Red blood cell distribution width: A severity indicator in patients with COVID-19.

Red blood cell distribution width (RDW) was frequently assessed in COVID-19 infection and reported to be associated with adverse outcomes. However, there was no consensus regarding the optimal cutoff value for RDW. Records of 98 patients with COVID-19 from the First People's Hospital of Jingzhou were reviewed. They were divided into two groups according to the cutoff value for RDW on admission by receiver operator characteristic curve analysis: ≤11.5% (n = 50) and >11.5% (n = 48). The association of RDW with the severity and outcomes of COVID-19 was analyzed. The receiver operating characteristic curve indicated that the RDW was a good discrimination factor for identifying COVID-19 severity (area under the curve = 0.728, 95% CI: 0.626-0.830, p < 0.001). Patients with RDW > 11.5% more frequently suffered from critical COVID-19 than those with RDW ≤ 11.5% (62.5% vs. 26.0%, p < 0.001). Multivariate logistic regression analysis showed RDW to be an independent predictor for critical illness due to COVID-19 (OR = 2.40, 95% CI: 1.27-4.55, p = 0.007). A similar result was obtained when we included RDW > 11.5% into another model instead of RDW as a continuous variable (OR = 5.41, 95% CI: 1.53-19.10, p = 0.009). RDW, as an inexpensive and routinely measured parameter, showed promise as a predictor for critical illness in patients with COVID-19 infection. RDW > 11.5% could be the optimal cutoff to discriminate critical COVID-19 infection.

Prognostic value of central venous-to-arterial carbon dioxide difference in patients with bloodstream infection.

Background: Bloodstream infection (BSI) are prone to circulation disorders, which portend poor outcome. The central venous-to-arterial carbon dioxide difference (Pcv-aCO2) is a biomarker for circulation disorders, but the prognostic value of Pcv-aCO2 in BSI patients remains unclear. This study was to investigate the association of Pcv-aCO2 with adverse events in BSI patients. Methods: The patients with BSI between August 2014 and August 2017 were prospectively enrolled. Clinical characteristic and laboratory results were collected. We analyzed the association of the level of Pcv-aCO2 with clinical variables and 28-day mortality. Results: A total of 152 patients were enrolled. The Pcv-aCO2 was positively correlated with white blood cell count (r=0.241, p=0.003), procalcitonin (r=0.471, p<0.001), C-reactive protein (r=0.192, p=0.018), lactate (r=0.179, p=0.027), Sequential Organ Failure Assessment (r=0.318, p<0.001) and Acute Physiology And Chronic Health Evaluation II score (r=0.377, p<0.001), while that was negatively correlated with central venous oxygen saturation (r=-0.242, p<0.001) and platelet (r=-0.205, p=0.011). Kaplan-Meier curves demonstrated that patients with Pcv-aCO2 >6mmHg had a worse prognosis than those without (log rank=32.10, p<0.001). Multivariate analysis showed Level of Pcv-aCO2 was an independent risk factor for 28-day mortality (HR: 3.10, 95% CI: 1.43-6.74, p=0.004). The area under the receiver operating characteristic curve of Pcv-aCO2 for prediction of 28-day mortality in patients with BSI was 0.794. Pcv-aCO2>6 mmHg had 81.1% sensitivity and 78.8% specificity for predicting 28-day mortality. Conclusion: Pcv-aCO2 may be a simple and valuable biomarker to assessment of 28-day mortality in patients with BSI.

An Accurate and Comprehensive Clinical Sequencing Assay for Cancer Targeted and Immunotherapies.

