Biomarkers Improve Diagnostics of Sepsis in Adult Patients With Suspected Organ Dysfunction Based on the Quick Sepsis-Related Organ Failure Assessment (qSOFA) Score in the Emergency Department.

OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.

Micromotor-based dual aptassay for early cost-effective diagnosis of neonatal sepsis.

Given the long-life expectancy of the newborn, research aimed at improving sepsis diagnosis and management in this population has been recognized as cost-effective, which at early stages continues to be a tremendous challenge. Despite there is not an ideal-specific biomarker, the simultaneous detection of biomarkers with different behavior during an infection such as procalcitonin (PCT) as high specificity biomarker with one of the earliest biomarkers in sepsis as interleukin-6 (IL-6) increases diagnostic performance. This is not only due to their high positive predictive value but also, since it can also help the clinician to rule out infection and thus avoid the use of antibiotics, due to their high negative predictive value. To this end, we explore a cutting-edge micromotor (MM)-based OFF-ON dual aptassay for simultaneous determination of both biomarkers in 15 min using just 2 µL of sample from low-birth-weight neonates with gestational age less than 32 weeks and birthweight below 1000 g with clinical suspicion of late-onset sepsis. The approach reached the high sensitivities demanded in the clinical scenario (LODPCT = 0.003 ng/mL, LODIL6 = 0.15 pg/mL) with excellent correlation performance (r > 0.9990, p < 0.05) of the MM-based approach with the Hospital method for both biomarkers during the analysis of diagnosed samples and reliability (Er < 6% for PCT, and Er < 4% for IL-6). The proposed approach also encompasses distinctive technical attributes in a clinical scenario since its minimal sample volume requirements and expeditious results compatible with few easy-to-obtain drops of heel stick blood samples from newborns admitted to the neonatal intensive care unit. This would enable the monitoring of both sepsis biomarkers within the initial hours after the manifestation of symptoms in high-risk neonates as a valuable tool in facilitating prompt and well-informed decisions about the initiation of antibiotic therapy.These results revealed the asset behind micromotor technology for multiplexing analysis in diagnosing neonatal sepsis, opening new avenues in low sample volume-based diagnostics.

The budget impact of procalcitonin-guided antibiotic stewardship compared to standard of care for patients with suspected sepsis admitted to the intensive care unit in Belgium.

In Belgium, antibiotic resistance leads to approximately 530 deaths with a €24 million financial burden annually. This study estimated the impact of procalcitonin-guided antibiotic stewardship programs to reduce antibiotic consumption versus standard of care in patients with suspected sepsis. A decision analytic tree modelled health and budget outcomes of procalcitonin-guided antibiotic stewardship programs for patients admitted to the intensive care unit (ICU). A literature search, a survey with local clinical experts, and national database searches were conducted to obtain model input parameters. The main outcomes were total budget impact per patient, reduction in number of antibiotic resistance cases, and cost per antibiotic day avoided. To evaluate the impact of parameter uncertainty on the source data, a deterministic sensitivity analysis was performed. A scenario analysis was conducted to investigate budget impact when including parameters for reduction in length of ICU stay and mechanical ventilation duration, in addition to base-case parameters. Based on model predictions, procalcitonin-guided antibiotic stewardship programs could reduce the number of antibiotic days by 66,868, resulting in €1.98 million savings towards antibiotic treatment in current clinical practice. Antibiotic resistance cases could decrease by 7.7% (6.1% vs 9.2%) in the procalcitonin-guided setting compared with standard of care. The base-case budget impact suggests an investment of €1.90 per patient. The sensitivity analysis showed uncertainty, as the main drivers can alter potential cost savings. The scenario analysis indicated a saving of €1,405 per patient, with a reduction of 1.5 days in the ICU (14.8 days vs 12.8 days), and a reduction of 22.7% (18.1-27.2%) in mechanical ventilation duration. The associated sensitivity analysis was shown to be robust in all parameters. Procalcitonin-guided antibiotic stewardship programs are associated with clinical benefits that positively influence antimicrobial resistance in Belgium. A small investment per patient to implement procalcitonin testing may lead to considerable cost savings.

