Infected Necrosis in Severe Pancreatitis - Combined Nonsurgical Multi-Drainage with Directed Transabdominal High-Volume Lavage in Critically Ill Patients

Background: Infection of pancreatic necrosis is a life-threatening complication during the course of acute pancreatitis. In critically ill patients, surgical or extended endoscopic interventions are associated with high morbidity and mortality. Minimally invasive procedures on the other hand are often insufficient in patients suffering from large necrotic areas containing solid or purulent material. We present a strategy combining percutaneous and transgastric drainage with continuous high-volume lavage for treatment of extended necroses and liquid collections in a series of patients with severe acute pancreatitis. Patients and Methods: Seven consecutive patients with severe acute pancreatitis and large confluent infected pancreatic necrosis were enrolled. In all cases, the first therapeutic procedure was placement of a CT-guided drainage catheter into the fluid collection surrounding peripancreatic necrosis. Thereafter, a second endosonographically guided drainage was inserted via the gastric or the duodenal wall. After communication between the separate drains had been proven, an external to internal directed high-volume lavage with a daily volume of 500 ml up to 2,000 ml was started. Results: In all patients, pancreatic necrosis/liquid collections could be resolved completely by the presented regime. No patient died in the course of our study. After initiation of the directed high-volume lavage, there was a significant clinical improvement in all patients. Double drainage was performed for a median of 101 days, high-volume lavage for a median of 41 days. Several endoscopic interventions for stent replacement were required (median 8). Complications such as bleeding or perforation could be managed endoscopically, and no subsequent surgical therapy was necessary. All patients could be dismissed from the hospital after a median duration of 78 days. Conclusion: This approach of combined percutaneous/endoscopic drainage with high-volume lavage shows promising results in critically ill patients with extended infected pancreatic necrosis and high risk of surgical intervention. Neither surgical nor endoscopic necrosectomy was necessary in any of our patients. Copyright (C) 2009 S. Karger AG, Basel and IA

Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney

BACKGROUND: The role of cyclooxygenase(COX)-1 and COX-2 in the saluretic and renin-angiotensin responses to loop diuretics in the cat is unknown. We propose in vivo characterisation of isoform roles in a furosemide model by administering non-steroidal anti-inflammatory drugs (NSAIDs) with differing selectivity profiles: robenacoxib (COX-2 selective) and ketoprofen (COX-1 selective). RESULTS: In this four period crossover study, we compared the effect of four treatments: placebo, robenacoxib once or twice daily and ketoprofen once daily concomitantly with furosemide in seven healthy cats. For each period, urine and blood samples were collected at baseline and within 48 h of treatment starting. Plasma renin activity (PRA), plasma and urinary aldosterone concentrations, glomerular filtration rate (GFR) and 24 h urinary volumes, electrolytes and eicosanoids (PGE(2), 6-keto-PGF1(α,) TxB(2)), renal injury biomarker excretions [N-acetyl-beta-D-glucosaminidase (NAG) and Gamma-Glutamyltransferase] were measured. Urine volume (24 h) and urinary sodium, chloride and calcium excretions increased from baseline with all treatments. Plasma creatinine increased with all treatments except placebo, whereas GFR was significantly decreased from baseline only with ketoprofen. PRA increased significantly with placebo and once daily robenacoxib and the increase was significantly higher with placebo compared to ketoprofen (10.5 ± 4.4 vs 4.9 ± 5.0 ng ml(−1) h(−1)). Urinary aldosterone excretion increased with all treatments but this increase was inhibited by 75 % with ketoprofen and 65 % with once daily robenacoxib compared to placebo. Urinary PGE(2) excretion decreased with all treatments and excretion was significantly lower with ketoprofen compared to placebo. Urinary TxB(2) excretion was significantly increased from baseline only with placebo. NAG increased from baseline with all treatments. Immunohistochemistry on post-mortem renal specimens, obtained from a different group of cats that died naturally of non-renal causes, suggested constitutive COX-1 and COX-2 co-localization in many renal structures including the macula densa (MD). CONCLUSIONS: These data suggest that both COX-1 and COX-2 could generate the signal from the MD to the renin secreting cells in cats exposed to furosemide. Co-localization of COX isoenzymes in MD cells supports the functional data reported here. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0598-z) contains supplementary material, which is available to authorized users