BACKGROUND: Incorporation of next-generation sequencing (NGS) technology into clinical utility in targeted and immunotherapies requires stringent validation, including the assessment of tumor mutational burden (TMB) and microsatellite instability (MSI) status by NGS as important biomarkers for response to immune checkpoint inhibitors. MATERIALS AND METHODS: We designed an NGS assay, Cancer Sequencing YS panel (CSYS), and applied algorithms to detect five classes of genomic alterations and two genomic features of TMB and MSI. RESULTS: By stringent validation, CSYS exhibited high sensitivity and predictive positive value of 99.7% and 99.9%, respectively, for single nucleotide variation; 100% and 99.9%, respectively, for short insertion and deletion (indel); and 95.5% and 100%, respectively, for copy number alteration (CNA). Moreover, CSYS achieved 100% specificity for both long indel (50-3,000 bp insertion and deletion) and gene rearrangement. Overall, we used 33 cell lines and 208 clinical samples to validate CSYS's NGS performance, and genomic alterations in clinical samples were also confirmed by fluorescence in situ hybridization, immunohistochemistry, and polymerase chain reaction (PCR). Importantly, the landscape of TMB across different cancers of Chinese patients (n = 3,309) was studied. TMB by CSYS exhibited a high correlation (Pearson correlation coefficient r = 0.98) with TMB by whole exome sequencing (WES). MSI measurement showed 98% accuracy and was confirmed by PCR. Application of CSYS in a clinical setting showed an unexpectedly high occurrence of long indel (6.3%) in a cohort of tumors from Chinese patients with cancer (n = 3,309), including TP53, RB1, FLT3, BRCA2, and other cancer driver genes with clinical impact. CONCLUSION: CSYS proves to be clinically applicable and useful in disclosing genomic alterations relevant to cancer target therapies and revealing biomarkers for immune checkpoint inhibitors. IMPLICATIONS FOR PRACTICE: The study describes a specially designed sequencing panel assay to detect genomic alterations and features of 450 cancer genes, including its overall workflow and rigorous clinical and analytical validations. The distribution of pan-cancer tumor mutational burden, microsatellite instability, gene rearrangement, and long insertion and deletion mutations was assessed for the first time by this assay in a broad array of Chinese patients with cancer. The Cancer Sequencing YS panel and its validation study could serve as a blueprint for developing next-generation sequencing-based assays, particularly for the purpose of clinical application.

Diagnostic value of cardiopulmonary ultrasound in elderly patients with acute respiratory distress syndrome.

BACKGROUND: Lung ultrasound and echocardiography are mainly applied in critical care and emergency medicine. However, the diagnostic value of cardiopulmonary ultrasound in elderly patients with acute respiratory distress syndrome (ARDS) is still unclear. METHODS: Consecutive patients admitted to ICU with the diagnosis of suspected ARDS based on clinical grounds were enrolled. Cardiopulmonary ultrasound was performed as part of monitoring on day 1, day 2 and day 3. On each day a bedside ultrasound was performed to examine the lungs and calculate the Left Ventricular Ejection Fraction (LVEF). On day 3, a thoracic CT was performed on each patient as gold standard for ARDS imaging diagnosis. According to the results from CT scan, patients were grouped into ARDS group or Non-ARDS group. The relation between the cardiopulmonary ultrasound results on each day and the results of CT scan was analyzed. RESULTS: Fifty one consecutive patients aged from 73 to 97 years old were enrolled. Based on CT criteria, 33 patients were classified into the ARDS group, while 18 patients were included in non-ARDS group. There was no significant difference between the two groups in baseline characteristics, including gender, age, underlying disease, comorbidities, APACHE II score, SOFA score, and PaO2/FiO2 ratio (P > 0.05). Lung ultrasound (LUS) examination results were consistent with the CT scan results in diagnosis of pulmonary lesions. The Kappa values were 0.55, 0.74 and 0.82 on day 1, day 2 and day 3, respectively. The ROC analysis showed that the sensitivity, specificity and area under curve of ROC (AUROC) for lung ultrasound in diagnose ARDS were 0.788,0.778,0.783;0.909,0.833,0.871;0.970,0.833,0.902 on day 1, day 2 and day 3, respectively. However, cardiopulmonary ultrasound performed better in diagnosing ARDS in elderly patients. The sensitivity, specificity and AUROC were 0.879,0.889,0.924;0.939,0.889,0.961;and 0.970,0.833,0.956 on day 1, day 2 and day 3, respectively. The combined performances of cardiopulmonary ultrasound, N-terminal pro-brain natriuretic peptide (NT-proBNP), and PaO2/FiO2 ratio improved the specificity of the diagnosis of ARDS in elderly patients. CONCLUSIONS: LUS examination results were consistent with the CT scan results in diagnosis of pulmonary lesions. Cardiopulmonary ultrasound has a greater diagnostic accuracy in elderly patients with ARDS, compared with LUS alone. The combined performances of cardiopulmonary ultrasound, NT-proBNP, and PaO2/FiO2 increased the specificity of the diagnosis of ARDS in elderly patients.

