A prospective observation on nutrition support in adult patients with severe burns.

Nutrition therapy is considered an important treatment of burn patients. The aim of the study was to delineate the nutritional support in severe burn patients and to investigate association between nutritional practice and clinical outcomes. Severe burn patients were enrolled (n 100). In 90 % of the cases, the burn injury covered above 70 % of the total body surface area. Mean interval from injury to nutrition start was 2·4 (sd 1·1) d. Sixty-seven patients were initiated with enteral nutrition (EN) with a median time of 1 d from injury to first feed. Twenty-two patients began with parenteral nutrition (PN). During the study, thirty-two patients developed EN intolerance. Patients received an average of about 70 % of prescribed energy and protein. Patients with EN providing <30 % energy had significantly higher 28- d and in-hospital mortality than patients with EN providing more than 30 % of energy. Mortality at 28 d was 11 % and in-hospital mortality was 45 %. Multiple regression analysis demonstrated that EN providing <30 % energy and septic shock were independent risk factors for 28- d prognosis. EN could be initiated early in severe burn patients. Majority patients needed PN supplementation for energy requirement and EN feeding intolerance. Post-pyloric feeding is more efficient than gastric feeding in EN tolerance and energy supplement. It is difficult for severe burn patients to obtain enough feeding, especially in the early stage of the disease. More than 2 weeks of underfeeding is harmful to recovery.

Factors Associated With Prolonged Viral Shedding in Patients With Avian Influenza A(H7N9) Virus Infection.

Background: Data are limited on the impact of neuraminidase inhibitor (NAI) treatment on avian influenza A(H7N9) virus RNA shedding. Methods: In this multicenter, retrospective study, data were collected from adults hospitalized with A(H7N9) infection during 2013-2017 in China. We compared clinical features and A(H7N9) shedding among patients with different NAI doses and combination therapies and evaluated factors associated with A(H7N9) shedding, using Cox proportional hazards regression. Results: Among 478 patients, the median age was 56 years, 71% were male, and 37% died. The median time from illness onset to NAI treatment initiation was 8 days (interquartile range [IQR], 6-10 days), and the median duration of A(H7N9) RNA detection from onset was 15.5 days (IQR, 12-20 days). A(H7N9) RNA shedding was shorter in survivors than in patients who died (P < .001). Corticosteroid administration (hazard ratio [HR], 0.62 [95% confidence interval {CI}, .50-.77]) and delayed NAI treatment (HR, 0.90 [95% CI, .91-.96]) were independent risk factors for prolonged A(H7N9) shedding. There was no significant difference in A(H7N9) shedding duration between NAI combination treatment and monotherapy (P = .65) or between standard-dose and double-dose oseltamivir treatment (P = .70). Conclusions: Corticosteroid therapy and delayed NAI treatment were associated with prolonged A(H7N9) RNA shedding. NAI combination therapy and double-dose oseltamivir treatment were not associated with a reduced A(H7N9) shedding duration as compared to standard-dose oseltamivir.

Enteral nutrition feeding in Chinese intensive care units: a cross-sectional study involving 116 hospitals.

BACKGROUND: There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. METHODS: This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. RESULTS: A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2-19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2-3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353-0.599; p < 0.001). AGI 4 was significantly associated with lower hazard of EN administration (HR 0.056; 95% CI 0.008-0.398; p = 0.004). In a linear regression model, greater Sequential Organ Failure Assessment scores (coefficient - 0.002, 95% CI - 0.008 to - 0.001; p = 0.024) and male gender (coefficient - 0.144, 95% CI - 0.203 to - 0.085; p < 0.001) were found to be associated with lower EN proportion. As compared with AGI 1, AGI 2-3 was associated with lower EN proportion (coefficient - 0.206, 95% CI - 0.273 to - 0.139; p < 0.001). CONCLUSIONS: The study showed that EN delivery was suboptimal in Chinese ICUs. More attention should be paid to EN use in the early days after ICU admission.

The Chronic and Short-Term Effects of Gefinitib on Airway Remodeling and Inflammation in a Mouse Model of Asthma.

