The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

Acute gastrointestinal injury in critically ill patients with COVID-19 in Wuhan, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading rapidly around the world. Most critically ill patients have organ injury, including acute respiratory distress syndrome, acute kidney injury, cardiac injury, or liver dysfunction. However, few studies on acute gastrointestinal injury (AGI) have been reported in critically ill patients with COVID-19. AIM: To investigate the prevalence and outcomes of AGI in critically ill patients with COVID-19. METHODS: In this retrospective study, demographic data, laboratory parameters, AGI grades, clinical severity and outcomes were collected. The primary endpoints were AGI incidence and 28-d mortality. RESULTS: From February 10 to March 10 2020, 83 critically ill patients out of 1314 patients with COVID-19 were enrolled. Seventy-two (86.7%) patients had AGI during hospital stay, of these patients, 30 had AGI grade I, 35 had AGI grade II, 5 had AGI grade III, and 2 had AGI grade IV. The incidence of AGI grade II and above was 50.6%. Forty (48.2%) patients died within 28 days of admission. Multiple organ dysfunction syndrome developed in 58 (69.9%) patients, and septic shock in 16 (19.3%) patients. Patients with worse AGI grades had worse clinical variables, a higher incidence of septic shock and 28-d mortality. Sequential organ failure assessment (SOFA) scores (95%CI: 1.374-2.860; P < 0.001), white blood cell (WBC) counts (95%CI: 1.037-1.379; P = 0.014), and duration of mechanical ventilation (MV) (95%CI: 1.020-1.340; P = 0.025) were risk factors for the development of AGI grade II and above. CONCLUSION: The incidence of AGI was 86.7%, and hospital mortality was 48.2% in critically ill patients with COVID-19. SOFA scores, WBC counts, and duration of MV were risk factors for the development of AGI grade II and above. Patients with worse AGI grades had a higher incidence of septic shock and 28-d mortality.

Surviving 2019 novel coronavirus pneumonia: A successful critical case report.

BACKGROUND: . An outbreak of acute respiratory illness was proved to be infected by a novel coronavirus, officially named Coronavirus Disease 2019 (COVID-19) from World Health Organization (WHO), was confirmed first in Wuhan, China, and has become endemic worldwide, which was a serious threaten to public health all over the world. Herein, we reported a successful critical case of COVID-19 and shared our experience of treatment, which would do a favor for other COVID-19 patients. CASE SUMMARY: . A 65-year-old man, Wuhan citizen, was infected by COVID-19, and his pulmonary lesions progressed quickly in five days. On admission to Tongji Hospital, Wuhan, China, the immediate arterial blood gas(ABG) analysis showed the PaO2/FiO2(P/F) ratio was 134.4mmHg, moderate acute respiratory distress syndrome(ARDS) was diagnosed. Emergency tracheal intubation was performed, and the initial ventilator mode and parameters were set up based on the lung-protective ventilation strategy, but the P/F ratio could not be improved, and then the prone position ventilation was carried out for four consecutive days, as long as 16 hours every day, the P/F ratio rose to 180mmHg approximately, which still did not reach to the standard of extubation. And then we found that it was complicated with acute cor pulmonale(ACP) by ultrasound examination, dobutamine and diuretic were used for the treatment of ACP caused by ARDS successfully, and the P/F ratio went up to about 250mmHg. Seven days later after admission, the endotracheal intubation was successfully removed, after extubation, High-Flow nasal cannula(HFNC) oxygen therapy was used as a sequential strategy to prevent reintubation. Ultimately, he was discharged on day 34 after admission. CONCLUSION: . Our case presented the treatment process of a critical COVID-19. Effective therapy was crucial to heal COVID-19, and organ function support therapy, especially the cardiorespiratory function support therapy, was the core of treatment.

Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease 2019.

The aim of this study was to investigate the correlations between serum calcium and clinical outcomes in patients with coronavirus disease 2019 (COVID-19). In this retrospective study, serum calcium levels, hormone levels and clinical laboratory parameters on admission were recorded. The clinical outcome variables were also recorded. From February 10 to February 28, 2020, 241 patients were enrolled. Of these patients, 180 (74.7%) had hypocalcemia on admission. The median serum calcium levels were 2.12 (IQR, 2.04-2.20) mmol/L, median parathyroid hormone (PTH) levels were 55.27 (IQR, 42.73-73.15) pg/mL, and median 25-hydroxy-vitamin D (VD) levels were 10.20 (IQR, 8.20-12.65) ng/mL. The serum calcium levels were significantly positively correlated with VD levels (P =0.004) but negatively correlated with PTH levels (P =0.048). Patients with lower serum calcium levels (especially ≤2.0 mmol/L) had worse clinical parameters, higher incidences of organ injury and septic shock, and higher 28-day mortality. The areas under the receiver operating characteristic curves of multiple organ dysfunction syndrome, septic shock, and 28-day mortality were 0.923 (P <0.001), 0.905 (P =0.001), and 0.929 (P <0.001), respectively. In conclusion, serum calcium was associated with the clinical severity and prognosis of patients with COVID-19. Hypocalcemia may be associated with imbalanced VD and PTH levels.

