Summary Background Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of ...AKI and assess the availability of diagnosis and treatment in China. Methods We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and National Bureau of Statistics. Findings Of 2 223 230 patients admitted to the 44 hospitals screened in 2013, 154 950 (7·0%) were suspected of having AKI by electronic screening, of whom 26 086 patients (from 374 286 total admissions) were reviewed with medical records to confirm the diagnosis of AKI. The detection rate of AKI was 0·99% (3687 of 374 286) by KDIGO criteria and 2·03% (7604 of 374 286) by expanded criteria, from which we estimate that 1·4–2·9 million people with AKI were admitted to hospital in China in 2013. The non-recognition rate of AKI was 74·2% (5608 of 7555 with available data). Renal referral was done in 21·4% (1625 of 7604) of the AKI cases, and renal replacement therapy was done in 59·3% (531 of 896) of those who had the indications. Delayed AKI recognition was an independent risk factor for in-hospital mortality, and renal referral was an independent protective factor for AKI under-recognition and mortality Interpretation AKI has become a huge medical burden in China, with substantial underdiagnosis and undertreatment. Nephrologists should take the responsibility for leading the battle against AKI. Funding National 985 Project of China, National Natural Science Foundation of China, Beijing Training Program for Talents, International Society of Nephrology Research Committee, and Bethune Fund Management Committee.
Summary Background Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation, and has many components including mucus hypersecretion, oxidative stress, and airway ...inflammation. We aimed to assess whether carbocisteine, a mucolytic agent with anti-inflammatory and antioxidation activities, could reduce the yearly exacerbation rate in patients with COPD. Methods We did a randomised, double-blind, placebo-controlled study of 709 patients from 22 centres in China. Participants were eligible if they were diagnosed as having COPD with a postbronchodilator forced expiratory volume in 1 s (FEV1 ) to forced vital capacity (FVC) ratio (FEV1 /FVC) of less than 0·7 and an FEV1 between 25% and 79% of the predicted value, were aged between 40 and 80 years, had a history of at least two COPD exacerbations within the previous 2 years, and had remained clinically stable for over 4 weeks before the study. Patients were randomly assigned to receive 1500 mg carbocisteine or placebo per day for a year. The primary endpoint was exacerbation rate over 1 year, and analysis was by intention to treat. This trial is registered with the Japan Clinical Trials Registry ( http://umin.ac.jp/ctr/index/htm ) number UMIN-CRT C000000233. Findings 354 patients were assigned to the carbocisteine group and 355 to the placebo group. Numbers of exacerbations per patient per year declined significantly in the carbocisteine group compared with the placebo group (1·01 SE 0·06 vs 1·35 SE 0·06), risk ratio 0·75 (95% CI 0·62–0·92, p=0·004). Non-significant interactions were found between the preventive effects and COPD severity, smoking, as well as concomitant use of inhaled corticosteroids. Carbocisteine was well tolerated. Interpretation Mucolytics, such as carbocisteine, should be recognised as a worthwhile treatment for prevention of exacerbations in Chinese patients with COPD. Funding Kyorin Pharmaceuticals.
Abstract Background Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation (LT) is the only curative option. However, there are little published data on ...risk factors and outcomes of LT for ACLF. Methods The objective of this study was to analyze preoperative, intraoperative, postoperative, and overall survival data on 100 consecutive cases with ACLF in order to try to determine for which patients LT are futile. Results One hundred consecutive patients with pathology-confirmed ACLF who underwent LT from June 2004 to September 2012 were enrolled. The preoperative data showed that all patients were in a serious condition with a median high model for end-stage liver disease (MELD) score of 32, total bilirubin of 440.20 umol/L, international normalized ratio (INR) of 3.012, and at least one organ dysfunction as assessed by a Sequential Organ Failure Assessment (SOFA) score of ≥9. The patients had either deceased or a living donor LT with an overall mortality of 20%. The 1-, 3-, and 5-year cumulative survival rates were 76.8%, 75.6%, and 74.1%, respectively, and graft 1-, 3-, and 5-y accumulative survival rates were 73.3%, 72.1%, and 70.6%, respectively. However, the area under receiver operating characteristic of SOFA score, MELD score, as well as Child-Pugh score were 0.552, 0.547, and 0.547, respectively. Conclusions Both deceased and living donor LT are effective therapeutic options for patients with ACLF and the short- and long-term survival rates are encouraging. It is important to conduct more prospective and multi-center studies to define preoperatively which patients would benefit from LT.
