Objective To systemically review the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis. Methods Such databases as MEDLINE, EMbase, The Cochrane Library, VIP, CNKI and CBM were electronically searched for comprehensively collecting randomized controlled trials (RCTs) on the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis from inception to July 2012. References of included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.0 software. Results Totally, five RCTs involving 6 307 patients were included. The results of meta-analysis showed that, no significant difference was found in 28-day mortality (RR=1.00, 95%CI 0.84 to 1.19, P=1.00) and 90-day mortality (RR=1.00, 95%CI 0.87 to 1.14, P=0.96) between the rhAPC group and the placebo group. The results of subgroup analysis showed that, the two groups were similar in the 28-day mortality of patients with different Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (APACHE II scorelt;25: RR=1.06, 95%CI 0.93 to 1.21, P=0.37; APACHE II score≥25: RR=0.93, 95%CI 0.69 to 1.24, P=0.60), and in the 28-day mortality by protein C deficiency class (APC deficiencylt;80%: RR=0.96, 95%CI 0.56 to 1.65, P=0.89; APC deficiencygt;80%: RR=0.61, 95%CI 0.34 to 1.08, P=0.09). Besides, bleeding risk in the rhAPC group was 1.62 fold more than that in the placebo group (RR=1.62, 95%CI 1.17 to 2.23, P=0.004). No significant difference was found in the incidence of adverse reaction (RR=1.04, 95%CI 0.92 to 1.18, P=0.53). Conclusion Current evidence suggests that, rhAPC could not improve the prognosis of patients with severe sepsis, but it significantly increases bleeding risk.
Sepsis 已经成为危重症医学中较为常见的一种综合征，它定义为因病原体感染而引起的全身性炎症反应综合征。严重Sepsis患者预后不佳，治疗上也较为困难，特别是合并Septic Shock和多器官功能不全综合征（MODS）的患者，死亡率仍然较高，因此近年来在临床及研究上均已引起明显的重视。为了能促进Sepsis的研究及治疗，国际上多个医学专科分会联合发起“拯救Sepsis运动（Surviving Sepsis Campaign, SSC）”，并于2004年首次发表了相应的指南，即Surviving Sepsis Campaign Guideline for Management of Severe Sepsis and Septic Shock。今年初SSC再次发表了新版的指南，主要是结合近年的研究成果而在原版的基础上进行适当的补充和更新，以指导临床上严重Sepsis的抢救及治疗。
Objective To investigate the protective mechanism of ulinastatin（UTI） in pulmonary microvascular endothelial cells （PMVECs） attacked by serum from the patients with severe sepsis. Methods PMVECs were cultured in vitro and randomly divided into 4 groups，ie. a normal group （culture medium with 10% fetal bovine serum，group N），a health group （culture medium with 10% healthy human serum，group H），a patient group （culture medium with 10% human septic shock serum，group S），and a ulinastatin group （culture medium with 1000 U/mL UTI and 10% human septic shock serum，group U）. The proliferation activity of PMVECs was measured by MTT expressed by optical density （OD）. The concentration of TNF-α in supernatant of culture medium was examined by ELISA at 0，1，2，4，6 hours. The expression of NF-κB was examined by immunohistochemistry at 1 hour. Results Compared with group N，the cell proliferation activity of group S decreased significantly，and the cell proliferation activity of group U decreased slightly at each time poi nt. Compared with group N，the cell proliferation activity of group S and group U at 1，4，6 hours were significant different （Plt;0.05 ）. Compared with group S，the cell proliferation activity of group U at 1，2，6 hours increased significantly （Plt;0.05）. Obviously positive expression of NF-κB in PMVECs could be seen in group S，a little positive expression in group S，and no expression in group N and group H. Compared with group N，the TNF-α levels of group S and group U increased significantly at each time point with significant differences （Plt;0.01）. Compared with group S，the TNF-α levels were significantly reduced at each time point in group U （Plt;0.01）. Conclusions UTI can reduce the release of TNF-α by inhibiting NF-κB activation，thus reduce PMVECs injury attacked by serum from severe sepsis patients.
Objective To investigate the pathological characteristics of hepatic energy metabolism changes due to biliary sepsis. Methods The hepatic mitochondrial respiratory function and content of ATP was dynamically measured in the self controlled rabbit model of biliary sepsis.Results The mitochondrial S3, respiration control rate (RCR) and phosphorus/oxygen (P/O) were significantly dropping in the infective hepatic lobe 12 hrs after operation with S4 increasing markedly, and the oxidative phosphorylation was uncoupled from 48 hrs after operation onward. The hepatic mitochondrial RCR showed early ascending and then dropping in the non-infective hepatic lobe. The content of ATP and mitochondrial respiratory activity decreased synchronously in both hepatic lobes. Conclusion The hepatic energy metabolic failure was induced in the early stage by biliary sepsis. This is probably the pathological basis of biliary sepsis that is highly critical and always lead to MOF following acute liver function failure.
