Prediction of attributable mortality in pediatric patients with cancer admitted to the intensive care unit for suspected infection: A comprehensive evaluation of risk scores.

OBJECTIVE: To evaluate the performance of existing sepsis scores for prediction of adverse outcomes in children with cancer admitted to the ICU with suspected sepsis. DESIGN: Retrospective chart review using data available at 1, 6, 12, and 24 h after ICU admission to calculate the Pediatric Risk of Mortality 3 (PRISM-3), Pediatric Sequential Organ Failure Assessment (pSOFA), Paediatric Logistic Organ Dysfunction 2 (PELOD-2), and Quick Pediatric Sequential Organ Failure Assessment (qSOFA) scores. Area under the receiver operator characteristic curve (AUROC) was used to evaluate performance for prediction of attributable mortality. Sensitivity analyses included recalculation of scores using worst preceding values for each variable, excluding hematologic parameters, and prediction of alternative outcomes. SETTING: St. Jude Children's Research Hospital, a pediatric comprehensive cancer center in the USA. PATIENTS: Pediatric patients (<25 years of age) receiving conventional therapy for cancer admitted to the ICU with suspected sepsis between 2013 and 2019. RESULTS: Of 207 included episodes of suspected sepsis, attributable mortality was 16 (7.7%) and all evaluated sepsis scores performed poorly (maximal AUROC of 0.73 for qSOFA at 1 and 24 h). Sensitivity analyses did not identify an alternative approach that significantly improved prediction. CONCLUSIONS: Currently available sepsis scores perform poorly for prediction of attributable mortality in children with cancer who present to ICU with suspected sepsis. More research is needed to identify reliable predictors of adverse outcomes in this population.

Inhibitory Activities of Rare Ginsenoside Rg4 on Cecal Ligation and Puncture-Induced Sepsis.

Sepsis is an uncontrolled response to inflammatory infection and is associated with high levels of mortality and morbidity. Rg4 is a rare ginsenoside mainly found in the leaves of Panax ginseng C. A. Meyer and the major protopanaxatriol-type ginsenoside of black ginseng. In this study, we determined whether Rg4 affects cecal ligation and puncture (CLP)-induced sepsis. Animals were separated into the following six groups: control group, CLP-operated group, CLP plus maslinic acid (MA), and CLP plus Rg4 (5, 10, or 15 mg/kg). Survival rate, body weight changes, inflammatory cytokines, and histological analyses were assessed. Human endothelial cells were activated with the high-mobility group box 1 (HMGB1) protein and Rg4. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to assess inflammation and gene expression, respectively. After CLP surgery, the Rg4-administered group exhibited a higher survival rate and body weight compared with the untreated control group. Rg4 treatment reduced cytokine levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, as well as nitric oxide (NO) levels and renal inflammation. After Rg4 treatment of HMGB1-activated cells, the expressions of toll-like receptor (TLR) 4 and TNF-α were decreased, and the activation of phosphoinositide 3-kinase (PI3K)/AKT signaling increased cell viability. In summary, Rg4 inhibited inflammation and exhibited a protective effect against CLP-induced sepsis, thereby reinforcing cell survival against septic responses.

Lipid-Enriched Parenteral Nutrition and Bloodstream Infections in Hospitalized Patients: Is It a Real Concern?

Today, few clinicians are still convinced that lipids are sepsis risk factors in patients receiving parenteral nutrition. This dogma is principally based on old literature. This review deals with the most recent literature search that provided up-to-date data over the past ten years. Systematic research was performed on Pubmed, MEDLINE, and Web of Science. The recent evidence does not justify the exclusion of lipid emulsions in patients receiving parenteral nutrition for fear of bloodstream infection risk. Moreover, lipids represent a substantial proportion of the energy source providing essential fatty acids, potentially improving clinical outcomes in patients often malnourished. Understanding the actual risk factors of sepsis during parenteral nutrition is necessary to optimize patient nutritional status and care and avoid essential fatty acid deficiency. There is an urgent need to make updated nutrition training available at all levels of medical education.

Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury.

BACKGROUND: Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. METHODS: First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. RESULTS: Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1ß (IL-1ß) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. CONCLUSION: Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.

Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats.

Sepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.

Omega-3 fatty acid lipid emulsions are safe and effective in reducing endotoxemia and sepsis in acute-on-chronic liver failure: An open-label randomized controlled trial.

