Sepsis Group Research Articles

Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

Extraction of echinacoside from Cistanche tubulosa (Schenk) R. Wight and investigation of its protective effect on liver injury in sepsis rats

In this study, echinacoside was extracted from Cistanche tubulosa (Schenk) R. Wight, and its protective effect on liver injury in sepsis rats was investigated. Forty-five rats were randomly divided into control, sepsis and echinacoside groups, 15 rats in each group. The sepsis model was established in sepsis and echinacoside groups. In echinacoside group, the rats were treated with echinacoside at 1 h before modeling. At 24 h after modeling, compared with sepsis group, in echinacoside group the serum aspartate aminotransferase and alanine aminotransferase levels were decreased, the liver injury score and hepatocyte apoptosis rate were decreased, the serum monocyte chemoattractant protein-1, tumor necrosis factor α, interleukin 6 and interleukin 1β levels were decreased, the liver tissue catalase, superoxide dismutase and glutathione peroxidase levels were increased, the liver tissue malondialdehyde level was decreased, and the liver tissue nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein expression levels were increased. The difference of all above comparisons was significant (P < 0.05). In conclusion, echinacoside can inhibit the inflammatory response, activate the Nrf2/HO-1 signal pathway, and reduce the oxidative stress, thus alleviating the liver injury in sepsis rats.

LUNG PROTECTIVE EFFECTS OF CLOPIDOGREL IN POLYMICROBIAL SEPSIS.

Aim: The goal of this experiment was to examine if Clopidogrel might protect the lungs during sepsis by modulating the inflammatory and oxidative stress markers. Materials and Methods: Twenty-four adult male Swiss-albino mice aged 8-12 weeks, with a weighing of 20-30 g, were randomized into 4 equal groups (n=6): sham (Laparotomy without cecal ligation and puncture [CLP]), CLP (laparotomy plus CLP), vehicle (DMSO 1 hour prior to CLP), Clopidogrel (50 mg/g IP 1 hour before to CLP). ELISA was used to assess Lung tissue levels of pro-inflammatory and oxidative stress markers. Results: F2 isoprostane levels were significantly higher in the sepsis group (p<0.05) in comparison with sham group, while Clopidogrel was considerably lower (p<0.05) in the inflammatory and oxidative stress markers in comparison to sepsis group. Histologically, all mice in the sepsis group had considerable (p=0.05) lung tissue damage, but Clopidogrel considerably decreased lung tissue injury (p=0.05). Conclusion: Clopidogrel was found to reduce lung tissue cytokine concentrations (IL-1, TNF a, IL-6, F2 isoprostane, GPR 17, MIF) in male mice during CLP-induced polymicrobial sepsis by modulation of pro-inflammatory and oxidative stress cascade signaling pathways, to the best of our abilities, no study has looked at the effect of Clopidogrel on MIF levels.

The role of red blood cell distribution width (RDW) in the diagnosis of pediatric sepsis.

Early diagnosis of pediatric sepsis is difficult, so it is necessary to find a reliable auxiliary diagnostic method. The purpose of the study was to assess the role of RDW in the diagnosis of pediatric sepsis. We did a case control study reviewing pediatric inpatients (≥28 days, < 18 years old) who were diagnosed with sepsis between April 2020 and November 2022. According to the sepsis-3 and Pediatric Sequential Organ Failure Assessment (pSOFA) scoring standards, 66 septic inpatients of the pediatric intensive care unit (PICU) were included in the sepsis group and 66 non-septic inpatients of the PICU were included by using the random sampling method during the same period as the control group. RDW values in the sepsis group were higher than those in the control group (P < 0.001). The cut-off value, sensitivity, specificity and area under curve of RDW for sepsis were 39.15, 0.955, 0.758 and 0.943,respectively. Our study confirms that RDW may have a good value on the early diagnosis of pediatric sepsis.