Objective To investigate the effects of ulinastatin on Treg/Th17 and immune status in patients with severe sepsis.Methods A total of 80 patients with severe sepsis, who were hospitalized in ICU during October 2011 to July 2012, were randomly divided into a routine group and a ulinastatin group. The patients in the ulinastatin group were intravenously administered 30mg ulinastatin three times per day for 5 days in addition to routine bundle treatment. The expression of Treg, Th17 and HLA-DR were detected on the first day in ICU and 5 days after treatment. 20 healthy individuals served as controls. Results Compared with the control group, the severe sepsis group had overexpression of Treg and Th17 ( P lt;0. 01) , higher ratio of Treg/Th17( P lt;0. 01) , and decreased HLA-DR expression of CD14 monocyte ( P lt; 0. 01) . In the severe sepsis patients, ulinastatin injection reduced the abnormal expression of Treg and Th17 ( P lt; 0. 01) , decreased the ratio of Treg/Th17( P lt; 0. 01) , and improved the expression of HLA-DR ( P lt; 0. 01) more effectively compared with the routine treatment. Ulinastatin also lowered 28-day mortality of the patients with sepsis, but the difference between the ulinastatin group and the routine group was not significant. Conclusions In severe sepsis patients, there were abnormal overexpression of Treg and Th17, imbalance of Treg/Th17, and underexpression of HLA-DR which imply an immune suppression. Ulinastatin can decrease the expression of Treg and Th17, inverses the ratio of Treg/Th17, and improve the expression of HLA-DR, so as to improve the prognosis of severe sepsis patients.
ObjectiveTo examine and compare the value of procalcitonin (PCT), C-reactive protein (CRP) and interleukin (IL)-6 in diagnosing fetal sepsis in premature neonates. MethodsPreterm neonates with premature rupture of membrane between January 2010 and September 2012 were screened, and the serum levels of PCT, CRP and IL-6 were detected in the first day of life. All preterm neonates were divided into two groups according to the development of sepsis (45 cases with sepsis and 39 cases without sepsis). ResultsThe levels of PCT, CRP and IL-6 in premature neonates with sepsis were all significantly higher than those without sepsis. The cut-off value of PCT in diagnosis of sepsis was 2.14 μg/L, with a sensitivity and specificity of 76% and 85% respectively; the cut-off value of CRP in diagnosis of sepsis was 7.90 mg/L, with a sensitivity and specificity of 67% and 61% respectively. For IL-6, the cut-off value in diagnosis of sepsis was 13.80 ng/L, and its sensitivity and specificity were high to 90% and 94%, respectively. ConclusionIL-6 is the most reliable biochemical marker for the detection of early-onset sepsis in preterm neonates with premature rupture of membrane.
ObjectiveTo evaluate mid-term results of total hip arthroplasty (THA) for treatment of osteoarthritis secondary to hip sepsis. MethodsBetween February 2003 and January 2009, 62 patients (62 hips) with osteoarthritis secondary to hip sepsis underwent THA. There were 32 males and 30 females with an average age of 39.9 years (range, 18-67 years). The original infection included pyogenic arthritis in 40 hips and tuberculosis in 22 hips. After infection, 35 patients underwent non-operative treatment, and 27 patients received operative management. The average time interval between initial infection and THA was 28.7 years (range, 12-53 years). The preoperative Harris hip score was 24.6±9.2. The Trendelenburg sign was positive in all hips. Leg discrepancy was observed in 25 cases, and the mean discrepancy of bilateral lower extremities was 3.8 cm (range, 2.6-6.5 cm) preoperatively. All hips had no evidence of active hip sepsis. ResultsAll patients were followed up 72 months on average (range, 54-115 months). Intraoperative complications included sciatic nerve injury (2 cases) and femoral shaft fractures (2 cases); postoperative complications included hip anterior dislocation (1 case) and periprosthetic infection (1 case). At last follow-up, 1 hip, 5 hips, 18 hips, and 38 hips were found to have severe pain, moderate pain, slight pain, and no pain respectively. Claudication occurred in 30 patients (mild in 19, moderate in 8, and severe in 3). The Trendelenburg sign was positive in 18 hips. After THA, only 5 patients had a leg length discrepancy of 2.9 cm on average (range, 2.6-3.5 cm). The Harris score was significantly increased to 82.3±11.4 at last follow-up when compared with preoperative one (t=-31.241, P=0.000). The results of subjective satisfaction were very satisfactory in 43 cases, satisfactory in 12 cases, unsatisfactory in 4 cases, and unsatisfactory at all in 3 cases. No sign of aseptic loosening of prosthesis was found during follow-up period. Roentgenographic results showed no radiolucent line or osteolysis in the other patients except 2 patients having local radiolucent. After THA, 12 hips had heterotopic ossification. ConclusionThe mid-term clinical and radiographic results of THA for treatment of osteoarthritis secondary to hip sepsis are good, with the advantages of high satisfactory rate, good function recovery, and low complication incidence.
