New diagnostic and prognostic markers of ventilator-associated pneumonia

PURPOSE OF REVIEW: The purpose of this review is to analyze the potential advantages and drawbacks of using biomarkers of bacterial infection for the diagnosis and prognosis of ventilator-associated pneumonia. RECENT FINDINGS: Whereas procalcitonin and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have both greater diagnostic accuracies than most commonly used clinical parameters and other biomarkers of infection, such as C-reactive protein, they can be increased in noninfectious conditions or remain low in patients with true infection. Furthermore, these assays cannot determine the causative organisms and associated patterns of antibiotic susceptibility. SUMMARY: Procalcitonin and sTREM-1 should be used only as a complementary tool, to reinforce the usual diagnostic work-up. However, serial serum procalcitonin and sTREM-1 measurements may provide an opportunity to change the treatment early in the course of patients with ventilator-associated pneumonia, either to intensify treatment when their levels stay high, or to avoid unnecessary prolonged courses of antibiotics when their levels rapidly decrease. Whether procalcitonin and/or sTREM-1 guidance can reduce antibiotic use in such a setting will require additional studies, but such a strategy appears promising.     

Risk and prognostic factors of ventilator-associated pneumonia in trauma patients

OBJECTIVE: To assess the risk and prognostic factors of ventilator-associated pneumonia in trauma patients, with an emphasis on the inflammatory response. DESIGN: Case-control study. SETTING: Trauma intensive care unit. PATIENTS: Of 190 consecutive mechanically ventilated patients, those with microbiologically confirmed pneumonia (n = 62) were matched with 62 controls without pneumonia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical, microbiological, and outcome variables were recorded. Cytokines were measured in serum and blind bronchoalveolar lavage specimens at onset of pneumonia. Multivariate analyses of risk and prognostic factors for ventilator-associated pneumonia were done. Increased severity of head and neck injury (odds ratio, 11.9; p < .001) was the only independent predictor of pneumonia. Among patients with pneumonia, serum levels of interleukin-6 (p = .019) and interleukin-8 (p = .036) at onset of pneumonia were higher in nonresponders to treatment. Moreover, serum levels of tumor necrosis factor-alpha (p = .028) and interleukin-6 (p = .007) at onset of pneumonia were higher in nonsurvivors. Mortality in the intensive care unit was 23% in cases and controls. Nonresponse to antimicrobial treatment (odds ratio, 22.2; p = .001) and the use of hyperventilation (p = .021) were independent predictors of mortality in the intensive care unit for patients with pneumonia. CONCLUSIONS: Severe head and neck trauma is strongly associated with ventilator-associated pneumonia. A higher inflammatory response is associated with nonresponse to treatment and mortality among patients with pneumonia. Although pneumonia did not influence mortality, nonresponse to treatment independently predicted mortality among these patients.     

Copeptin is a predictive biomarker of severity in acute pancreatitis

Background

Acute pancreatitis remains a common intraabdominal disease with a complex pathophysiology. The overall outcome has improved, but specific treatment remains elusive. The challenge is the early identification and treatment of patients who will develop severe acute pancreatitis. Therefore, the aim of the present study is to investigate plasma levels of copeptin in the initial phase of predicted severe acute pancreatitis.

Methods

Between August 2008 and December 2011, 57 patients with acute pancreatitis and 30 healthy individuals were included in the study. Four blood samples, for serum copeptin measurement, were taken from each individual in each group. The first measurement was taken from the admission blood sample. The subsequent 3 samples were taken at 12, 24, and 48 hours after the onset of pain.

Results

Copeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients.

Conclusions

Copeptin plasma concentrations were significantly higher in patients with acute pancreatitis when compared with healthy controls. Copeptin plasma concentrations in severe pancreatitis patients were significantly higher than in mild pancreatitis patients.     

Prevention of ventilator-associated pneumonia or ventilator-associated complications: a worthy, yet challenging, goal

Ventilator-associated pneumonia is a difficult diagnosis to establish in the critically ill patient because of the presence of underlying cardiopulmonary disorders (e.g., pulmonary contusion, acute respiratory distress syndrome, atelectasis) and the nonspecific radiographic and clinical signs associated with this infection. However, the escalating antimicrobial resistance of the bacterial pathogens associated with ventilator-associated pneumonia, as well as with other nosocomial infections, has created an imperative to reduce their occurrence and the unnecessary use of antibiotics. Hospital-based process improvement initiatives aimed at the prevention of ventilator-associated pneumonia, and other ventilator-associated complications, have been successfully used despite the limitations of clinical criteria for establishing the diagnosis of ventilator-associated pneumonia. Given current restrictions in hospital resources, absence of available new antimicrobial agents, and potential lack of reimbursement for patients with development of ventilator-associated pneumonia, hospitals need to develop and successfully implement programs aimed at reducing ventilator-associated pneumonia. The use of evidence-based bundles targeting ventilator-associated pneumonia seems to be a reasonable first step in addressing this important clinical problem.     