Effect of PA-MSAH preprocessing on the expression of TLR-4-NF-κB pathway and inflammatory factors in the intestinal tract of rats with septic shock.

Effects of Pseudomona blank s aeruginosa-mannose sensitive hemagglutini (PA-MSHA) preprocessing on toll like receptor (TLR)-4-NF-κB pathway and inflammatory factors expression in the intestinal tract of rats with septic shock were investigated. A total of 30 rats were randomly divided into 3 groups (n=10): Blank control, septic shock, and PA-septic shock group. After the model was successfully established, the average arterial pressure in rats was monitored. The concentration of cytokine interleukin-l (IL-1), IL-6 and tumor necrosis factor-α (TNF-α) were determined by ELISA method. Flow cytometry was performed to detect TLR-4 expression. Number of in vitro chemotaxised neutrophils was detected by Transwell chamber. The expression of TLR-4, NF-κB and ICAM-1 and VCAM-1 was detected by western blot analysis. The concentration of cytokine IL-1, IL-6, TNF-α in the peritoneal lavage fluid and the intestinal tissue significantly increased in the septic shock group and the PA-septic shock group (P<0.05), and the concentration in the PA-septic shock group was significantly lower than that of the septic shock group (P<0.05). Compared to the control group, the expression of TLR-4, NF-κB and ICAM-1 and VCAM-1 increased in the septic shock and PA-septic shock group (P<0.05), and the expression level of PA-septic shock group was lower than the septic shock group (P<0.05). The expression of TLR-4 in the PA-septic shock group was lower than the septic shock group (P<0.05). PA-MSHA pretreatment reduced inflammation, thus preventing the intestinal injury caused by septic shock.

Percutaneous catheter drainage combined with peritoneal dialysis for treating acute severe pancreatitis: a single-center prospective study.

BACKGROUND: To investigate the efficacy of percutaneous catheter drainage (PCD) and peritoneal dialysis (PD) in the treatment of severe acute pancreatitis (SAP) and its underlying mechanism. METHODS: Totally 64 SAP patients were included in our study and randomly assigned into PCD+PD group (the combination group, N.=32) and convention group (N.=32). SAP patients in the combination group were treated with percutaneous catheter drainage combined with peritoneal dialysis, while those in the convention group were treated with conventional method. The treatment efficacy of both methods were evaluated by comparing levels of plasma inflammatory cytokines (IL-6, IL-8, TNF-α, C-reactive protein, procalcitonin and leukocyte count), relative indexes of important organs (aspartate aminotransferase, alanine aminotransferase, creatinine and urea nitrogen) and other clinical data (amelioration time of abdominal pain and abdominal distension, Balthazar CT scores, acute physiology and chronic health enquiry II score, length of hospital stay, complications and prognosis). RESULTS: The expression levels of inflammatory cytokines were significantly decreased in the combination group in a time-dependent manner in comparison with those of the convention group. In addition, the amelioration time of abdominal pain and abdominal distension, length of hospital stay, Balthazar CT scores and the acute physiology and chronic health care II scores in the combination group were also significantly decreased in comparison with those of the convention group. CONCLUSIONS: The combination treatment of PCD and PD effectively relieves the clinical symptoms of SAP by clearing plasma inflammatory cytokines.

Effects of early enteral nutrition on T helper lymphocytes of surgical septic patients: A retrospective observational study.

The aim of this study was to investigate the effects of early enteral nutrition (EEN) on T helper lymphocytes and the subpopulations ratios of surgical septic patients.We performed a retrospective study including 107 eligible patients from February 2014 to December 2015. Patients were divided into EEN, delayed enteral nutrition (DEN), or total parenteral nutrition (TPN) group according to the duration before enteral feeding. Th1, Th2, Th17, and Treg lymphocyte percentages were collected on days 3, 7, and 14 after admission. The disease severity and clinical outcome variables were also recorded.The Th1, Th17 percentages, and Th1/Th2, Th17/Treg ratios of EEN group were significantly lower than those of DEN or TPN group on the 14th day after admission (P < .05). Compared with TPN, DEN might have a tendency to decrease the Th1 and Th17 percentages. EEN could improve the disease severity and clinical outcomes of septic patients, however, no difference on 28-day mortality was found between EEN and DEN group.EEN could improve the dysregulation of Th1/Th2 and Th17/Treg ratios during early stage of sepsis. Compared with DEN, EEN could improve the disease severity and clinical outcomes, but not decrease the 28-day mortality of surgical septic patients.

