Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor.

In response to stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, and consequently glucocorticoids are released by the adrenal gland into the blood circulation. A large body of research has illustrated that excessive glucocorticoids in the hippocampus exerts negative feedback regulation of the HPA axis through glucocorticoid receptor (GR), which is critical for the homeostasis of the HPA axis. Maternal prenatal stress causes dysfunction of the HPA axis feedback mechanism in their offspring in adulthood. Here we report that telomerase reverse transcriptase (TERT) gene knockout causes hyperactivity of the HPA axis without hippocampal GR deficiency. We found that the level of TERT in the dentate gyrus (DG) of the hippocampus during the developmental stage determines the responses of the HPA axis to stressful events in adulthood through modulating the excitability of the dentate granular cells (DGCs) rather than the expression of GR. Our study also suggests that the prenatal high level of glucocorticoids exposure-induced hypomethylation at Chr13:73764526 in the first exon of mouse Tert gene accounted for TERT deficiency in the DG and HPA axis abnormality in the adult offspring. This study reveals a novel GR-independent mechanism underlying prenatal stress-associated HPA axis impairment, providing a new angle for understanding the mechanisms for maintaining HPA axis homeostasis.

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BACKGROUND: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. METHODS: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. RESULTS: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups. CONCLUSIONS: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. TRIAL REGISTRATION: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

Agomelatine: An Astounding Sui-generis Antidepressant?

Major depressive disorder (MDD) is one of the foremost causes of disability and premature death worldwide. Although the available antidepressants are effective and well tolerated, they also have many limitations. Therapeutic advances in developing a new drug's ultimate relation between MDD and chronobiology, which targets the circadian rhythm, led to a renewed focus on psychiatric disorders. In order to provide a critical analysis about antidepressant properties of agomelatine, a detailed PubMed (Medline), Scopus (Embase), Web of Science (Web of Knowledge), Cochrane Library, Google Scholar, and PsycInfo search was performed using the following keywords: melatonin analog, agomelatine, safety, efficacy, adverse effects, pharmacokinetics, pharmacodynamics, circadian rhythm, sleep disorders, neuroplasticity, MDD, bipolar disorder, anhedonia, anxiety, generalized anxiety disorder (GAD), and mood disorders. Agomelatine is a unique melatonin analog with antidepressant properties and a large therapeutic index that improves clinical safety. Published articles revealed that agomelatine is a melatonin receptors (MT1 and MT2) agonist and 5HT2C receptor antagonist. The effects receptors' on melatonin receptors enable the resynchronization of irregular circadian rhythms with beneficial effects on sleep architectures. In this way, agomelatine is accredited for its unique mode of action, which helps to exert antidepressant effects and resynchronize the sleep-wake cycle. To sum up, an agomelatine has not only antidepressant properties but also has anxiolytic effects.

Abnormal expression profile of plasma-derived exosomal microRNAs in patients with treatment-resistant depression.

Whether microRNAs (miRNAs) from plasma exosomes might be dysregulated in patients with depression, especially treatment-resistant depression (TRD), remains unclear, based on study of which novel biomarkers and therapeutic targets could be discovered. To this end, a small sample study was performed by isolation of plasma exosomes from patients with TRD diagnosed by Hamilton scale. In this study, 4 peripheral plasma samples from patients with TRD and 4 healthy controls were collected for extraction of plasma exosomes. Exosomal miRNAs were analyzed by miRNA sequencing, followed by image collection, expression difference analysis, target gene GO enrichment analysis, and KEGG pathway enrichment analysis. Compared with the healthy controls, 2 miRNAs in the plasma exosomes of patients with TRD showed significant differences in expression, among which has-miR-335-5p were significantly upregulated and has-miR-1292-3p were significantly downregulated. Go and KEGG analysis showed that dysregulated miRNAs affect postsynaptic density and axonogenesis as well as the signaling pathway of axon formation and cell growths. The identification of these miRNAs and their target genes may provide novel biomarkers for improving diagnosis accuracy and treatment effectiveness of TRD.

