Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection.

BACKGROUND: A neurocognitive phenotype of post-COVID-19 infection has recently been described that is characterized by a lack of awareness of memory impairment (i.e., anosognosia), altered functional connectivity in the brain's default mode and limbic networks, and an elevated monocyte count. However, the relationship between these cognitive and brain functional connectivity alterations in the chronic phase with the level of cytokines during the acute phase has yet to be identified. AIM: Determine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6-9 months after infection. METHODS: We analyzed the predictive value of the concentration of acute cytokines (IL-1RA, IL-1ß, IL-6, IL-8, IFNγ, G-CSF, GM-CSF) (cytokine panel by multiplex immunoassay) in the plasma of 39 patients (mean age 59 yrs, 38-78) in relation to their anosognosia scores for memory deficits via stepwise linear regression. Then, associations between the different cytokines and brain functional connectivity patterns were analyzed by MRI and multivariate partial least squares correlations for the whole group. RESULTS: Stepwise regression modeling allowed us to show that acute TNFα levels predicted (R2 = 0.145; ß = -0.38; p = .017) and were associated (r = -0.587; p < .001) with scores of anosognosia for memory deficits observed 6-9 months post-infection. Finally, high TNFα levels were associated with hippocampal, temporal pole, accumbens nucleus, amygdala, and cerebellum connectivity. CONCLUSION: Increased plasma TNFα levels in the acute phase of COVID-19 predict the presence of long-term anosognosia scores and changes in limbic system functional connectivity.

Frequency of Abnormally Low Neuropsychological Scores in Post-COVID-19 Syndrome: the Geneva COVID-COG Cohort.

OBJECTIVE: Several studies have reported poor long-term neuropsychological performances in patients following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but none has yet considered the effect of administering multiple intercorrelated neuropsychological tests and assessed the frequency of cognitive deficits in a normative population. Our aim was therefore to assess the presence of cumulative neuropsychological deficits in an actual post-coronavirus disease of 2019 (COVID-19) comparison group versus one simulated using Monte-Carlo methods. METHOD: Validated neuropsychological Monte-Carlo simulation methods were applied to scores from a battery of neuropsychological tests (memory, executive, attentional, perceptual, logical reasoning, language, and ideomotor praxis) administered to 121 patients who had had mild, moderate, or severe COVID-19 (mean age: 56.70 years; 32% women), 222 ± 43 days post-infection. The cumulative percentages of the three severity subgroups were compared with the results of a false discovery rate-corrected probability analysis based on normative data. RESULTS: The cumulative percentages of deficits in memory and executive functions among the severe and moderate patients were significantly higher than those estimated for the normative population. Moderate patients also had significantly more deficits in perception and logical reasoning. In contrast, the mild group did not have significantly more cumulative deficits. CONCLUSIONS: Moderate and severe forms of COVID-19 cause greater long-term neuropsychological deficits than those that would be found in a normative population, reinforcing the hypothesis of long-term effects of SARS-CoV-2 on cognitive function, independent of the severity of the initial infection.

Outbreak of Pseudomonas aeruginosa producing VIM carbapenemase in an intensive care unit and its termination by implementation of waterless patient care.

BACKGROUND: Long-term outbreaks of multidrug-resistant Gram-negative bacilli related to hospital-building water systems have been described. However, successful mitigation strategies have rarely been reported. In particular, environmental disinfection or replacement of contaminated equipment usually failed to eradicate environmental sources of Pseudomonas aeruginosa. METHODS: We report the investigation and termination of an outbreak of P. aeruginosa producing VIM carbapenemase (PA-VIM) in the adult intensive care unit (ICU) of a Swiss tertiary care hospital with active case finding, environmental sampling and whole genome sequencing (WGS) of patient and environmental strains. We also describe the implemented control strategies and their effectiveness on eradication of the environmental reservoir. RESULTS: Between April 2018 and September 2020, 21 patients became either infected or colonized with a PA-VIM strain. For 16 of them, an acquisition in the ICU was suspected. Among 131 environmental samples collected in the ICU, 13 grew PA-VIM in sink traps and drains. WGS confirmed the epidemiological link between clinical and environmental strains and the monoclonal pattern of the outbreak. After removing sinks from patient rooms and implementation of waterless patient care, no new acquisition was detected in the ICU within 8 months after the intervention. DISCUSSION: Implementation of waterless patient care with removal of the sinks in patient rooms was successful for termination of a PA-VIM ICU outbreak linked to multiple environmental water sources. WGS provides highly discriminatory accuracy to investigate environment-related outbreaks.