BACKGROUND: Asthma is a complex and heterogeneous chronic inflammatory disorder which is characterized by airway remodeling and airway inflammation, including goblet cell and airway smooth muscle cell hyperplasia, mucus hypersecretion and eosinophils infiltration. Epidermal growth factor receptor (EGFR) plays an important role in goblet cell hyperplasia and mucus hypersecretion. We aimed to investigate the effects of gefitinib, an EGFR inhibitor, on ovalbumin (OVA)-induced airway remodeling and inflammation of a mouse model of asthma. METHODS: Pathological changes of OVA sensitization of BALB/c mice were measured by H&E and PAS staining; pEGFR, Bcl-2 and Bax expression was measured by western blot; ELISA was used to measure the level of muc5ac, IL-13 and IFN-x03B3;; TUNEL staining was used to detect goblet cell apoptosis. RESULTS: At the present study, H&E and PAS staining showed that mice pretreated with gefinitib developed fewer pathological changes compared with asthmatic mice and gefinitib treatment asthmatic mice, such as a remarkable reduction in airway inflammation, goblet cell and airway smooth muscle cell hyperplasia. Chronic gefitinib treatment or short-term gefitinib treatment significant down-regulate the expression of pEGFR compared with asthma group. Also, chronic gefitinib treatment markedly decreased the levels of muc5ac and IL-13 in BALF, whereas the level of IFN-x03B3; did not change obviously. TUNEL staining showed that the goblet cell apoptosis rate was much higher in the short-term gefinitib treatment group compared with the asthma and chronic gefitinib treatment group which was accompanied by a decrease in Bcl-2 levels and an increase in Bax expression in goblet cells. CONCLUSION: In summary, our results suggested that gefinitib may have a potential role in airway remodeling and inflammation, and may be an effective pharmacotherapy for asthma.

Patient self-inflicted lung injury associated pneumothorax/pneumomediastinum is a risk factor for worse outcomes of severe COVID-19: a case-control study.

We aimed to determine the clinical characteristics of patient self-inflicted lung injury (P-SILI)-associated pneumothorax/pneumomediastinum, to reveal its risk factors, and to assess its impact on severe COVID-19 cases. In total, 229 patients were included in this case-control study. They were randomly divided into either the case group or the control group as per the inclusion and exclusion criteria. The two groups were further analyzed to reveal the risk factors of spontaneous pneumothorax/pneumomediastinum (SP/P). Finally, risk factors for death were analyzed in the case group and the relationship between death and SP/P was also analyzed among all patients. The mean age of patients was 59.69 ± 17.01 years, most of them were male (74.2%), and 62.0% of them had comorbidities upon admission. A respiratory rate higher than 30 BPM was a risk factor for SP/P (OR 7.186, 95% CI 2.414-21.391, P < 0.001). Patients with delayed intubation due to early application of HFNC or NIV had a higher mortality rate when they developed SP/P (P < 0.05). Additionally, advanced age increased the risk of death (P < 0.05). Finally, SP/P may be a risk factor for death among patients with severe COVID-19 (OR 2.047). P-SILI occurs in severe COVID-19 with acute respiratory failure. It is necessary to identify the risk factors of P-SILI, the indicators of severe P-SILI, and the preventive measures.

Unilateral pulmonary oedema: a case report and literature review.

Acute myocarditis is often secondary to an acute virus infection, which can be the first manifestation of upper respiratory tract symptoms, followed by chest tightness, shortness of breath, palpitations, chest pain and other non-specific symptoms. In severe cases, it can quickly progress to serious complications such as heart failure, shock and respiratory failure. Laboratory examinations can show an increase of myocardial injury markers, infection and inflammatory indicators. Cardiac ultrasound can detect the weakening of the myocardial contraction and valve regurgitation. On imaging, bilateral pulmonary oedema demonstrates symmetrical infiltration along the hilum of lung, called the "butterfly shadow". This current case report describes a patient with unilateral pulmonary oedema caused by myocarditis that was initially misdiagnosed and treated as pneumonia. The patient was subsequently treated with the application of extracorporeal membrane oxygenation and he made a full recovery. A review of this case highlights that when a patient's symptoms are not typical, a comprehensive examination and evaluation are required to avoid incorrect treatment.

Prospective Study on Energy Expenditure in Patients With Severe Burns.