Correlation Between Serum Procalcitonin Levels and 28-Day Mortality in Patients with Surgical Sepsis and Septic Shock.

Background: Sepsis is a major medical emergency accounting for approximately 48.9 million cases and 11 million deaths worldwide, representing 19.7% of all global deaths. This study was conducted to evaluate the correlation between procalcitonin values and 28-day mortality. Methods: A retrospective study was conducted that included patients with sepsis and septic shock, treated in the surgical departments of the Sf. Apostol Andrei Galati County Emergency Clinical Hospital between January 2020 and December 2021. Results: 125 patients (mean age 65 years), mostly men (56%, n=70) were included. The mean procalcitonin value at admission in the sepsis group (28%, n=35) was 5.98 ng/mL, and in the septic shock group (72%, n=90) was 40.09 ng/mL. The most significant correlation was between procalcitonin at discharge, 28-day mortality (r = 0.437; p 0.0001) and SOFA score (r = 0.356; p 0.0001). Conclusions: Procalcitonin at discharge was positively correlated with 28-day mortality and SOFA score. The procalcitonin value at discharge can be used in the prognosis of the patient with surgical sepsis, but for better results the association between procalcitonin, SOFA score and the clinical status of the patient is recommended.

The determination of the protective role of sildenafil administration in rats with sepsis-induced liver injury.

Sepsis is a complex syndrome which comes out after infection, characterized by activation of inflammation and infection and has a high morbidity and mortality. Sildenafil (SLD) is a selective phosphodiesterase Type 5 enzyme inhibitor and is used in the treatment of erectile dysfunction effectively all over the world. In this study, we investigated whether SLD had protective effect or not by studying the effect of SLD on reactive oxygen species and antioxidants in cecal ligation and puncture (CLP) polymicrobial sepsis model in rat liver histopathologically and biochemically. Rats were divided into four groups: (1) 10 mg/kg SLD given CLP group; (2) 20 mg/kg SLD given CLP group; (3) CLP group; and (4) SHAM operated group. CLP polymicrobial sepsis model was applied to the rats. All rats in our study were sacrificed by overdose general anesthetic after 16 h (thiopental sodium, 50 mg/kg). Specimens of rat liver were analyzed histopathologically and biochemically. In the study, superoxide dismutase (SOD) and glutathione (GSH) parameters were measured to indicate the antioxidant activity in liver during sepsis. To evaluate the oxidant activity, myeloperoxidase (MPO) and lipid peroxidation (LPO) parameters were measured in liver tissue. SOD and MPO activities and GSH and LPO levels were high in CLP polymicrobial sepsis model when compared to SHAM group (p<0.05). In all SLD groups, GSH levels were high when compared to CLP group. In 20 mg/kg SLD given sepsis group, high GSH levels were observed according to SHAM group. In addition, while all SLD dose groups had a significant decrease versus CLP group in LPO levels (p<0.05), they had a significant increase in MPO activities. In 20 mg/kg SLD administrated rats, an improvement observed in biochemical parameters. In this study, SOD and MPO activities which were low in SHAM group increased in CLP polymicrobial sepsis model. When SLD administrated, MPO activity increased in both SHAM and CLP groups. In this study, GSH and LPO levels also increase in septic liver tissue. When SLD administrated to SHAM group, it increased VI protective GSH level and decreased detrimental LPO level. In histopathological examination, it was observed that 10 mg/kg SLD administration had a curative effect in liver tissue partly. It was shown that acute SLD administration decreased liver damage in septic rats dose-dependently in this study. In addition, it was observed that it corrected the broken oxidant-antioxidant balance. This might mediate the protective effect of SLD in liver. However, we believe that new experimental and clinical studies should be in the future to understand the protective effect of SLD in liver.

