Identification of polymorphic markers for germplasm conservation of three precious Chinese palace goldfish using whole-genome sequencing.

China was the first country in the world to breed goldfish and has generated many unique goldfish varieties, including the most aristocratic Chinese palace goldfish. Due to the lack of scientific research on Chinese palace goldfish, their selection and breeding are mainly carried out through traditional hybridization, leading to serious inbreeding and the degradation of germplasm resources. To this end, whole-genome resequencing was performed to understand the genetic variation among three different varieties (eggpompons, goosehead, and tigerhead) from nine core conserved populations in China. A total of 15 polymorphic SSRs were developed for population genetics, and all tested populations were considered moderately polymorphic with an average polymorphism information content value of 0.4943. Genetic diversity in different varieties showed that all conserved populations were well protected with the potential for continued exploitation. This study provides reliable molecular tools and a basis for designing conservation and management programs in Chinese palace goldfish.

Bioresponsive nanocomplex integrating cancer-associated fibroblast deactivation and immunogenic chemotherapy for rebuilding immune-excluded tumors.

Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC). The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Due to the modification with hyaluronic acid, the GNC preferentially accumulated in the tumor periphery and responsively released cargos, mitigating the tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.

Association of Monocyte-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratios With Persistent Critical Illness in Patients With Severe Trauma.

BACKGROUND: Neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio are reported to reflect the inflammation and immune status in critically ill patients, but their role in severe trauma patients with persistent critical illness remains to be elucidated. OBJECTIVE: We aimed to evaluate the relationship of neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio with persistent critical illness in severe trauma patients. METHODS: In a single-center retrospective cohort study, persistent critical illness was defined as intensive care unit length of stay of more than 10 days. Monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were computed individually and categorized into 3 tertiles. Logistic regression analysis was used to assess the relationship of monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with persistent critical illness. Receiver operating characteristic curves and the Youden index were used to evaluate the discriminatory threshold of persistent critical illness. RESULTS: A total of 851 eligible patients were enrolled in the study: 328 patients with persistent critical illness and 523 without. The median levels of maximum neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio during intensive care unit stay were all higher in patients with persistent critical illness than in those without (11.46 vs. 9.13, p < .001 and 0.62 vs. 0.46, p < .001). Multivariate analysis revealed that the second (≥0.385, <0.693) and third (≥0.693) maximum monocyte-to-lymphocyte ratio tertiles were significantly associated with persistent critical illness after adjusting for confounding factors (odds ratio: 1.89, 95% confidence interval: 1.10-3.26, p = .021 and odds ratio 2.69, 95% confidence interval: 1.44-5.02, p = .002, respectively), whereas maximum neutrophil-to-lymphocyte ratio was not significantly correlated with persistent critical illness. The area under the curve for the maximum monocyte-to-lymphocyte ratio was 0.63 (95% confidence interval: 0.59-0.67), and the optimal cutoff was 0.65 for persistent critical illness. CONCLUSION: A high maximum monocyte-to-lymphocyte ratio during intensive care unit stay was independently related to persistent critical illness following severe trauma, although with limited sensitivity and specificity.

Temperature Variability Does Not Attenuate the Beneficial Effects of Therapeutic Hypothermia on Cellular Apoptosis and Endoplasmic Reticulum Stress in the Cerebral Cortex of a Swine Cardiac Arrest Model.