New application of an old drug proparacaine in treating epilepsy via liposomal hydrogel formulation.

Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic treatment with PPC-HCl did not cause obvious cytotoxicity, neuropsychiatric adverse effects, hepatotoxicity, cardiotoxicity, and even genotoxicity that evaluated by whole genome-scale transcriptomic analyses. Only when in a high dose (50 mg/kg), the QRS interval measured by electrocardiography was slightly prolonged, which was similar to the impact of levetiracetam. Nevertheless, to overcome this potential issue, we adopt a liposome encapsulation strategy that could alleviate cardiotoxicity and prepared a type of hydrogel containing PPC-HCl for sustained release. Implantation of thermosensitive chitosan-based hydrogel containing liposomal PPC-HCl into the subcutaneous tissue exerted immediate and long-lasting remission from spontaneous recurrent seizure in epileptic mice without affecting QRS interval. Therefore, this new liposomal hydrogel formulation of proparacaine could be developed as a transdermal patch for treating epilepsy, avoiding the severe toxicity after chronic treatment with current antiepileptic drugs in clinic.

A novel method for automatic pharmacological evaluation of sucrose preference change in depression mice.

Sucrose preference test (SPT) is a most frequently applied method for measuring anhedonia, a core symptom of depression, in rodents. However, the method of SPT still remains problematic mainly due to the primitive, irregular, and inaccurate various types of home-made equipment in laboratories, causing imprecise, inconsistent, and variable results. To overcome this issue, we devised a novel method for automatic detection of anhedonia in mice using an electronic apparatus with its program for automated detecting the behavior of drinking of mice instead of manual weighing the water bottles. In this system, the liquid surface of the bottles was monitored electronically by infrared monitoring elements which were assembled beside the plane of the water surface and the information of times and duration of each drinking was collected to the principal machine. A corresponding computer program was written and installed in a computer connected to the principal machine for outputting and analyzing the data. This new method, based on the automated system, was sensitive, reliable, and adaptable for evaluation of stress- or drug-induced anhedonia, as well as taste preference and effects of addictive drugs. Extensive application of this automated apparatus for SPT would greatly improve and standardize the behavioral assessment method of anhedonia, being instrumental in novel antidepressant screening and depression researching.

Ultrasound Guidance Enhances the Efficiency of Brachial Plexus Block and Ameliorates the Vascular Injury Compared with Nerve Stimulator Guidance in Hand Surgery Patients.

Background: Nerve stimulation guidance and ultrasound guidance are two major methods that have been widely accepted and applied in axillary brachial plexus block. However, the differences between the effects of these two types of guidance still need to be further elucidated for clinical usage. Materials and Methods: Overall, 208 patients undergoing elective upper limb surgeries and receiving axillary brachial plexus block were recruited in our study. The patients were randomly assigned to receive either ultrasound guidance (group U, n = 112) or nerve stimulation (group N, n = 96). Pinprick test was performed for assessing the sensory blockades. The pain was evaluated by visual analog scale (VAS). Reactive oxygen species (ROS) levels were measured by dichloro-dihydro-fluorescein diacetate staining and serum levels of nitric oxide (NO), nitric oxide synthases (NOS), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein 1 (MCP1) were evaluated by ELISA. Results: Ultrasound guidance significantly enhanced the quality of the sensory blockade and reduced the VAS scores when compared with the nerve stimulator guidance. In addition, the production of ROS, NO, NOS, TNF-α, and MCP-1 were significantly alleviated by ultrasound guidance. Conclusion: Ultrasound-guided brachial plexus block relieves pain during operation, provides higher success rates in the nerve block, causes less vascular damage and results in lower levels of inflammatory cytokines secretion when compared with neurostimulator-directed brachial plexus blockage.

Breast cancer cell-derived exosomal miR-20a-5p promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1.

