Simplified Rapid Hydration Prevents Contrast-Associated Acute Kidney Injury Among CKD Patients Undergoing Coronary Angiography.

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.

A Double-Blind Randomized Placebo-Controlled Phase 3 Trial of Tobramycin Inhalation Solution in Adults With Bronchiectasis With Pseudomonas aeruginosa Infection.

BACKGROUND: Few large-scale studies have demonstrated the efficacy of tobramycin nebulization in bronchiectasis. We evaluated the efficacy and safety of nebulized tobramycin inhalation solution (TIS) in adults with bronchiectasis with Pseudomonas aeruginosa infection. RESEARCH QUESTION: Can TIS effectively reduce sputum P aeruginosa density and improve the bronchiectasis-specific quality of life in patients with bronchiectasis with P aeruginosa infection? STUDY DESIGN AND METHODS: This was a phase 3, 16-week, multicenter, randomized, double-blind, placebo-controlled trial. Eligible adults with bronchiectasis were recruited from October 2018 to July 2021. On the basis of usual care, patients nebulized TIS (300 mg/5 mL twice daily) or normal saline (5 mL twice daily) via vibrating-mesh nebulizer. Treatment consisted of two cycles, each consisting of 28 days on-treatment and 28 days off-treatment. The coprimary end points included changes from baseline in P aeruginosa density and Quality-of-Life Bronchiectasis Respiratory Symptoms score on day 29. RESULTS: The modified intention-to-treat population consisted of 167 patients in the tobramycin group and 172 patients in the placebo group. Compared with placebo, TIS resulted in a significantly greater reduction in P aeruginosa density (adjusted mean difference, 1.74 log10 colony-forming units/g; 95% CI, 1.12-2.35; P < .001) and greater improvement in Quality-of-Life Bronchiectasis Respiratory Symptoms score (adjusted mean difference, 7.91; 95% CI, 5.72-10.11; P < .001) on day 29. Similar findings were observed on day 85. TIS resulted in a significant reduction in 24-h sputum volume and sputum purulence score on days 29, 57, and 85. More patients became culture negative for P aeruginosa in the tobramycin group than in the placebo group on day 29 (29.3% vs 10.6%). The incidence of adverse events and serious adverse events were comparable between the two groups. INTERPRETATION: TIS is an effective treatment option and has an acceptable safety profile in patients with bronchiectasis with P aeruginosa infection. TRIAL REGISTRATION: ClinicalTrials.gov; No. NCT03715322; URL: www. CLINICALTRIALS: gov.

Hydration for prevention of kidney injury after primary coronary intervention for acute myocardial infarction: a randomised clinical trial.

OBJECTIVE: To evaluate the efficacy of aggressive hydration compared with general hydration for contrast-induced acute kidney injury (CI-AKI) prevention among patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). METHODS: The Aggressive hydraTion in patients with STEMI undergoing pPCI to prevenT Contrast-Induced Acute Kidney Injury study is an open-label, randomised controlled study at 15 teaching hospitals in China. A total of 560 adult patients were randomly assigned (1:1) to receive aggressive hydration or general hydration treatment. Aggressive hydration group received preprocedural loading dose of 125/250 mL normal saline within 30 min, followed by postprocedural hydration performed for 4 hours under left ventricular end-diastolic pressure guidance and additional hydration until 24 hours after pPCI. General hydration group received ≤500 mL 0.9% saline at 1 mL/kg/hour for 6 hours after randomisation. The primary end point is CI-AKI, defined as a >25% or 0.5 mg/dL increased in serum creatinine from baseline during the first 48-72 hours after primary angioplasty. The safety end point is acute heart failure. RESULTS: From July 2014 to May 2018, 469 patients were enrolled in the final analysis. CI-AKI occurred less frequently in aggressive hydration group than in general hydration group (21.8% vs 31.1%; risk ratio (RR) 0.70, 95% CI 0.52 to 0.96). Acute heart failure did not significantly differ between the aggressive hydration group and the general hydration group (8.1% vs 6.4%, RR 1.13, 95% CI 0.66 to 2.44). Several subgroup analysis showed the better effect of aggressive hydration in CI-AKI prevention in male, renal insufficient and non-anterior myocardial infarction participants. CONCLUSIONS: Comparing with general hydration, the peri-operative aggressive hydration seems to be safe and effective in preventing CI-AKI among patients with STEMI undergoing pPCI.

