The nasal microbiota is a potential diagnostic biomarker for sepsis in critical care units.

This study aimed to characterize the composition of intestinal and nasal microbiota in septic patients and identify potential microbial biomarkers for diagnosis. A total of 157 subjects, including 89 with sepsis, were enrolled from the affiliated hospital. Nasal swabs and fecal specimens were collected from septic and non-septic patients in the intensive care unit (ICU) and Department of Respiratory and Critical Care Medicine. DNA was extracted, and the V4 region of the 16S rRNA gene was amplified and sequenced using Illumina technology. Bioinformatics analysis, statistical processing, and machine learning techniques were employed to differentiate between septic and non-septic patients. The nasal microbiota of septic patients exhibited significantly lower community richness (P = 0.002) and distinct compositions (P = 0.001) compared to non-septic patients. Corynebacterium, Staphylococcus, Acinetobacter, and Pseudomonas were identified as enriched genera in the nasal microbiota of septic patients. The constructed machine learning model achieved an area under the curve (AUC) of 89.08, indicating its efficacy in differentiating septic and non-septic patients. Importantly, model validation demonstrated the effectiveness of the nasal microecological diagnosis prediction model with an AUC of 84.79, while the gut microecological diagnosis prediction model had poor predictive performance (AUC = 49.24). The nasal microbiota of ICU patients effectively distinguishes sepsis from non-septic cases and outperforms the gut microbiota. These findings have implications for the development of diagnostic strategies and advancements in critical care medicine.IMPORTANCEThe important clinical significance of this study is that it compared the intestinal and nasal microbiota of sepsis with non-sepsis patients and determined that the nasal microbiota is more effective than the intestinal microbiota in distinguishing patients with sepsis from those without sepsis, based on the difference in the lines of nasal specimens collected.

[Design and application of extracorporeal membrane oxygenation transport vehicle].

With the widespread application of extracorporeal membrane oxygenation (ECMO) technology, ECMO centers have been established in most regions of China, and the demand for ECMO transport is also increasing. Critically ill patients with ECMO carry many catheters. ECMO devices and accessories are cumbersome and numerous, requiring a large amount of manpower to assist in the transfer. At present, most of ECMO transport equipment are vertical carts provided by equipment suppliers, which cannot accommodate all ancillary equipment and are difficult to be loaded into ambulances for transportation. Therefore, critically ill patients face many risks if they need to be transported inter-hospital. A specific vehicle for ECMO patients was designed by the medical staff of the department of critical care medicine of Zhujiang Hospital of Southern Medical University, which integrates the ECMO host, oxygenator, centrifugal pump, portable ventilator, coagulation instrument, injection pump, monitor, oxygen cylinder, and etc., to greatly facilitate the transportionation. This invention obtained the National Utility Model Patent of China (ZL 2019 2 1201261.4). The new ECMO transport vehicle can facilitate the interhospital transport of critically ill patients, reduce the occurrence of accidents, shorten the transport time and reduce the number of transport personnel, and has a good clinical application value.

High-Fat Diet-Induced Fatty Liver Is Associated with Immunosuppressive Response during Sepsis in Mice.

High-fat diet-induced fatty liver is an indolent and chronic disease accompanied by immune dysfunction and metabolic disturbances involving numerous biological pathways. This study investigated how this abnormal metabolic disorder influences sepsis in mice. Mice were fed with normal chow (NC) or high-fat diet (HFD), and palmitic acid (PA) was used to treat hepatocytes to mimic fat accumulation in vitro. Lipopolysaccharide (LPS) was used to induce sepsis and related immune responses. Mice fed on a high-fat diet displayed higher mortality and more severe liver damage but compromised immunoreaction. The supernatant from PA-treated primary hepatocytes markedly diminished the inflammatory cytokine expression of macrophages after LPS stimulation, which showed a state of immunosuppression. Metabolomics analysis indicated the level of many key metabolites with possible roles in immunoreaction was altered in the HFD and PA groups compared with corresponding controls; specifically, ß-hydroxybutyric acid (BHB) showed an immunosuppressive effect on Raw264.7 cells during the LPS stimulation. Transcriptomic analysis suggested that several differential signaling pathways may be associated with the alteration of immune function between the NC and HFD groups, as well as in the in vitro model. Our study suggests that the consumption of HFD may alter the hepatic metabolic profile, and that certain metabolites may remold the immune system to immunosuppressive state in the context of sepsis.

PK/PD study of tigecycline in severely infected patients with continuous renal replacement therapy.