BACKGROUND: Endoplasmic reticulum stress (ERS) plays a vital role in mediating apoptosis in the brain following cardiac arrest (CA). Studies have shown that therapeutic hypothermia (TH) provides neuroprotection through anti-apoptosis; however, the effects of temperature variability in TH on the brain remain unclear. In this study, we investigated the different effects of temperature variability through extracorporeal membrane oxygenation on apoptosis and ERS in the brain following CA. METHODS: Eighteen male domestic pigs underwent 6-min duration of no-flow induced by ventricular fibrillation. Extracorporeal cardiopulmonary resuscitation was then performed, and the return of spontaneous circulation (ROSC) was achieved. The animals were randomly assigned to the following groups: normothermia, non-temperature variability, and temperature variability. TH (core temperature, 33-35 °C) was maintained for 24 h post-ROSC, and the animals were rewarmed for 8 h. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry for Bax and Bcl-2 transcripts and proteins, respectively, were used to investigate apoptosis in the cerebral cortex. Expression levels of the ERS molecules, GRP78 and CHOP, were also detected by qRT-PCR, and cellular morphology was evaluated using transmission electron microscopy. RESULTS: qRT-PCR and immunohistochemistry results revealed that TH significantly increased the expression levels of Bcl-2 and GRP78 and decreased that of Bax and CHOP than under normothermia conditions. Compared to the non-temperature variability group, temperature variability did not decrease the expression levels of Bcl-2 and GRP78 and not increase the levels of Bax and CHOP. Endoplasmic reticulum ultrastructural changes were significantly improved under TH. No statistical difference was observed between the temperature variability and non-temperature variability groups. CONCLUSION: TH can reduce neuronal apoptosis by ERS, while temperature variability does not attenuate this beneficial effect.

Clinical Features of Fatal Pandemic Influenza A/H1N1 Infection Complicated by Invasive Pulmonary Fungal Infection.

BACKGROUND: Severe pneumonia caused by influenza virus infection can be secondary to invasive pulmonary fungal (IPF) infection. OBJECTIVES: This study aimed to summarize the incidence of IPF infection secondary to influenza virus infection and further explore its etiologic mechanism and high-risk factors. METHODS: All adult patients with confirmed influenza A (H1N1) virus infection admitted to the intensive care units (ICUs) of Nanjing Drum Hospital from November 2017 to March 2018 were retrospectively selected. The differences in baseline factors, risk factors, immune function and outcome parameters were studied between patients with and without IPF. RESULTS: Of the 19 critically ill patients with H1N1 infection, 11 (57.9%) developed IPF infection after 7 days of ICU admission. Two patients had proven and nine probable IPF infection. A difference in human leukocyte antigen-DR isotype (△HLA-DR; day 7-day 1) was found between the two groups. △HLA-DR (day 7-day 1) was higher in patients with no IPF infection than in those with IPF infection [(14.52 ± 14.21)% vs ( - 11.74 ± 20.22)%, P = 0.019]. The decline in HLA-DR indicated impaired immune function secondary to fungal infection in patients with H1N1 infection. CONCLUSIONS: IPF infection was diagnosed in 57.9% of critically ill patients with H1N1 virus infection after a median of 7 days following ICU admission. A continuous decline in immune function could lead to the development of IPF infections. Dynamic monitoring of immune function may help in the early detection of IPF infection.

Immune cell-derived extracellular vesicles for precision therapy of inflammatory-related diseases.

Inflammation-related diseases impose a significant global health burden, necessitating urgent exploration of novel treatment modalities for improved clinical outcomes. We begin by discussing the limitations of conventional approaches and underscore the pivotal involvement of immune cells in the inflammatory process. Amidst the rapid growth of immunology, the therapeutic potential of immune cell-derived extracellular vesicles (EVs) has garnered substantial attention due to their capacity to modulate inflammatory response. We provide an in-depth examination of immune cell-derived EVs, delineating their promising roles across diverse disease conditions in both preclinical and clinical settings. Additionally, to direct the development of the next-generation drug delivery systems, we comprehensively investigate the engineered EVs on their advanced isolation methods, cargo loading techniques, and innovative engineering strategies. This review ends with a focus on the prevailing challenges and considerations regarding the clinical translation of EVs in future, emphasizing the need of standardized characterization and scalable production processes. Ultimately, immune cell-derived EVs represent a cutting-edge therapeutic approach and delivery platform, holding immense promise in precision medicine.

A novel mini-invasive step-up approach for the treatment of severe acute pancreatitis with extensive infected necrosis: A single center case series study.

