Clinical Role of Serum Lactate Dehydrogenase Assessment in Critically Ill Pediatric Patients with Sepsis

Sepsis is a systemic inflammatory disorder that may be associated with higher rate of morbidity and mortality in pediatric patients admitted to intensive care unit with sepsis. Usage of different biomarkers may be helpful for early detection and appropriate management of sepsis. Our objectives was to investigate the role of serum lactate dehydrogenase in prediction of sepsis in critical pediatric patients, and its relation with prognostic scoring systems. A prospective cohort study was conducted at El Galaa teaching hospital between January 2020 and December 2020. A total of 168 pediatric patients were divided into the septic group (84) critically ill patients with sepsis from the pediatric intensive care unit (PICU)] and control group (84 stable patients admitted to the inpatient word). Demographic and clinical data were collected, routine laboratory investigation including LDH on admission and after 24 hours were performed. Pediatric Risk of Mortality III (PRISMIII) and Sequential Organ Failure Assessment (pSOFA) were assessed. Serum LDH level was significantly higher in septic group than control (P=0.000) and in non-survivor than survivor group (P=0.000). Also there was statistically significant correlation between survivor and non-survivor as regarding length of hospitality, pSOFA score and PRISMIII score. There was statistically significant positive correlation between LDH, PRISMIII (r=0.842, P<0.001) and pSOFA (r=0.785, P<0.001). We concluded that LDH is a useful marker in predicting of sepsis in critically ill pediatric patients especially when combined with prognostic scoring systems.

Serum MicroRNAs as Biomarkers of Sepsis and Resuscitation

There is a lack of biomarkers of sepsis and the resuscitation status. Our objective was to prove that the serum expression of certain microribonucleic acids (miRNAs) is differentially regulated in sepsis and is sensitive to different resuscitation regimes. Anesthetized pigs (Sus scrofa domesticus) received no treatment (n = 15) or intravenous live E. coli (n = 24). The septic animals received 0.9% saline at 4 mL/kg/h (n = 8) (low resuscitation group (LoR)) or 10–17 mL/kg/h (high resuscitation group (HiR)) (n = 8 each group). Blood samples were obtained at the end of the experiment for measurement of seven different miRNAs (RT-qPCR, Qiagen, Hilden, Germany). The serum expression of miR-146a-5p and miR-34a-5p increased significantly in the septic group, and miR-146a-5p was significantly lower in the HiR group than in the LoR group. The toll-like receptor signaling pathway involving 22 target proteins was significantly (adjusted p = 3.87 × 10−4) regulated by these two microRNAs (KEGG). Highly significant (p value = 2.22 × 10−16) protein–protein interactions (STRING) were revealed for these 22 hits. MiR-146a-5p and miR-34a-5p were identified as biomarkers of sepsis, and miRNA146a-5p seemed to be a biomarker of the intensity of the resuscitation.

Lipoprotein concentration in patients requiring extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO), a relevant technology for patients with acute respiratory distress syndrome (ARDS) or acute cardiac failure (ACF), is a frequent cause of systemic inflammatory response syndrome. During sepsis, HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) concentrations decrease, and an association between low lipoprotein levels and poor outcomes was reported. There are no data from patients undergoing ECMO. The goal of this study was to characterize the lipoprotein profiles of ICU patients requiring ECMO. All consecutive patients admitted for ARDS or ACF requiring ECMO were prospectively included. Daily lipoprotein levels and short-term prognosis outcome were assessed. 25 patients were included. On admission, lipoprotein concentrations were low, under the reference values ([HDL-C] = 0.6[0.4–0.8]mmol/L;[LDL-C] = 1.3[1.0–1.7]mmol/L). A statistically significant rise in lipoproteins overtime was observed during the ICU stay. We found no relationship between lipoproteins concentrations and mortality on Day-28 (p = 0.689 and p = 0.979, respectively). Comparison of surviving patients with non-surviving patients did not reveal any differences in lipoproteins concentrations. Stratification between septic and non-septic patients demonstrated that septic patients had lower lipoproteins concentrations on admission (HDL-C: 0.5[0.3–0.6]mmol/l vs 0.8[0.6–0.9]mmol/l, p = 0.003; LDL-C: 1.1[0.9–1.5]mmol/l vs 1.5[1.3–2.6]mmol/l; p = 0.012), whereas these two groups were comparable in terms of severity and outcomes. HDL-C concentrations during ICU hospitalization were also significantly lower in the septic group than in the non-septic group (p = 0.035). In conclusion, Lipoprotein concentrations are low in patients requiring ECMO but are not associated with poor outcomes. The subpopulation of septic patients had lower lipoprotein levels overtime, which reinforces the potential key-role of these particles during sepsis.

