von Willebrand factor antigen is an independent marker of poor outcome in patients with early acute lung injury.

OBJECTIVE: The primary objective of this study was to test the hypothesis that the degree of systemic endothelial activation, as measured by the release of von Willebrand factor antigen into the circulation and pulmonary edema fluid, is an important determinant of outcome from acute lung injury and acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Intensive care unit patients in a tertiary university hospital and a university-affiliated city hospital. PATIENTS: Fifty-one intubated, mechanically ventilated intensive care unit patients with acute lung injury or acute respiratory distress syndrome as defined by the North American European Consensus Conference definitions. INTERVENTIONS: Undiluted pulmonary edema fluid and plasma were collected within 1 hr of endotracheal intubation in all patients. MEASUREMENTS: von Willebrand factor antigen concentrations and protein concentration were measured in pulmonary edema fluid and in plasma. MAIN RESULTS: At the time of intubation, median plasma von Willebrand factor antigen was 251%, two-fold higher than the median pulmonary edema fluid von Willebrand factor antigen of 130%. Median edema fluid and plasma von Willebrand factor antigen concentrations were significantly higher in patients who did not survive hospitalization. Plasma von Willebrand factor antigen was also higher in those patients who had a longer duration of mechanical ventilation (as measured by ventilator-free days). Plasma von Willebrand factor antigen was also significantly higher in patients with sepsis and two or more organ system failures. According to stepwise logistic regression analysis, plasma von Willebrand factor antigen was independently associated with in hospital death. The positive predictive value for death if the plasma von Willebrand factor antigen concentration was >450% was 83%. A plasma von Willebrand factor antigen concentration of >450% previously has been shown to predict the development of acute respiratory distress syndrome. CONCLUSIONS: These findings suggest that the degree of systemic endothelial activation and injury at the onset of acute lung injury is an important determinant of the outcome from acute lung injury.     

Role of activated neutrophils in chest trauma-induced septic acute lung injury

More than 50% of severely injured patients have chest trauma. Second insults frequently result in acute lung injury (ALI), with sepsis being the main underlying condition. We aimed to develop a standardized, reproducible, and clinically relevant double-hit mouse model of ALI induced by chest trauma and polymicrobial sepsis and to investigate the pathophysiologic role of activated neutrophils. Lung contusion was applied to C57Bl/6 mice via a focused blast wave. Twenty-four hours later, sepsis was induced by cecal ligation and puncture. For polymorphonuclear leukocyte (PMN) depletion, animals received intravenous injections of PMN-depleting antibody. In response to blunt chest trauma followed by sepsis as well as after sepsis alone, a significant local and systemic inflammatory response with increased cytokine/chemokine levels in lung and plasma was observed. In contrast, lung apoptosis was markedly elevated only after a double hit. Intra-alveolar neutrophils and total bronchoalveolar lavage protein concentrations were markedly increased following isolated chest trauma or the combined insult, but not after sepsis alone. Lung myeloperoxidase activity was enhanced only in response to the double hit accompanied by histological disruption of the alveolar architecture, lung congestion, and marked cellular infiltrates. Neutrophil depletion significantly diminished lung interleukin 1β and interleukin 6 concentrations and reduced the degree of septic ALI. Here we have established a novel and highly reproducible mouse model of chest trauma-induced septic ALI characterizing a clinical relevant double-hit scenario. In particular, the depletion of neutrophils substantially mitigated the extent of lung injury, indicating a pathomechanistic role for neutrophils in chest trauma-induced septic ALI.     

Increased plasma concentrations of brain natriuretic peptide in patients with acute lung injury

: This study was performed to elucidate the pathophysiological role of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in acute lung injury. : We sequentially measured plasma concentrations of immunoreactive BNP and ANP in 10 patients (mean age, 63 years) with acute lung injury and compared those with hemodynamic parameters and pulmonary functions. : Plasma concentrations of immunoreactive BNP and ANP were markedly elevated at entry into the study. Plasma BNP concentrations during the early course (3 days) showed significant (P < .01) positive correlations with systemic vascular resistance index (r = .708) and pulmonary vascular resistance index (r = .573), but a negative correlation with cardiac index (r = −.608). Plasma ANP concentrations showed a significant (P < .05) positive correlation with pulmonary capillary wedge pressure (r = .398). Plasma BNP in 4 patients who died and 1 patient with acute renal failure remained elevated during the entire hospital length of stay (12 days). : These findings suggest that circulating BNP plays an important role in acute lung injury along with ANP as a compensatory mechanism for cardiac dysfunction accompanied by increased systemic vascular resistance index and pulmonary vascular resistance index. Circulating BNP may be a sensitive humoral marker for the degree of ventricular dysfunction associated with acute lung injury.     