Assessment of amino-terminal C-type natriuretic peptide serum level and its correlation with high-density lipoprotein structure and function in patients with end stage renal disease before and after kidney transplantation.

We aimed to investigate serum amino-terminal C-type natriuretic peptide (NT-proCNP) and its relationship with quantitative and qualitative HDL-parameters in patients with end-stage renal disease (ESRD) before, then 1 and 6 months after kidney transplantation (TX). Seventy patients (47 males, 23 females, mean age 51.7 ± 12.4 years) were enrolled in a prospective follow-up study. We examined serum creatinine, C-reactive protein, procalcitonin, fasting glucose and lipid parameters before, then 1 and 6 months after TX. High-density lipoprotein- (HDL)-associated paraoxonase-1 (PON1) paraoxonase and arylesterase activities were measured spectrophotometrically. Lipoprotein subfractions were determined by Lipoprint. NT-proCNP and oxidized low-density lipoprotein (oxLDL) levels were measured by ELISA. Mean NT-proCNP was 45.8 ± 21.9 pmol/L before renal transplantation and decreased markedly 1 month and 6 months after transplantation (5.3 ± 2.5 and 7.7 ± 4.9 pmol/L, respectively, P = 1 × 10-4). During the 6 months' follow-up, PON1 arylesterase, paraoxonase and salt-stimulated paraoxonase activities improved. NT-proCNP positively correlated with procalcitonin and creatinine and negatively with GFR, LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C). There was a negative correlation between serum NT-proCNP and PON1 arylesterase activity. According to the multiple regression analysis, the best predicting variables of NT-proCNP were serum procalcitonin, creatinine and PON1 arylesterase activity. NT-proCNP might be a novel link between HDL dysfunction and impaired vascular function in ESRD, but not after kidney transplantation. Further studies in larger populations are needed to clarify the exact role of NT-proCNP in the risk prediction for cardiovascular comorbidities and complications in ESRD.

The value of right ventricular ultrasound assessment and cardiac biomarkers in the prognosis of sepsis.

OBJECTIVE: The aim of this study was to explore the risk factors affecting the prognosis of patients with sepsis using a prospective design. PATIENTS AND METHODS: From January 2022 to March 2023, a prospective study was conducted in the Intensive Care Unit (ICU) of Cangzhou Central Hospital, including 58 patients who met the diagnostic criteria for sepsis. Patients were divided into a survival group (39 cases) and a death group (19 cases) based on outcome. Within 24 hours, the following indicators were collected: gender, age, underlying diseases, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, cardiac troponin I (cTnI), B-type natriuretic peptide (BNP), lactate, procalcitonin, ejection fraction (EF), tricuspid annular plane systolic excursion (TAPSE), systolic velocity (S'), and global longitudinal strain/strain rate (GLS/GLSr) and global circumferential strain/strain rate (GCS/GCSr) by speckle tracking. Logistic regression analysis was used to evaluate the risk factors for mortality in septic patients, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of various risk factors for sepsis-related death. RESULTS: There was no significant difference in gender, age, underlying diseases, BNP, procalcitonin, EF, TAPSE, S', GLSr, GCS, or GCSr between the two groups (p>0.05). There were statistically significant differences in APACHE II score, SOFA score, cTnI, lactate, and GLS between the two groups (p<0.05). Logistic regression analysis showed that SOFA score (OR=2.32, 95% CI: 1.067-5.289, p<0.05), cTnI (OR=1.19, 95% CI: 1.001-1.312, p<0.05), and GLS (OR=1.58, 95% CI: 1.012-2.721, p<0.05) were risk factors for sepsis-related death (p<0.05). The areas under the ROC curves for SOFA score, cTnI, and GLS were 0.769, 0.757, and 0.846, respectively. CONCLUSIONS: SOFA score, cTnI, and GLS are independent risk factors for mortality in patients with sepsis. Among these factors, GLS has the highest predictive value for patient prognosis. Therefore, when predicting the prognosis of patients with sepsis, the assessment of right ventricular ultrasound can be used in clinical practice.

