Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial.

BACKGROUND: The combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock. METHODS: This single-center, double-blind RCT enrolled adult patients with diagnosis of septic shock within 12 h from Northern Jiangsu People's Hospital between February 2019 and June 2021. Recruited patients were randomized 1:1 to receive intervention (hydrocortisone 200 mg daily, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h) or placebo (0.9% saline) for 5 days or until ICU discharge. The primary endpoint was 90-day mortality. The secondary endpoints included mortality at day 28, ICU discharge, and hospital discharge; shock reversal; 72-h Delta SOFA score; ICU-free days, vasopressor-free days, and ventilator support -free days up to day 28; ICU length of stay (LOS) and hospital LOS. RESULTS: Among 426 patients randomized, a total of 408 patients with septic shock were included in the per-protocol (PP) analysis, of which 203 were assigned to the intervention group and 205 to the placebo group. In the PP population, the primary outcome of 90-day mortality was 39.9% (81/203) and 39.0% (80/205) in the intervention and the placebo groups, respectively, and was not significantly different (P = 0.86). There was no significant difference between two groups in 28-day mortality (36.5% vs. 36.1%, P = 0.94) or the ICU mortality (31.5% vs. 28.8%, P = 0.55) and hospital mortality (34.5% vs. 33.2%, P = 0.78). No other secondary outcomes showed significant differences between two groups, including shock reversal, vasopressor-free days, and ICU LOS. Intention-to-treat analysis included all the 426 patients and confirmed these results (all P > 0.05). CONCLUSION: Among adult patients with septic shock, early use of hydrocortisone, vitamin C, and thiamine combination therapy compared with placebo did not confer survival benefits. Trial registration ClinicalTrials.gov: NCT03872011 , registration date: March 12, 2019.

Enhanced Strength and Plasticity of CoCrNiAl0.1Si0.1 Medium Entropy Alloy via Deformation Twinning and Microband at Cryogenic Temperature.

The synthesis of lightweight yet strong-ductile materials has been an imperative challenge in alloy design. In this study, the CoCrNi-based medium-entropy alloys (MEAs) with added Al and Si were manufactured by vacuum arc melting furnace subsequently followed by cool rolling and anneal process. The mechanical responses of CoCrNiAl0.1Si0.1 MEAs under quasi-static (1 × 10-3 s-1) tensile strength showed that MEAs had an outstanding balance of yield strength, ultimate tensile strength, and elongation. The yield strength, ultimate tensile strength, and elongation were increased from 480 MPa, 900 MPa, and 58% at 298 K to 700 MPa, 1250 MPa, and 72% at 77 K, respectively. Temperature dependencies of the yield strength and strain hardening were investigated to understand the excellent mechanical performance, considering the contribution of lattice distortions, deformation twins, and microbands. Severe lattice distortions were determined to play a predominant role in the temperature-dependent yield stress. The Peierls barrier height increased with decreasing temperature, owing to thermal vibrations causing the effective width of a dislocation core to decrease. Through the thermodynamic formula, the stacking fault energies were calculated to be 14.12 mJ/m2 and 8.32 mJ/m2 at 298 K and 77 K, respectively. In conclusion, the enhanced strength and ductility at cryogenic temperature can be attributed to multiple deformation mechanisms including dislocations, extensive deformation twins, and microbands. The synergistic effect of multiple deformation mechanisms lead to the outstanding mechanical properties of the alloy at room and cryogenic temperature.

Effect of Low-Dose Hydrocortisone Therapy in Adult Patients With Septic Shock: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy of low-dose hydrocortisone therapy in the management of septic shock remains controversial in critical care for many years. Hence, we performed this meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA) to evaluate its effect on clinical outcome among adult patients with septic shock. METHODS: We identified relevant RCTs published from inception to March 7, 2018 comparing low-dose hydrocortisone with placebo or no intervention in adults admitted to the intensive care unit (ICU) for septic shock. Meta-analyses were performed for the primary and secondary outcomes. The risk of bias was assessed using the Cochrane Collaboration's instrument. Trial sequential analysis was used to pool the results from the included studies for the primary outcomes. RESULTS: Thirteen studies were retrieved by our literature search strategy. There were no significant differences in 28-day mortality (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.81-1.00; P = .05) and hospital mortality (OR = 0.91, 95% CI = 0.82-1.02; P = .09) between the 2 groups, which were confirmed by TSA. However, there was a significant improvement in shock reversal in the hydrocortisone group (OR = 1.33, 95% CI = 1.02-1.72; P = .03). Furthermore, subgroup analyses revealed that hydrocortisone plus fludrocortisone statistically reduced the rate of 28-day mortality (OR = 0.79, 95% CI = 0.64-0.97; P = .03), ICU mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .02), and hospital mortality (OR = 0.77, 95% CI = 0.63-0.95; P = .01) in comparison with the placebo, the results were also confirmed by TSA. CONCLUSION: Among adult patients with septic shock, the use of low-dose hydrocortisone compared with control did not confer overall survival benefits, albeit improving shock reversal rate. The benefit of reducing 28-day mortality, ICU mortality, and hospital mortality was observed in combination use of hydrocortisone and fludrocortisone.