Transplantation of placenta-derived mesenchymal stem cells enhances angiogenesis after ischemic limb injury in mice.

Mesenchymal stem cell-based therapy has emerged as a promising approach for the treatment of peripheral arterial disease. The purpose of this study was to examine the potential effects of human placenta-derived mesenchymal stem cells (PMSCs) on mouse hindlimb ischemia. PMSCs were isolated from human placenta tissue and characterized by flow cytometry. An in vivo surgical ligation-induced murine limb ischemia model was generated with fluorescent dye (CM-DiI) labelled PMSCs delivered via intramuscular injection. Our data show that PMSCs treatment significantly enhanced microvessel density, improved blood perfusion and diminished pathologies in ischemic mouse hindlimbs as compared to those in the control group. Further immunostaining studies suggested that injected PMSCs can incorporate into the vasculature and differentiate into endothelial and smooth muscle cells to enhance angiogenesis in ischemic hind limbs. This may in part explain the beneficial effects of PMSCs treatment. Taken together, we found that PMSCs treatment might be an effective treatment modality for treatment of ischemia-induced injury to mouse hind limbs by enhancement of angiogenesis.

Akt/eNOS signaling pathway mediates inhibition of endothelial progenitor cells by palmitate-induced ceramide.

Palmitate (PA) impairs endothelial progenitor cells (EPCs). However, the molecular mechanism underlying the suppressive function of PA remains largely unknown. Ceramide, a free fatty acid metabolite, mediates multiple cellular signals. We hypothesized that ceramide acts as an intermediate molecule to mediate inhibition of EPCs by PA. We first demonstrated that PA could inhibit the attachment, migration, and tube formation of EPCs through suppression of the Akt/endothelial nitric oxide (NO) synthase (eNOS) signaling pathway. In addition, we observed that PA could induce ceramide accumulation in EPCs. To test whether the accumulation of ceramide causes EPC dysfunction, the ceramide synthesis inhibitors myriocin and fumonisin B1 were used. We that found both inhibitors could effectively abolish PA-mediated EPC inhibition. Furthermore, the ceramide deacylation inhibitor N-oleoylethanolamine could augment the inhibitory effect of PA on EPCs, indicating that it is ceramide, not its metabolites, that mediates the suppression of EPCs by PA. We have previously shown that Akt/eNOS phosphorylation was reduced after PA treatment, which, in turn, hampered the normal bioavailability of NO, leading to impaired functions of EPCs. To test the role for ceramide in this process, a clinically used NO donor, sodium nitroprusside, was used. We found that sodium nitroprusside could rescue the suppressive effects of ceramide on EPCs, suggesting that ceramide-mediated EPC inhibition might be through reduction of NO production. Taken together, our findings indicated that ceramide-induced reduction of NO might be the molecular mechanism for PA-mediated EPC inhibition; thus, targeting either ceramide or NO production might be an effective means for improvement of EPC functions in diseases.

Urinary Trypsin Inhibitor Attenuates Acute Lung Injury by Improving Endothelial Progenitor Cells Functions.

