急危重病人血流动力学最佳化状态治疗研究的Meta分析

目的　探讨有关急危重病人血流动力学状态达到最佳化治疗研究中肺动脉导管 (Swan -Ganz)与复苏治疗的关系 ,评估生理、临床、治疗等方面因素对复苏治疗效果的影响。方法　从MEDLINE(英文医学文献资料网库 )中搜集所有与Swan -Ganz和血流动力学状态有关的 71篇研究文献。按照限定条件进行筛选 :①病人类型 :急性病 ,高危外科手术病人 ,创伤 ;②达到血流动力学指标正常值或超常值标准 ;③控制组死亡率 >2 0 % (危重组 )或 <15 % (一般组 ) ;④治疗后达到血流动力学指标的早晚 ;其中 2 1项研究接受Meta分析。结果　在危重组 ,早期达到血流动力学超常值治疗 ,2 1项研究中的 7项显示在控制组与治疗组之间死亡率有显著性的差别 (P <0 0 5 ) ;而晚期达到血流动力学超常值治疗的 6项研究 ,两组之间死亡率无显著性的差别 (P >0 0 5 )。在一般组 ,达到血流动力学正常值治疗的 5项研究和超常值治疗的 3项研究显示 ,控制组与治疗组之间死亡率无显著性的差别。结论　经Swan -Ganz引导早期达到血流动力学超常值治疗 ,能降低重病组的死亡率。     

Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell death in cultured human neurons and fibroblasts.

Thimerosal is an organic mercurial compound used as a preservative in biomedical preparations. Little is known about the reactions of human neuronal and skin cells to its micro- and nanomolar concentrations, which can occur after using thimerosal-containing products. A useful combination of fluorescent techniques for the assessment of thimerosal toxicity is introduced. Short-term thimerosal toxicity was investigated in cultured human cerebral cortical neurons and in normal human fibroblasts. Cells were incubated with 125-nM to 250-microM concentrations of thimerosal for 45 min to 24 h. A 4', 6-diamidino-2-phenylindole dihydrochloride (DAPI) dye exclusion test was used to identify nonviable cells and terminal transferase-based nick-end labeling (TUNEL) to label DNA damage. Detection of active caspase-3 was performed in live cell cultures using a cell-permeable fluorescent caspase inhibitor. The morphology of fluorescently labeled nuclei was analyzed. After 6 h of incubation, the thimerosal toxicity was observed at 2 microM based on the manual detection of the fluorescent attached cells and at a 1-microM level with the more sensitive GENios Plus Multi-Detection Microplate Reader with Enhanced Fluorescence. The lower limit did not change after 24 h of incubation. Cortical neurons demonstrated higher sensitivity to thimerosal compared to fibroblasts. The first sign of toxicity was an increase in membrane permeability to DAPI after 2 h of incubation with 250 microM thimerosal. A 6-h incubation resulted in failure to exclude DAPI, generation of DNA breaks, caspase-3 activation, and development of morphological signs of apoptosis. We demonstrate that thimerosal in micromolar concentrations rapidly induce membrane and DNA damage and initiate caspase-3-dependent apoptosis in human neurons and fibroblasts. We conclude that a proposed combination of fluorescent techniques can be useful in analyzing the toxicity of thimerosal.     

Changes in functional outcome and quality of life in patients and caregivers after aneurysmal subarachnoid hemorrhage.