From ventilator-associated tracheobronchitis to ventilator-associated pneumonia

Ventilator-associated complications (VACs) are those complications that develop during the period of intubation. The most frequent VAC is infection. Ventilator-associated tracheobronchitis (VAT) is one of the ventilator-associated complications occurring in the critically ill patient. This infection represents an intermediate process between lower respiratory tract colonization and ventilator-associated pneumonia. Increased duration of mechanical ventilation has been reported in patients with VAT because of increased sputum production and airway inflammation. Two studies have shown a beneficial effect of antimicrobial treatment in patients with VAT. The optimal duration of antimicrobial treatment in patients with VAT should be further investigated because short courses of antimicrobials might be sufficient. Aerosolized antibiotics also need to be compared to systemic antibiotics in these patients.     

改良型临床肺部感染评分在呼吸机相关性肺炎预后评估中的价值

目的 探讨改良型临床肺部感染评分(CPIS)在呼吸机相关性肺炎预后评估中的价值。方法 选取2018年10月至2020年10月榆林市第二医院收治的100例呼吸机相关性肺炎患者作为研究对象。对所有患者进行呼吸机相关性肺炎的规范化治疗,并根据治疗后的效果将患者分为预后良好组(n=62)和预后不良组(n=38)。比较两组患者治疗前、后的血清学指标(PCT、CRP)、血气指标(PO₂、PCO₂、OI)及改良型CPIS评分,并分析改良型CPIS评分与PCT、CRP、PO₂、PCO₂、OI的相关性。结果 治疗前,两组的血清PCT、CRP水平比较,差异无统计学意义(P>0.05);治疗后,两组的血清PCT、CRP水平均较治疗前明显降低,且预后良好组低于预后不良组,差异具有统计学意义(P<0.05)。治疗前,两组的PO₂、PCO₂、OI比较,差异无统计学意义(P>0.05);治疗后,两组的PO₂、OI较治疗前明显升高,PCO_...     

Clinical significance of kallikrein 5 as a novel prognostic biomarker in gastric adenocarcinoma

BackgroundsGastric cancer is one of the most common cancers with unsatisfied prognosis. It is challenging to predict gastric cancer prognosis due to its highly heterogeneous nature. Kallikrein 5 (KLK5) belongs to the family of kallikreins, which plays a crucial role in serine proteolysis and exerts diverse physiological functions. The role of KLK5 in human gastric adenocarcinoma (GAC) has not been elucidated. In the present study, we aimed to examine the expression level of KLK5 and dissect whether the KLK5 expression was associated with GAC prognosis.Patients and methodsClinicopathological analyses were performed in a retrospective GAC patient cohort (n = 138). The expression of KLK5 was tested by quantitative RT‐PCR and immunohistochemistry staining. The prognostic role of KLK5 in GAC was assessed by univariate and multivariate analyses. The effects of KLK5 on cell proliferation, migration, and invasion were examined through cellular experiments.ResultsThe data showed that KLK5 expression was elevated in GAC tissues compared with normal stomach tissues. Protein expression of KLK5 was positively correlated with tumor invasion depth and lymph node metastasis. Patients with higher KLK5 expression had poorer overall survival. KLK5 was identified to be an independent risk factor according to multivariate analysis. Using human GAC cell lines, we found that KLK5 can promote tumor cell migration and invasion.ConclusionsOur study demonstrated that higher expression of KLK5 was significantly correlated with a poorer prognosis of GAC patients, implying the potential of KLK5 as a novel prognostic biomarker in GAC.     

Cost-effectiveness issues in ventilator-associated pneumonia

Ventilator-associated pneumonia has attracted considerable interest as a subject of clinical efficacy assessment research. This article summarizes recommendations made by the United States Public Health Service Panel on Cost-Effectiveness in Health and Medicine and by a panel convened by the American Thoracic Society to address economic analyses in critical care. The following recommendations are made for the performance of cost-efficacy studies in ventilator-associated pneumonia. For mortality-based studies, only data from prospective and blinded randomized trials are suitable for analysis. For cost-minimization studies, observational studies may be useful but should use rigorous matching schemes. Estimates for the quality of life of patients surviving an episode of ventilator-associated pneumonia should be based on the disease that required mechanical ventilation or compared to data available for survivors of the respiratory distress syndrome, whichever diagnosis provides a lessened quality of life. Within an individual intensive care unit the greatest cost savings come from constructing a cohesive and unified approach to many issues seen in the unit.     

