Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis

AIM: To determine the clinical impact of portal vein thrombosis in terms of both mortality and hepatic decompensations (variceal hemorrhage, ascites, portosystemic encephalopathy) in adult patients with cirrhosis. METHODS: We identified original articles reported through February 2015 in MEDLINE, Scopus, Science Citation Index, AMED, the Cochrane Library, and relevant examples available in the grey literature. Two independent reviewers screened all citations for inclusion criteria and extracted summary data. Random effects odds ratios were calculated to obtain aggregate estimates of effect size across included studies, with 95%CI. RESULTS: A total of 226 citations were identified and reviewed, and 3 studies with 2436 participants were included in the meta-analysis of summary effect. Patients with portal vein thrombosis had an increased risk of mortality (OR = 1.62, 95%CI: 1.11-2.36, P = 0.01). Portal vein thrombosis was associated with an increased risk of ascites (OR = 2.52, 95%CI: 1.63-3.89, P < 0.001). There was insufficient data available to determine the pooled effect on other markers of decompensation including gastroesophageal variceal bleeding or hepatic encephalopathy. CONCLUSION: Portal vein thrombosis appears to increase mortality and ascites, however, the relatively small number of included studies limits more generalizable conclusions. More trials with a direct comparison group are needed

The GOGREEN Survey: A deep stellar mass function of cluster galaxies at 1.0 < z < 1.4 and the complex nature of satellite quenching

We study the stellar mass functions (SMFs) of star-forming and quiescent galaxies in 11 galaxy clusters at 1.0 < z < 1.4 drawn from the Gemini Observations of Galaxies in Rich Early ENvironments (GOGREEN) survey. Based on more than 500 h of Gemini/GMOS spectroscopy and deep multi-band photometry taken with a range of observatories, we probe the SMFs down to a stellar mass limit of 109.7 M⊙ (109.5 M⊙ for star-forming galaxies). At this early epoch, the fraction of quiescent galaxies is already highly elevated in the clusters compared to the field at the same redshift. The quenched fraction excess (QFE) represents the fraction of galaxies that would be star-forming in the field but are quenched due to their environment. The QFE is strongly mass dependent, and increases from ∼30% at M⋆ = 109.7 M⊙ to ∼80% at M⋆ = 1011.0 M⊙. Nonetheless, the shapes of the SMFs of the two individual galaxy types, star-forming and quiescent galaxies, are identical between cluster and field to high statistical precision. Nevertheless, along with the different quiescent fractions, the total galaxy SMF is also environmentally dependent, with a relative deficit of low-mass galaxies in the clusters. These results are in stark contrast with findings in the local Universe, and therefore require a substantially different quenching mode to operate at early times. We discuss these results in light of several popular quenching models.G.R. acknowledges support from the National Science Foundation grants AST-1517815, AST-1716690, and AST-1814159 and NASA HST grant AR-14310.. R.D. gratefully acknowledges support from the Chilean Centro de Excelencia en Astrofísica y Tecnologías Afines (CATA) BASAL grant AFB-170002.P.C. acknowledges the support of the ALMACONICYT grant no 31180051. This work is supported by the National Science Foundation through grant AST-1517863, by HST program number GO-15294, and by grant number 80NSSC17K0019 issued through the NASA Astrophysics Data Analysis Program (ADAP)This work was supported in part by NSF grants AST-1815475 and AST-1518257. Additional support was provided by NASA through grant AR-14289 from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 769130). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 833824). BV acknowledges financial contribution from the grant PRIN MIUR 2017 n.20173ML3WW_001 (PI Cimatti) and from the INAF main-stream funding programme (PI Vulcani). Based on observations obtained at the Gemini Observatory (GS LP-1 and GN LP-4), which is operated by the Association of Universities for Research in Astronom

The GOGREEN Survey: Evidence of an excess of quiescent disks in clusters at 1.0<z<1.41.0<z<1.4

