Ultrasensitive Electrochemiluminescence Biosensor with Silver Nanoclusters as a Novel Signal Probe and α-Fe2O3-Pt as an Efficient Co-reaction Accelerator for Procalcitonin Immunoassay.

Herein, a high-efficiency biosensor based on ternary electrochemiluminescence (ECL) system was constructed for procalcitonin (PCT) detection. Specifically, silver nanoclusters (Ag NCs) with stable luminescence properties were prepared with small-molecule lipoic acid (LA) as the ligand, and its ECL emission in persulfate (S2O82-) was first reported. Meanwhile, the prepared Ag NCs possessed ligand-to-metal charge-transfer characteristics, thus transferring energy from LA to Ag+ for luminescence. Based on the small particle size, good biocompatibility, and molecular binding ability, Ag NCs-LA was used as an ideal luminescent probe. In addition, α-Fe2O3-Pt was introduced to facilitate the activation of S2O82-, thereby generating more sulfate radicals to react with the free radicals of Ag NCs to enhance ECL emission. The synergistic effect of the variable valence state of transition metals and high catalytic activity of noble metals endows α-Fe2O3-Pt with excellent catalytic ability for S2O82-. Importantly, the sensing mechanism was systematically demonstrated by UV-vis, fluorescence, and ECL analysis, as well as density functional theory calculations. At last, NKFRGKYKC was designed for specific immobilization of antibodies, thus releasing the antigen binding sites to improve the antigen recognition efficiency. Based on this, the developed biosensor showed high sensitivity for PCT detection, with a wide linear range (10 fg/mL-100 ng/mL) and a low detection limit (3.56 fg/mL), which could be extended to clinical detection of multiple biomarkers.

Reducing unnecessary routine laboratory testing for noncritically ill patients with COVID-19.

BACKGROUND: Reducing unnecessary routine laboratory testing is a Choosing Wisely® recommendation, and new areas of overuse were noted during the COVID-19 pandemic. OBJECTIVE: To reduce unnecessary repetitive routine laboratory testing for patients with COVID-19 during the pandemic across a large safety net health system. DESIGNS, SETTINGS AND PARTICIPANTS: This quality improvement initiative was initiated by the System High-Value Care Council at New York City Health + Hospitals (H + H), the largest public healthcare system in the United States consisting of 11 acute care hospitals. INTERVENTION: four overused laboratory tests in noncritically ill hospitalized patients with COVID-19 were identified: C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and procalcitonin. A two-pronged electronic health record intervention was implemented consisting of (1) nonintrusive, informational nudge statements placed on selected order sets, and (2) a forcing function of one consecutive day limit on ordering. MAIN OUTCOME AND MEASURES: The average of excess tests per encounter days (ETPED) for each of four target laboratory testing only in patients with COVID-19. OBJECTIVE: Interdisciplinary System High-Value Care Council identified four overused laboratory tests (inflammatory markers) in noncritically ill hospitalized patients with COVID-19: C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and procalcitonin. Within an 11-hospital safety net health system, a two-pronged electronic health record intervention was implemented consisting of (1) nonintrusive, informational nudge statements placed on selected order sets, and (2) a forcing function of one consecutive day limit on ordering. The preintervention period (March 16, 2020 to January 24, 2021) was compared to the postintervention period (January 25, 2021 to March 22, 2022). RESULTS: Time series linear regression showed decreases in CRP (-17.9%, p < .05), ferritin (-37.6%, p < .001), and LDH (-30.1%, p < .001). Slope differences were significant (CRP, ferritin, and LDH p < 0.001; procalcitonin p < 0.05). Decreases were observed across weekly averages: CRP (-19%, p < .01), ferritin (-37.9%, p < .001), LDH (-28.7%, p < .001), and procalcitonin (-18.4%, p < .05). CONCLUSION: This intervention was associated with reduced routine inflammatory marker testing in non-intensive care unit COVID-19 hospitalized patients across 11 hospitals. Variation was high among individual hospitals.