Prognostic value of platelet combined with serum procalcitonin in patients with sepsis.

Sepsis, a common and life-threatening condition in critically ill patients, is a leading cause of death in intensive care units. Over the past few decades, there has been significant improvement in the understanding and management of sepsis. However, the mortality rate remains unacceptably high, posing a prominent challenge in modern medicine and a significant global disease burden. A total of 295 patients with sepsis admitted to the hospital from January 2021 to December 2022 were collected and divided into survival group and death group according to their 28-day survival status. The differences in general clinical data and laboratory indicators between the 2 groups were compared. Receiver operating characteristic curve analysis was used to evaluate the predictive value of platelet (PLT) and procalcitonin (PCT) for the prognosis of sepsis patients within 28 days. A total of 295 patients were diagnosed with sepsis, and 79 died, with a mortality rate of 26.78%. The PLT level in the death group was lower than that in the survival group; the PCT level in the death group was higher than that in the survival group. The receiver operating characteristic curve showed that the area under the curve of PCT and PLT for evaluating the prognosis of sepsis patients were 0.808 and 0.804, respectively. Kaplan-Meier survival analysis showed that the 28-day survival rate of the low PLT level group was 19.0% and that of the high PLT level group was 93.1% at the node of 214.97 × 109/L, and the difference between the 2 groups was statistically significant (χ2 = 216.538, P < .001). The 28-day survival rate of the low PCT level group was 93.4% and that of the high PCT level group was 51.7% at the node of 2.85 ng/mL, and the difference between the 2 groups was statistically significant (χ2 = 63.437, P < .001). There was a negative correlation between PCT level and PLT level (r = -0.412, P < .001). Platelet combined with serum procalcitonin detection has high predictive value for judging the 28-day prognosis of sepsis, and it can be used as an index for evaluating the patient's condition and prognosis, and is worthy of clinical promotion and application.

[Value of serum procalcitonin and acute physiology and chronic health evaluation II score on predicting the prognosis of sepsis in elderly patients].

OBJECTIVE: To explore the value of serum procalcitonin (PCT) and acute physiology and chronic health evaluation II (APACHE II) score on predicting prognosis of elderly patients with sepsis. METHODS: A retrospective cohort study, patients with sepsis who admitted to the department of emergency and the department of geriatric medicine of Peking University Third Hospital from March 2020 to June 2021 were enrolled. Patients' demographics, routine laboratory examinations, APACHE II score that within 24 hours of admission were obtained from their electronic medical records. The prognosis during the hospitalization and one year after discharge were collected, retrospectively. Univariate and multivariate analysis of prognostic factors were performed. And Kaplan-Meier survival curves were used to examine overall survival. RESULTS: A total of 116 elderly patients met inclusion criteria, 55 were alive and 61 were died. On univariate analysis, clinical variables such as lactic acid [Lac, hazard ratio (HR) = 1.16, 95% confidence interval (95%CI) was 1.07-1.26, P < 0.001], PCT (HR = 1.02, 95%CI was 1.01-1.04, P < 0.001), alanine aminotransferase (ALT, HR = 1.00,95%CI was 1.00-1.00, P = 0.143), aspartate aminotransferase (AST, HR = 1.00, 95%CI was 1.00-1.01, P = 0.014), lactate dehydrogenase (LDH, HR = 1.00, 95%CI was 1.00-1.00, P < 0.001), hydroxybutyrate dehydrogenase (HBDH, HR = 1.00, 95%CI was 1.00-1.00, P = 0.001), creatine kinase (CK, HR = 1.00, 95%CI was 1.00-1.00, P = 0.002), MB isoenzyme of creatine kinase (CK-MB, HR = 1.01, 95%CI was 1.01-1.02, P < 0.001), Na (HR = 1.02, 95%CI was 0.99-1.05, P = 0.183), blood urea nitrogen (BUN, HR = 1.02, 95%CI was 0.99-1.05, P = 0.139), fibrinogen (FIB, HR = 0.85, 95%CI was 0.71-1.02, P = 0.078), neutrophil ratio (NEU%, HR = 0.99, 95%CI was 0.97-1.00, P = 0.114), platelet count (PLT, HR = 1.00, 95%CI was 0.99-1.00, P = 0.108) and total bile acid (TBA, HR = 1.01, 95%CI was 1.00-1.02, P = 0.096) shown to be associated with poor prognosis. On multivariable analysis, level of PCT was an important factor influencing the outcome of sepsis (HR = 1.03, 95%CI was 1.01-1.05, P = 0.002). Kaplan-Meier survival curve showed that there was no significant difference with respect to the overall survival between the two groups, with patients of PCT ≤ 0.25 µg/L and PCT > 0.25 µg/L (P = 0.220). It also showed that the overall survival rate in patients with high APACHE II score (> 27 points) was significantly lower than that in patients with low APACHE II score (≤ 27 points, P = 0.015). CONCLUSIONS: Serum PCT level is valuable prognostic factors of elderly patients with sepsis, and higher APACHE II score (> 27 points) indicates a poor prognosis.