Subseafloor microbial communities in hydrogen-rich vent fluids from hydrothermal systems along the Mid-Cayman Rise

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Microbiology 18 (2016): 1970–1987, doi:10.1111/1462-2920.13173.Warm fluids emanating from hydrothermal vents can be used as windows into the rocky subseafloor habitat and its resident microbial community. Two new vent systems on the Mid-Cayman Rise each exhibits novel geologic settings and distinctively hydrogen-rich vent fluid compositions. We have determined and compared the chemistry, potential energy yielding reactions, abundance, community composition, diversity, and function of microbes in venting fluids from both sites: Piccard, the world's deepest vent site, hosted in mafic rocks; and Von Damm, an adjacent, ultramafic-influenced system. Von Damm hosted a wider diversity of lineages and metabolisms in comparison to Piccard, consistent with thermodynamic models that predict more numerous energy sources at ultramafic systems. There was little overlap in the phylotypes found at each site, although similar and dominant hydrogen-utilizing genera were present at both. Despite the differences in community structure, depth, geology, and fluid chemistry, energetic modelling and metagenomic analysis indicate near functional equivalence between Von Damm and Piccard, likely driven by the high hydrogen concentrations and elevated temperatures at both sites. Results are compared with hydrothermal sites worldwide to provide a global perspective on the distinctiveness of these newly discovered sites and the interplay among rocks, fluid composition and life in the subseafloor.National Aeronautics and Space Administration Grant Number: NNX09AB756; Alfred P. Sloan Foundation; NSF Grant Number: OCE10618

Evidence for the Role of Endosymbionts in Regional-Scale Habitat Partitioning by Hydrothermal Vent Symbioses

Deep-sea hydrothermal vents are populated by dense communities of animals that form symbiotic associations with chemolithoautotrophic bacteria. To date, our understanding of which factors govern the distribution of host/symbiont associations (or holobionts) in nature is limited, although host physiology often is invoked. In general, the role that symbionts play in habitat utilization by vent holobionts has not been thoroughly addressed. Here we present evidence for symbiont-influenced, regional-scale niche partitioning among symbiotic gastropods (genus Alviniconcha) in the Lau Basin. We extensively surveyed Alviniconcha holobionts from four vent fields using quantitative molecular approaches, coupled to characterization of high-temperature and diffuse vent-fluid composition using gastight samplers and in situ electrochemical analyses, respectively. Phylogenetic analyses exposed cryptic host and symbiont diversity, revealing three distinct host types and three different symbiont phylotypes (one ε-proteobacteria and two γ-proteobacteria) that formed specific associations with one another. Strikingly, we observed that holobionts with ε-proteobacterial symbionts were dominant at the northern fields, whereas holobionts with γ-proteobacterial symbionts were dominant in the southern fields. This pattern of distribution corresponds to differences in the vent geochemistry that result from deep subsurface geological and geothermal processes. We posit that the symbionts, likely through differences in chemolithoautotrophic metabolism, influence niche utilization among these holobionts. The data presented here represent evidence linking symbiont type to habitat partitioning among the chemosynthetic symbioses at hydrothermal vents and illustrate the coupling between subsurface geothermal processes and niche availability.Organismic and Evolutionary Biolog

Nonequilibrium clumped isotope signals in microbial methane

Methane is a key component in the global carbon cycle with a wide range of anthropogenic and natural sources. Although isotopic compositions of methane have traditionally aided source identification, the abundance of its multiply-substituted “clumped” isotopologues, e.g., 13CH3D, has recently emerged as a proxy for determining methane-formation temperatures; however, the impact of biological processes on methane’s clumped isotopologue signature is poorly constrained. We show that methanogenesis proceeding at relatively high rates in cattle, surface environments, and laboratory cultures exerts kinetic control on 13CH3D abundances and results in anomalously elevated formation temperature estimates. We demonstrate quantitatively that H2 availability accounts for this effect. Clumped methane thermometry can therefore provide constraints on the generation of methane in diverse settings, including continental serpentinization sites and ancient, deep groundwaters.National Science Foundation (U.S.) (EAR-1250394)National Science Foundation (U.S.) (EAR-1322805)Deep Carbon Observatory (Program)Natural Sciences and Engineering Research Council of CanadaDeutsche Forschungsgemeinschaft (Gottfried Wilhelm Leibniz Program)United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship)Neil & Anna Rasmussen FoundationGrayce B. Kerr Fund, Inc. (Fellowship)MIT Energy Initiative (Shell-MITEI Graduate Fellowship)Shell International Exploration and Production B.V. (N. Braunsdorf and D. Smit of Shell PTI/EG grant