Diagnostic accuracy of procalcitonin and interleukin-6 for postoperative infection in major gastrointestinal surgery: a systematic review and meta-analysis.

BACKGROUND: We aim to assess the diagnostic accuracy of procalcitonin (PCT) and interleukin-6 (IL-6) as diagnostic biomarkers for postoperative infection/sepsis following major abdominal surgery. Postoperative infection is an important cause for morbidity and mortality in major surgery. Early diagnosis and antimicrobial treatment improves outcomes, and high-performing biomarkers could guide clinical decision making. METHODS: A systematic database search was conducted for studies reporting diagnostic performance of biomarkers (including PCT and IL-6) for infection/sepsis following major abdominal surgery. Studies were assessed for reporting of diagnostic accuracy, relevance and quality. Data were extracted for meta-analysis. RESULTS: Ten studies with 1,611 participants reported the diagnostic accuracy of PCT, with pooled sensitivity, specificity and summary receiver operator curve of 72% (95% CI 66-78), 62% (95% CI 59-64) and 0.766, respectively. Four studies with 175 participants reported the diagnostic accuracy of IL-6, with pooled sensitivity, specificity and summary receiver operator curve of 84% (95% CI 72-92), 76% (95% CI 68-84) and 0.878, respectively There was variability in the timing of sampling and cut-off values and significant heterogeneity and inconsistency between studies (I2 diagnostic odds ratio (DOR)= 43.2% for PCT, I2 DOR=0% for IL-6). CONCLUSIONS: PCT performs only moderately well as a diagnostic test for postoperative infection/sepsis in major abdominal surgery, demonstrating limited sensitivity and specificity. Heterogeneity between studies is a limitation of the meta-analysis. There is an ongoing need for a rapid, accurate biomarker for postoperative infection or sepsis.

Efficient ABEI-Dissolved O2-Ce(III, IV)-MOF Ternary Electrochemiluminescent System Combined with Self-Assembled Microfluidic Chips for Bioanalysis.

A signal-amplified electrochemiluminescent (ECL) sensor chip was developed for sensitive analysis of procalcitonin (PCT). Herein, we first prepared a self-enhanced luminophore, which enhanced ECL responses through intramolecular reactions. Second, Au-Pd bimetallic nanocrystals and mixed-valence Ce-based metal-organic frameworks (MOFs) were introduced as co-reaction promoters to facilitate the reduction of dissolved O2. Based on the synergistic catalysis of Au and Pd, the spontaneous cyclic reaction of Ce(III)/Ce(IV), and the high electrochemical active surface area of Ce(III, IV) MOF, a large number of superoxide anion radicals (O2•-) and hydroxyl radicals (OH•) were produced. Therefore, the luminescence efficiency of N-(aminobutyl)-N-(ethylisoluminol)-dissolved O2 (ABEI-O2) systems were greatly improved, providing a new prospect for the application of dissolved O2 in ECL analysis. In addition, the affinity peptide ligands were used for the directional connection of antibodies to provide protection for the bioactivity of the proposed sensor. Finally, the microfluidic technology was applied to ECL analysis to integrate the three-electrode detection system into the self-assembled microfluidic chip, which realized the automation and portability of the detection process. The developed sensor showed high sensitivity for PCT detection with a detection limit of 3.46 fg/mL, which possessed positive significance for the clinical diagnosis of sepsis.

Elucidating the role of procalcitonin as a biomarker in hospitalized COVID-19 patients.

Our objectives were to evaluate the role of procalcitonin in identifying bacterial co-infections in hospitalized COVID-19 patients and quantify antibiotic prescribing during the 2020 pandemic surge. Hospitalized COVID-19 patients with both a procalcitonin test and blood or respiratory culture sent on admission were included in this retrospective study. Confirmed co-infection was determined by an infectious diseases specialist. In total, 819 patients were included; 335 (41%) had an elevated procalcitonin (>0.5 ng/mL) and of these, 42 (13%) had an initial bacterial co-infection. Positive predictive value of elevated procalcitonin for co-infection was 13% while the negative predictive value was 94%. Ninety-six percent of patients with an elevated procalcitonin received antibiotics (median 6 days of therapy), compared to 82% with low procalcitonin (median 4 days of therapy) (adjusted OR:3.3, P < 0.001). We observed elevated initial procalcitonin in many COVID patients without concurrent bacterial co-infections which potentially contributed to antibiotic over-prescribing.