We present results on the measured shapes of 832 galaxies in 11 galaxy clusters at 1.0 < z <1.4 from the GOGREEN survey. We measure the axis ratio ($q$), the ratio of the minor to the major axis, of the cluster galaxies from near-infrared Hubble Space Telescope imaging using S\'ersic profile fitting and compare them with a field sample. We find that the median $q$ of both star-forming and quiescent galaxies in clusters increases with stellar mass, similar to the field. Comparing the axis ratio distributions between clusters and the field in four mass bins, the distributions for star-forming galaxies in clusters are consistent with those in the field. Conversely, the distributions for quiescent galaxies in the two environments are distinct, most remarkably in $10.1\leq\log(M/{\rm M}_{\odot})<10.5$ where clusters show a flatter distribution, with an excess at low $q$. Modelling the distribution with oblate and triaxial components, we find that the cluster and field sample difference is consistent with an excess of flattened oblate quiescent galaxies in clusters. The oblate population contribution drops at high masses, resulting in a narrower $q$ distribution in the massive population than at lower masses. Using a simple accretion model, we show that the observed $q$ distributions and quenched fractions are consistent with a scenario where no morphological transformation occurs for the environmentally quenched population in the two intermediate mass bins. Our results suggest that environmental quenching mechanism(s) likely produce a population that has a different morphological mix than those resulting from the dominant quenching mechanism in the field.Comment: Accepted for publication in ApJ. 25 pages, 15 figure

Gogreen : A critical assessment of environmental trends in cosmological hydrodynamical simulations at z approximate to 1

Peer reviewe

Gemini Observations of Galaxies in Rich Early Environments (GOGREEN) I : survey description

We describe a new Large Program in progress on the Gemini North and South telescopes: Gemini Observations of Galaxies in Rich Early Environments (GOGREEN). This is an imaging and deep spectroscopic survey of 21 galaxy systems at 1 10 in halo mass. The scientific objectives include measuring the role of environment in the evolution of low-mass galaxies, and measuring the dynamics and stellar contents of their host haloes. The targets are selected from the SpARCS, SPT, COSMOS, and SXDS surveys, to be the evolutionary counterparts of today's clusters and groups. The new red-sensitive Hamamatsu detectors on GMOS, coupled with the nod-and-shuffle sky subtraction, allow simultaneous wavelength coverage over lambda similar to 0.6-1.05 mu m, and this enables a homogeneous and statistically complete redshift survey of galaxies of all types. The spectroscopic sample targets galaxies with AB magnitudes z' <24.25 and [3.6] mu m <22.5, and is therefore statistically complete for stellar masses M* greater than or similar to 10(10.3) M-circle dot, for all galaxy types and over the entire redshift range. Deep, multiwavelength imaging has been acquired over larger fields for most systems, spanning u through K, in addition to deep IRAC imaging at 3.6 mu m. The spectroscopy is similar to 50 per cent complete as of semester 17A, and we anticipate a final sample of similar to 500 new cluster members. Combined with existing spectroscopy on the brighter galaxies from GCLASS, SPT, and other sources, GOGREEN will be a large legacy cluster and field galaxy sample at this redshift that spectroscopically covers a wide range in stellar mass, halo mass, and clustercentric radius.Peer reviewe

Acute Hepatic Porphyrias: Review and Recent Progress.

The acute hepatic porphyrias (AHPs) are a group of four inherited diseases of heme biosynthesis that present with episodic, acute neurovisceral symptoms. The four types are 5-aminolevulinic acid (ALA) dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Their diagnoses are often missed or delayed because the clinical symptoms mimic other more common disorders. Recent results indicate that acute intermittent porphyria, the most severe of the more common types of AHP, is more prevalent than previously thought, occurring in about 1 in 1600 Caucasians, but with low clinical penetrance (approximately 2%-3%). Here we provide an updated review of relevant literature and discuss recent and emerging advances in treatment of these disorders. Symptomatic attacks occur primarily in females between 14 and 45 years of age. AHP is diagnosed by finding significantly elevated levels of porphyrin precursors ALA and porphobilinogen in urine. Acute attacks should be treated promptly with intravenous heme therapy to avoid the development of potentially irreversible neurologic sequelae. All patients should be counseled about avoiding potential triggers for acute attacks and monitored regularly for the development of long-term complications. Their first-degree relatives should undergo targeted gene testing. Patients who suffer recurrent acute attacks can be particularly challenging to manage. Approximately 20% of patients with recurrent symptoms develop chronic and ongoing pain and other symptoms. We discuss newer treatment options in development, including small interfering RNA, to down-regulate ALA synthase-1 and/or wild-type messenger RNA of defective genes delivered selectively to hepatocytes for these patients. We expect that the newer treatments will diminish and perhaps obviate the need for liver transplantation as treatment of these inborn metabolic disorders

