Mutations in the perforin gene in children with hemophagocytic lymphohistiocytosis

Background Recent studies have reported germline mutations in the perforin gene （PRF1） in some types of hemophagocytic lymphohistiocytosis （HLH）. However, the prevalence of PRF1 mutations in HLH in Chinese pediatric patients has not been extensively studied. The aim of this study was to investigate the prevalence of mutations and sequence variations in the PRF1 gene in Chinese pediatric patients with HLH. Methods Polymerase chain reaction （PCR） was performed with five pairs of primers for the coding exons and the flanking intron sequences of PRF1. Sequencing of PCR products was subsequently applied in 30 pediatric patients with HLH and in 50 controls. Results Three heterozygous mutations in a coding region were found, which resulted in amino acid changes （C102F, S108N and T450M） in three patients. These mutations were not detected in control subjects. One patient had compound heterozygous mutations （S108N and T450M） in PRF1 as the background defect, and documented familial HLH type 2 （FHL2）. One synonymous sequence variant （Q540Q） was observed in one patient but not in the controls. Two SNPs （A274A, H300H） in the coding region were detected in HLH patients and controls, but without differences in the heterozygosity rate between the two groups （P 〉0.05 for all comparisons）. Conclusions We have identified three patients with three heterozygous missense mutations in PRF1; two of those three mutations （C102F and S108N） have so far been found only from Chinese patients. These findings are useful in evaluating the prevalence of PRF1 mutations in Chinese pediatric patients with HLH, and to correlate their genotype with phenotype. Some patients without familial history probably have primary HLH, which should be suspected even beyond the usual age range.     

Impact of multidisciplinary team working on the management of colorectal cancer

Background  The continual and rapid development of techniques which are used for diagnosis and treatment makes management of colorectal cancer more difficult depending on single discipline. Colorectal cancer multidisciplinary team (MDT) working model is recommended by UK and other countries, but there is little information on the impact of MDT working on management of colorectal cancer in China. The aim of this study was to assess the effect on management of colorectal cancer after the inception of an MDT.

Methods  A total of 595 consecutive colorectal cancer patients were referred to the Department of Gastroenterological Surgery, the pre-MDT cohort include 297 patients, recruited from January 1999 to November 2002, and the MDT cohort had 298 patients enrolled from December 2002 to September 2006. Information recorded included: TNM stage from histological reports, degree of differentiation, the number of examined lymph nodes and CT TNM staging performed or not, and its accuracy, including local and distant recurrence.

Results  The number of examined lymph nodes and the accuracy of TNM staging by CT in the MDT group were significantly more than those in pre-MDT group. CT TNM staging was more accurate in the MDT group compared to the pre-MDT group (P=0.044). The rate of tumor recurrence in the MDT group was lower than pre-MDT group (log-rank test, P <0.001). Multivariate analysis revealed that age (P=0.001), management after inception of the MDT (P=0.002), degree of differentiation (P=0.003), number of examined lymph nodes (P=0.002), and TNM stage (P=0.000) were important factors that independently influence overall survival.

Conclusions  The inception of MDT working improved the diagnostic accuracy and overall survival of colorectal cancer patients. MDT working promoted communication and cooperation between disciplines and ensured high-quality diagnosis, evidence-based decision making, and optimal treatment planning.

     

Evaluation of global and regional left ventricular systolic function in patients with frequent isolated premature ventricular complexes from the right ventricular outflow tract

Background  Frequent premature ventricular complexes from the right ventricular outflow tract (RVOT-PVCs) are associated with left ventricular dysfunction. This study adopted two-dimensional speckle tracking imaging to evaluate global and regional left ventricular myocardial function in patients with frequent RVOT-PVCs.
Methods  This study included 30 patients with frequent RVOT-PVCs and 30 healthy subjects. Aortic systolic velocity-time integral (AoVTI) and myocardium strain in circumferential (CS), radial (RS) and longitudinal (LS) directions were evaluated by conventional echocardiography and speckle tracking imaging. All values of patients with RVOT-PVCs were recorded during sinus (PVC-S) and PVC beats (PVC-V).
Results  Significant differences were demonstrated in global CS, RS and LS between the control subjects and the PVC-V (CS: (17.46±2.48)% vs. (11.52±3.28)%, RS: (48.26±10.20)% vs. (20.92±9.78)%, LS: (19.89±2.62)% vs. (11.79±3.66)%, P <0.01), and in segmental RS and LS of nearly all the left ventricular segments. Statistical differences in segmental CS between the PVC-V and the control subjects were only observed in anterior, anteroseptal and septal segments (only seen in anteroseptal and septal segments at apex). Furthermore, V/S AoVTI (AoVTI during the PVC beat divided by AoVTI during the sinus beat, then multiplied by 100%) correlated with coupling interval (r=0.67, P <0.001) and global strain (CS: r=0.48, P=0.007; RS: r=0.65, P <0.001; LS: r=0.65, P <0.001).
Conclusions  Frequent RVOT-PVCs can induce global and regional left ventricular systolic dysfunction. The reduction of hemodynamic parameters relates to the coupling interval and the global systolic function.