Perioperative intravenous S(+)-ketamine for acute postoperative pain in adults: study protocol for a multicentre, randomised, open-label, positive-controlled, pragmatic clinical trial (SAFE-SK-A trial).

INTRODUCTION: Postoperative pain remains incompletely controlled for decades. Recently, multimodal analgesia is emerging as a potential approach in the management of postoperative pain. Therein, S(+)-ketamine is appealing as an adjuvant drug in multimodal analgesia due to its unique pharmacological advantages. This pragmatic clinical trial (SAFE-SK-A trial) is designed to investigate the analgesic effect and safety of S(+)-ketamine for acute postoperative pain in adults and explore the optimal strategy of perioperative intravenous S(+)-ketamine in a real-world setting. METHODS AND ANALYSIS: This multicentre, randomised, open-label, positive-controlled, pragmatic clinical trial (SAFE-SK-A study) is planned to conduct in 80 centres from China and recruit a total of 12 000 adult participants undergoing a surgical procedure under general anaesthesia. Patient recruitment started in June 2021 and will end in June 2022. Participants will be randomised in a ratio of 2:1 to either receive perioperative intravenous S(+)-ketamine plus conventional anaesthesia or conventional anaesthesia only. Given the pragmatic nature of the study, no specific restriction as to the administration dosage, route, time, synergistic regimen or basic analgesics. Primary endpoints are the area under the broken line of Numerical Rating Scale (NRS) scores for pain intensity and the total opioid consumption within 48 hours postoperative. Secondary endpoints are postoperative NRS scores, the anaesthesia recovery time, time of first rescue analgesia, the incidence of rescue analgesia, the incidence of postoperative delirium, patient questionnaire for effect, changes from baseline in cognitive function and anxiety and depression, as well as the adverse events and pharmacoeconomic outcomes. The general linear model will be used for the primary endpoint, and appropriate methods will be used for the secondary endpoints. ETHICS AND DISSEMINATION: This trial has been approved by the local Institutional Review Board (S2021-026-02) and conducted following the Declaration of Helsinki. Results of this trial will be publicly disclosed and published in scientific journals. TRIAL REGISTRATION NUMBER: NCT04837170; Pre-results.

Effect of Recombinant Human Granulocyte Colony-Stimulating Factor for Patients With Coronavirus Disease 2019 (COVID-19) and Lymphopenia: A Randomized Clinical Trial.

Importance: Lymphopenia is common and correlates with poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether a therapy that increases peripheral blood leukocyte and lymphocyte cell counts leads to clinical improvement in patients with COVID-19. Design, Setting and Participants: Between February 18 and April 10, 2020, we conducted an open-label, multicenter, randomized clinical trial at 3 participating centers in China. The main eligibility criteria were pneumonia, a blood lymphocyte cell count of 800 per µL (to convert to ×109/L, multiply by 0.001) or lower, and no comorbidities. Severe acute respiratory syndrome coronavirus 2 infection was confirmed with reverse-transcription polymerase chain reaction testing. Exposures: Usual care alone, or usual care plus 3 doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF, 5 µg/kg, subcutaneously at days 0-2). Main Outcomes and Measures: The primary end point was the time from randomization to improvement of at least 1 point on a 7-category disease severity score. Results: Of 200 participants, 112 (56%) were men and the median (interquartile range [IQR]) age was 45 (40-55) years. There was random assignment of 100 patients (50%) to the rhG-CSF group and 100 (50%) to the usual care group. Time to clinical improvement was similar between groups (rhG-CSF group median of 12 days (IQR, 10-16 days) vs usual care group median of 13 days (IQR, 11-17 days); hazard ratio, 1.28; 95% CI, 0.95-1.71; P = .06). For secondary end points, the proportion of patients progressing to acute respiratory distress syndrome, sepsis, or septic shock was lower in the rhG-CSF group (rhG-CSF group, 2% vs usual care group, 15%; difference, -13%; 95%CI, -21.4% to -5.4%). At 21 days, 2 patients (2%) had died in the rhG-CSF group compared with 10 patients (10%) in the usual care group (hazard ratio, 0.19; 95%CI, 0.04-0.88). At day 5, the lymphocyte cell count was higher in the rhG-CSF group (rhG-CSF group median of 1050/µL vs usual care group median of 620/µL; Hodges-Lehmann estimate of the difference in medians, 440; 95% CI, 380-490). Serious adverse events, such as sepsis or septic shock, respiratory failure, and acute respiratory distress syndrome, occurred in 29 patients (14.5%) in the rhG-CSF group and 42 patients (21%) in the usual care group. Conclusion and Relevance: In preliminary findings from a randomized clinical trial, rhG-CSF treatment for patients with COVID-19 with lymphopenia but no comorbidities did not accelerate clinical improvement, but the number of patients developing critical illness or dying may have been reduced. Larger studies that include a broader range of patients with COVID-19 should be conducted. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000030007.