Validation of a commercially available SARS-CoV-2 serological immunoassay.

OBJECTIVES: To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19. METHODS: In this unmatched (1:2) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 326 controls collected before SARS-CoV-2 emergence. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay. RESULTS: COVID-19 patients were more likely to be male and older than controls, and 50.3% were hospitalized. ROC curve analyses indicated that IgG and IgA had high diagnostic accuracies with AUCs of 0.990 (95% Confidence Interval [95%CI]: 0.983-0.996) and 0.978 (95%CI: 0.967-0.989), respectively. IgG assays outperformed IgA assays (p=0.01). Taking an assessed 15% inter-assay imprecision into account, an optimized IgG ratio cut-off > 2.5 displayed a 100% specificity (95%CI: 99-100) and a 100% positive predictive value (95%CI: 96-100). A 0.8 cut-off displayed a 94% sensitivity (95%CI: 88-97) and a 97% negative predictive value (95%CI: 95-99). Substituting the upper threshold for the manufacturer's, improved assay performance, leaving 8.9% of IgG ratios indeterminate between 0.8-2.5. CONCLUSIONS: The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in patient samples, with no obvious gains from IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals in our study population have been exposed to SARS-CoV-2 or not. IgG serology should however not be considered as a surrogate of protection at this stage.

Impact of a multifaceted prevention program on ventilator-associated pneumonia including selective oropharyngeal decontamination.

PURPOSE: We describe the impact of a multifaceted program for decreasing ventilator-associated pneumonia (VAP) after implementing nine preventive measures, including selective oropharyngeal decontamination (SOD). METHODS: We compared VAP rates during an 8-month pre-intervention period, a 12-month intervention period, and an 11-month post-intervention period in a cohort of patients who received mechanical ventilation (MV) for > 48 h. The primary objective was to assess the effect on first VAP occurrence, using a Cox cause-specific proportional hazards model. Secondary objectives included the impact on emergence of antimicrobial resistance, antibiotic consumption, duration of MV, and ICU mortality. RESULTS: Pre-intervention, intervention and post-intervention VAP rates were 24.0, 11.0 and 3.9 VAP episodes per 1000 ventilation-days, respectively. VAP rates decreased by 56% [hazard ratio (HR) 0.44, 95% CI 0.29-0.65; P < 0.001] in the intervention and by 85% (HR 0.15, 95% CI 0.08-0.27; P < 0.001) in the post-intervention periods. During the intervention period, VAP rates decreased by 42% (HR 0.58, 95% CI 0.38-0.87; P < 0.001) after implementation of eight preventive measures without SOD, and by 70% after adding SOD (HR 0.30, 95% CI 0.13-0.72; P < 0.001) compared to the pre-intervention period. The incidence density of intrinsically resistant bacteria (to colistin or tobramycin) did not increase. We documented a significant reduction of days of therapy per 1000 patient-days of broad-spectrum antibiotic used to treat lower respiratory tract infection (P < 0.028), median duration of MV (from 7.1 to 6.4 days; P < 0.003) and ICU mortality (from 16.2 to 13.5%; P < 0.049) for patients ventilated > 48 h between the pre- and post-intervention periods. CONCLUSIONS: Our preventive program produced a sustained decrease in VAP incidence. SOD provides an additive value.

[Bevacizumab and lung cancer: eligible patients in daily practice]. / Bévacizumab et cancer bronchique: population cible en pratique quotidienne.

