Completion gastrectomy with esophagojejunostomy for management of complications of benign foregut surgery

Background: With the worldwide epidemic of obesity, an increasing number of bariatric operations and antireflux fundoplications are being performed. Despite low morbidity of the primary foregut surgery, completion gastrectomy may be necessary as a definitive procedure for complications of prior foregut surgery; however, the literature evaluating outcomes after completion gastrectomy with esophagojejunostomy (EJ) for benign diseases is limited. We present our experience of completion gastrectomy with Roux-en-Y EJ in the setting of benign disease at a single tertiary center. Methods and Procedures: All patients who underwent total, proximal, or completion gastrectomy with EJ for complications of benign foregut surgery from January 2006 to December 2015 were retrospectively identified. All cancer operations were excluded. Results: There were 23 patients who underwent gastrectomy with EJ (13 laparoscopic EJ [LEJ] and 10 open EJ). The index operations included 12 antireflux, 9 bariatric, and 2 peptic ulcer disease surgeries. Seventy-eight percent of patients had surgical or endoscopic interventions before EJ, with a median of one prior intervention and a median interval from the index operation to EJ of 25 months (interquartile range 9–87). The 30-day perioperative complication rate was 30% with 17% classified being major (Clavien–Dindo ≥ III) and no 30-day perioperative mortality. Comparing laparoscopic and open approaches showed similar operative times, estimated blood loss, and overall complication rate. LEJ was associated with a shorter length of stay (LOS) (P < .001), fewer postoperative ICU days (P = .002), fewer 6-month complication rates (P < .007), and decreased readmission rate (P = .024). Conclusion: Our series demonstrates that EJ is a reasonable option for reoperative foregut surgery. The laparoscopic approach appears to be associated with decreased LOS and readmissions

Glutathione and Bcl-2 targeting facilitates elimination by chemoradiotherapy of human A375 melanoma xenografts overexpressing bcl-xl, bcl-2, and mcl-1

<p>Abstract</p> <p>Background</p> <p>Bcl-2 is believed to contribute to melanoma chemoresistance. However, expression of Bcl-2 proteins may be different among melanomas. Thus correlations among expression of Bcl-2-related proteins and <it>in vivo </it>melanoma progression, and resistance to combination therapies, was investigated.</p> <p>Methods</p> <p>Human A375 melanoma was injected s.c. into immunodeficient nude mice. Protein expression was studied in tumor samples obtained by laser microdisection. Transfection of siRNA or ectopic overexpression were applied to manipulate proteins which are up- or down-regulated, preferentially, during melanoma progression. Anti-<it>bcl</it>-2 antisense oligonucleotides and chemoradiotherapy (glutathione-depleting agents, paclitaxel protein-binding particles, daunorubicin, X rays) were administered in combination.</p> <p>Results</p> <p><it>In vivo </it>A375 cells down-regulated pro-apoptotic <it>bax </it>expression; and up-regulated anti-apoptotic <it>bcl-2</it>, <it>bcl-xl</it>, and <it>mcl-1</it>, however only Bcl-2 appeared critical for long-term tumor cell survival and progression <it>in vivo</it>. Reduction of Bcl-2, combined with partial therapies, decreased melanoma growth. But only Bcl-2 targeting plus the full combination of chemoradiotherapy eradicated A375 melanoma, and led to long-term survival (> 120 days) without recurrence in 80% of mice. Tumor regression was not due to immune stimulation. Hematology and clinical chemistry data were within accepted clinical toxicities.</p> <p>Conclusion</p> <p>Strategies to target Bcl-2, may increase the effectiveness of antitumor therapies against melanomas overexpressing Bcl-2 and likely other Bcl-2-related antiapoptotic proteins.</p

Contribution of 24-h Blood Pressure Variability to Dementia-Related Disorders in Hispanics

