Temporal patterns of organ dysfunction in COVID-19 patients hospitalized in the intensive care unit: A group-based multitrajectory modeling analysis.

BACKGROUND: The course of organ dysfunction (OD) in Corona Virus Disease 2019 (COVID-19) patients is unknown. Herein, we analyze the temporal patterns of OD in intensive care unit-admitted COVID-19 patients. METHODS: Sequential organ failure assessment scores were evaluated daily within 2 weeks of admission to determine the temporal trajectory of OD using group-based multitrajectory modeling (GBMTM). RESULTS: A total of 392 patients were enrolled with a 28-day mortality rate of 53.6%. GBMTM identified four distinct trajectories. Group 1 (mild OD, n = 64), with a median APACHE II score of 13 (IQR 9-21), had an early resolution of OD and a low mortality rate. Group 2 (moderate OD, n = 140), with a median APACHE II score of 18 (IQR 13-22), had a 28-day mortality rate of 30.0%. Group 3 (severe OD, n = 117), with a median APACHR II score of 20 (IQR 13-27), had a deterioration trend of respiratory dysfunction and a 28-day mortality rate of 69.2%. Group 4 (extremely severe OD, n = 71), with a median APACHE II score of 20 (IQR 17-27), had a significant and sustained OD affecting all organ systems and a 28-day mortality rate of 97.2%. CONCLUSIONS: Four distinct trajectories of OD were identified, and respiratory dysfunction trajectory could predict nonpulmonary OD trajectories and patient prognosis.

Clinical characteristics, risk factors, and outcomes of patients with polymicrobial Pseudomonas aeruginosa bloodstream infections.

BACKGROUND: Previous studies on polymicrobial Pseudomonas aeruginosa bloodstream infections (Pa-BSIs) are dated, and it is necessary to reanalyze polymicrobial Pa-BSIs. The aim of this study was to investigate clinical characteristics and risk factors for polymicrobial Pa-BSI in comparison with monomicrobial Pa-BSI. METHODS: A double-center retrospective observational study was performed between January 1, 2013 and June 30, 2022, in two tertiary hospitals. All patients with Pa-BSI were enrolled, and their clinical data were collected by reviewing electronic medical records. RESULTS: A total of 278 patients with Pa-BSI were enrolled, including 77 patients (27.7%) with polymicrobial Pa-BSI. Compared with monomicrobial Pa-BSI, the main source of polymicrobial Pa-BSI was pneumonia (49.4% vs 31.3%, p < 0.01), whereas the main source of monomicrobial Pa-BSI was primary BSIs (21.9% vs 2.6%, p = 0.04). In multivariate analysis, a history of cerebrovascular accident (CVA) (adjusted odds ratio [OR], 3.62; 95% CI, 1.46-8.92) was independently associated with polymicrobial Pa-BSI. Primary BSI was associated with monomicrobial Pa-BSI (OR, 0.08; 95% CI, 0.02-0.38). Patients with polymicrobial Pa-BSI had a longer intensive care unit (ICU) length of stay after onset of BSI than those with monomicrobial Pa-BSI (2 [2, 16] vs 13 [3.75, 29], p = 0.02). CONCLUSION: Patients with Pa-BSI and the presence of CVA need to be alert to the possibility of polymicrobial BSI occurrence. Prolonged ICU stay and pneumonia as a source of BSI warrant clinician attention for polymicrobial Pa-BSI, and primary BSIs are likely associated with monomicrobial BSIs.

THE ALARMIN EFFECT OF HMGB1/RIP3 ON TRANSFUSION-RELATED ACUTE LUNG INJURY VIA TLR4/NF-ΚB OR MAPK PATHWAY.