Investigation of procalcitonin and beta-defensin2 in the serum and feces of dogs with acute diarrhea.

BACKGROUND: Acute diarrhea is a common clinical condition where clinical parameters are used to assess disease severity, course, and prognosis. OBJECTIVES: The aim of this study was to investigate procalcitonin (PCT) and beta-defensin2 (Bdef2) as biomarkers for disease severity, course, and prognosis of dogs with acute diarrhea. METHODS: Dogs with acute diarrhea (enteritis group [EG], n = 35) were compared with 30 healthy controls. The dogs in the EG were scored using the Canine Acute Diarrhea Severity (CADS) index and grouped by bacterial fecal culture results. Procalcitonin and Bdef2 were analyzed in serum and feces. RESULTS: Dogs with acute diarrhea showed higher serum PCT concentrations (P < 0.0001) and lower fecal Bdef2 concentrations (P = 0.0001) than unaffected dogs. Serum PCT was moderately and positively related to the extent of disease classified by the CADS score. Dogs with Clostridium perfringens or hemolyzing Escherichia coli as predominant pathogen had increased serum Bdef2 concentrations (P < 0.01). Differentiation between uncomplicated (≤3 days) and complicated (>3 days) disease courses, determined by receiver operating characteristic (ROC) curves, resulted in a sensitivity of 0.74 and a specificity of 0.69 for serum PCT at a cutoff of 3.9 ng/mL. The serum PCT and fecal Bdef2 quotient resulted in a sensitivity of 0.80 and a specificity of 0.92, with a cutoff of 80.5. CONCLUSIONS: The results of the present study indicate that PCT and Bdef2 are potential biomarkers that can provide information on the severity, course, and prognosis of acute diarrhea in dogs.

Bio-Functionalized Magnetic Nanoparticles for the Immunoassay of C-Reactive Protein and Procalcitonin in Cervicovaginal Secretions of Pregnant Women with Preterm Prelabor Rupture of Membranes to Predict Early-Onset Neonatal Sepsis.

PURPOSE: Early-onset sepsis is a major cause of neonatal morbidity and mortality. C-reactive protein (CRP) and procalcitonin (PCT) are acute phase reactants related to infection. The aim of this study was to explore the feasibility of measuring CRP and PCT concentrations in cervicovaginal secretions of pregnant women with preterm prelabor rupture of membranes (PPROM) using an immunomagnetic reduction (IMR) assay to predict early-onset neonatal sepsis. PATIENTS AND METHODS: This prospective study was performed at Mackay Memorial Hospital, Taipei, Taiwan from February 2015 to January 2018. Pregnant women with PPROM between 22 and 34 weeks of gestation were recruited. CRP and PCT concentrations in cervicovaginal secretions were measured using an IMR assay. RESULTS: Thirty-five cervicovaginal secretion samples were obtained. After excluding two neonatal deaths, early-onset neonatal sepsis was diagnosed in 15 of the 33 surviving neonates. There was no significant relationship between cervicovaginal secretion CRP level and neonatal sepsis; however, cervicovaginal secretion PCT levels were significantly higher in the neonatal sepsis group than in the non-sepsis group (45.99 vs 9.54 ng/mL, P = 0.039). Receiver operating characteristic (ROC) curve analysis revealed a PCT cut-off level of 20.60 ng/mL to predict early-onset sepsis, and the area under the ROC curve was 0.71 (95% confidence interval 0.52 to 0.90, P = 0.039), with sensitivity and specificity of 73.3% and 77.8%, respectively. CONCLUSION: Measuring the concentration of PCT in cervicovaginal secretions with an IMR assay can predict early-onset sepsis in neonates born to mothers with PPROM.

Comparison of the value of immature retyculocyte and immature platelet in the diagnosis of sepsis.

