Insufficient evidence of benefit regarding mortality due to albumin substitution in HCC-free cirrhotic patients undergoing large volume paracentesis.

BACKGROUND: Current guidelines for clinical practice recommend the infusion of human albumin after large volume paracentesis. After inspecting the current evidence behind this recommendation, we decided to conduct a systematic review and meta-analysis in order to address the effect of albumin on mortality and morbidity in the context of large volume paracentesis. METHODS: We performed a comprehensive search of large databases and abstract books of conference proceedings up to March 15th 2016 for randomized controlled trials, testing the infusion of human albumin against alternatives (vs no treatment, vs plasma expanders; vs vasoconstrictors) in HCC-free patients suffering from cirrhosis. We analyzed these trials with regard to mortality, changes in plasma renin activity (PRA), hyponatremia, renal impairment, recurrence of ascites with consequential re-admission into hospital and additional complications. We employed trial sequential analysis in order to calculate the number of patients required in controlled trials to be able to determine a statistically significant advantage of the administration of one agent over another with regard to mortality. RESULTS: We were able to include 21 trials totaling 1277 patients. While the administration of albumin prevents a rise in PRA as well as hyponatremia, no improvement in strong clinical endpoints such as mortality could be demonstrated. Trial sequential analysis showed that at least 1550 additional patients need to be recruited into RCTs and analyzed with regard to this question in order to detect or disprove a 25% mortality effect. CONCLUSIONS: There is insufficient evidence that the infusion of albumin after LVP significantly lowers mortality in HCC-free patients with advanced liver disease.

CT imaging of bone and bone marrow infiltration in malignant melanoma--Challenges and limitations for clinical staging in comparison to 18FDG-PET/CT.

Rationale of this study was the evaluation of the diagnostic value of computed tomography (CT) in the detection of bone marrow infiltration in comparison to PET/CT. Fifty patients (age 61 ± 15.12 years) with metastatic malignant melanoma underwent 18F-FDG-PET/CT, including contrast-enhanced CT. 2 readers evaluated the CT images in consensus for bone and bone marrow lesions focusing on lesion location, type and size. PET/CT was used as reference standard to estimate sensitivity, specificity, negative and positive predictive value. Moreover, the bone marrow density was estimated in the long bones and the sacral bone. Serum hamoglobin, thrombocyte level and S100 protein were correlated with the presence or absence of bone and bone marrow lesions. According to PET/CT as standard of reference, of 594 bone and medullary lesions 495 were considered malignant. Of these 77.8% were medullary, 20.4% lytic, 1% sclerotic and 0.8% mixed lytic/sclerotic. Contrast-enhanced CT yielded a lesion-based sensitivity of 36.8% and a specificity of 87.9% (PPV 93.8%; NPV 21.8%). Patient-based sensitivity and specificity were 78.8% and 82.4%, respectively. Of the missed lesions, most were medullary (95.8%). A disseminated bone marrow involvement (defined as >10 bone marrow lesions or diffuse infiltration of a whole body segment) was described in 11 cases, in 6 cases the disseminated involvement was underestimated or missed on CT. In cases with disseminated bone marrow involvement the bone marrow density was significantly higher in the humerus (p=0.04), but not in the femur or sacral bone (p=0.06). Multivariate analysis revealed no isolated effect of bone metastases on S100 serum and hemoglobin level, but both were significantly altered in patients with disseminated bone marrow involvement (p<0.05). In conclusion, the diagnostic value of computed tomography for the detection of bone marrow metastases in patients with melanoma, is limited. Especially in cases with disseminated bone marrow involvement about 50% of the cases were missed or underestimated.

Factors associated with reclassification of hyperplastic polyps after pathological reassessment from screening and surveillance colonoscopies.

INTRODUCTION: A substantial interobserver variation in the differential diagnosis of hyperplastic polyps (HPs) and sessile or traditional serrated adenomas (SSAs/TSAs) has been described. METHODS: The aim of this study is to determine the magnitude of reclassification of HPs and associated factors after pathological reassessment of specimens from screening and surveillance colonoscopies, and to estimate its consequences for follow-up recommendations. RESULTS: Among 1694 screening and surveillance colonoscopies, a total of 536 polyps were initially diagnosed as HPs and remained unchanged in 88.5% (n = 474), whereas 7.6 (n = 41) and 1.1% (n = 6) were reclassified as SSA and TSA, respectively. Compared to definite HPs, SSAs were found more frequently in men than in women (82.9 vs. 61.2%, p < 0.05), and in individuals ≥65.0 years (51.2 vs. 31.6%, p = 0.05). Also, more SSAs were >5 mm in size (36.6 vs. 6.3%, p < 0.05) and were localized in the proximal colon (31.7 vs. 11.8%, p < 0.05). In a mixed model analysis, age ≥65.0 years (OR 4.13, 95% CI 1.22-14.2), snare polypectomy (OR 23.6, 95% CI 4.86-115), and coincident advanced adenomas (OR 7.56, 95% CI 1.31-43.5) were significantly (p < 0.05) associated with reclassification to SSAs. Only 0.53% of patients had received false recommendations for follow-up visits based on the incorrect HP diagnosis. A c.1799T>A, p.V600E BRAF mutation was detected in 21.9 % (n = 9) of reclassified SSAs. CONCLUSION: Considering these factors may be helpful in serrated lesions that are difficult to allocate. Incorrect recommendations regarding control colonoscopy intervals due to misdiagnosed HPs can explain only a small fraction of interval colorectal cancers.