ABSTRACT: Nonantibody-mediated transfusion-related acute lung injury (TRALI) may account for up to 25% of TRALI cases. This indicates the need for further research to understand the pathophysiological mechanisms involved beyond antibody mediation fully. During this research, a TRALI rat model was developed using the trauma-blood loss-massive transfusion method. The severity of pulmonary edema was checked via measurement of lung histopathological changes and the amount of Evans blue dye fluid and bronchoalveolar lavage fluid protein leakage. In addition, potential mechanisms of pathophysiological pathways and inflammation cascades were investigated in TRALI rats in vivo . The findings indicated that TRALI increased inflammatory cytokines and triggered elevated levels of high-mobility group box 1 (HMGB1)/receptor-interacting protein kinase 3 (RIP3), apoptosis protein, and mRNAs in the TM (TRALI model) group as opposed to the normal control. Furthermore, TRALI activated the toll-like receptor 4/nuclear factor kappa B and mitogen-activated protein kinase signaling pathways, which partially regulated the inflammatory response in the TRALI rats. A significant increase was observed in the inflammatory mediators HMGB1 and RIP3 during the early stages of TRALI, suggesting that these mediators could be used as diagnostic markers for TRALI. In addition, HMGB1 and RIP3 promoted the inflammatory response by stimulating the toll-like receptor 44/nuclear factor kappa B and mitogen-activated protein kinase signaling pathways in the lung tissue of rats. Identifying efficient agents from inflammatory mediators such as alarmin can be an innovative scheme for diagnosing and preventing TRALI. These findings give HMGB1 and RIP3 a strong theoretical and experimental foundation for clinical use.

Use of venous-venous extracorporeal membrane oxygenation in the treatment of postpartum pulmonary hypertension crisis.

The incidence of heart disease in pregnancy ranges from 0.5% to 3.0% and is regarded as one of the top three causes of maternal death. The mortality rate of patients with pulmonary hypertension and Eisenmenger syndrome is as high as 16.7%-50%. Changes in haemodynamics during pregnancy and childbirth increase the burden on the heart, and induced pulmonary hypertension crisis is one of the main causes of maternal death. Extracorporeal Membrane Oxygenation (ECMO) is the last-resort treatment strategy to treat patients with pulmonary hypertension crisis. We report a ventricular septal defect in a pregnant woman with pulmonary hypertension and Eisenmenger's syndrome, which is a postpartum pulmonary hypertension crisis that leads to respiratory and circulatory disorders. The patient was successfully treated with venous-venous extracorporeal membrane oxygenation.

Emergence of Extensively Drug-Resistant ST170 Citrobacter portucalensis with Plasmids pK218-KPC, pK218-NDM, and pK218-SHV from a Tertiary Hospital, China.

The objective of this study is to characterize the molecular mechanism of a clinical carbapenem-resistant Citrobacter portucalensis strain K218, which coproduces KPC and NDM carbapenemases. K218 was isolated from a patient's blood sample in a Chinese tertiary hospital. Carbapenemases were detected by the immunocolloidal gold technique. The MIC values were determined by VITEK2. Whole-genome sequencing was performed on K218 and sequence data were analyzed using phylogenetics and extensive genomic comparison. This study reveals that K218 contains a single 5.08 Mb chromosome (51.8% GC content) and four plasmids, pK218-KPC (106 Kb), pK218-NDM (111 Kb), pK218-SHV (191 Kb), and pK218-NR (5 Kb). Twenty-nine types of antibiotic resistance genes were carried on K218, including blaKPC-2 harbored on pK218-KPC and blaNDM-1 harbored on pK218-NDM. Detailed comparison of related plasmids of pK218-KPC, pK218-NDM, and pK218-SHV showed that they shared similar conserved backbone regions, respectively. Comprehensive annotation revealed large accessory modules were recombined on the genome of K218. Further analysis speculated that mobile genetic elements bearing abundant resistance genes facilitated the formation of these accessory modules. In conclusion, this study provides an in-depth understanding of the genomic characterization of K218, an extensively drug-resistant C. portucalensis strain coproducing NDM and KPC carbapenemase. To the best of our knowledge, this is the first report of C. portucalensis strain coharboring blaKPC-2 and blaNDM-1 from the clinical setting. IMPORTANCE This is the first report of extensively drug-resistant C. portucalensis harboring both blaKPC-2 and blaNDM-1. This study will not only extend the understanding of the structural dissection of plasmids and chromosomes carried in C. portucalensis, but also expand knowledge of the genetic environment of the blaKPC-2 and blaNDM-1 genes. blaKPC-2 and blaNDM-1 genes have been suggested to facilitate the propagation and persistence of their host bacteria under different antimicrobial selection pressures. Large accessory regions carrying blaKPC-2 and blaNDM-1 genes have become hot spots for transposition and integration, and their structural variation and evolution should receive attention. The multidrug-resistant plasmids pK218-KPC, pK218-NDM, and pK218-SHV with several multidrug resistance regions and the chromosome cK218 with two novel transposons Tn7410 and Tn7411 contribute to the formation of extensively drug-resistant C. portucalensis.

