Inflammatory biomarker-based clinical practice in patients with pneumonia: A systematic review of randomized controlled trials.

Objectives: Biomarker-based clinical practice is currently gaining ground and increasingly affects decision making. A variety of biomarkers have been studied through the years and some of them have already an established role in modern medicine, such as procalcitonin (PCT) which has been proposed to reduce antibiotic exposure. We purposed to systematically review all biomarkers examined for guiding the clinical practice in patients with pneumonia. METHODS: A systematic review on PubMed was performed on April 2023 by two independent researchers using the PRISMA guidelines. Randomized trials which enrolled patients with pneumonia and compared biomarker-guided strategies to standard of care were included. RESULTS: 1242 studies were recorded, from whom 16 were eligible for this study. 14 studies investigated PCT as a biomarker. From these, 8 studies reported on community acquired pneumonia (CAP), 2 on ventilator associated pneumonia (VAP), 1 on aspiration pneumonia, 1 on hospital acquired pneumonia (HAP) and 2 on exacerbation of chronic obstructive pulmonary disease (ECOPD). There was 1 study, referred to VAP, that investigated interleukin-1ß (IL-1ß) and interleukin-8 (IL-8) and 1 study that reported the role of C-reactive protein (CRP) in ECOPD. In a total of 4751 patients in 15 studies, the biomarker-based approach did not lead to increased mortality [OR: 0.998 (95%CI: 0.74-1.34, p value: 0.991). I2:19%]. Among different types of pneumonia and time-points of assessment, biomarker-guided practice appeared to improve antibiotic-related outcomes, such as rate of antibiotic prescription, duration of antibiotic therapy and rate of antibiotic exposure, while 5 studies reported a possible decrease in antibiotic-related adverse effects. Biomarker-guided practice did not seem to lead in an increase in other adverse outcomes such as need for hospitalization and duration of hospitalization. However, the included studies have high risk of bias mainly due to improper blinding of participants/personnel and outcome assessors. CONCLUSION: Biomarker-guided clinical practice improves provided healthcare, in terms of reduced antibiotic consumption with no inferiority to mortality, relapses and exacerbations in patients with different types of pneumonia. Thus, such approaches should be further evaluated to achieve personalized medicine.

The role of cerebrospinal fluid levels of neutrophil gelatinase-associated lipocalin (NGAL) and electroencephalography in the assessment of impaired consciousness in the context of infection.

INTRODUCTION: The sepsis syndrome is potentially affecting several organs and systems irrespectively of the primary source of the infection. Alterations of the brain function in sepsis patients may result either from a primary central nervous system (CNS) infection or could be part of the sepsis-associated encephalopathy (SAE), a common complication of sepsis, characterized by a diffuse dysfunction of the brain due to an infection elsewhere in the body without overt CNS infection. Aim of the study was to evaluate the usefulness of electroencephalography and the biomarker neutrophil gelatinase-associated lipocalin (NGAL) when measured in the cerebrospinal fluid (CSF) in the management of these patients. METHODS: Patients presenting at the emergency department with altered mental status and signs of infection were included in this study. Among initial assessment and treatment of the patients based on the international guidelines for treating sepsis, NGAL was measured in the cerebrospinal fluid (CSF) using ELISA technique. Electroencephalography was performed when possible within 24 hours after admission and EEG abnormalities were recorded. RESULTS: 32 of 64 patients included in this study were diagnosed with central nervous system (CNS) infection. CSF NGAL was significantly higher in patients with CNS infection compared to patients without CNS infection (18.1 [5.1-71.1] vs 3.6 [1.2-11.6]; p<0.001). There was a trend for higher CSF NGAL in patients with EEG abnormalities, which did not reach statistical significance (p=0.106). CSF NGAL levels were similar between survivors and non-survivors (medians: 7.04 vs 11.79). CONCLUSION: In patients presenting at the emergency department with altered mental status and signs of infection, CSF NGAL was significantly higher in patients with CSF infection. Its role in this acute setting should be evaluated further. CSF NGAL could be suggestive of EEG abnormalities.