BACKGROUND: Sepsis is one of the causes of pre-treatment morbidity and mortality in the pediatric age group. In the present study, we investigated the place of the immature granulocyte percentage, (IG) immature reticulocyte fraction (IRF), and immature platelet fraction (IPF) in the diagnosis of sepsis. METHODS: Complete blood count, C-reactive protein, (CRP) procalcitonin (PCT) and blood cultures were measured in 125 critical patients who were followed-up in the intensive care unit with the suspicion of sepsis and 65 healthy children between 2017 and 2019. In addition to the complete blood counts and routine parameters, IG, IRF, and IPF were examined in the patients. RESULTS: When the critical patient group and the healthy control group were compared, it was found that the total number of leukocytes (white blood cells), neutrophil count, platelet count, CRP, PCT, IG, IRF, and IPF values were higher at statistically significant levels. When septic and non-septic patients were compared, it was found that the CRP, PCT,IGP, and IPF were higher at statistically significant levels in the septic patients. CONCLUSIONS: It was concluded that CRP, PCT, IG, and IPF were significant in determining sepsis and that PCT was the most sensitive and specific biomarker in these parameters. We believe that these parameters may be suitable for practical use in determining sepsis because they give faster results and suggest the diagnosis of sepsis.

Effects of atorvastatin doses on serum level of procalcitonin and predictors for major adverse cardiovascular events in patients with acute myocardial infarction: a pilot study and post hoc analysis.

BACKGROUND: Inflammation plays an important role in acute myocardial infarction (AMI). Procalcitonin levels rise in response to proinflammatory stimuli. This study aimed to investigate the effects of different doses of atorvastatin on the serum inflammatory profiles, especially procalcitonin and major adverse cardiovascular events (MACEs) in patients with AMI during hospitalization. METHODS: The patients who were admitted to the Coronary Care Unit of The Third Medical Center of PLA General Hospital (Beijing, China) between January 2015 and December 2015 with a diagnosis of AMI were enrolled, and randomized to atorvastatin 20 mg/day postoperatively (20-mg group), 40 mg/day postoperatively (40-mg group) and 80 mg preoperatively+40 mg/day postoperatively (80/40-mg group). Serum procalcitonin and high-sensitivity C-reactive protein (hs-CRP) were evaluated before and at 1 and 3 days after percutaneous coronary intervention (PCI). RESULTS: A total of 112 patients with AMI (23 women and 89 men) were prospectively eligible for the study. There were no significant differences in most clinical data among the three groups. The 80/40-mg group showed significantly reduced serum procalcitonin levels at 1 and 3 days after PCI (P < 0.001) and reduced hs-CRP levels at 3 days P = 0.001) compared with 20-mg and 40-mg groups. Serum procalcitonin (OR, 4.593; 95% CI, 1.476-8.387; P = 0.005), hs-CRP (OR, 1.149; 95% CI, 1.012-1.338; P = 0.018), highly sensitive cardiac troponin T (OR, 1.255; 95% CI, 1.004-1.569, P = 0.009) and Gensini score (OR, 1.022; 95% CI, 1.045-1.062; P = 0.013) were independently associated with MACEs during hospitalization. CONCLUSION: The use of atorvastatin 80 mg before and 40 mg/day after PCI in patients with AMI can effectively reduce serum inflammatory factors. procalcitonin and hs-CRP were independently associated with in-hospital MACEs.

Predictors of 1­year mortality in ambulatory patients with advanced heart failure awaiting heart transplant.