Sulfasalazine prevents lung injury due to intra-abdominal sepsis in rats: possible role of Nrf2 and angiopoietin-2

This study aimed to investigate the effect of sulfasalazine in preventing and treating intra-abdominal sepsis-induced acute respiratory distress syndrome (ARDS) in a rat model. Forty male Wistar albino rats were used. The rats were randomly divided into four equal groups, and sepsis was induced in 30 rats by intraperitoneal administration of a fecal saline solution prepared from rat feces. Group 1: normal control (n=10) [non-surgical], Group 2: fecal intraperitoneal injection (FIP) (n=10) [untreated septic group], Group 3: FIP+saline (placebo) (n=10) [saline administered intraperitoneally], Group 4 (n=10): FIP+sulfasalazine [250 mg/kg per day administered intraperitoneally]. Computed tomography was performed and blood samples were collected for biochemical and blood gas analysis. The lungs were removed for histopathological studies. Statistically significant reductions in interleukin (IL)-6, IL1-β, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), and angiopoietin-2 (ANG-2) levels were observed in the sulfasalazine group compared to the FIP+saline group (P<0.001). Nrf2 levels were significantly higher in the sulfasalazine-treated group than in the FIP and FIP+saline groups (P<0.01). Lung tissue scores were significantly reduced in the sulfasalazine group compared to the other sepsis groups. The Hounsfield unit (HU) value was significantly lower in the sulfasalazine group than in the FIP+saline group (P<0.001). PaO2 values were significantly higher in the sulfasalazine-treated group than in the FIP+saline-treated group (P<0.05). Sulfasalazine was shown to be effective in preventing and treating ARDS.

Early-Onset Neonatal Sepsis: Inflammatory Biomarkers and MicroRNA as Potential Diagnostic Tools in Preterm Newborns.

Mortality and morbidity of newborns with sepsis can be improved by early and accurate diagnosis and targeted therapy. To evaluate the early molecular events associated with inflammation and infection, we evaluated markers of endothelial activation and injury and circulating plasma miRNAs in preterm newborns with sepsis. The study group consisted of newborns with gestational age ≤ 32 weeks, with culture-positive early-onset neonatal sepsis (sepsis group, N = 8), and as a control group, we enrolled newborns without sepsis (control group, N = 12). Soluble markers of inflammation were measured using Luminex-based multiplex assay. Platelet-free plasma RNA was used to construct the library for miRNA sequencing analysis. Normalized counts were calculated and used to measure differential expression of individual detected miRNAs. We found a significant increase of interleukin 18 (IL-18) in the cord blood of the sepsis group (mean ± SEM, 104.7 ± 30.4 pg/ml vs 52.7 ± 5.6 pg/ml, P = 0.02). In peripheral blood of sepsis group patients, we found a significant increase of VEGF-A compared to controls (196.0 ± 70.5 pg/ml vs 59.6 ± 8.5 pg/ml, P = 0.02). In the cord blood plasma, eight miRNAs had significantly differential expression (P &lt; 0.05), four miRNAs were up-regulated and four miRNAs down-regulated. In peripheral blood plasma, all nine miRNAs with significant differential expression were up-regulated. In conclusion, in early-onset neonatal sepsis, IL-18 and VEGF-A might be considered in diagnostic workup. Early-onset sepsis in preterm newborns is associated with significant changes in the circulating miRNA pattern.

NEPHROPROTECTIVE EFFECT OF GAMMA-SECRETASE INHIBITOR ON SEPSIS- INDUCED RENAL INJURY IN MOUSE MODEL OF CLP.

