Monocyte distribution width (MDW): a useful biomarker to improve sepsis management in Emergency Department

Objectives Sepsis is a time-dependent and life-threating condition. Despite several biomarkers are available, none of them is completely reliable for the diagnosis. This study aimed to evaluate the diagnostic utility of monocyte distribution width (MDW) to early detect sepsis in adult patients admitted in the Emergency Department (ED) with a five part differential analysis as part of the standard clinical practice. Methods A prospective cohort study was conducted on 985 patients aged from 18 to 96 and included in the study between November 2019 and December 2019. Enrolled subjects were classified into four groups based on sepsis-2 diagnostic criteria: control, Systemic Inflammatory Response Syndrome (SIRS), infection and sepsis. The hematology analyzer DxH 900 (Beckman Coulter Inc.) provides the new reportable parameter MDW, included in the leukocyte 5 part differential analysis, cleared by Food and Drug administration (FDA) and European Community In-Vitro-Diagnostic Medical Device (CE IVD) marked as early sepsis indicator (ESId). Results MDW was able to differentiate the sepsis group from all other groups with Area Under the Curve (AUC) of 0.849, sensitivity of 87.3% and specificity of 71.7% at cut-off of 20.1. MDW in combination with white blood cell (WBC) improves the performance for sepsis detection with a sensitivity increased up to 96.8% when at least one of the two biomarkers are abnormal, and a specificity increased up to 94.6% when both biomarkers are abnormal. Conclusions MDW can predict sepsis increasing the clinical value of Leukocyte 5 Part Differential analysis and supporting the clinical decision making in sepsis management at the admission to the ED.

cfDNA and DNases: New Biomarkers of Sepsis in Preterm Neonates—A Pilot Study

Introduction: An early and accurate diagnosis of early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) is essential to improve the outcome of this devastating conditions. Especially, preterm infants are at risk. Reliable biomarkers are rare, clinical decision-making depends on clinical appearance and multiple laboratory findings. Markers of NET formation and NET turnover might improve diagnostic precision. Aim of this study was to evaluate the diagnostic value of NETs in sepsis diagnosis in neonatal preterm infants. Methods: Plasma samples of neonatal preterm infants with suspected sepsis were collected. Blood samples were assayed for markers of NET formation and NET turnover: cfDNA, DNase1, nucleosome, NE, and H3Cit. All clinical findings, values of laboratory markers, and epidemiological characteristics were collected retrospectively. Two subpopulations were created to divide EONS from LONS. EMA sepsis criteria for neonatal sepsis were used to generate a sepsis group (EMA positive) and a control group (EMA negative). Results: A total of 31 preterm neonates with suspected sepsis were included. Out of these, nine patients met the criteria for sepsis according to EMA. Regarding early onset neonatal sepsis (3 EONS vs. 10 controls), cfDNA, DNase I, nucleosome, and CRP were elevated significantly. H3Cit and NE did not show any significant elevations. In the late onset sepsis collective (6 LONS vs. 12 controls), cfDNA, DNase I, and CRP differed significantly compared to control group.

CLINICAL-ANAMNESTIC AND ECHOCARDIOGRAPHIC MARKERS OF NEONATAL SEPSIS AT DIFFERENT GESTATION AGE OF NEWBORN

neonatal sepsis remains one of the leading causes of morbidity and mortality in the neonatal age. The involvement of the myocardium in sepsis remains insufficiently studied, in particular in neonatology, where issues of myocardial dysfunction in neonatal generalized infection seem even more controversial, especially in neonatal sepsis at different gestational terms. Objective. To study specific clinical and anamnestic and echocardiographic parameters in infants depending on gestational age for optimization of the prognosis in neonatal sepsis. Material and research methods. To achieve this goal, we observed 57 newborns with a verified diagnosis of "Neonatal sepsis". Group I (23 patients – 40.3%) included newborns with a gestational age of 37-42 weeks, Group II – 34 premature infants (59.7%) with a gestation of up to 36 weeks. The latter group, depending on the gestational age, was divided into IIA subgroup, which was formed by 21 prematurely born patients with NS with a gestational age of 32-36 weeks, and the IIB subgroup – 13 newborns born before 32 weeks of gestation. Research results. The analysis showed that the severity of the impairment in the general condition of the examined newborns general condition was assessed as severe in 47.8% of newborns of group I, in 88.2% of cases in group II (PI: II <0.05), in 85.7% of representatives of subgroup IIA (PI: IIA <0.05) and in 92.3% of children of subgroup IIB (PI: IIB <0.001). It is shown that every third child (30.4%) of group I, 67.6% of newborns of group II (PI: II <0.05), half (52.4%) of the representatives of subgroup IIA (PII: IIA <0.01) and all seriously ill patients (92.3%) of subgroup IIB (PI: IIB, IIA: IIB <0.05) required cardiopulmonary resuscitation in the delivery room. Thus, in relation to full-term patients, the risk of this significant postnatal factor of emergency is likely to increase: for group II: OR - 4.77 (95% CI 2.63-8.68), RR - 2.17 (95% CI 1.57-3.0), AR = 0.37; and for premature babies with a gestational age of less than 32 weeks (IIB subgroup), respectively: OR – 27.44 (95% CI 11.73-64.19), RR – 7.55 (95% CI 5.58-10.21 ), AR – 0.65. The correlation analysis showed that in premature infants suffering from NS, the increase in the functional capacity of the left ventricular myocardium was associated with the female sex (for EF r = 0.94, P = 0.0001, for FS - r = 0, 94, P = 0.0001) and the number of days of inotropic support (for EF r = 0.68, P = 0.043, for FS - r = 0.71, P = 0.03). Conclusions. The analysis of echocardiographic parameters in the group of premature infants revealed a direct correlation between the ejection fraction and cardiovascular resuscitation immediately after birth (r = 0.64) and the duration of inotropic drugs (r = 0.68).