Bone metastasis of breast cancer makes patients suffer from pain, fractures, spinal cord compression, and hypercalcemia, and is almost incurable. Although the mechanisms of bone metastasis in breast cancers have been studied intensively, novel specific target will be helpful to the development of new therapeutic strategy of breast cancer. Herein, we focused on the microRNA of tumor cell-derived exosomes to investigate the communication between the bone microenvironment and tumor cells. The expression of miR-20a-5p in the primary murine bone marrow macrophages (BMMs), MCF-10A, MCF-7, and MDA-MB-231 cell lines, as well as the cell-derived exosomes were assessed by qRT-PCR. Transwell assays were used to evaluate the effects of miR-20a-5p on tumor cell migration and invasion. The expression of exosomes marker including CD63and TSG101 was detected by Western Blot. Cell cycle distribution of BMMs was analyzed by flow cytometry. 3-UTR luciferase reporter assays were used to validate the putative binding between miR-20a-5p and SRCIN1. MiR-20a-5p was highly expressed in breast tumor tissues and the exosomes of MDA-MB-231 cells. MiR-20a-5p promoted migration and invasion in MDA-MB-231 cells, and the proliferation and differentiation of osteoclasts. MDA-MB-231 cell-derived exosomes transferred miR-20a-5p to BMMs and facilitated the osteoclastogenesis via targeting SRCIN1. The present work provides evidence that miR-20a-5p transferred from breast cancer cell-derived exosomes promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1, providing scientific foundations for the development of exosome or miR-20a-5p targeted therapeutic intervention in breast cancer progression.

The Value of the Inferior Vena Cava Area Distensibility Index and its Diameter Ratio for Predicting Fluid Responsiveness in Mechanically Ventilated Patients.

INTRODUCTION: It is necessary to evaluate fluid responsiveness before fluid resuscitation. We evaluated the value of inferior vena cava (IVC) area respiratory variation and the IVC diameter ratio (IVC DR) for predicting fluid responsiveness in mechanically ventilated patients. METHODS: A prospective observational study was performed in the intensive care unit between December 2017 and March 2018. Mechanically ventilated patients were enrolled and received ultrasound monitoring. IVC diameter distensibility index from the subxiphoid area (IVC-sx DDI), IVC diameter distensibility index from the right midaxillary line (IVC-rm DDI), IVC area distensibility index (IVC ADI), and IVC DR in cross-section were calculated by ultrasound monitoring IVC parameters. The enrolled patients were classified as nonresponders group and responders group according to whether the cardiac output increased by >10% after passive leg raising. RESULTS: Data from 67 mechanically ventilated patients were analyzed. 55.2% of patients had positive fluid responsiveness. The area of receiver operating characteristic curves evaluating the ability of the IVC-sx DDI, IVC-rm DDI, IVC ADI, and IVC DR to predict the fluid responsiveness were 0.702, 0.686, 0.749, and 0.829, respectively. IVC DR level of 1.43 was predictive of positive fluid responsiveness with 90.0% specificity and 67.6% sensitivity. IVC ADI level of 10.2% was predictive of positive fluid responsiveness with 40.0% specificity and 97.3% sensitivity. CONCLUSIONS: IVC ADI and its diameter ratio in cross-section had more value than IVC diameter distensibility index for predicting fluid responsiveness in mechanically ventilated patients.

Upregulation of circular RNA circ_0001721 predicts unfavorable prognosis in osteosarcoma and facilitates cell progression via sponging miR-569 and miR-599.

Osteosarcoma (OS) is the most frequent bone malignancy in human. Growing evidence suggests that circular RNAs (circRNAs) play a significant role in regulating tumorigenesis and progression. Previously, circ_0001721 was identified upregulated in OS tissues screened by circRNA microarrays. In the current study, circ_0001721 expression in OS tissue samples and cells were measured by qRT-PCR. Its clinical value was also explored. For the part of functional assays, CCK-8, clone-forming, flow cytometric, Transwell, xenograft assays were performed. Dual luciferase reporter assays were used to examine the mechanism of circ_0001721. We found that circ_0001721 was enhanced in OS tissue samples and cell lines and the overexpression of circ_0001721 is closely related to clinical severity. In addition, circ_0001721 may be used as a prognostic indicator for OS patients. What's more, loss-of-function and gain-of-function assays demonstrated circ_0001721 facilitates cell progression in OS. Circ_0001721 could sponge miR-569 and miR-599. The oncogenic properties of circ_0001721 is partly attributed to its repression on miR-569 and miR-599. Collectively, the present data reveal the participation of circ_0001721 in tumorigenesis of OS cells, and may indicate a novel therapeutic target.