The aim: This study was set out to assess the potential protective impact of MK0752 (a gamma secretase inhibitor) on sepsis-induced renal injury through modulation of inflammatory and oxidative stress pathways. Materials and methods: Twenty-four Swiss-albino mice aged between eight and twelve week and weighted twenty to thirty-seven grams were randomly allocated into four groups (n=6 in each group). Sham group (laparotomy without cecal ligation and puncture (CLP), sepsis group (laparotomy with CLP), vehicle-treated group (equivalent volume of DMSO before the CLP), MK0752 treated group (5 mg/kg) single daily dose for three days before the CLP. Blood samples were used to assess the serum levels of urea and creatinine. The kidneys were used to assess tissue levels of the TNF-α, IL-10, IL-6, TNFR1, VEGF, notch1, jagged1 and tissue damage by histopathological analysis. Results: The current study shows that pretreatment with MK0752 ameliorates the renal damage by significantly reducing the proinflammatory cytokines and notch1 signaling. Conclusions: Taken together, these results suggest that MK0752 could be protective against the renal injury induced by sepsis through its ameliorative impact on renal architecture and modulating cytokines and Notch1 singling pathway. Further studies regarding the role of Notch signaling pathways would be worthwhile.

The Prognostic Value of Procalcitonin Clearance and Procalcitonin to Albumin Ratio in Sepsis Patients.

The goal was to investigate the prognostic value of serum procalcitonin (PCT), procalcitonin clearance (PCTc), and procalcitonin/albumin (PCT/ALB) in patients with sepsis. We conducted a retrospective study on 128 adult patients with sepsis in the Department of Intensive Care Unit (ICU) and in the Department Infectious Disease in the Affiliated Cancer Hospital of Zhengzhou University. We observed PCT, ALB, arterial blood gas analysis (ABGs) and other main indicators of patients within 5 days after admittance from June 2020 to June 2021. The acute physiological function and chronic health status system II (APACHE II) scores, sepsis related organ failure assessment (SOFA) scores, procalcitonin clearance and PCT/ALB ratio were calculated, respectively. SPSS 22.0 and Graph pad 6.0 statistical software were used for statistical analysis. The septic shock group had higher PCT, lower ALB, higher PCT/ALB ratio and higher APACHE II score than the sepsis group (p = 0.01733, p = 0.0142, p = 0.0030, p = 0.0061, respectively). The 28 day mortality group had lower ALB value, higher PCT/ALB ratio and higher APACHE II score than the survival group (p = 0.0105, p = 0.0345, p = 0.0152, respectively). The PCTc-day3 and PCTc-day5 were both significantly higher in patients who survived than in the 28 day mortality group (p = 0.0159, p = 0.0042, respectively). The AUC of PCT/ ALB for predicted the septic shock was 0.8966 (95% CI: 0.8370 to 0.9562, p < 0.0001), and the cutoff value, sensitivity and specificity was 0.87, 81.25%, and 85.19%, respectively. The AUC of PCT/ALB for the predicted 28 day mortality was 0.8353 (95% CI: 0.7534 to 0.9171, p < 0.0001), and the cutoff value, sensitivity and specificity was 0.83, 70.83% and 92.59%, respectively. The PCT/ALB ratio was an important indicator for predicting septic shock and 28 day mortality in sepsis patients compared to PCT or ALB alone.

Identification of potential diagnostic and prognostic biomarkers for sepsis based on machine learning

BackgroundTo identify potential diagnostic and prognostic biomarkers of the early stage of sepsis. MethodsThe differentially expressed genes (DEGs) between sepsis and control transcriptomes were screened from GSE65682 and GSE134347 datasets. The candidate biomarkers were identified by the least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) analyses. The diagnostic and prognostic abilities of the markers were evaluated by plotting receiver operating characteristic (ROC) curves and Kaplan–Meier survival curves. Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were performed to further elucidate the molecular mechanisms and immune-related processes. Finally, the potential biomarkers were validated in a septic mouse model by qRT-PCR and western blotting. ResultsEleven DEGs were identified between the sepsis and control samples, including YOD1, GADD45A, BCL11B, IL1R2, UGCG, TLR5, S100A12, ITK, HP, CCR7 and C19orf59 (all AUC>0.9). Furthermore, the survival analysis identified YOD1, GADD45A, BCL11B and IL1R2 as the prognostic biomarkers of sepsis. According to GSEA, four DEGs were significantly associated with immune-related processes. In addition, ssGSEA demonstrated a significant difference in the enriched immune cell populations between the sepsis and control groups (all P < 0.05). Moreover, YOD1, GADD45A and IL1R2 were upregulated, and BCL11B was downregulated in the heart, liver, lungs, and kidneys of the septic mice model. ConclusionsWe identified four potential immune-releated diagnostic and prognostic gene markers for sepsis that offer new insights into its underlying mechanisms.