Association Between Maternal and Neonatal Serum Vitamin D Levels and the Incidence of Early-Onset Sepsis

Background: Early-onset neonatal sepsis (EOS) is a systemic infection that occurs within the first week of life. Objectives: This study investigated the association of serum vitamin D levels in pregnant women and their neonates with the prevalence of EOS. Methods: This case-control study was performed among 50 term/late pre-term neonates admitted to our NICU due to EOS, alongside 50 healthy neonates matched for gestational age range and sex. Maternal and neonatal serum vitamin D levels were measured. The criteria for diagnosing EOS included any/combination of: respiratory, cardiovascular, hemodynamic, neurological, gastrointestinal, body temperature, or metabolic signs. For sepsis cases, CBC, CRP, blood type, blood culture, chest X ray, and in some cases, and CSF analysis and culture were tested. Mothers’ clinical history was collected. Results: Each group included 30 (60%) male and 20 (40%) female neonates. Birth weight averages were 2772 ± 667 and 3215 ± 349 grams in the case and control groups, respectively (P < 0.001). The mean serum vitamin D levels were 49.75 ± 25.53 and 56.41 ± 18.17 nmol/L in the case and control groups, respectively. The control group mothers had a significantly higher vitamin D level (68.24 nmol/L versus 55.01 in mothers of sepsis cases, p=0.005) and showed a correlation with the vitamin D levels of their neonates (R = 0.731, P < 0.001), while the data failed to show a correlation between vitamin D level in mothers and their neonates in the sepsis group (R = 0.241, P = 0.115). C-section delivery was more prevalent among the sepsis cases (P < 0.001). Conclusions: Early-onset neonatal sepsis is associated with vitamin D deficiency in neonates and their mothers, low birth weight, and being delivered by C-section.

Puerarin mitigates acute liver injury in septic rats by regulating proinflammatory factors and oxidative stress levels

Purpose: To determine the protective effect of puerarin against acute liver injury in septic rats, and the mechanism involved.Methods: Eighty-seven Sprague-Dawley (SD) rats were assigned to control, sepsis and puerarin groups (each having 29 rats). Serum levels of NF-kB, TNF-α, IL-1 β, IL-6, ALT and AST were assayed. Liver lesions and levels of NO, SOD, iNOS and malondialdehyde (MDA) were measured using standard procedures.Results: Compared with the control group, the levels of NF-kB, TNF-α, IL-1β, IL-6, AST, ALT, NO, MDA and iNOS significantly increased in the sepsis group, while SOD level decreased significantly. In contrast, there were marked decreases in NF-kB, TNF-α, IL-1β, AST, ALT, NO, MDA and iNOS in puerarin group, relative to the sepsis group, while SOD expression level was significantly increased (p <0.05). The level of p-p38 in liver of septic rats was up-regulated, relative to control rats, while Nrf2 significantly decreased (p < 0.05). The expression level of p-p38 in the puerarin group was significantly decreased, relative to the sepsis group, while the expression level of Nrf2 significantly increased (p < 0.05).Conclusion: Puerarin mitigates acute liver injury in septic rats by inhibiting NF-kB and p38 signaling pathway, down-regulating proinflammatory factors, and suppressing oxidative stress. Thus, puerarin may be developed for use in the treatment liver injury.

