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.

Knowledge and Attitudes of Healthcare Workers towards Antibiotic Use and Antimicrobial Resistance in Two Major Tertiary Hospitals in Western Greece.

Antibiotic resistance (ABR) and antimicrobial stewardship arethe two sides of the same coin that constitute a public health hydra. This study aimed to assessthe knowledge and attitude of healthcare workers (HCWs), on antibiotic use and antimicrobial resistance in Western Greece. A total of 200 healthcare workers (doctors, nurses, and others) from the two largest tertiary hospitals in Western Greece were included in our survey. HCWs seem not to decide based on patient opinion in order to prescribe antibiotics. Approximately 97% of them are aware of their main adverse effects. Remarkably, 25% of respondents prescribe antibiotics due to diagnostic uncertainty, and 32.5% of them prescribe antibiotics based on their experience. HCWs statedthat they do not report adverse effects often. Inappropriate antibiotic prescriptions were mentioned as the main reason for bacterial resistance to antimicrobials. Monitoring the patient's treatment progress, using electronic prescriptions, and adhering to international guidelines were suggested as solutions to the problem. Post Hoc analysis showed that nursing staff apply to the national guidelines (p: 0.011) and use electronic prescriptions (p: 0.003) less often compared to consultants, doctor directors, and trainees. The findings of our survey may be useful for the development of future national education programs and interventions thatmay improve healthcare workers' knowledge and ability to manage antibiotics.

The Role of the Pancreatic Stone Protein in Predicting Intra-Abdominal Infection-Related Complications: A Prospective Observational Single-Center Cohort Study.

BACKGROUND: The Pancreatic Stone Protein (PSP) is an acute-phase protein that is mainly secreted by pancreatic cells in response to stress. The current literature supports its use as a predictor of sepsis. Its prognostic role has recently been evaluated in a point-of-care setting, mostly in high-risk patients. We conducted a prospective observational cohort study to evaluate its utility in the prognosis of patients admitted to the hospital with a diagnosis of intra-abdominal infection. METHODS: Adult patients consecutively admitted to the Internal Medicine Department of the University Hospital of Patras, Greece, with a diagnosis of intra-abdominal infection were enrolled. PSP levels were measured within 24 h of admission in whole blood. RESULTS: a total of 40 patients were included after being diagnosed with IAI. PSP was used as an independent predictive factor for sepsis after adjusting for age with OR = 7.888 (95% CI: 1.247-49.890). PSP also predicted readmission and the need for treatment escalation (p: <0.01) and was an excellent prognostic factor regarding these outcomes (AUC = 0.899, 95% CI: 0.794-1.0, and AUC = 0.862, 95% CI: 0.748-0.976, respectively). PSP also proved superior to CRP, ferritin, and fibrinogen in sepsis diagnosis, treatment escalation, and readmission prediction with an AUC of 0.862, 0.698, and 0.899, respectively. CONCLUSIONS: PSP can predict unfavorable outcomes, such as sepsis development, readmission, and the need for treatment escalation among patients with intra-abdominal infections.

Evaluation of Reliability and Validity of the RALE and BRIXIA Chest-X Ray Scores in Patients Hospitalized with COVID-19 Pneumonia.

INTRODUCTION: Chest X-rays are commonly used to assess the severity in patients that present in the emergency department with suspected COVID-19 pneumonia, but in clinical practice quantitative scales are rarely employed. AIMS: To evaluate the reliability and validity of two semi-quantitative radiological scales in patients hospitalized for COVID-19 pneumonia (BRIXIA score and RALE score). METHODS: Patients hospitalized between October 2021 and March 2022 with confirmed COVID-19 pneumonia diagnosis were eligible for inclusion. All included patients had a chest X-ray taken in the ED before admission. Three raters that participated in the treatment and management of patients with COVID-19 during the pandemic independently assessed chest X-rays. RESULTS: Intraclass coefficients for BRIXΙA and RALES was 0.781 (0.729-0.826) and 0.825 (0.781-0.862) respectively, showing good to excellent reliability overall. Pairwise analysis was performed using quadratic weighted kappa showing significant variability in the inter-rater agreement. The prognostic accuracy of the two scores for in-hospital mortality for all raters was between 0.753 and 0.763 for BRIXIA and 0.737 and 0.790 for RALES, demonstrating good to excellent prognostic value. Both radiological scores were significantly associated with inhospital mortality after adjustment for 4C Mortality score. We found a consistent upwards trend with significant differences between severity groups in both radiological scores. CONCLUSION: Our findings suggest that BRIXIA and RALES are reliable and can be used to assess the prognosis of patients with COVID-19 requiring hospitalization. However, the inherent subjectivity of radiological scores might make it difficult to set a cut-off value suitable for all assessors.