BACKGROUND: Combining bevacizumab with platinum-based chemotherapy significantly improves survival for patients with advanced non-squamous non-small cell lung cancer. The objective of this study was to assess the proportion of patients who could receive this combined therapy. METHODS: This was a retrospective single centre analysis of patients treated between 2007 and 2008. Exclusion criteria for bevacizumab included: squamous cell carcinoma, contraindication to platinum-based chemotherapy, uncontrolled hypertension, haemoptysis superior to 2.5 mL, recent surgery, and/or tomodensitometric criteria after independent review by two radiologists (contact with a proximal vessel, tracheobronchial involvement, cavitation). Cardiovascular diseases and central tumour location were not systematically considered as contraindications. RESULTS: Among 194 patients analysed, 21 (10.8%) to 35 (18%) patients were eligible for bevacizumab, whether or not cardiovascular diseases and central tumour location were considered as contraindications. The kappa coefficient was 0.49. CONCLUSION: Even though the proportion of patients who can receive chemotherapy plus bevacizumab may vary according to the eligibility criteria chosen and the interpretation of the CT scan, it is unlikely to exceed 25% of patients in daily practice.

Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure.

Acute renal failure (ARF) in critically ill patients is associated with high mortality. Optimal method and dose of continuous renal replacement therapy could improve survival in these patients. We studied the hypothesis that an increase in dialysis dose obtained by continuous veno-venous hemodiafiltration (CVVHDF) is associated with a better survival than continuous veno-venous hemofiltration (CVVH) among critically ill patients with ARF. In a prospective randomized trial, these two methods were compared in patients undergoing renal replacement therapy in two intensive care units (ICUs). The patients had either CVVH (1-2.5 l/h replacement fluid) or continuous CVVHDF (1-2.5 l/h replacement fluid+1-1.5 l/h dialysate) according to their body weight. 28- and 90-day mortalities, renal recovery, and duration of ICU stay were the main outcome measures. Two hundred and six patients were randomized from October 2000 to December 2003. Twenty-eight-day survivals (%) were, respectively, 39 and 59 (P=0.03) in the CVVH and CVVHDF groups. Three months survivals (%) were, respectively, 34 and 59 (P=0.0005) in the CVVH and CVVHDF groups. Apache II score, age, baseline blood urea nitrogen, and hemodiafiltration (hazard ratio 0.59, 95% confidence interval 0.40-0.87; P=0.008) were independent predictors of survival at 90 days. Renal recovery rate among survivors (71 versus 78% in the CVVH and CVVHDF groups respectively, P=0.62) was not affected by the type of renal replacement therapy. These results suggest that increasing the dialysis dose especially for low molecular weight solutes confers a better survival in severely ill patients with ARF.

Lack of effect of combination antibiotic therapy on mortality in patients with pneumococcal sepsis.

In order to determine whether combination antibiotic therapy decreases mortality after severe pneumococcal infection, a retrospective study of a cohort of 1,840 adult patients with severe sepsis or septic shock enrolled in two multicenter clinical trials between 1994 and 1999 was conducted. Among 107 patients with monobacterial pneumococcal sepsis, the case-fatality rate was 20% (five of 25) for patients who received antibiotic monotherapy compared with 19.5% (16 of 82) for patients who received combination therapy (adjusted hazard ratio, 1.1; 95% CI, 0.4-3.1). Similarly, monotherapy did not increase the risk of death (adjusted hazard ratio, 1.0; 95% CI, 0.2-4.8) among bacteremic patients (n=75). However, the latter analysis may have been underpowered (power, 58%) to detect a difference in mortality. Overall, in contrast to recently published reports, these results suggest that combination antibiotic therapy does not decrease mortality after severe pneumococcal sepsis.

Burden of illness imposed by severe sepsis in Switzerland.