RATIONALE: Complete removal of necrosis is critical for treating patients with severe acute pancreatitis (SAP) presenting infection of pancreatic necrosis (IPN). Frequently used mini-invasive methods include the surgical step-up approach suitable for necrosis extending laterally, whereas the endoscopic step-up approach is suitable for medial necrosis. However, in patients with extensive IPN, either approach alone usually has limited treatment effects. PATIENT CONCERNS: We describe a case series of combined mini-invasive step-up approach for treating extensive IPN. DIAGNOSES: Patients were diagnosed with SAP and had extensive IPN. INTERVENTIONS: Seven patients with SAP and extensive IPN were enrolled. All patients underwent a combined step-up approach comprising 4 steps: percutaneous catheter drainage, continuous negative pressure irrigation (CNPI), percutaneous endoscopic necrosectomy (PEN), and transgastric necrosectomy (TN). OUTCOMES: The median interval from symptom onset to percutaneous catheter drainage and CNPI was 11 days (range, 6-14) and 18 days (range, 14-26), and the median CNPI duration was 84 days (range, 54-116). The median interval from the onset of symptoms to PEN and TN was 36 days (range, 23-42) and 41 days (range, 34-48), respectively, and the median number of procedures was 2 (range, 1-2) for PEN and 3 (range, 2-4) for TN. Only a minor case of abdominal bleeding and a pancreatic-cutaneous fistula were reported, both resolved after conservative treatment. The median length of stay in the intensive care unit was 111 days (range, 73-133); all patients survived. LESSONS: This mini-invasive step-up approach shows promising clinical effects and is relatively safe in critically ill patients with extensive IPN and high-risk surgical intervention.

Acute gastrointestinal injury and altered gut microbiota are related to sepsis-induced cholestasis in patients with intra-abdominal infection: a retrospective and prospective observational study.

Background: Sepsis-associated liver dysfunction (SALD) has high incidence and mortality in patients with intra-abdominal infection (IAI). The associations between acute gastrointestinal injury (AGI), gut microbiota, and SALD were evaluated in patients with IAI. Methods: A retrospective study was conducted to assess the relationship between AGI and SALD in patients with IAI. Patients were divided into non-SALD and sepsis-induced cholestasis (SIC) groups, which is a subtype of SALD. SIC was defined as total bilirubin >2 mg/dL. AGI incidences between the two groups were compared using Chi-square test. Subsequently, a prospective study was conducted to investigate the gut microbiota differences between patients without SALD and those with SIC. Fecal samples were collected on days 1, 3, and 7 after admission to analyze changes in gut microbiota using 16S ribosomal ribonucleic acid sequencing. Results: One hundred thirty-four patients with IAI were included retrospectively, with 77 SALD and 57 non-SALD cases. Among patients with SALD, 71 were diagnosed with SIC. Patients with SIC had a higher incidence of AGI compared to those without SALD (28.07% vs. 56.34%, p < 0.05), and a severity-dependent relationship was found between AGI grade and SIC occurrence. Subsequently, 20 patients with IAI were recruited prospectively, with 10 patients each assigned to the non-SALD and SIC groups. Patients with SIC had a more severe gut microbiota disorder on day 7 than those without SALD, including lower microbiota diversities, decreased abundance of Firmicutes and Bacteroidetes, and increased abundance of Proteobacteria and Actinobacteria at the phylum level. Furthermore, Burkholderia - Caballeronia - Paraburkholderia and Delftia, the two most abundant genera, were significantly higher in the SIC group than in the non-SALD group. Functional prediction analysis showed that the top three KEGG pathways were ribosome, pyrimidine metabolism, and the two-component system. During the first week, the abundance of Proteobacteria decreased significantly, whereas Cyanobacteria increased in the non-SALD group; however, the phyla taxa did not change significantly in the SIC group. Conclusion: There exists a severity-dependent relationship between AGI grade and SIC occurrence in adult patients with IAI. A severe gut microbiota disorder was discovered in SIC during the first week of the intensive care unit stay.

Corrigendum: Acute gastrointestinal injury and altered gut microbiota are related to sepsis-induced cholestasis in patients with intra-abdominal infection: a retrospective and prospective observational study.