Management of Low-Energy Basicervical Proximal Femoral Fractures by Proximal Femoral Nail Anti-Rotation.

OBJECTIVE: To evaluate clinical and radiological outcomes of proximal femoral nail anti-rotation (PFNA-II) devices and demonstrate the effectiveness of PFNA-II for the treatment of basicervical fractures in elderly patients. METHODS: A retrospective review of all patients treated with PFNA-II for a proximal femoral fracture between January 2013 and February 2017 at three different institutions (Shanghai General Hospital, Shanghai Punan Hospital and Shanghai Seventh People's Hospital) was conducted. The X-ray films were strictly reviewed by three trauma surgeons and a professional radiology doctor. Patients over 60 years of age who met the following criteria were included: (i) sustained low-energy trauma; (ii) a two-part fracture; (iii) fracture line located at the base of the femoral neck and that was medial to the intertrochanteric line and exited above the lesser trochanter but was more lateral than a classic transcervical fracture. Follow-up time should be longer than 6 months. A total of 52 patients who met the inclusion criteria were selected. The average age at diagnosis was 75.1 years (range, 63-91 years); 13 patients were men and 39 were women. The same proximal femoral nail anti-rotation devices and the same surgical procedures were applied to all patients. Postoperative radiographic union time and modified Harris hip scores were used as major indicators for evaluating the effectiveness of surgery. RESULTS: The average follow-up period was 22.5 months (18.5, 23.9, and 21.2 months, respectively) and radiographic unions were observed at an average of 19.6 weeks (range, 12-28 weeks). The patients were evaluated immediately after surgery, as well as 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. Of the 49 patients, 38 had good reduction qualities (75.5%), 9 acceptable (18.3%), and 3 poor (6.1%). Radiographic union was confirmed in all fractures at an average of 19.6 weeks (range, 12-28 weeks). The mean Harris hip score was 84.9 (range, 65-99): excellent in 9 patients (18.36%), good in 30 (61.22%), medium in 8 (16.32%), and poor in 2 (4.08%). Slight persistent pain occurred in 3 patients, but these patients could still walk with the help of a cane. Two patients had symptoms of excessive telescoping. Eight patients experienced postoperative medical complications, mainly pneumonia and urinary tract infection. CONCLUSION: Based on the clinical and radiological outcomes, the PFNA-II devices provide strong rotational stability and excellent clinical prognosis, and are an appropriate treatment option for basicervical proximal femoral fracture in elderly patients.

Predictive accuracy of Sepsis-3 definitions for mortality among adult critically ill patients with suspected infection.

BACKGROUND: Sepsis-3 definitions have been published recently; however, their diagnostic value remains controversial. This study was to assess the accuracy of Sepsis-3 definitions compared to Sepsis-1 definitions by stratifying mortality among adult critically ill patients with suspected infection. METHODS: A multicenter, prospective cohort study was conducted from November 10, 2017 to October 10, 2018, in five Intensive Care Units (ICUs) at four teaching hospitals. Thirty-day mortality was compared across categories for both Sepsis-3 definitions and Sepsis-1 definitions, which were evaluated by logistic regression analysis followed by measurement of the area under the receiver operating characteristic curve (AUROC) for predicting 30-day mortality rates. RESULTS: Of the 749 enrolled patients, 644 (85.9%) were diagnosed with sepsis according to the Sepsis-1 definitions. Among those patients, 362 were diagnosed with septic shock (362/749, 48.3%). However, according to the Sepsis-3 definitions, there were 483 patients with a diagnosis of sepsis (483/749, 64.5%), among whom 299 patients were diagnosed with septic shock (299/749, 39.9%). According to the Sepsis-3 definitions, sepsis (sepsis and septic shock) patients had higher 30-day mortality (41.8%) than sepsis patients according to the Sepsis-1 definitions (31.8%, χ = 5.552, P = 0.020). The AUROC of systemic inflammatory response syndrome (SIRS) and quick sequential organ failure assessment (qSOFA) scores with regard to 30-day mortality rates were 0.609 (0.566-0.652) and 0.694 (0.654-0.733), respectively. However, the AUROC of SOFA scores (0.828 [0.795-0.862]) were significantly higher than that of SIRS or qSOFA scores (P < 0.001). CONCLUSION: In adult critically ill patients with suspected infection, the Sepsis-3 definitions were relatively accurate in stratifying mortality and were superior to the Sepsis-1 definitions. TRIAL REGISTRATION: www.chictr.org.cn (ChiCTR-OOC-17013223).