Background The technique of endoscopic submucosal dissection (ESD), which was developed for en bloc resection of large lesions in the stomach, has been widely accepted for the treatment of early ...gastric cancer. It is being used for muscularis propria tumors of the digestive tract and has produced positive therapeutic effects. Objective To study the feasibility of ESD for the removal of esophageal muscularis propria tumors and to evaluate the efficacy and safety of ESD for this treatment. Design Single-center, retrospective study. Setting University hospital. Patients Thirty esophageal muscularis propria tumors from 28 patients were treated with ESD between December 2008 and December 2010. We defined esophageal muscularis propria tumors as esophageal submucosal tumors originating from the muscularis propria layer. Intervention ESD. Main Outcome Measurements Tumor characteristics, complications, en bloc resection rate, and local recurrence rate were evaluated. Results Among the 28 patients, 11 were women (39.3%). The median age was 49.32 years (range 22-62 years). Mean (±SD) tumor size was 1.25 ± 0.70 cm (range 0.5-3.0 cm). Except for 2 failed cases (one changed to surgery and the other changed to nylon ligation), 26 cases with 28 tumors (2 cases had 2 tumors) originating from the muscularis propria of the esophagus were successfully resected by ESD. The en bloc resection rate was 93.3% (28/30). The median ESD procedure time was 73.5 minutes (range 30-120 minutes). Perforation occurred in 2 cases during dissection of the lesion, which was closed with metal endoclips. Pneumothorax occurred after the treatment in both cases. Closed thoracic drainages were initiated, and the patients recovered quickly without surgery. Pathological examination confirmed 27 leiomyomas and 1 GI stromal tumor. The curative resection rate was 100% (28/28). There was no recurrence during a 3 to 27–month follow-up period. Limitations The limitation of the study was its retrospective design. Conclusion ESD offers the promise of localized treatment of esophageal muscularis propria tumors with relatively few complications and low mortality. It makes the resection of whole lesions possible and provides precise histologic information.
Summary Macrophages constitute a major component of the leukocyte infiltrate of tumors and perform distinct roles in different tumor microenvironments. This study attempted to investigate the ...prognostic values of tumor-infiltrating macrophages in patients with hepatocellular carcinoma after resection, paying particular attention to their tissue microlocalization. The CD68+ macrophages were assessed by immunohistochemistry in tissues from 137 patients with hepatocellular carcinoma. Prognostic value of intratumoral, marginal, and peritumoral macrophage densities was evaluated by Kaplan-Meier analysis and Cox regression. Both intratumoral and marginal macrophage densities were associated inversely with overall survival ( P = .034 and .004, respectively) and disease-free survival ( P = .006 and .008, respectively). In contrast, peritumoral macrophage density was associated with neither overall survival nor disease-free survival. Intratumoral macrophage density emerged as an independent prognosticator of overall survival (hazard ratio = 1.721, P = .049) and disease-free survival (hazard ratio = 2.165, P = .007). Marginal macrophage density, but not intratumoral macrophage density, was associated with vascular invasion, tumor multiplicity, and fibrous capsule formation. Our results demonstrate that high macrophage infiltration predicts poor prognosis in patients with hepatocellular carcinoma. These results, together with our previous report showing the distinct activation patterns of macrophages in different areas of tumor tissue, implies that macrophages in those areas may use different strategies to promote the tumor progression.
Summary Mammary analogue secretory carcinoma (MASC) of salivary glands is a newly recognized tumor entity. To explore a more practical and convenient immunohistochemical approach to distinguish MASC ...from other tumors arising from salivary glands as well as to expand the immunologic and genetic lineage of MASC, we examined 17 MASC using clinicopathologic, immunohistochemical and molecular analysis. 18 cases of acinic cell carcinoma (AciCC), 18 cases of adenoid cystic carcinoma (ACC), 22 cases of mucoepidermoid carcinoma (MEC), and 14 cases of basal cell adenocarcinoma (BCA) were brought in for comparison. 17 MASC not only shared similar architectures with intraluminal or intracellular secretion but also low-grade vesicular nuclei. In addition, they were all immunoreactive for S-100 and SOX-10, while only 3 of 17 demonstrated reactivity for GATA-3, P63, and 4 of 17 were focally positive for CD117. ETV6 translocation was detected in 10 cases by fluorescence in situ hybridization (FISH), whereas intact ETV6 was noted in 2 cases. Our data proposed a combined immunohistochemical panel to distinguish MASC from other tumors arising from salivary glands and expanded the immunologic and genetic lineage of MASC.