Low-cost, facile droplet modification of screen-printed arrays for internally validated electrochemical detection of serum procalcitonin.

This manuscript presents the design and facile production of screen-printed arrays (SPAs) for the internally validated determination of raised levels of serum procalcitonin (PCT). The screen-printing methodology produced SPAs with six individual working electrodes that exhibit an inter-array reproducibility of 3.64% and 5.51% for the electrochemically active surface area and heterogenous electrochemical rate constant respectively. The SPAs were modified with antibodies specific for the detection of PCT through a facile methodology, where each stage simply uses droplets incubated on the surface, allowing for their mass-production. This platform was used for the detection of PCT, achieving a linear dynamic range between 1 and 10 ng mL-1 with a sensor sensitivity of 1.35 × 10-10 NIC%/ng mL-1. The SPA produced an intra- and inter-day %RSD of 4.00 and 5.05%, with a material cost of £1.14. Internally validated human serum results (3 sample measurements, 3 control) for raised levels of PCT (>2 ng mL-1) were obtained, with no interference effects seen from CRP and IL-6. This SPA platform has the potential to offer clinicians vital information to rapidly begin treatment for "query sepsis" patients while awaiting results from more lengthy remote laboratory testing methods. Analytical ranges tested make this an ideal approach for rapid testing in specific patient populations (such as neonates or critically ill patients) in which PCT ranges are inherently wider. Due to the facile modification methods, we predict this could be used for various analytes on a single array, or the array increased further to maintain the internal validation of the system.

Utility and impact of early diagnostic assessment of sepsis on mortality in an emergency department of a tertiary hospital in Lagos, Nigeria.

Context: Currently, little is known about the timely application of clinical screening tools and blood sampling for decision-making in the management of patients with suspected sepsis in the accident and emergency units of hospitals in Nigeria. Aim: The aim of the study was to ascertain the association between the time taken for the conduct of serum lactate and blood culture investigations following a clinical suspicion of sepsis, and the mortality of patients admitted to a Nigerian tertiary hospital. Methods: Over a 6-month period (November 2021 to April 2022), 119 patients hospitalised for sepsis or septic shock at the Lagos University Teaching Hospital were followed until discharge or death. The proportion of patients whose serum lactate, serum procalcitonin and blood culture samples was taken was also determined. Predictors of mortality were determined using bivariate analysis and logistic regression. Kaplan-Meier plots were used to predict survival using sepsis diagnostic criteria. Results: Eighty (67%) of 119 sepsis patients met systemic inflammatory response syndrome or quick sequential (sepsis-related) organ failure assessment criteria. Only 3 (2.5%) patients had blood cultures and serum procalcitonin and 0 (0%) had serum lactate tests. Forty-one (34.5%) patients died, but clinical and laboratory procedures for sepsis management were not linked to death. A shorter hospital stay increased the death risk (χ2 = 14.83, P = 0.002). Conclusion: This study revealed low compliance with sepsis care guidelines and no impact of timely clinical and laboratory procedures on sepsis mortalities. Further study is needed to explore patient care models that can improve the objective assessment and treatment of sepsis patients in emergency departments of busy tertiary hospitals.