BACKGROUND: Nutrition therapy is recognized as one of the most significant treatment aspects for burn patients. However, data were limited regarding the actual nutrition practices in patients with severe burn injury. This study aims to explore the measured energy expenditure (MEE) changes in severe burn patients and to evaluate the precision of commonly used predictive formulas for estimating predictive energy expenditure (PEE) in burn patients. METHODS: A prospective multicenter trial was conducted in the intensive care units in the hospitals enrolling the severely burned patients. Data on MEE and PEE were collected and analyzed. RESULTS: Forty-three patients were enrolled from 3 hospitals. All the patients had severe burns. MEE was measured by metabolic cart, and the MEE on the seventh day after severe burns was as high as 65 kcal/kg, which was 267% of the basal metabolic rate. The presence of hypermetabolism was sustained throughout the 21-day afterburn and decreased gradually to 34 kcal/kg thereafter until 4 weeks after injury. Wound percentage after skin-grafting therapy, time course of burn injury, the existence of severe sepsis, and blood infection were significantly associated with higher MEE. Compared with PEE and MEE, Toronto formula could estimate patients' energy requirements with more accuracy; Curreri and Pennisi formula both significantly overestimated the patient's energy expenditure, whereas underestimation occurred with the Harris-Benedict formula. CONCLUSIONS: Severe burn patients were hypermetabolic at the early stage and sustained this status over a long time. The Toronto formula was the unbiased method to predict energy expenditure.

An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19.

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 can interact with the nucleocapsid (N) protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.

Efficacy and Safety of High Vs Standard Daptomycin Doses Examined in Chinese Patients With Severe Burn Injuries by Pharmacokinetic Evaluation.

Previous studies and the concentration-dependent antibacterial actions of daptomycin suggested that a high dose would be needed for difficult-to-treat infections in burn patients. Here, we evaluated the effects of administration of low and high doses of daptomycin in patients with severe burn injuries. The study retrospectively analyzed 10 patients with severe burn injuries, using pharmacokinetic (PK) and pharmacodynamic (PD) evaluations of daptomycin doses given to combat serious infections. Daptomycin was administered as a single dose or by multiple doses intravenously at a standard dose of 6 mg/kg/d or a high dose of 12 mg/kg/d for 7 to 14 days. The serum concentrations of daptomycin from patients were analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Burn injury patients treated with high-dose daptomycin had a linear PK profile and a negative correlation between the AUC0-24 and Baux score (R2 = .953 and R2 = .801). The Cmax, AUC0-24, and t(h)½ increased significantly compared with patients given a standard dose. The efficacy of daptomycin against Staphylococcus aureus showed significantly higher rates of (AUC0-24)/MIC and Cmax/MIC after high-dose daptomycin compared with the standard dose, reflected in a significant correlation between a high dose and the Baux score (r = .976, P < .001). Positive S. aureus cultures from two of three high-dose and none of two daptomycin low-dose patients converted from positive to negative after therapy. No serious adverse events or discontinuation of the drug occurred during the treatment period. Daptomycin doses up to 12 mg/kg/d were well tolerated in Chinese patients with severe burn injuries, which were complicated by infections with S. aureus.

Clinical features and mortality-related factors of extensive burns among young adults: the Kunshan disaster experience.

BACKGROUND: The aim of the study was to identify the clinical features and the factors associated with burn induced mortality among young adults after exposure to indoor explosion and fire. METHODS: This is an observational study which included burn patients who were admitted to eighteen ICUs after a fire disaster. Epidemiologic and clinical characteristics, as well as therapy were recorded. The primary outcome was 90-day mortality. The mortality-related factors were also analyzed. RESULTS: There were 167 burn patients enrolled in the study, the median age was 38 years, 62 (37.1%) patients died within 90 days. Seventy-one percent of patients had a burn size ≥90% TBSA, and 73.7% of patients had a full-thickness burn area above 50% TBSA. The survivors had lower Baux scores, and received earlier escharectomy and autologous skin grafts. The 50% mortality rates (LA50s) for burn size and full-thickness burn area were 95.8% and 88.6% TBSA, respectively. The multivariate analysis showed that full-thickness burn area over 50% TBSA and residual burned surface area (RBSA)/TBSA at 28 days were strong predictors of mortality among burn patients (odds ratio 2.55; 95% CI, 1.01 to 6.44, P=0.047; odds ratio 1.07; 95% CI, 1.04 to 1.09, P<0.001). The ROC curve-based cut-off values of RBSA/TBSA at 28 days for predicting 90-day mortality were 62.5%. CONCLUSIONS: Burn size and full-thickness burn area were the main risk factors for poor outcome in patients with extensive burns. Earlier escharectomy and autologous skin grafts may improve outcomes.