BACKGROUND AND AIM: Sepsis is an important determinant of the outcome of acute-on-chronic liver failure (ACLF) patients. Omega-3 fatty acids (FAs) are known to suppress inflammation, reduce morbidity, and mortality in postoperative and critically ill patients. We aimed to evaluate the effect of intravenous omega-6 and omega-3 FA lipid emulsions in ACLF patients. METHODS: Ninety ACLF patients were randomly allocated to three groups: Gr. A received no lipid emulsions, Gr. B received omega-6 FAs, and Gr. C received omega-3 FAs. The primary and secondary aims were to compare the effects of lipid emulsions on immune modulation, the incidence of bacterial sepsis, and mortality at day 28. RESULTS: The baseline characteristics of the patients were comparable. Serum endotoxin levels remained suppressed by 22% in Gr. C compared with a 4% and 12% rise in Gr. B and A (P < 0.001). Omega-3 FAs also suppressed C-reactive protein levels and neutrophil-to-lymphocyte ratio in Gr. C. Compared with Gr. A, omega-3 FAs reduced sepsis by 86% (HR, 0.14; 95% CI 0.04-0.43; P < 0.001). Omega-3 FAs significantly increased the expression of TLR2 and TLR4 on both CD14+ and CD16+ monocytes, and TLR4, on macrophages and neutrophils. There were no serious adverse events, except transient flushing in 20% and 16.6% of patients receiving omega-6 FAs and omega-3 FAs, respectively. CONCLUSION: Omega-3 FAs are safe and effective in reducing systemic inflammation, endotoxemia, and sepsis in patients with ACLF. These lipid emulsions could also be considered as effective sources of immunonutrition in such sick patients.

Reduning injection and its effective constituent luteoloside protect against sepsis partly via inhibition of HMGB1/TLR4/NF-κB/MAPKs signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Reduning injection (RDN), a popular traditional Chinese medicine, formulated by three herbs (i.e., Artemisia carvifolia Buch.-Ham. ex Roxb., Lonicera japonica Thunb., and Gardenia jasminoides J. Ellis), has been widely used to treat upper respiratory infectious diseases in China. AIM OF THE STUDY: To investigate the protective effect of RDN on both lipopolysaccharides (LPS)- and cecal ligation and puncture (CLP)-induced septic mice. To identify the potentially effective constituent, and to determine its protective effect and underlying mechanism in vivo and in vitro. MATERIALS AND METHODS: Male C57BL/6 mice were used to establish septic model by tail intravenous injection of 4 mg/kg LPS or CLP surgery. After modeling, mice were administered by tail intravenous injection of RDN in the dose of 16 or 8 mL/kg/day. The mortality, histopathology, plasma levels of inflammatory cytokines were evaluated respectively. In addition, we screened the potentially effective substances of RDN against sepsis by detecting the nitric oxide (NO) production in LPS-stimulated Raw 264.7 cells and verified the effect of luteoloside in CLP-induced septic mice subsequently. Finally, the underlying mechanisms of RDN and luteoloside were investigated in the inflammatory model in vitro. RESULTS: Administration of RDN significantly reduced the mortality and increased the survival rate in both LPS- and CLP-induced septic mice. Meanwhile, RDN reduced the release of inflammatory cytokines accompanied by alleviating the organs damage of lung, liver, and kidney in CLP-induced septic mice. Moreover, several components from Gardenia jasminoides J. Ellis extract (ZZ) or Lonicera japonica Thunb and Artemisia carvifolia Buch.-Ham. ex Roxb extract (JQ) as well as the constituents of luteoloside, quercetin, and caffeic acid were screened out to have obvious anti-inflammatory activity, which may be the potentially effective substances of RDN against sepsis. We further verified the protective role of luteoloside in CLP-induced septic mice. In addition, RDN and luteoloside significantly inhibited both the secretion and translocation of mobility group box (HMGB)1, and HMGB1-mediated activation of TLR4/NF-κB/MAPKs signaling pathways. CONCLUSION: RDN and its effective constituent luteoloside exhibited a significant protective effect against sepsis, which were potential candidate drugs for treatment of sepsis. The mechanism of antisepsis partly was related to inhibition of HMGB1/TLR4/NF-κB/MAPKs signaling pathways. The results provide an evidence base for the follow-up clinical application of RDN in treatment of sepsis.