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

Clinical Characteristics of Coronavirus Disease 2019 in China.

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).

Effects of ambient temperature on ambulance emergency call-outs in the subtropical city of Shenzhen, China.

The associations between meteorological factors and mortality have been well documented worldwide, but limited evidence is available for the non-fatal health impacts of ambient temperature, particularly there are few population-based investigations on the impacts of emergency ambulance dispatches in Asia. In this study, based on 809,906 ambulance emergency call-outs (AECOs) for the total population from 2010-2016 in the subtropical city of Shenzhen, China, a Poisson regression combined with a distributed lag nonlinear model was used to simultaneously assess the nonlinear and lag effects of daily mean temperature on AECOs. Stratified analyses by age and sex were performed to identify vulnerable subpopulations. A U-shaped relationship was found between temperature and AECOs. Cold effects were delayed and persisted for 3-4 weeks, with a cumulative relative risk (RR) and 95% confidence interval (CI) of 1.23 (1.10-1.38) and 1.25 (1.16-1.35) over lag 0-28 when comparing the 1st and 5th percentile of the temperature distribution to the optimal (i.e. minimum AECOs) temperature, respectively. Hot effects were immediate and diminished quickly in 5 days, with an increase of 19% (RR = 1.19, 95%CI: 1.14-1.23) and 21% (RR = 1.21, 95%CI: 1.16-1.26) in AECOs over lag 0-5 when comparing the 95th and 99th percentile of temperature to the optimal temperature. Children and the elderly were more vulnerable to cold effects. The youth and middle-aged people suffered more from high temperature. The effects of temperature were similar between males and females. In summary, significant increases were observed in the frequency of AECOs during cold and hot days, and the weather-associated increases in AECOs are different among age groups. This information has valuable implications in ambulance demand prediction and service provision planning.

Optimal hydration volume among high-risk patients with advanced congestive heart failure undergoing coronary angiography.

We investigated the relationship between weight-adjusted hydration volumes and the risk of developing contrast-induced acute kidney injury (CI-AKI) and worsening heart failure (WHF) and explored the relative safety of optimal hydration volumes in patients with advanced congestive heart failure (CHF) undergoing coronary angiography (CAG) or percutaneous coronary intervention. We included 551 patients with advanced CHF (New York Heart Association class > 2 or history of pulmonary edema) undergoing CAG (follow-up period 2.62 ± 0.9 years). There was a significant association between hydration volume-to-weight ratio (HV/W) (quintile Q1, Q2, Q3, Q4, and Q5) and the incidence of CI-AKI (3.7%, 14.6%, 14.3%, 21.1%, and 31.5%, respectively) and WHF (3.6%, 5.4%, 8.3%, 13.6%, and 19.1%, respectively) (all P-trend < 0.001). Receiver operating curve analysis indicated that HV/W = 15 mL/kg and the mean HV/W (60.87% sensitivity and 64.96% specificity) were fair discriminators for CI-AKI (C-statistic 0.696). HV/W >15 mL/kg independently predicted CI-AKI (adjusted odds ratio [OR] 2.33; P = 0.016) and WHF (adjusted OR 2.13; P = 0.018). Moreover, both CI-AKI and WHF were independently associated with increased long-term mortality. Thus, for high-risk patients with advanced CHF undergoing CAG, HV/W > 15 mL/kg might be associated with an increased risk of developing CI-AKI and WHF. The potential benefits of a personalized limitation of hydration volume need further evaluation.