Effects of artemisinin and hydroxychloroquine on cytokines in experimental sepsis.

Pro-and anti-inflammatory cytokines mediate the inflammatory response in sepsis. Therefore, regulation of cytokines with medications in risky situations may protect the patients from sepsis. Hydroxychloroquine and artemisinin are antimalarial drugs with immunomodulatory properties. In this study, we intended to investigate the effects of artemisinin and hydroxychloroquine on the cytokines released during sepsis in the rat model. Twenty-four rats were randomized into four groups. The control group received oral saline, the sepsis group received oral saline and intraperitoneal lipopolysaccharide toxin (LPS), the artemisinin-treated sepsis group received oral 33.33 mg/kg of artemisinin, and the hydroxychloroquinetreated sepsis group received oral 33.33 mg/kg of hydroxychloroquine before LPS injection. Three hours later, serum cytokines were measured. An increase was detected in TNF-a, IL-1, and IL-6 levels in the sepsis group compared to the control (p<0.01). Oral pretreatment with artemisinin resulted in significant downregulation only of IL-1 levels (p<0.01). Cytokines IL-1 and IL-6 were significantly downregulated in the serum of LPS-induced rats pretreated with oral hydroxychloroquine than rats with sepsis (p<0.01). Decreases observed in TNF-a and IL-10 levels were insignificant. These results demonstrated that both artemisinin and hydroxychloroquine attenuate the release of pro-inflammatory cytokines three hours after LPS-induced sepsis in rats. A significant decrease was observed in serum IL-1 and IL-6 levels with hydroxychloroquine and IL-1 levels with artemisinin. Based on our findings, we suggest that the therapeutic potential of artemisinin and hydroxychloroquine may be beneficial in preventing cytokine storm during sepsis, and further research is needed to determine the optimal timing of administration.

Role of Neutrophil CD64 in the Diagnosis of Neonatal Sepsis

Introduction: Neutrophil surface CD64 (Cluster of differentiation 64), the highaffinity Fc receptor, is quantitatively up-regulated during infection and sepsis. The diagnostic utility of NCD64 as a reliable marker of neonatal sepsis has not been explored so far. Hence this study has been conducted to compare NCD64 with other currently used infection markers including total leucocyte count, platelet count, absolute neutrophil count (ANC), band:neutrophil ratio and highly sensitive C reactive protein (hs-CRP). Methods: Consecutively born neonates between March 2014 to November 2014 were enrolled with documented sepsis (n = 81), clinical sepsis (n = 35), and no sepsis (n = 87). NCD64 was analyzed by flow cytometry. Results: Sepsis episodes had a higher median CD64 index of 10.35 (Range: 15.88, 6.87) as against 2.97 (Range: 5.53, 1.64) in the control group (p &lt; 0.001). The percentage of NCD64 positive cells was also significantly higher in the sepsis group compared to the control group (63.90 ± 2.67 vs 15.07 ± 1.95; p = 0.001). In the ROC curve analysis NCD64, percentage of NCD64 positive cells had the highest AUC (AUC-0.914) using a cutoff of 28.01%, followed by CD64 mean fluorescence intensity (MFI) with an AUC of 0.850 using a cutoff of 5.54. NCD64 was significantly elevated in the groups with documented and clinical sepsis (p &lt; 0.001). Conclusions: NCD64 is a highly sensitive marker for neonatal sepsis. Prospective studies incorporating NCD64 into a sepsis scoring system are warranted.