     

Effects of cloned tumstatin-related and angiogenesis-inhibitory peptides on proliferation and apoptosis of endothelial cells

Background Tumstatin is a recently developed endogenous vascular endothelial growth inhibitor that can be applied as an anti-angiogenesis and antineoplastic agent. The study aimed to design and synthesize the small molecular angiogenesis inhibition-related peptide （peptide 21）, to replicate the structural and functional features of the active zone of angiogenesis inhibition using tumstatin and to prove that synthesized peptide 21 has a similar activity： specifically inhibiting tumor angiogenesis like tumstatin. Methods Peptide 21 was designed and synthesized using biological engineering technology. To determine its biological action, the human umbilical vein endothelial cell line ECV304, the human ovarian cancer cell line SKOV-3 and the mouse embryo-derived NIH3T3 fibroblasts were used in in vitro experiments to determine the effect of peptide 21 on proliferation of the three cell lines using the MTT test and growth curves. Transmission electron microscopy （TEM） and flow cytometry （FCM） were applied to analyze the peptide 21-induced apoptosis of the three cell lines qualitatively and quantitatively. In animal experiments, tumor models in nude mice subcutaneously grafted with SKOV-3 were used to observe the effects of peptide 21 on tumor weight, size and microvessel density （MVD）. To initially investigate the role of peptide 21, the effect of peptide 21 on the expression of vascular endothelial growth factors （VEGFs） by tumor tissue was semi-quantitatively analyzed. Results The in vitro Ml-r test and growth curves all indicated that cloned peptide 21 could specifically inhibit ECV304 proliferation in a dose-dependent manner （P 〈0.01）; TEM and FCM showed that peptide 21 could specifically induce ECV304 apoptosis （P 〈0.01）. Results of in vivo experiments showed that tumors in the peptide 21 group grew more slowly. The weight and size of the tumors after 21 days of treatment were smaller than those in the control group （P 〈0.05）, with a mean tumor inhibition rate of 67.86%; MVD     

Comparison of clinical curative effect between open surgery and endovascular repair of abdominal aortic aneurysm in China

Objective   To compare clinical curative effects of open surgery (OS) or endovascular repair (EVAR) for patients with abdominal aortic aneurysm (AAA) in China.

Data sources  We performed a comprehensive search of both English and Chinese literatures involving case studies on retrograde OS or EVAR of AAA in China from January 1976 to December 2010.

Study selection  According to the inclusion criteria, 76 articles were finally analyzed to compare patient characteristics, clinical success, complications, and prognosis.

Results  We analyzed a total of 2862 patients with 1757 undergoing OS (OS group) and 1105 undergoing EVAR (EVAR group). There was no significant difference in the success rate of the procedures. Operative time, length of ICU stay, fasting time, duration of total postoperative stay, blood loss, and blood transfusion requirements during the procedure were significantly lower in the EVAR group. A 30-day follow up revealed more cardiac, renal, pulmonary, and visceral complications in the OS group (P <0.01). Low-limb ischemia, however, was more common in the EVAR group (P <0.05). The 30-day mortality rate, including aorta-related and non-aorta related mortality, was significantly lower in the EVAR group (P <0.01). In the follow-up period, there were more patients with occlusions of artificial vessel and late endoleak in the EVAR group (P <0.01). The overall late mortality rate was higher in the OS group (P <0.01), especially non-aorta-related late mortality and mortality during the fourth to the sixth year (P <0.01).

Conclusions  EVAR was safer and less invasive for AAA patients. Patients suffered fewer complications and recovered sooner. However, complications such as artificial vessel occlusion, low-limb ischemia, and endoleak were common in EVAR. Clinicians should carry out further research to solve these complications and improve the efficacy of EVAR.

