Successful aging after elective surgery II: Study cohort description.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description of the enrolled cohort, which details the baseline characteristics and data completion. We also describe the study modifications necessitated by the COVID-19 pandemic, and lay the foundation for future work using this cohort. METHODS: SAGES II is a prospective observational cohort study of community-dwelling adults age 65 and older undergoing major non-cardiac surgery. Participants were assessed preoperatively, throughout hospitalization, and at 1, 2, 6, 12, and 18 months following discharge to assess cognitive and physical functioning. Since participants were enrolled throughout the COVID-19 pandemic, procedural modifications were designed to reduce missing data and allow for high data quality. RESULTS: About 420 participants were enrolled with a mean (standard deviation) age of 73.4 (5.6) years, including 14% minority participants. Eighty-eight percent of participants had either total knee or hip replacements; the most common surgery was total knee replacement with 210 participants (50%). Despite the challenges posed by the COVID-19 pandemic, which required the use of novel procedures such as video assessments, there were minimal missing interviews during hospitalization and up to 1-month follow-up; nearly 90% of enrolled participants completed interviews through 6-month follow-up. CONCLUSION: While there are many longitudinal studies of older adults, this study is unique in measuring health outcomes following surgery, along with risk factors for delirium through the application of novel biomarkers-including fluid (plasma and cerebrospinal fluid), imaging, and electrophysiological markers. This paper is the first to describe the characteristics of this unique cohort and the data collected, enabling future work using this novel and important resource.

Identification of risk factors for hypertension in overweight and obese people and analysis of risk factor interactions: an R-based analysis.

Objective: This study identified the independent risk factors for hypertension in overweight and obese people and also analyzed the interaction between the risk factors. Methods: A total of 5,098 overweight and obese people were enrolled in this study. First, the clinical metabolic characteristics of hypertension and control groups were compared. The logistic regression (LR) and classification and regression trees (CRT)-based decision tree (DT) models were used to screen the independent risk factors for hypertension in overweight and obese people. The multiplicative and additive scale analyses were used to analyze the two risk factors with interaction from the perspective of statistics and biological interaction. Finally, the receiver operating characteristic (ROC) and calibration curves were used to analyze the accuracy and identification ability of the LR and DT models. Results: Age, UA, FPG, SBP, Cr, AST, TG, and FPG were higher in the hypertension group than in the control group (P < 0.05). The results of LR revealed that NAFLD, FPG, age, TG, LDL-c, UA, and Cr were positively correlated with hypertension in overweight and obese people, and GFR was negatively correlated with hypertension in overweight and obese people (P < 0.05). The DT model suggested that the risk factors of age, FPG, and UA interacted with each other. The multiplicative single and multiple factor analysis for FPG + UA, age + UA, age + FPG revealed a positive multiplicative interaction (P < 0.05, B ≠ 0, OR > 1). The additive single and multiple factor analysis for age + UA indicated a positive additive interaction. The ROC and calibration curve analysis indicated that the CRT decision tree, FPG + UA, age + UA, and age + FPG have certain accuracy and discrimination ability. Conclusion: The independent risk factors for hypertension in overweight and obese people included NAFLD, FPG, age, TG, LDL-c, UA, and Cr. Among these, age + UA exhibited synergistic interaction, thereby providing a reference for the prevention and control of hypertension in overweight and obese people.

Application of neural network and nomogram for the prediction of risk factors for bone mineral density abnormalities: A cross-sectional NHANES-based survey.