BACKGROUND: Urinary Trypsin Inhibitor (UTI) is involved in various aspects of tissue repair, regeneration and development. However, the potential role of UTI in protection against acute lung injury (ALI) remains largely unknown. In the present study, we demonstrated that UTI treatment could ameliorate ALI induced by oleic acid (OA) treatment in rabbit model. METHODS: Intravenous application of UTI (10000 U/kg/d) significantly improved the pathologies associated with OA-induced ALI. The lungs were stained with hematoxylin and eosin to scored the lung injury. Peripheral blood mononuclear cells were isolated by density gradient centrifugation with Ficoll-Plaque Plus. The proliferation and ability of tube structure formation of EPCs were observed and the level of phosphorylated Akt protein expression and eNOS protein expression were assayed. RESULTS: Consistent with pathological scores, UTI treatment significantly reduced wet/dry ratio of OA injured lungs. A quantification of capillary density revealed that UTI treatment led to about 2 fold increase over uninjured control and about 1.5 fold increase over PBS treatment. The capacity for tube formation of EPCs on ECM gel was significantly reduced in the ALI group and recovered with UTI treatment. Quantification of western blot bands was summarized and showed that UTI treatment activates Akt/eNOS signaling. NO production could contribute to the improvement of EPCs function by UTI treatment. CONCLUSIONS: UTI-induced phosphorylation/activation of eNOS and Akt, increases the intracellular level of NO, thereby improving tube formation and proliferation function of EPCs. EPCs function is crucial for re-endothelialization after denuding injuries of arteries.

Stromal cell-derived factor-1α attenuates oleate-induced acute lung injury in rabbits.

The stromal cell-derived factor-1α/C-X-C chemokine receptor 4 (SDF-1/CXCR4) axis is involved in various aspects of tissue repair, regeneration and development. However, the role of SDF-1/CXCR4 in acute lung injury (ALI) remains largely unknown. The aim of the present investigation is to examine pathological changes in a rabbit model with ALI induced by oleic acid (OA) and to explore the protective effect of SDF-1α on ALI. Intravenous application (i.v.) of oleic acid (0.1 ml/kg/h for 2h) provoked pulmonary hemorrhage, edema, and protein leakage, resulting in severe ALI. When the rabbit received an infusion of SDF-1α (20 µg/kg/24h) for 30 min before OA treatment, SDF-1α seemed to significantly improve the pathologies associated with OA-induced ALI. While dissecting the molecular mechanisms underlying the beneficial effects of SDF-1α, we found that SDF-1/CXCR4 is expressed in uninjured lung tissues but is greatly reduced after OA treatment. Interestingly, intravenous delivery of SDF-1α could target an injured lung and rescue expression of CXCR4, which in turn activates anti-apoptotic proteins, Bcl-1 and Bcl-xl, but does not affect pro-apoptotic proteins, such as Bad and Bax. These data suggested that SDF-1α could protect rabbit lungs from AIL. The molecular mechanism might be associated with upregulating anti-apoptosis family expression through CXCR4. Thus, SDF-1/CXCR4 signaling pathway may be a promising target for treatment of patients with ALI.

Circular RNAs as potential biomarkers for male severe sepsis.

Circular RNAs (circRNAs) play important roles in many human diseases. However, their role in the development of severe sepsis, a condition that remains one of the main causes of death in intensive care units, has not yet been defined. In this study, we interrogated the molecular mechanisms of circRNAs in severe sepsis. We profiled the expression levels of 5,680 circRNAs in plasma extracted from blood samples of 9 severe sepsis cases or 9 controls (male, age 78 ± 7) using the Human circRNA Array. To enrich protein-coding genes hosting severe sepsis-related circRNAs, we conducted gene ontology and pathways analyses. Out of the identified 760 differentially expressed circRNAs, 404 were upregulated while 356 were downregulated (fold change [FC] ≥2 or ≤-2, and false discovery ratio <0.05). Circ-0008285 (located in exons of CDYL), showed significant upregulation in severe sepsis with an FC of 13.7, and Bonferroni-corrected P < 0.05/5. In silico analysis identified Circ-0008285 interacting microRNAs as well as protein-coding genes. We systematically investigated the differential expression pattern of circRNAs in severe sepsis. The circRNAs we identified might serve as potential biomarkers for diagnosis and prognosis of sepsis.

Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases.