     

Ultrasound facilitates identification of combined spinal-epidural puncture in obese parturients

Background  The palpation method is widely used in clinical practice to identify the puncture site of combined spinal-epidural (CSE) blocks, but it is usually difficult to accurately locate the puncture site in obese parturients. Accurate identification of the puncture site is crucial for successful CSE block. The objective of this study was to evaluate the impact of ultrasound imaging on the success rate of CSE puncture in obese parturients.

Methods  Sixty obese parturients with a body mass index ³30 kg/m² who were scheduled for caesarean section were randomized into two equal-sized groups for location of the puncture site: an ultrasound group and a palpation group. The success rate of puncture at the first puncture site, the number of puncture attempts, duration of CSE procedure, time taken to determine the puncture site, and the depth of the epidural space were compared between groups. The frequencies of complications such as puncture site hemorrhage, neurological damage, and inadvertent dural puncture were also studied.

Results  There were no differences in age, body weight, height, body mass index, or gestational age between the two groups. The success rate of puncture at the first puncture site was significantly higher in the ultrasound group than the palpation group (100.00% vs. 70.00%, P=0.004). The number of puncture attempts was significantly lower in the ultrasound group than the palpation group (c²=6.708, P=0.035). The time taken for determining the puncture site was (0.30±0.12) minutes in the palpation group and (2.60±0.61) minutes in the ultrasound group (P <0.001). The duration of CSE procedure was (7.67±1.52) minutes in the palpation group and (9.37±1.35) minutes in the ultrasound group (P <0.001). The depth of the epidural space was similar in both groups (P=0.586). Puncture site hemorrhage was observed in 6 (20.00%) patients in the palpation group and 2 (6.67%) patients in the ultrasound group (P=0.255).

Conclusions  Ultrasound imaging improves the rate of successful puncture at the first puncture site and decreases the number of puncture attempts. It facilitates CSE puncture in obese parturients.

     

Efficacy of the long-acting octreotide formulation in patients with thyroid-stimulating hormone-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure

Background  Little information about the current management of patients with thyroid-stimulating hormone (TSH)-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure. 

Methods  Fifteen patients with TSH-secreting pituitary adenomas (8 men and 7 women), who previously underwent incomplete surgical resection and/or adjuvant radiotherapy (n=12) and failure of octreotide treatment (n=15), followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables.

Results  After two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine (FT4) ((16.02±1.72) pmol/L) and free triiodothyronine (FT3) ((2.87±0.43) pmol/L) levels of 15 patients significantly decreased compared with those after octreotide-treatment (FT4, (35.36±7.42) pmol/L, P <0.001; FT3, (17.85±7.22) pmol/L, P <0.001). Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment ((0.72±0.21) mU/L) and were significantly lower than the pretreatment value ((5.27±1.04) mU/L, P <0.001), post-surgery value ((3.37±0.31) mU/L, P <0.001) and post-octreotide-treatment value ((4.52±0.41) mU/L, P <0.001). In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis.

Conclusion  The long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.

     

Expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4^＋ T cells in CBA/J×DBA/2 mouse model,selectively induced by IL-4 and IL-10, regulates the embryo resorption rate

Background Chemokines and their receptors have been a research focus in transplantation immunology. Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process. This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4^＋ T cells in CBA/J×DBA/2 mouse model and to explore the role of CCR3, CCR5, CXCR3 in immune tolerance in pregnancy. Methods The mouse model of spontaneous abortion （CBA/J×DBA/2） and the normal pregnant mouse model （CBA/J×BALB/c） were used. CBA/J×DBA/2 mice were injected with IL-4 （CBA/J×DBA/2-IL-4）, IL-4 and IL-10 （CBA/J×DBA/2-IL-4＋IL-10）, or normal saline （CBA/J×DBA/2-NS） as a control. The expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells from mouse peripheral blood was measured by the double-labelled FCM method, and the embryo resorption rate was also examined. Results The embryo resorption rate in the CBA/J×DBA/2 group without any treatment was significantly higher than that in the CBA/J×BALB/c group （17.9% vs 3.7%, P 〈0.01）. The embryo resorption rate in the CBA/J×DBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased, compared with that in the control and NS groups respectively. CCR3 expression on CD4^＋ T cells in the CBA/J×DBA/2 group without any treatment was significantly lower than that in the CBA/J×BALB/c group （0.3738±0.3575 vs 1.2190±0.2772, P 〈0.01）; both CCR5 （3.0900±1.5603 vs 1.2390±0.6361, P〈0.01） and CXCR3 （2.4715±0.9074 vs 0.9200±0.5585, P 〈0.01） expressions on CD4^＋ T cells of the CBA/J×DBA/2 group without any treatment were significantly higher than those of the CBA/J×BALB/c group. Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/J×DBA/2 group treated with IL-4 （CCR3： 2.0360±0.6944, CXCR3： 1.3510±0.5263, P〈0.01） or IL-4 and IL-10 （CCR3： 1.8160±1.0947, CXCR3：1.0940±0.7168, P〈0.01）. Because of the CCR5, IL-4 and IL-10 （1.9400±0.8504 vs 3.0900±1.5603, P 〈0.05）, but IL-4 alone （2.5310±1.3595 vs 3.0900±1.5603, P 〉0.05） treatment significantly decreased the expression of CCR5 in CBA/J×DBA/2. Conclusions The abnormal expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells may play an important role in the pathogenesis of spontaneous abortion. The pregnancy immune tolerance may be induced through selective induction of CCR3, CCR5 and CXCR3 expressions by IL-4 together with IL-10.     