High-Voltage, Pulsed Electric Fields Eliminate Pseudomonas aeruginosa Stable Infection in a Mouse Burn Model.

Objective: The incidence of severe infectious complications after burn injury increases mortality by 40%. However, traditional approaches for managing burn infections are not always effective. High-voltage, pulsed electric field (PEF) treatment shortly after a burn injury has demonstrated an antimicrobial effect in vivo; however, the working parameters and long-term effects of PEF treatment have not yet been investigated. Approach: Nine sets of PEF parameters were investigated to optimize the applied voltage, pulse duration, and frequency or pulse repetition for disinfection of Pseudomonas aeruginosa infection in a stable mouse burn wound model. The bacterial load after PEF administration was monitored for 3 days through bioluminescence imaging. Histological assessments and inflammation response analyses were performed at 1 and 24 h after the therapy. Results: Among all tested PEF parameters, the best disinfection efficacy of P. aeruginosa infection was achieved with a combination of 500 V, 100 µs, and 200 pulses delivered at 3 Hz through two plate electrodes positioned 1 mm apart for up to 3 days after the injury. Histological examinations revealed fewer inflammatory signs in PEF-treated wounds compared with untreated infected burns. Moreover, the expression levels of multiple inflammatory-related cytokines (interleukin [IL]-1α/ß, IL-6, IL-10, leukemia inhibitory factor [LIF], and tumor necrosis factor-alpha [TNF-α]), chemokines (macrophage inflammatory protein [MIP]-1α/ß and monocyte chemoattractant protein-1 [MCP-1]), and inflammation-related factors (vascular endothelial growth factor [VEGF], macrophage colony-stimulating factor [M-CSF], and granulocyte-macrophage colony-stimulating factor [G-CSF]) were significantly decreased in the infected burn wound after PEF treatment. Innovation: We showed that PEF treatment on infected wounds reduces the P. aeruginosa load and modulates inflammatory responses. Conclusion: The data presented in this study suggest that PEF treatment is a potent candidate for antimicrobial therapy for P. aeruginosa burn infections.

Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.

Parenteral and Enteral Nutrition: A Bridge to Healing and Biological Therapy in a Patient With Enterocutaneous Fistula and Sepsis Complicated Crohn's Disease.

Inflammatory bowel disease (IBD) patients with severe infections, abscess, or sepsis are ineligible for standard treatment using biological and immunosuppressive drug regimens. We report a case of complicated Crohn's disease with ruptured abdominal abscess, presence of enterocutaneous fistula, and sepsis. We also report and discuss patient management with parenteral nutrition (PN) and enteral nutrition (EN) and treatment outcomes. We report a case of a 31-year-old female with a 10-year history of IBD in clinical remission, who, after previous total proctocolectomy with J-pouch, presented to the clinic with severe abdominal pain of 2 days, unintentional weight loss, fatigue, fever, and abdominal abscess, which ruptured, and her clinical state became complicated by sepsis. PN was initiated using individually prepared admixture according to patient requirements, because of inability to tolerate any oral intake. Following the remittance of ileus symptoms, EN was added using a semielemental formula via a nasojejunal tube. Upon completion of the treatment, the fistula resolved, the wound had healed, and Crohn's Disease Activity Index score showed remission. This qualified the patient for initiation of biological therapy with infliximab. Patients with severe infections, abscesses, or sepsis are ineligible for standard IBD treatment using biological and immunosuppressive drug regimens. Furthermore, usually patients' nutrition condition prevents them from combating infection and initiating proper healing process. This case demonstrates the importance of considering nutrition therapy-PN and EN-in unstable patients who cannot be treated with standard pharmacological therapy. Nutrition therapy offers a bridge that allows patients to stabilize and heal before starting standard pharmacological treatment with immunosuppressive agents or biological therapy.

Adverse outcomes after major surgery in children with intellectual disability.