Is plasma neutrophil gelatinase-associated lipocalin a predictive biomarker for acute kidney injury in sepsis patients? A systematic review and meta-analysis

PurposeNeutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for early diagnosis of acute kidney injury (AKI). However, the diagnostic value of NGAL for predicting AKI in sepsis patients is unclear.MethodsMEDLINE, EMBASE, and Cochrane Library databases were searched to identify research publications.ResultsTwelve studies from 9 countries including a total of 1582 patients, of whom 315 (19.9%) developed AKI, were included in the study; plasma NGAL levels were significantly higher in adult sepsis patients with AKI than in those without AKI (mean difference, 274.65; 95% confidence interval [CI], 106.16-443.15; I² = 94%). Urine NGAL levels were not significantly different. The diagnostic odds ratio of plasma NGAL for predicting AKI in sepsis patients was 6.64 (95% CI, 3.80-11.58). The diagnostic accuracy of plasma NGAL was 0.881 (95% CI, 0.819-0.923) for sensitivity, 0.474 (95% CI, 0.367-0.582) for specificity, 0.216 (95% CI, 0.177-0.261) for positive predictive value and 0.965 (95% CI, 0.945-0.977) for negative predictive value.ConclusionPlasma NGAL has a high sensitivity and a high negative predictive value for detection of AKI in adult sepsis patients. However, its low specificity and low positive predictive value could limit its clinical utility. The usefulness of urine NGAL was not revealed in this study.     

还原型谷胱甘肽对大鼠脓毒症肺损伤外周血淋巴细胞凋亡率及TNF-α、IL-6水平的影响

目的观察还原型谷胱甘肽对大鼠脓毒症肺损伤外周血淋巴细胞凋亡率及血浆细胞因子TNF-α、IL-6水平的影响，探讨还原型谷胱甘肽对大鼠脓毒症肺损伤的保护作用及其机制。方法应用盲肠结扎穿孔（CLP）法复制大鼠脓毒症肺损伤模型。将清洁级雄性SD大鼠112只，随机分成假手术组（Sham）、脓毒症肺损伤组（ALI）、还原型谷胱甘肽治疗组（GSH）、左旋氧氟沙星治疗组（LEV），每组再分为3、6、12、24h等4个亚组，每个亚组n=7。观察大鼠脓毒症肺损伤肺组织的病理形态学改变，并检测外周血淋巴细胞凋亡率及血浆TNF-α、IL-6水平的变化。结果在脓毒症肺损伤组及左旋氧氟沙星治疗组淋巴细胞凋亡率较假手术组及GSH治疗组明显升高（P〈0．05）；在脓毒症肺损伤组血浆TNF-α水平在CLP术后6h出现升高，较GSH治疗组升高明显（P〈0．01）。脓毒症肺损伤组大鼠血浆IL-6水平于CLP术后3h升高，GSH治疗组CLP术后3h血浆IL-6水平较脓毒症肺损伤组低（P〈0．05）。脓毒症肺损伤组大鼠病理显示明显肺损伤，GSH治疗组大鼠肺损伤程度明显减轻。结论还原型谷胱甘肽能显著抑制外周血淋巴细胞凋亡及血浆TNF-α和IL-6表达水平，对大鼠脓毒症急性肺损伤具有明显的保护作用。     

Expression patterns of plasma von Willebrand factor and serum interleukin-8 in patients with early-stage severe pulmonary contusion