Background: The risk of bone mineral density abnormalities is inconsistent between eastern and western regions owing to differences in ethnicity and dietary habits. A diet comprising carbohydrates and dietary fiber is not the common daily diet of the American population. Thus far, no studies have assessed the risk of bone mineral density abnormalities in the American population, and no predictive model has considered the intake of carbohydrates, dietary fiber, and coffee, as well as levels of various electrolytes for assessing bone mineral density abnormalities, especially in the elderly. This study conducted a neural network analysis and established a predictive nomogram considering an unusual diet to determine risk factors for bone mineral density abnormalities in the American population, mainly to provide a reference for the prevention and treatment of related bone mineral density abnormalities. Methods: Overall, 9871 patients who had complete data were selected from the National Health and Nutrition Examination Survey database during 2017-2020 as the research object, and patients' general clinical characteristics were compared. Neural networks and nomograms were analyzed to screen for and quantify risk factors for bone mineral density abnormalities. Finally, the receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), and community indifference curve (CIC) were constructed to comprehensively verify the accuracy, differential ability, and clinical practicability of the neural network and nomogram. Results: The important risk factors for bone mineral density abnormalities were caffeine intake, carbohydrate consumption, body mass index (BMI), height, blood sodium, blood calcium, blood phosphorus, blood potassium, dietary fiber, vitamin D, participant age, weight, race, family history, and sex. The nomogram revealed that caffeine intake, carbohydrate consumption, blood potassium, and age were positively correlated with bone mineral density abnormalities, whereas BMI, height, blood phosphate, dietary fiber, and blood sodium were negatively correlated with bone mineral density abnormalities. Women were more prone to these abnormalities than men. The area under the ROC curve values of the neural network and nomogram were 85.8 % and 77.7 %, respectively. The Youden index was 58.04 % and 41.87 %, respectively. The detection sensitivity was 75.73 % and 65.06 %, respectively, and the specificity was 82.31 % and 76.81 %, respectively. Calibration curves of the neural network and nomogram showed better discrimination ability from the standard curve (P > 0.05). DCA and CIC analyses showed that the application of the neural network and nomogram to explore risk factors for bone mineral density abnormalities had certain clinical practicability, and the overall predictive effect of the model was good. Conclusion: The outcomes of the neural network and nomogram analyses suggested that diet structure and electrolyte changes are important significant risk factors for bone mineral density abnormalities, especially with increasing carbohydrate and caffeine intake and decreasing dietary fiber intake. The established model can also provide a reference for future risk prediction.

One-year Medicare costs associated with delirium in older hospitalized patients with and without Alzheimer's disease dementia and related disorders.

INTRODUCTION: One-year health-care costs associated with delirium in older hospitalized patients with and without Alzheimer's disease and related dementias (ADRD) have not been examined previously. METHODS: Medicare costs were determined prospectively at discharge, and at 30, 90, and 365 days in a cohort (n = 311) of older adults after hospital admission. RESULTS: Seventy-six (24%) patients had ADRD and were more likely to develop delirium (51% vs. 24%, P < 0.001) and die within 1 year (38% vs. 21%, P = 0.002). In ADRD patients with versus without delirium, adjusted mean difference in costs associated with delirium were $34,828; most of the excess costs were incurred between 90 and 365 days (P = 0.03). In non-ADRD patients, delirium was associated with increased costs at all timepoints. Excess costs associated with delirium in ADRD patients increased progressively over 1 year, whereas in non-ADRD patients the increase was consistent across time periods. DISCUSSION: Our findings highlight the complexity of health-care costs for ADRD patients who develop delirium, a potentially preventable source of expenditures. HIGHLIGHTS: Novel examination of health-care costs of delirium in persons with and without Alzheimer's disease and related dementias (ADRD). Increased 1-year costs of $34,828 in ADRD patients with delirium (vs. without). Increased costs for delirium in ADRD occur later during the 365-day study period. For ADRD patients, cost differences between those with and without delirium increased over 1 year. For non-ADRD patients, the parallel cost differences were consistent over time.

Development of a large-field streak tube for underwater imaging lidar.

Streak tube imaging lidar (STIL) can obtain 4-D images of a target, and its performance is mainly determined by the streak tube sensor. To obtain a large field of view, we developed a streak tube with a photocathode length as large as 35.3 mm, which is larger than the commonly used ST-HDR (30 mm). At the same time, the temporal resolution and dynamic spatial resolution are 60 ps and 12 lp/mm, which are very suitable to obtain accurate target coordinates for 4-D imaging. In addition, the streak tube has a high detection sensitivity of 46 mA/W at 500 nm and, hence, prospects in remote imaging. To test the performance of the streak tube, an underwater STIL experiment was conducted. Echo signal processing was performed by means of a bandpass filter and a matched filter, and then the peak detection algorithm was used to reconstruct the image. The results indicate that a spatial resolution better than 9 mm is achieved in the limpid water with a depth of 20 m, and a range accuracy of 1 cm is achieved in the turbid water with a depth of 10 m. Such a performance suggests that the large-field streak tube is of great potential for underwater target imaging and other remote imaging applications.