OBJECTIVE: This study aims to determine the burden of illness imposed by severe sepsis in Switzerland by evaluating the direct and indirect patient-related costs for critically ill patients with severe sepsis. METHODS: In order to estimate the direct costs a retrospective analysis was undertaken using records from 61 adult patients treated in three intensive care units (ICUs) in three different University hospitals in Switzerland, in 2001. Resource use was determined by a bottom up approach and valued using centre-specific unit costs for medication, nutrition, blood products, disposables and official tariffs for laboratory and microbiology analysis, diagnostic services, and clinical procedures. By adding centre-specific personnel and basic bed (hotel) costs total direct costs in the ICU were calculated. Indirect costs resulting from unfitness for work, early retirement, and premature death were calculated using official Swiss statistics for the years 1998-2000. RESULTS: The mean total direct costs for a severely septic patient are CHF 41,790 (+/- 33,222 CHF) or CHF 3244 (+/- 757 CHF) per day. Nonsurvivors cause significantly higher costs than survivors (CHF 45,956 vs. CHF 37,759, p <0.001). The total intensive care costs in Switzerland due to severe sepsis amount to CHF 146-355 million. Indirect costs were estimated to range from CHF 347 to 844 million (predominantly due to premature death). Consequently the burden of illness of severe sepsis can be estimated to range from CHF 493 to 1199 million per year in Switzerland (1 CHF = 0.662 Euro in 2001). CONCLUSION: Patients suffering from severe sepsis in Switzerland have a high mortality rate and spend a prolonged time in the ICU, leading to high direct and indirect costs. Particularly productivity losses due to premature death represent a considerable burden to the Swiss society.

Clinical signs and scores for the diagnosis of ventilator-associated pneumonia.

The diagnosis of a pneumonia which occurs in critically ill patients undergoing positive pressure mechanical ventilation (ventilator-associated pneumonia, VAP) is often a problem. This is mainly due to the lack of sensitivity and specificity of clinical and radiographic signs of pneumonia in this patient population. Many studies investigated some clinical variables (fever, tracheal aspirates, blood leukocytosis, radiographic criteria): none of these, individually considered, resulted predictive enough to be useful for the bedside diagnosis of VAP. The Clinical Pulmonary Infection Score (CPIS) developed in 1991, based on 6 variables (fever, leukocytosis, tracheal aspirates, oxygenation, radiographic infiltrates, and semi-quantitative cultures of tracheal aspirates with Gram stain) is more sensitive to diagnose VAP. Compared with other associations of clinical variables this one is more flexible and it allows for the signs not to be all present at the same time.

Cytokine balance in the lungs of patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) involves an intense inflammatory response in the lungs, with accumulation of both pro- and antiinflammatory cytokines in bronchoalveolar lavage fluid (BALF). Our goal was to determine how the balance between pro- and antiinflammatory mediators in the lungs changes before and after the onset of ARDS. We identified 23 patients at risk for ARDS and 46 with established ARDS and performed serial bronchoalveolar lavage (BAL). We used immunoassays to measure tumor necrosis factor alpha (TNF-alpha) and soluble TNF-alpha receptors I and II; interleukin 1 beta (IL-1 beta), IL-1 beta receptor antagonist, and soluble IL-1 receptor II; IL-6 and soluble IL-6 receptor; and IL-10. We used sensitive bioassays to measure net TNF-alpha, IL-1 beta, and IL-6 activity. Although individual cytokines increased before and after onset of ARDS, greater increases occurred in cognate receptors and/or antagonists, so that molar ratios of agonists/antagonists declined dramatically at the onset of ARDS. The molar ratios remained low for 7 d or longer, limiting the activity of soluble IL-1 beta and TNF-alpha in the lungs at the onset of ARDS. This significant antiinflammatory response early in ARDS may provide a key mechanism for limiting the net inflammatory response in the lungs.

The crucial role of systemic responses in the innate (non-adaptive) host defense.

We suggest that successful defense against microbial invasion requires both local inflammation and systemic anti-inflammation. The key systemic responses involve the hypothalamic-pituitary-adrenocortical axis, the sympathetic-adrenomedullary axis, acute phase protein production, thermoregulation and alterations in leukocyte responsiveness to agonists such as bacterial endotoxin. These integrated responses raise blood and tissue concentrations of several anti-infective molecules, mobilize leukocytes into the circulation, and increase blood flow to injured or infected sites. They also neutralize cytokines, proteases and oxidants that enter the bloodstream from inflamed local sites and forestall endothelial activation in distant vessels. Together, these forces help concentrate activated phagocytes at injured or infected local sites while preventing potentially damaging inflammation in uninvolved tissues.