Correction: Predictive value of post-procedural early (within 24 h) increase in cystatin C for contrast-induced acute kidney injury and mortality following coronary angiography or intervention.

[This corrects the article DOI: 10.18632/oncotarget.19034.].

Association of post-procedural early (within 24h) increases in serum creatinine with all-cause mortality after coronary angiography.

BACKGROUND: The majority of patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) are discharged early, with only early (within 24h) serum creatinine (SCr) data available without evidence of clinical prognosis. We aimed to systemically evaluate the association between post-procedural early increase in SCr and all-cause mortality following CAG. METHODS: We performed a retrospective sub-study analysis within a prospective observational study including 3091 consecutive patients with baseline and post-procedural early (within 24h) SCr data. The degree (mild, moderate, or large) of absolute and relative increases in SCr from baseline. The mean follow-up time was 2.49years. RESULT: Moderate or large early increases in SCr were relatively rare (large increase: >1.0mg/dl [0.5%], >100% [0.4%]), whereas mild absolute and relative increases in SCr were more common (mild increase: 0.25 to 0.50mg/dl [4.5%], 25% to 50% [5.9%]). During the follow-up period, there were 136 post-procedural deaths (5.6%). After adjustment for confounders, mild absolute and relative increases in SCr were associated with increased mortality (hazard ratio [HR]: 1.9 and 1.8, respectively, both P<0.05). Moderate or large increases in SCr were associated with higher mortality, even higher than with pre-existing renal dysfunction (HR: 5.36 and 4.12 for moderate increase [0.5 to 1.0mg/dl] and estimated glomerular filtration rate<60ml/min). CONCLUSION: Post-procedural mild, moderate, or large early increase in SCr, is associated with significantly increased long-term mortality. Although moderate or large increase in SCr following CAG was relatively rare, the prognosis is more serious, and is worse than that of pre-existing renal dysfunction. CLINICAL TRIAL REGISTRATION: Predictive Value of Contrast Volume to Creatinine Clearance Ratio (PRECOMIN, ClinicalTrials.govNCT01400295).

Comparing common doses (double-dose vs usual-dose) of atorvastatin for preventing contrast-induced acute kidney injury and mortality after coronary angiography.

High-dose atorvastatin pretreatment was proved reducing the risk of contrast-induced acute kidney injury (CI-AKI), especially in patients with high C-reactive protein (CRP) levels. We evaluated the effects of common atorvastatin doses (double vs usual) on the risk of CI-AKI and mortality.We recorded outcomes from 1319 patients who were administered periprocedural common doses of atorvastatin. The risks of CI-AKI and mortality between double-dose (40 mg/d) and usual-dose atorvastatin (20 mg/d) were compared using multivariable regression models in all patients or CRP tertile subgroups.Seventy-six (5.8%) patients developed CI-AKI. Double-dose atorvastatin compared with usual-dose did not further reduce the risk of CI-AKI (adjusted odds ratio [OR]: 2.28, 95% confidence interval [CI]: 0.92-5.62, P = .074), even for patients in the highest CRP tertile (>8.33 mg/L; adjusted OR: 3.76, 95% CI: 0.83-17.05, P = .086). Similar results were observed in reducing mortality in all patients (adjusted hazard ratio: 0.47, 95% CI: 0.10-2.18; P = .339) and in the highest CRP tertiles (P = .424). In the subgroup analysis, double-dose atorvastatin increased risk of CI-AKI in patients with creatinine clearance (CrCl) < 60 mL/min, anemia, contrast volume > 200 mL and > 2 stents implanted (P = .046, .009, .024, and .026, respectively).Daily periprocedural double-dose atorvastatin was not associated with a reduced risk of CI-AKI compared with usual-dose, and did not provide an improved long-term prognosis, even in patients with high CRP levels. However, it increased the risk of CI-AKI in patients with a high contrast volume/CrCl.