Uncommon complication of nasoenteral feeding tube: A case report.

BACKGROUND: The jejunal nutrition tube has increasingly been used in clinical practice, and the results in frequent complications. CASE SUMMARY: We present the case of a 74-year-old male patient who had been admitted to the intensive care unit for aspiration pneumonia and respiratory failure. When confirming the position of the jejunal tube by X-ray, we found that the feeding tube had been placed into the chest. The complications was a disaster, though the misplacement of jejunal feeding tube are uncommon. CONCLUSION: We introduced a way of ultrasound-guided jejunum feeding tube placement to avert the disaster, which was convenient and economical.

ΔPCO2 and ΔPCO2/C(a-cv)O2 Are Not Predictive of Organ Dysfunction After Cardiopulmonary Bypass.

Background: Cardiac surgery is associated with a substantial risk of major adverse events. Although carbon dioxide (CO2)-derived variables such as venous-to-arterial CO2 difference (ΔPCO2), and PCO2 gap to arterial-venous O2 content difference ratio (ΔPCO2/C(a-cv)O2) have been successfully used to predict the prognosis of non-cardiac surgery, their prognostic value after cardiopulmonary bypass (CPB) remains controversial. This hospital-based study explored the relationship between ΔPCO2, ΔPCO2/C(a-cv)O2 and organ dysfunction after CPB. Methods: We prospectively enrolled 114 intensive care unit patients after elective cardiac surgery with CPB. Patients were divided into the organ dysfunction group (OI) and non-organ dysfunction group (n-OI) depending on whether organ dysfunction occurred or not at 48 h after CPB. ΔPCO2 was defined as the difference between central venous and arterial CO2 partial pressure. Results: The OI group has 37 (32.5%) patients, 27 of which (23.7%) had one organ dysfunction and 10 (8.8%) had two or more organ dysfunctions. No statistical significance was found (P = 0.84) for ΔPCO2 in the n-OI group at intensive care unit (ICU) admission (9.0, 7.0-11.0 mmHg), and at 4 (9.0, 7.0-11.0 mmHg), 8 (9.0, 7.0-11.0 mmHg), and 12 h post admission (9.0, 7.0-11.0 mmHg). In the OI group, ΔPCO2 also showed the same trend [ICU admission (9.0, 8.0-12.8 mmHg) and 4 (10.0, 7.0-11.0 mmHg), 8 (10.0, 8.5-12.5 mmHg), and 12 h post admission (9.0, 7.3-11.0 mmHg), P = 0.37]. No statistical difference was found for ΔPCO2/C(a-cv)O2 in the n-OI group (P = 0.46) and OI group (P = 0.39). No difference was detected in ΔPCO2, ΔPCO2/C(a-cv)O2 between groups during the first 12 h after admission (P > 0.05). Subgroup analysis of the patients with two or more failing organs compared to the n-OI group showed that the predictive performance of lactate and Base excess (BE) improved, but not of ΔPCO2 and ΔPCO2/C(a-cv)O2. Regression analysis showed that the BE at 8 h after admission (odds ratio = 1.37, 95%CI: 1.08-1.74, P = 0.009) was a risk factor for organ dysfunction 48 h after CBP. Conclusion : ΔPCO2 and ΔPCO2/C(a-cv)O2 cannot be used as reliable indicators to predict the occurrence of organ dysfunction at 48 h after CBP due to the pathophysiological process that occurs after CBP.