Autophagy has been referred to as a double-edged sword in tumorigenesis and tumor progression. Emerging evidence suggests that pharmacological modulation of autophagy is a promising therapeutic strategy for cancer. However, few autophagy-modulating compounds are currently approved for clinical use in humans. Matrine is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Recently, matrine has been reported to induce autophagy and autophagic cell death in cancer cells, although the underlying mechanisms have yet to be elucidated. Here, we systematically examined the autophagic events induced by matrine in SGC7901 cells. The accumulation of autophagic vacuoles in matrine-treated cells was verified by the conversion of microtubule-associated protein light chain 3 as well as confocal and transmission electron microscopy. Furthermore, we demonstrated that matrine blocked autophagic degradation by impairing the activities of lysosomal proteases. Moreover, confocal microscopy and gradient ultracentrifugation revealed that the trafficking processes and proteolytic activation of cathepsins were inhibited by matrine. Using a pH sensor probe, we found elevated pH values in endosomes/lysosomes in response to matrine treatment. Therefore, matrine seems to be a novel autophagy inhibitor that can modulate the maturation process of lysosomal proteases.

Clinical evaluation of Sepsis-1 and Sepsis-3 in infective endocarditis.

BACKGROUND: Sepsis is associated with poor survival outcomes in patients with infective endocarditis (IE). However, the prognostic value of the Sepsis-1 and Sepsis-3 criteria of sepsis for IE patients is unclear. METHODS: A total of 1354 patients with IE was enrolled and classified into the sepsis and non-sepsis groups according to the Sepsis-1 and Sepsis-3. Multivariate regression analysis was performed to test the predictive performances of the Sepsis-1 and Sepsis-3 in assessing the risk of mortality in patients with IE. RESULTS: Sepsis was diagnosed in 347 (25.6%) patients according to the Sepsis-1 and 496 (36.6%) patients with the Sepsis-3. The in-hospital mortality rate was 11.5% in the Sepsis-1 group and 14.3% in the Sepsis-3 group. Kaplan-Meier survival curve analysis showed that both Sepsis-1 (Log-rank = 17.2, p < 0.001) and Sepsis-3 (Log-rank = 94.3, p < 0.001) were significantly associated with 6-month mortality. Multivariate regression analysis demonstrated that the Sepsis-3 was independently associated with the in-hospital mortality (odds ratio = 2.89, 95% CI 1.68-4.97, p < 0.001) and the 6-month mortality (hazard ratio = 3.24, 95% CI 2.08-5.04, p < 0.001). CONCLUSIONS: Sepsis-3 shows better predictive performance than Sepsis-1 criteria in assessing the risk of mortality in patients with IE.

Hypernatremia in brain-dead patients.

OBJECTIVES: Hypernatremia often occurs in patients with brain death. This study summarizes its characteristics. METHODS: We recorded 57 patient's highest blood sodium value, as well as daily NT-proBNP, blood creatinine, and urine output. Further, we analyzed the time of the first rise in blood sodium, and the relationship between NT-proBNP, serum creatinine, urine output, and serum sodium. RESULTS: There was no hyponatremia in these patients, and only seven of the 53 patients registered blood sodium between 137 and 150 mmol/L. We found that blood sodium started to rise at 36.0 (28.5-52.3) h, reaching the highest value in 79.0 (54.0-126.0) h. Urine volume and creatinine have no correlation with serum sodium level, while NT-proBNP has a significant correlation with serum sodium level. CONCLUSION: It is necessary to conduct volume assessments and urine electrolyte testing on patients with brain death. BNP has a protective effect on water and electrolytes to prevent hypernatremia.

Pcv-aCO2 and procalcitonin levels for the early diagnosis of bloodstream infections caused by gram-negative bacteria.