Astragalus mongholicus polysaccharides ameliorate hepatic lipid accumulation and inflammation as well as modulate gut microbiota in NAFLD rats.

Hepatic lipid accumulation, inflammation and gut microbiota dysbiosis are hallmarks of non-alcoholic fatty liver disease (NAFLD), which is the leading cause of chronic liver disease with no therapeutic consensus. The aim of the present study was to elucidate the mechanism of the effects of Astragalus mongholicus polysaccharides (mAPS) on lipid metabolism, inflammation and gut microbiota in a rat model of NAFLD induced by a high-fat diet (HFD). Our results showed that mAPS and Berberine supplementation reduced HFD-induced increases in body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and homeostasis model assessment of insulin resistance (HOMA-IR), and these changes were accompanied by improved histological changes in the liver. Moreover, administration of mAPS and Berberine resulted in lower levels of serum triglycerides, total cholesterol and low-density lipoprotein cholesterol (LDL-c) but higher levels of high-density lipoprotein cholesterol (HDL-c) in HFD-fed rats. mAPS and Berberine treatment markedly reduced HFD-induced hepatic lipid accumulation, which was associated with increased expression of phosphorylated- adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-α (PPAR-α) but decreased expression of sterol-regulatory element binding proteins (SREBP-1). Pretreatment with mAPS or Berberine reduced HFD-induced expression of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α). In addition, mAPS downregulated the expression of colonic and hepatic Toll-like receptor 4 (TLR4) as well as phosphorylated- nuclear factor-κB (NF-κB) and nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) but upregulated the expression of zonula occludens-1 (ZO-1) and occludin in HFD-fed rats. Notably, mAPS treatment reshaped the intestinal microbiome by lowering the Firmicutes to Bacteroidetes (F/B) ratio and increasing the abundance of Proteobacteria and Epsilonbacteria. mAPS supplementation had little effect on the profile of fecal short-chain fatty acids (SCFAs), but it significantly decreased the expression of colonic and hepatic G-protein coupled receptor (GPR) 41 and 43. Therefore, mAPS supplementation ameliorates hepatic inflammation and lipid accumulation in NAFLD by modulating the gut microbiota and SCFA-GPR signaling pathways. The present study provides new evidence for mAPS as a natural active substance in the treatment of NAFLD.

The Role of Inflammation after Surgery for Elders (RISE) study: Examination of [11C]PBR28 binding and exploration of its link to post-operative delirium.

Major surgery is associated with a systemic inflammatory cascade that is thought, in some cases, to contribute to transient and/or sustained cognitive decline, possibly through neuroinflammatory mechanisms. However, the relationship between surgery, peripheral and central nervous system inflammation, and post-operative cognitive outcomes remains unclear in humans, primarily owing to limitations of in vivo biomarkers of neuroinflammation which vary in sensitivity, specificity, validity, and reliability. In the present study, [11C]PBR28 positron emission tomography, cerebrospinal fluid (CSF), and blood plasma biomarkers of inflammation were assessed pre-operatively and 1-month post-operatively in a cohort of patients (N = 36; 30 females; ≥70 years old) undergoing major orthopedic surgery under spinal anesthesia. Delirium incidence and severity were evaluated daily during hospitalization. Whole-brain voxel-wise and regions-of-interest analyses were performed to determine the magnitude and spatial extent of changes in [11C]PBR28 uptake following surgery. Results demonstrated that, compared with pre-operative baseline, [11C]PBR28 binding in the brain was globally downregulated at 1 month following major orthopedic surgery, possibly suggesting downregulation of the immune system of the brain. No significant relationship was identified between post-operative delirium and [11C]PBR28 binding, possibly due to a small number (n = 6) of delirium cases in the sample. Additionally, no significant relationships were identified between [11C]PBR28 binding and CSF/plasma biomarkers of inflammation. Collectively, these results contribute to the literature by demonstrating in a sizeable sample the effect of major surgery on neuroimmune activation and preliminary evidence identifying no apparent associations between [11C]PBR28 binding and fluid inflammatory markers or post-operative delirium.