Efficacy analysis of Arbidol treatment in patients with 2019 novel coronavirus pneumonia: a retrospective cohort study.

BACKGROUND: The aim of this study was to determine whether Arbidol has a good antiviral effect on coronavirus disease 2019 (COVID-19). METHODS: A retrospective cohort study was performed in one of the treatment centers for COVID-19 patients in China from January 2020 to March 2020. The antiviral drug Arbidol (ARB) was administrated to some of the patients at 0.2 g tid po for 7 to 10 days. According to whether patients were given ARB, they were divided into 2 groups: the ARB group and the Non-ARB group. The primary outcome was the 14-day COVID-19 negativity rate. RESULTS: Of 146 patients, 140 were included. A total of 79 (56.4%) patients received ARB during hospitalization. In the overall cohort, the time of COVID-19 negativity in the ARB group compared with the Non-ARB group was 12.9 days versus 12.7 days (P=0.175; >0.05). The rates of 14-day COVID-19 negativity were 60.8% and 65.6% in the ARB and non-ARB groups, respectively (P=0.559; >0.05). Using an adjusted model, there were no obvious differences in the time of COVID-19 negativity and the rates of 14-day COVID-19 negativity (P>0.05). According to Kaplan-Meier analysis, the probabilities of 14-day COVID-19 negativity were similar in the 2 groups (log-rank P=0.130; >0.05). In a multivariate Cox analysis, the variables of age [hazard ratio (HR) 0.91, 95% confidence interval (CI): 0.83 to 0.99; P=0.039] and glucose (HR 0.90, 95% CI: 0.82 to 0.98; P=0.021) were independently associated with 14-day COVID-19 negativity. CONCLUSIONS: Our results suggest that there was no apparent favorable clinical response with ARB both in clinical symptoms and the 14-day COVID-19 negativity rate.

Effects of early enteral nutrition on the prognosis of patients with sepsis: secondary analysis of acute gastrointestinal injury study.

BACKGROUND: The time of enteral nutrition (EN) administration on patients with sepsis is controversial. The study was to explore the effect of early enteral nutrition (EEN) on the prognosis of patients with sepsis. METHODS: We performed a secondary analysis of the acute gastrointestinal injury grade study. The patients were divided into two groups from the time of EN administration: EEN group (n=85): EN within 24 hours; Control group (N=78): EN after 24 hours. The key observation was the length of ICU stay, and length of hospital stay, and 28- and 60-day mortality. RESULTS: Of 676 patients, 163 were included. There are no significant between-group differences in the characteristics at baseline. The overall mortality rate at 28 days in the EEN group was 28.2% vs. 43.6% in the control group (P=0.041). The mortality rate at 60 days in the EEN group was 36.5% vs. 52.6% in the control group (P=0.039). In a subgroup analysis of patients who whether used vasoactive drugs: the EEN group was found to be significantly associated with 60-day mortality (P=0.039). The ICU stay length in the EEN group was longer than in the control group {11 [8-22] vs. 10 [6-16]; P=0.022}. Also, the length of the hospital stay was longer than in the Control group {23 [14-53] vs. 18 [10-39]; P=0.023}. Univariate Cox regression analysis showed that EEN, using vasoactive drugs, Acute kidney injury (AKI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and the global acute gastrointestinal injury (AGI) grade were significantly (P<0.05) associated with 60-day mortality. In a multivariate analysis including these variables, EEN (HR1.68, 95% CI: 1.02-2.62; P=0.040, global AGI grade (HR2.28, 95% CI: 1.30-4.00; P=0.004), and APACHE II score (HR 1.04, 95% CI: 1.01-1.07; P=0.021) were independently associated with 60-day mortality. CONCLUSIONS: EEN within 24 hours can improve the survival of patients with sepsis, and that is an independent prognostic factor.