Hypoalbuminemia Within One Hour After Surgery as a Predictor of Post-Operative Urosepsis in Patients Undergoing Flexible Ureteroscopy Lithotripsy: A Retrospective Study.

Abstract Background: To investigate retrospectively whether changes in serum albumin levels within one hour of flexible ureteroscopy (fURS) lithotripsy can be used as a predictor of post-operative urosepsis. Patients and Methods: Eligible patients with unilateral upper urinary calculi who underwent fRUS lithotripsy performed by a single surgeon at our center were included in the analysis. The patients were divided into sepsis and non-sepsis groups. The change ratio of albumin and white blood cell (WBC) count was calculated by post-operative/pre-operative index*100%. Univariable and multivariable logistic regression analyses were used to assess whether there was a correlation between risk factors and post-operative urosepsis. The receiver operating characteristic (ROC) curve was used to analyze factors that showed significant differences in multivariable logistic regression analysis. Results: A total of 314 patients were included in the analysis, 20 of whom had post-operative urosepsis and five developed septic shock; no deaths occurred. Multivariable logistic regression analysis showed that urine culture results, WBC counts within one hour after surgery, post-operative albumin levels, and the degree of albumin changes after surgery were independent predictors of post-operative urosepsis. Receiver operating characteristic curve analysis showed that noteworthy hypoalbuminemia after surgery and positive pre-operative urine culture could help screen high-risk patients for post-operative urosepsis effectively. Conclusions: Hypoalbuminemia shortly after operation can be utilized as a predictor for early diagnosis of post-operative urosepsis in patients undergoing fURS lithotripsy.

SCREENING OF POTENTIAL CORE GENES IN PERIPHERAL BLOOD OF ADULT PATIENTS WITH SEPSIS BASED ON TRANSCRIPTION REGULATION FUNCTION.

Objective: The aim of the study is to screen transcription factor genes related to the prognosis of adult patients with sepsis. Methods: Twenty-three patients with sepsis and 10 healthy individuals admitted for RNA-seq. Differential factors were enriched by four transcription factor databases, and survival analysis was adopted for core factors. Then, target genes were submitted to STRING to constitute the protein-protein interaction network. Single-cell technology was used to localize cell lines. Finally, a transcription-target gene regulation network was constituted. Results: A total of 4,224 differentially expressed genes were obtained between sepsis and normal control groups. Protein-protein interaction results showed that FOXO3, NFKB1, SPI1, STAT5A, and PPARA were located in the center of the network. Target genes were related to cytokine-mediated signaling pathway and transcription regulator activity, etc. SPI1 was mainly located in monocyte cell lines, while FOXO3, PPARA, SP1, STAT3, and USF1 were expressed in monocyte cell lines, NK-T cell lines, and B cell lines. Compared with those in the control group, FOXO3, SP1, SPI1, STAT3, and USF1 were highly expressed in the sepsis group, while PPARA had low expression. Conclusions: Transcription factors, such as FOXO3, PPARA, SP1, SPI1, STAT3, and USF1, are correlated with the prognosis of sepsis patients and thus may have a potential research value. Clinical Trial Registration: The clinical trial registration number is ChiCTR1900021261.

The role of nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in diagnosis of late onset neonatal sepsis.

Neonatal sepsis is a major cause of morbidity and mortality among neonates. Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a core element for innate immune protection. The study aims to estimate the expression of NLRP3 inflammasome in full term newborn infants who suffer from late onset sepsis, in order to assess its diagnostic value. This case-control study was conducted in NICU. 40 newborns with late onset sepsis, and 40 control neonates were included. The analysis of NLRP3 inflammasome was done by ELISA. There was a significant elevation of NLRP3 inflammasome in the serum of neonates with late onset sepsis group than the control group, P values were < 0.001, and the best cut off value of NLRP3 to detect late onset septic was > 3 ng/ml with sensitivity of 92.5% and specificity of 97.5%. Receiver operating characteristic curve showed that the best cut off point of NLRP3 to predict mortality in cases group was > 7.29 with sensitivity of 75.0%, specificity of 91.67%, PPV of 50.0%, NPV of 97.1% and total accuracy of 0.84%. n-SOFA scoring system increased significantly among LOS group and there was positive correlation with NLRP 3 inflammasome, P < 0.012. NLRP3 inflammasome can be used for the diagnosis of late onset neonatal sepsis. The increase of its values was not affected by gender, birth weight, gestational age and postnatal age. It was the novel sepsis markers that were not fully studied in neonatal population. The prognostic values may need further studies.