INTRODUCTION: Heart failure (HF) is a complex syndrome involving diverse pathways and pathological processes that can manifest themselves in circulation as abnormal levels of various biomarkers. OBJECTIVE: The aim of the study was to assess the factors associated with a worse prognosis in patients with advanced HF awaiting heart transplant during a 1­year follow­up. PATIENTS AND METHODS: We prospectively assessed the data of 203 adult patients with advanced HF, who were hospitalized at our institution between 2016 and 2018. The study end point was all­cause death during a 1­year follow­up. RESULTS: The median age of patients was 57 years (range, 52-60); 87.7% of patients were male. During follow­up, 62 patients (30.5%) died. Serum levels of procalcitonin (hazard ratio [HR], 1.027; 95% CI, 1.020-1.034; P <0.001; per 10­unit increase), high­sensitivity C­reactive protein (hs­CRP; HR, 1.099; 95% CI, 1.016-1.883; P = 0.02; per 1­unit increase), sodium (HR, 1.171; 95% CI, 1.076-1.272; P <0.001; per 1 ­unit increase), and N ­terminal pro-B ­type natriuretic peptide (NT ­proBNP; HR, 1.068; 95% CI, 1.033-1.105; P <0.001; per 1000­unit increase) were independent risk factors for mortality. Procalcitonin generated the largest area under the curve (0.780; 95% CI, 0.712-0.848). CONCLUSIONS: Our study showed that higher serum hs ­CRP, NT­proBNP, and procalcitonin levels and lower serum sodium levels were independent risk factors for death during a 1­year follow­up in patients with advanced HF. Procalcitonin showed the strongest predictive power, sensitivity, and specificity, allowing for an effective identification of 1­year survivors and nonsurvivors awaiting heart transplant.

Neutrophil CD64: a potential biomarker for the diagnosis of infection in patients with haematological malignancies.

METHODS: The clinical data of 76 patients with haematological malignancies and infection who were treated in our department between January 2014 and October 2019 were retrospectively analysed. To evaluate the diagnostic value of some biomarkers, infection indexes such as white blood cell count (WBC), neutrophil count (NEUT), neutrophil CD64 and procalcitonin (PCT) were compared across the patients with confirmed infection status and infection-control status. Sensitivity, specificity and area under the receiver operating characteristic curve (AUC) were also determined. RESULTS: The WBC and NEUT did not differ significantly, whereas the neutrophil CD64 and PCT levels were significantly elevated in patients with a confirmed infection status (p < 0.05), with sensitivity of 31.0%, 45.2%, 76.2% and 50%, respectively, and specificity of 90.5%, 69%, 71.4% and 64.3%, respectively. The AUC of WBC, NEUT, neutrophil CD64 and PCT was 0.528, 0.517, 0.844 and 0.599, respectively. Further highlighting their diagnostic value, the neutrophil CD64 and PCT levels in neutropenia patients were significantly upregulated in patients with infection status (p < 0.05) but the WBC and NEUT were unchanged, with sensitivity of 73.7%, 63.2%, 68% and 68.4%, respectively, and specificity of 68.4%, 52.6%, 57.9% and 63.2%, respectively. The AUC of neutrophil CD64, PCT, WBC and NEUT was 0.864, 0.593, 0.419 and 0.403, respectively. CONCLUSION: These results indicate that neutrophil CD64 is a promising biomarker with superior sensitivity and specificity for diagnosing infection in patients with haematological malignancies, especially neutropenia patients.

Ultrasensitive Photochemical Immunosensor Based on Flowerlike SnO2/BiOI/Ag2S Composites for Detection of Procalcitonin.

Based on the necessity and urgency of detecting infectious disease marker procalcitonin (PCT), a novel unlabeled photoelectrochemical (PEC) immunosensor was prepared for the rapid and sensitive detection of PCT. Firstly, SnO2 porous nanoflowers with good photocatalytic performance were prepared by combining hydrothermal synthesis and calcining. BiOI nanoflowers were synthesized by facile ultrasonic mixed reaction. Ag2S quantum dots were deposited on SnO2/BiOI composites by in situ growth method. The SnO2/BiOI/Ag2S composites with excellent photoelectric properties were employed as substrate material, which could provide significantly enhanced and stable signal because of the energy level matching of SnO2, BiOI and Ag2S and the good light absorption performance. Accordingly, a PEC immunosensor based on SnO2/BiOI/Ag2S was constructed by using the layered modification method to achieve high sensitivity analysis of PCT. The linear dynamic range of the detection method was 0.50 pg·mL-1~100 ng·mL-1, and the detection limit was 0.14 pg·mL-1. In addition, the designed PEC immunosensor exhibited satisfactory sensitivity, selectivity, stability and repeatability, which opened up a new avenue for the analyzation of PCT and further provided guidance for antibiotic therapy.