Pulmonary function of patients with 2019 novel coronavirus induced-pneumonia: a retrospective cohort study.

BACKGROUND: The aim of this study was to investigate the pulmonary function of patients with 2019 novel coronavirus (COVID-19)-induced pneumonia. METHODS: A retrospective analysis of 137 patients with COVID-19-induced pneumonia who were discharged from the Enze Hospital, Taizhou Enze Medical Center (Group) from January 31 2020 to March 11 2020 was conducted. Follow-up occurred 2 weeks after hospital discharge, during which patients underwent a pulmonary function test. RESULTS: Of the 137 patients who underwent a pulmonary function test 2 weeks after discharge, 51.8% were male, and the mean age was 47 years. Only 19.7% of the patients were identified as having severe COVID-19-induced pneumonia. The pulmonary function tests showed that for a small number of patients the forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC)/% values were <70%, and the mean forced inspiratory volume (IVC) and FVC values were 2.4±0.7 and 3.2±0.8 L, respectively. In severe cases, 88.9% of patients had an IVC <80% of the predicted value, and 55.6% of patients had an FVC <80% of the predicted value. The proportion of patients with maximum expiratory flow rate at 25%, 50% and 75% of the vital capacity (MEF25, MEF50, and MEF75) values <70% were 55.6%, 40.7%, and 25.9%, respectively. In the non-severe group, 79.1% of patients had an IVC <80% of the predicted value, and 16.4% of patients had an FVC <80% of the predicted value. The mean MEF25, MEF50, and MEF75 <70% values were 57.3%, 30%, and 13.6%, respectively. CONCLUSIONS: Our results demonstrated that the pulmonary function of patients with COVID-19-induced pneumonia predominantly manifested as restrictive ventilation disorder and small airway obstruction, which was increased in critically ill patients.

Dynamics of peripheral immune cells and their HLA-G and receptor expressions in a patient suffering from critical COVID-19 pneumonia to convalescence.

OBJECTIVES: Host immune responses are indispensable to combat the disease. We report the dynamics of peripheral immune cells, cytokines, and human leucocyte antigen-G (HLA-G) and its receptor expressions in a patient suffering from critical COVID-19 pneumonia to convalescence. METHODS: Clinical data of the patient were collected from medical records. The expressions of HLA-G and receptors ILT2, ILT4 and KIR2DL4 in peripheral immune cells were measured with flow cytometry. RESULTS: From critical COVID-19 to the convalescent stage, early lymphopenia was improved (median: 0.6 × 109 L-1 vs. 0.9 × 109 L-1, P = 0.009), and an obvious fluctuation in WBC and neutrophil counts was observed. Initially, low levels of CD4+ T cells (from 120 to 528 µL-1) and CD8+ T cells (from 68 to 362 µL-1) gradually increased to normal levels. Meanwhile, high IL-6 (from 251.8 to 6.32 pg mL-1), IL-10 (from 39.53 to 5.21 pg mL-1) and IFN-γ (from 13.55 to 3.16 pg mL-1) levels decreased, and IL-4 (from 2.36 to 3.19 pg mL-1) and TNF-α (from 2.27 to 20.2 pg mL-1) levels increased quickly when the viral RNA returned negative. Moreover, the percentage of HLA-G+ T cells, B cells and monocytes follows high-low-high pattern, while the percentage of receptors ILT2-, ILT4- and KIR2DL4-expressing cells remained relatively stable. CONCLUSION: Our findings provide valuable information on the dynamics of early peripheral immunological responses in SARS-CoV-2 infection. CD4+ and CD8+ T cells, cytokines and HLA-G+ immune cells are associated with the natural history of the critical COVID-19 patient; however, future studies are necessary.

Clinical characteristics of 60 discharged cases of 2019 novel coronavirus-infected pneumonia in Taizhou, China.