Down-regulation of GRP78 alleviates lipopolysaccharide-induced acute kidney injury.

PURPOSE: Acute kidney injury (AKI) is accompanied with life-threatening sepsis. It is necessary to develop effective therapy agent or strategy for treating AKI. LPS is a primary pathogenic factor that induces sepsis. Glucose-regulated protein 78 (GRP78) is closely related to cell injuries. The objective of this study was to examine the role of GRP78 in LPS-induced AKI. METHODS: Cell counting kit-8 (CCK-8) assay and flow cytometry (FCM) were respectively performed to assess the cell viability and apoptosis. Available commercial kits were used to detect the reactive oxygen species (ROS) contents and the activity of oxidative indicators. The expressions of the relevant factors were determined by real-time PCR (RT-PCR) and Western blot. RESULTS: The results showed that the expression of GRP78 was apparently increased by LPS treatment, and that the down-regulation of GRP78 by small RNA interference improved the proliferation ability of renal cells in comparison to LPS group. The LPS-induced immune response and oxidative stress was alleviated by the depletion of GRP78. Moreover, the LPS-induced apoptosis was reduced in the GRP78 group by regulating the expression of mitochondrial apoptosis (Bcl-2, Bax) and endoplasmic reticulum (ER) stress (CHOP, caspase-12)-associated proteins. In addition, the protective role of GRP78 reduction was partly related to the balance of NF-κB/IκB. CONCLUSIONS: Down-regulation of GRP78 attenuated LPS-induced AKI through inhibiting immune response/oxidative stress-associated apoptosis.

A survey of the enteral nutrition practices in patients with neurological disorders in the tertiary hospitals of China.

BACKGROUND AND OBJECTIVES: With the development of enteral nutrition in patients with neurological disorders in China, related guidelines were published in 2011. The Chinese Society for Parenteral and Enteral Nutrition conducted a survey to evaluate the status quo of enteral nutrition practices in these patients. METHODS AND STUDY DESIGN: This multicenter prospective investigation was conducted from April 2012 to April 2013 and involved 18 tertiary hospitals in China. The survey using standardized questionnaires sought information about the basic protocols for enteral nutrition (devices and staffing) and specific information about patients with neurological conditions who received nutrition by way of enteral feeding. RESULTS: In the 18 hospitals from 13 provinces, 83.3% patients were configured with an enteral nutrition infusion pump, 77.8% had a percutaneous endoscopic gastrostomy (PEG) device, and 88.9% had a clinical nutrition support group. Four hundred four patients participated in this survey (259 men, 145 women; mean age 61.3±14.7 years), 85.7% had suffered a stroke, 83.9% had impaired consciousness, and 98.0% had dysphagia. Of the 10 guidelines for enteral nutrition practices, setting the energy target, choosing the enteral nutrition tube, and monitoring the patient received unsatisfactory ratings were in poor compliance (56.2%, 30.0% and 38.9%, respectively); the remaining seven guidelines were in good compliance (each >75%). CONCLUSION: The survey suggested that configuration of the enteral nutritional devices and staffing was adequate in China's tertiary hospitals. However, some associated practices had not yet reached the desired levels of competency, indicating a need for this to be understood and for improved training.

The efficacy of simultaneous bilateral axillary brachial plexus block under the guidance of neurostimulator or ultrasound: a prospective study.