Alterations in Laboratory Parameters Related to Disease Severity in Vaccinated Patients Against SARS-CoV-2.

Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide with global financial and health care systems consequences. It is already well recognized that immunization against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a precondition for blocking mutations and prevent the emergence of variants. The aim of the study was to investigate the possible relationship between COVID-19 vaccines and the commonly used disease-related blood biomarkers. Methods: Adult patients with confirmed SARS-CoV-2 infection who were hospitalized from November 8, 2021, to December 31, 2021, were included. The retrospective study was conducted in Patras University Hospital, Greece. Two groups of patients were assessed, the ones who were previously vaccinated against SARS-CoV-2 (group A, n = 21), and those who were not (group B, n = 55). After analysis of peripheral blood, we calculated on admission day for each patient the total white blood cell (WBC), absolute lymphocytes count (ALC), absolute monocyte count, D-dimers, C-reactive protein (CRP) plasma levels, lactate dehydrogenase (LDH), ferritin, high-sensitive troponin, as well as the arterial oxygen partial pressure/fractional inspired oxygen (PO2/FiO2) ratio. Results: The median age of all patients was 65.3 ± 15.2 years old; 68.4% were men and 31.6% were women. Comorbidities were present in 51 patients (67.1%). Hypertension and diabetes were observed as the most common comorbidities (33.3%). About 72.4% of the patients were unvaccinated or have received the first dose of vaccine, and 27.6% were completely vaccinated. No statistical difference was found in the total WBC count and ALC between the two groups (group A vs. group B: 8,168.95 ± 7,584.4 vs. 8,521.9 ± 6,571.3, P = 0.848 and 3,052.1 ± 7,230.7 vs. 1,279.6 ± 1,218.6, P = 0.087). Monocytes count in both groups did not show statistical difference: group A vs. group B: 672.6 ± 384.7 vs. 637.9 ± 477.8 (P = 0.754). Similarly, no difference for D-dimers (1,348.5 ± 1,397.6 vs. 1,850.9 ± 3,877.5, P = 0.575), ferritin (1,082.8 ± 1,399.5 vs. 1,327.4 ± 1,307.8, P = 0.508), high-sensitive troponin (113.6 ± 318.1 vs. 157.5 ± 48.8, P = 0.252), and CRP (6.92 ± 4.9 vs. 7.4 ± 5.9, P = 0.732). For LDH plasma levels, the statistical difference was significant (274.2 ± 85.6 vs. 387.5 ± 223.4, P = 0.003), as well as for the PO2/FiO2 ratio (355.6 ± 129.7 vs. 260.5 ± 123.3, P = 0,006). Conclusions: In a mixed population hospitalized for COVID-19, only LDH plasma levels and the PaO2/FiO2 on admission day showed statistically significant difference between vaccinated and unvaccinated patients. Although unvaccinated patients are more likely to develop severe illness, they did not express significantly higher values of commonly used plasma biomarkers such as ferritin, CRP, and D-dimers which are related to disease severity.

Varicella-zoster virus aseptic meningitis: an atypical presentation in an immunocompetent male patient.

Varicella-zoster virus (VZV) reactivation causes a relatively common disease in immunocompromised patients characterized by rash and radiating pain. Aseptic meningitis is a rare complication of VZV infection and commonly is associated with exanthem and neurological signs. We present an atypical case of VZV meningitis in a healthy 56-year-old male who was initially presented with persistent headache as the only symptom. Anti-VZV immunoglobulin G titer both in serum and in cerebrospinal fluid (CSF) and the polymerase chain reaction (PCR) CSF analysis revealed VZV infection. Our case highlights the importance of considering VZV aseptic meningitis in immunocompetent individuals even in the absence of the typical presentation of meningitis. Screening techniques such as CSF, PCR as well as anti-VZV antibodies in CSF show that VZV meningitis is a common cause of aseptic meningitis and allows the early recognition of CNS involvement in the VZV infection.