The efficacy of the traditional Chinese medicine Jia Wei Niu Bang Zi granule combined with methotrexate in treating active rheumatoid arthritis: A multicenter, randomized, double-blinded controlled clinical trial.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic and autoimmune inflammatory disease ending with the destruction of joints. Current therapies can relieve RA symptoms, but some also bring severe adverse events. Therefore, an effective and safe therapeutic strategy remains to be created to benefit patients with RA by large. Jia Wei Niu Bang Zi granule (NBZG) consisting of RA-fighting Chinese herbals has been used in Longhua Hospital in the last several decades. NBZG has potential therapeutic effect on RA, which should be evaluated by larger sample clinical trial. METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trials will be conducted to determine the efficiency of NBZG in pain relief and joint protection. A total of 120 patients with active RA will be enrolled, and treated with NBZG or placebo for 12 weeks. The primary outcome measurements include rate of American College of Rheumatology (ACR) 50 at 12 weeks' treatment. The 2nd outcome measurements include rate change of ACR20, ACR70, the disease activity score (DAS) 28, 36-item Short-Form Health Survey Questionnaire, Health Assessment Questionnaire - Disability Index, score changes of Patient Assessment of Arthritis Pain, Patient Global Assessment of Arthritis, and the Athens insomnia scale at the same time points. DISCUSSION: Although NBZG has shown efficacy in treating RA in Longhua Hospital for decades, the universality of this efficacy needs evaluated. The results of this trial will provide a convincing evidence about NBZG's efficacy in treating active RA in a large population. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03173040 (registered on May 30, 2017).

Early initiation of low-dose hydrocortisone treatment for septic shock in adults: A randomized clinical trial.

BACKGROUND: Physiologic dose hydrocortisone is part of the suggested adjuvant therapies for patients with septic shock. However, the association between the corticosteroid therapy and mortality in patients with septic shock is still not clear. Some authors considered that the mortality is related to the time frame between development of septic shock and start of low dose hydrocortisone. Thus we designed a placebo-controlled, randomized clinical trial to assess the importance of early initiation of low dose hydrocortisone for the final outcome. METHODS: A total of 118 patients with septic shock were recruited in the study. All eligible patients were randomized to receive hydrocortisone (n=58) or normal saline (n=60). The study medication (hydrocortisone and normal saline) was initiated simultaneously with vasopressors. The primary end-point was 28-day mortality. The secondary end-points were the reversal of shock, in-hospital mortality and the duration of ICU and hospital stay. RESULTS: The proportion of patients with reversal of shock was similar in the two groups (P=0.602); There were no significant differences in 28-day or hospital all-cause mortality; length of stay in the ICU or hospital between patients treated with hydrocortisone or normal saline. CONCLUSION: The early initiation of low-dose of hydrocortisone did not decrease the risk of mortality, and the length of stay in the ICU or hospital in adults with septic shock. TRIAL REGISTRATION: www.clinicaltrials.govNCT02580240.

Genetic polymorphism in matrix metalloproteinase-9 and transforming growth factor-ß1 and susceptibility to combined pulmonary fibrosis and emphysema in a Chinese population.