De-escalation therapy in ventilator-associated pneumonia

PURPOSE OF REVIEW: To describe the use of a 'de-escalation' strategy to deliver appropriate empiric therapy for ventilator-associated pneumonia, without the overuse of antibiotics. RECENT FINDINGS: Initial empiric therapy can be appropriate in 80-90% of ventilator-associated pneumonia patients, if it is selected on the basis of local microbiologic data or individual patient surveillance cultures. Following initial empiric therapy, de-escalation means using microbiologic and clinical data to change from an initial broad-spectrum, multidrug empiric therapy regimen to a therapy with fewer antibiotics and agents of narrower spectrum. In spite of early success with this approach there is an opportunity to de-escalate more often, particularly in patients with negative pretherapy cultures, and in those whose cultures show multidrug-resistant organisms, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. In addition, it is possible to reduce the total duration of therapy, particularly when the initial therapy is accurate. When de-escalation has been employed, it has led to less antibiotic usage, shorter durations of therapy, fewer episodes of secondary pneumonia and reduced mortality, without increasing the frequency of antibiotic resistance. SUMMARY: De-escalation is a promising strategy for optimizing the responsible use of antibiotics while allowing the delivery of prompt and appropriate empiric therapy of ventilator-associated pneumonia.     

支气管镜对耐多药呼吸机相关性肺炎的干预

目的 探讨支气管镜干预在耐多药呼吸机相关性肺炎治疗过程中的价值.方法 耐多药呼吸机相关性肺炎患者78例,治疗过程中分为接受支气管镜检查治疗组(干预组)和未行支气管镜检查治疗组(对照组),比较2组血气分析变化、首次痰培养阳性率、临床肺部感染评分及病死率.结果 治疗后干预组与对照组比较pH、p(O2)升高,p(CO2)降低(P＜0.05);首次痰培养阳性率明显高于对照组,临床肺部感染评分、病死率明显低于对照组,差异均有统计学意义(P＜0.05).结论 在耐多药呼吸机相关性肺炎患者治疗过程中早期进行支气管镜检查治疗,短期内可改善预后.     

De-escalation therapy in ventilator-associated pneumonia

OBJECTIVE: To evaluate de-escalation of antibiotic therapy in patients with ventilator-associated pneumonia. DESIGN: Prospective observational study during a 43-month period. SETTING: Medical-surgical intensive care unit. PATIENTS: One hundred and fifteen patients admitted to the intensive care unit with clinical diagnosis of ventilator-associated pneumonia. All the episodes of ventilator-associated pneumonia received initial broad-spectrum coverage followed by reevaluation according to clinical response and microbiology. Quantitative cultures obtained by bronchoscopic examination or tracheal aspirates were used to modify therapy. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty-one episodes of ventilator-associated pneumonia were diagnosed. Change of therapy was documented in 56.2%, including de-escalation (the most frequent cause) in 31.4% (increasing to 38% if isolates were sensitive). Overall intensive care unit mortality rate was 32.2%. Inappropriate antibiotic therapy was identified in 9% of cases and was associated with 14.4% excess intensive care unit mortality. Quantitative tracheal aspirates and bronchoscopic samples (58 protected specimen brush and three bronchoalveolar lavage) were associated with 32.7% and 29.5% intensive care unit mortality and 29.3% and 34.4% de-escalation rate. De-escalation was lower (p < .05) in the presence of nonfermenting Gram-negative bacillus (2.7% vs. 49.3%) and in the presence of late-onset pneumonia (12.5% vs. 40.7%). When the pathogen remained unknown, half of the patients died and de-escalation was not performed. CONCLUSION: De-escalation was the most important cause of antibiotic modification, being more feasible in early-onset pneumonia and less frequent in the presence of nonfermenting Gram-negative bacillus. The impact of quantitative tracheal aspirates or bronchoscopic techniques was comparable in terms of mortality.     

Copeptin: a new and promising diagnostic and prognostic marker

The study conducted by Seligman and coworkers included in the previous issue of Critical Care demonstrates that copeptin is a promising marker to predict outcome in patients with ventilator-associated pneumonia. In recent years, copeptin has emerged as a new prognostic marker in a variety of diseases, such as sepsis, community-acquired pneumonia, chronic obstructive pulmonary failure, heart failure and myocardial infarction. What is the pathophysiological basis for these findings? Copeptin together with vasopressin is co-secreted from the posterior pituitary and therefore mirrors the amount of vasopressin in the circulation. Vaso-pressin is a main secretagogue of the hypothalamo–pituitary–adrenal axis, thereby mirroring the individual stress level. Furthermore, vasopressin is an important hormone in salt and volume regulation. In this context, copeptin is also a diagnostic marker in patients with diabetes insipidus and in patients with disordered water states.     