Chemical Strain Engineering of MAPbI(3) Perovskite Films

This study introduces a new chemical method for controlling the strain in methylammonium lead iodide (MAPbI3) perovskite crystals by varying the ratio of Pb(Ac)2 and PbCl2 in the precursor solution. To observe the effect on crystal strain, a combination of piezoresponse force microscopy (PFM) and X-ray diffraction (XRD) is used. The PFM images show an increase in the average size of ferroelastic twin domains upon increasing the PbCl2 content, indicating an increase in crystal strain. The XRD spectra support this observation with strong crystal twinning features that appear in the spectra. This behavior is caused by a strain gradient during the crystallization due to different evaporation rates of methylammonium acetate and methylammonium chloride as revealed by time-of-flight secondary ion mass spectroscopy and grazing incidince X-ray diffraction measurements. Additional time-resolved photoluminescence shows an increased carrier lifetime in the MAPbI3 films prepared with higher PbCl2 content, suggesting a decreased trap density in films with larger twin domain structures. The results demonstrate the potential of chemical strain engineering as a simple method for controlling strain-related effects in lead halide perovskites.publishe

Methane Clumped Isotopes: Progress and Potential for a New Isotopic Tracer

The isotopic composition of methane is of longstanding geochemical interest, with important implications for understanding petroleum systems, atmospheric greenhouse gas concentrations, the global carbon cycle, and life in extreme environments. Recent analytical developments focusing on multiply substituted isotopologues (‘clumped isotopes’) are opening a valuable new window into methane geochemistry. When methane forms in internal isotopic equilibrium, clumped isotopes can provide a direct record of formation temperature, making this property particularly valuable for identifying different methane origins. However, it has also become clear that in certain settings methane clumped isotope measurements record kinetic rather than equilibrium isotope effects. Here we present a substantially expanded dataset of methane clumped isotope analyses, and provide a synthesis of the current interpretive framework for this parameter. In general, clumped isotope measurements indicate plausible formation temperatures for abiotic, thermogenic, and microbial methane in many geological environments, which is encouraging for the further development of this measurement as a geothermometer, and as a tracer for the source of natural gas reservoirs and emissions. We also highlight, however, instances where clumped isotope derived temperatures are higher than expected, and discuss possible factors that could distort equilibrium formation temperature signals. In microbial methane from freshwater ecosystems, in particular, clumped isotope values appear to be controlled by kinetic effects, and may ultimately be useful to study methanogen metabolism

Ultramafic-influenced submarine venting on basaltic seafloor at the Polaris site, 87°N, Gakkel Ridge

The nature of deep-sea hydrothermal systems is commonly inferred from physicochemical plume characteristics and seafloor observations, as was the case for the 'Polaris' site on the ultraslow-spreading Gakkel Ridge, Earth's northernmost hydrothermal system. Initial reports showing temperature and turbidity anomalies in its hydrothermal plume combined with its location on a neovolcanic axial seamount suggested a volcanically-hosted 'black smoker'-type system. That interpretation, however, is inconsistent with our more complete data set derived from extensive water column sampling and seafloor surveys. The buoyant plume exhibits minor turbidity anomalies and low metal concentrations (dissolved Mn <= 3.1 nM), but contains substantial concentrations of H2 (275 nM) and 13C-enriched CH4 (365 nM, delta 13C = -13.2). Instead of a 'black smoker' vent field, we observed small-scale chimney structures at the seafloor. Together, these data imply intermediate-temperature reaction of hydrothermal fluids with ultramafic rock in the subseafloor before discharge through pillow basalt outcrops at the seafloor. Our study challenges the ability of established approaches to vent exploration, reliant exclusively on in situ sensing to reveal the full geodiversity of subseafloor hydrothermal venting. Ultramafic-influenced systems, releasing H2 and CH4 into the ocean, may be a recurring feature along the entire 25% of the global ridge system that is ultraslow-spreading