Prediction of Postoperative Sepsis Based on Changes in Presepsin Levels of Critically Ill Patients with Acute Kidney Injury after Abdominal Surgery

Presepsin (PSP) is a viable biomarker for the detection of bacterial infection, but it lacks accuracy when acute kidney injury (AKI) develops. Herein, we evaluated the diagnostic and prognostic value of PSP in predicting postoperative sepsis after abdominal surgery respective to the degree of AKI. A total of 311 patients who underwent abdominal surgery and were admitted to a surgical intensive care unit were enrolled and classified into non-AKI, mild-AKI (stage 1, stage 2 and stage 3 without renal replacement therapy (RRT)) and severe-AKI (stage 3 with RRT) group, according to the Kidney Disease Improving Global Outcomes criteria. In each group, PSP and other biomarkers were statistically analyzed between non-sepsis and postoperative sepsis at the admission (T0), 24 h (T1), 48 h (T2) and 72 h (T3) after surgery. In non-AKI and mild-AKI group, PSP levels were significantly higher in postoperative sepsis than non-sepsis group, whereas no difference was detected in the severe-AKI group. Cutoff values of PSP in the mild-AKI group for the prediction of postoperative sepsis were 544 pg/mL (AUC: 0.757, p < 0.001) at T0 and 458.5 pg/mL (AUC: 0.743, p < 0.001) at T1, significantly higher than in non-AKI group. In multivariate analysis, predictors of postoperative sepsis in the mild-AKI group were PSP at T2 (odds ratio (OR): 1.002, p = 0.044) and PSP at T3 (OR: 1.001, p = 0.049). PSP can be useful for predicting newly developed sepsis in patients with transient AKI after abdominal surgery with modified cutoff values.

Albumin and fibrinogen kinetics in sepsis: a prospective observational study

Background The measurement of circulating substrate concentrations does not provide information about substrate kinetics. It, therefore, remains unclear if a decrease in plasma concentration of albumin, as seen during critical illness, is a consequence of suppressed production in the liver or increased peripheral clearance. In this study, using stable isotope tracer infusions, we measured albumin and fibrinogen kinetics in septic patients and in a control group of non-septic subjects. Methods With the approval from the institutional Research Ethics Board and after obtaining written informed consent from patients or their substitute decision maker, mechanically ventilated patients with sepsis and patients scheduled for elective coronary artery bypass grafting were enrolled. Patients in the non-sepsis group were studied on the day before surgery. The stable isotope L-[ring-2H5]phenylalanine was used to measure absolute synthesis rates (ASR) of albumin and fibrinogen. A priming dose of L-[ring-2H5]phenylalanine (4 µmol/kg) was given followed by a six-hour infusion at a rate of 0.15 µmol/kg/min. At baseline and hourly thereafter, blood was drawn to measure isotope enrichments by gas chromatography/mass spectrometry. Very low density lipoprotein apolipoprotein-B 100 isotopic enrichment was used to represent the isotopic enrichment of the phenylalanine precursor pool from which the liver synthesizes proteins. Plasma albumin and fibrinogen concentrations were also measured. Results Mean plasma albumin in septic patients was decreased when compared to non-septic patients, while synthesis rates were comparable. Mean plasma fibrinogen and ASR in septic patients was increased when compared to non-septic patients. In non-septic patients, no statistically significant correlation between plasma albumin and ASR was observed but plasma fibrinogen significantly correlated with ASR. In septic patients, plasma albumin and fibrinogen significantly correlated with ASR. Conclusions While septic patients showed lower plasma albumin levels than non-septic patients, albumin synthesis was similar in the two groups suggesting that hypoalbuminemia during sepsis was not caused by suppressed hepatic production but a result of enhanced clearance from the circulation. Hyperfibrinogenemia in septic patients was a consequence of increased fibrinogen production. Trial registration: ClinicalTrials.gov: NCT02865408 (registered on August 12, 2016) and ClinicalTrials.gov: NCT02549443 (registered on September 15, 2015).

Lower Vitamin D Level as a Risk Factor for Late Onset Neonatal Sepsis: An Observational Case–Control Study

Objective The aim of the study is to investigate the relation of neonatal and maternal vitamin D and late-onset sepsis (LOS) Study Design One-hundred twenty term neonates along with their mothers were enrolled in this case–control study. Sixty neonates who were admitted in the neonatal intensive care unit by LOS and had not been previously admitted for last 48 hours and did not receive antibiotics or vitamin D were enrolled as cases (sepsis) group. On the other hand, 60 healthy term neonates were referred as control group. Maternal and neonatal serum 25-OH vitamin D levels were assessed in both the cohorts. Results Maternal and neonatal 25-OH vitamin D levels in cases (17.2 and 16.1 ng/mL, respectively) were significantly lower than in controls (22.7 and 21 ng/mL, respectively) p = 0.001. In the study group, the neonatal 25-OH vitamin D was negatively correlated with C-reactive protein and length of hospital stay (r = −0.616 and −0.596, respectively) p <0.001 for both. With a cut-off value of 12.9 ng/mL, the specificity and positive predictive value of neonatal vitamin D were 83.3 and 74.4%, respectively. The odds ratio was 1.088 (95% CI = 1.034–1.144)) for LOS in vitamin D-deficient neonates. Conclusion Neonates with higher vitamin D level are at lower risk of LOS than those with vitamin D deficiency. Maternal vitamin D correlates with neonatal vitamin D. These data suggest that maternal vitamin supplementation during pregnancy may lower the risk of LOS. Key Points