AIM: To evaluate outcomes after major surgery in children and adolescents with intellectual disability. METHOD: We used 2004 to 2013 claims data from Taiwan's National Health Insurance programme to conduct a nested cohort study, which included 220 292 surgical patients aged 6 to 17 years. A propensity score matching procedure was used to select 2173 children with intellectual disability and 21 730 children without intellectual disability for comparison. Logistic regression was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the postoperative complications and 30-day mortality associated with intellectual disability. RESULTS: Children with intellectual disability had a higher risk of postoperative pneumonia (OR 2.16, 95% CI 1.48-3.15; p<0.001), sepsis (OR 1.67, 95% CI 1.28-2.18; p<0.001), and 30-day mortality (OR 2.04, 95% CI 1.05-3.93; p=0.013) compared with children without intellectual disability. Children with intellectual disability also had longer lengths of hospital stay (p<0.001) and higher medical expenditure (p<0.001) when compared with children with no intellectual disability. INTERPRETATION: Children with intellectual disability experienced more complications and higher 30-day mortality after surgery when compared with children without intellectual disability. There is an urgent need to revise the protocols for the perioperative care of this specific population. WHAT THIS PAPER ADDS: Surgical patients with intellectual disability are at increased risk of postoperative pneumonia, sepsis, and 30-day mortality. Intellectual disability is associated with higher medical expenditure and increased length of stay in hospital after surgical procedures. The influence of intellectual disability on postoperative outcomes is consistent in both sexes and those aged 10 to 17 years. Low income and a history of fractures significantly impacts postoperative adverse events for patients with intellectual disability.

The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective.

Sepsis and septic shock are still a leading cause of mortality and morbidity in intensive care units worldwide. Sepsis is an uncontrolled and excessive response of the innate immune system toward the invading infectious microbes, characterized by the hyper-production of pro-inflammatory mediators such as interleukin (IL)-1ß, IL-6, tumor-necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB1). In severe sepsis, the overwhelming production of pro-inflammatory cytokines and reactive oxygen species may compromise organ function and lead to the induction of abnormal apoptosis in different organs, resulting in multiple organ dysfunction syndrome and death. Hence, compounds that are able to attenuate inflammatory responses may have therapeutic potential for sepsis treatment. Understanding the pathophysiology and underlying molecular mechanisms of sepsis may provide useful insights in the discovery and development of new effective therapeutics. Therefore, numerous studies have invested much effort into elucidating the mechanisms involved with the onset and development of sepsis. The present review mainly focuses on the molecules and signaling pathways involved in the pathogenicity of sepsis. Additionally, several well-known natural bioactive herbal compounds and phytochemicals, which have shown protective and therapeutic effects with regard to sepsis, as well as their mechanisms of action, are presented. This review suggests that these phytochemicals are able to attenuate the overwhelming inflammatory responses developed during sepsis by modulating different signaling pathways. Moreover, the anti-inflammatory and cytoprotective activities of phytochemicals make them potent compounds to be included as complementary therapeutic agents in the diets of patients suffering from sepsis in an effort to alleviate sepsis and its life-threatening complications, such as multi-organ failure.

Vitamin C-An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19.

There are limited proven therapies for COVID-19. Vitamin C's antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6-24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients' vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19.

Perioperative improvement in serum albumin level in patients with left ventricular assist device.

BACKGROUND: The negative impact of baseline hypoalbuminemia on clinical outcome following left ventricular assist device (LVAD) implantation is well known. However, the implications of perioperative change in serum albumin levels on post-LVAD outcomes remain uninvestigated. METHODS: Among consecutive patients with baseline serum albumin <3.5 g/dl who received durable LVAD implantation between April 2014 and August 2017 and were followed for 1 year, the impact of perioperative change in serum albumin level from baseline to 3 months post-LVAD on the incidence of adverse events was investigated. RESULTS: Sixty-eight patients (median 60 years and 69% male) were included. Serum albumin change was an independent predictor of the occurrence of adverse events with an adjusted hazard ratio of 0.32 (95% confidence interval, 0.13-0.78) and a cutoff change of 0.7 g/dl. Those with albumin increase >0.7 g/dl had higher 1-year freedom from adverse events (45% vs. 14%, p = .008), dominantly due to lower incidence of death or sepsis compared with those without (p < .05 for both). CONCLUSION: Among those with baseline hypoalbuminemia, a considerable perioperative increase in serum albumin levels following LVAD implantation was associated with lower mortality and morbidity. The implication of aggressive nutrition intervention on LVAD patients is the next concern.

[Catheter-related bloodstream infections in patients receiving central parenteral nutrition: prevalence, associated factors, and treatment]. / Bacteriemia en pacientes con nutrición parenteral central: prevalencia, factores asociados y tratamiento.