Chemistry of hot springs along the Eastern Lau Spreading Center

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 75 (2011): 1013-1038, doi:10.1016/j.gca.2010.12.008.The Eastern Lau Spreading Center (ELSC) is the southernmost part of the back-arc spreading axis in the Lau Basin, west of the Tonga trench and the active Tofua volcanic arc. Over its 397-km length it exhibits large and systematic changes in spreading rate, magmatic/tectonic processes, and proximity to the volcanic arc. In 2005 we collected 81 samples of vent water from six hydrothermal fields along the ELSC. The chemistry of these waters varies both within and between vent fields, in response to changes in substrate composition, temperature and pressure, pH, water/rock ratio, and input from magmatic gases and subducted sediment. Hot-spring temperatures range from 229º to 363ºC at the five northernmost fields, with a general decrease to the south that is reversed at the Mariner field. The southernmost field, Vai Lili, emitted water at up to 334°C in 1989 but had a maximum venting temperature of only 121ºC in 2005, due to waning activity and admixture of bottom seawater into the subseafloor plumbing system. Chloride varies both within fields and from one field to another, from a low of 528 mmol/kg to a high of 656 mmol/kg, and may be enriched by phase separation and/or leaching of Cl from the rock. Concentrations of the soluble elements K, Rb, Cs, and B likewise increase southward as the volcanic substrate becomes more silica-rich, especially on the Valu Fa Ridge. Iodine and δ7Li increase southward, and δ11B decreases as B increases, apparently in response to increased input from subducted sediment as the arc is approached. Species that decrease southward as temperature falls are Si, H2S, Li, Na/Cl, Fe, Mn, and 87Sr/86Sr, whereas pH, alkalinity, Ca, and Sr increase. Oxygen isotopes indicate a higher water/rock ratio in the three systems on Valu Fa Ridge, consistent with higher porosity in more felsic volcanic rocks. Vent waters at the Mariner vent field on the Valu Fa Ridge are significantly hotter, more acid and metal-rich, less saline, and richer in dissolved gases and other volatiles, including H2S, CO2, and F, than the other vent fields, consistent with input of magmatic gases. The large variations in geologic and geophysical parameters produced by back-arc spreading along the ELSC, which exceed those along mid-ocean ridge spreading axes, produce similar large variations in the composition of vent waters, and thus provide new insights into the processes that control the chemistry of submarine hot springs.We thank the U.S. National Science Foundation and its RIDGE 2000 Program for funding this study via grants OCE0241826 (to MJM), OCE0242902 (to PJM), OCE0241796 (to JSS, MKT), and OCE0242088 (to CGW), as well as the Deep Ocean Exploration Institute at WHOI (to GP, ER)

Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors

PURPOSE: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression. METHODS: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole. Those that discontinued for intolerance were offered protocol-directed crossover to the other AI after a washout period. Changes in PROs, including pain [Visual Analog Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were compared after 3 months on the first versus the second AI. Estradiol and drug concentrations were measured. RESULTS: Eighty-three patients participated in the crossover protocol, of whom 91.3% reported improvement in symptoms prior to starting the second AI. Functional status worsened less after 3 months with the second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: -0.05 [SD 0.36]; p = 0.001); change in pain scores was similar between the first and second AI (VAS mean change AI #1: 0.8 [SD 2.7] vs. AI #2: -0.2 [SD 2.8]; p = 0.19). No statistical differences in estradiol or drug concentrations were found between those that continued or discontinued AI after crossover. CONCLUSIONS: Although all AIs act via the same mechanism, a subset of patients intolerant to one AI report improved PROs with a different one. The mechanism of this tolerance remains unknown, but does not appear to be due to non-adherence to, or insufficient estrogen suppression by, the second AI