Rapid Diagnostic Tests to Guide Case Management of and Improve Antibiotic Stewardship for Pediatric Acute Respiratory Illnesses in Resource-Constrained Settings: a Prospective Cohort Study in Southwestern Uganda.

Pediatric acute respiratory illness (ARI) is one of the most common reasons for evaluation at peripheral health centers in sub-Saharan Africa and is frequently managed based on clinical syndrome alone. Although most ARI episodes are likely caused by self-limited viral infections, the majority are treated with antibiotics. This overuse contributes to the development of antimicrobial resistance. To evaluate the preliminary feasibility and potential impact of adding pathogen-specific and clinical biomarker diagnostic testing to existing clinical management algorithms, we conducted a prospective, observational cohort study of 225 children presenting with malaria-negative, febrile ARI to the outpatient department of a semi-urban peripheral health facility in southwestern Uganda from October 2019 to January 2020. In addition to routine clinical evaluation, we performed influenza and Streptococcus pneumoniae antigen testing and measured levels of C-reactive protein, procalcitonin, and lactate in the clinic's laboratory, and conducted a follow-up assessment by phone 7 days later. Almost one-fifth of participants (40/225) tested positive for influenza. Clinical biomarker measurements were low with C-reactive protein of >40 mg/L in only 11% (13/222) of participants and procalcitonin >0.25 ng/mL in only 13% (16/125). All but two children received antibiotic treatment; only 3% (7/225) were admitted. At follow-up, 59% (118/201) of caregivers reported at least one persistent symptom, but fever had resolved for all children. Positive influenza testing was associated with persistent symptoms. In summary, we demonstrate that simple, rapid pathogen-specific testing and biomarker measurement are possible in resource-limited settings and could improve syndromic management and, in turn, antibiotic stewardship. IMPORTANCE Globally, respiratory illness is one of the most common reasons that children seek care. It is often treated inappropriately with antibiotics, which can drive the development of antibiotic resistance. In resource-rich settings, testing for specific pathogens or measurement of clinical biomarkers, such as procalcitonin and C-reactive protein, is often employed to help determine which children should receive antibiotics. However, there are limited data on the use of these tests in resource-constrained, outpatient contexts in sub-Saharan Africa. We enrolled children with respiratory illness presenting to a clinic in southwestern Uganda and performed testing for influenza, Streptococcus pneumoniae, C-reactive protein, and procalcitonin on-site. Almost all children received antibiotics. We demonstrate that employing clinical algorithms that include influenza and clinical biomarker testing could significantly decrease antibiotic prescriptions. Our study therefore provides preliminary data to support the feasibility and potential utility of diagnostics to improve management of respiratory illness in resource-constrained settings.

Rapid FRET-based homogeneous immunoassay of procalcitonin using matched carbon dots labels.

A novel method for the detection of procalcitonin in a homogeneous system by matched carbon dots (CDs) labeled immunoprobes was proposed based on the principle of FRET and double antibody sandwich method. Blue-emitting carbon dots with a strong fluorescence emission range of 400-550 nm and red-emitting carbon dots with the best excitation range of 410-550 nm were prepared before they reacted with procalcitonin protoclone antibody pairs to form immunoprobes. According to the principles of FRET, blue-emitting carbon dots were selected as the energy donor and red-emitting carbon dots as the energy receptor. The external light source excitation (310 nm) could only cause weak luminescence of CDs. However, once procalcitonin was added, procalcitonin and antibodies would be combined with each other quickly (≤20 min). Here, blue-emitting carbon dots acquired energy could be transferred to red-emitting carbon dots efficiently, causing the emitted fluorescence enhancement of red-emitting carbon dots. The fluorescence detection results in PBS buffer solution and diluted rabbit blood serum showed that the fluorescence intensity variation was linear with the concentration of procalcitonin. There was a good linear relationship betweenF/F0 and procalcitonin concentrations in PBS buffer solution that ranged from 0 to 100 ng ml-1, and the linear equation wasF/F0 = 0.004 *Cpct + 0.98359. Detection in the diluted rabbit serum led to the results that were linear in two concentration ranges, including 0-40 ng ml-1and 40-100 ng ml-1, and the detection limit based on 3σK-1was 0.52 ng ml-1. It is likely that this matched CDs labeled immunoprobes system can provide a new mode for rapid homogeneous detection of disease markers.