BACKGROUND: von Willebrand factor (vWF) is only released from endothelial cells and platelets and is an in vivo and in vitro marker of endothelial injury in septic patients with acute lung injury (ALI). Interleukin-8 (IL-8), as a proinflammatory mediator causing recruitment of inflammatory cells, induces an increase in oxidant stress mediators and makes it as a key parameter for localized inflammation. However, it has not been well established whether the level of serum IL-8 is associated with the severity of lung injury and whether it is a prognosis marker for severe lung contusion. This study was to investigate the expression of plasma vWF and IL-8 and their association with the severity and outcomes of severe pulmonary contusion.METHODS: A total of 63 patients were divided into a severe pulmonary contusion with acute respiratory distress syndrome (ARDS) group and a non-ARDS group, or a survivor group and a non-survivor group, or an injury severity score (ISS) <20 group and an ISS ≥20 group. Another 20 healthy volunteers served as controls. The levels of plasma vWF and serum IL-8 were measured by enzyme-linked immunosorbent assay (ELISA) at 1, 3, 5 and 7 days after injury. The expression patterns of the plasma vWF and serum IL-8 were compared between different groups.RESULTS: The concentrations of plasma vWF and serum IL-8 were significantly increased in all severe pulmonary contusion patients at all time points in comparison with the control group. The concentrations of plasma vWF in patients with ARDS increased during the whole study period, but vWF in patients with non-ARDS increased gradually until day 5 and then decreased at day 7. The concentration of serum IL-8 showed a similar expression pattern in both groups, but the expression increased more significantly in the ARDS group than in the non-ARDS group. Interestingly, both plasma vWF and serum IL-8 levels steadily increased in the non-survivor group. Furthermore, the level of plasma vWF was higher in the ISS≥20 group than in the ISS<20 group. The level of serum IL-8 in the ISS≥20 group was consistently high, while that in the ISS<20 group peaked at day 3 and decreased at day 5. In addition, the level of plasma vWF was positively correlated with platelet count, but negatively correlated with oxygen index. The level of serum IL-8 was positively correlated with white blood cell count and ISS score, and inversely correlated with oxygen index.CONCLUSION: The elevated levels of plasma vWF and serum IL-8 in severe pulmonary contusion patients reflect the severity of pulmonary injury and patients outcomes, suggesting that the plasma vWF and serum IL-8 are sensitive markers for clinical evaluation of the severity of pulmonary injury and predication of patient prognosis.     

A pilot study of a new test to predict extubation failure

Introduction

In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge.

Methods

Endostatin was measured by ELISA and western blotting.

Results

Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels.

Conclusions

Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation.     

Type XVIII collagen degradation products in acute lung injury

Introduction

In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge.

Methods

Endostatin was measured by ELISA and western blotting.

Results

Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels.

Conclusions

Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation.     

Thromboxane A2 and granulocyte elastase after severe trauma--relationship to complications and survival rates

Of 64 polytraumatized patients with a mean injury severity score of 33.1, 42 showed marked systemic release of thromboxane B2 and granulocyte elastase during the initial 18 hours after trauma, reaching peak arterial levels of greater than 1,000 pg/ml and ng/ml, respectively. If those patients ("responders": plasma TXB2 greater than 250 pg/ml) were compared with the remaining 22 ("non-responders": TXB2 less than 250 pg/ml) the following became obvious: "Late" mortality (greater than 3 d) was 31% in responders, which is significantly higher than in non-responders (9%). No correlation was observed between "early" mortality (less than 3 d) and mediator release. There was no difference in the incidence of the adult respiratory distress syndrome (ARDS) (38% versus 32%) or the late sepsis syndrome (17% versus 18%) between responders and non-responders. Morbidity, however, differed markedly in that ARDS in responders was associated with significantly higher elastase levels, a higher mortality and 10 times higher incidence of sepsis as compared to responders without ARDS. ARDS in non-responders, by contrast, did not change elastase maxima or the mortality rate as compared to non-responders without ARDS. It is concluded that TXB2 is not a predictor of posttraumatic ARDS, but is related to a complicated course, in particular to sepsis and mortality. Elastase with high probability predicts ARDS and/or the late sepsis syndrome. Simultaneous determination of TXB2 further enhances the predictive value of elastase.     