[Advances in immunomodulatory effects of catecholamines in critical illness].

OBJECTIVE: Immune disorders are common in critically ill patients. Catecholamines play a crucial role in theimmune regulation and modulation. Immune cells can synthesize catecholamines and express adrenergic receptors. Catecholamine has a wide-ranging regulatory effect on innate immunity such as neutrophils, monocyte macrophages, dendritic cells, natural killer cells, and lymphocyte-mediated acquired immunity. Catecholamines exert different immunomodulatory effects by binding to α receptors, ß receptors, and dopamine receptor subtypes on immune cells. In-depth study of the effect and mechanism of catecholamine on immune function in critically ill patients will provide new ideas for the prevention and treatment of immune dysfunction in critical illness.

Venovenous extra-corporeal membrane oxygenation for severe acute respiratory distress syndrome: a matched cohort study.

BACKGROUND: Although the use of extra-corporeal membrane oxygenation (ECMO) has been rapidly increasing, the benefit of ECMO in patients with acute respiratory distress syndrome (ARDS) remains unclear. Our objective was to investigate the effect of venovenous ECMO (VV-ECMO) on adult patients with severe ARDS. METHODS: We conducted a multi-center, retrospective, cohort study in the intensive care units (ICUs) of six teaching hospitals between January 2013 and December 2018. Patients with severe ARDS who received VV-ECMO support were included. The detailed demographic data and physiologic data were used to match ARDS patients without ECMO. The primary endpoint was the 28-day mortality. RESULTS: Ninety-nine patients with severe ARDS supported by VV-ECMO and 72 patients without ECMO were included in this study. The acute physiology and chronic health evaluation II score was 23.1 ±â€Š6.3 in the ECMO group and 24.8 ±â€Š8.5 in the control group (P = 0.1195). The sequential organ failure assessment score was 12.8 ±â€Š3.4 in the ECMO group and 13.7 ±â€Š3.5 in the control group (P = 0.0848). The 28-day mortality of patients with ECMO support was 39.4%, and that of the control group was 55.6%. The survival analysis curve showed that the 28-day mortality in the ECMO group was significantly lower than that in the control group (P = 0.0097). Multivariate Cox regression analysis showed that the independent predictors of the 28-day mortality were the requirement of vasopressors before ECMO (hazard ratio [HR]: 1.006; 95% confidence interval [CI]: 1.001-1.013; P = 0.030) and duration of mechanical ventilation before ECMO (HR: 3.299; 95% CI: 1.264-8.609; P = 0.034). CONCLUSIONS: This study showed that ECMO improved the survival of patients with severe ARDS. The duration of mechanical ventilation and the requirement of vasopressors before ECMO might be associated with an increased risk of death.

Neutrophil gelatinase-associated lipocalin predicts myocardial dysfunction and mortality in severe sepsis and septic shock.

BACKGROUND: This study examines the clinical utility of plasma neutrophil gelatinase-associated lipocalin (NGAL) as an indicator of myocardial dysfunction and mortality in severe sepsis and septic shock. METHODS: We designed a prospective cohort study in an intensive care unit, and 53 patients with severe sepsis or septic shock were included. Data were used to determine a relationship between NGAL and the development of myocardial dysfunction and mortality. These associations were determined by the Mann-Whitney test, multiple logistic regression, plotting the receiver operating characteristic (ROC) curve, Kaplan-Meier curves and Spearman test. RESULTS: The High NGAL group had higher need for inotropic/vasopressor support (92% vs. 52%, p=0.0186), higher incidence of regional wall motion abnormalities (46% vs. 13%, p=0.0093), higher B-type natriuretic peptide (BNP) level (p=0.0197), higher cardiac troponin I (cTnI) level (p=0.0016), lower ejection fraction (EF) (p<0.0001) and higher mortality (p=0.0262) compared to the Low NGAL group. Patients with High NGAL were more likely to manifest electrocardiogram (ECG) abnormalities (p=0.042) and demonstrate clinical myocardial dysfunction (p=0.0186) as evidenced by clinical or radiological evidence of pulmonary edema as compared to those with Low NGAL group. NGAL, BNP, Acute Physiology and Chronic Health Evaluation (APACHE) II score, cTnI, and PaO2/FIO2 ratio were independent predictor of death by multiple logistic regression analysis. The area under the ROC curve showed that plasma NGAL as a predictor of death in septic shock was significant. CONCLUSIONS: High plasma NGAL correlates with high mortality and myocardial dysfunction in severe sepsis and septic shock.