Background The epidemic of obesity has been paralleled by an increase in the incidence of chronic kidney disease. However, epidemiological data for obesity-related glomerulopathy (ORG) from ...developing countries, including China, are very limited. Study Design Case series. ORG defined as body mass index (BMI) of 28.0 kg/m2 or greater; urinary protein excretion of 0.4 g/24 h or greater, and glomerulomegaly (glomerular volume > 3.27 × 106 μm3 ) with or without focal segmental glomerulosclerosis (FSGS). Setting & Participants 10,093 renal biopsy samples from patients obtained from February 2002 to November 2006 at the Research Institute of Nephrology, Nanjing University School of Medicine, China. Predictor Obesity defined as a BMI of 28.0 kg/m2 or greater. Subjects were divided into 3 groups: mild-obesity group with BMI of 28.0 to less than 30 kg/m2 , moderate-obesity group with BMI of 30 to less than 35 kg/m2 , and severe-obesity group with BMI of 35 kg/m2 or greater. Outcomes & Measurements Clinicoepidemiological and histopathologic characteristics of patients with ORG at the time of biopsy were described separately. Results ORG was observed in 90 biopsy specimens (0.89%); frequency increased from 0.62% to 1.0% during the last 5 years ( P = 0.02). Mean age was 37.5 ± 9.3 (SD) years, 67% were men, mean BMI was 31.2 ± 3.3 kg/m2 , waist circumference was 103 cm (range, 89.4 to 124 cm) in men and 96.5 cm (range, 88.5 to 113 cm) in women, waist-hip ratio was 0.95 ± 0.07, and 100% had visceral obesity. Of the total, 49%, 37%, and 14% had mild, moderate, and severe obesity, respectively. Mean urinary protein excretion of subjects was 1.48 ± 1.2 g/24 h; 51%, 39%, and 10% had proteinuria with protein of 0.4 to 1.0, 1.0 to 3.5, and greater than 3.5 g/d, respectively. Mean measured creatinine clearance (Ccr) was 109 ± 32.2 mL/min/1.73 m2 , with 42%, 36%, and 22% with a Ccr greater than 120, 90 to 120, and less than 90 mL/min/1.73 m2 , respectively. Glucose dysmetabolism, insulin resistance, dyslipidemia, and hypertension were observed in 77%, 88%, 76%, and 63% of patients, respectively. FSGS was observed in 70%. Mean foot-process width was 534 ± 176 nm. Foot-process fusion was seen in 36% of patients. Greater BMI was associated with greater proteinuria ( P < 0.02), greater Ccr ( P < 0.03), and greater foot-process width ( P < 0.04). Limitations Inability to compute prevalence or incidence from case series. BMI was calculated at time of renal biopsy. Conclusions Most patients with ORG had mild obesity, visceral obesity, minor proteinuria, preserved Ccr, and FSGS.
This study aims to test the lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity in patients with chronic kidney disease (CKD) and to analyze their connection of Lp-PLA2 with the ...development of disease and with the occurrence of atherosclerosis in this population.
In total, 59 patients older than 18 years and with a diagnosis of CKD were recruited. Kidney function was evaluated by serum creatinine, serum urea and estimated glomerular filtration rate according to Chronic Kidney Disease Epidemiology Collaboration formula and clinical data were collected. A total of 24 healthy volunteers served as healthy controls. Lp-PLA2 mass is measured by enzyme-linked immunosorbent assay. Lp-PLA2 activity is determined by an enzymatic platelet-activating factor acetylhydrolase assay.
Serum mass and activity of Lp-PLA2 were higher in patients with CKD compared with healthy controls (P < 0.001 and P = 0.031). There was a positive linear relationship betweenLp-PLA2 mass and activity in the patients with CKD (r = 0.586, P < 0.001). The similar result was observed in the healthy controls (r = 0.585, P = 0.003). However, the ratio of Lp-PLA2 mass to activity in the patients with CKD was significantly higher than those of healthy controls (P < 0.001). Lp-PLA2 mass and activity were correlated with low-density lipoprotein (r = 0.366 and r = 0.303, P = 0.004 and P = 0.02).
Lp-PLA2 mass and activity increase in patients with CKD. Elevated mass and activity of Lp-PLA2 related to inflammation and atherosclerosis may take part in the development of kidney injury and atherosclerosis in patients with CKD.
Objective Proanthocyanidins are abundantly found in grape seeds and have been suggested to inhibit the pathogenesis of systemic diseases. We investigated the antithrombotic effects of ...proanthocyanidins in a rat model of deep vein thrombosis (DVT) and examined the underlying mechanisms. Methods DVT was induced in rat model by inferior vena cava (IVC) ligation. Grape seed proanthocyanidins extract (GSPE, 400 mg/kg/d) dissolved in saline (2 mL) was orally administered to the experimental rats. Control rats were administrated saline (2 mL) only. The thrombi were harvested and weighed. The IVC was analyzed histologically and by transmission electron microscopy. The cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. Expression of cellular adhesion molecules (CAMs) in thrombi was examined by Western blot. Results GSPE significantly reduced thrombus length and weight ( P < .01) and protected the integrity of the endothelium. GSPE inhibited thrombogenesis-promoting factors P-selectin, von Willebrand factor, and CAMs, and promoted thrombogenesis-demoting factors CD34, vascular endothelial growth factor receptor-2, and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type one motif, member 13). Compared with the control, GSPE significantly lowered the cytokines IL-6 (74.19 ± 13.86 vs 189.54 ± 43.76 pg/mL; P < .01), IL-8 (80.71 ± 21.42 vs 164.56 ± 39.54 pg/mL; P < .01), and TNF-α (43.11 ± 17.58 vs 231.84 ± 84.11 pg/mL; P < .01). Conclusions GSPE significantly inhibited the propagation of thrombus induced by IVC ligation in a rat model. The antithrombotic properties of proanthocyanidins are likely to be directly associated with endothelial protection and regeneration, platelet aggregation, and inhibition of inflammatory cell and thrombus adhesion. Thus, proanthocyanidins may have a clinical application in DVT treatment.
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