Rapid changes in alcoholic hepatitis histology under steroids: correlation with soluble intercellular adhesion molecule-1 in hepatic venous blood.

BACKGROUND/AIMS: In alcoholic hepatitis (AH), enhanced expression of intercellular adhesion molecule-1 (ICAM-1) correlates to neutrophil infiltration and histology. In severe AH under steroids, the evolution of the hepatocyte membranous ICAM-1 expression and its soluble form (sICAM-1) is not known. METHODS: Twenty-six consecutive patients with biopsy-proven severe AH had liver tissue studies for hepatocyte membranous ICAM-1 expression by immunostaining. Lobular neutrophils (mean per high power field) were counted after chloracetate esterase staining. Histological damage was assessed semiquantitatively. Circulating levels of sICAM-1 and TNFalpha in peripheral and hepatic vein were measured using immunoassays. After 8 days on steroids, 19 patients had repeat biopsy. RESULTS: At baseline, hepatocyte membranous ICAM-1 correlated both to histology (r=0.55, P<0.01) and to lobular neutrophils (r=0.56, P<0.01). On steroids, sICAM-1 in hepatic vein and TNFalpha in both vascular beds decreased. Hepatocyte membranous ICAM-1 and hepatocellular damage decreased, but lobular neutrophils increased. Changes in sICAM-1 in hepatic vein correlated to histological changes (r=0.68, P<0.01). CONCLUSIONS: In severe AH under steroids, the short term histological improvement was associated with a decrease in circulating TNFalpha, a decrease in ICAM-1 expression, and correlated to hepatic vein sICAM-1 changes.

Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis.

To assess the diagnostic value of procalcitonin (PCT), interleukin (IL)-6, IL-8, and standard measurements in identifying critically ill patients with sepsis, we performed prospective measurements in 78 consecutive patients admitted with acute systemic inflammatory response syndrome (SIRS) and suspected infection. We estimated the relevance of the different parameters by using multivariable regression modeling, likelihood-ratio tests, and area under the receiver operating characteristic curves (AUC). The final diagnosis was SIRS in 18 patients, sepsis in 14, severe sepsis in 21, and septic shock in 25. PCT yielded the highest discriminative value, with an AUC of 0.92 (CI, 0.85 to 1.0), followed by IL-6 (0.75; CI, 0.63 to 0.87), and IL-8 (0.71; CI, 0.59 to 0.83; p < 0.001). At a cutoff of 1.1 ng/ml, PCT yielded a sensitivity of 97% and a specificity of 78% to differentiate patients with SIRS from those with sepsis-related conditions. Median PCT concentrations on admission (ng/ ml, range) were 0.6 (0 to 5.3) for SIRS; 3.5 (0.4 to 6.7) for sepsis; 6.2 (2.2 to 85) for severe sepsis; and 21.3 (1.2 to 654) for septic shock (p < 0.001). The addition of PCT to a model based solely on standard indicators improved the predictive power of detecting sepsis (likelihood ratio test; p = 0.001) and increased the AUC value for the routine value-based model from 0.77 (CI, 0.64 to 0.89) to 0.94 (CI, 0.89 to 0.99; p = 0.002). In contrast, no additive effect was seen for IL-6 (p = 0.56) or IL-8 (p = 0.14). Elevated PCT concentrations appear to be a promising indicator of sepsis in newly admitted, critically ill patients capable of complementing clinical signs and routine laboratory parameters suggestive of severe infection.

Local inflammatory responses following bronchial endotoxin instillation in humans.