急性胰腺炎早期患者IL-10、IL-6变化的临床意义

【目的】了解急性胰腺炎 (AP)早期患者IL 10、IL 6的变化及临床意义。【方法】分别在AP病人入院后d1和d3 采血 ,回顾性分析其IL 6、IL 10的早期变化并与健康献血人群比较。【结果】AP患者血浆IL 10阳性检测率在入院d1为 4 4 .6 %、d3 为 2 4 .4 % ,正常人群无阳性结果 (P <0 .0 5 )。血浆IL 6入院d1SAP组血浆IL 6浓度明显高于MAP组及正常对照组 (P <0 .0 1) ,MAP组与正常组IL 6浓度也有显著差异 (P <0 .0 1) ,最佳截断值为 10 5 pg/ml,预测SAP的敏感性 84 .6 2 % ,特异性 94 .12 % ,阳性预断值 93.5 2 % ,阴性预断值 85 .95 % ,可用度为 78.73% ;入院d3 SAP组血浆IL 6浓度仍明显高于MAP组和正常组 (P <0 .0 1) ,MAP组与正常组相比差异无显著性 (P >0 .0 5 )。【结论】IL 10在正常人中一般不能检测出 ,在AP时升高 ;SAP早期IL 6浓度明显升高 ,检测IL 6可能对于早期鉴诊有一定的意义 ,其监测SAP的敏感性、特异性较高 ,且稳定性较好 ,可作为其临床诊断参考指标之一     

Extravascular lung water in patients with severe sepsis: a prospective cohort study

Introduction

Few investigations have prospectively examined extravascular lung water (EVLW) in patients with severe sepsis. We sought to determine whether EVLW may contribute to lung injury in these patients by quantifying the relationship of EVLW to parameters of lung injury, to determine the effects of chronic alcohol abuse on EVLW, and to determine whether EVLW may be a useful tool in the diagnosis of acute respiratory distress syndrome (ARDS).

Methods

The present prospective cohort study was conducted in consecutive patients with severe sepsis from a medical intensive care unit in an urban university teaching hospital. In each patient, transpulmonary thermodilution was used to measure cardiovascular hemodynamics and EVLW for 7 days via an arterial catheter placed within 72 hours of meeting criteria for severe sepsis.

Results

A total of 29 patients were studied. Twenty-five of the 29 patients (86%) were mechanically ventilated, 15 of the 29 patients (52%) developed ARDS, and overall 28-day mortality was 41%. Eight out of 14 patients (57%) with non-ARDS severe sepsis had high EVLW with significantly greater hypoxemia than did those patient with low EVLW (mean arterial oxygen tension/fractional inspired oxygen ratio 230.7 ± 36.1 mmHg versus 341.2 ± 92.8 mmHg; P < 0.001). Four out of 15 patients with severe sepsis with ARDS maintained a low EVLW and had better 28-day survival than did ARDS patients with high EVLW (100% versus 36%; P = 0.03). ARDS patients with a history of chronic alcohol abuse had greater EVLW than did nonalcoholic patients (19.9 ml/kg versus 8.7 ml/kg; P < 0.0001). The arterial oxygen tension/fractional inspired oxygen ratio, lung injury score, and chest radiograph scores correlated with EVLW (r² = 0.27, r² = 0.18, and r² = 0.28, respectively; all P < 0.0001).

Conclusions

More than half of the patients with severe sepsis but without ARDS had increased EVLW, possibly representing subclinical lung injury. Chronic alcohol abuse was associated with increased EVLW, whereas lower EVLW was associated with survival. EVLW correlated moderately with the severity of lung injury but did not account for all respiratory derangements. EVLW may improve both risk stratification and management of patients with severe sepsis.     