Predictive value of post-procedural early (within 24 h) increase in cystatin C for contrast-induced acute kidney injury and mortality following coronary angiography or intervention.

OBJECTIVE: To investigate the predictive value of post-procedural early (within 24 h) increase in cystatin C for contrast-induced acute kidney injury (CI-AKI) and all-cause mortality following coronary angiography or intervention. METHODS: We prospectively investigated 1042 consecutive patients with both baseline and early post-procedural cystatin C measurement undergoing coronary angiography or intervention. CI-AKI was defined as an increase ≥0.3 mg/dL or >50% in serum creatinine from baseline within 48 h post-procedure. Mean follow-up was 2.26 years. RESULTS: Overall, the patients had a CI-AKI incidence was 3.6% (38/1042), mean serum creatinine of 87 µmol/L. Compared with Mehran risk score, post-procedural early absolute increase (AUC: 0.584 vs. 0.706, P = 0.060) and relative increase (AUC: 0.585 vs. 0.706, P = 0.058) in cystatin C had poorer predictive value for CI-AKI. According to multivariate analysis, post-procedural significant early increase (≥0.3 mg/dL or ≥10%) in cystatin C developed in 231 patients (22.2%), was not independent predictor of CI-AKI (adjusted OR: 1.23, 95% CI, 0.56-2.69, P = 0.612), and long-term mortality (adjusted HR: 0.90; P = 0.838). CONCLUSIONS: Our data suggested post-procedural early increase (within 24 h) in cystatin C was not effective for predicting CI-AKI or all-cause mortality following coronary angiography or intervention among patients at relative low risk of CI-AKI, the negative finding of poor predictive value should be further evaluated in larger multicenter trials.

Could late measurement of serum creatinine be missed for patients without early increase in serum creatinine following coronary angiography?

Most patients are discharged early (within 24 hours) after coronary angiography (CAG) and may miss identification the late (24-48 hours) increase in serum creatinine (SCr), whose characteristics and prognosis have been less intensively investigated.We prospectively recruited 3065 consecutive patients with SCr measurement, including only1344 patients with twice SCr measurement (both early and late). The late contrast-induced acute kidney injury (CI-AKI) was defined as significantly increase in SCr (≥0.3 mg/dL or ≥50%) not in early phase, but only in late phase after the procedure, and the early CI-AKI experienced a significantly increase in early phase.Overall, CI-AKI developed in 134 patients (10%), and the incidence of late and early CI-AKI were 3.6% and 6.4%, respectively. There were no difference in age, renal, and heart function, contrast volume among patients with late and early CI-AKI. With mean follow-up period of 2.45 years, long-term mortality (3 years, 29.7% and 35.6%, respectively, P = .553) was similar for patients with late and early CI-AKI. Cox analysis showed that both late (adjusted HR 2.05; 95% CI, 1.02-4.15) and early (adjusted HR 2.68; 95% CI, 1.57-4.59) CI-AKI was significantly associated with long-term mortality (all P < .001).Only late increase in SCr, as late CI-AKI, accounted for about one-third of CI-AKI incidence and has similar good predictive value for long-term mortality with that of an early increase, early CI-AKI, among patients with SCr measured twice, supporting the importance of late repeating SCr measurement after CAG, even without an early significant increase in SCr.

Preprocedural High-Sensitivity C-Reactive Protein Predicts Contrast-Induced Nephropathy and Long-Term Outcome After Coronary Angiography.