Dated Plant Phylogenies Resolve Neogene Climate and Landscape Evolution in the Cape Floristic Region.

In the context of molecularly-dated phylogenies, inferences informed by ancestral habitat reconstruction can yield valuable insights into the origins of biomes, palaeoenvironments and landforms. In this paper, we use dated phylogenies of 12 plant clades from the Cape Floristic Region (CFR) in southern Africa to test hypotheses of Neogene climatic and geomorphic evolution. Our combined dataset for the CFR strengthens and refines previous palaeoenvironmental reconstructions based on a sparse, mostly offshore fossil record. Our reconstructions show remarkable consistency across all 12 clades with regard to both the types of environments identified as ancestral, and the timing of shifts to alternative conditions. They reveal that Early Miocene land surfaces of the CFR were wetter than at present and were dominated by quartzitic substrata. These conditions continue to characterize the higher-elevation settings of the Cape Fold Belt, where they have fostered the persistence of ancient fynbos lineages. The Middle Miocene (13-17 Ma) saw the development of perennial to weakly-seasonal arid conditions, with the strongly seasonal rainfall regime of the west coast arising ~6.5-8 Ma. Although the Late Miocene may have seen some exposure of the underlying shale substrata, the present-day substrate diversity of the CFR lowlands was shaped by Pliocene-Pleistocene events. Particularly important was renewed erosion, following the post-African II uplift episode, and the reworking of sediments on the coastal platform as a consequence of marine transgressions and tectonic uplift. These changes facilitated adaptive radiations in some, but not all, lineages studied.

A Novel Easy-to-Use Prediction Scheme for Upper Gastrointestinal Bleeding: Cologne-WATCH (C-WATCH) Risk Score.

Acute upper gastrointestinal bleeding (UGIB) is the leading indication for emergency endoscopy. Scoring schemes have been developed for immediate risk stratification. However, most of these scores include endoscopic findings and are based on data from patients with nonvariceal bleeding. The aim of our study was to design a pre-endoscopic score for acute UGIB--including variceal bleeding--in order to identify high-risk patients requiring urgent clinical management. The scoring system was developed using a data set consisting of 586 patients with acute UGIB. These patients were identified from the emergency department as well as all inpatient services at the University Hospital of Cologne within a 2-year period (01/2007-12/2008). Further data from a cohort of 322 patients who presented to our endoscopy unit with acute UGIB in 2009 served for external/temporal validation.Clinical, laboratory, and endoscopic parameters, as well as further data on medical history and medication were retrospectively collected from the electronic clinical documentation system. A multivariable logistic regression was fitted to the development set to obtain a risk score using recurrent bleeding, need for intervention (angiography, surgery), or death within 30 days as a composite endpoint. Finally, the obtained risk score was evaluated on the validation set. Only C-reactive protein, white blood cells, alanine-aminotransferase, thrombocytes, creatinine, and hemoglobin were identified as significant predictors for the composite endpoint. Based on the regression coefficients of these variables, an easy-to-use point scoring scheme (C-WATCH) was derived to estimate the risk of complications from 3% to 86% with an area under the curve (AUC) of 0.723 in the development set and 0.704 in the validation set. In the validation set, no patient in the identified low-risk group (0-1 points), but 38.7% of patients in the high-risk group (≥ 2 points) reached the composite endpoint. Our easy-to-use scoring scheme is able to distinguish high-risk patients requiring urgent endoscopy, from low-risk cases who are suitable candidates for outpatient management or in whom endoscopy may be postponed. Based on our findings, a prospective validation of the C-WATCH score in different patient populations outside the university hospital setting seems warranted.

Delivery of marine larvae to shore requires multiple sequential transport mechanisms.

Most sedentary marine animals disperse from their place of origin during their initial life stages as larvae. The delivery of planktonic larvae back to coastal adult habitats after weeks or months of offshore development is commonly thought to be stochastic, resulting in large recruitment fluctuations and making predictive understanding of population dynamics difficult. Time series of invertebrate settlement on intertidal shores have been used to infer how various oceanographic processes deliver planktonic larvae ashore. However, the possibility that successful settlement may involve a series of different transport mechanisms, which are sequentially utilized by late-stage larvae, has received little attention. To address this, we monitored both the delivery of mussel and barnacle larvae to inner-shelf moorings positioned 200-1400 m from the shore, and larval settlement in the intertidal adult habitat, at two contrasting sites: a headland forming an upwelling center and a downstream bay. Model selection was employed to determine the most likely scenario(s) of larval onshore transport from four a priori transport mechanisms individually and in combination: (1) upwelling or relaxation/downwelling, (2) tidal motions, (3) diurnal sea breezes, and (4) surface waves. Mussel larvae were delivered to the inner shelf during upwelling in the bay, but during downwelling at the headland, and were further transported to the shore by surface waves at both locales. In contrast, the delivery of barnacle larvae to the inner shelf occurred during relaxation/downwelling events at both sites, and intertidal settlement coincided with spring tides, suggesting a role for internal tides in their onshore transport. Thus, sequential mechanisms appear to be utilized by larvae to get to the shore, involving interactions of regional-scale upwelling/downwelling processes and local-scale tidal and surface-wave processes, which differ among taxa and among sites with different topography. A bottleneck for larval delivery across the surf zone may be a result of out-of-phase steps in sequential transport mechanisms leaving larvae lost "in transit."