In this study, we aimed to explore the association of genetic polymorphism in matrix metalloproteinase-9 (MMP-9) and transforming growth factor-ß1 (TGF-ß1) and the susceptibility to combined pulmonary fibrosis and emphysema (CPFE). We examined the polymorphisms of the MMP-9 C-1562T and TGF-ß1 T869C in 38 CPFE patients, 50 pulmonary emphysema patients, and 34 idiopathic pulmonary fibrosis (IPF) patients. The frequencies of polymorphic genotypes in MMP-9 were 78.95% CC and 21.05% CT in CPFE group, 76.0% CC and 24.0% CT in emphysema group, and 100.0% CC in IPF group. There were highly statistically significant increased frequencies of the CT genotype and T allele in CPFE and emphysema groups compared with IPF group (p < 0.05). The frequencies of polymorphic genotypes in TGF-ß1 were 2.63% CC, 28.95% CT, 68.42% TT in CPFE group, 4.00% CC, 16.00% CT, 80.00% TT in emphysema group, and 5.88% CC, 41.18% CT, 52.94% TT in IPF group. Significant increases in the TT genotype and T allele frequencies were observed in emphysema group compared with IPF group (p < 0.05). Our study has showed that T allele in MMP-9 (C-1562T) and T allele in TGF-ß1 (T869C) are risk factors of pulmonary emphysema. The T allele in MMP-9 (C-1562T) possibly predisposes patients with pulmonary fibrosis to develop emphysema.

Validation of the Chinese version of Addenbrooke's Cognitive Examination III for diagnosing dementia.

OBJECTIVE: The aim of this study was to validate the reliability of the Chinese version of Addenbrooke's Cognitive Examination III (ACE-III) for detecting dementia. Furthermore, the present study compares the diagnostic accuracy of ACE-III with that of mini-mental state examination (MMSE). METHODS: One hundred seventy-seven patients with dementia and 180 healthy controls were included in the study. RESULTS: The reliability of ACE-III was very good (α-coefficient = 0.888). There was a significant negative correlation between Clinical Dementia Rating Scale score and total ACE-III score. Further, there was a positive correlation between MMSE score and total ACE-III score. Age exerted a significant effect on total ACE-III score, memory score, and language score. In the present study, the cutoff score of 83 showed a sensitivity of 91.1% and a specificity of 83.1%. CONCLUSIONS: The present findings support that the Chinese version of ACE-III is a reliable assessment tool for dementia. Copyright © 2017 John Wiley & Sons, Ltd.

Differing Expression of Cytokines and Tumor Markers in Combined Pulmonary Fibrosis and Emphysema Compared to Emphysema and Pulmonary Fibrosis.

This study aimed to explore the different pathogeneses of combined pulmonary fibrosis and emphysema (CPFE) from emphysema and pulmonary fibrosis. The levels of transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), Krebs Von Den Lungen-6 (KL-6), matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinases-1 (TIMP-1), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC), and the telomerase activity in peripheral blood were measured in 38 CPFE patients, 50 pulmonary emphysema patients, and 34 idiopathic pulmonary fibrosis (IPF) patients. The results demonstrated that the levels of VEGF and TGF-ß1 in IPF patients were significantly higher than those in emphysema patients (p < 0.05), and no significant differences were detected between CPFE patients and other two groups (p > 0.05). The levels of KL-6 and CYFRA21-1 in IPF patients were significantly higher than those in emphysema and CPFE patients (p < 0.05), and the latter had the similar levels (p > 0.05). Among the three groups, the levels of SCC, MMP-9, TIMP-1, MMP-9/TIMP-1 ratio, and telomerase activity were not different (p > 0.05). Our study showed that VEGF, TGF-ß1, KL-6, and CYFRA21-1 may play a role in the pathogenesis of pulmonary fibrosis. The lower levels of KL-6 and CYFRA21-1 in CPFE patients may be one of the reasons why these patients develop emphysema on the basis of fibrosis.

Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China: A multicenter survey from 2011 to 2014.

Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China.We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year.The mean age at diagnosis was 72.0 ±â€Š10.0 years (range 38-96 years), and the mean age at onset of AD was 69.8 ±â€Š9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ±â€Š7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11-2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09-3.06).Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset.

The oncogenetic role of stanniocalcin 1 in lung adenocarcinoma: a promising serum candidate biomarker for tracking lung adenocarcinoma progression.