To study local lung inflammation, 34 subjects had endotoxin (1-4 ng/kg) instilled into a lung segment and saline instilled into a contralateral segment followed by bronchoalveolar lavage (BAL) at 2 h, 6 h, 24 h, or 48 h. Endotoxin instillation resulted in a focal inflammatory response with a distinct time course. An early phase (2 h to 6 h) revealed an increase in neutrophils (p = 0.0001) with elevated cytokines (tumor necrosis factor [TNF]-alpha, TNF receptors [TNFR], interleukin [IL]-1beta, IL-1 receptor antagonist, IL-6, granulocyte-colony-stimulating factor [G-CSF], all p < or = 0.002, but no change in IL-10) and chemokines (IL-8, epithelial neutrophil activating protein-78, monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, all p < or = 0.001, but no change in growth-regulated peptide-alpha). A later phase (24 h to 48 h) showed increased neutrophils, macrophages, monocytes, and lymphocytes (all p < or = 0.02), and a return to basal levels of most mediators. Elevated levels of inflammatory markers (TNFR(1), TNFR(2), L-selectin, lactoferrin, and myeloperoxidase) persisted in the BAL at 48 h (p < or = 0.001). Increased permeability to albumin occurred throughout both phases (p = 0.001). Blood C-reactive protein, serum amyloid A, IL-6, IL-1ra, G-CSF, but not TNF-alpha increased by 8 h (all p < or = 0.008). The local pulmonary inflammatory response to endotoxin has a unique qualitative and temporal profile of inflammation compared with previous reports of intravenous endotoxin challenges. This model provides a means to investigate factors that initiate, amplify, and resolve local lung inflammation.

Pulmonary edema fluid from patients with acute lung injury augments in vitro alveolar epithelial repair by an IL-1beta-dependent mechanism.

Efficient alveolar epithelial repair is crucial for the restoration of the injured alveolar epithelial barrier in patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). We hypothesized that pulmonary edema fluid from patients with ALI /ARDS would inhibit alveolar epithelial repair as measured in an in vitro epithelial wound-repair model using the human alveolar epithelial-like cell line A549. In contrast to our initial hypothesis, pulmonary edema fluid from patients with ALI/ARDS increased alveolar epithelial repair by 33 +/- 3% compared with pooled plasma from healthy donors (p < 0.01). By contrast, the plasma and the pulmonary edema fluid from patients with hydrostatic pulmonary edema, and the plasma from patients with ALI/ARDS had similar effects on epithelial repair as pooled plasma from healthy donors. Inhibition of interleukin-1beta (IL-1beta) activity by IL-1 receptor antagonist reduced alveolar epithelial repair induced by ALI/ARDS edema fluid by 46 +/- 4% (p < 0.001), indicating that IL-1beta contributed significantly to the increased epithelial repair. In summary, pulmonary edema fluid collected early in the course of ALI/ARDS increased alveolar epithelial repair in vitro by an IL-1beta-dependent mechanism. These data demonstrate a novel role for IL-1beta in patients with ALI/ARDS, indicating that IL-1beta may promote repair of the injured alveolar epithelium.

Procalcitonin is not an accurate marker of spontaneous bacterial peritonitis in patients with cirrhosis.

BACKGROUND/AIMS: The clinical features of peritonitis are usually absent in cirrhotic patients with an ascitic fluid infection, raising the interest for specific biological markers of inflammation. METHODOLOGY: We prospectively measured the plasma and ascitic fluid levels of procalcitonin, an innovative infection parameter, interleukin-6, and C-reactive protein in 20 cirrhotics with or without spontaneous bacterial peritonitis. The patient's condition was followed-up for 12 weeks after paracentesis. RESULTS: None of the 10 patients with spontaneous bacterial peritonitis presented with severe systemic signs of infection. Procalcitonin level in plasma, but not in ascites, was significantly higher in patients with spontaneous bacterial peritonitis compared to controls (0.74 +/- 0.6 vs. 0.2 +/- 0.1 ng/mL, P < 0.05). Interleukin-6 levels in ascites were similar between groups. C-reactive protein concentrations were higher both in plasma and in ascitic fluid in patients with spontaneous bacterial peritonitis compared to controls (85.3 +/- 63 vs. 18.6 +/- 19 mg/dL, 24.6 +/- 25 vs. 4.5 +/- 4 mg/dL, P < 0.05, respectively). Three patients with spontaneous bacterial peritonitis died, but the outcome was not related to the concentrations of biological markers. CONCLUSIONS: In spontaneous bacterial peritonitis, procalcitonin measurement is not an accurate diagnostic test, possibly due to the absence of systemic inflammatory response syndrome in this condition. In addition, the diagnostic value of C-reactive protein is limited by the wide overlap between values.