Prospective selected biomarkers in COVID-19 diagnosis and treatment.

COVID-19 has become a global health concern, due to the high transmissible nature of its causal agent and lack of proper treatment. Early diagnosis and nonspecific medical supports of the patients appeared to be effective strategy so far to combat the pandemic caused by COVID-19 outbreak. Biomarkers can play pivotal roles in timely and proper diagnosis of COVID-19 patients, as well as for distinguishing them from other pulmonary infections. Besides, biomarkers can help in reducing the rate of mortality and evaluating viral pathogenesis with disease prognosis. This article intends to provide a broader overview of the roles and uses of different biomarkers in the early diagnosis of COVID-19, as well as in the classification of COVID-19 patients into multiple risk groups.

Dexamethasone and tocilizumab treatment considerably reduces the value of C-reactive protein and procalcitonin to detect secondary bacterial infections in COVID-19 patients.

BACKGROUND: Procalcitonin (PCT) and C-reactive protein (CRP) were previously shown to have value for the detection of secondary infections in critically ill COVID-19 patients. However, since the introduction of immunomodulatory therapy, the value of these biomarkers is unclear. We investigated PCT and CRP kinetics in critically ill COVID-19 patients treated with dexamethasone with or without tocilizumab, and assessed the value of these biomarkers to detect secondary bacterial infections. METHODS: In this prospective study, 190 critically ill COVID-19 patients were divided into three treatment groups: no dexamethasone, no tocilizumab (D-T-), dexamethasone, no tocilizumab (D+T-), and dexamethasone and tocilizumab (D+T+). Serial data of PCT and CRP were aligned on the last day of dexamethasone treatment, and kinetics of these biomarkers were analyzed between 6 days prior to cessation of dexamethasone and 10 days afterwards. Furthermore, the D+T- and D+T+ groups were subdivided into secondary infection and no-secondary infection groups to analyze differences in PCT and CRP kinetics and calculate detection accuracy of these biomarkers for the occurrence of a secondary infection. RESULTS: Following cessation of dexamethasone, there was a rebound in PCT and CRP levels, most pronounced in the D+T- group. Upon occurrence of a secondary infection, no significant increase in PCT and CRP levels was observed in the D+T- group (p = 0.052 and p = 0.08, respectively). Although PCT levels increased significantly in patients of the D+T+ group who developed a secondary infection (p = 0.0003), this rise was only apparent from day 2 post-infection onwards. CRP levels remained suppressed in the D+T+ group. Receiver operating curve analysis of PCT and CRP levels yielded area under the curves of 0.52 and 0.55, respectively, which are both markedly lower than those found in the group of COVID-19 patients not treated with immunomodulatory drugs (0.80 and 0.76, respectively, with p values for differences between groups of 0.001 and 0.02, respectively). CONCLUSIONS: Cessation of dexamethasone in critically ill COVID-19 patients results in a rebound increase in PCT and CRP levels unrelated to the occurrence of secondary bacterial infections. Furthermore, immunomodulatory treatment with dexamethasone and tocilizumab considerably reduces the value of PCT and CRP for detection of secondary infections in COVID-19 patients.

Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study.

BACKGROUND: Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP). METHODS: Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP). RESULTS: A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78-0.84] and 0.86 [0.84-0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79-0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84-0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83-0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2-7.1, 95% CI] and Sepsis-3 by 7.6 [5.1-11.3, 95% CI]. CONCLUSIONS: MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department. Trial Registration ClinicalTrials.gov (NCT03588325).