PURPOSE: This study was designed to investigate the risk of local anesthetic toxicity and efficacy of simultaneous bilateral axillary brachial plexus block performed under the guidance of ultrasound or a neurostimulator. METHODS: One hundred and twenty patients who were anesthetized with bilateral axillary plexus block simultaneously between February 2012 and March 2014 were enrolled in the study. The patients were anesthetized under the guidance of a neurostimulator (group N, n = 60) or ultrasound (group U, n = 60). The block performance time, procedure-related pain, adverse events, total and free plasma concentrations of ropivacaine, and other data were recorded. The comparison was analyzed statistically. RESULTS: The block performance time, and onset of the sensory and motor block, of group N was longer than that of group U (p < 0.001). The procedure-related pain of group N was more serious than that of group U (p < 0.05). The patient satisfaction rate of group U was higher than that of group N (p < 0.05). The total plasma concentrations of ropivacaine in group N were comparable to those of group U, except for the value at 50 min after injection (p < 0.05). The free plasma concentrations of ropivacaine of group N at 5 min were significantly higher than that of group U (p < 0.001). No apparent serious adverse events were observed perioperatively in both groups. CONCLUSIONS: Simultaneous bilateral axillary brachial plexus block guided by neurostimulator or ultrasound in bilateral distal upper extremity surgery seems to have a low risk of local anesthetic toxicity and to be effective. The ultrasound-guided block is superior in terms of providing the same degree of anesthesia with shorter duration, less pain, and faster onset of sensory and motor blockades, which is important in clinical practice.

Early Enteral Combined with Parenteral Nutrition Treatment for Severe Traumatic Brain Injury: Effects on Immune Function, Nutritional Status and Outcomes.

Objective To compare the conjoint effect of enteral nutrition (EN) and parenteral nutrition (PN) with single EN or PN on immune function, nutritional status, complications and clinical outcomes of patients with severe traumatic brain injury (STBI). Methods A prospective randomized control trial was carried out from January 2009 to May 2012 in Neurological Intensive Care Unit (NICU). Patients of STBI who met the enrolment criteria (Glasgow Coma Scale score 6~8; Nutritional Risk Screening ≥3) were randomly divided into 3 groups and were admi- nistrated EN, PN or EN+PN treatments respectively. The indexes of nutritional status, immune function, complications and clinical outcomes were examined and compared statistically. Results There were 120 patients enrolled in the study, with 40 pationts in each group. In EN+PN group, T lymthocyte subsets CD3+%, CD4+%, ratio of CD3+/CD25+, ratio of CD4+/CD8+, the plasma levels of IgA, IgM, and IgG at 20 days after nutritional treatment were significantly increased compared to the baseline(t=4.32-30.00, P<0.01), and they were significantly higher than those of PN group (t=2.44-14.70; P<0.05,or P<0.01) with exception of CD4+/CD8+, higher than those of EN group (t=2.49-13.31, P<0.05, or P<0.01) with exceptions of CD3+/CD25+, CD4+/CD8+, IgG and IgM. For the nutritional status, the serum total protein, albumin, prealbumin and hemoglobin were significantly higher in the EN (t=5.87-11.91; P<0.01) and EN+PN groups (t=6.12-13.12; P<0.01) than those in PN group after nutrition treatment. The serum prealbumin was higher in EN+PN group than that in EN group (t=2.08; P<0.05). Compared to the PN group, the complication occurrence rates of EN+PN group were significantly lower in stress ulcer (22.5% vs. 47.5%; χ2= 8.24, P<0.01), intracranial infection (12.5% vs 32.5%;χ2= 6.88, P<0.01) and pyemia (25.0% vs. 47.5%; χ2= 6.57, P<0.05). Compared to the EN group, the complication occurrence rates of EN+PN group were significantly lower in aspirated pneumonia (27.5% vs. 50.0%; χ2= 6.39, P<0.05), hypoproteinemia (17.5% vs. 55.0%; χ2= 18.26, P<0.01) and diarrhea (20.0% vs. 60.0%; χ2= 20.00, P<0.01). The EN+PN group also had significant less length of stay in NICU (t=2.51, 4.82; P<0.05, P<0.01), number of patients receiving assisted mechanical ventilation (χ2= 6.08, 12.88; P<0.05, P<0.01) and its durations (t=3.41, 9.08; P<0.05, P<0.01), and the death rate (χ2=7.50, 16.37; P<0.05, P<0.01) than those of EN or PN group. Conclusion Early EN+PN treatment could promote the recovery of the immune function, enhance nutritional status, decrease complications and improve the clinical outcomes in patients with severe traumatic brain injury.