Does Alzheimer's Disease and Related Dementias Modify Delirium Severity and Hospital Outcomes?

OBJECTIVES: We examined the association between delirium severity and outcomes of delirium among persons with and without Alzheimer's disease and related dementias (ADRD). DESIGN: Prospective cohort study. SETTING: Academic tertiary medical center. PARTICIPANTS: A total of 352 medical and surgical patients. MEASUREMENTS: Delirium incidence and severity were rated daily using the Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) score during hospitalization. Severe delirium was defined as a CAM-S Short Form score in the highest tertile (3-7 points out of 7). ADRD status was determined by a clinical consensus process. Clinical outcomes included prolonged length of stay (>6 d), discharge to post-acute nursing facility, any decline in activities of daily living (ADLs) at 1 month from prehospital baseline, ongoing nursing facility stay, and mortality. RESULTS: Patients with ADRD (n = 85 [24%]) had a significantly higher relative risk (RR) for incident delirium (RR = 2.31; 95% confidence interval [CI] = 1.64-3.28) and higher peak CAM-S scores (mean difference = 1.24 points; CI = .83-1.65; P < .001). Among patients with ADRD, severe delirium significantly increased the RR for nursing facility stay (RR = 2.22; CI = 1.05-4.69; P = .04) and increased the RR for mortality (RR = 2.10; CI = .89-4.98; P = .09). Among patients without ADRD, severe delirium was associated with a significantly increased risk for all poor outcomes except mortality including prolonged length of stay in the hospital (RR = 1.47; CI = 1.18-1.82) and discharge to a post-acute nursing facility (RR = 2.17; CI = 1.58-2.98) plus decline in ADLs (RR = 1.30; CI = 1.05-1.60) and nursing facility stay at 1 month (RR = 1.93; CI = 1.31-2.83). CONCLUSION: Severe delirium is associated with increased risk for poor clinical outcomes in patients with and without ADRD. In both groups, severe delirium increased risk of nursing home placement. In patients with ADRD, delirium was more severe and associated with a trend toward increased mortality at 1 month. Although the increased risk remains substantial by RR, the study had limited power to examine the rarer outcome of death. J Am Geriatr Soc 68:1722-1730, 2020.

The Role of Inflammation after Surgery for Elders (RISE) study: Study design, procedures, and cohort profile.

INTRODUCTION: The Role of Inflammation after Surgery for Elders study correlates novel inflammatory markers measured in blood, cerebrospinal fluid (CSF) assays, and [11C]-PBR28 positron-emission tomography imaging. METHODS: This study involved a prospective cohort design with patients who underwent elective hip and knee arthroplasty under spinal anesthesia. Sixty-five adults participated with their family members. Inflammatory biomarker assays were measured preoperatively on day 1 and postoperatively at one month. RESULTS: On average, participants were 75 years old, and 72% were female. 54% underwent total knee arthroplasty, and 46% underwent total hip arthroplasty. The mean Modified Mini-Mental State (3MS) Examination score was 89.3; four patients (6%) scored ≤77 points. Plasma assays were completed in 63 (97%) participants, cerebrospinal fluid assays in 61 (94%), and PET imaging in 44 (68%). DISCUSSION: This complex study presents an innovative effort to correlate peripheral and central inflammatory biomarkers before and after major surgery in older adults. Strengths include collecting concurrent blood, cerebrospinal fluid, and positron-emission tomography with detailed clinical characterization of delirium, cognition, and functional status.

Effect of Stress on the Work Ability of Aging American Workers: Mediating Effects of Health.