Endothelin production in sepsis and the adult respiratory distress syndrome

Objective Septic shock is characterised by a decrease in systemic vascular resistance. Nevertheless, regional increases in vascular resistance can occur which may predispose to organ dysfunction, including the adult respiratory distress syndrome (ARDS). Because endothelial damage is a major feature of acute lung injury, we examined whether the potent endothelial vasoconstrictor peptide endothelin-1 plays a pathophysiological role in sepsis of ARDS.Design Plasma endothelin was measured in mixed venous, pulmonary capillary and arterial blood, and the relationship with outcome measures was determined.Setting The intensive care unit of a university teaching hospital.Patients and participants A consecutive series of well-characterised patients with sepsis syndrome, both with (n=11) and without (n=15) ARDS, and ventilated controls without sepsis or ARDS (n=7).Measurements and results Plasma endothelin was significantly elevated in patients with sepsis alone and in patients with sepsis and ARDS. Plasma endothelin did not differ among mixed venous, pulmonary capillary and systemic arterial blood. On multiple regression analysis, plasma endothelin correlated positively with organ failure score and with oxygen consumption, and negatively with the P_aO₂FiO₂ ratio. There was no correlation with plasma creatinine, suggesting that decreased renal clearance did not account for the high plasma endothelin concentrations.Conclusions Although the lung does not appear to be the major site of endothelin production in critically ill patients with sepsis, increased endothelin production may contribute to regional increases in vacular resistance, hypoperfusion, and the development of organ failure, including ARDS, in patients with sepsis.     

Antithrombin III in critically ill patients

To assess the role of antithrombin III (ATIII) in the thrombotic complications of acutely ill patients who suffered from septicemia or trauma, with or without evidence of acute lung injury, we measured the plasma concentration of ATIII-related antigen (ATIII:Ag) in 146 patients with acute lung injury and in 43 critically ill patients without lung injury. We found plasma ATIII:Ag levels of both groups of acutely ill patients to be significantly lower than those of normal subjects (n = 21). The plasma ATIII:Ag levels of patients with acute lung injury, however, were significantly higher than those without lung injury (P < .01). By separating post-trauma acutely ill patients with lung injury from those with septicemia, we noted that their plasma ATIII:Ag levels were identical to those of normal subjects despite activation of blood coagulation. This finding led us to examine ATIII functional activity (ATIII:Fn) and search for ATIII-enzyme(s) complexes in 46 patients with acute lung injury (30 patients with sepsis and 16 post-trauma patients) and in 12 acutely ill patients without lung injury (eight patients with sepsis and four post-trauma patients). These 58 patients were representative of the groups studied and had no evidence of hepatic or renal dysfunction. We found significantly reduced ATIII:Ag and ATIII:Fn in septic patients, with or without lung injury, as compared with the normal levels (P < .05). After trauma, patients with or without lung injury had normal ATIII:Ag, but the ATIII:Fn levels were disproportionately lower. Following trauma, the ATIII:Ag/ATIII:Fn ratio was significantly higher than in septicemia patients or in normal patients. Patients who died from septicemia and post-trauma had higher ATIII:Ag to ATIII:Fn ratios, while surviving patients had ATIII:Ag to ATIII:Fn ratios closer to normal. In addition, in all post-trauma or septicemia patients, there was evidence of ATIII-enzyme(s) complex formation by cross-immunoelectrophoresis despite ATIII levels and the presence or absence of acute lung injury. High ATIII:Ag to ATIII:Fn ratios and the presence of circulating ATIII:enzyme(s) complexes were associated with high mortality. The ATIII alterations, however, did not allow us to determine the presence of acute lung injury. The ATIII changes observed in our patients appeared to be primarily influenced by the differing pathways of blood activation that occurred in septicemia and trauma.     

Increased plasma and ventricular fluid interleukin-6 levels in patients with head injury

The cytokine interleukin-6 (IL-6) plays a major role in initiating the acute phase response, especially in the production of acute phase reactants such as C-reactive protein. The objectives of this study were to determine whether plasma or ventricular fluid IL-6 levels were elevated at time of admission after head injury and whether plasma IL-6 levels related temporally to clinical improvement of levels of acute phase reactants. Thirty patients with Glasgow Coma Scale (GCS) scores of 3 through 10 were observed for 15 days after head injury. Peak elevation of plasma IL-6 occurred on admission (85 +/- 12 U/ml; normal level is less than 2 U/ml) and then decreased during the hospital course to a level of 29 +/- 4 U/ml on day 15. Plasma IL-6 levels decreased significantly faster in patients with admission peak 24-hour GCS scores of 8 through 10 compared with patients with GCS score less than 8 (p less than 0.01). Patients had markedly elevated and variable ventricular fluid IL-6 levels on admission (mean 3880 +/- 2022 U/ml; normal, less than 2 U/ml). A temporal relationship was found between plasma IL-6 levels and multiple acute phase reactants thought to be mediated by IL-6. We conclude that plasma and ventricular fluid levels of IL-6 are elevated after head injury and that plasma IL-6 level is temporally related to acute phase reactants and clinical improvement. We suggest that IL-6 may play an etiologic role in many of the metabolic or nutritional sequelae of head injury.     