Peripheral Extracorporeal Membrane Oxygenation is a safe and effective support modality for pediatric patients with sepsis

Background Extracorporeal Membrane Oxygenation (ECMO) can be used as a treatment modality for pediatric patients with refractory septic shock. Previous studies indicate central ECMO, with direct cardiac cannulation, is superior for septic patients. At Riley Hospital for Children, we believe that peripheral ECMO support, through cervical or femoral vessels, is an effective and safe method of supporting pediatric septic patients in a less invasive manner. Methods We reviewed pediatric (30 days to 18 years) patients supported with ECMO for septic shock from 2005-2019 at Riley Hospital for Children and compared them to non-septic respiratory failure patients supported with ECMO. Pre-ECMO data points, demographics, cannulation sites, flow rates, lab values, Vasoactive Ionotropic Score(VIS), P-Prep score, and outcomes were collected and analyzed using t-test and multivariate analyses. We defined a significance as p=0.05. Results 35 of 80 ECMO patients were supported for septic shock. Septic patients were larger (25.1kg vs 11.4kg, p=0.005) and older (85.6 vs 18.8 months, p=0.001). Pre-ECMO VIS and P-Prep were both greater in the septic group (p=0.007 and p<0.001). Pre-ECMO serum lactate level was higher in the septic group (3.7 vs 1.4, p=0.012) , but by 96hrs, lactate normalized in both groups. Flow rates at 24 hours were similar between the two groups (91mL/kg/min vs 88mL/kg/min, p=0.079). No significant difference in bleeding complications or blood product administration was found, but there was a higher incidence of renal failure in septic patients. Survival in the septic group was similar to the comparison group (51.4% vs 62.2%, p-0.37). Hours on ECMO and length of stay were also similar. Conclusion and Potential Impact Despite septic patients appearing more ill prior to ECMO, they had similar mortality, support parameters, and outcomes, showing that septic shock is not a contraindication to peripheral ECMO support in pediatric patients.

Innate Lymphocyte Th1 and Th17 Responses in Elderly Hospitalised Patients with Infection and Sepsis

Background: the role of innate immunity in human sepsis must be fully clarified to identify potential avenues for novel immune adjuvant sepsis therapies. Methods: A prospective observational study was performed including patients with sepsis (septic group), infection without sepsis (infection group), and healthy controls (control group) in the setting of acute medical wards and intensive care units in a 1000-bed university hospital. A total of 42 patients with sepsis, 30 patients with infection, and 30 healthy controls were studied. The differentiation states of circulating mucosal associated invariant T (MAIT) cells and Natural Killer T (NKT) cells were characterised as naive (CD45RA+, CD197+), central memory (CD45RA−, CD197+), effector memory (CD45RA−, CD197−), or terminally differentiated (CD45RA+, CD197−). The differentiation states of circulating gamma-delta T lymphocytes were characterised as naive (CD45RA+, CD27+), central memory (CD45RA−, CD27+), effector memory (CD45RA−, CD27−), or terminally differentiated (CD45RA+, CD27−). The expression of IL-12 and IL-23 receptors, the transcription factors T-Bet and RORγt, and interferon-γ and IL-17a were analysed. Results: MAIT cell counts were lower in the septic group (p = 0.002) and the infection group (p < 0.001) than in the control group. The MAIT cell T-Bet expression in the infection group was greater than in the septic group (p = 0.012). The MAIT RORγt expression in the septic group was lower than in the control group (p = 0.003). The NK cell counts differed in the three groups (p < 0.001), with lower Natural Killer (NK) cell counts in the septic group (p < 0.001) and in the infection group (p = 0.001) than in the control group. The NK cell counts increased in the septic group in the 3 weeks following the onset of sepsis (p = 0.028). In lymphocyte stimulation experiments, fewer NK cells expressed T-Bet in the septic group than in the infection group (p = 0.002), and fewer NK cells expressed IFN-γ in the septic group than in the control group (p = 0.002). The NKT cell counts were lower in the septic group than both the control group (p = 0.05) and the infection group (p = 0.04). Fewer NKT cells expressed T-Bet in the septic group than in the infection group (p = 0.004). Fewer NKT cells expressed RORγt in the septic group than in the control group (p = 0.003). Fewer NKT cells expressed IFN-γ in the septic group than in both the control group (p = 0.002) and the infection group (p = 0.036). Conclusion: The clinical presentation of infection and or sepsis in patients is linked with a mosaic of changes in the innate lymphocyte Th1 and Th17 phenotypes. The manipulation of the innate lymphocyte phenotype offers a potential avenue for immune modulation in patients with sepsis.