Endothelial progenitor cell mediates transport of hepatitis B

Health authorities in Shanghai said yesterday that investigations have found no contamination at the city＇s umbilical cord blood bank and gave the assurance that supplies remain safe for use.     

Racial and ethnic differences in time to acute reperfusion therapy for patients hospitalized with myocardial infarction

Context  Nonwhite patients experience significantly longer times to fibrinolytic therapy (door-to-drug times) and percutaneous coronary intervention (door-to-balloon times) than white patients, raising concerns of health care disparities, but the reasons for these patterns are poorly understood. Objectives  To estimate race/ethnicity differences in door-to-drug and door-to-balloon times for patients receiving primary reperfusion for ST-segment elevation myocardial infarction; to examine how sociodemographic factors, insurance status, clinical characteristics, and hospital features mediate racial/ethnic differences. Design, Setting, and Patients  Retrospective, observational study using admission and treatment data from the National Registry of Myocardial Infarction (NRMI) for a US cohort of patients with ST-segment elevation myocardial infarction or left bundle-branch block and receiving reperfusion therapy. Patients (73 032 receiving fibrinolytic therapy; 37 143 receiving primary percutaneous coronary intervention) were admitted from January 1, 1999, through December 31, 2002, to hospitals participating in NRMI 3 and 4. Main Outcome Measure  Minutes between hospital arrival and acute reperfusion therapy. Results  Door-to-drug times were significantly longer for patients identified as African American/black (41.1 minutes), Hispanic (36.1 minutes), and Asian/Pacific Islander (37.4 minutes), compared with patients identified as white (33.8 minutes) (P<.01 for all). Door-to-balloon times for patients identified as African American/black (122.3 minutes) or Hispanic (114.8 minutes) were significantly longer than for patients identified as white (103.4 minutes) (P<.001 for both). Racial/ethnic differences were still significant but were substantially reduced after accounting for differences in mean times to treatment for the hospitals in which patients were treated; significant racial/ethnic differences persisted after further adjustment for sociodemographic characteristics, insurance status, and clinical and hospital characteristics (P<.01 for all). Conclusion  A substantial portion of the racial/ethnic disparity in time to treatment was accounted for by the specific hospital to which patients were admitted, in contrast to differential treatment by race/ethnicity inside the hospital.      

Preemptive Epidural Analgesia and Recovery From Radical Prostatectomy: A Randomized Controlled Trial

Context.— Preemptive analgesia can decrease the sensitization of the central nervous system that would ordinarily amplify subsequent nociceptive input, but a clear demonstration of its clinical efficacy is necessary for it to become a routine component of acute pain therapy. Objective.— To determine the impact of preemptive epidural analgesia on postoperative pain and other clinically important outcome variables after radical retropubic prostatectomy. Design and Setting.— A block randomized double-blind clinical trial lasting 20 months at a single academic medical center. Patients.— A total of 100 generally healthy and neurologically intact patients scheduled for radical retropubic prostatectomy for the treatment of prostate cancer in whom an epidural catheter for treating postoperative pain was to be placed prior to the induction of general anesthesia. Interventions.— Epidural bupivacaine, epidural fentanyl, or no epidural drug was administered prior to induction of anesthesia and throughout the entire operation, followed by aggressive postoperative epidural analgesia for all patients. Main Outcome Measures.— Daily pain scores during hospitalization and pain scores obtained 3.5, 5.5, and 9.5 weeks after hospital discharge. Results.— The patients who received epidural fentanyl or bupivacaine prior to surgical incision (preemptive analgesia) experienced 33% less pain while hospitalized (P=.007). Pain scores in those receiving preemptive analgesia were significantly lower at 9.5 weeks (P=.02), but were not significantly different at 3.5 or 5.5 weeks. At 9.5 weeks, 32 (86%) of 37 patients receiving preemptive analgesia were pain-free compared with 9 (47%) of 19 control patients (P=.004). Patients receiving preemptive analgesia were more active 3.5 weeks after surgery (P=.01), but not at 5.5 or 9.5 weeks. Conclusions.— Even in the presence of aggressive postoperative pain management, preemptive epidural analgesia significantly decreases postoperative pain during hospitalization and long after discharge, and is associated with increased activity levels after discharge.      