[This corrects the article DOI: 10.3389/fmed.2023.1144786.].

Relationship between serum sodium level and sepsis-induced coagulopathy.

Purpose: A discussion about the correlation between the level of serum sodium and sepsis-induced coagulopathy (SIC). Materials and methods: A retrospective analysis was conducted on sepsis patients who were admitted to the Intensive Care Unit (ICU) of Nanjing Drum Tower Hospital from January 2021 to December 2022. Based on the presence of coagulation disorders, the patients were divided into two groups: sepsis-induced coagulopathy (SIC) and non-sepsis-induced coagulopathy (non-SIC) groups. We recorded demographic characteristics and laboratory indicators at the time of ICU admission, and analyzed relationship between serum sodium level and SIC. Results: One hundred and twenty-five patients with sepsis were enrolled, among which, the SIC and the non-SIC groups included 62 and 63 patients, respectively. Compared to patients in the non-SIC group, the level of serum sodium of those in the SIC was significantly higher (p < 0.001). Multi-factor logistic regression showed serum sodium level was independently associated with SIC (or = 1.127, p = 0.001). Pearson's correlation analysis indicated that the higher the serum sodium level, the significantly higher the SIC score was (r = 0.373, p < 0.001). Additionally, the mortality rate of patients with sepsis in the ICU were significantly correlated with increased serum sodium levels (p = 0.014). Conclusion: An increase in serum sodium level was independently associated with an increased occurrence of SIC and also associated with the poor prognosis for patients with sepsis.

Clinical Characteristics and Immune Status of Patients with Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel infectious disease caused by bunya virus. The purpose of this study was to investigate the clinical characteristics of SFTS patients and their virus-related immune disorders in vivo. Patients with SFTS admitted to Nanjing Drum Tower Hospital from 2017 to 2020 were retrospectively analyzed, and divided into survival group and death group according to the 28-day survival. Clinical characteristics and laboratory examination results of SFTS patients were recorded, and dynamic changes of immune function and inflammatory factors were statistically analyzed. Prolonged activated prothrombin time (APTT) (p = 0.001), high viral load (p = 0.001), and elevated human leukocyte antigen DR (HLA-DR) level (p = 0.002) were independent prognostic risk factors for SFTS patients. Compared to the survival group, the nonsurvival group was more prone to hemorrhagic and neurological symptoms (p < 0.05). Natural kill (NK) cell count, interleukin-10, interferon-α, and tumor necrosis factor-α scores in the nonsurvival group continued to increase after admission, while CD3+ T, CD4+ T, and CD8+ T cell counts continued to decrease. CD3+ T lymphocyte count was negatively correlated with viral load (R = 0.3883, p < 0.001), CD4+ T lymphocyte count was negatively correlated with viral load (R = 0.28933, p < 0.001), CD8+ T lymphocyte count was negatively correlated with viral load (R = 0.781, p < 0.001), and HLA-DR was positively correlated with viral load (R = 0.489, p < 0.001). High viral load, prolonged APTT time, and elevated HLA-DR level are independent prognostic risk factors for SFTS patients. The T lymphocyte subsets of SFTS patients continue to decrease after infection, and the number of T lymphocyte subsets can reflect the severity of the disease.

Massive pulmonary haemorrhage due to severe trauma treated with repeated alveolar lavage combined with extracorporeal membrane oxygenation: A case report.