Use of Mannose-Binding Lectin Gene Polymorphisms and the Serum MBL Level for the Early Detection of Neonatal Sepsis

Background Mannose-binding lectin (MBL) is a component of innate immunity and is particularly important in neonates, in whom adaptive immunity has not yet completely developed. MBL deficiency and MBL2 gene polymorphisms are associated with an opsonization defect and have been associated with neonatal sepsis. Aim The aim of our study was to assess serum MBL levels and genotype MBL2 genes to determine whether they can serve as markers for predicting neonatal sepsis in neonatal intensive care units. Patients and Methods A case-control study was conducted with 114 neonates classified into two groups: the septic group included 64 neonates (41 preterm and 23 full-term infants), and the non-septic control group included 50 neonates (29 preterm and 21 full-term infants). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to genotype MBL2 gene exon 1 (rs1800450) and (rs1800451) SNPs. Enzyme-linked immunosorbent assay (ELISA) was used to measure MBL serum concentrations. Results The polymorphic genotypes BB and AC at codons 54 and 57, respectively, showed higher frequencies than the wild-type genotype (AA) (14.1% versus 12.9% and 28.1% versus 19.4% respectively) in both groups, and this difference was greater in the septic group than in the non-septic group; however, the differences did not reach statistical significance. The B and C allele frequencies were also higher in the septic group than in the non-septic group, but the differences did not reach statistical significance (p = 0.282 and 0.394, respectively). The serum levels of MBL were significantly lower in the septic group than in the non-septic group (p = 0.028). Conclusion This study found no association between MBL levels or MBL2 exon 1 genotypes or alleles and neonatal sepsis risk. Further studies with larger sample sizes are needed to determine the role of the MBL2 gene as a risk factor and early predictor of neonatal sepsis.

Similar Outcomes of Two-Stage Revisions for Infection and One-Stage Revisions for Aseptic Revisions of Knee Endoprostheses

Two-stage revision knee arthroplasty using an antibiotic-loaded spacer is the most widely performed procedure for infected knee arthroplasties. The clinical outcome of this type of surgery compared with aseptic joint revision with exchange of tibial and femoral components is still controversial. Therefore, we analyzed clinical outcomes of septic two-stage revisions compared with aseptic one-stage revision total knee arthroplasties (TKAs). In a retrospective study, we assessed 135 consecutive patients who underwent two-stage revision for septic TKA (52 patients) and one-stage aseptic total knee revision arthroplasty (83 patients). The average follow-up was 26.1 months for the aseptic group and 26.5 months for the septic group. For clinical evaluation, we used the Knee Society Score, Oxford Knee Score, Kujala score, Turba score, and the Short Form 36 (SF-36). Postoperative pain level was determined using the visual analog pain scale. The surgeries were performed 51 months (aseptic group) and 24 months (septic group) after primary TKA on average. The main indications for aseptic revision surgeries were instability (40%), aseptic loosening (22.4%), anterior knee pain due to pathologies of the patella (11.8%), or material wear (5.9%). In the clinical outcome, patients achieved 124.8 points in the aseptic group and 105.4 points in the septic group in the Knee Society Score. The Oxford Knee Score revealed 29.9 points for the aseptic group and 33.9 points for the septic group. For the Kujala score, we found 53.2 points in the aseptic group and 48.5 points in the septic group. For the Turba score, we found 8.4 points in the aseptic group and 10.8 points in the septic group. The SF-36 (psychical) showed 52.2 versus 49.5 points and the SF-36 (physical) showed 36.5 versus 35.4 points. Mean level of persisting pain on the visual analog scale was 3.0 (aseptic group) and 3.5 (septic group). Performing septic two-stage or aseptic one-stage tibial and femoral revision knee arthroplasty showed similar clinical outcomes in relation to objective and subjective outcome measures.