Gastrointestinal bleeding in athletes.

Gastrointestinal (GI) bleeding (GIB) in athletes has previously been reported in several studies, as an important factor of underperformance in competitive sports events. Yet it is still underreported, partly because it is usually occult and self-limited soon after the effort. It can originate in either the upper or the lower GI tract and can be proportionally related to the amount and duration of effort. Key pathophysiological factors seem to include splanchnic hypoperfusion, mechanical trauma of the GI wall, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Appropriate nutrition, hydration and regulation of exercise, along with substances such as arginine and citrulline can relieve upper and lower GI symptoms, including nausea, vomiting, cramping, diarrhea, and possibly hemorrhage. Cessation of NSAIDs, use of proton pump inhibitors and H2-receptor-antagonists, as well as "training" the gut, also seem to be effective in reducing the incidence of GIB in athletes. Maintenance of hemodynamic stability and identification of the source of bleeding are key elements in the management of this condition. Endoscopy might be necessary for both. GIB should not be immediately attributed to endurance exercise, and endoscopy should always be performed to rule out other existing pathology.

A Literature Review of Pathophysiology, Clinical Manifestations, Medications and Optimal Dosage, Outpatient, and Post-hospitalization Use of Anticoagulation in COVID-19 Patients.

Since severe acute respiratory syndrome coronavirus 2 led to a world pandemic, extensive research has been conducted to identify its characteristics and form an appropriate management plan. One recognized complication of COVID-19 is coagulation defects that can lead to thromboembolic events. We have reviewed the literature to summarize and present the latest research about the pathophysiology, clinical manifestations, anticoagulation use and appropriate dose in COVID-19 patients, as well as the effect of anticoagulation in outpatient and post-hospital settings. The pathophysiology of coagulation abnormalities in COVID-19 is not fully understood yet, but multiple mechanisms appear to be involved, such as a direct viral attack, hyperinflammation, increased immune response, blood stasis, and endothelial injury. Clinical manifestations are mainly venous thromboembolism (deep vein thrombosis and pulmonary embolism), arterial thromboembolism, ischemic stroke, central venous sinus thrombosis, and central retinal vein occlusion. Anticoagulation is widely used in hospitalized patients with COVID-19, unless it is contraindicated. Heparinoid is the main anticoagulant used. However, the appropriate dosage is still debated as research is trying to find a balance between benefits and risks. In outpatients, it appears that anticoagulation has no benefit in contrast to post-hospitalization use, where benefit could be observed in severely affected patients. We concluded that thromboprophylaxis should be used in treating hospitalized COVID-19 patients, but the dosage is still a matter of debate. More research needs to be done on outpatient and post-hospitalized patients to derive accurate conclusions.

Impact of Bacterial Infections on COVID-19 Patients: Is Timing Important?

BACKGROUND: Along with important factors that worsen the clinical outcome of COVID-19, it has been described that bacterial infections among patients positive for a SARS-CoV-2 infection can play a dramatic role in the disease process. Co-infections or community-acquired infections are recognized within the first 48 h after the admission of patients. Superinfections occur at least 48 h after admission and are considered to contribute to a worse prognosis. Microbiologic parameters differentiate infections that happen after the fifth day of hospitalization from those appearing earlier. Specifically, after the fifth day, the detection of resistant bacteria increases and difficult microorganisms emerge. OBJECTIVES: The aim of the study was to evaluate the impact of bacterial infections in patients with COVID-19 on the length of the hospital stay and mortality. METHODS: A total of 177 patients hospitalized due to COVID-19 pneumonia were consecutively sampled during the third and fourth wave of the pandemic at a University Hospital in Greece. A confirmed bacterial infection was defined as positive blood, urinary, bronchoalveolar lavage (BAL) or any other infected body fluid. Patients with confirmed infections were further divided into subgroups according to the time from admission to the positive culture result. RESULTS: When comparing the groups of patients, those with a confirmed infection had increased odds of death (odds ratio: 3.634; CI 95%: 1.795-7.358; p < 0.001) and a longer length of hospital stay (median 13 vs. 7 days). A late onset of infection was the most common finding in our cohort and was an independent risk factor for in-hospital death. Mortality and the length of hospital stay significantly differed between the subgroups. CONCLUSION: In this case series, microbial infections were an independent risk factor for a worse outcome among patients with COVID-19. Further, a correlation between the onset of infection and a negative outcome in terms of non-infected, community-acquired, early hospital-acquired and late hospital-acquired infections was identified. Late hospital-acquired infections increased the mortality of COVID-19 patients whilst superinfections were responsible for an extended length of hospital stay.