Stanniocalcin 1 (STC1) is reported to functionally participate in the development of several cancers. However, the role of STC1 in the tumorigenesis and progression of lung adenocarcinoma remains to be fully elucidated. Here, we found that the average levels of serum STC1 were 5.47, 5.53, and 6.94 ng/mL (P = 0.0045) in the healthy subjects and patients with lung adenocarcinoma at tumor stages I-II and III-IV according to Union for International Cancer Control (UICC), respectively. Subsequently, the positive correlation between the STC1 expression level in lung adenocarcinoma tissues and tumor stages was confirmed by immunohistochemical staining assay. Additionally, studies in the STC1-overexpressing or STC1-silenced stable cell lines showed that STC1 increased cell proliferation by promoting G1/S transition in cell cycle progression via up-regulating cyclin B1 and cyclin E. Moreover, studies in the STC1-overexpressing or STC1-silenced stable cell lines also showed that STC1 inhibited cell apoptosis by up-regulating the expression of anti-apoptosis proteins Bcl-2 and Bcl-xl and down-regulating the expression of pro-apoptosis proteins Bax, Bak, and Bid via the activation of the ERK and JNK signaling pathway. In addition, neutralization of STC1 with monoclonal antibody significantly increased the apoptosis of A549 cells. Taken together, our findings strongly suggest that elevated expression of STC1 protein at the III-IV stage of lung adenocarcinoma promotes tumorigenesis of lung adenocarcinoma and positively associates with the cancer progression, which may be of potential value as tumor marker in clinical tracking lung adenocarcinoma progression.

The diagnostic value of circulating stanniocalcin-1 mRNA in non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: Previous studies have suggested that the aberrant expression of Stanniocalcin-1 (STC1) occurs in tumor cells. In this study, we explored whether the circulating STC1 mRNA is a promising biomarker in the peripheral blood in patients with non-small cell lung cancer (NSCLC). METHODS: The level of circulating STC1 mRNA was determined with a sensitive quantitative real-time reverse transcription PCR assay. and the data were analyzed by the statistical methods of one-way ANOVA, Mann-Whitney-Wilcoxon U-Test, and Receiver operating characteristic (ROC) curve analysis. RESULTS: The level of circulating STC1 mRNA in patients with NSCLC was significantly higher than in patients with benign pulmonary disease (P < 0.001) or healthy volunteers (P < 0.001). Higher levels of circulating STC1 mRNA were associated with more advanced tumor stages and histological subtypes. Using a cutoff of 0.055, the sensitivity and specificity of STC1 mRNA levels to differentiate between patients with NSCLC and patients with benign pulmonary diseases was 66.7 and 90.9%, and it was 63.7 and 99.8% for patients with NSCLC and healthy volunteers, respectively. CONCLUSIONS: These findings support our hypothesis that circulating STC1 mRNA is a promising biomarker in the peripheral blood.

[Effects of erythromycin on the twitching motility of Pseudomonas aeruginosa].

OBJECTIVE: To observe the effects of low concentration of erythromycin on the twitching motility of Pseudomonas aeruginosa. METHODS: Pseudomonas aeruginosa 1244 (PA1244) was cultured in LB plate or LB broth with added erythromycin at different concentrations 2.5, 0.5, 0.25 mg/L, and in cultures without erythromycin as the control. The changes of PA1244's twitching motility was observed by naked eyes, immunofluorescence, Western blot, dot blot and electron microscope. RESULTS: SubMIC erythromycin inhibited the halation of twitching motility on the culture plates. The average diameters of bacterial halation after culture for 18 h were as below: group of 2.5 mg/L was (0.48 +/- 0.14) cm, group of 0.5 mg/L was (0.64 +/- 0.20) cm, group of 0.25 mg/L was (0.95 +/- 0.18) cm; the control group was (1.40 +/- 0.21) cm (F = 123.15, P < 0.01). After culture for 24 h: group of 2.5 mg/L was (0.67 +/- 0.12) cm, group of 0.5 mg/L was (0.82 +/- 0.23) cm, group of 0.25 mg/L was (1.18 +/- 0.24) cm; the control group was (1.58 +/- 0.28) cm (F = 76.37, P < 0.01). After culture for 36 h: group of 2.5 mg/L was (0.91 +/- 0.17) cm, group of 0.5 mg/L was (1.04 +/- 0.32) cm, group of 0.25 mg/L was (1.49 +/- 0.31) cm; the control group was (2.07 +/- 0.38) cm (F = 54.75, P < 0.01). Immunofluorescence showed that the key component of twitching motility was pilus VI located at the pole of the PA body. Western blot showed that the expression of pilus VI was increased with the decreasing concentration of erythromycin. Dot blot showed that pilus VI was expressed mostly at the outmost of the twitching zone and there was no significant difference between groups. Through transmission electron microscope, PA of the group of 2.5 mg/L had fewer pilus than the control group. CONCLUSION: Diverse concentrations of erythromycin have inhibitory actions on the twitching motility of Pseudomonas aeruginosa.