Artificial Intelligence Imaging to Observe the Protective Effect of Hydrogen Sulfide on Acute Kidney Injury Caused by Urinary Sepsis

With the development of medical technology products and the rapid development of computer technology, medical AI has become a hotbed in scientific research and clinical practice. Some medical AI-assisted diagnosis has been applied to the clinic to assist doctors in formulating treatment plans. The traditional method of clinical diagnosis and treatment is that the physician makes an intentional diagnosis and then performs ancillary tests. The clinician performs diagnosis and treatment by identifying clinical symptoms and analyzing auxiliary examination results. Modern medical AI is based on big data collection and analyzes the test results through artificial intelligence and computer algorithms. It can output diagnostic results with high sensitivity and specificity for clinical tests. Acute kidney injury (AKI) is a common clinical emergency. The main clinical features are elevated blood creatinine, decreased urine output, and sharp decline in renal function within a short period of time, and it is a hot spot worldwide. In this experiment, a rabbit sepsis model was replicated by inoculating E. coli bacteria into the rabbit’s unilateral ureteral lumen and ligation. NaHS was used as an exogenous hydrogen sulfide donor to observe the effects of hydrogen sulfide on UTIs. The protective effect of oxidative stress and inflammatory response in acute kidney injury with hyperemia. In the experiment, the production of endogenous hydrogen sulfide was decreased in the Sepsis group, and the renal CSE activity was decreased, while the content of endogenous hydrogen sulfide in the NaHS group was higher than that of the Sepsis group, and the CSE activity of renal tissue was increased. It can be seen that the plasma hydrogen sulfide and renal tissue SCE levels in septic acute kidney injury increased after NaHS intervention, and the renal tissue damage was reduced, suggesting that hydrogen sulfide is mainly generated endogenously through the action of CSE, which causes damage to the kidneys. The expressions of iNOS and HO-1 in renal tissues of urinary sepsis are increased. H2S can play a certain protective effect on acute kidney injury in urinary sepsis by down-regulating iNOS and up-regulating the expression of HO-1.

Potential interaction between sepsis and acute respiratory distress syndrome and effect on the 6-month clinical outcomes: A preliminary secondary analysis of a prospective observational study

Background The effect of the interaction between sepsis and acute respiratory distress syndrome (ARDS) on the clinical outcomes is unclear. Therefore, this study aimed to investigate the effect of the potential interaction between the two conditions on mortality and the occurrence of post-intensive care syndrome (PICS). Methods This secondary analysis of a prospective multicenter observational study included patients who were expected to receive mechanical ventilation for more than 48 h. Patients were stratified based on the incidence of sepsis and further subdivided according to the presence of ARDS. The primary endpoints for patients whose follow-up information was available included mortality (n=162) and the occurrence of PICS (n=96) at six months. The diagnosis of PICS was based on any of the following criteria: (1) decrease ≥ 10 points in the physical component score of the 36-item Short Form (SF36) questionnaire; (2) decrease ≥ 10 points in the mental component score of the SF-36; or (3) decline in the Short Memory Questionnaire (SMQ) score and SMQ score < 40 at six months after ICU admission. We conducted multivariate logistic regression analyses to assess the effect of the potential interaction between ARDS and sepsis on the 6-month clinical outcomes. Result The mortality in the ARDS sub-group was higher than that in the non-ARDS subgroup [47% (7/15) versus 21% (18/85)] in the non-sepsis group. However, the mortality in the ARDS and non-ARDS subgroups was similar in the sepsis group. Multiple logistic regression analyses revealed that ARDS was significantly associated with mortality in the non-sepsis group (adjusted OR: 5.25; 95% CI: 1.45–19.09; p = 0.012), but not in the sepsis group (P-value for the interaction=0.087). Multiple logistic regression analyses showed ARDS was not associated with PICS occurrence in the non-sepsis and sepsis groups (P-value for the interaction=0.039). Conclusions Our findings suggested that the effect of ARDS on the 6-month outcomes depended on the presence or absence of sepsis. The findings of this hypothesis-generating study should be validated by future studies.