Development of a Multidisciplinary Program to Expedite Care of Esophageal Emergencies

Background Level 1 programs have improved outcomes by expediting the multidisciplinary care of critically ill patients. We established a novel level 1 program for the management of esophageal emergencies. Methods After institutional review board approval, we performed a retrospective analysis of patients referred to our level 1 esophageal emergency program from April 2013 through November 2015. A historical comparison group of patients treated for the same diagnosis in the previous 2 years was used. Results Eighty patients were referred and transported an average distance of 56 miles (range, 1–163 miles). Median time from referral to arrival was 2.4 hours (range, 0.4-12.9 hours). Referrals included 6 (7%) patients with esophageal obstruction and 71 (89%) patients with suspected esophageal perforation. Of the patients with suspected esophageal perforation, causes included iatrogenic (n = 26), Boerhaave’s syndrome (n = 32), and other (n = 13). Forty-six percent (n = 33) of patients were referred because of pneumomediastinum, but perforation could not be subsequently demonstrated. Initial management of patients with documented esophageal perforation included operative treatment (n = 25), endoscopic intervention (n = 8), and supportive care (n = 5). Retrospective analysis demonstrated a statistically significant difference in mean Pittsburgh severity index score (PSS) between esophageal perforation treatment groups (p < 0.01). In patients with confirmed perforations, there were 3 (8%) mortalities within 30 days. More patients in the esophageal level 1 program were transferred to our institution in less than 24 hours after diagnosis than in the historical comparison group (p < 0.01). Conclusions Development of an esophageal emergency referral program has facilitated multidisciplinary care at a high-volume institution, and early outcomes appear favorable

Evaluation of timed barium esophagram after per-oral endoscopic myotomy to predict clinical response

Background and study aims: The aim of this study was to evaluate whether timed barium esophagram within 24 hours post-per-oral endoscopic myotomy (POEM) (TBE-PP) could predict clinical outcomes. Patients and methods: This was a single-center retrospective study of prospectively collected data on consecutive patients with ≥ 6-month follow-up who underwent POEM followed by TBE-PP. Esophageal contrast retention 2 minutes after TBE-PP was assessed as Grade 1 ( 90 %). Eckardt score, esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM) and function lumen imaging probe (FLIP) of the esophagogastric junction (EGJ) were obtained at baseline. These tests along with pH testing of antisecretory therapy were repeated 6 and 24 months after POEM. Clinical response by Eckardt score ≤ 3, EGJ-distensibility index (EGJ-DI) > 2.8 mm 2 /mm Hg, and integrated relaxation pressure (IRP) < 15 mm Hg and incidence of gastroesophageal reflux disease (GERD) were compared by transit time. Results: Of 181 patients (58 % male, mean 53 ± 17 yr), TBE-PP was classified as Grade 1 in 122 (67.4 %), Grade 2 in 41 (22.7 %), Grade 3 in 14 (7.7 %) and Grade 4 in 4 (2.2 %). At 6 months, overall clinical response by ES (91.7 %), IRP (86.6 %), EGJ-DI (95.7 %) and the diagnosis of GERD (68.6 %) was similar between Grade 1 and Grade 2-4 TBE-PP. At 24 months, Grade 1 had a higher frequency of a normal IRP compared to Grades 2-4 (95.7 % vs. 60 %, P = 0.021) but overall response by ES (91.2 %), EGJ-DI (92.3 %) and the diagnosis of GERD (74.3 %) were similar. Conclusions: Contrast emptying rate by esophagram after POEM has limited utility to predict clinical response or risk of post-procedure GERD

Association of anthropometry and weight change with risk of dementia and its major subtypes : A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m(2)), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m(2)) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.Peer reviewe

Dietary Blue Pigments Derived from Genipin, Attenuate Inflammation by Inhibiting LPS-Induced iNOS and COX-2 Expression via the NF-κB Inactivation