OBJECTIVE: The aim of this study was to analyze the pharmacokinetics/pharmacodynamics (PK/PD) of higher-dose tigecycline (100 mg q12h) in severely infected intensive care unit (ICU) patients receiving continuous renal replacement therapy (CRRT). MATERIALS AND METHODS: In this prospective single-center observational study, severely infected patients receiving intravenous tigecycline were enrolled. They were divided into a CRRT group (7 cases) and a non-CRRT group (9 cases). The blood samples and CRRT ultrafiltrate were collected. The drug concentration in each sample was determined by a HPLC-UV method. The pharmacokinetic parameters were simulated and calculated with DAS 2.0. The PK/PD parameters were evaluated according to published data. The registration number of this study is NCT02931526 in ClinicalTrials.gov. RESULTS: In the non-CRRT group, Cmax, Cmin, and AUC0-24 were 1.00 ± 0.66 µg×mL-1, 0.20 ± 0.12 µg×mL-1, and 22.12 ± 14.46 µg×h×mL-1, respectively. The clinical efficiency was 55.6%, and the bacterial clearance rate was 77.8%. In the CRRT group, Cmax, Cmin, and AUC0-24 were 0.96 ± 0.31 µg×mL-1, 0.22 ± 0.12 µg×mL-1, and 19.90 ± 8.14 µg×h×mL-1, respectively. The clinical efficiency was 28.6%, and the bacterial clearance rate was 28.6%. The individual differences of tigecycline plasma concentrations in our study were widely variable, and the differences of the two groups' PK/PD parameters had no statistical significance (p < 0.05). CONCLUSION: CRRT may have had little influence in tigecycline metabolism in our study, and therapeutic drug monitoring needs to be introduced for critically ill patients because of various pharmacokinetic parameters.

Continuous positive airway pressure improves respiratory mechanics and efficiency of neural drive in stable COPD: an exploratory study.

BACKGROUND: Continuous positive airway pressure (CPAP) is a major treatment strategy for severe chronic obstructive pulmonary disease (COPD), especially with respiratory failure. However, it remains inconclusive whether CPAP affects respiratory mechanics and neural drive in stable COPD patients without respiratory failure. METHODS: Twenty-two COPD patients without respiratory failure received CPAP starting from 4 to 10 cmH2O in 1 cmH2O increments. Respiratory pattern, end expiatory lung volume (EELV), dynamic PEEPi (PEEPidyn), airway resistance (Raw), pressure-time product of diaphragmatic pressure (PTPdi) and esophageal pressure (PTPeso), root mean square (RMS) of diaphragm electromyogram (EMGdi) and ratio of ventilation (Ve) to EMGdi (i.e., Ve/RMS) were measured before and at each level of continue positive airway pressure (CPAP). A subgroup analysis was performed between patients with and without inspiratory muscle weakness. RESULTS: Nineteen patients completed the treatment. The respiratory pattern improved significantly after CPAP. Raw, PTPdi, and Pdi decreased significantly. ΔEELV decreased at 4 cmH2O (P<0.05), but increased significantly at >8 cmH2O. PEEPidyn decreased from 2.18±0.98 to 1.37±0.55 cmH2O. RMS increased while Ve/RMS improved significantly after CPAP (P<0.05). Besides, CPAP could significantly improve respiratory mechanics in patients with inspiratory muscle weakness. CONCLUSIONS: CPAP improves respiratory pattern, PEEPi, Raw, work of breathing and efficiency of neural drive in COPD patients without respiratory failure, but easily increases dynamic pulmonary hyperinflation. These effects on respiratory mechanics are significant in patients with inspiratory muscle weakness.

Combined Treatment With Hydrocortisone, Vitamin C, and Thiamine for Sepsis and Septic Shock: A Randomized Controlled Trial.

BACKGROUND: Whether hydrocortisone, vitamin C, and thiamine treatment can reduce the mortality of patients with sepsis is controversial. RESEARCH QUESTION: To evaluate the efficacy and safety of hydrocortisone, vitamin C, and thiamine combination treatment for patients with sepsis or septic shock (HYVCTTSSS). STUDY DESIGN AND METHODS: This single-blind, randomized controlled trial evaluated treatment with hydrocortisone (50 mg every 6 h for 7 days), vitamin C (1.5 g every 6 h for 4 days), and thiamine (200 mg every 12 h for 4 days) vs placebo (normal saline) in patients with sepsis. The intention-to-treat analysis was used. Primary outcome was 28-day all-cause mortality, and secondary outcomes were organ protection, procalcitonin reduction, and adverse events related to hydrocortisone, vitamin C, and thiamine. RESULTS: Eighty patients were randomized to receive combination treatment (n = 40) or normal saline (n = 40). No difference in 28-day all-cause mortality was observed (27.5% vs 35%, respectively; P = .47); however, treatment was associated with a significant improvement of 72-h change in Sequential Organ Failure Assessment score (P = .02). In adverse events analysis, the treatment group exhibited more incidents of hypernatremia (P = .005). In prespecified subgroup analysis, patients of the treatment subgroup diagnosed with sepsis within 48 h showed lower mortality than those in the control subgroup (P = .02). The study was terminated after the midterm analysis. INTERPRETATION: Among patients with sepsis or septic shock, the combination of hydrocortisone, vitamin C, and thiamine did not reduce mortality compared with placebo. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03258684; URL: www.clinicaltrials.gov.