BACKGROUND: Massive pulmonary haemorrhage can spoil the entire lung and block the airway in a short period of time due to severe bleeding, which quickly leads to death. Alveolar lavage is an effective method for haemostasis and airway maintenance. However, patients often cannot tolerate alveolar lavage due to severe hypoxia. We used extracorporeal membrane oxygenation (ECMO) to overcome this limitation in a patient with massive pulmonary haemorrhage due to severe trauma and succeeded in saving the life by repeated alveolar lavage. CASE SUMMARY: A 22-year-old man sustained multiple injuries in a motor vehicle accident and was transferred to our emergency department. On admission, he had a slight cough and a small amount of bloody sputum; computed tomography revealed multiple fractures and mild pulmonary contusion. At 37 h after admission, he developed severe chest tightness, chest pain, dizziness and haemoptysis. His oxygen saturation was 68%. Emergency endotracheal intubation was performed, and a large amount of bloody sputum was suctioned. After transfer to the intensive care unit, he developed refractory hypoxemia and heparin-free venovenous ECMO was initiated. Fibreoptic bronchoscopy revealed diffuse and profuse blood in all bronchopulmonary segment. Bleeding was observed in the trachea and right bronchus, and repeated alveolar lavage was performed. On day 3, the patient's haemoptysis ceased, and ECMO support was terminated 10 d later. Tracheostomy was performed on day 15, and the patient was weaned from the ventilator on day 21. CONCLUSION: Alveolar lavage combined with ECMO can control bleeding in trauma-induced massive pulmonary haemorrhage, is safe and can be performed bedside.

[Analysis of risk factors of polymyxin B-associated acute kidney injury in intensive care unit patients with severe infection].

OBJECTIVE: To investigate the incidence and risk factors of polymyxin B-associated acute kidney injury (AKI) in patients with severe infections caused by extensive drug resistance Gram negative bacteria (XDR-GNB) in intensive care unit (ICU). METHODS: A retrospective study of adult patients with severe infection who received polymyxin B for more than 3 days in the department of critical care medicine of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from April 1st 2018 to January 31st 2020 were performed. AKI was diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The baseline data, indicators during treatment period and prognostic factors were compared between AKI group and non-AKI group. Factors with statistically significant difference in univariate analysis and important clinical factors were included in the Logistic regression model to analyze the risk factors of AKI. RESULTS: Seventy-two patients were treated with polymyxin B for more than 3 days. Forty-nine patients were finally enrolled, with 32 patients developing polymyxin B-associated AKI, and the incidence was 44.4%. The baseline data was balanced in AKI group and non-AKI group, and there was no significant difference in the prognosis [death or discharge without medial order (cases): 14 vs. 6, discharged for improvement (cases): 18 vs. 11, χ2 = 0.329, P = 0.566]. Polymyxin B-associated AKI occurred from 1 day to 14 days after treatment, with an average of (6.8±3.8) days. Among the 32 AKI patients, 2 cases were lost to follow up after discharge, while renal function recovered in 18 cases and unrecovered in 12 cases. The prognosis of patients without recovery of renal function was significantly worse than that of patients with renal function recovery [death or discharge without medial order (cases): 12 vs. 2, discharged for improvement (cases): 0 vs. 16, P = 0.000]. Single factor analysis showed that daily dosage of polymyxin B in AKI group was higher than that in non-AKI group (mg: 151.6±23.7 vs. 132.4±30.3), numbers of patients with daily polymyxin B dose ≥ 150 mg, using vasoactive drugs, or severe hypoalbuminemia (albumin ≤ 25 g/L) were higher than those in non-AKI group (cases: 29 vs. 10, 18 vs. 4, 9 vs. 0), with statistically significant differences (all P < 0.05). Multivariate Logistic regression analysis showed that daily dosage of polymyxin B ≥ 150 mg and use of vasoactive drugs were independent risk factors for polymyxin B-associated AKI [odds ratio (OR) = 37.466, 95% confidence interval (95%CI) was 2.676-524.586, P = 0.007; OR = 22.960, 95%CI was 1.710-308.235, P = 0.018]. CONCLUSIONS: Comparing with non-AKI patients, more patients with polymyxin B-associated AKI had severe hypoalbuminemia, and the probability of using vasoactive drugs and the daily dose of polymyxin B were higher than non-AKI patients. Daily dose of polymyxin B ≥ 150 mg and using vasoactive drugs were independent risk factors for polymyxin B-associated AKI.

Fibroblast activation protein-α-adaptive micelles deliver anti-cancer drugs and reprogram stroma fibrosis.