Rotational Alignment in Total Knee Arthroplasty: Nonimage-based Navigation System Versus Conventional Technique

Background  Proper rotational alignment during total knee arthroplasty (TKA) is important for adequate postoperative patellofemoral and tibiofemoral kinematics, as well as for achieving balanced flexion space at 90º. The effects of computer navigation-assisted total knee replacement and conventional total knee arthroplasty on rotational alignment, mechanical axis, component position and clinical outcomes were compared.

Methods  Two methods were used in 82 patients and the rotation of the femoral and tibial components in the transverse plane, the combined rotation of the two components, the mismatch between them, and the mechanical axis of the lower limb were analyzed. All of these parameters were measured from postoperative radiographs and computed tomography images. Functional outcomes were compared at 6 weeks and 6 months postoperatively.

Results  Significant differences were found between the two techniques (P <0.05) in the following parameters: average rotation of the femoral component ((1.51±3.55)º vs. (−0.63±3.04)º); combined rotation of the femoral and tibial components (2.85±4.07)º vs. (0.28±3.43)º); and mismatch between the femoral and tibial components ((1.44±4.55)º vs. (−0.43±2.86)º). Differences in the rotation of the tibial component were not statistically significant. The prevalence of outliers (malalignment >±3° internal/external rotation) of the femoral component (31.7% vs. 12.5%) and the tibial component (36.6% vs. 15%) were significantly reduced when the navigation system was used (P <0.05). In addition, while patients in the navigation group had significantly better mechanical axis and functional outcomes at 6 weeks after surgery (P <0.05), there was no significant difference between the two groups (P >0.05) with respect to functional outcomes at 6 months.

Conclusion  The navigation system exhibited higher accuracy than the conventional technique in the transverse and coronal plane, and provided better early functional outcomes.

     

Publication Bias and Research on Passive Smoking: Comparison of Published and Unpublished Studies

Context.— The results of reviews may be biased by delays in publication and failure to publish nonsignificant results. Objective.— To determine the extent of unpublished results on the health effects of passive smoking and whether passive smoking studies with statistically nonsignificant results would have longer time to publication than those with statistically significant results. Design.— Semistructured telephone interviews of principal investigators of published or unpublished studies funded between 1981 and 1995, identified by information obtained from 76 (85%) of 89 organizations contacted that potentially funded research on passive smoking. Participants.— Seventy-eight investigators were eligible and could be located; 65 (83%) responded. They had conducted 61 studies of the health effects of passive smoke in humans or animals between 1981 and 1995 that met the criteria for the analysis of time to publication. Main Outcome Measure.— Time to publication for published studies and statistical significance of results of published and unpublished studies. Results.— Fourteen of the 61 studies were unpublished. Median time to publication was 5 years (95% confidence interval [CI], 4-7 years) for statistically nonsignificant studies and 3 years (95% CI, 3-5 years) for statistically significant studies (P=.004). Statistically significant results (P=.004), experimental study design (P=.01), study size less than or equal to 500 (P=.01), and animals as subjects (P=.03) were predictive of time to publication. When the studies with human participants were analyzed separately, only statistically significant data were predictive of publication (P=.007). Multivariate analysis of all studies indicated that statistical significance (P=.001) and study design (P=.01) were the only independent predictors of time to publication, while for the human studies only statistical significance was predictive of publication (P=.007). Conclusion.— There is a publication delay for passive smoking studies with nonsignificant results compared with those with significant results.      