The edible blue pigments produced by gardenia fruits have been used as value-added colorants for foods in East Asia for 20 years. However, the biological activity of the blue pigments derived from genipin has not been reported.The anti-inflammatory effect of blue pigments was studied in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage in vitro. The secretions of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) were inhibited in concentration-dependent manner by blue pigments. Real-time reverse-transcription polymerase chain reaction (Real-time RT-PCR) analyses demonstrated that the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) was inhibited, moreover, ELISA results showed that the productions of IL-6 and TNF-α were inhibited. Cell-based ELISA revealed the COX-2 protein expression was inhibited. The proteome profiler array showed that 12 cytokines and chemokines involved in the inflammatory process were down-regulated by blue pigments. Blue pigments inhibited the nuclear transcription factor kappa-B (NF-κB) activation induced by LPS, and this was associated with decreasing the DNA-binding activity of p65 and p50. Furthermore, blue pigments suppressed the degradation of inhibitor of κB (IκB) α, Inhibitor of NF-κB Kinase (IKK) α, IKK-β, and phosphorylation of IκB-α. The anti-inflammatory effect of blue pigments in vivo was studied in carrageenan-induced paw edema and LPS-injecting ICR mice. Finally, blue pigments significantly inhibited paw swelling and reduced plasma TNF-α and IL-6 production in vivo.These results suggest that the anti-inflammatory properties of blue pigments might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1β, and TNF-α expression through the down-regulation of NF-κB activation, which will provide strong scientific evidence for the edible blue pigments to be developed as a new health-enhancing nutritional food for the prevention and treatment of inflammatory diseases

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Using CubeSat/micro-satellite technology to demonstrate the Autonomous Assembly of a Reconfigurable Space Telescope (AAReST)

Future space telescopes with diameter over 20 m will require new approaches: either high-precision formation flying or in-orbit assembly. We believe the latter holds promise at a potentially lower cost and more practical solution in the near term, provided much of the assembly can be carried out autonomously. To gain experience, and to provide risk reduction, we propose a combined micro/nano-satellite demonstration mission that will focus on the required optical technology (adaptive mirrors, phase-sensitive detectors) and autonomous rendezvous and docking technology (inter-satellite links, relative position sensing, automated docking mechanisms). The mission will involve two “3U” CubeSat-like nanosatellites (“MirrorSats”) each carrying an electrically actuated adaptive mirror, and each capable of autonomous un-docking and re-docking with a small central “15U” class micro/nano-satellite core, which houses two fixed mirrors and a boom-deployed focal plane assembly. All three spacecrafts will be launched as a single ~40 kg micro-satellite package. The spacecraft busses are based on heritage from Surrey׳s SNAP-1 and STRaND-1 missions (launched in 2000 and 2013 respectively), whilst the optics, imaging sensors and shape adjusting adaptive mirrors (with their associated adjustment mechanisms) are provided by CalTech/JPL. The spacecraft busses provide precise orbit and attitude control, with inter-satellite links and optical navigation to mediate the docking process. The docking system itself is based on the electromagnetic docking system being developed at the Surrey Space Centre (SSC), together with rendezvous sensing technology developed for STRaND-2. On orbit, the mission profile will firstly establish the imaging capability of the compound spacecraft before undocking, and then autonomously re-docking a single MirrorSat. This will test the docking system, autonomous navigation and system identification technology. If successful, the next stage will see the two MirrorSat spacecraft undock and re-dock to the core spacecraft in a linear formation to represent a large (but sparse) aperture for high resolution imaging. The imaging of stars is the primary objective, but other celestial and terrestrial targets are being considered. Teams at CalTech and SSC are currently working on the mission planning and development of space hardware. The autonomous rendezvous and docking system is currently under test on a 2D air-bearing table at SSC, and the propulsion and precision attitude control system is currently in development. Launch is planned for 2016. This paper details the mission concept; technology involved and progress to date, focussing on the spacecraft buses

Regulation of Phospholipase Isozymes by Nuclear Factor-kB in Human Gestational Tissues in Vitro

C1 - Journal Articles Referee

Interval routine appendectomy following conservative treatment of acute appendicitis: Is it really needed

Conservative management of acute appendicitis (AA) is gradually being adopted as a valuable therapeutic choice in the treatment of selected patients with AA. This approach is based on the results of many recent studies indicating that it is a valuable and effective alternative to routine emergency appendectomy. Existing data do not support routine interval appendectomy following successful conservative management of AA; indeed, the risk of recurrence is low. Moreover, recurrences usually exhibit a milder clinical course compared to the first episode of AA. The role of routine interval appendectomy is also questioned recently, even in patients with AA complicated by plastron or localized abscess formation. Surgical judgment is required to avoid misdiagnosis when selecting a conservative approach in patients with a presumed “appendiceal” mass