INTRODUCTION: Background: catheter-related infection is one of the complications of central parenteral nutrition treatment with the highest morbidity and mortality. Objectives: the primary endpoint of this study was to analyze the prevalence of bloodstream infection in patients with central parenteral nutrition. Secondary objectives included: a) an assessment of whether type of central catheter, duration of parenteral nutrition treatment, body mass index, or being admitted to the intensive care unit are factors associated with the development of bloodstream infection; b) an analysis of the therapeutic approach. Methods: this was a retrospective observational study. All patients who received central parenteral nutrition after surgery between July 2018 and March 2019 were included. The association between the different variables and the development of bloodstream infection was analyzed by logistic regression. Results: the prevalence of bloodstream infection was 7.3 % (95 % CI: 3.9-13.3) (n = 9/123 patients). The duration of central parenteral nutrition was the only variable associated with the development of bloodstream infection (OR = 1.12; 95 % CI:1.05-1.20; p = 0.001). Conclusions: the prevalence of catheter-related bloodstream infection in this study is low, and the duration of central parenteral nutrition seems to be related to its development. However, further studies are needed to identify risk factors that might help reduce this kind of complications.

INTRODUCCIÓN: Introducción: la infección relacionada con el catéter es una de las complicaciones del tratamiento con nutrición parenteral central (NPC) que generan una mayor morbimortalidad. Objetivos: el objetivo principal fue analizar la prevalencia de la bacteriemia asociada al catéter en pacientes con nutrición parenteral central. Los objetivos secundarios fueron: a) evaluar si el tipo de catéter central, la duración de la nutrición parenteral central, el índice de masa corporal o la estancia en la unidad de cuidados intensivos son factores asociados al desarrollo de bacteriemia; b) analizar el manejo terapéutico de la infección. Material y métodos: se trata de un estudio observacional retrospectivo. Se incluyeron los pacientes que recibieron nutrición parenteral central tras una intervención quirúrgica entre julio de 2018 y marzo de 2019. La asociación de las variables con el desarrollo de la bacteriemia se analizó mediante regresión logística. Resultados: el 7,3 % (IC 95 %: 3,9-13,3) (n = 9/123) de los pacientes desarrollaron bacteriemia relacionada con el catéter. El único factor asociado al desarrollo de la infección fue la duración de la nutrición parenteral central (OR = 1,12; IC 95 %: 1,05-1,20; p = 0,001). Conclusiones: la prevalencia de la bacteriemia relacionada con el catéter en este estudio es baja. La duración del tratamiento con nutrición parenteral central parece estar relacionada con el desarrollo de la bacteriemia. Sin embargo, se necesitan más estudios para identificar factores de riesgo que permitan minimizar este tipo de complicaciones.

Efficacy of Shenfu decoction on sepsis in rats with condition induced by cecal ligation and puncture.

OBJECTIVE: To evaluate the efficacy of Shenfu decoction (SFD) prepared with a traditional Chinese formula, on sepsis in rats with the condition induced by cecal ligation and puncture (CLP), and to study the possible mechanism underlying its action. METHODS: Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups: normal control group (NCG, n = 10), model control group (MCG, n = 15) and Shenfu decoction group (SFDG, n = 15). Sham-operated rats in NCG were served as operation control, while rats in both MCG and SFDG were exposed to CLP, a procedure to develop experimental sepsis. Rats in SFDG were administered with SFD by gavage (3 mg/g of body weight, twice a day) 2 h prior to CLP and directly after successful CLP, while rats in NCG and MCG were gavaged with equivalent volume of sterilized water. Rats in all groups were starved with free access to drink. After 24 h of administration, the mortality of rats in each group was assessed. The indicators of inflammatory response [the peritoneal inflammation by Simon's method Classification as well as serum concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by enzyme linked immunosorbent assay (ELISA)] in survival rats were evaluated. The indicators of gut barrier [The intestinal mucosal injury index, serum concentrations of D-lactic acid and secretory IgA (sIgA) in intestinal mucosa by ELISA, as well as gut microbiota by16S rRNA gene sequencing] in survival rats were evaluated. RESULTS: The mortality (20%) of rats in SFDG was lower than that (33.3%) of the MCG (P < 0.01). The mortality (20%) of rats in SFDG was lower than that (33.3%) of the MCG (χ2 = 6.533, P = 0.011). Compared with the MCG,the peritoneal inflammation as well as serum concentrations of TNF-α and IL-6 decreased significantly in SFDG (all P < 0.01). Compared with the MCG, the IMII, serum concentrations of D-lactic acid, sIgA in intestinal mucosa were alleviated by SFD treatment (all P < 0.01). Increase in levels of Proteobacteria and reduction levels of Bacteroidetes induced by sepsis were observed, and these two disturbed gut microbiota phyla could be regulated after SFD treatment. Increase in levels of Proteobacteria and reduction levels of Bacteroidetes induced by sepsis were observed, and these two disturbed gut microbiota phyla could be regulated after SFD treatment. CONCLUSION: SFD may play a protective role in sepsis by alleviating sepsis-induced inflammatory response and gut barrier damage in rats.