Assessment of the role of neutrophil extracellular traps in SARS-CoV-2 pneumonia.

BACKGROUND: Abnormal neutrophil extracellular traps are associated with lung diseases, thrombosis, increased mucosal secretion in the airways. The aim of this study is to evaluate the possible place of the most specific NETosis marker Cit-H3 protein in diagnostic algorithms by revealing its relationship with the severity, mortality and prognosis of SARS-CoV-2 pneumonia. PATIENTS AND METHODS: Patients (n = 78) who applied to the Emergency Department between March 11, 2020 and June 10, 2020, with positive SARS-CoV-2 polymerase chain reaction (PCR) test and lung involvement were included in the prospective study. Serum Cit-H3 levels and critical laboratory parameters were measured at baseline on the day of clinical deterioration and before recovery/discharge/death. Cit-C3 levels were determined by enzyme immunassay method. RESULTS: Cit-H3 levels in patients with SARS-CoV-2 pneumonia during their first admission to the hospital were significantly higher compared to the healthy control group (p < 0.05). Repeated measurements of Cit-H3 levels of the patients significantly correlated with D-dimer, procalcitonin, Neutrophil/ Lymphocyte ratio, lymphocyte, CRP, and oxygen saturation. Cit-H3 levels of the patients who died were significantly higher than that of those who survived (p < 0.05). Cit-H3 levels were found to be statistically significantly higher in patients who developed acute respiratory distress syndrome, were admitted to the intensive care unit, and had mortality (p < 0.05). CONCLUSIONS: Cit-H3 plays a role in inflammatory processes in SARS-CoV-2 pneumonia, and changes in serum Cit-H3 levels of these patients can be used to determine prognosis and mortality (Tab. 5, Fig. 1, Ref. 21).

PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality. METHODS AND ANALYSIS: PRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation. ETHICS AND DISSEMINATION: The trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ISRCTN54006056.

Perinatal presepsin assessment: a new sepsis diagnostic tool?

Perinatal sepsis constitutes a medical emergency and is still one of the major causes of mortality and morbidity. The possibility of an early diagnosis of sepsis is still debated and controversial. In particular, clinical symptoms can be hidden by the association of sepsis with other perinatal diseases and/or by therapeutic strategies performed. In this context, there is evidence that the accuracy of standard of care diagnostic parameters (i.e. blood culture, C-reactive protein, procalcitonin) can be biased by additional confounding factors (gestational age, birth-weight, acute-chronic hypoxia). Therefore, the inclusion in clinical daily practice of new biomarkers of sepsis is of utmost importance. Of a panel of biomarkers, Presepsin (P-SEP) plays an important role in the development and response of the immune system and as an early marker of sepsis both in adult and pediatric patients. Therefore, in the present review we aim to offer an overview of the role of P-SEP in the early detection of perinatal sepsis as a trustworthy marker according to actual statements of official international institutions. Future perspectives regard the possibility of a longitudinal non-invasive biological fluids P-SEP assessment thus limiting the sample stress in high risk newborns.

Cost-effectiveness of procalcitonin for detection of serious bacterial infections in children presenting with fever without source.

INTRODUCTION: Procalcitonin (PCT) offers better specificity than C-reactive protein (CRP) to detect SBI. However, their cost limited their use and routine application. The objective of this work is to determine the cost-effectiveness of PCT against CPR or Rochester scale in infants between 1 and 3 months from the perspective of the third payer in Colombia. METHODS: A Monte Carlo simulation was performed with a hypothetical cohort of 10,000 patients with fever without focus (FWS) between 1 to 3 months, to estimate the number of cases correctly diagnosed for each test and the associated costs with each test. RESULTS: The test with the highest number of correctly diagnosed cases was PCT 79%, followed by C-reactive protein 75%, and the Rochester scale 68%. The test with the lowest cost per patient was PCT $645 (95% CI US$646-US$645) followed by C-reactive protein U$ 653 (95% CI US$655-$645) and Rochester scale US$804 (95% CI US$807-US$804). This position of dominance of PCT eliminated the need to calculate an incremental cost effectiveness ratio. CONCLUSIONS: PCT is the most cost-effective strategy for the detection of IBS in infants with FWS. These results should be interpreted within the clinical context of the patient and not as a single method for therapeutic decision-making.