Adjunctive granisetron therapy in patients with sepsis or septic shock (GRANTISS): Study protocol for a randomized controlled trial.

INTRODUCTION: The incidence, mortality, and treatment costs of sepsis are high and, thus, present a major challenge for critical care medicine. Our previous studies suggest that intestinal metabolite granisetron has a potential therapeutic effect on sepsis. Granisetron is a clinically widely used antiemetic, which is safe, inexpensive, and reliable. However, its value in the treatment of sepsis remains unclear. This study aims to explore the efficacy and safety of granisetron in the treatment of sepsis. METHODS AND ANALYSIS: A single-center, single-blind, randomized, controlled clinical trial will be conducted on 154 patients with sepsis. Patients who meet sepsis 3.0 diagnostic criteria, aged ≥18 and ≤80 years, with PCT ≥ 2 ng/mL will be recruited. Patients will be randomized to receive intravenous granisetron 3 mg every 8 hours (n = 77) or an equal volume of normal saline (n = 77) for a treatment period of 4 days or to ICU discharge. The primary outcome is 28-day all-cause mortality. Secondary outcome measures include requirements for organ function support, changes of organ function, changes in infection biomarkers, changes in inflammatory and immune biomarkers, and the proportion of new organ failure. Adverse events and serious adverse events also will be observed closely. ETHICS AND DISSEMINATION: The study was approved by the Clinical Ethics Committee of Zhujiang Hospital of Southern Medical University (2018-ZZJHZX-009). The trial results will be disseminated at national and international conferences and through peer-reviewed journal. TRIAL REGISTRATION: NCT03924518.URL: www.clinicaltrials.gov. PROTOCOL DATE: 1 May 2019. version 2.1.

Septic patients in the intensive care unit present different nasal microbiotas.

AIM: The primary objective of this study was to evaluate correlations among mortality, intensive care unit (ICU) length of stay and airway microbiotas in septic patients. MATERIALS & METHODS: A deep-sequencing analysis of the 16S rRNA gene V4 region was performed. RESULTS: The nasal microbiota in septic patients was dominated by three nasal bacterial types (Corynebacterium, Staphylococcus and Acinetobacter). The Acinetobacter type was associated with the lowest diversity and longest length of stay (median: 9 days), and the Corynebacterium type was associated with the shortest length of stay. We found that the Acinetobacter type in the >9-day group was associated with the highest mortality (33%). CONCLUSION: Septic patients have three nasal microbiota types, and the nasal microbiota is related to the length of stay and mortality.

Applying Regional Citrate Anticoagulation in Continuous Renal Replacement Therapy for Acute Kidney Injury Patients with Acute Liver Dysfunction: a Retrospective Observational Study.

BACKGROUND/AIMS: Continuous renal replacement therapy (CRRT) is a treatment for acute kidney injury (AKI) patients. It has become a controversy about whether patients with liver dysfunction should perform CRRT with regional citrate anticoagulation (RCA). METHODS: This retrospective observational study enrolled 145 AKI patients (275 CRRT sessions) who received CRRT with RCA and had no history of chronic liver disease. Circuit survival time, blood pressure, trans-membrane pressure (TMP), acid-base and electrolyte status were recorded and analyzed. The severity of liver dysfunction was determined by total bilirubin (TBil) and international normalized ratio (INR), while the accumulation degree of citrates was quantified by total/ ionized calcium (tCa/iCa) raito. RESULTS: Our results showed that there was no correlation of tCa/iCa ratio with TBil or INR. And tCa/iCa ratio was not related to the disturbances of pH, lactates, sodium, magnesium, blood pressure or TMP despite that high tCa/iCa ratios might be related to the decrease of circuit survival time. TBil did not correlate with the above indexes, except for lactates levels. INR did not correlate with the above indexes except for lactates levels and blood pressure. In addition, neither was TBil, INR, nor tCa/iCa ratio, related with fatal outcomes (22.76% of the patients). CONCLUSION: The present study demonstrated that, with proper monitoring and adjustment of citrates and calcium infusion, applying RCA in CRRT is reasonably safe for AKI patients with acute liver dysfunction, as long as circuit time stays below roughly 50 hours.

Procalcitonin levels in patients with positive blood culture, positive body fluid culture, sepsis, and severe sepsis: a cross-sectional study.