Diagnostic Virology-Based Spectrum of Neonatal Viral Infections at a Tertiary Center: Time to Switch Over

Background: Viral infections are important etiologies of neonatal sepsis, especially in premature/immune-compromised babies, and are associated with long-term morbidity and mortality. Timely diagnosis of viral infections using newer diagnostic tests in neonates is a necessary prerequisite for reducing the global burdens of neonatal morbidity and mortality. Objectives: This study aimed to assess the patterns of viral infections in newborns over one year. Methods: A total of 660 newborns were included in this hospital-based, cross-sectional, and observational study based on inclusion/exclusion criteria and after obtaining the required clearance from the institutional ethical committee. All newborns admitted in NICUs for suspected clinical sepsis were included except those with congenital malformation, hypoxic-ischemic encephalopathy (HIE), pre-term for care, and negative consent. Results: This study investigated 660 subjects with suspected sepsis, out of which 560 had non-viral sepsis (group one) and 100 had viral sepsis (group two). A significant difference was observed between the two groups in terms of mean hemoglobin level, mean platelet counts, and mean transaminases level. Cytomegaloviruses (CMV), rubella, and herpes simplex virus (HSV) were found in 9.1%, 4.5%, and 3.8% of the subjects, respectively. Conclusions: It was recommended that all neonatologists and pediatricians involved in neonatal care should suspect a viral agent as a possible cause of sepsis and utilize the diagnostic and treatment facilities with antiviral agents whenever and wherever possible.

Monocyte distribution width (MDW) as a useful indicator for early screening of sepsis and discriminating false positive blood cultures.

Severe sepsis and septic shock are the leading cause of in-hospital death. As sepsis progresses, expression and activity of endogenous mediators of inflammation change. Early detection of biomarkers can play a role in sepsis screening and in improvement of patient outcomes. Recent studies suggest that increase in monocyte volume may be helpful in early detection of sepsis. Therefore, we evaluated the utility of monocyte distribution width (MDW) for the early assessment of sepsis compared with the blood culture and other inflammatory biomarkers. Medical records of 1,404 patients (aged ≥19 years) who were admitted to the emergency department owing to clinically suspected infectious disease and requested blood cultures from Oct 2019 to Jan 2021 were reviewed. The patients were grouped based on Sepsis-3 criteria. They had undergone other laboratory tests to evaluate their clinical status. MDW was analyzed using DxH900 hematology analyzer (Beckman Coulter, Brea, California, USA). To determine the diagnostic performance of MDW, C-reactive protein (CRP), and procalcitonin (PCT) for sepsis, the area under the curve (AUC) of receiver operating characteristics curves and their sensitivity and specificity were measured. Among 1,404 patients, 520 patients were designated the sepsis group based on Sepsis-3 criteria. In the sepsis group, MDW value was 24.1 (median, IQR 21.6-28.1); AUC values for MDW, CRP, and PCT were 0.67 (95% CI, 0.64-0.69), 0.66 (95% CI, 0.63-0.68), and 0.75 (95% CI, 0.72-0.77), respectively. For diagnosis of the sepsis, the cut-off value of MDW was 21.7 (sensitivity 74% and specificity 54%). Measured values of MDW were higher for the blood culture positive group than that of the blood culture contamination group (P<0.001, 95% CI, -5.9 to -3.0) or blood culture negative group (P<0.001, 95% CI = -5.8 to -4.2). MDW is a new hematological parameter that is simultaneously calculated during complete blood cell counting by Beckman Coulter hematology analyzer. MDW is expected to serve as a useful indicator for early screening of sepsis in conjunction with CRP and PCT. MDW is especially useful for sepsis assessment in patients with a suspected infection. MDW can also assist in discriminating false positive blood cultures.