Plasma DNA as a prognostic marker in trauma patients

BACKGROUND: Recently, much interest has developed in the potential use of plasma DNA as a diagnostic and monitoring tool. We hypothesized that plasma DNA is increased in patients with trauma and may be prognostic in such patients. METHODS: We studied 84 patients who had sustained an acute blunt traumatic injury. We measured plasma DNA by a real-time quantitative PCR assay for the beta-globin gene. Blood samples were collected at a median time of 60 min following injury. Blood samples were also obtained from 27 control subjects. RESULTS: The median plasma DNA concentrations in the control, minor/moderate trauma (Injury Severity Score <16; n = 47), and major trauma (Injury Severity Score > or =16; n = 37) groups were 3154 kilogenome-equivalents/L, 13 818 kilogenome-equivalents/L, and 181 303 kilogenome-equivalents/L, respectively. Plasma DNA concentrations in patients with adverse outcomes, including acute lung injury, acute respiratory distress syndrome, and death, had 11. 6- to 12-fold higher plasma DNA concentrations than those who did not develop these complications. At a cutoff of 232 719 kilogenome-equivalents/L, the sensitivities of plasma DNA analysis for the prediction of acute lung injury, acute respiratory distress syndrome, and death were 100% (95% confidence interval, 100-100%), 100% (95% confidence interval, 100-100%), and 78% (95% confidence interval, 40-97%), respectively. The respective specificities were 81% (95% confidence interval, 71-89%), 80% (95% confidence interval, 70-88%), and 82% (95% confidence interval, 71-90%). CONCLUSIONS: Plasma DNA is increased after trauma and may be a potentially valuable prognostic marker for these patients.     

心钠素对急性呼吸困难的诊断和鉴别诊断意义

目的：探讨心钠素在急性呼吸困难中的诊断和鉴别诊断意义。方法：急性呼吸困难患者110例,测定血浆心钠素水平,以ANP=0．29pg／I,为阳性界定值对其诊断心衰的价值进行评价。结果：心衰患者ANP明显高于非心衰患者,以ANP=0．29pg／L为阳性界定值,ANP诊断心源性呼吸困难的敏感性为95．00％,特异性为88．64％,阳性预测值为86．36％,阴性预测值为95．12％。结论：ANP对于诊断和鉴别诊断急性呼吸困难,具有重要意义。     

Angiotensin converting enzyme: an in vivo and in vitro marker of endothelial injury.

An elevated level of von Willebrand factor (vWf) is a well-established marker for both in vivo and in vitro endothelial cell injury. Recent studies indicate that the plasma level of angiotensin-converting enzyme (ACE) in systemic sclerosis is reduced in association with elevated vWf levels. Because the endothelial cell is capable of producing both mediators, and because endothelial cell injury is a fundamental process in systemic sclerosis, we investigated in this study the effect of in vitro endothelial cell injury on the synthesis of both factors. Endothelial cells derived from human umbilical veins, in the second passage, were activated by exposure to interleukin-1 or lymphotoxin or were injured by radiation, actinomycin, or trypsin (each can be shown to induce dose-dependent endothelial cell cytotoxicity). ACE (spectrophotometric method) and vWf levels (enzyme-linked immunosorbent assay method) were determined in the supernatant and in the cell lysate 48 hours after cellular injury and activation. An increase in vWf levels was found in the lysate and in the supernatant from the cells that underwent injury or activation, whereas ACE levels were increased after activation but decreased after injury. Next, and as an in vivo clinical corollary to the in vitro endothelial cell injury, we evaluated ACE and vWf levels in the plasma of seven children in the acute phase of Kawasaki disease, a disorder characterized by widespread vascular injury. Plasma ACE levels were significantly lower than control levels, whereas vWf levels were increased, reflecting the known prominent endothelial cell injury in this disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