BACKGROUND: The number of patients with pneumonia stemming from the 2019 novel coronavirus (COVID-19) infection has increased rapidly. However, the clinical characteristics of discharged patients remain little known. Here, we attempt to describe the clinical characteristics and treatment experiences of discharged cases from Taizhou, China. METHODS: A total of 60 patients with COVID-19-infected pneumonia who were discharged from Taizhou Enze Medical Center (Group), from January 31, 2020, to February 16, 2020, were included in the analysis. The discharge criteria were based on the New Coronavirus Pneumonia Prevention and Control Program (Fifth Edition, China). RESULTS: Of the 60 patients, the median age was 41 years, and 58.3% were male. Only 13.3% of patients were identified as having severe novel coronavirus pneumonia. All patients received combined antiviral treatment on admission, including ß-interferon, lopinavir/tonavir, Abidol and oseltamivir. All patients with severe conditions received gamma globulin and hormone therapy. No patients had endotracheal intubation or died. The median duration from symptom onset to hospitalization was 3 (range, 0-15) days. The median duration of COVID-19 shedding was 14 (range, 5-26) days, and the median duration of hospital stay was 15 (range, 7-23) days. CONCLUSIONS: Early therapy and comprehensive therapy are key to the outcome for patients with COVID-19-infected pneumonia, especially for those with severe pneumonia. TRIAL REGISTRATION NUMBER: ChiCTR2000029866.

[Dynamic inflammatory response in a critically ill COVID-19 patient treated with corticosteroids].

OBJECTIVE: To investigate the effect of corticosteroids therapy on the inflammatory response in a critically ill coronavirus disease 2019 (COVID-19) patient. METHODS: A 55-year old female patient with critical ill COVID-19 was admitted in Taizhou Hospital on January 19, 2020. The patient was treated with methylprednisolone 80 mg on the 2nd day after admission. Thereafter, the dose was adjusted in a timely manner and the therapy lasted for 13 days. The peripheral lymphocyte subsets (CD3+T, CD4+ T, CD8+ T, NK cells, B cells), as well as serum levels of lymphocyte factors (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were dynamically monitored. RESULTS: On D1 of admission, the numbers of peripheral blood CD3+ T, CD4+ T, CD8+ T, and NK cells were significantly lower than the normal range. With the improvement of the disease, the numbers of CD3+ T, CD8+ T and CD4 + T cells gradually recovered and showed a linear growth trend (linear fitting equation: Y=18.59X+109.4, P<0.05). On D2 of admission, the patient's IL-6 and IL-10 levels were significantly higher than normal values, IFN-γ was at a normal high value, and then rapidly decreased; IL-2, IL-4, and TNF-α were all in the normal range. On the D6 and D7, the IL-6 and IL-10 decreased to the normal range for the first time. On the D18, the sputum virus nucleic acid test was negative for the first time, and the fecal virus nucleic acid test was still positive; on the D20 the sputum and fecal virus nucleic acid test were both negative. On D34, the patient recovered and was discharged. At the discharge the muscle strength score of the patient was 44 and the daily life ability evaluation was 90. CONCLUSIONS: In the absence of effective antiviral drugs, early use of appropriate doses of corticosteroids in critically ill patient with COVID-19 can quickly alleviate inflammatory response and improve clinical symptoms, however, it may reduce the number of T cells, and to adjust the dose in time is necessary.

Ultra-high pre-membrane lung oxygen saturation in a patient on veno-arterial extracorporeal membrane oxygenation.

A 55-year-old man who suffered from acute myocardial infarction complicated with cardiogenic shock was administered veno-arterial extracorporeal membrane oxygenation. Ultra-high pre-membrane lung oxygen saturation of 93% was observed. Transthoracic echocardiography revealed the presence of patent foramen ovale. The four-chamber view showed that the tip of the cannula was located in the patent foramen ovale, which resulted in a left-to-right shunt. Without adjusting the position of the drainage cannula, the patient was weaned from extracorporeal membrane oxygenation at 136 hours after initiation and survived to hospital discharge.

Prognostic Value of Prolonged Feeding Intolerance in Predicting All-Cause Mortality in Critically Ill Patients: A Multicenter, Prospective, Observational Study.