OBJECT: Although the case-fatality rate after subarachnoid hemorrhage (SAH) does not change considerably after the first 4 weeks, functional outcome and the quality of life (QOL) may. To assess the extent of changes in functional outcome and QOL after SAH, the authors conducted a follow-up study at 18 months in patients and caregivers who had participated in a previous study of QOL 4 months after SAH. METHODS: In a consecutive series of 98 patients admitted with SAH, 68 had survived until 4 months postbleed, at which time an initial outcome assessment had been performed in 64 of them. This series of 64 patients was contacted again at a median of 18 months after SAH. In all patients, functional outcome was assessed by means of the modified Rankin Scale (mRS). In 48 patients and 35 caregivers QOL was assessed using the SF-36, the Sickness Impact Profile (SIP), and a visual analog scale. The results were compared with the scores that had been obtained at 4 months after SAH. Thirty-two patients (50%) had improved at least one point on the mRS, in 23 patients functional outcome had remained unchanged, six patients had deteriorated one point on the mRS, and three had died. No major changes in the QOL of patients and caregivers could be found on the SIP, but on the SF-36 an improved QOL was detected in patients with better Rankin grades. On both instruments, the QOL at 18 months was still reduced compared with the reference population in all patients. CONCLUSIONS: Functional outcome improves significantly between 4 months and 18 months post-SAH; studies on functional outcome after SAH can be compared only if outcome is assessed at the same time interval. The improved functional outcome seems to be accompanied by an improved QOL.     

Donor nephrectomy: less fatigue and better quality of life following laparoscopic kidney removal compared with an open procedure by mini-incision: blind randomised study

OBJECTIVE: Determining possible differences in living donor nephrectomy procedures: laparoscopy against mini-incision concerning discomfort to the donor and the maintenance of good graft function. DESIGN: Blind randomized study. METHOD: In two university medical centres, one hundred living kidney donors were randomly assigned to either total laparoscopic donor nephrectomy or mini-incision muscle-splitting open donor nephrectomy. Primary outcome was physical fatigue measured with the 'Multidimensional Fatigue Inventory' (MFI-20) during one-year follow-up. Secondary outcomes were physical function measured with the 'Short form-36' questionnaire, postoperative hospital stay, amount of pain, operating times and graft and patient survival. RESULTS: Donors who underwent laparoscopy experienced less fatigue (difference: -1.3; 95% CI: -2.4 - (-0.1)) and physical function was better (difference: 6.2; 95% CI: 2.0-10.3) during one-year follow-up. Those donors who underwent laparoscopy required less morphine (16 mg versus 25 mg; p = 0.005) and the duration of hospital stay was shorter (3 versus 4 days; p = 0.003). The laparoscopic procedure resulted in a longer operation time (221 versus 164 min; p < 0.001) a longer first warm ischaemia time (6 versus 3 min; p < 0.001) and less blood loss (100 versus 240 ml; p < 0.001). Recipient renal function and one-year graft survival rates did not differ. The number of preoperative and postoperative complications did not differ significantly between both surgery techniques. Conversions did not occur. CONCLUSION: Donor nephrectomy through laparoscopy led to less fatigue and a better quality of life compared with the open procedure. The safety factors for donors and recipients were comparable for both techniques. Laparoscopic donor nephrectomy is therefore the better surgical choice for kidney donor programmes with living donors.     

Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL

We performed sensitive polymerase chain reaction-based minimal residual disease (MRD) analyses on bone marrow samples at 9 follow-up time points in 71 children with T-lineage acute lymphoblastic leukemia (T-ALL) and compared the results with the precursor B-lineage ALL (B-ALL) results (n = 210) of our previous study. At the first 5 follow-up time points, the frequency of MRD-positive patients and the MRD levels were higher in T-ALL than in precursor-B-ALL, reflecting the more frequent occurrence of resistant disease in T-ALL. Subsequently, patients were classified according to their MRD level at time point 1 (TP1), taken at the end of induction treatment (5 weeks), and at TP2 just before the start of consolidation treatment (3 months). Patients were considered at low risk if TP1 and TP2 were MRD negative and at high risk if MRD levels at TP1 and TP2 were 10(-3) or higher; remaining patients were considered at intermediate risk. The relative distribution of patients with T-ALL (n = 43) over the MRD-based risk groups differed significantly from that of precursor B-ALL (n = 109). Twenty-three percent of patients with T-ALL and 46% of patients with precursor B-ALL were classified in the low-risk group (P =.01) and had a 5-year relapse-free survival (RFS) rate of 98% or greater. In contrast, 28% of patients with T-ALL were classified in the MRD-based high-risk group compared to only 11% of patients with precursor B-ALL (P =.02), and the RFS rates were 0% and 25%, respectively (P =.03). Not only was the distribution of patients with T-ALL different over the MRD-based risk groups, the prognostic value of MRD levels at TP1 and TP2 was higher in T-ALL (larger RFS gradient), and consistently higher RFS rates were found for MRD-negative T-ALL patients at the first 5 follow-up time points.     

Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality

CONTEXT: Adequate adrenal function is pivotal to survive meningococcal sepsis. OBJECTIVES: The objective of the study was to evaluate adrenocortical function in meningococcal disease. DESIGN: This was an observational cohort study. SETTING: The study was conducted at a university-affiliated pediatric intensive care unit. PATIENTS: Sixty children with meningococcal sepsis or septic shock participated in the study. MAIN OUTCOME MEASURES: The differences in adrenal function between nonsurvivors (n = 8), shock survivors (n = 43), and sepsis survivors (n = 9) on pediatric intensive care unit admission were measured. RESULTS: Nonsurvivors had significantly lower median cortisol to ACTH ratio than shock survivors and sepsis survivors. Because cortisol binding globulin and albumin levels did not significantly differ among the groups, bioavailable cortisol levels were also significantly lower in nonsurvivors than sepsis survivors. Nonsurvivors had significantly lower cortisol to 11-deoxycortisol ratios but not lower 11-deoxycortisol to 17-hydroxyprogesterone ratios than survivors. Using multiple regression analysis, decreased cortisol to ACTH ratio was significantly related to higher IL-6 levels and intubation with etomidate (one single bolus), whereas decreased cortisol to 11-deoxycortisol ratio was significantly related only to intubation with etomidate. Aldosterone levels tended to be higher in nonsurvivors than shock survivors, whereas plasma renin activity did not significantly differ. CONCLUSIONS: Our study shows that the most severely ill children with septic shock had signs of adrenal insufficiency. Bioavailable cortisol levels were not more informative on adrenal function than total cortisol levels. Besides disease severity, one single bolus of etomidate during intubation was related to decreased adrenal function and 11beta-hydroxylase activity. Decreased adrenal function was not related to decreased 21-hydroxylase activity. Based on our results, it seems of vital importance to take considerable caution using etomidate and consider combining its administration with glucocorticoids during intubation of children with septic shock.     

Patient preference and willingness to pay for transient elastography versus liver biopsy: A perspective from British Columbia

BACKGROUND:

The cost of liver biopsy (LB) is publicly funded in British Columbia, while the cost of transient elastography (FibroScan [FS], Echosens, France) is not. Consequently, there is regional variation regarding FS access and monitoring of liver disease progression.

OBJECTIVE:

To evaluate patient preference for FS versus LB and to assess the willingness to self-pay for FS.

METHODS:

Questionnaires were distributed in clinic and via mail to LB-experienced and LB-naive patients who underwent FS at Vancouver General Hospital, Vancouver, British Columbia.

RESULTS:

The overall response rate was 76%. Of the 422 respondents, 205 were LB-experienced. The mean age was 53.5 years, 50.2% were male, 54.7% were Caucasian, 38.2% had hepatitis C and 26.3% had an annual household income >$75,000. Overall, 95.4% of patients preferred FS to LB. FS was associated with greater comfort than LB, with the majority reporting no discomfort during FS (84.1% versus 7.8% for LB), no discomfort after (96.2% versus 14.6% LB) and no feelings of anxiety after FS explanation (78.2% versus 12.7% LB). FS was also associated with greater speed, with the majority reporting short test duration (97.2% versus 48.3% LB) and short wait for the test result (95.5% versus 30.2% LB). Most (75.3%) respondents were willing to self-pay for FS, with 26.3% willing to pay $25 to $49. Patients with unknown liver disease preferred LB (OR [FS preference] 0.20 [95% CI 0.07 to 0.53]).

CONCLUSIONS:

FS was the preferred method of assessing liver fibrosis among patients, with the majority willing to self-pay. To ensure consistency in access, provincial funding for FS is needed. However, LB remains the procedure of choice for individuals with an unknown diagnosis.