Circadian Variation in Arterial Blood Pressure and Glaucomatous Optic Neuropathy--A Systematic Review and Meta-Analysis.

BACKGROUND: Epidemiological studies have led to equivocal results concerning the role of arterial blood pressure as a risk factor for the development of glaucomatous damage and progressive visual field loss in glaucoma has been attributed to low nighttime blood pressure, especially when oral antihypertensives have been combined with beta-blocking eyedrops. In order to answer the question whether nocturnal blood pressure or blood pressure dip during ambulatory blood pressure monitoring are associated with progressive visual field loss we performed a systematic review and meta-analysis of studies in patients with primary open-angle glaucoma and normal tension glaucoma. METHODS: After searching MEDLINE, the Cochrane Library, and EMBASE, only 5 studies could be found reporting information on the method of ambulatory blood pressure measurements, separate data for daytime and nighttime blood pressure, definition of nocturnal blood pressure dip, and assessment of visual fields over a period of at least 2 years. RESULTS: There was no difference in mean systolic or diastolic diurnal and nocturnal blood pressure between patients with or without progressive visual field loss. The odds ratio for deteriorating visual fields over 2 years with nocturnal dips >10% in systolic or diastolic blood pressure was 3.32 (1.84-6.00) and 2.09 (1.20-3.64), respectively. Data allowing a separate analysis of over-dipping were not available. CONCLUSIONS: Nocturnal blood pressure fall is a risk factor for progressive visual field loss in glaucoma. However, prospective studies are needed to define a tolerable degree of dipping. Antihypertensive therapy in glaucomatous patients should be controlled with ambulatory blood pressure monitoring.

Topography as a driver of diversification in the Cape Floristic Region of South Africa.

The rugged topography of the Cape Floristic Region (CFR), South Africa, is frequently invoked to explain the spectacular radiation of the Cape flora, but the mechanisms involved remain unclear. Where recent authors emphasize the importance of elevation gradients as stimuli for ecological speciation, earlier workers stressed the role of topography as an isolating mechanism, particularly in montane lineages. Using six Cape plant lineages, we tested whether elevation niches are phylogenetically conserved. We then assessed whether high-elevation species are more consistently range-restricted than low-elevation species, and whether high-elevation sisters show stronger range exclusivity (allopatry) and weaker ecological and phenotypic differentiation, suggestive of nonecological speciation. Elevation niches tend to be phylogenetically conserved. Also, high-elevation species are more consistently range-restricted than low-elevation species, potentially explaining the generally stronger range exclusivity of high-elevation sisters. While the high-elevation zone is less homogeneous ecologically, more data are required to demonstrate that high-elevation sister species show generally weaker ecological and phenotypic differentiation. Topographic complexity promotes geographical isolation at high elevations, thereby providing opportunities for nonecological, vicariant speciation. While recognizing the need for additional data, we suggest that the upland and lowland floras of the CFR may differ with regard to predominant speciation mode.

Nutrient availability moderates transpiration in Ehrharta calycina.

Transpiration-driven 'mass-flow' of soil-water can increase nutrient flow to the root surface. Here it was investigated whether transpiration could be partially regulated by nutrient status. Seeds of Ehrharta calycina from nine sites across a rainfall gradient were supplied with slow-release fertilizer dibbled into the sand surrounding the roots and directly available through interception, mass-flow and diffusion (dubbed 'interception'), or sequestered behind a 40-microm mesh and not directly accessible by the roots, but from which nutrients could move by diffusion or mass-flow (dubbed 'mass-flow'). Although mass-flow plants were significantly smaller than interception plants as a consequence of nutrient limitation, they transpired 60% faster, had 90% higher photosynthesis relative to transpiration (A/E), and 40% higher tissue P, Ca and Na concentrations than plants allowed to intercept nutrients directly. Tissue N and K concentrations were similar for interception and mass-flow plants. Transpiration was thus higher in the nutrient-constrained 'mass-flow' plants, increasing the transport of nutrients to the roots by mass-flow. Transpiration may have been regulated by N availability, resulting in similar tissue concentration between treatments. It is concluded that, although transpiration is a necessary consequence of photosynthetic CO(2) uptake in C(3) plants, plants can respond to nutrient limitation by varying transpiration-driven mass-flow of nutrients.