Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.
Treatment with statins, inhibitors of HMG-CoA reductase, extends the survival of septic mice. However, the molecular mechanisms underlying the cholesterol-lowering, independent beneficial effects of statins in sepsis are poorly understood. The inhibition of protein isoprenylation, namely farnesylation and geranylgeranylation, has been proposed as a mediator of the pleiotropic protective effects of statins, although direct evidence is lacking. Major features of sepsis-induced immune suppression include T-cell dysfunction, which is characterized by apoptosis of splenic T cells, increased CD4ϩ Foxp3 ϩ regulatory T cells (Tregs), and suppression of type 1 helper T-cell response [e.g., interferon-␥ (IFN-␥) secretion] in mice. Here, we show that the induction of sepsis by cecal ligation and puncture (CLP) resulted in increases in farnesyltransferase activity and farnesylated proteins in the spleen relative to sham operation. Treatment with farnesyltransferase inhibitor N-[4-[2(R)-amino-3-mercaptopropyl]amino-2-phenylbenzoyl]methionine methyl ester trifluoroacetate salt (FTI-277) (25 mg/kg b.wt. i.p.) at 2 h after CLP blocked the increase in farnesylated proteins and improved survival and bacterial clearance of septic mice. FTI-277 reverted to or mitigated sepsis-induced apoptosis in spleen and thymus, increased splenic CD4 ϩ Foxp3ϩ Tregs, and suppressed IFN-␥ secretion and proliferation of splenocytes in response to anti-CD3ϩCD28 antibodies in mice. Moreover, FTI-277 promoted macrophage phagocytotic activity in septic mice. These results indicate that elevation in protein farnesylation plays a role in derangements in immune function and mortality of septic mice. These findings suggest that prevention of immune dysfunction might contribute to FTI-277-induced improvement in survival of septic mice. These data highlight protein farnesyltransferase as a novel potential molecular target to reduce the mortality of patients with sepsis.
Background:To assess whether the ultrasound (US) is a reliable approach in detecting lower-limb deep-vein thrombosis (DVT) in patients without symptoms of DVT.Methods:The research team performed a systematic search in PubMed, Ovid, Cochrane, and Web of Science without language or date restrictions. Full-text reports on prospective diagnostic studies involve the detection of lower-limb proximal and distal DVT in patients without symptoms of DVT using US and venography. A meta-analysis was performed using Meta-DiSc (version 1.4), providing the pooled sensitivity, specificity, positive (LR+) and negative (LR–) likelihood ratios of the detection accuracy of US. There were 4 different classes of subgroup analysis—the class of patients stratified by location of US exam (proximal, distal, whole leg), the class stratified by technique (color/doppler, compression, both modalities), the class stratified by kind of surgery (orthopedic, otherwise hospitalized) and the class stratified by era of publishing (1980s, 1990s, 2000s). The study quality and the risk of bias were evaluated using QUADAS-2, with heterogeneity was assessed and quantified by the Q score and I2 statistics, respectively.Results:The meta-analysis included 26 articles containing 41 individual studies with a total of 3951 patients without symptoms of DVT. Using venography as the gold standard, US for proximal DVT had a pooled sensitivity of 59% (95% confidence interval (CI) = 51%–66%) and a pooled specificity of 98% (95% CI = 97%–98%), US for distal DVT had a poor sensitivity of 43% (95% CI = 38%–48%) and a pooled specificity of 95% (95% CI = 94%–96%), US for whole-leg DVT had a pooled sensitivity of 59% (95% CI = 54%–64%) and a pooled specificity of 95% (95% CI = 94%–96%), US for post-major orthopedic surgery patients had a pooled sensitivity of 52% (95% CI = 49%–55%), and US for other types of patients had a pooled sensitivity of 58% (95% CI = 43%–72%). Pure compression technique for DVT had a poor sensitivity of 43% (95% CI = 39%–48%), pure color/doppler technique for DVT had a pooled sensitivity of 58% (95% CI = 53%–63%), compression and color/doppler technique for DVT had a pooled sensitivity of 61% (95% CI = 48%–74%).Conclusion:US could be a useful tool for diagnosing DVT, but it has a lower positive rate and a higher false negative rate. The rate of missed diagnosis of lower-limb DVT by US amounts to 50% or so in the patients without symptoms of DVT. The negative results do not preclude the possibility of DVT and if appropriate heightened surveillance and continued monitoring or try a more accurate inspection method is warranted. The whole leg evaluation and color/doppler technique should be the preferred approach.
Background:Controversy persists about whether early enteral nutrition administration is related to worse prognosis than delayed enteral nutrition for patients with gastrointestinal bleeding.Objectives:To systematically evaluate the effect of early enteral nutrition on the patient with gastrointestinal bleeding through the meta-analysis.Methods:Such electronic databases including PubMed, EMBASE, Cochrane Library, CNKI, and CBM were searched from 1985 to March 2018. Randomized controlled trials that compared early enteral nutrition versus delayed enteral nutrition in patients with gastrointestinal bleeding were considered eligible. Data extraction and the methodological quality assessment of the included trials were carried out according to the Cochrane Handbook. We calculated the pooled risk ratio, weighted mean difference, and the corresponding 95% confidential interval using RevMan5.3.Result:A total of 5 trials involving 313 patients were included. Compared with delayed enteral nutrition, there was a tendency for a decreased rebleeding rate in the early enteral nutrition group, but the trend was not statistically significant (risk ratio = 0.75, 95% confidential interval: 0.34–1.64, I2 = 0). As for mortality within 30 days, no significant difference was found between the 2 groups (risk ratio = 0.74, 95% confidential interval: 0.23–2.39, I2 = 0). In addition, the pooled analysis showed that early enteral nutrition was related to reduced hospitalized days (weighted mean difference = −1.69, 95% confidential interval: −2.15 to −1.23; I2 = 27%)Conclusion:For patients with gastrointestinal bleeding, early enteral nutrition within 24 hours does not result in the significantly higher risk of rebleeding and mortality compared with delayed enteral nutrition, but decrease hospitalized days. Patients who are at low risk for rebleeding can be fed early and discharged early. However, larger, high-quality randomized controlled trials are needed to verify these findings, and when the gastrointestinal bleeding patient start enteral nutrition is worth studying.
The current progression in tissue engineering and local gene delivery systems has enhanced applications for cartilage tissue engineering. In this study, porous chitosan/collagen scaffolds were prepared through a freezedrying process and loaded with plasmid encoding human transforming growth factor-1 (TGF1). Human bone marrow stem cells were seeded in this scaffold, and gene transfection was traced by enhanced green fluorescent protein (EGFP). The expression of type II collagen and aggrecan was detected with reverse transcription-polymerase chain reaction, and cell proliferation was measured every day for six days using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. The pore diameter of the gene-combined scaffolds was lower than that of the pure chitosan/collagen scaffold. The scaffold containing TGF1 plasmid exhibited the highest proliferation rate, and the expression of type II collagen and aggrecan was upregulated in the pEGFP-TGF1 scaffold. The potential for chitosan/collagen scaffold combined with pEGFP-TGF1 as a substrate candidate in cartilage tissue engineering has been investigated.
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