Objective To compare clinical outcomes of percutaneous nephrolithotomy (PCNL) in patients who initially presented with and without urosepsis. Methods The study included patients who underwent PCNL for renal and ureter urolithiasis removal from January 2010 to December 2014 in our hospital. A 1∶1 matched-pair analysis was performed to compare outcomes and complications of patients who had obstructive urolithiasis with urosepsis initially (OUU) with patients who had obstructive urolithiasis with no urosepsis initially (NOUU) before PCNL. Results A total of 172 patients were included involving 122 (71%) males and 50 (29%) females with a mean age of 46.2 years (range 32 to 65 years). There were no significant differences between two groups in age, gender, BMI, complications, the size of the stones, stone's number and stone location (P>0.05). OUU groups had the similar stone-free rates (86.0%vs. 84.8%, P=0.829) as the NOUU group. OUU group had higher overall complications rate, longer duration of nephrostomy tube (NT), longer hospital length of stay (LOS), longer courses of postoperative antibiotics and higher grade of antibiotics after PCNL (all P<0.05). Higher fever developed postoperatively (11.6%vs. 3.5%, P=0.043), higher asymptomatic bacteriuria (11.6% vs. 3.5%, P=0.043) and symptomatic urinary tract infections (10.5% vs. 2.3%, P=0.029) were also found in OUU groups. There was no significant difference between two groups in sepsis (2.3% vs. 1.2%, P=0.560). Conclusion PCNL after decompression for urolithiasis-related urosepsis has similar success but higher complication rates than obstructive urolithiasis with no urosepsis initially.
Objective To systematically review the diagnostic value of Presepsin for sepsis. Methods Literatures were searched from PubMed, The Cochrane Library (Issue 6, 2017), EMbase, CNKI, CBM, VIP, and WanFang database, and the time was from inception to June 2017, to collect diagnostic studies about Presepsin for sepsis. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies by QUADAS-2 tool. Then meta-analysis was performed by using RevMan 5.3 and Meta-Disc 1.4 software. Pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic curve (SROC) were calculated to assess the diagnostic value of individual diagnostic tests. Results A total of 23 studies with 2 925 sepsis patients and 1 852 controls were finally included. The results of meta-analysis showed that the pooled Sen, Spe, LR+, LR-, DOR, and AUC was 0.80 ［95% CI was (0.78, 0.81), P<0.000 1］, 0.83 ［95%CI was (0.81, 0. 84), P<0.000 1］, 4.78 ［95%CI was (3.62, 6.31), P<0.000 1］, 0.22 ［95%CI was (0.18, 0.27), P<0.000 1］, 23.64 ［95%CI was (16.00, 34.92), P<0.000 1］, and 0.91 ［95%CI was (0.89, 0.94), P<0.001］, respectively. Subgroup analysis showed that the pooled Sen, Spe, LR+, LR-, DOR, and AUC in Caucasian was 0.83 ［95% CI was (0.80, 0.86), P=0.000 1］, 0.79 ［95% CI was (0.76, 0.82), P<0.000 1］, 4.38 ［95%CI was (2.40, 8.02), P<0.000 1］, 0.23 ［95%CI was (0.16, 0.31), P=0.007 8］, 21.09 ［95% CI was (8.82, 50.41), P<0.000 1］, and 0.91 ［95%CI was (0.87, 0.92), P<0.001］ respectively, and in Asian was 0.79 ［95% CI was (0.77, 0.80), P<0.000 1］, 0.85 ［95%CI was (0.83, 0.87), P<0.000 1］,4.74 ［95%CI was (3.82, 5.89), P=0.011 1］, 0.22 ［95% CI was (0.17, 0.28), P<0.000 1］, 24.95 ［95%CI was (16.07, 38.74), P<0.000 1］, and 0.92 ［95%CI was (0.90, 0.95), P=0.001］ respectively, there was no significant difference between Caucasian and Asian in diagnostic accuracy of Presepsin (Z=0.41, P>0.05). Conclusion Current evidence indicates that Presepsin has great early diagnostic value for sepsis.
ObjectiveTo explore the application value of damage control in intra-abdominal sepsis. MethodsThe related literatures were searched by searching literatures with " damage control” " damage control resuscitation” damage control surgery”, and " intra-abdominal sepsis”, to made an review. Results Despite significant advances in management and treatment, mortality from intra-abdominal sepsis remained still high. Due to its unique anatomic and microbial environment, initial operation could not completely remove the source of infection and avoid complications. Therefore, it was becoming increasingly popular to utilize a damage control strategy with abbreviated laparotomy and planned reoperations. ConclusionsDamage control is characterized by staged treatment, and is widely accepted used to manage intra-abdominal sepsis.