Effect of manual hyperinflation on recurrent atelectasis in a ventilator-dependent C3 complete spinal cord injury patient: A case report.

CLINICAL CASE: We present here the case of a ventilator-dependent 76-year-old man with C3 complete spinal cord injury (SCI) who presented with recurrent left lung atelectasis managed with manual hyperinflation (MH). Atelectasis was primarily assessed with chest X-ray (CXR). Additional monitoring included blood gas analysis, serum procalcitonin, and the Modified Borg Dyspnea Scale (MBS), as an objective measure of reported dyspnea. We found that MH successfully reversed the radiographic appearance of atelectasis after the first treatment and maintained this effect for the duration of the 2-week intervention period as well as at 2 weeks of follow-up post-intervention. Furthermore, MH decreased the patient's oxygen requirements and was associated with a decrease in serum procalcitonin. Clinically, the patient reported reduced subjective dyspnea post-MH, which was reflected as an improvement on the MBS. We conclude that MH may represent a therapeutic modality for consideration in the routine management of recurrent atelectasis in mechanically ventilated patients.

National external quality assessment and direct method comparison reflect crucial deviations of Procalcitonin measurements in Germany.

BACKGROUND AND AIMS: Sepsis is a major concern worldwide, affecting 49 million individuals and being related to 11 million deaths. Its fast diagnosis is the key factor to guarantee a positive prognosis. Procalcitonin (PCT) has emerged as one powerful biomarker to early diagnose sepsis and for monitoring of antibiotic treatment. However, its clinical utility is jeopardized by missing standardisation. MATERIALS AND METHODS: Here we present a 1-year follow-up of the External Quality Assessment (EQA) in Germany, depicting substantial discrepancies among manufacturers and the used assay technology of current PCT measurements. A direct method comparison on two immunoassays (Abbott vs. DiaSys) on a set of 135 routine samples was used to analyse the causes of observed deviations. RESULTS: All BRAHMS-licensed manufacturers (Thermo, Roche, Abbott, Siemens, Biomérieux), the Beckman and DiaSys immunoassays as well as all assay types (fluorescence, luminescence, PETIA) reveal substantial recovery differences between each other. However, upon a non-linear re-standardization of calibrators, the two directly compared methods (Abbott, DiaSys) are well interchangeable. CONCLUSION: This work demonstrates the heterogenic situation of PCT measurements in Germany among manufacturers and all methods. By introducing dedicated correction factors, comparable results of PCT can be achieved. This work also strengthens the inevitability of calibrator traceability and higher metrological reference materials on PCT.

Quick Sequential Organ Failure Assessment, Sequential Organ Failure Assessment, and Procalcitonin for Early Diagnosis and Prediction of Death in Elderly Patients with Suspicion of Sepsis in the Emergency Department, Based on Sepsis-3 Definition.