Correlation of lactate/albumin ratio level to organ failure and mortality in severe sepsis and septic shock.

BACKGROUND: This study examines the clinical utility of the increased lactate/albumin ratio as an indicator of multiple-organ dysfunction syndrome (MODS) and mortality in severe sepsis and septic shock. METHODS: We designed a prospective cohort study in an intensive care unit, and 54 patients with severe sepsis or septic shock were included. Data were used to determine a relationship between lactate/albumin ratio and the development of MODS and mortality. These associations were determined by the Mann-Whitney test, multiple logistic regression, plotting the receiver operating characteristic curve and Spearman test. RESULTS: Lactate/albumin ratio level was higher in MODS patients on day 1 (median [interquartile range, or IQR], 2.295 [1.818-3.065]; n = 30, P < .0001) than in those without (median [IQR], 1.550 (1.428-1.685); n = 24), and on day 2, (median [IQR], 1.810 [1.377-2.448]; n = 26, P = .0022) it was higher than in those without (median [IQR], 1.172 (1.129-1.382); n = 23) on day 2. We found that lactate/albumin ratio was an independent predictor of the development of MODS (odds ratio, 5.5; P = .033; 95% confidence interval, 1.1-26.1) during intensive care unit stay. The area under the receiver operating characteristic curve showed that lactate/albumin ratio could predict MODS (0.8458) and mortality (0.8449). Furthermore, the higher the Acute Physiology and Chronic Health Evaluation II score, the more lactate/albumin ratio was discovered on day 1 (r = 0.5315, P < .0001) and day 2 (r = 0.5408, P < .0001), whereas the lower partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, the more lactate/albumin ratio was illustrated on day 1 (r = -0.5143, P < .0001) and day 2 (r = -0.5420, P < .0001). CONCLUSIONS: Increased lactate/albumin ratio correlates with the development of MODS and mortality in patients with severe sepsis and septic shock.

Increased Neutrophil Gelatinase-Associated Lipocalin is Associated with Mortality and Multiple Organ Dysfunction Syndrome in Severe Sepsis and Septic Shock.

BACKGROUND: This study examines the clinical utility of increased neutrophil gelatinase-associated lipocalin (NGAL) as an indicator of mortality and multiple organ dysfunction syndrome (MODS) in severe sepsis and septic shock. METHODS: We designed a prospective cohort study in an intensive care unit, and 123 patients with severe sepsis or septic shock were included. Data were used to determine a relationship between NGAL and the development of MODS and mortality. These associations were determined by the Mann-Whitney U test, log-rank test, Cox proportional hazards regression analyses, and plotting the receiver operating characteristic curve. RESULTS: Patients with high NGAL (75th percentile) had increased risk of mortality and MODS compared with patients with low NGAL (log-rank test, P < 0.05). There were 39 patients (32%) with mortality during follow-up at 12 months, 10 patients (8%) with MODS on day 1, and 37 patients (30%) on day 7. The area under the receiver operating characteristic curve showed that high NGAL could predict mortality (0.6385) during intensive care unit stay. After adjustment for confounding risk factors chosen by backward elimination by Cox regression analysis, high NGAL remained an independent predictor of mortality and MODS (hazard ratios, 2.128 [95% confidence interval, 1.078-4.203; P = 0.030] and 1.896 [95% confidence interval, 1.012-3.552; P = 0.046], respectively). CONCLUSIONS: High plasma NGAL independently predicts mortality and MODS in severe sepsis and septic shock.