Role of α-II-spectrin breakdown products in the prediction of the severity and clinical outcome of acute traumatic brain injury.

αII-spectrin breakdown products are regarded as potential biomarkers for traumatic brain injury (TBI). The aim of the present study was to further evaluate these biomarkers by assessing their clinical utility in predicting the severity of injury and clinical outcome of patients with TBI. Eligible patients with acute TBI (n=17), defined by a Glasgow Coma Scale (GCS) score of ≤8, were enrolled. Ventricular cerebrospinal fluid (CSF) was sampled from each patient at 24, 72 and 120 h following TBI. An immunoblot assay was used to determine the concentrations of SBDPs in the CSF samples. The concentrations of SBDPs combined with the GCS score at 24 h after injury and the Glasgow Outcome Score (GOS) at 30 days after injury were compared and analyzed. The levels of SBDPs in CSF were markedly increased following acute TBI in comparison with those in the control group. In the early period after TBI, the levels of SBDPs were closely associated with GCS score. Comparisons of the SBDP levels with the severity of injury revealed significant differences between patients with the most severe brain injury and patients with severe brain injury in the first 24 h post-injury (P<0.05). The levels and dynamic changes of SBDPs in CSF exhibited a close association with GOS at 30 days after injury. The levels of SBDPs differed significantly between patients grouped according to prognosis (P<0.05). These results suggest that in the early period after TBI, the levels and dynamic changes of SBDPs in CSF can be useful in the prediction of the severity of injury and clinical outcome of patients.

Risk factors and prognosis of hypoalbuminemia in surgical septic patients.

The aim of this study was to investigate the risk factors of hypoalbuminemia and effects of different albumin levels on the prognosis of surgical septic patients. We preformed a retrospective clinical study including 135 adult patients from September 2011 to June 2014. The albumin levels and severity markers were recorded during the first 48 h after enrollment, and logistic regression analyses were used to determine the risk factors. The outcomes of patients with different albumin levels were also compared. The acute physiology and chronic health evaluation II (APACHE II) score (OR 1.786, 95% CI [1.379-2.314], P < 0.001), C-reactive protein (CRP) (OR 1.016, 95% CI [1.005-1.027], P = 0.005), and blood lactate (OR 1.764, 95% CI [1.141-2.726], P = 0.011) were established as the independent risk factors of hypoalbuminemia in patients with surgical sepsis. The severity markers and outcomes of patients with albumin levels ≤20 g/L were significantly worse than that of 21-25 g/L and ≥26 g/L, whereas the latter two groups had similar prognosis. Every 1 g/L decrease of albumin level below the optimal cut-off (23 g/L) was associated with a 19.4% increase in hospital mortality and a 28.7% increase in the incidence of multiple organ dysfunction syndrome. In conclusion, APACHE II score (≥14.5), CRP (≥34.25 mg/L), and blood lactate (≥.35 mmol/L) were established as the independent risk factors of hypoalbuminemia in the early stage of surgical sepsis. Patients with baseline albumin level ≤20 g/L had worse prognosis than that of albumin level ≥21 g/L. Albumin levels were negatively correlated the prognosis of surgical sepsis when below about 23 g/L.

Carbon Monoxide-Releasing Molecule-2 Reduces Intestinal Epithelial Tight-Junction Damage and Mortality in Septic Rats.

OBJECTIVE: Damage to intestinal epithelial tight junctions plays an important role in sepsis. Recently we found that Carbon Monoxide-Releasing Molecule-2 (CORM-2) is able to protect LPS-induced intestinal epithelial tight junction damage and in this study we will investigate if CORM-2 could protect intestinal epithelial tight junctions in the rat cecal ligation and puncture (CLP) model. MATERIALS AND METHODS: The CLP model was generated using male Sprague-Dawley (SD) rats according to standard procedure and treated with CORM-2 or inactive CORM-2 (iCORM-2), 8 mg/kg, i.v. immediately after CLP induction and euthanized after 24h or 72h (for mortality rate only). Morphological changes were investigated using both transmission electron and confocal microscopy. The levels of important TJ proteins and phosphorylation of myosin light chain (MLC) were examined using Western blotting. Cytokines, IL-1ß and TNF-α were measured using ELISA kits. The overall intestinal epithelial permeability was evaluated using FD-4 as a marker. RESULTS: CORM-2, but not iCORM-2, significantly reduced sepsis-induced damage of intestinal mucosa (including TJ disruption), TJ protein reduction (including zonula occludens-l (ZO-1), claudin-1 and occludin), MLC phosphorylation and proinflammatory cytokine release. The overall outcomes showed that CORM-2 suppressed sepsis-induced intestinal epithelial permeability changes and reduced mortality rate of those septic rats. CONCLUSIONS: Our data strongly suggest that CORM-2 could be a potential therapeutic reagent for sepsis by suppressing inflammation, restoring intestinal epithelial barrier and reducing mortality.