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.

N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis.

BACKGROUND: N-acetylcysteine (NAC) is a mucolytic agents with anti-inflammatory properties that has been suggested as an adjunctive therapy in patients with COVID-19 pneumonia. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate available evidence on the possible beneficial effects of NAC on SARS-CoV-2 infection. METHODS: In September 2022, we conducted a comprehensive search on Pubmed/Medline and Embase on randomized controlled trials (RCTs) and observational studies on NAC in patients with COVID-19 pneumonia. Study selection, data extraction and risk of bias assessment was performed by two independent authors. RCTs and observational studies were analyzed separately. RESULTS: We included 3 RCTs and 5 non-randomized studies on the efficacy of NAC in patients with COVID-19, enrolling 315 and 20826 patients respectively. Regarding in-hospital mortality, the summary effect of all RCTs was OR: 0.85 (95% CI: 0.43 to 1.67, I2=0%) and for non-randomized studies OR: 1.02 (95% CI: 0.47 to 2.23, I2=91%). Need for ICU admission was only reported by 1 RCT (OR: 0.86, 95% CI:0.44-1.69, p=0.66), while all included RCTs reported need for invasive ventilation (OR:0.91, 95% CI:0.54 to 1.53, I2=0). Risk of bias was low for all included RCTs, but certainty of evidence was very low for all outcomes due to serious imprecision and indirectness. CONCLUSION: The certainty of evidence in the included studies was very low, thus recommendations for clinical practice cannot be yet made. For all hard clinical outcomes point estimates in RCTs are close to the line of no effect, while observational studies have a high degree of heterogeneity with some of them suggesting favorable results in patients receiving NAC. More research is warranted to insure that NAC is both effective and safe in patients with COVID-19 pneumonia.

Burnout Among Healthcare Workers During Covid-19 Pandemic: Results from Seven Hospitals in Western Greece.

Background: Burnout is increasingly being recognized as a major concern, affecting the physical and mental well-being of Healthcare workers (HCWs). Objective: The aim of the study was to investigate the incidence of occupational exhaustion in healthcare workers (doctors, nurses, paramedics, assistants, administrative staff) and possible contributing factors during the COVID-19 pandemic. Methods: This study was conducted from March to September 2022 in seven (7) hospitals in Western Greece. It was carried out using an anonymous questionnaire. The questionnaire was designed based on results of previously published studies and consisted of 22 multiple-choice questions. Results: There were 259 (60.2%) female and 178 (39.8%) male participants enrolled in the study. The majority of the respondents were nurses (n=207, 48.1%), followed by doctors (n+ 178, 41.4%). There was a marked increase in emotional exhaustion, depersonalization, personal fulfillment and pandemic-related total burnout in participants older than 61 years old (40,05±2,2, 27,16±1,0, 21,11±4,1, 88,32±4,3, respectively). Widow/ers healthcare workers were mostly affected from pandemic related burnout compared to married, unmarried, and divorced healthcare workers. Respondents without postgraduate education demonstrated significantly greater prevalence of emotional exhaustion, depersonalization and pandemic-related total burnout in comparison to those with doctoral/master degree. The prevalence of personal and work-related burnout among paramedics and administrative staff was higher than that seen in doctors and nurses(32,82±3,8 vs32,08±5,0/29,11±4,7 22,33±4,0 vs21,57±3,1/18,89±5,4 19,60±3,9 vs17,26±2,8/15,24±3,7 74,76±10,4 vs70,92±9,5/63,23±12,1).The prevalence of emotional exhaustion and work-related total burnout was significantly higher among doctors, nurses, paramedics, and administrative staff working with direct contact with COVID-19 patients than those among healthcare workers working without direct contact with COVID-19 patients. Conclusion: The present study highlights the impact of the COVID-19 pandemic on healthcare workers.