We investigated whether high-sensitivity C-reactive protein (hsCRP) levels were associated with contrast-induced nephropathy (CIN) and long-term mortality after coronary angiography (CAG). Patients (N = 2133) undergoing CAG with preprocedural hsCRP were consecutively enrolled. High-sensitivity C-reactive protein was measured before angiography. Median follow-up was 2.3 years. The overall incidence of CIN was 2.77% (59 of 2133). There was a positive trend of hsCRP quartiles (Q) with rates of CIN: 0.9% for Q1 (<1.6 mg/L), 0.9% for Q2 (1.6-3.9 mg/L), 2.4% for Q3 (4.0-11.3mg/L), and 6.8% for Q4 (>11.3 mg/L; P < .05). The receiver operating characteristic (ROC) analysis showed that the cutoff point of hsCRP was 7.3 mg/L for predicting CIN with a 72.7% sensitivity and a 67.0% specificity (area under the curve [AUC] = 0.742, 95% confidence interval [CI] 0.672-0.810; P < .05). The predictive value of hsCRP was similar to the Mehran score for CIN (AUChsCRP = 0.742 vs AUCMehran = 0.801; P = .228). After adjustment for other potential risk factors, hsCRP >7.3 mg/L still was an independent predictor of CIN (odds ratio [OR] = 2.83, 95% CI: 1.44-5.58; P = .003). Furthermore, hsCRP >7.3 mg/L was associated with higher mortality (OR = 2.04, 95% CI: 1.30-3.19; P = .002).

Development and Validation of a Risk Score for Prediction of Acute Kidney Injury in Patients With Acute Decompensated Heart Failure: A Prospective Cohort Study in China.

BACKGROUND: Although several risk factors for acute kidney injury (AKI) have been identified, early detection of AKI in acute decompensated heart failure patients remains a challenge. The aim of this study was to develop and validate a risk score for early prediction of AKI in acute decompensated heart failure patients. METHODS AND RESULTS: A total of 676 consecutive acute decompensated heart failure participants were prospectively enrolled from 6 regional central hospitals. Data from 507 participants were analyzed. Participants from 4 of the 6 hospitals (n=321) were used to develop a risk score and conduct internal validation. External validation of the developed risk score was conducted in participants from the other 2 hospitals (n=186). Sequential logistic regression was used to develop and validate the risk score. The c statistic and calibration plot were used to assess the discrimination and calibration of the proposed risk score. The overall occurrence of AKI was 33.1% (168/507). The risk score, ranging from 0 to 55, demonstrated good discriminative power with an optimism-corrected c statistic of 0.859. Similar results were obtained from external validation with c statistic of 0.847 (95% CI 0.819-0.927). The risk score had good calibration with no apparent over- or under-prediction observed from calibration plots. CONCLUSIONS: The novel risk score is a simple and accurate tool that can help clinicians assess the risk of AKI in acute decompensated heart failure patients, which in turn helps them plan and initiate the most appropriate disease management for patients in time.

Estimating years of life lost from cardiovascular mortality related to air pollution in Guangzhou, China.

Previous studies have mainly used mortality or morbidity as the health outcome to examine the air pollution-health association. Little evidence is available on relationships between air pollutants and years of life lost (YLL). We aimed to estimate the YLL from cardiovascular mortality due to air pollution. Daily data on weather and air pollutants and individual data of all registered deaths for years 2004-2007 were obtained in Guangzhou, China. The generalized additive model was used to assess the YLL associated with 10µg/m3 increases in NO2, SO2 and PM10. We found that the mean daily YLL was 248, 87.5 and 73.7 for deaths from cardiovascular disease (CVD), stroke and ischemic heart disease (IHD), respectively. A significant linear correlation was observed between air pollution and YLL due to cardiovascular disease. The effects of air pollutants on YLL were immediate and lasted for two days. A 10µg/m3 increase above the corresponding threshold of 55.6µg/m3, 40.4µg/m3 and 0µg/m3 in NO2, PM10 and SO2 was related to YLL increase of 1.8 (95% CI: 0.8-2.9), 2.8 (1.7-3.8) and 2.6 (1.2-4.0) years at lag 0-1days for CVD, respectively. The estimates of YLL associated with NO2 and PM10 were higher in men than women. The air pollutants-related YLL was higher among young people and those with low education level, compared to the elderly and those with high education level, respectively. These findings confirmed YLL provides a complementary strategy for assessing the health effect of air pollution. This study underscores the necessity of the reduction of air pollution benefiting public health.

The burden of COPD mortality due to ambient air pollution in Guangzhou, China.