The Role of Oxidative Stress in Decreased Acetylcholinesterase Activity at the Neuromuscular Junction of the Diaphragm during Sepsis

Our recent study demonstrated that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm decreased during sepsis. However, the mechanisms were not clearly identified. In this study, we aimed to investigate whether the decreased AChE activity was related to oxidative stress by observing AChE activity in different grades of sepsis induced by caecal ligation and puncture (CLP). At 24 h after surgery, an assay of thiobarbituric acid reactive species (TBARS) and protein carbonyls, as well as the myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity, was conducted. AChE activity was measured by biochemical and histological detection. AChE and CAT activity in the diaphragm decreased, while the contents of TBARS and protein carbonyls, the activity of MPO and SOD, and the SOD/CAT ratios increased. The above changes were much more significant in the mid-grade septic group than in the low-grade septic group. The colour of the AChE activity staining at the NMJ gradually lightened from the sham surgery group to the mid-grade septic group. AChE activity was significantly negatively correlated with the levels of TBARS and protein carbonyls. We consider that oxidative stress might be responsible for decreased AChE activity in the diaphragms of rats induced with sepsis.

Hemodynamic Analysis of Pediatric Septic Shock and Cardiogenic Shock Using Transpulmonary Thermodilution

Septic shock and cardiogenic shock are the two most common types of shock in children admitted to pediatric intensive care units (PICUs). The aim of the study was to investigate which hemodynamic variables were associated with mortality in children with shock. We retrospectively analyzed 50 children with shock (37 septic shock cases and 13 cardiogenic shock cases) in the PICU and monitored their hemodynamics using transpulmonary thermodilution from 2003 to 2016. Clinical factors were analyzed between the patients with septic and cardiogenic shock. In addition, hemodynamic parameters associated with mortality were analyzed. The 28-day mortality was significantly higher in the septic group than in the cardiogenic group (p=0.016). Initially, the parameters of cardiac output and cardiac contractility were higher in the septic group (p<0.05) while the parameters of preload and afterload were all higher in the cardiogenic group (p<0.05). Cardiac index was significantly lower in the nonsurvivors of cardiogenic shock at the time of initial admission and after the first 24 hours (bothp<0.05), while systemic vascular resistance index (SVRI) was significantly lower in the nonsurvivors of septic shock (p<0.001). Therefore, during the first 24 hours after intensive care, SVRI and cardiac index are the most important hemodynamic parameters associated with mortality.

Endoscopic Olecranon Bursal Resection for Olecranon Bursitis: A Comparative Study for Septic and Aseptic Olecranon Bursitis

Background: Open excision of the olecranon bursa has been performed traditionally. However, surgical complications such as wound healing problems and recurrence may occur after the surgery. The purpose of this study was to report on the clinical outcomes of endoscopic olecranon bursal resection performed in both septic and aseptic olecranon bursitis.Methods: We retrospectively reviewed 30 patients who underwent endoscopic olecranon bursal resection from June 2007 to January 2012. There were 20 males and 10 females. The ages ranged from 22 to 80 years, with an average age of 57.4 years and the average follow-up was 21.1 months (6–61.5 months). There were 15 cases in the septic group. The treatment outcome was measured according to the following; the rate of recurrence, range of motion, complications associated with surgery, VAS and QuickDASH.Results: There were no complications such as postoperative infection or neurovascular injuries. In the septic group, the VAS and QuickDASH scores were significantly improved from 5.6 to 0.1 and from 28 to 1.3, respectively. In the aseptic group, the VAS and QuickDASH scores were improved from 0.6 to 0.1 and from 25.7 to 0.5, respectively. In all cases, there were no recurrences and no limitations of joint motion until the final follow-up.Conclusions: We were able to obtain excellent outcomes without recurrence by performing endoscopic olecranon bursal resection in both septic and aseptic olecranon bursitis.