External validation of the 4C Mortality Score and PRIEST COVID-19 Clinical Severity Score in patients hospitalized with COVID-19 pneumonia in Greece.

Background: Prognostic scores can be used to facilitate better management of patients suffering from life-threatening diseases, provided that they have been tested in the population of interest. Aim: To perform external validation of the 4C Mortality Score and PRIEST COVID-19 Clinical Severity Score. Study Design: Prospective observational Study. Methods: Patients hospitalized with COVID-19 pneumonia in a tertiary hospital in Greece were enrolled in the study. The prognostic scores were calculated based on hospital admission data and ROC curve analysis was performed. We assessed a composite outcome of either in-hospital death or need for invasive ventilation. Results: Both 4C and PRIEST scores showed good discriminative ability with an AUC value of 0.826 (CI 95%: 0.765-0.887) and 0.852 (CI 95%: 0.793-0.910) respectively. Based on the Youden Index the optimal cut-off for the 4C score was 11 (Sensitivity 75%, Specificity 75.5%) and 10 for the PRIEST score (Sensitivity 83% and Specificity 69.4%). Calibration was adequate for both scores, except for the low and very high risk groups in the PRIEST score. Conclusion: The 4C Mortality Score and PRIEST COVID-19 Clinical Severity Score can be used for early identification of patients with poor prognosis in a Greek population cohort hospitalized with COVID-19.

The role of soluble urokinase plasminogen activator receptor (suPAR) in patients with cancer: a review of the current literature.

Aim Several biomarkers are currently used as diagnostic and prognostic tools in patients with cancer. Soluble urokinase plasminogen activator receptor (suPAR) is elevated in acute and chronic inflammatory procedures and several observational studies during the last 20 years have investigated its role in oncology. The purpose of this article was to review the current literature regarding suPAR's role in clinical practice. Methods A systematic literature search of PubMed, Scopus, OpenGrey and Cochrane Library databases through September 2021 was conducted using the following search terms: "supar"or "soluble urokinase plasminogen receptor" and "cancer" or "malignancy". Original articles reporting on suPAR's role in the diagnosis, prognosis and prediction of therapeutic outcomes in patients with confirmed or suspected cancer were included. Results Among 45 found articles, the most were observational cohort studies. The included studies were further categorized by cancer site. SuPAR level was higher in patients with cancer compared to healthy controls, but its diagnostic and prognostic accuracy differs depending on the site of cancer. Conclusion SuPAR has promising aspects in the field of oncology and public health and future research should further investigate its use in clinical practice. As it is elevated in different types of cancer, it could potentially serve as an adjunctive tool for the mass screening of patients with non-specific signs of cancer, but larger cohort studies that support these findings must be conducted.

Accidental ingestion of a dental bur in an 84-year-old male.

This report describes the case of an 84-year-old male who was brought to the emergency room because a dental bur was swallowed accidentally during a dental procedure. The foreign body was successfully removed by gastroenterologists endoscopically 8 days after the ingestion and was identified as a 2-cm-long dental bur.

Common anti-oxidant vitamin C as an anti-infective agent with remedial role on SARS-CoV-2 infection. An update.

Coronavirus disease 2019 (COVID-19) has led to a worldwide multifaceted crisis. The medical world agonizes to contend with the problem, but a string of tested medications has been proven unavailing. Vitamin C is well described as a salutary antioxidant and some trials conclude that it may be a potential antiviral drug. In high doses, vitamin C can alternate crucial steps in the pathogenesis of sepsis and acute respiratory distress syndrome. This dynamic was the driving force behind trials around the world that tried immunonutrition as a weapon against clinical entities. We summarize the mechanisms of action of vitamin C and its role against infections and the current literature referring to the potential role of vitamin C in SARS-CoV-2 infection, also as a contingent treatment agent.