BACKGROUND: The central venous-to-arterial carbon dioxide difference (Pcv-aCO2) is a biomarker for tissue perfusion, but the diagnostic value of Pcv-aCO2 in bacteria bloodstream infections (BSI) caused by gram-negative (GN) bacteria remains unclear. This study evaluated the expression levels and diagnostic value of Pcv-aCO2 and procalcitonin (PCT) in the early stages of GN bacteria BSI. METHODS: Patients with BSI admitted to the intensive care unit at Guangdong Provincial People's Hospital between August 2014 and August 2017 were enrolled. Pcv-aCO2 and PCT levels were evaluated in GN and gram-positive (GP) bacteria BSI patients. RESULTS: A total of 132 patients with BSI were enrolled. The Pcv-aCO2 (8.32 ± 3.59 vs 4.35 ± 2.24 mmHg p = 0.001) and PCT (30.62 ± 34.51 vs 4.92 ± 6.13 ng/ml p = 0.001) levels were significantly higher in the GN group than in the GP group. In the diagnosis of GN bacteria BSI, the area under the receiver operating characteristic curve (AUROC) for Pcv-aCO2 was 0.823 (95% confidence interval (CI): 0.746-0.900). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.90%, 88.00%, 74.07% and 78.21%, respectively. The AUROC for PCT was 0.818 (95% CI: 0.745-0.890). The sensitivity, specificity, PPV and NPV were 57.90%, 94.67%, 71.93% and 74.67%, respectively. CONCLUSIONS: Pcv-aCO2 and PCT have similar and high diagnostic value for the early diagnosis of BSI caused by GN bacteria.

Transcriptome sequencing reveals differential expression of circRNAs in sepsis induced acute respiratory distress syndrome.

circRNAs play important roles in regulating gene expression at both transcriptional and post transcriptional levels and involve in a variety of human diseases. But up to now, it is still unclear whether circRNAs are involved in the occurrence and development of sepsis induced acute respiratory distress syndrome (ARDS). In the present research, we collected lung tissues of sepsis induced ARDS patients (n = 3) and brain dead patients without ARDS (n = 3). From the results of genome-wide sequencing, a total of 272 significantly up-regulated and 231 significantly down-regulated circRNAs were obtained. Combining the previous sequencing results in the plasma of ARDS patients, 11 up-regulated and 3 down-regulated circRNAs simultaneously in plasma and lung tissues were identified. Pathway enrichment analysis showed that the co differentially expressed circRNAs might be involved in the regulation of ECM-receptor interaction and adherens junction etc. In conclusion, these data indicates that circRNAs may involve in the progression of sepsis induced ARDS.

Efficacy of vitamin C in patients with sepsis: An updated meta-analysis.

Previous studies have suggested the beneficial effects of vitamin C in patients with sepsis. However, the results could not be reproduced in the subsequent studies. This meta-analysis aimed to reevaluate the value of vitamin C treatment in patients with sepsis. Electronic databases were searched from inception to August 2019 for the studies comparing the effect of vitamin C versus non-vitamin C infusion in patients with sepsis. Data from 10 studies (4 randomized controlled trials [RCTs] and 6 retrospective studies) involving 1671 patients (495 in the vitamin C treatment group and 1176 in the control group) were included. The use of vitamin C did not reduce the risk of 28-day (OR = 0.84, P = 0.611, I2 = 56.3%), intensive care unit (ICU; OR = 0.79, P = 0.319, I2 = 46.2%), or in-hospital mortality (OR = 0.76, P = 0.251, I2 = 51.0%). No difference in the duration of vasopressor usage and the length of ICU or hospital stay was present. The subgroup analysis for two RCTs suggested that vitamin C treatment showed reduced 28-day mortality (OR = 0.22, P = 0.014, I2 = 35.7%), whereas this beneficial effect did not occur in subgroup analysis for three retrospective studies (OR = 1.11, P = 0.527, I2 = 0%). Retrospective meta-analysis could not reveal the beneficial effect of vitamin C on patients with sepsis. Therefore, in order to clarify the role of vitamin C in sepsis the high-quality RCTs will be required in the future study.

The Association of Circulating Selenium Concentrations with Diabetes Mellitus.