Ⅲa期非小细胞肺癌综合治疗方法的探讨

目的探讨总结Ⅲa期非小细胞肺癌患者的治疗经验。方法分析比较对188例Ⅲa期非小细胞肺癌患者,进行术前化疗+手术+术后化疗、手术+术后化疗和单纯手术治疗、单纯化疗对1、3年生存率及中位生存期(MST)的影响。术前与术后化疗方案相同(紫杉醇+卡铂或吉西他滨+卡铂),术前行2个周期,术后行4~6个周期。单纯化疗也采用上述方案4~6个周期。结果术前化疗+手术+术后化疗组的1、3年生存率均明显高于单纯手术治疗组(P<0.01),与手术+术后化疗组相比,二者1年生存率差异有统计学意义(P<0.05),而3年生存率差异无统计学意义(P>0.05)。手术+术后化疗组的1年生存率优于单纯手术治疗组,但差异无统计学意义(P=0.069)。单纯化疗组3年无生存者,MST仅为9个月,远低于术前化疗+手术+术后化疗组和手术+术后化疗组。结论对于Ⅲa期非小细胞肺癌患者,均应尽量手术治疗(完全切除或减瘤术),淋巴结清扫的效果是肯定的。术后化疗可提高生存率。新辅助化疗提高了手术的切除率,有利于改善生存期。单纯化疗效果不佳。     

Is the European System for Cardiac Operative Risk Evaluation useful in Chinese patients undergoing heart valve surgery?

Background  The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is one of the most widely used risk models for the predicting mortality after cardiac surgery. The aim of this study was to validate the EuroSCORE model for predicting operative mortality in heart valve surgery on a Chinese multicenter database and comparing the performance of EuroSCORE with our new risk stratification system, the Sino System for Coronary Operative Risk Evaluation (SinoSCORE).

Methods  Data from patients undergoing heart valve surgery between January 2007 and December 2008 were retrospectively collected, from 43 hospitals in China. The EuroSCORE and the SinoSCORE were calculated for each patient. Mortality was defined as any in-hospital death. Area under the receiver operating characteristics curve (AUC) was used to study the discriminatory abilities of the models. The Hosmer-Lemeshow (H-L) goodness-of-fit test was used to study the calibration of the predictive models.

Results  A total of 15 367 patients were analyzed. For the entire cohort, the observed mortality was 2.34%, the predicted mortality was 3.71% (additive), 3.19% (logistic) and 3.66% (SinoSCORE). AUC was 0.747 for SinoSCORE, 0.699 additive and 0.696 for logistic EuroSCORE. Calibration of SinoSCORE and additive EuroSCORE was good (H-L: P=0.250 and P=0.051, respectively), but the logistic EuroSCORE model had a poor calibration (H-L: P<0.05). The discriminatory ability and calibration of the SinoSCORE were good in low- and high-risk patients. However, the discriminatory ability of the EuroSCORE model was poor in all risk deciles.

Conclusions  The EuroSCORE does not accurately predict mortality in Chinese patients with heart valve surgery, and the SinoSCORE is superior to the EuroSCORE at predicting in-hospital mortality in Chinese heart valve surgery patients.

     

Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing cabg surgery: a randomized controlled trial

Context  Renal dysfunction is a complication of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB) that is associated with increased morbidity and mortality. N-acetylcysteine, an antioxidant and vasodilator, counteracts renal ischemia and hypoxia. Objective  To determine whether perioperative intravenous (IV) N-acetylcysteine preserves renal function in high-risk patients undergoing CABG surgery with CPB compared with placebo. Design, Setting, and Patients  Randomized, quadruple blind, placebo-controlled trial (October 2003-September 2004) in operating rooms and general intensive care units (ICUs) of 2 Ontario tertiary care centers. The 295 patients required elective or urgent CABG and had at least 1 of the following: preexisting renal dysfunction, at least 70 years old, diabetes mellitus, impaired left ventricular function, or undergoing concomitant valve or redo surgery. Interventions  Patients received 4 (2 intraoperative and 2 postoperative) doses of IV N-acetylcysteine (600 mg) (n = 148) or placebo (n = 147) over 24 hours. Main Outcome Measures  The primary outcome was the proportion of patients developing postoperative renal dysfunction, defined by an increase in serum creatinine level greater than 0.5 mg/dL (44 µmol/L) or a 25% increase from baseline within the first 5 postoperative days. Secondary outcomes included postoperative interventions and complications, the requirement for renal replacement therapy (RRT), adverse events, hospital mortality, and ICU and hospital length of stay. Results  There was no difference in the proportion of patients with postoperative renal dysfunction (29.7% vs 29.0%, P = .89; relative risk [RR], 1.03 [95% confidence interval {CI}, 0.72-1.46]) in the N-acetylcysteine and placebo groups, respectively. We noted nonsignificant differences in postoperative interventions and complications, the need for RRT (0.7% vs 2.1%; P = .37), total (6.1% vs 9.6%; P = .26) and serious adverse events, hospital mortality (3.4% vs 2.7%; P>.99), and ICU and hospital length of stay between the N-acetylcysteine and placebo groups. A post hoc subgroup analysis of patients (baseline creatinine level >1.4 mg/dL [120 µmol/L]) showed a nonsignificant trend toward fewer patients experiencing postoperative renal dysfunction in the N-acetylcysteine group compared with the placebo group (25.0% vs 37.1%; P = .29). Conclusions  N-acetylcysteine did not prevent postoperative renal dysfunction, interventions, complications, or mortality in high-risk patients undergoing CABG surgery with CPB. Further research is required to identify CABG patients at risk for postoperative renal events, valid markers of renal dysfunction, and to establish renal thresholds associated with important clinical outcomes.      