The Use of Electroencephalography in Patients with Sepsis: a Review of The Literature.

Sepsis-associated encephalopathy (SAE) is the term used to define brain dysfunction related to infections that are principally located outside the central nervous system (CNS). A number of published studies report that electroencephalography (EEG) has been used in the evaluation of patients with sepsis, alone or usually in combination, to evoked potentials and neuroimaging. This was in an effort to assess if EEG can be a tool in the diagnosis and monitoring of the neurological status in sepsis patients. Although there is no specific test for the diagnosis and prognosis of sepsis related encephalopathy, our literature review suggests that EEG has a role in the assessment of this clinical entity. Due to its low cost and simplicity in its performance, EEG could be a potential aid in the assessment of sepsis neurological complications even in the early, subclinical stages of the syndrome. The aim of this review is to summarize the published literature regarding the application and utility of electroencephalography in adult patients with sepsis.

Soluble Urokinase Plasminogen Activator Receptor as a Diagnostic and Prognostic Biomarker in Cardiac Disease.

This review summarizes the published literature referring to the use and validity of the biomarker soluble urokinase plasminogen activator receptor (suPAR) when used for the assessment of patients with cardiac diseases. It is measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples. In cardiology a cut-off value range of 3.5 - 4.5 ng/mL has been commonly utilized. Different cut-off values may be applied based on the measuring kit used, the patient population and the clinical setting. A PubMed/Medline search was conducted aiming to identify all publications relevant to the use of suPAR in patients with cardiac diseases. A total of 39 studies were included in this review. suPAR as a marker of inflammation has been used more extensively in recent years, alone or in combination with other biomarkers of inflammation and cardiac pathology in the assessment of patients with acute and chronic cardiac diseases. suPAR is closely related to the pathophysiology of cardiac disease, and a number of publications encourages its use as a valuable biomarker in the assessment of patients presenting to the cardiology service. It may be most valuable in the risk assessment of patients with acute coronary syndromes and congestive heart failure, as suPAR elevation may be an independent predictor of mortality in these conditions. In conclusion, among several biomarkers used for clinical entities with underlying inflammatory pathophysiology including cardiac diseases, suPAR is a novel attractive index for the prognostic risk stratification of cardiac patients. More research is warranted to confirm its diagnostic and prognostic validity, alone or combined with other cardiac and inflammatory biomarkers.

Correlation of Positive Blood Cultures with Peripherally Inserted Central Catheter Line Infection in Oncology Patients.

INTRODUCTION: The use of peripherally inserted central catheter (PICC) lines offers several advantages compared to traditional central venous catheters (CVCs) as the insertion procedure is minimally invasive, they may be retained safely for longer periods of time, and their use is associated with fewer catheter-related infections. Their use in patients suffering from a malignant disease is common but may pose a greater risk of complications due to the severe immunosuppression associated with treatment. This study was conducted to evaluate the safety of PICC lines in this group. METHODS: This was a retrospective study of oncology patients being treated in a Mediterranean tertiary center. Patients with PICC lines were enrolled in the study if a positive blood culture necessitated the removal of the PICC and subsequent culture of the PICC tip. A comparison was conducted between patients with positive and negative PICC cultures. RESULTS: Thirty patients were included, four of whom had a positive PICC culture. The most commonly isolated pathogens were coagulase-negative Staphylococci and Corynebacteria. No statistically significant difference was noted in white blood cell (WBC) counts, C-reactive protein (CRP), and Michigan PICC central line associated bloodstream infection (MPC) score between the two groups. Staphylococcus epidermidis was the most commonly isolated pathogen. DISCUSSION: Though limited by a small sample size and the retrospective design, the findings of this study seem to corroborate existing literature on the subject which suggests that the use of PICC lines in oncology patients is feasible and does not pose unacceptable risk. Further research is indicated to determine subgroups which may be at greater risk of PICC related infections.

Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain.