Benefits of prophylactic heme therapy in severe acute intermittent porphyria

Acute intermittent porphyria (AIP), an autosomal dominant inborn error of metabolism, is the most common and severe form of the acute porphyrias. Attacks of severe abdominal pain, often with hypertension, tachycardia, are cardinal features of AIP, often requiring hospital admissions. Frequent recurrent attacks of AIP, defined as >3 attacks in one year, during which at least one attack requires intravenous heme therapy, are associated with significant morbidity, lost productivity, and health care burden. We report two patients with such frequent attacks of AIP, who have been managed with prophylactic heme therapy on a weekly basis. We describe results particularly in relation to symptom control, biochemical findings, health care costs, quality of life, and utilization of resources. During 11-month duration of weekly prophylactic heme infusions, we observed a 100% decrease in acute attacks and inpatient admissions in one subject and a 75% decrease in the other. During this time, we also observed a significant decrease in the number of emergency room visits. The decrease in number of acute attacks requiring hospital admission was associated with significantly decreased health care costs and improved quality of life. Reduction of both emergency room visits and hospital admissions decreased the utilization of health care services. Outpatient weekly infusions were also noted to be associated with better reimbursements and reduced overall costs of health care for the subjects. Both our subjects also endorsed better symptom control, quality of life and better understanding of disease. Thus, prophylactic heme therapy, through a multi-disciplinary approach, decreases the incidence of acute attacks, decreases health care costs and leads to better patient satisfaction and quality of life. Keywords: Acute hepatic porphyria, Health care costs, Health-related quality of life, Heme therapy, Prophylactic therap

Pilot study of mitochondrial bioenergetics in subjects with acute porphyrias

Background and aimsThe acute porphyrias are characterized by defects in heme synthesis, particularly in the liver. In some affected patients, there occurs a critical deficiency in a regulatory heme pool within hepatocytes that leads to up-regulation of 5-aminolevulinic acid [ALA] synthase-1, which is the first and normally rate-controlling enzyme in the pathway. In earlier work, we described defects in mitochondrial functions in cultured skin fibroblasts from patients with acute intermittent porphyria [AIP]. Others described defects in livers of murine models of AIP. Here, we explored mitochondrial energetics in peripheral blood mononuclear cells [PBMCs] and platelets in persons with AIP and hereditary coproporphyria [HCP]. Our hypotheses were that there are deficits in bioenergetic capacity in acute porphyrias and that subjects with more severe acute porphyria have more pronounced reductions in mitochondrial oxygen consumption rates [OCR].MethodsWe studied 17 subjects with acute hepatic porphyrias, 14 with classical AIP, one with severe AIP due to homozygous deficiency of hydroxymethylbilane synthase [HMBS], 2 with HCP, and 5 non-porphyric controls. We collected peripheral blood, isolated PBMCs, which we assayed either immediately or after frozen storage [80C] for up to 14 days. Using Seahorse XF-24-3, we measured OCR in the presence of glucose + pyruvate under basal condition, and after additions of oligomycin, carbonylcyanide p-trifluoromethoxyphenylhydrazone [FCCP], and antimycin+rotenone.ResultsMost subjects [13/17, 76%] were female. Subjects with moderate/severe symptoms associated with acute porphyria had significantly lower basal and maximal-OCR than those with no/mild symptoms who were the same as controls. We observed significant inverse correlation between urinary porphobilinogen [PBG] excretion and OCR. The subject with homozygous AIP had a much lower-OCR than his asymptomatic parents.Summary/conclusionsResults support the hypothesis that active acute hepatic porphyria is characterized by a deficiency in mitochondrial function that is detectable in PBMCs, suggesting that limitations in electron transport and ATP production exist in such individuals