PURPOSE: The relationship between circulating selenium and diabetes mellitus (DM) remains inconsistent. Therefore, the relationship between circulating selenium and DM was investigated in the present study. PATIENTS AND METHODS: All participants (aged ≥18 years) were included from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Selenium concentrations from the fasting serum samples were determined using inductively coupled mass spectrometry, then grouped into quartiles. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multivariate logistic regression analysis and the results were stratified by age and sex. RESULTS: A total of 2,903 (61.9±13.7 years old) participants (49.3% males) were enrolled, and 580 (19.97%) of them had DM. The mean levels of selenium were 136.4±19.6 µg/L. Patients with DM (138.76±20.02 vs 135.88±19.44, P=0.002) had higher selenium levels compared to those without DM. The OR for DM was 1.12 (95% CI=1.01-1.24; P=0.0270) for each 10 µg/L increment in selenium, and subjects in the highest quartile of selenium levels (>147.00 uµg/L) had 2.82 (95% CI=1.55-5.11; P=0.0007) times higher risk of DM compared to the lowest quartile of selenium levels. Subgroup analysis showed that selenium was independently associated with DM only in female aged <65 years. CONCLUSION: Circulating selenium levels were positively associated with the odds of DM, but difference in sex and age.

Role of Neuromuscular Blocking Agents in Acute Respiratory Distress Syndrome: An Updated Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The therapeutic role of neuromuscular blocking agents (NMBA) in patients with acute respiratory distress syndrome (ARDS) remains controversial. METHODS: We systematically reviewed randomized controlled trials investigating the use of NMBA in ARDS patients from inception to July 2019. Relative risk (RR) was calculated for the incidence of barotrauma and mortality using the random-effect or fixed-effect model according to heterogeneity analysis. RESULTS: Data were combined from five randomized controlled trials that included 1,461 patients (724 in the NMBA group and 737 in the control group). Pooled analysis showed that NMBA infusion did not reduce 28-day mortality (RR = 0.72, 95% confidence interval (CI) 0.44 to 1.17, P=0.180, I-squared = 62.8%), but was associated with lower intensive care unit (ICU) mortality (RR = 0.60, 95% CI 0.41 to 0.88, P = 0.009, I-squared = 9.2%). In addition, the incidence of barotrauma was significantly lower in patients treated with NMBA (RR = 0.53, 95% CI 0.33 to 0.84, P = 0.007, I-squared = 0). However, infusion of NMBA might increase the risk of ICU-acquired weakness (RR = 1.34, 95% CI 0.97 to 1.84, P = 0.066, I-squared = 0). CONCLUSION: Infusion of NMBA could reduce ICU mortality and the incidence of barotrauma. The risk of ICU-acquired weakness was higher in moderate-to-severe ARDS patients treated with NMBA. The real effects of NMBA need to be further evaluated and confirmed by a study with a stricter design.

Palmitic and linoleic acids impair endothelial progenitor cells by inhibition of Akt/eNOS pathway.

BACKGROUND: Endothelial progenitor cells (EPCs) are involved in adult neovasculogenesis and maintenance of vascular integrity. Scarce data have been provided for the individual effect of elevated free fatty acids (FFAs) on EPCs. This study was designed to investigate the association between Akt/eNOS signal pathway changes and the proliferation/function of EPCs in the presence of palmitic and linoleic acids. METHODS: After 14-day culture, EPCs were stimulated with different concentrations of palmitic and linoleic acids, with or without SNP, L-NAME, or LY294002. The proliferation and ability of adhesion, migration and tube structure formation of EPCs were observed and the level of phosphorylated Akt protein expression and eNOS protein expression were assayed. RESULTS: Incubation with palmitic and linoleic acids at concentrations of 0.2 muM or higher inhibited EPCs proliferation, significantly reduced migratory rate, reduced adhesion to fibronectin and impaired ability of EPCs to form tube structure in a dose-dependent manner. A simultaneous dose-dependent NO generation and Akt phosphorylation decrease as well as eNOS expression reduction at protein levels were also observed. However, all of the detrimental effects were attenuated by pretreating EPCs with SNP, NO donor. AKT and eNOS inhibitor, LY294002 and L-NAME, respectively, augmented palmitic and linoleic acids inhibitory effects on EPCs. CONCLUSIONS: These findings suggest that palmitic and linoleic acids downregulated AKT/eNOS signal pathway, which contributed to overall poor function and decrease proliferation of EPCs. These changes induced by palmitic and linoleic acids in signaling offer a novel explanation for the overall poor function of EPCs in diabetes mellitus.