BACKGROUND: Numerous investigations on procalcitonin (PCT) have been carried out, although few with large sample size. To deal with the complexity of sepsis, an understanding of PCT in heterogeneous clinical conditions is required. METHODS: Hospitalized patients aged 10-79 years were included in this retrospective and cross-sectional study. PCT tests were assayed within 2 days of blood culture. RESULTS: A total of 2952 cases (from 2538 patients) were enrolled in this study, including 440 cases in the 'positive BC' group, 123 cases in the 'positive body fluid culture' group, and 2389 cases in the 'negative all culture' group. Median PCT values were 4.53 ng/ml, 2.95 ng/ml, and 0.49 ng/ml, respectively. Median PCT values in the gram-negative BC group and gram-positive BC group, respectively, were 6.99 ng/ml and 2.96 ng/ml. Median PCT values in the 'positive hydrothorax culture' group, 'positive ascites culture' group, 'positive bile culture' group, and 'positive cerebrospinal fluid culture' group, respectively, were 1.39 ng/ml, 8.32 ng/ml, 5.98 ng/ml, and 0.46 ng/ml. In all, 357 cases were classified into the 'sepsis' group, 150 of them were classified into the 'severe sepsis' group. Median PCT values were 5.63 ng/ml and 11.06 ng/ml, respectively. CONCLUSIONS: PCT could be used in clinical algorithms to diagnose positive infections and sepsis. Different PCT levels could be related to different kinds of microbemia, different infection sites, and differing severity of sepsis.

[Intensive hemoperfusion and long-term hemofiltration for treatment of paraquat poisoning: a case report].

OBJECTIVE: A 20-year-old male patient was admitted in our department 14 h after paraquat poisoning at the dose of about 50 mL. The patient underwent intensive hemoperfusion for 2 h (3 times a day) for 9 consecutive days and received continuous renal replacement therapy (CRRT) in the mode of continuous veno-venous hemofiltration (CVVH) for 10 consecutive days in addition to routine medications. The biochemical indexes were monitored during the therapy. After the treatment, paraquat concentrations in the blood and urine were decreased, and the patient's urine volume (UV) increased, serum creatinine (Cr) level decreased, and the oxygenation index became normal. Dynamic CT scan showed no obvious pulmonary fibrosis. The patient was followed up for 6 months after discharge and no complaint of discomforts was reported. This case suggests that early intensive hemoperfusion and long-term CVVH may help improve the prognosis after paraquat poisoning.

[Role of central venous pressure, global end diastolic volume index and extravascular lung water index in evaluating fluid resuscitation in patients with septic shock].

OBJECTIVE: To explore the role of central venous pressure (CVP), global end diastolic volume index (GEDI) and extravascular lung water index (ELWI) monitoring in patients with septic shock during fluid resuscitation by pulse induced continuous cardiac output (PiCCO) test. METHODS: Forty-six patients with severe sepsis and septic shock were enrolled in this study. Hemodynamic monitoring was performed during fluid resuscitation and the data including CVP, GEDI and ELWI were collected to analyze their relationship and the clinical values. RESULTS: In patients with septic shock, CVP showed a weak linear correlation with GEDI during fluid resuscitation (r=0.137, P=0.009). In the subgroups stratified with CVP cut-off values of 8 mmHg and 12 mmHg, the correlation coefficient between CVP and GEDI was 0.149 (P=0.029) in CVP<8 mmHg group, 0.075 (P=0.462) in 8 mmHg ≤ CVP ≤ 12 mmHg group, and 0.049 (P=0.726) in CVP>12 mmHg group. In the total of 367 data groups obtained, CVP showed no linear correlation with ELWI (r=0.040, P=0.445). In the CVP subgroups, CVP and ELWI were weakly correlated in CVP<8 mmHg group (r=0.221, P=0.001), but they showed no correlations in 8 mmH g≤ CVP ≤ 12 mmHg and CVP>12 mmHg groups (r=-0.047, P=0.646; r=0.042, P=0.765). CONCLUSION: There is no significant linear correlation between CVP and GEDI or between CVP and ELWI in patients with septic shock. CVP can not reflect the circulatory blood volume or the degree of pulmonary edema.

[Organ-protective effect of continuous renal replacement therapy in a patient with severe polymyositis and dermatomyositis].

OBJECTIVE: A patient with skin rash, skin denudation, anuria, general dropsy and dyspnea for unknown etiology underwent continuous renal replacement therapy (CRRT) for 3 consecutive days. The biochemical indexes were monitored during the therapy and biopsy was performed on the right thigh. Pathological examination of the biopsy sample established the diagnosis of polymyositis(PM) and dermatomyositis(DM). After the start of CRRT, the patient's heart, liver, kidney and lung injuries showed obvious improvement, and the urine volume (UV) increased and serum creatinine (Cr), urea, total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) levels all decreased promptly. The patient showed progressive improvement of the physiological condition even after CRRT, and was discharged 10 days later. This case suggests the efficacy of CRRT in the management of severe PM/DM and its value as a good option for treatment of severe autoimmune disease, especially systemic inflammatory response syndrome.