We examined how stress affects the work ability of an aging workforce, how health mediates this relationship, and how the effects of stress on work ability differ in relation to social status. We analyzed data from the Health and Retirement Survey, namely, 2921 observations in 2010, 2289 observations in 2012, and 2276 observations in 2014. Ongoing chronic stress, social status, health status, and associations with individual work ability were assessed with ordinary least squares regression. Stress was significantly inversely associated with work ability. Health may function as a mediator between individual stress and work ability. The effects of stress and health on work ability decreased as social status increased. To cope with the challenges of aging workforces, future policy-makers should consider job resources and social status.

The Better Assessment of Illness Study for Delirium Severity: Study Design, Procedures, and Cohort Description.

BACKGROUND/OBJECTIVES: To describe the design, procedures, and cohort for the Better ASsessment of ILlness -(BASIL) study, which is conducted to develop and test new delirium severity measures, compare them with existing measures, and examine related clinical outcomes. METHODS: Prospective cohort study with 1 year follow-up of study participants at a large teaching hospital in Boston, Massachusetts. After brief cognitive testing and the Delirium Symptom Interview, delirium and delirium severity were rated daily in the hospital using the Confusion Assessment Method (CAM) and CAM-Severity score, the Delirium Rating Scale-Revised-98 (DRS-R-98), and the Memorial Delirium Assessment Scale (MDAS). Other key study variables included comorbidity, physical function (basic and instrumental activities of daily living [ADL]), ratings of subjective health and well-being, and clinical outcomes (length of stay, 30 day rehospitalization, nursing home admission, healthcare utilization). Follow-up interviews occurred at 1- and 12-month with patients and families. In 42 patient interviews, inter-rater reliability for key variables was assessed. RESULTS: Of 768 eligible patients approached, 469 were screened and 352 enrolled, yielding an overall study response rate of 67% for potentially eligible participants. The mean participant was 80.3 years old (SD 6.8) and 203 (58%) were female. The majority of patients were medically complex with Charlson Comorbidity Scores ≥2 (192 patients, 55%), and 102 (29%) met criteria for dementia. Inter-rater reliability assessments (n = 42 pairs) were high for overall ratings of presence or absence of delirium by CAM (κ = 1.0), delirium severity by DRS-R-98 and MDAS (weighted kappa, κ = 1.0 for each) and for ADL impairment (κ = 1.0). For eligible participants at each time point, 278 out of 308 (90%) completed the 1-month follow-up and 132 out of 256 (53%) have completed the 12-month follow-up to date, which is still in progress. Among those who completed interviews, there was only 1-3% missing data on most major outcomes (delirium, basic ADL, and readmission). CONCLUSION: The BASIL study presents an innovative effort to advance the conceptualization and measurement of delirium severity. Unique strengths include the diverse cohort with complete high quality data and longitudinal follow-up, along with detailed collection of multiple delirium measures daily during hospitalization.

Demineralized Dentin Matrix Induces Odontoblastic Differentiation of Dental Pulp Stem Cells.

The aim of this study was to investigate the effect of demineralized dentin matrix (DDM) on dental pulp stem cells (DPSCs) and the potential of complexes with DPSCs and DDM for mineralized tissue formation. Stem cells derived from the dental pulp of healthy pigs aged 18 months were isolated and cultured. DPSCs were incubated with alpha-minimum essential medium treated with DDM extract at 1 mg/ml (DDM1) or 10 mg/ml (DDM10). The concentrations of 3 growth factors in DDM extract was measured by enzyme-linked immunosorbent assay. Adhesion of DPSCs on DDM and hydroxyapatite-tricalcium phosphate (HA-TCP) surfaces was observed using scanning electron microscopy. Cell proliferation was evaluated with cell counting kit-8 and migration by Transwell migration assays. Odontoblastic differentiation was assessed by alkaline phosphatase (ALP) and alizarin red staining, ALP activity and real-time polymerase chain reaction analysis of markers of ALP, runt-related transcription factor 2, type I collagen, dentin matrix acidic phosphoprotein-1, osteonectin and dentin sialophosphoprotein (DSPP). Finally, DPSCs were combined with DDM and placed subcutaneously in nude mice for 12 weeks; DPSCs combined with HA-TCP and DDM alone served as controls. DDM could promote DPSC adhesion, migration and odontoblastic differentiation. Mineralized tissue formation was observed with the DPSC and DDM combination and the DPSC and HA-TCP combination. The mineralized tissue of the DPSC + DDM combination stained positive for DSPP, similar to the dentin tissue. These results indicate that DDM induces DPSC odontoblastic differentiation, suggesting applications for dentin regeneration.