BACKGROUND: The 2012 European Society of Intensive Care Medicine (ESICM) guidelines provided a clear definition of feeding intolerance (FI). The study aimed to investigate the association between FI based on the current ESICM definition and clinical outcome and to further explore the effect of the duration of FI on mortality. METHODS: Adult patients from 14 general intensive care units (ICUs) with an expected ICU stay ≥24 hours were prospectively studied. Based on FI duration in the first week of admission to the ICU, FI was categorized as 7-day persistent feeding tolerance (FT), delayed FT, delayed FI, and 7-day persistent FI. The primary outcomes were 28-day and 60-day all-cause mortality. RESULTS: Of 499 patients, the prevalence of 3-day and 7-day persistent FI was 39.2% (n = 196) and 25.4% (n = 106), respectively. The patients with 3-day FT had lower risk of 28-day and 60-day mortality rates and higher prevalence in ventilator weaning and vasoactive medication on the seventh day of ICU admission than those with 3-day FI. Three-day FI remained an independent predictor for 60-day mortality. In a subgroup analysis including 418 patients with 7-day survival, compared with those with 7-day persistent FT, the odds ratios of 60-day mortality were 1.67, 1.97, and 2.62 in the patients with delayed FT, delayed FI, and 7-day persistent FI, respectively. CONCLUSION: FI was associated with increased mortality and longer duration of mechanical ventilation and vasoactive support. Prolonged or relapsing FI represented an incremental risk of adverse outcomes in critically ill patients.

Effectiveness of enteral feeding protocol on clinical outcomes in critically ill patients: A before and after study.

BACKGROUND AND OBJECTIVE: Enteral nutrition (EN) feeding protocol was proposed to have positive impact on critically ill patients. However, current studies showed conflicting results. The present study aimed to investigate whether enteral feeding protocol was able to improve clinical outcomes in critically ill patients. METHODS: A before (stage 1) and after (stage 2) interventional study was performed in 10 tertiary care hospitals. All patients expected to stay in the intensive care unit (ICU) for over three days were potentially eligible. Clinical outcomes such as 28-day mortality, ICU length of stay, duration of mechanical ventilation (MV), and nosocomial infection were compared between the two stages. MAIN RESULTS: A total of 410 patients were enrolled during the study period, including 236 in stage 1 and 174 in stage 2. EN feeding protocol was able to increase the proportion of EN in day 2 (41.8±22.3 vs. 50.0±28.3%; p = 0.006) and day 6 (70.3±25.2 vs. 77.6±25.8%; p = 0.006). EN percentages tended to be higher in stage 1 than that in stage 2 on other days, but statistical significance was not reached. There was no difference in 28-day mortality between stage 1 and 2 (0.14 vs. 0.14; p = 0.984). Implementation of EN feeding protocol marginally reduced ICU length of stay (19.44±18.48 vs. 16.29±16.19 days; p = 0.077). There was no difference in the duration of MV between stage a and stage 2 (14.24±14.49 vs. 14.51±17.55 days; p = 0.877). CONCLUSIONS: The study found that the EN feeding protocol was able to increase the proportion of EN feeding, but failed to reduce 28-day mortality, incidence of nosocomial infection or duration of MV.

Severity of acute gastrointestinal injury grade is a predictor of all-cause mortality in critically ill patients: a multicenter, prospective, observational study.