中性粒细胞与淋巴细胞比值和中性粒细胞胞外诱捕网与脓毒症肝损伤的临床研究

目的:探讨外周血中性粒细胞与淋巴细胞比值（neutrophil/lymphocyte ratio, NLR）联合中性粒细胞胞外诱捕网(neutrophil extracellular traps, NETs)对预测脓毒症患者发生肝损伤的临床价值。方法:采用前瞻性观察性研究方法,选择2019年03月至2020年06月南京医科大学附属无锡人民医院重症医学科收治的符合脓毒症3.0诊断标准、肝损伤诊断标准的患者作为研究对象,记录患者的基础资料,根据入院时血常规计算NLR,使用PicoGreen荧光定量检测试剂盒检测患者入院时外周血浆游离DNA（cf-DNA/NETs）定量水平,根据是否发生肝损伤,将患者分为脓毒症非肝损伤组和脓毒症肝损伤组,二元logistics回归分析发生脓毒症肝损伤的危险因素,绘制受试者工作特征曲线（ROC）,并分析NLR、NETs、NLR联合NETs对预测脓毒症患者发生肝损伤的价值。结果:入选脓毒症患者122例,其中发生脓毒症肝损伤的患者45例,发生率为36.89%。脓毒症肝损伤组NLR为（21.63±4.71）,脓毒症非肝损伤组NLR为（15.03±4.71）,脓毒症肝损伤组NETs水平为（505.86±250.05）μg/L,脓毒症非肝损伤组NETs水平为（179.27±67.20）μg/L,两组间比较差异均有统计学意义（均 P<0.05）。二元Logistics回归分析发现,入院时NLR（ OR=1.470, 95% CI:1.121~1.926, P<0.05）、NETs（ OR=1.018, 95% CI: 1.005~1.030, P<0.05）是脓毒症患者发生肝损伤的独立危险因素。NLR的最佳截断值为16.68,NETs的最佳截断值为317μg/L,联合应用NLR和NETs预测脓毒症患者发生肝损伤的灵敏度为77.78%,特异度为98.70%,曲线下面积为0.930,约登指数为0.765。 结论:外周血NLR和NETs水平是脓毒症患者发生肝损伤的独立危险因素,联合应用NLR和NETs对脓毒症患者发生肝损伤具有一定的预测价值。以NLR为16.68、NETs为317 μg/L作为界值,可以作为预测脓毒症患者发生肝损伤的早期预警指标。     

The inflammation–coagulation axis as an important intermediate pathway in acute lung injury

Markers of inflammation, coagulation, and fibrinolysis predict an adverse outcome in patients with sepsis. These markers also seem predictive of an adverse outcome in patients with localized infection and inflammation, such as in acute lung injury. Whether this is entirely related to the disease or is also due to ventilation strategies that may be harmful for the lungs, however, is not clear. In the present issue of Critical Care, McClintock and colleagues demonstrate that these biomarkers retain their predictive effect even if lung-protective ventilation strategies are applied. Besides being biomarkers that predict outcome in patients with acute lung injury, their activation of inflammation and coagulation seems also to play a pivotal role in the pathogenesis of acute lung injury, and may thereby represent an interesting novel target for therapeutic intervention.     

血清降钙素原预测慢性阻塞性肺疾病急性加重期患者院内感染的临床价值

目的评估血清降钙素原（PCT）在慢性阻塞性肺疾病急性加重期（AECOPD）患者预测院内感染的临床价值。方法选取2009年1月至2011年10月收治入院的AECOPD患者78例,行血、痰细菌培养及胸片检查,监测患者体温、肺部体征、痰液性状等的变化及院内感染情况。应用半定量固相免疫法测定PCT水平,同时测定C反应蛋白（CRP）水平及白细胞（wBC）计数。观察各指标预测院内感染的敏感度、特异度、准确度、阳性预测值、阴性预测值。结果脓毒症、严重脓毒症的AECOPD患者在住院期间有较高的院内感染发生率。PCT平均增加值在0．12～0．30μg／L时,预测院内感染的敏感度为86．7％,特异度为66．7％,准确度为82．1％,阳性预测值为89．7％,均高于CRP、WBC、体温。结论血清PCT具有高敏感性和高特异性,可作为早期预测AECOPD患者院内感染的炎性指标。