The Language of Delirium: Keywords for Identifying Delirium from Medical Records.

Electronic medical records (EMRs) offer the opportunity to streamline the search for patients with possible delirium. The purpose of the current study was to identify words and phrases commonly noted in charts of patients with delirium. The current study included 67 patients (nested within a cohort study of 300 patients) ages 70 and older undergoing major elective surgery with evidence of confusion in their medical charts. Eight keywords or phrases had positive predictive values of 60% to 100% for delirium. Keywords were charted more often in nursing notes than physician notes. A brief list of keywords may serve as a building block for a methodology to screen for possible delirium from charts, with particular attention to nursing notes, for research and real-time clinical decision making.

Relation of mitochondrial oxygen consumption in peripheral blood mononuclear cells to vascular function in type 2 diabetes mellitus.

Recent studies have shown mitochondrial dysfunction and increased production of reactive oxygen species in peripheral blood mononuclear cells (PBMCs) and endothelial cells from patients with diabetes mellitus. Mitochondria oxygen consumption is coupled to adenosine triphosphate (ATP) production and also occurs in an uncoupled fashion during formation of reactive oxygen species by components of the electron transport chain and other enzymatic sites. We therefore hypothesized that diabetes would be associated with higher total and uncoupled oxygen consumption in PBMCs that would correlate with endothelial dysfunction. We developed a method to measure oxygen consumption in freshly isolated PBMCs and applied it to 26 patients with type 2 diabetes mellitus and 28 non-diabetic controls. Basal (192 ± 47 vs 161 ± 44 pmoles/min, p = 0.01), uncoupled (64 ± 16 vs 53 ± 13 pmoles/min, p = 0.007), and maximal (795 ± 87 vs 715 ± 128 pmoles/min, p=0.01) oxygen consumption rates were higher in diabetic patients compared to controls. There were no significant correlations between oxygen consumption rates and endothelium-dependent flow-mediated dilation measured by vascular ultrasound. Non-endothelium-dependent nitroglycerin-mediated dilation was lower in diabetics (10.1 ± 6.6 vs 15.8 ± 4.8%, p = 0.03) and correlated with maximal oxygen consumption (r = -0.64, p=0.001). In summary, we found that diabetes mellitus is associated with a pattern of mitochondrial oxygen consumption consistent with higher production of reactive oxygen species. The correlation between oxygen consumption and nitroglycerin-mediated dilation may suggest a link between mitochondrial dysfunction and vascular smooth muscle cell dysfunction that merits further study. Finally, the described method may have utility for the assessment of mitochondrial function in larger scale observational and interventional studies in humans.

A tale of two methods: chart and interview methods for identifying delirium.

OBJECTIVES: To compare chart- and interview-based methods for identification of delirium. DESIGN: Prospective cohort study. SETTING: Two academic medical centers. PARTICIPANTS: Individuals aged 70 and older undergoing major elective surgery (N = 300) (majority orthopedic surgery). MEASUREMENTS: Participants were interviewed daily during hospitalization for delirium using the Confusion Assessment Method (CAM; interview-based method), and their medical charts were reviewed for delirium using a validated chart-review method (chart-based method). Rate of agreement of the two methods and characteristics of those identified using each approach were examined. Predictive validity for clinical outcomes (length of stay, postoperative complications, discharge disposition) was compared. In the absence of a criterion standard, predictive value could not be calculated. RESULTS: The cumulative incidence of delirium was 23% (n = 68) according to the interview-based method, 12% (n = 35) according to the chart-based method, and 27% (n = 82) according to the combined approach. Overall agreement was 80%; kappa was 0.30. The methods differed in detection of psychomotor features and time of onset. The chart-based method missed delirium in individuals that the CAM identified who were lacking features of psychomotor agitation or inappropriate behavior. The CAM-based method missed chart-identified cases occurring during the night shift. The combined method had high predictive validity for all clinical outcomes. CONCLUSIONS: Interview- and chart-based methods have specific strengths for identification of delirium. A combined approach captures the largest number and broadest range of delirium cases.