PLGA/poloxamer nanoparticles loaded with EPAS1 siRNA for the treatment of pancreatic cancer in vitro and in vivo.

Endothelial PAS domain protein 1 (EPAS1) is a hypoxia-inducible protein that contributes to tumor progression. Hypoxia is involved in tumor aggressiveness and resistance to chemotherapy and ionizing radiation. In this study, we aimed to assess the effects of EPAS1 silencing using polyethylenimine-poly(lactide-coglycolide) (PLGA)/poloxamer nanoparticles loaded with EPAS1 siRNA on BxPC-3 pancreatic cancer cells and in a mouse model of ectopic pancreatic cancer. PLGA/poloxamer nanoparticles loaded with EPAS1 siRNA or scramble siRNA were prepared using the emulsion/solvent evaporation method. BxPC-3 pancreatic cancer cells were cultured under hypoxic conditions and treated with or without the nanoparticles. MTT and apoptosis assays were then performed. A xenograft nude mouse model of pancreatic cancer was established and the mice were treated with or without the nanoparticles. The mRNA and protein expression levels of EPAS1 in the tumor tissues were determined by semi-quantitative RT-PCR and western blot analysis, respectively. Vascular endothelial growth factor (VEGF) and tumor microvessel density indicated by CD34 were determined by immunohistochemistry. The in vitro release of EPAS1 siRNA from the nanoparticles exerted a sustained-release effect. EPAS1 siRNA nanoparticles inhibited BxPC-3 cell proliferation, and induced cell apoptosis under hypoxic conditions, compared with the nanoparticles loaded with scramble siRNA (all P<0.05). EPAS1 expression was significantly decreased in the pancreatic tumors of the mice injected with the nanoparticles loaded with EPAS1 siRNA. The pancreatic tumors of the mice injected with nanoparticles loaded with EPAS1 siRNA were significantly smaller in size and had a lower number of microvessels and a percentage of VEGF-positive cells compared with those of the mice injected with the nanoparticles loaded with scramble siRNA (all P<0.05). In conclusion, the results from the present study suggest that PLGA/poloxamer nanoparticles loaded with EPAS1 siRNA inhibit pancreatic cancer cell proliferation, induce cell apoptosis under hypoxic conditions and significantly inhibit the formation of microvessels and tumor growth in vivo.

Effect of timing of tracheotomy on clinical outcomes: an update meta-analysis including 11 trials.

OBJECTIVE: To estimate the relative effect of early vs. late tracheotomy on clinical end-points in unselected intensive care unit (ICU) patients undergoing mechanical ventilation. METHODS: We searched electronic databases (up to February 27, 2013) for both randomized control trials and observational studies satisfying the predefined inclusion criteria. RESULTS: We retrieved 11 reports of studies including a total of 13 705 patients. Early tracheotomy was associated with significant reductions in mortality [33.3% vs. 36.3%; relative risk (RR); 0.92; 95% confidence interval (CI): 0.88, 0.97; I(2): 29%], length of ICU stay (mean difference: -6.55 days; 95% CI: -8.19, -4.90; I(2): 98%) and duration of mechanical ventilation (mean difference: -6.53 days; 95% CI: -11.43, -1.63; I(2): 100%). However, as compared with late tracheotomy, early tracheotomy did not reduce the incidence of hospital pneumonia (21.9% vs. 21.0%, RR: 0.85; 95% CI: 0.68, 1.06; I(2): 67%). CONCLUSIONS: Early tracheotomy can reduce length of ICU stay, duration of mechanical ventilation and mortality but has no influence on hospital pneumonia when compared with late tracheotomy. Once the decision has been made about tracheotomy, clinical physicians should not hesitate to perform the procedure.