Carbapenems versus ciprofloxacin/metronidazole for decreasing complications and hospital stay following complicated acute appendicitis surgery: A prospective cohort in an Ecuadorian population.

BACKGROUND: After appendectomy due to complicated acute appendicitis (CAA), there are some alternatives as antibiotic scheme: ciprofloxacin/metronidazole; as well as monoscheme based on carbapenems: ertapenem, meropenem, and imipenem. AIM: This study aims to prove the efficacy of carbapenems versus ciprofloxacin/metronidazole in CAA post-operative management in terms of preventing complications during post-operative period and decreasing hospital stay. MATERIALS AND METHODS: This was an observational, analytical, longitudinal, and prospective cohort study (March 2014-November 2016). Patients were classified into two groups, according to the prescribed antibiotic scheme: some carbapenems or ciprofloxacin/metronidazole. RESULTS: Ninety-eight patients were enrolled. There was an requirement for antibiotic therapy rotation only in the ciprofloxacin/metronidazole (7/49, 14.3%; p = 0.004). Carbapenems reached a mean hospital stay of 4.45 days, in contrast with ciprofloxacin/metronidazole, 8.29 days (p = 0.020). In post-surgical follow-up, there were more cases of curative resolution in the group in the carbapenems group (35/49 vs. 15/49 p < 0.001) as well as a greater number of cases with some late infection in the ciprofloxacin/metronidazole group (1/49 vs. 10/49, p = 0.010). CONCLUSION: In the post-operative management of CAA, carbapenems represent an important indication to be considered as first-line antibiotic therapy.

ANTECEDENTES: Tras la cirugía por apendicitis aguda complicada existen varias alternativas de esquema antibiótico, entre las que destacan ciprofloxacino/metronidazol, o bien monoterapia con algún carbapenémico, como ertapenem, meropenem e imipenem. OBJETIVO: Determinar la eficacia de los carbapenémicos en comparación con ciprofloxacino/metronidazol en el manejo posquirúrgico de la apendicitis aguda complicada, en términos de prevención de complicaciones durante el ­posoperatorio y de reducción de la estancia hospitalaria. MÉTODO: Estudio observacional, analítico, longitudinal, prospectivo y de cohorte, de marzo de 2014 a noviembre de 2016. Los pacientes fueron clasificados en dos grupos según el esquema antibiótico prescrito: un carbapenémico o ciprofloxacino/metronidazol. RESULTADOS: Se seleccionaron 98 pacientes. Solo hubo necesidad de rotación de antibiótico en el grupo de ciprofloxacino/metronidazol (7 de 49, 14.3%; p = 0.004). En el grupo de carbapenémico, la media de estancia hospitalaria fue de 4.45 días, y en el grupo de ciprofloxacino/metronidazol fue de 8.29 días (p = 0.020). En el seguimiento posquirúrgico hubo más casos de resolución curativa en el grupo de carbapenémico (35 de 49 vs. 15 de 49; p < 0.001), así como un mayor número de casos con alguna infección tardía en el grupo de ciprofloxacino/metronidazol (1 de 49 vs. 10 de 49; p < 0.001). CONCLUSIÓN: En el manejo posquirúrgico de la apendicitis aguda complicada, los carbapenémicos representan una importante indicación que debe considerarse como antibioticoterapia de primera línea.

Tubeimoside I improves survival of mice in sepsis by inhibiting inducible nitric oxide synthase expression.

