Background Abelmoschus manihot , a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess ...its efficacy and safety in patients with primary glomerular disease. Study Design Prospective, open-label, multicenter, randomized, controlled, clinical trial. Setting & Participants From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. Interventions A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50 mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50 mg/d. The duration of intervention was 24 weeks. Outcomes & Measurements The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. Results Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot , losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2 , respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of −508, −376, and −545 mg/d, respectively ( P = 0.003 for A manihot vs losartan and P < 0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups ( P > 0.05), and there were no severe adverse events in any group. Limitations Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. Conclusions A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.
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.
Background In a previous study of Chinese patients with idiopathic pulmonary arterial hypertension (IPAH) in the nontargeted therapy era (defined as the time before 2006 when new pulmonary arterial ...hypertension-specific drugs were not available in China), we reported 1- and 3-year survival estimates of only 68% and 39%, respectively. However, it is not yet known whether the survival of patients with pulmonary arterial hypertension is improved in the modern treatment era (defined in China as after 2006). Methods A retrospective cohort study was undertaken in 276 consecutive patients with newly diagnosed incident IPAH and connective tissue disease-related pulmonary arterial hypertension (CTDPAH) who were referred between 2007 and 2009. Baseline characteristics and survival rates in the two groups were compared. Results The 1- and 3-year survival estimates were 92.1% and 75.1%, respectively, in patients with IPAH, and 85.4% and 53.6%, respectively, in patients with CTDPAH. Patients with CTDPAH had a significantly lower mean pulmonary artery pressure, more pericardial effusion, and more severe impairment of the diffusion capacity of the lung for carbon monoxide than patients with IPAH. A diagnosis of CTDPAH, World Health Organization functional class III or IV, single-breath diffusion capacity of the lung for carbon monoxide < 80% predicted, and the presence of pericardial effusion were independent predictors of mortality. The 1- and 3-year survival rates of male patients were 93.5% and 77.5%, respectively, in those with IPAH, and 71.1% and 47.4%, respectively, in those with CTDPAH. Conclusions The survival rates of patients with pulmonary arterial hypertension have improved in China in the modern treatment era, despite the high costs of treatment and financial constraints. However, the survival rates of patients with CTDPAH are inferior to those of patients with IPAH. Our study also indicates poorer survival rates in male patients with CTDPAH.
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 Locally produced IgE contributes to the initiation and development of eosinophilic inflammation in eosinophilic nasal polyps independent of systemic atopy. However, whether CXCR5+ CD4+ T ...follicular helper (TFH ) cells are involved in local IgE production at mucosal sites remains unexplored. Objective We sought to explore the presence, phenotype, and function of CXCR5+ CD4+ TFH cells in eosinophilic nasal polyp tissues compared with noneosinophilic nasal polyp and control normal nasal tissues. Methods TFH cell-surface phenotypes and subsets and B-cell subsets in nasal tissues and peripheral blood were studied by means of flow cytometry. Immunohistochemistry was used to detect the tissue location of TFH cells. Sorted nasal TFH cells and CXCR5− T cells were cultured with autologous naive B cells purified from blood. Results Nasal TFH cells expressed inducible costimulator, programmed cell death protein 1, and the transcription factor B-cell lymphoma 6 (Bcl-6) at an intermediate level when compared with bona fide TFH cells in tonsils and circulating TFH cells. Although counts of total TFH cells and IL-21+ , IFN-γ+ , and IL-17+ TFH cells were increased in both eosinophilic and noneosinophilic nasal polyp tissues compared with those in normal nasal tissues, IL-4+ TFH cell counts were only increased in eosinophilic polyp tissues. IL-4 and IL-21 were involved in polyp TFH cell–induced IgE production from naive B cells, and nasal IL-4+ TFH cell counts correlated highly with local IgE levels in vivo . IL-4+ Bcl-6+ CD4+ TFH cells were identified in ectopic lymphoid structures in eosinophilic nasal polyps. TFH cells also positively correlated with germinal center B cells and plasma cells in nasal tissues. Conclusion Nasal IL-4+ TFH cells might be involved in local IgE production in eosinophilic nasal polyps.
Background Xuezhikang (XZK) is an extract of fermented red yeast rice that has lipid-lowering properties. Objective To evaluate the effects of XZK on lipids in subjects with dyslipidemia but no ...coronary heart disease. Methods A total of 116 adults with baseline non−high-density lipoprotein cholesterol (non−HDL-C) levels of approximately 208 mg/dL and low-density lipoprotein cholesterol (LDL-C) levels of approximately 175 mg/dL were randomized to either placebo or XZK 1200 or 2400 mg daily and treated for 12 weeks. Results A majority of the patients were white (53.4%) or Asian (37.1%). Daily XZK 1200 mg and 2400 mg for 4 to 12 weeks resulted in statistically significant ( P < .001) and clinically meaningful decreases in non−HDL-C (∼24% reduction) and LDL-C (∼27% reduction) compared with placebo. XZK treatment at either dose enabled approximately 50% of subjects to reduce their LDL-C levels by ≥ 30%. Doubling the XZK daily dose from 1200 to 2400 mg at treatment week 8 caused an additional 4.6% reduction in LDL-C. Significant benefits were also observed across secondary efficacy variables, including total cholesterol (TC), apolipoprotein B (Apo B), triglycerides, HDL-C, the TC/HDL-C ratio, and the Apo B/Apo A-I ratio, at treatment week 8 or 12. XZK was safe and well tolerated. Safety and tolerability profiles were similar across treatment groups. Most adverse events were gastrointestinal. No subject experienced myopathy or markedly elevated liver transaminases or creatine kinase. Conclusion Xuezhikang significantly reduced non−HDL-C and LDL-C, and was well tolerated. Further, longer-term studies in more diverse patient populations are needed to corroborate these findings.
To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of ...nasopharyngeal carcinoma (NPC).
Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis-free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared.
Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis-free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging.
Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease.
Summary Background The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is ...unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. Methods We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III–IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18–59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m2 on day 1), intravenous cisplatin (60 mg/m2 on day 1), and continuous intravenous fluorouracil (600 mg/m2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov , number NCT01245959. Findings Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38–49), 3-year failure-free survival was 80% (95% CI 75–85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66–78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48–0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 42% vs 17 7%), leucopenia (98 41% vs 41 17%), and stomatitis (98 41% vs 84 35%). Interpretation Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. Funding Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).
The aim of this study was to analyze a single institution's experience in the clinical management of intraoral lymphoepithelial cyst (LEC).
From 1993 to 2010, a total of 120 consecutive patients with ...intraoral LEC underwent surgery and were retrospectively investigated regarding its clinical appearance, clinical differential diagnosis, treatment, and prognosis.
Of the 120 patients, 37 were male and 83 female, their ages ranging from 2 to 75 years with a mean of 44.1 years. The most common locations were the tongue (50%) and floor of mouth (38.3%). The course of disease ranged from 2 months to 10 years with a mean of 8.0 months, and 75.8% of the patients had a course of disease <6 months. Routine laboratory examinations were within normal limits. All patients underwent complete surgical removal of the lesions. During the follow-up period, no lesion recurrence occurred, and the quality of life of each patient was good.
The clinical characteristics of intraoral LEC are not specific and may be confused with other intraoral lesions. The first choice of treatment is surgical excision, which results in a good prognosis.
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