A study of microalbuminuria in sepsis with reference to acute physiology and chronic health evaluation II score in patients admitted to a medical intensive care unit

Background: Prediction of outcome of critically ill patients helps in early aggressive therapy, optimum resource allocation and counselling of the family. This study was conceived to assess the predictive value of microalbuminuria, which is an underutilised biomarker. Methods: This was a longitudinal observational study conducted at Sri Venkateswara Institute of between March 2018 and June 2019 to assess the microalbuminuria in patients with and without sepsis and to evaluate whether the degree of microalbuminuria could predict mortality in sepsis, and its association with to the acute physiology and chronic health evaluation II (APACHE II) score and the sequential organ failure assessment (SOFA) scores. Results: Among the 105 patients studied, 56 (53.3%) were male. This included patients with sepsis (n = 51) and without-sepsis (n = 54). The mean APACHE II score in sepsis group was 11.5 ± 3.5, in non-sepsis group was 8.2 ± 3.7 and overall was 9.8 ± 4.0. SOFA score in sepsis group was 3.0 ± 1.5, in non-sepsis group was 1.19 ± 1.15 and overall was 2.0 ± 1.6. The mean albumin/creatinine ratio (ACR) 1 and ACR2 among survivors were 150.5 ± 95.2 and 152.2 ± 87.2 and among non-survivors were 230.9 ± 43.9 and 287.8 ± 8.70, respectively. ACR2 performed similar to APACHE II in predicting mortality (difference between areas = 0.239; standard error = 0.0593 [95% confidence intervals: 0.123–0.355]; P = 0.0001). Conclusions: ACR2 had the highest value among ACR1, ACR2 and APACHE II for predicting mortality.

Establishment of a nomogram model for the early diagnosis of childhood sepsis

To establish a nomogram model for the early diagnosis of sepsis in children. A total of 76 children with sepsis who were admitted to Sichuan Maternal and Child Health Hospital from January 2018 to June 2021 were retrospectively selected as the sepsis group. After matching for sex and age (±2 years) at a ratio of 1:1:1, 76 children with local infection who were hospitalized during the same period were enrolled as the local infection group, and 76 children with non-infectious diseases were enrolled as the control group. The three groups were compared in terms of laboratory markers and the results of quick Sequential Organ Failure Assessment (qSOFA) and Pediatric Critical Illness Score (PCIS). A multivariate logistic regression analysis was used to investigate the association between the above indicators and sepsis. R4.1.3 software was used to establish and validate the nomogram model for the early diagnosis of sepsis based on the results of the multivariate analysis. A receiver operating characteristic (ROC) curve analysis was used to evaluate the value of the nomogram model, and the Bootstrap method was used to perform the internal validation of the model. The multivariate logistic regression analysis showed that soluble triggering receptor expressed on myeloid cells-1, qSOFA score, PCIS score, C-reactive protein, interleukin-6, and interleukin-10 were independently associated with childhood sepsis (P<0.05). The above indicators were used to establish a nomogram for the early diagnosis of sepsis, with an area under the ROC curve of 0.837 (95%CI: 0.760-0.914), and the calibration curve results showed a mean absolute error of 0.024, suggesting that the performance of this model was basically consistent with that of the ideal model. The indicators soluble triggering receptor expressed on myeloid cells-1, qSOFA score, PCIS score, C-reactive protein, interleukin-6, and interleukin-10 are independently associated with childhood sepsis, and the nomogram model established based on these indicators has high discriminatory ability and accuracy in the early diagnosis of sepsis in children.