Bedside ultrasound diagnosis of a malpositioned central venous catheter: A case report.

RATIONALE: Central venous catheter (CVC) placement is commonly performed in intensive care unit. And CVC placement is associated with risks including CVC malposition, pneumothorax. Many of the previously reported cases are about catheter misplacement detected by bedside ultrasound, chest x-ray (CXR) and computed tomography. In this case, malposition was detected by bedside ultrasound incidentally particularly with no clinical manifestation. PATIENT CONCERNS: An 88-year-old male with severe diabetic peripheral neuropathy secondary to type 2 diabetes mellitus was admitted for further treatment. DIAGNOSES: We cannulated a single-lumen CVC via the right subclavian vein, and the tip ended up in the internal jugular vein on the same side. With bedside ultrasound, we discovered the malposition though it was mistaken by aspiration of venous blood. Later, CXR revealed malposition of the tip once again. INTERVENTIONS: Since the patient was asymptomatic and the catheter was functioning normally, the catheter was used for the following 20 days without complications. Ultimately, we carefully performed the catheter removal. OUTCOMES: After the inserted catheter was removed, we attempted a new CVC through the left internal jugular vein. After the procedure, bedside ultrasound and CXR confirmed the correct position of CVC. Following successful replacement of the central catheter, no further complications were observed. LESSONS: Bedside ultrasound offers safety and effectiveness during insertion of CVC. It also exhibits promptness and accuracy compared to post-intervention radiological imaging.

[Predictive value of central venous-to-arterial carbon dioxide difference on the prognosis of elderly patients with sepsis].

OBJECTIVE: To investigate the predictive value of central venous-to-arterial carbon dioxide difference (Pcv-aCO2) on the prognosis of elderly patients with sepsis. METHODS: 208 elderly patients who met the diagnostic criteria of the Sepsis-3 and with the age of more than 60 years old, and admitted to intensive care unit (ICU) of Guangdong General Hospital from January to December in 2017 were enrolled. According to the prognosis, the patients were divided into death group (n = 46) and survival group (n = 162). The Pcv-aCO2, central venous oxygen saturation (ScvO2), serum procalcitonin (PCT), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) were collected for all patients. The differences of each index between the two groups were compared. The correlations between Pcv-aCO2 and ScvO2, PCT, CRP, SOFA, APACHE II scores were analyzed respectively with Pearson correlation. The prognostic value of Pcv-aCO2 in elderly patients with sepsis was assessed by receiver operating characteristic curve (ROC). RESULTS: Compared with survival group, the Pcv-aCO2, PCT, CRP, SOFA and APACHE II scores in death group were significantly increased [Pcv-aCO2 (mmHg, 1 mmHg = 0.133 kPa): 6.13±3.33 vs. 4.40±2.65, PCT (µg/L): 31.41±12.83 vs. 3.01±2.69, CRP (mg/L): 130.51±42.23 vs. 104.46±50.12, SOFA: 12.01±2.25 vs. 9.05±2.06, APACHE II: 29.52±5.03 vs. 20.01±3.21, all P < 0.05], and ScvO2 in death group was significantly decreased (0.571±0.136 vs. 0.685±0.106, P < 0.01). Correlation analysis showed that the Pcv-aCO2 was negatively correlated with ScvO2 (r = -0.762, P = 0.001) and was positively correlated with PCT, CRP, SOFA and APACHE II scores (r value was 0.737, 0.625, 0.738, 0.713, respectively, all P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of Pcv-aCO2 prediction of death in patients with sepsis was 0.826, the cut-off was 6.62 mmHg, the sensitivity was 84.7%, the specificity was 77.5%, the positive likelihood ratio was 3.76, and the negative likelihood ratio was 0.19. CONCLUSIONS: Pcv-aCO2 has a great value in evaluating the prognosis of elderly patients with sepsis and can accurately determine the prognosis of sepsis.