Three hours continuous injection of adenosine improved left ventricular function and infarct size in patients with ST-segment elevation myocardial infarction

Background  The definitive treatment for myocardial ischemia is reperfusion. However, reperfusion injury has the potential to cause additional reversible and irreversible damage to the myocardium. One likely candidate for a cardioprotection is adenosine. The present study aimed at investigating the effect of intravenous adenosine on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). 

Methods  Patients with STEMI within 12 hours from the onset of symptoms were randomized by 1:1:1 ratio to receive either adenosine 50 µg∙kg^-1∙min^-1 (low-dose group, n=31), or 70 µg∙kg^-1∙min^-1 (high-dose group, n=32), or saline 1 ml/min (control group, n=27) for three hours. Drugs were given to the patients immediately after the guide wire crossed the culprit lesion. Recurrence of no-reflow, TIMI flow grade (TFG) and TIMI myocardial perfusion grade (TMPG), and collateral circulation were recorded. The postoperative and preoperative ST segment elevation sum of 18-lead electrocardiogram (ECG) and their ratio (STsum-post/STsum-pre) were recorded, as well as the peak time and peak value of CK-MB enzyme. Serial cardiac echo and myocardial perfusion imaging were performed at 24 hours and 6 months post-stenting. The primary endpoint was left ventricular function, and infarct size. The secondary end-point was the occurrence of cardiac and non-cardiac death, non-fatal myocardial infarction, and heart failure.

Results  A total of 90 STEMI patients were studied. No-reflow immediately after stent procedure was seen in 11 (35.5%) patients in the control group, significantly different from 6.3% in the low-dose group or 3.7% in the high-dose group (both P=0.001). STsum-post/STsum-pre in the low-dose and high-dose groups was significantly different from the control group (low-dose group vs. control group, P=0.003 and high-dose group vs. control group, P=0.001), without a dose-dependent pattern (P=0.238). The peak value of CK-MB enzyme was significantly reduced in the high-dose group compared to the control group (P=0.024). Compared to the left ventricular ejection fraction (LVEF) in control group, LVEF in the low-dose group increased by 5.8% at 24 hours (P=0.012) and by 10.9% at 6 months (P=0.007), LVEF in the high-dose group increased by 9.5% at 24 hours (P=0.001) and by 10.0% at 6 months (P=0.001), respectively. Significant reduction of infarct size by 24.2% was detected in the high-dose group vs. low-dose or control groups (P=0.008). There was no significant difference regarding secondary endpoints at 6 months among the treated groups. Cardiac function by NYHA classification in both the low-dose and the high-dose groups was improved significantly (P=0.013, P=0.016).

Conclusion  Intravenous adenosine administration might significantly reduce the recurrence of no-reflow, with resultant improved left ventricular systolic function. High-dose adenosine was further associated with significant reduction of infarct size.

     

Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial

Context  Controlling postoperative pain after knee replacement while reducing opiod-induced adverse effects and improving outcomes remains an important challenge. Objective  To assess the effect of combined preoperative and postoperative administration of a selective inhibitor of cyclooxygenase 2 on opioid consumption and outcomes after total knee arthroplasty (TKA). Design, Setting, and Patients  Randomized, placebo-controlled, double-blind trial conducted June 2001 through September 2002, enrolling 70 patients aged 40 to 77 years and undergoing TKA at a university hospital in the United States. Interventions  Patients were randomly assigned to receive 50 mg of oral rofecoxib at 24 hours and at 1 to 2 hours before TKA, 50 mg daily for 5 days postoperatively, and 25 mg daily for another 8 days, or matching placebo at the same times. Main Outcome Measures  Postoperative outcomes including postsurgical analgesic consumption and pain scores achieved, nausea and vomiting, joint range of motion, sleep disturbance, patient satisfaction with analgesia, and hematologic and coagulation parameters. Results  Total epidural analgesic consumption and in-hospital opioid consumption were less in the group receiving rofecoxib compared with the group receiving placebo (P<.05). Median pain score (visual analog scale [VAS], 0-10) achieved for the knee was lower in the rofecoxib group compared with the placebo group during hospital stay (2.2 [interquartile range {IQR}, 1.4-3.2] vs 3.5 [IQR, 2.7-4.3], P<.001) and 1 week after discharge (2.6 [IQR, 1.4-3.5] vs 3.7 [IQR, 2.9-4.7], P = .03). There was less postoperative vomiting in the rofecoxib group (6%) compared with the placebo group (26%) (P = .047), as well as a decrease in sleep disturbance compared with the placebo group on the night of surgery (P = .006) and on the first (P = .047) and second (P<.001) days postoperatively. Knee flexion was increased in the rofecoxib group compared with the placebo group at discharge (active flexion: mean [SD], 84.2° [11.1°] vs 73.2° [13.6°], P = .03; passive flexion: 90.5° [6.8°] vs 81.8° [13.4°], P = .05) and at 1 month postoperatively (109.3° [8.5°] vs 100.8° [11.8°], P = .01), with shorter time in physical therapy to achieve effective joint range of motion. The rofecoxib group was more satisfied with analgesia and anesthesia at discharge compared with the placebo group (median satisfaction score, 4.3 [IQR, 3.0-4.7] vs 3.3 [IQR, 2.3-4.3], respectively; P = .03), and the differences persisted at 2-week and at 1-month follow-up. There was no intergroup difference in surgical blood loss (P>.05 for both intraoperative and postoperative blood loss). Conclusion  Perioperative use of an inhibitor of cyclooxygenase 2 is an effective component of multimodal analgesia that reduces opioid consumption, pain, vomiting, and sleep disturbance, with improved knee range of motion after TKA.      

Duration of anticoagulation following venous thromboembolism: a meta-analysis

David Ost, MD; Josh Tepper, MD; Hanako Mihara, MD, MPH; Owen Lander, MD; Raphael Heinzer, MD; Alan Fein, MD

JAMA. 2005;294:706-715.

Context  Patients with venous thromboembolism (VTE) are susceptible to recurrent events, but whether prolonging anticoagulation is warranted in patients with VTE remains controversial.

Objective  To review the available evidence and quantify the risks and benefits of extending the duration of anticoagulation in patients with VTE.

Data Sources  PubMed, EMBase Pharmacology, the Cochrane database, clinical trial Web sites, and a hand search of reference lists.

Study Selection  Included studies were randomized controlled trials with results published from 1969 through 2004 and evaluating the duration of anticoagulation in patients with VTE that measured recurrent VTE. Excluded studies were those enrolling only pure populations of high-risk patients. Two independent reviewers assessed each article for inclusion and exclusion criteria, with adjudication by a third reviewer in cases of disagreement. Fifteen of 67 studies were included in the analysis.

Data Extraction  Two independent reviewers performed data extraction using a standardized form, with adjudication by the remainder of the investigators in cases of disagreement. Data regarding recurrent VTE, major bleeding, person-time at risk, and study quality were extracted.

Data Synthesis  If patients in the long-term therapy group remained receiving anticoagulation, the risk of recurrent VTE with long- vs short-term therapy was reduced (weighted incidence rate, 0.020 vs 0.126 events/person-year; rate difference, –0.106 [95% confidence interval {CI}, –0.145 to –0.067]; P<.001; pooled incidence rate ratio [IRR], 0.21 [95% CI, 0.14 to 0.31]; P<.001). If anticoagulation in the long-term therapy group was discontinued, the risk reduction was less pronounced (weighted incidence rate, 0.052 vs 0.072 events/person-year; rate difference, –0.020 [95% CI, –0.039 to –0.001]; P = .04; pooled IRR, 0.69 [95% CI, 0.53 to 0.91]; P = .009). The risk of major bleeding with long- vs short-term therapy was similar (weighted incidence rate, 0.011 vs 0.006 events/person-year; rate difference, 0.005 [95% CI, –0.002 to 0.011]; P = .14; pooled IRR, 1.80 [95% CI, 0.72 to 4.51]; P = .21).

Conclusions  Patients who receive extended anticoagulation are protected from recurrent VTE while receiving long-term therapy. The clinical benefit is maintained after anticoagulation is discontinued, but the magnitude of the benefit is less pronounced.