BACKGROUND: In 2012, the European Society of Intensive Care Medicine proposed a definition for acute gastrointestinal injury (AGI) based on current medical evidence and expert opinion. The aim of the present study was to evaluate the feasibility of using the current AGI grading system and to investigate the association between AGI severity grades with clinical outcome in critically ill patients. METHODS: Adult patients at 14 general intensive care units (ICUs) with an expected ICU stay ≥24 h were prospectively studied. The AGI grade was assessed daily on the basis of gastrointestinal (GI) symptoms, intra-abdominal pressures, and feeding intolerance (FI) in the first week of admission to the ICU. RESULTS: Among the 550 patients enrolled, 456 patients (82.9%) received mechanical ventilation, and 470 patients were identified for AGI. The distribution of the global AGI grade was 24.5% with grade I, 49.4% with grade II, 20.6% with grade III, and 5.5% with grade IV. AGI grading was positively correlated with 28- and 60-day mortality (P < 0.0001). Univariate Cox regression analysis showed that age, sepsis, diabetes mellitus, coronary artery disease, the use of vasoactive drugs, serum creatinine and lactate levels, mechanical ventilation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and the global AGI grade were significantly (P ≤ 0.02) associated with 60-day mortality. In a multivariate analysis including these variables, diabetes mellitus (HR 1.43, 95% CI 1.03-1.87; P = 0.05), the use of vasoactive drugs (HR 1.56, 95% CI 1.12-2.11; P = 0.01), serum lactate (HR 1.15, 95% CI 1.06-1.24; P = 0.03), global AGI grade (HR 1.65, 95% CI 1.28-2.12; P = 0.008), and APACHE II score (HR 1.04, 95% CI 1.02-1.06; P < 0.001) were independently associated with 60-day mortality. In a subgroup analysis of 402 patients with 7-day survival, in addition to clinical predictors and the AGI grade on the first day of ICU stay, FI within the first week of ICU stay had an independent and incremental prognostic value for 60-day mortality (χ2 = 41.9 vs. 52.2, P = 0.007). CONCLUSIONS: The AGI grading scheme is useful for identifying the severity of GI dysfunction and could be used as a predictor of impaired outcomes. In addition, these results support the hypothesis that persistent FI within the first week of ICU stay is an independent determinant for mortality. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR-OCS-13003824 . Registered on 29 September 2013.

Effectiveness of enteral feeding protocol on clinical outcomes in critically ill patients: a study protocol for before-and-after design.

INTRODUCTION: Enteral feed is an important component of nutritional therapy in critically ill patients and underfeeding has been associated with adverse outcomes. The article developed an enteral feeding protocol and planed a before-and-after comparative trial to explore whether implementation of enteral feeding protocol was able to improve clinical outcomes. METHODS AND ANALYSIS: The study will be conducted in intensive care units (ICUs) of ten tertiary care academic centers. Critically ill patients expected to stay in ICU for over 3 days and require enteral nutrition (EN) were potentially eligible. This is a before-and-after study comprising three phases: The first phase is the period without enteral feeding protocol; the second phase involves four-week training program, and the last phase is to perform the protocol in participating centers. We plan to enroll a total of 350 patients to provide an 80% power and 0.05 error rate to detect a 15% reduction of mortality. The primary outcome is 28-day mortality. ETHICS AND DISSEMINATION: Ethical approval to conduct the research has been obtained from all participating centers. Additionally, the results will be published in peer-reviewed journal. TRIAL REGISTRATION: The study was registered at International Standard Registered Clinical/soCial sTudy Number (ISRCTN) registry (ISRCTN10583582).

PCB-77 disturbs iron homeostasis through regulating hepcidin gene expression.

PCBs are a family of persistent environmental toxicants with a wide spectrum of toxic features, such as immunotoxicity, hepatoxicity, endocrine disruption effects, and oncogenic effects. To date, little has been done to investigate the potential influence of PCB exposure on iron metabolism. Deregulated iron would lead to either iron deficiency or iron excess, coupled with various diseases such as anemia or hemochromatosis. Iron metabolism is strictly governed by the hepcidin-ferroportin axis, and hepcidin is the key regulator that is secreted by hepatocytes. Here, we found that PCB-77 could go through plasma membrane and accumulate in hepatocytes. PCB-77 was demonstrated to suppress hepcidin expression in HepG2 and L-02 hepatocytes. Moreover, hepatic hepcidin was observed to be inhibited in mice upon administration of PCB-77. Due to reduced hepcidin concentration, serum iron content was increased, with a significant reduction of splenic iron content. Together, we deciphered the molecular mechanism responsible for PCB-conducted disturbance on iron homeostasis, i.e. through misregulating hepatic hepcidin expression.