Even though the early reports from China provided advance warning of what was to come, the COVID-19 pandemic has spread throughout the world with devastating consequences. Emergency measures are being implemented to reduce the magnitude of the public health crisis, prevent healthcare facilities from becoming overwhelmed and reduce the death toll of the disease. Containment strategies to mitigate viral transmission and emergency measures to increase the capacity of each country to provide intensive care are at the forefront of the public health management of the epidemic, even though the detrimental social and psychological effects of quarantine are evident on a global scale. Optimal management of critically ill patients with COVID-19 is also unclear, and the initial suggestion for early intubation as in typical ARDS may have caused significant harm. The management of mild cases of confirmed infection is another point of controversy, as drugs which may be repurposed for COVID-19 treatment have significant, potentially irreversible toxic effects and their use in mild cases of a viral illness which is typically self-limited may be harmful.

Neutrophil-to-lymphocyte Ratio Relation to Sepsis Severity Scores and Inflammatory Biomarkers in Patients with Community-acquired Pneumonia: A Case Series.

BACKGROUND AND OBJECTIVES: Neutrophil to lymphocyte ratio (NLR) as calculated from the white cell differential blood count is considered a promising marker for the prognosis of patients with various diseases, including sepsis. This study was designed to assess the possible use of neutrophil-to-lymphocyte ratio in the prediction of survival outcomes in patients with community acquired pneumonia (CAP). A secondary objective was to compare the prognostic accuracy of NLR with the commonly used severity scores of sepsis SOFA, APACHE II and SAPS II. METHODS: This was a retrospective study based on data extracted from 26 patients suffering from acute CAP. The study period was from February 01, 2017 until April 30, 2017. All patients with CAP were presented in the Emergency Department (ED) of the University Hospital of Patras, Greece and were treated after admission in the Internal Medicine Department. The neutrophil-to-lymphocyte ratio (NLR) was calculated from the white blood cell count (WBC) values measured from a peripheral venous blood specimen drawn on admission. It was then compared with C-reactive protein (CRP) serum levels and the sepsis calculated prognostic scores APACHE II, SAPS II and SOFA. The impact of the above parameters was evaluated in relation to the final outcome. RESULTS: The mean period of hospitalization for the enrolled patients was 9.3 days (SD 5.8 days). Twenty-four patients (92.3%) got finally discharged from the hospital and two (7.7%) died during the hospitalization. Mean NLR and serum CRP values on admission were 10.2 ± 8.8 (min 1.4; max 34.7) and 11.4 ± 11 mg/dL (min 0.4; max 42.6) respectively. Based on the correlation analysis, serum CRP was more strongly positively correlated with NLR (r = 0.543, P = 0.004), than total WBC (r = 0.454, P = 0.02). None of the biomarkers of inflammation measured or computed in the study (CRP, WBC, NLR) showed any correlation with either the days of hospitalization or the sepsis prognostic scores. CONCLUSIONS: NLR shows a statistical significant correlation to the commonly used inflammatory markers CRP and total WBC in the small sample size of patients with CAP that we assessed. Although NLR is a simple, cheap and rapidly available measurement in the ED, future, larger prospective studies are warranted to confirm its possible value as a prognostic index in sepsis patients with CAP.

Procalcitonin as a diagnostic and prognostic marker in diabetic foot infection. A current literature review.

Diabetic foot ulcers (DFUs) are a very common cause of mortality and morbidity. The distinction between infected and non-infected DFU remains a very challenging task for clinicians in everyday practice. Even when infection is documented, the spectrum of diabetic foot infection is wide, ranging from cellulitis and soft tissue infection to osteomyelitis. Procalcitonin (PCT), a well-established sepsis biomarker, has been used in the diagnosis of several infections including osteomyelitis in patients with diabetes mellitus. This review gathers and presents all the relevant data, up until now, regarding the use of PCT as an assessment tool in diabetic patients with foot infection. Current evidence suggests that PCT levels could aid clinicians in distinguishing infected from non-infected DFUs as well as in the distinction between soft tissue infection and bone involvement, but further and larger studies are warranted to confirm these findings.