Therapy of ventilator-associated pneumonia

Therapy of ventilator-associated pneumonia should be a patient-based approach focusing on some key features are listed here: early initial therapy should be based on broad-spectrum antibiotics. Empirical treatment may be targeted after direct staining and should be modified according to good-quality quantitative microbiological findings, but should never be withdrawn in presence of negative direct staining or delayed until microbiological results are available. Courses of therapy should be given at high doses according to pharmacodynamic and tissue penetration properties. Prolonging antibiotic treatment does not prevent recurrences. Methicillin-sensitive Staphylococcus aureus should be expected in comatose patients. Methicillin-resistant Staphylococcus aureus should not be expected in patients without previous antibiotic coverage. Pseudomonas aeruginosa should be covered with combination therapy. Antifungal therapy, even when Candida spp is isolated in significant concentrations, is not recommended for intubated nonneutropenic patients. Vancomycin, given at the standard doses and route of administration for the treatment of VAP caused by Gram-positive pathogens, is associated with poor outcomes. The choice of initial antibiotic should be based on the patient's previous antibiotic exposure and comorbidities, and local antibiotic susceptibility patterns, which should be updated regularly.     

Diagnosis of ventilator-associated pneumonia

Introduction

Ventilator-associated pneumonia (VAP) is difficult to diagnose. Recent data suggest quantitative endotracheal aspirate (ETA) may be noninferior diagnostically to quantitative bronchoalveolar lavage (BAL). We hypothesized this would be the case.

Methods

Blind quantitative ETA and BAL were performed on 150 consecutive ventilated patients with suspected VAP in a prospective single-centre medical intensive care unit study over a 2-year inclusion period. Patients were either antibiotic-naive or antibiotic-free for 72 hours. Diagnostic yield, Gram stain and culture results, and impact on antibiotic therapy were assessed. The independent impact of a positive BAL or ETA result on ventilator settings and 28-day mortality was calculated. The BAL/ETA safety was assessed hemodynamically.

Results

Bronchoalveolar lavage had significantly higher diagnostic yield (49.3% vs 34.0%, P = .01), more frequent impact on antibiotic therapy (usually de-escalation) (48.0% vs 32.7%, P = .01), and greater sensitivity (64.1% vs 42.6%, P = .0003) than ETA. There was moderate intertest agreement and no difference in specificity and positive and negative predictive values. A positive BAL or ETA result did not independently alter the frequency of ventilator changes or 28-day mortality. Both procedures were well tolerated.

Conclusion

Quantitative BAL is safe and has greater diagnostic utility than ETA for VAP facilitates de-escalation. This study provides support for quantitative BAL in VAP diagnosis.     

Prevention of ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) is an important source of morbidity and mortality in critically ill patients. Many interventions are touted to prevent VAP but studies supporting these interventions are difficult to interpret owing to an exceedingly poor correlation between clinical diagnosis of VAP and the presence of an invasive pneumonia. There is consequently a risk that purported decreases in VAP rates may reflect decreases in oropharyngeal colonization rates more than reductions in invasive disease. To circumvent this source of error, it is critical to assess the impact of intervention measures on patient outcomes rather than on VAP rates alone. This article will review selected VAP prevention methods using this framework and advocate for the development of a new surveillance definition that will more reliably predict patient outcomes.     

LIPG is a novel prognostic biomarker and correlated with immune infiltrates in lung adenocarcinoma

BackgroundAlthough many biomarkers for lung adenocarcinoma (LUAD) have been identified, their specificity and sensitivity remain unsatisfactory. Endothelial lipase gene (LIPG) plays an important role in a variety of cancers, but its role in lung adenocarcinoma remains unclear.MethodsTCGA, GEO, K‐M plotter, CIBERSORT, GSEA, HPA, and GDSC were used to analyze LIPG in LUAD. Data analysis was mainly achieved by R 4.0.3.ResultsThe expression of LIPG in LUAD tissues was higher than that in adjacent normal tissues, especially in women, patients aged >65 years, and those with lymph node metastasis. High expression predicted a poor prognosis. The results of enrichment analysis suggest that LIPG may exert profound effects on the development of LUAD through multiple stages of lipid metabolism and immune system regulation. In addition, LIPG expression was significantly correlated with the expression levels of multiple immune checkpoint genes and the abundance of multiple immune infiltrates, including the activated memory CD4 T cell, M1 macrophage, neutrophil, plasma cells, and T follicular helper (Tfh) cells in the LUAD microenvironment content. At the same time, patients with high LIPG expression respond well to a variety of antitumor drugs and have a low rate of drug resistance.Conclusions LIPG is a prognostic marker and is associated with lipid metabolism and immune infiltration in LUAD.