Sepsis is a disease with high mortality rate worldwide and inducible nitric oxide (iNOS) induced vascular hyporeactivity plays a key role in it. There is no effective drug to treat vascular hyporeactivity specifically. Tubeimoside I (TBM) is a triterpenoid saponin isolated from Rhizoma Bolbostemmatis. In this study, we found that 4 mg/kg TBM intraperitoneally injected 1 h before cecal ligation and puncture (CLP) partially improved survival, ameliorated mean arterial pressure (MAP) and enhanced vascular responsiveness to norepinephrine (NE) and KCl in wild-type septic mice. CLP activated TLR4-MyD88-NF-κB-iNOS pathway was also inhibited by TBM both in vitro and in vivo. However, iNOS gene knockout counteracted the protection provided by TBM. We conclude that TBM protects mice in sepsis by reducing excessive NO production through inhibiting the TLR4-MyD88-NF-κB-iNOS pathway. Our study suggests a possible therapeutic application of TBM in sepsis.

Effects of oropharyngeal administration of colostrum on the incidence of necrotizing enterocolitis, late-onset sepsis, and death in preterm infants: a meta-analysis of RCTs.

Necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) are two major contributors to death among preterm infants. Oropharyngeal administration of colostrum (OAC) has been proved as an easy, safe, and economically viable technique to help preterm neonates to build up their immunity. In this review, we assessed the effects of OAC on preterm infants. Several mainstream databases were searched including PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and a website of clinical trials. Randomized controlled trials (RCTs) comparing OAC vs. placebo or no intervention in preterm infants (gestation age <34 weeks or birth weight <1500 g) were eligible. Overall, nine RCTs (n = 689) were included in the review. Meta-analysis showed no statistical significance in terms of the incidence of NEC (RR = 0.59, 95% CI = 0.33-1.06, p = 0.08), LOS (RR = 0.78, 95% CI = 0.60-1.03, p = 0.08) and mortality rate (RR = 0.63, 95% CI = 0.38-1.05, p = 0.07). No significant difference was found in the subgroup analysis, apart from the group of the undeveloped region in NEC and mortality. In addition, time was significantly reduced in terms of achieving full enteral feeding (MD = -3.60, 95% CI = -6.55-0.64, p = 0.02) and hospital stay (MD = -10.38, 95% CI = -18.47-2.29, p = 0.01). The results show that OAC does not reduce the incidences of NEC, LOS, and death in preterm infants, but there is a trend toward a positive effect. It is therefore recommended as routine care for preterm infants in the NICU.

Targeting of reactive isolevuglandins in mitochondrial dysfunction and inflammation.

Inflammation is a major cause of morbidity and mortality in Western societies. Despite use of multiple drugs, both chronic and acute inflammation still represent major health burdens. Inflammation produces highly reactive dicarbonyl lipid peroxidation products such as isolevuglandins which covalently modify and cross-link proteins via lysine residues. Mitochondrial dysfunction has been associated with inflammation; however, its molecular mechanisms and pathophysiological role are still obscure. We hypothesized that inflammation-induced isolevuglandins contribute to mitochondrial dysfunction and mortality. To test this hypothesis, we have (a) investigated the mitochondrial dysfunction in response to synthetic 15-E2-isolevuglandin (IsoLG) and its adducts; (b) developed a new mitochondria-targeted scavenger of isolevuglandins by conjugating 2-hydroxybenzylamine to the lipophilic cation triphenylphosphonium, (4-(4-aminomethyl)-3-hydroxyphenoxy)butyl)-triphenylphosphonium (mito2HOBA); (c) tested if mito2HOBA protects from mitochondrial dysfunction and mortality using a lipopolysaccharide model of inflammation. Acute exposure to either IsoLG or IsoLG adducts with lysine, ethanolamine or phosphatidylethanolamine inhibits mitochondrial respiration and attenuates Complex I activity. Complex II function was much more resistant to IsoLG. We confirmed that mito2HOBA markedly accumulates in isolated mitochondria and it is highly reactive with IsoLGs. To test the role of mitochondrial IsoLGs, we studied the therapeutic potential of mito2HOBA in lipopolysaccharide mouse model of sepsis. Mito2HOBA supplementation in drinking water (0.1 g/L) to lipopolysaccharide treated mice increased survival by 3-fold, improved complex I-mediated respiration, and histopathological analyses supported mito2HOBA-mediated protection of renal cortex from cell injury. These data support the role of mitochondrial IsoLG in mitochondrial dysfunction and inflammation. We conclude that reducing mitochondrial IsoLGs may be a promising therapeutic target in inflammation and conditions associated with mitochondrial oxidative stress and dysfunction.