Introduction: As the number of people living with dementia is increasing at alarming rates worldwide, there is an urgent need to understand the physiopathology of dementia syndromes. Among the most important preventable risk factors, treatment of vascular risk factors such as high blood pressure (BP) decreases the risk of Alzheimer’s disease and related dementias (ADRD). Recent evidence suggests that examining BP variability provides additional physiopathological and predictive information above the mean BP level. However, studies examining the relationship between 24-h BP variability and ADRD are limited, and evidence of the association with dementia has not been documented yet. Therefore, we aimed in this study to assess the association of 24-h ambulatory BP variability with brain imaging and cognitive markers of ADRD. Methods: A cross-sectional observational study was conducted using a subset of 420 individuals from the Maracaibo Aging Study aged ≥40 years. Study participants underwent brain MRI scanning and 24-h ambulatory BP monitoring assessments. Markers of ADRD included 1) cerebral small vessel disease (CSVD, defined as white matter hyperintensities, presence of lacunes, cerebral microbleeds, and enlarged perivascular spaces, and hippocampal volume), 2) cognitive functioning addressed with the mini-mental state exam (EMEMS), and 3) diagnose of dementia at baseline. 24-h ambulatory BP variability was studied as the average real variability index. Adjusted linear and logistic regression models were used to analyze the association between 24-h BP and ADRD and accounted for age, sex, education level, body mass index (BMI), current smoking, alcohol intake, hypertension treatment, diabetes mellitus, serum total cholesterol, previous cardiovascular diseases, and cephalic circumference and 24-h mean BP level. Results: The mean age was 57.1±11.8 years old and 73.2% were women (n=303). In adjusted analysis, each unit increase in the 24-h systolic BP variability was significantly associated with lower hippocampus volume (β, -0.036; 95% confidence interval [CI], -0.064, -0.008, P=0.011), greater white matter hyper intensities volume (β, 0.026; 95% CI, 0.008, 0.044; P=0.006), lower cognitive scores (β, -0.370; 95% CI, -0.729, -0.011; P=0.044), greater presence of lacunes (Odds ratios [OR], 1.38; 95% CI, 1.10, 1.71; P=0.004), enlarged perivascular spaces (OR,1.34; 95% CI, 1.08, 1.67; P=0.007), and dementia prevalence (OR, 1.41; 95% CI, 1.07, 1.85; P=0.014). 24-hour diastolic blood pressure variability was only significantly associated with lacunes (OR, 1.42; 95% CI, 1.06, 1.90; P=0.017). In exploratory analysis, we found that neither daytime nor nighttime variability in BP significantly relate with ADRD. Conclusions: Excessive 24-h BP variability associates with ADRD independently of the mean BP level. Understanding the physiological mechanisms explaining the relationship between excessive 24-h BP variability and ADRD may be clinically relevant in the prevention of ADRDs

Super-acceleration on the Brane by Energy Flow from the Bulk

We consider a brane cosmological model with energy exchange between brane and bulk. Parameterizing the energy exchange term by the scale factor and Hubble parameter, we are able to exactly solve the modified Friedmann equation on the brane. In this model, the equation of state for the effective dark energy has a transition behavior changing from $w_{de}^{eff}>-1$ to $w_{de}^{eff}<-1$, while the equation of state for the dark energy on the brane has $w>-1$. Fitting data from type Ia supernova, Sloan Digital Sky Survey and Wilkinson Microwave Anisotropy Probe, our universe is predicted now in the state of super-acceleration with $w_{de0}^{eff}=-1.21$.Comment: Revtex, 11 pages including 2 figures,v2: tpos fixed, references added, to appear in JCA

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Discovery and characterisation of two Neptune-mass planets orbiting HD 212729 with TESS

We report the discovery of two exoplanets orbiting around HD 212729 (TOI\,1052, TIC 317060587), a $T_{\rm eff}=6146$K star with V=9.51 observed by TESS in Sectors 1 and 13. One exoplanet, TOI-1052b, is Neptune-mass and transits the star, and an additional planet TOI-1052c is observed in radial velocities but not seen to transit. We confirm the planetary nature of TOI-1052b using precise radial velocity observations from HARPS and determined its parameters in a joint RV and photometry analysis. TOI-1052b has a radius of $2.87^{+0.29}_{-0.24}$ R$_{\oplus}$, a mass of $16.9\pm 1.7$ M$_{\oplus}$, and an orbital period of 9.14 days. TOI-1052c does not show any transits in the TESS data, and has a minimum mass of $34.3^{+4.1}_{-3.7}$ M$_{\oplus}$ and an orbital period of 35.8 days, placing it just interior to the 4:1 mean motion resonance. Both planets are best fit by relatively high but only marginally significant eccentricities of $0.18^{+0.09}_{-0.07}$ for planet b and $0.24^{+0.09}_{-0.08}$ for planet c. We perform a dynamical analysis and internal structure model of the planets as well as deriving stellar parameters and chemical abundances. The mean density of TOI-1052b is $3.9^{+1.7}_{-1.3}$ g cm$^{-3}$ consistent with an internal structure similar to Neptune. A nearby star is observed in Gaia DR3 with the same distance and proper motion as TOI-1052, at a sky projected separation of ~1500AU, making this a potential wide binary star system.Comment: Accepted to MNRAS. 11 page

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012