[Relationship between antacid therapy and hospital acquired pneumonia in critically ill patients: a meta-analysis].

OBJECTIVE: To systematically review the effect of antacid medication on stress-related mucosal disease (SRMD) bleeding, hospital acquired pneumonia (HAP), and hospital mortality in critically ill patients admitted to intensive care unit (ICU). METHODS: Related articles were retrieved from Medline Database (from January 1980 to December 2012). Randomized control trials (RCTs) focused on comparison between antacid and sucralfate were collected, and then a meta-analysis was performed. RESULTS: Twelve studies including a total of 2537 patients admitted to ICU were qualified for analysis. Antacid medication significantly increased the incidence of HAP when compared with sucralfate in 11 trials [19.36% (249/1286) vs. 15.23% (184/1208), odds ratio (OR)=1.27, 95% confidence interval (95%CI): 1.03-1.57, P=0.02]. Subgroup analyses showed that antacid therapy significantly reduce the incidence of clinically significant bleeding compared with sucralfate [1.80% (12/667) vs. 3.86% (26/673), OR=0.46, 95%CI: 0.23-0.91, P=0.03], however, it did not lower the incidence of overt bleeding [7.09% (40/564) vs. 7.35% (36/490), OR=1.00, 95%CI: 0.62-1.62, P=0.99]. There was no significant difference between antacid group and sucralfate group on neither ICU mortality nor hospitalization mortality in 11 studies [25.58% (288/1126) vs. 23.65% (268/1133), OR=1.11, 95%CI: 0.92-1.35, P=0.28]. CONCLUSIONS: Antacid therapy used in critically ill patients may increase the incidence of HAP while reduce the rate of upper gastrointestinal bleeding, while it exerts no influence on mortality rate when compared with sucralfate treatment in this meta-analysis. It is imperative to restrict the overuse of such medication, and further RCTs focused on indication and withdrawal should be encouraged.

Surgical treatment of symptomatic Rathke's cleft cysts: clinical features, therapy considerations and outcomes.

BACKGROUND: Rathke's cleft cyst (RCC) is one of the most common incidentally discovered sellar lesions, while symptomatic cases are relatively rare. Surgical treatment is recommended for symptomatic patients to drain the cyst content and to remove the capsule safely. The aim of this study was to clarify the clinical features, surgery considerations and therapy outcomes of symptomatic RCCs. METHODS: Totally 42 patients (19 males and 23 females) were retrospectively reviewed with the diagnosis of RCCs under surgery resection at the Affiliated Hospital of Medical College, Qingdao University between January 2005 and December 2010. RESULTS: Patients' age ranged from 6 to 67 years (mean of 41.6 years). The duration of symptoms ranged from 4 days to 10 years. Headache (69%), visual impairment (36%), and pituitary dysfunction (10%) were the most common presenting symptoms. The maximum diameter of cysts ranged from 6.0 to 46.7 mm (mean of 20.07 mm). Of the 42 patients, 36 underwent endonasal transsphenoidal approach and the others underwent transcranial approach. Thirty patients had a subtotal resection and decompression, while 12 patients had a total cyst resection. Cysts of 28 patients were lined by simple cubical or columnar epithelium, and cysts of 34 patients were filled by amorphous colloid material, that was the characteristic of RCCs. The majority of patients presented with a simple headache, and 93% of this group experienced a complete improvement after surgery. Twelve of 15 patients (80%) with preoperative visual deficits experienced an improvement in their vision after surgery. All of those patients with pituitary dysfunction experienced an improved endocrine status. The endocrinological complication usually was diabetes insipidus, and postoperative transient diabetes insipidus occurred in 13 (31%) patients without any permanent diabetes insipidus. The overall recurrence rate was 7% at a mean follow-up of 22 months (range 12 - 60 months). CONCLUSIONS: Surgical treatment is to drain the contents of the cyst and to remove the capsule as much as possible under the precondition that does not increase the complications. Biopsy and decompression procedures are recommended for most cases.