BACKGROUND: Sepsis is a disease with a high mortality rate without prompt treatment. However, this entity is difficult to diagnose in the elderly population in the emergency room; for this reason, it is necessary to have diagnostic tools for early detection. OBJECTIVE: The aim of the study was to determine the highest diagnostic yield of procalcitonin (PCT), Quick Sequential Organ Failure Assessment (qSOFA), and Sequential Organ Failure Assessment (SOFA) for sepsis (based on the sepsis-3 consensus), on admission at the emergency department, in those older than 65 years. METHODS: This is a diagnostic test study of a historical cohort of 65-year-old patients with suspected sepsis. RESULTS: In the sample of 179 patients, 53.6% had confirmed sepsis. Significant differences were found (p < 0.0001), with a greater diagnostic and predictive capacity of PCT for the diagnosis of sepsis (receiver operating characteristics curve area [area under the curve (AUC) = 0.883, 95% CI: 0.835-0.931] than qSOFA (AUC = 0.559, 95% CI: 0.485-0.663) and SOFA (AUC = 0.662, 95% CI: 0.584-0.739); these results were similar in the cohort of patients ≥75 years. In positive PCT(≥0.5 ng/mL), the sensitivity was 71.8% (95% CI: 62.36-81.39), specificity of 89.1% (95% CI: 81.87-96.45%), V+ 88.4% (95% CI: 80.73-96.19%), V- of 73.2% (95% CI: 64.14-82.39%), positive likelihood ratio of 6.63 (95% CI: 3.53-12.44), and negative likelihood ratio of 0.32 (95% CI: 0.23-0.44); these results were similar in the cohort of patients ≥75 years. Lactate ≥2 mmol/L (RR = 1.659 [95% CI: 1.002-2.747]) and PCT ≥0.5 ng/mL (RR = 1.942 [95% CI: 1.157-3.261]) showed a significant association with in-hospital mortality. CONCLUSION: In the elderly population with suspicion of infection on admission to the emergency department, qSOFA presents a low diagnostic performance of confirmed sepsis and in-hospital mortality, for which other tools with higher diagnostic and prognostic performance should be added, such as PCT and lactate.

Cost impact of procalcitonin-guided decision making on duration of antibiotic therapy for suspected early-onset sepsis in neonates.

BACKGROUNDS: The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-minimization study of the NeoPInS trial, comparing health care costs of standard care and PCT-guided decision making based on the NeoPInS algorithm, and to analyze subgroups based on country, risk category and gestational age. METHODS: Data from the NeoPInS trial in neonates born after 34 weeks of gestational age with suspected EOS in the first 72 h of life requiring antibiotic therapy were used. We performed a cost-minimization study of health care costs, comparing standard care to PCT-guided decision making. RESULTS: In total, 1489 neonates were included in the study, of which 754 were treated according to PCT-guided decision making and 735 received standard care. Mean health care costs of PCT-guided decision making were not significantly different from costs of standard care (€3649 vs. €3616). Considering subgroups, we found a significant reduction in health care costs of PCT-guided decision making for risk category 'infection unlikely' and for gestational age ≥ 37 weeks in the Netherlands, Switzerland and the Czech Republic, and for gestational age < 37 weeks in the Czech Republic. CONCLUSIONS: Health care costs of PCT-guided decision making of term and late-preterm neonates with suspected EOS are not significantly different from costs of standard care. Significant cost reduction was found for risk category 'infection unlikely,' and is affected by both the price of PCT-testing and (prolonged) hospitalization due to SAEs.

Ability of Procalcitonin and C-Reactive Protein for Discriminating between Bacterial and Enteroviral Meningitis in Children Using Decision Tree.

Bacterial meningitis (BM) is a public health burden in developing countries, including Central Asia. This disease is characterized by a high mortality rate and serious neurological complications. Delay with the start of adequate therapy is associated with an increase in mortality for patients with acute bacterial meningitis. Cerebrospinal fluid culture, as a gold standard in bacterial meningitis diagnosis, is time-consuming with modest sensitivity, and this is unsuitable for timely decision-making. It has been shown that bacterial meningitis differentiation from viral meningitis could be done through different parameters such as clinical signs and symptoms, laboratory values, such as PCR, including blood and cerebrospinal fluid (CSF) analysis. In this study, we proposed the method for distinguishing the bacterial form of meningitis from enteroviral one. The method is based on the machine learning process deriving making decision rules. The proposed fast-and-frugal trees (FFTree) decision tree approach showed an ability to determine procalcitonin and C-reactive protein (CRP) with cut-off values for distinguishing between bacterial and enteroviral meningitis (EVM) in children. Such a method demonstrated 100% sensitivity, 96% specificity, and 98% accuracy in the differentiation of all cases of bacterial meningitis in this study. These findings and proposed method may be useful for clinicians to facilitate the decision-making process and optimize the diagnostics of meningitis.