=2.725), hypotension (OR=2.140), hypoproteinemia (OR=1.596), lactic acidosis (OR=2.164), organ failure>1 (OR=4.480), WBC>10×10 9L -1 (OR=4.166), serum creatinine (OR=4.401), PCT (OR=1.816), Cys-C (OR=7.046), mild anemia (OR=2.107), moderate anemia (OR=3.817), and severe anemia (OR=6.091) were all independent risk factors of SA-AKI. CONCLUSION: Several risk factors are related to the occurrence of SA-AKI in the ICU. Early identification and monitoring of risk factors for SA-AKI and early prevention of AKI can improve the prognosis of sepsis patients.

Liver extracellular volume fraction values obtained with magnetic resonance imaging can quantitatively stage liver fibrosis: a validation study in monkeys with nonalcoholic steatohepatitis.

OBJECTIVES: This study was to evaluate the diagnostic value of liver extracellular volume (LECV) for the staging of liver fibrosis in a cynomolgus monkey model of nonalcoholic steatohepatitis (NASH). METHODS: Forty-eight cynomolgus monkeys were enrolled in this prospective study. There are 17 healthy monkeys and 31 monkeys with NASH. Ten of these monkeys were used for repeatability assessment. The remaining 38 monkeys were used to compare LECV with other indicators including pathology fibrosis score, native T1, and serum chemical indexes by Spearman, Pearson correlation test, and ROC curves. The inter-reader variability was assessed by interclass correlation. The repeatability measurement of LECV was analyzed using Bland-Altman plots and the coefficient of variation. Partial correlation analysis was performed to assess the effects of fat content and inflammation scores on the correlation between LECV/T1 and liver fibrosis score. RESULTS: This study demonstrated a good intra-reader agreement (intraclass correlation = 0.79) of LECV in all monkeys and an excellent repeatability in 10 monkeys (coefficient of variation = 2.01%). The LECV has a strong correlation with the fibrosis score (r = 0.949; p < 0.0001), low-density lipoprotein (r = 0.72; p < 0.0001), and cholesterol (r = 0.70; p < 0.0001). LECV showed high diagnostic efficacy in the diagnosis of liver fibrosis (area under the curve of ROC, 0.945~1; p < 0.001). CONCLUSIONS: LECV may serve as a noninvasive valuable biomarker for the quantification and differentiating of the non-severe liver fibrosis (stage ≤ F3). However, circulating serum markers low-density lipoprotein and cholesterol (CHO) may not serve for this purpose. KEY POINTS: • This paper demonstrated the excellent repeatability (intraclass correlation coefficient = 0.79) of LECV in monkey animal model. • LECV-MRI has a strong correlation with histopathological fibrosis score stage (r = 0.949; p < 0.0001) and shows high diagnostic efficacy in the staging of non-severe liver fibrosis (the area under ROC curve ≥ 0.945). • The new fibrosis score maps appeared to provide a better imaging tool for the spatial assessment of liver fibrosis. It may eventually facilitate the diagnosis of liver fibrosis distribution.

Characterization of a Parkinson's disease rat model using an upgraded paraquat exposure paradigm.

Animal models of human diseases are crucial experimental tools to investigate the mechanisms involved in disease pathogenesis and to develop new therapies. In spite of the numerous animal models currently available that reproduce several neuropathological features of Parkinson disease (PD), it is challenging to have one that consistently recapitulates human PD conditions in both motor behaviors and biochemical pathological outcomes. Given that, we have implemented a new paradigm to expose rats to a chronic low dose of paraquat (PQ), using osmotic minipumps and characterized the developed pathologic features over time. The PQ exposure paradigm used lead to a rodent model of PD depicting progressive nigrostriatal dopaminergic neurodegeneration, characterized by a 41% significant loss of dopaminergic neuron in the substantia nigra pars compacta (SNpc), a significant decrease of 18% and 40% of dopamine levels in striatum at week 5 and 8, respectively, and a significant 1.5-fold decrease in motor performance. We observed a significant increase of microglia activation state, sustained levels of α-synucleinopathy and increased oxidative stress markers in the SNpc. In summary, this is an explorative study that allowed to characterize an improved PQ-based rat model that recapitulates cardinal features of PD and may represent an attractive tool to investigate several mechanisms underlying the various aspects of PD pathogenesis as well as for the validation of the efficacy of new therapeutic approaches that targets different mechanisms involved in PD neurodegeneration.

Intervention for early diabetic nephropathy by mesenchymal stem cells in a preclinical nonhuman primate model.

BACKGROUND: Diabetic nephropathy (DN) is one of the most severe chronic diabetic complications and the main cause of end-stage renal disease. Chronic inflammation plays a key role in the development of DN. However, few treatment strategies are available; therefore, new and effective strategies to ameliorate DN at the early stage must be identified. METHODS: Mesenchymal stem cells (MSCs) are characterized by anti-inflammatory and immune regulatory abilities. We developed a rhesus macaque model of DN and administered MSCs four times over 2 months. We measured blood glucose level, HbA1c, and levels of renal function parameters in the blood and urine, and cytokine levels in the kidney and blood circulatory system of rhesus macaques. Also, we analyzed the renal pathological changes of rhesus macaques. In vitro, we treated tubular epithelial cells (HK2) with 30 mmol/L glucose and 10 ng/mL human recombinant TNF-alpha (rhTNF-α) and explored the effects of MSCs on inflammation and Na+-glucose cotransporter 2 (SGLT2) expression in HK2. RESULTS: We found that MSCs decreased the blood glucose level and daily insulin requirement of DN rhesus macaques. Furthermore, MSCs had a dominant function in improving renal function and decreasing SGLT2 expression on renal tubular epithelial cells. Also, renal pathological changes were ameliorated after MSC treatment. Moreover, MSCs powerfully reduced inflammation, especially decreased the level of pro-inflammatory cytokine interleukin-16 (IL-16), in the kidney and blood circulatory system. CONCLUSIONS: Our study is an important step to explore the mechanism of MSCs in ameliorating the early stage of DN, potentially through influencing SGLT2 expression and resulting in improved glycemic control and anti-inflammation. We hope these findings would provide insights for the clinical application of MSCs in DN.

A simple risk score for prediction of sepsis associated-acute kidney injury in critically ill patients.

BACKGROUND: Sepsis is common and frequently fatal condition in critically ill patients and is a major cause of acute kidney injury (AKI). In this retrospective study, we sought to develop a comprehensive risk score model of sepsis associated-AKI (SA-AKI). METHODS: A total of 2617 patients were randomly assigned to a development (1554 patients) and a validation group (777 patients). The risk score model for SA-AKI was developed with multivariate regression analysis in development group and the model was further evaluated on validation group. RESULTS: We identified 16 independent predictors of SA-AKI in development group (age ≥ 60 years, hypertension/coronary heart disease, diabetes, chronic kidney disease, heart failure, chronic obstructive pulmonary disease, acute severe pancreatitis, hypotension, hypoproteinemia, lactic acidosis, the length of stay in intensive care unit(ICU), 60 g/L