Cancer-associated fibroblasts (CAFs) are the majority cell population of tumor stroma, and they not only play important roles in tumor growth and metastasis, but they also form a protective physical barrier for cancer cells. Herein, we designed a fibroblast activation protein-α (FAP-α)-adaptive polymeric micelle based on hyaluronic acid and curcumin conjugates. The polymeric micelle is composed of a CD44-targeting shell and a FAP-α-cleavable polyethylene glycol (PEG) coating. When FAP-α is encountered on the surface of CAFs in the tumor microenvironment, the PEG layer is released, hyaluronic acid is recovered on the surface of nanoparticles, and the nanoparticles effectively inhibit the growth of tumor cells and CAFs through CD44-mediated endocytosis. The FAP-α-adaptive polymeric micelle exhibited potent anti-cancer efficacy by enhancing CAF apoptosis and reducing collagen in tumor tissues. Collectively, FAP-α-adaptive nanoparticles may be a promising method for antitumor anticancer treatments via reprogramming of stroma fibrosis.

Association between HLA-DR Expression and Multidrug-resistant Infection in Patients with Severe Acute Pancreatitis.

Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP). This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP. A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study. The percentages of CD4+, CD8+, natural killer (NK), and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14, and 28 after admission were determined by flow cytometry. Eighteen patients presented with the symptoms of infection. Among them, 55.6% patients (10/18) developed MDR infection. The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii. The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections. In patients without infection, the HLA-DR percentage was maintained at a high level throughout the 28 days. Compared to the patients without any infection, the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28. In patients with MDR infection, the HLA-DR percentage remained below normal levels at all-time points. It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.

[Clinical study of vancomycin for appropriate dosing in severe infective patients with augmented renal clearance].

OBJECTIVE: To explore the impact of augmented renal clearance (ARC) on vancomycin pharmacokinetic target attainment in severe infective patients, and to analyze the initial dose of vancomycin based on the measured 12-hour urinary creatinine clearance (12 h-CLCR). METHODS: A retrospective observational study was conducted. The patients with severe infection, who receiving vancomycin empiric or targeted therapy, admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from February 2013 to December 2017 were enrolled. All patients were treated with vancomycin intravenously by intermittent bolus every 6-12 hours. After four or five doses, blood samples were drawn before the next dosage for serum trough vancomycin concentration (Cmin), and target concentration was defined between 15 mg/L and 20 mg/L. The urine creatinine (UCr) was measured, and CLCR was calculated. ARC was defined as 12 h-CLCR > 130 mL×min-1×1.73 m-2. According to 12 h-CLCR before treatment, the patients were divided into ARC group and non-ARC group. The basic renal function of the patients was monitored, and the dosage of vancomycin and the dosage of vancomycin when the blood concentration reached the target were recorded. The correlations between 12 h-CLCR and the dosage of vancomycin when the blood concentration reached the target as well as the blood concentration of vancomycin were analyzed by Spearman correlation analysis. Dosage stratification analysis was carried out according to different 12 h-CLCR. The predictive value of 12 h-CLCR for vancomycin dosage when the blood concentration reached the target was evaluated by using the receiver operator characteristic curve (ROC). RESULTS: Data was provided from a total of 135 patients with severe infection, in which 102 patients met the inclusion criteria. The patients with vancomycin treatment duration less than 72 hours, chronic kidney disease V phase, vancomycin treatment before entering ICU and those with incomplete data were excluded. The mean 12 h-CLCR was (114.31±73.38) mL×min-1×1.73 m-2. The 12 h-CLCR in ARC group (n = 44, 43.14%) was significantly higher than that in non-ARC group (n = 58, 56.86%) (mL×min-1×1.73 m-2: 179.37±59.04 vs. 65.95±35.71, P < 0.01). Target Cmin of vancomycin was achieved in 50.98% of patients (52/102), the target rate in ARC group was significantly lower than that in non-ARC group [29.55% (13/44) vs. 67.24% (39/58), P < 0.01], and the Cmin of vancomycin in ARC group was significantly lower than that in non-ARC group (mg/L: 10.98±6.09 vs. 14.67±6.20, P < 0.01). Spearman correlation analysis showed that there was a significantly negative correlation between 12 h-CLCR and initial Cmin of vancomycin (n = 102, r = -0.436, P < 0.001), but a positive correlation was found between 12 h-CLCR and vancomycin dosage when the blood concentration reached the target (n = 52, r = 0.275, P = 0.048). The patients with ARC need higher dosage for blood concentration reaching the target than those without ARC (mg×kg-1×d-1: 42.47±13.17 vs. 31.53±14.43, P < 0.01). According to 12 h-CLCR, the patients with initial treatment reaching the target were divided into five subgroups, < 40, 40-70, 71-100, 101-130 and > 130 mL×min-1×1.73 m-2. The results showed that as 12 h-CLCR increased, the attained dosage of vancomycin was also increased correspondingly. ROC curve analysis showed that when 12 h-CLCR≥69.83 mL×min-1×1.73 m-2, the attained dose of vancomycin when the blood concentration reached the target was greater than conventional dosage of 30 mg×kg-1×d-1. CONCLUSIONS: Patients with ARC have low concentrations of vancomycin and often fail to achieve therapeutic target. The initial dose of vancomycin can be selected according to 12 h-CLCR, the higher the 12 h-CLCR, the more the dosage of vancomycin is. When 12 h-CLCR is greater than or equal to 69.83 mL×min-1×1.73 m-2, the dosage of vancomycin should be higher than the conventional dosage.