Tracheal aspirate presepsin: a promising biomarker in early onset neonatal pneumonia.

The early recognition and management of early-onset neonatal pneumonia is a challenge facing intensivists. Presepsin is an emerging immunologic and inflammatory biomarker that has been used for early non-culture-based detection of infection. We aimed to clarify the potential of presepsin assessed in tracheal aspirate of newborns to identify pneumonia. This prospective case - control study was conducted on 60 intubated neonates: Thirty neonates with pneumonia diagnosed according to clinical, radiological, and laboratory criteria as pneumonia group and thirty age and sex-matched intubated neonates without pneumonia as a control group. All neonates underwent full clinical evaluation and laboratory investigations. Plasma and tracheal aspirate presepsin was determined on the first day of life. The means of tracheal aspirate and plasma presepsin and CRP (525.55 ± 94.62 pg/mL, 670.95 ± 120.38 pg/mL and 26.4 ± 11.2 mg/L, respectively) were significantly higher in pneumonia group than control group (252.51 ± 104.95 pg/mL, 553.79 ± 117.48 pg/mL, 15.1 ± 3.1 mg/L, respectively) (p < .001 each). Receiver operating characteristic curve analysis for tracheal aspirate and plasma presepsin and CRP levels for the prediction of early-onset neonatal pneumonia was designed. Sensitivity was 86.6, 70 and 56.7%, respectively, while specificity was 90, 73.3, 53.3%, respectively, at a cut-off point of 385 pg/mL, 605 pg/mL and 36 mg/L, respectively [area under the curve (AUC) = 0.97, 0.74 and 0.51, respectively, p < .001, .001 and .44, repectively]. In conclusion, tracheal aspirate presepsin is increased in early-onset neonatal pneumonia and outperformed other plasma biomarkers in diagnosing neonatal pneumonia.

Comparison of the Siemens Atellica BRAHMS and the Abbott Architect BRAHMS Procalcitonin Assays.

OBJECTIVE: In this study, we compared the Abbott Architect B.R.A.H.M.S procalcitonin (PCT) assay with the newly developed Siemens Atellica B.R.A.H.M.S PCT assay. METHODS: Residual 45 lithium heparin plasma/serum specimens were randomly selected from routine hospital orders, and PCT was measured on both systems and compared with Passing-Bablok regression. Bias was evaluated using the Bland-Altman method. Concordance correlation was used for agreement evaluation at the clinically diagnostic cutoff of 0.10, 0.25, 0.50, and 2.00 ng/mL. RESULTS: Weighted Deming regression analysis showed approximately 13% positive bias (Atellica PCT=1.13*Architect PCT+0.02, r=0.961). The Passing-Bablok regression analysis of the total sample range revealed approximately 12% positive bias of the Atellica PCT compared to the Architect PCT (Atellica PCT=1.12*Architect PCT+0.02, r=0.961). The Bland-Altman plot showed the agreement between Atellica and Architect PCT was on average 0.04±0.25 ng/mL in the clinically relevant range of 0.1-2.0 ng/mL. The concordance of both methods at the clinically diagnostic cutoff (0.1, 0.25, 0.5, 2.0 ng/mL) showed excellent overall agreement at each threshold (90-100%). CONCLUSIONS: The Siemens Atellica B.R.A.H.M.S PCT assay showed good correlation with the established Abbott Architect B.R.A.H.M.S PCT assay. Therefore, this technique can be used in clinical routine with the same clinical interpretation.

The role of procalcitonin in reducing antibiotics across the surgical pathway.

Procalcitonin (PCT) is widely considered as a highly sensitive biomarker of bacterial infection, offering general and emergency surgeons a key tool in the management of surgical infections. A multidisciplinary task force of experts met in Bologna, Italy, on April 4, 2019, to clarify the key issues in the use of PCT across the surgical pathway. The panelists presented the statements developed for each of the main questions regarding the use of PCT across the surgical pathway. An agreement on the statements was reached by the Delphi method, and this document reports the executive summary of the final recommendations approved by the expert panel.