[A comparative study of laparoscopic-assisted and open distal gastrectomy for advanced gastric cancer].

OBJECTIVE: To evaluate the safety, feasibility and the long-term outcomes of laparoscopy-assisted gastrectomy (LAG) for advanced gastric cancer (AGC). METHODS: The clinical and follow-up data of 46 cases after LAG from June 2008 to December 2009 were analyzed, and compared with 85 cases after conventional open gastrectomy (OG) for advanced gastric cancer at the same period at our hospital. The surgical safety, postoperative recovery, complications, radical degree, survival rate were compared. RESULT: As compared with OG group, operation time was longer in LATG group ((274 ± 78) min vs. ( 217 ± 41) min, t = 4.635, P = 0.000). Estimated blood loss in the LAG group ((254 ± 112) ml) was significantly less than in the OG group (t = 3.942, P = 0.000). Time to ambulation ((63 ± 16) hours), first flatus ((77 ± 20) hours), resumed liquid diet ((88 ± 15) hours), duration of analgesic medication ((53 ± 20) hours) and postoperative hospital stay ((11.1 ± 4.6) days) were significantly shorter in the LAG group (t = 5.549, 6.508, 9.436, 9.464 and 2.980 respectively, all P < 0.01). The distance of the proximal and distal resection margin were (5.7 ± 1.4) cm and (3.9 ± 1.5) cm in LAG group, (5.8 ± 1.1) cm and (4.7 ± 1.5) cm in OG group respectively, but the difference was not significant. The number of lymph node dissections was also similar, (30.5 ± 10.4) in LAG group and (32.6 ± 12.3) in OG group (t = 0.960, P = 0.339). The incidence of postoperative complications and mortality rate in LAG group (8.7% and 0 respectively) were also lower than in the OG group, with no statistically significant difference (P > 0.05). The mean follow-up was 31.0 months (range 6-48 months), and the cumulative survival of the 2 groups was similar (χ(2) = 1.594, P = 0.207). CONCLUSIONS: Laparoscopy-assisted gastrectomy for advanced gastric cancer is not significantly different with open surgery in surgical safety, radical degree, and survival rate. It is less traumatic and of fewer complications.

Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus.

BACKGROUND: Endothelial dysfunction contributes to the development of atherosclerosis in patients with diabetes mellitus, but the mechanisms of endothelial dysfunction in this setting are incompletely understood. Recent studies have shown altered mitochondrial dynamics in diabetes mellitus with increased mitochondrial fission and production of reactive oxygen species. We investigated the contribution of altered dynamics to endothelial dysfunction in diabetes mellitus. METHODS AND RESULTS: We observed mitochondrial fragmentation (P=0.002) and increased expression of fission-1 protein (Fis1; P<0.0001) in venous endothelial cells freshly isolated from patients with diabetes mellitus (n=10) compared with healthy control subjects (n=9). In cultured human aortic endothelial cells exposed to 30 mmol/L glucose, we observed a similar loss of mitochondrial networks and increased expression of Fis1 and dynamin-related protein-1 (Drp1), proteins required for mitochondrial fission. Altered mitochondrial dynamics was associated with increased mitochondrial reactive oxygen species production and a marked impairment of agonist-stimulated activation of endothelial nitric oxide synthase and cGMP production. Silencing Fis1 or Drp1 expression with siRNA blunted high glucose-induced alterations in mitochondrial networks, reactive oxygen species production, endothelial nitric oxide synthase activation, and cGMP production. An intracellular reactive oxygen species scavenger provided no additional benefit, suggesting that increased mitochondrial fission may impair endothelial function via increased reactive oxygen species. CONCLUSION: These findings implicate increased mitochondrial fission as a contributing mechanism for endothelial dysfunction in diabetic states.