[Analysis of clinical characteristics of bloodstream infection in patients with immune function inhibition].

OBJECTIVE: To analyze the clinical characteristics of bloodstream infection in patients with immune function inhibition. METHODS: A retrospective analysis was conducted. 234 patients with bloodstream infection admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 1st in 2015 to December 31st in 2017 were enrolled. According to the immune function on the day of bloodstream infection, they were divided into normal immune function group [human leukocyte antigen DR (HLA-DR) > 30%, n = 144] and immunosuppression group (HLA-DR ≤ 30%, n = 90). The gender, age, primary disease, complication, acute physiology and chronic health evaluation II (APACHE II) with 24 hours after ICU admission, sequential organ failure assessment (SOFA) score, etiology, infection parameters on the day of bloodstream infection [peak temperature, white blood count (WBC), neutrophils ratio, procalcitonin (PCT), and C-reactive protein (CRP)] and prognosis parameters (bacterial clearance time, the length of ICU and hospital stay, 28-day mortality) between the two groups were analyzed. RESULTS: 234 patients were enrolled in the final analysis, including 132 males and 102 females, with an average age of (60.5±18.4) years old. Severe pneumonia and abdominal infection were the main causes of primary diseases. There was no significant difference in gender composition, age, APACHE II, SOFA score, other complications and primary morbidity between the two groups except that the proportion of malignant tumors in the immunosuppressive group was higher than that in the normal immune function group [43.3% (39/90) vs. 41.7% (60/144), P < 0.05]. Compared with the normal immune function group, the Gram-positive cocci infection rate in the immunosuppressive group was significantly lowered [40.0% (36/90) vs. 56.2% (81/144)], Gram-negative bacilli infection rate [50.0% (45/90) vs. 39.6% (57/144)] and fungus infection rate [10.0% (9/90) vs. 4.2% (6/144)] were significantly increased (both P < 0.05). The levels of WBC, neutrophils ratio, and PCT on the day of bloodstream infection in the immunosuppressive group were significantly lower than those of normal immune function group [WBC (×109/L): 10.2±2.1 vs. 13.5±3.6, neutrophils ratio: 0.87±0.17 vs. 0.96±0.22, PCT (µg/L): 1.3±1.1 vs. 4.7±2.1, all P < 0.05], but no significant difference in the peak temperature (centigrade: 38.5±1.7 vs. 38.9±1.3) or CRP (mg/L: 134.0±42.6 vs. 164.0±55.8) was found as compared with normal immune function group (both P > 0.05). Compared with the normal immune function group, the bacterial clearance time in the immunosuppressive group was significantly prolonged (days: 16.0±10.1 vs. 12.3±4.7), 28-day mortality was significantly increased [61.1% (55/90) vs. 44.4% (64/144)] with statistical significances (both P < 0.05), but no significance was found in the length of ICU stay (days: 21.0±17.1 vs. 18.7±10.4) or the length of hospital stay (days: 36.0±28.1 vs. 33.8±16.8, both P > 0.05). CONCLUSIONS: Gram-negative bacilli was the main pathogen of bloodstream infection in immunosuppressive patients, and the fungal infection rate was high, inflammation reaction was not obvious, bacterial clearance time was long, and prognosis was poor.