Few studies have investigated the chronic obstructive pulmonary disease (COPD) mortality fraction attributable to air pollution and modification by individual characteristics of air pollution effects. We applied distributed lag non-linear models to assess the associations between air pollution and COPD mortality in 2007-2011 in Guangzhou, China, and the total COPD mortality fraction attributable to air pollution was calculated as well. We found that an increase of 10 µg/m(3) in particulate matter with an aerodynamic diameter of 10 µm or less (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2) was associated with a 1.58% (95% confidence interval (CI): 0.12-3.06%), 3.45% (95% CI: 1.30-5.66%) and 2.35% (95% CI: 0.42-4.32%) increase of COPD mortality over a lag of 0-15 days, respectively. Greater air pollution effects were observed in the elderly, males and residents with low educational attainment. The results showed 10.91% (95% CI: 1.02-9.58%), 12.71% (95% CI: 5.03-19.85%) and 13.38% (95% CI: 2.67-22.84%) COPD mortality was attributable to current PM10, SO2 and NO2 exposure, respectively. In conclusion, the associations between air pollution and COPD mortality differed by individual characteristics. There were remarkable COPD mortality burdens attributable to air pollution in Guangzhou.

Aggressive hydraTion in patients with ST-Elevation Myocardial infarction undergoing Primary percutaneous coronary intervention to prevenT contrast-induced nephropathy (ATTEMPT): Study design and protocol for the randomized, controlled trial, the ATTEMPT, RESCIND 1 (First study for REduction of contraSt-induCed nephropathy followINg carDiac catheterization) trial.

Adequate hydration is recommended for acute ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) to prevent contrast-induced nephropathy (CIN). However, the optimal hydration regimen has not been well established in these high-risk patients. The objective of this study is to evaluate the efficacy of a preprocedural loading dose plus postprocedural aggressive hydration with normal saline guided by the left ventricular end-diastolic pressure (LVEDP) compared with general hydration for CIN prevention. The ATTEMPT study is a multicenter, open-label, investigator-driven, randomized controlled trial in China. Approximately 560 patients with STEMI undergoing primary PCI will be randomized (1:1) to receive either periprocedural general hydration (control group) or aggressive hydration (treatment group). Patients in the control group receive periprocedural general hydration with ≤500 mL normal saline (within 6 hours) at a normal rate (0.5 or 1 mL/kg · h). Patients in the treatment group receive a preprocedural loading dose (125/250 mL) of normal saline within 30 minutes and intravenous hydration at a normal rate until LVEDP is available, followed by postprocedural aggressive hydration guided by LVEDP for 4 hours and then continuous intravascular hydration at the normal rate until 24 hours after PCI. The primary end point is CIN, defined as a >25% or 0.5-mg/dL increase in serum creatinine from baseline during the first 48 to 72 hours after procedure. The ATTEMPT study has the potential to identify optimal hydration regimens for STEMI patients undergoing PCI.

Impact of Timing following Acute Myocardial Infarction on Efficacy and Safety of Bone Marrow Stem Cells Therapy: A Network Meta-Analysis.

Background. The optimal timing for Bone Marrow Stem Cells (BMCs) therapy following acute myocardial infarction (AMI) remains unclear. Aims. To synthesize the evidence from trials using a multiple-treatment comparison method, thereby permitting a broader comparison across multiple timing of BMCs therapy. Methods and Results. Randomized controlled trials in patients with AMI receiving BMCs therapy were identified from PubMed, Ovid LWW, BIOSIS Previews, and the Cochrane Library through January 2015. 2 035 patients of 31 studies included in our analysis were allocated to 5 groups' treatments: 1~3 days, 4~7 days, 8~14 days, 15~30 days, or placebo/control group. The multiple-treatment meta-analysis showed that 4~7 days' group could lead to significantly increased left ventricular ejection fraction (LVEF) as compared with control (mean of MDs and 95% CI: 6 months, 3.05 (0.92~5.25); 12 months, 4.18 (2.30~5.84)). Only 4~7 days led to significant reduction of MACEs compared with control (OR and 95% CI 0.34 (0.13~0.96)) for 12-months follow-up. In simulated comparisons, the 4~7 days' group ranked better than other timing groups for improvement of LVEF or reduction of the incidence of major adverse cardiac events. Conclusions. 4~7 days after AMI might be the optimal timing for cell therapy in terms of efficacy or safety.