[Mean arterial pressure as an indicator of fluid responsiveness in patients with septic shock].

OBJECTIVE: To assess the value of mean arterial pressure (MAP) as an indicator for fluid responsiveness in patients with septic shock. METHODS: A retrospective analysis of clinical data of 68 patients with septic shock receiving volume resuscitation in intensive care unit (ICU) of Drum-tower Hospital Affiliated to Medical School of Nanjing University from June 2011 to February 2012 was conducted. The changes in heart rate (HR), MAP, systolic arterial pressure (SBP), diastolic arterial pressure (DBP), pluse pressure (PP), central venous pressure (CVP) were recorded before and after volume resuscitations. Cardiac index (CI), intrathoracic blood volume index (ITBVI), systemic vessel resistance index (SVRI) and extravascular lung water index (EVLWI) were evaluated by using the thermodilution technique of pulse induced continuous cardiac output (PiCCO). All the patients were divided into two groups, responded group (ΔCI%≥10%) and the unresponded group (ΔCI%<10%), according to the change in CI (ΔCI%). Then the patients were divided into two subgroups, namely low MAP group(LMAP, MAP≤65 mm Hg) and high MAP group(HMAP, MAP>65 mm Hg), according to the initial value of MAP. Then compared the changes in hemodynamic variables before and after volume resuscitation in each subgroup and assess the correlation between the changes in MAP (ΔMAP%) and ΔCI%. RESULTS: Forty-four (64.7%) patients responded to the fluid challenge according to the predetermined criteria, SBP, DBP, MAP, PP, CI, CVP, ITBVI were increased significantly (SBP: 126.5±23.8 mm Hg vs. 110.7±20.2 mm Hg, DBP: 58.1±14.8 mm Hg vs. 52.8±13.5 mm Hg, MAP: 80.3±19.2 mm Hg vs. 70.1±15.8 mm Hg, PP: 68.2±18.7 mm Hg vs. 58.0±15.8 mm Hg, CI: 70.0±21.7 ml×s(-1)×m(-2) vs. 53.3±20.0 ml×s(-1)×m(-2), CVP: 13.0±4.5 mm Hg vs. 10.2±4.4 mm Hg, ITBVI: 909.1±248.7 ml/m(2) vs. 773.5±220.7 ml/m(2), all P<0.01), and SVRI was decreased significantly (130.9±47.7 kPa×s×L(-1)×m(-2) vs. 157.1±59.1 kPa×s×L(-1)×m(-2), P<0.01). HR and EVLWI did not change significantly. There was no significant correlation between ΔMAP% and ΔCI% in all the patients (r=0.266,P=0.054). In the sub-group of LMAP (n=39), ΔMAP% was positively correlated with ΔCI% (r=0.473, P=0.03), the under the receiver operating characteristic curve (ROC curve, AUC) was 0.763, 95% confidence interval (95%CI) 0.554 - 0.973, P=0.231. However, there was no significant correlation between the ΔMAP% and ΔCI% (r=-0.088, P=0.633) in the sub-group of HMAP (n=29). CONCLUSION: MAP can be used as an indicator of fluid responsiveness when the initial value of MAP was at a relative low level (MAP≤65 mm Hg) in patients with septic shock.