Severe Metformin Poisoning Successfully Treated with Simultaneous Venovenous Hemofiltration and Prolonged Intermittent Hemodialysis

Metformin poisoning is a life-threatening condition with a high mortality rate. We present a patient case of metformin poisoning following intake of 80 g metformin resulting in severe lactate acidosis with a nadir pH of 6.73 and circulatory collapse, successfully treated with addition of prolonged intermittent hemodialysis (HD) to continuous venovenous hemofiltration (CVVH). The patient’s pH became normal 48 hours after metformin ingestion during simultaneous CVVH and addition of 22 hours of intermittent HD in the ICU. The highest metformin level was found to be 991 μmol/L (therapeutic range 3.9–23.2 μmol/L). We conclude that in cases of severe metformin poisoning with circulatory shock and extreme lactic acidosis, the usual CVVH modality might not efficiently clear metformin. Therefore, additional prolonged HD should be considered even in the state of cardiovascular collapse with vasopressor requirement

The Danish Shoulder Arthroplasty Registry: clinical outcome and short-term survival of 2,137 primary shoulder replacements

The Danish Shoulder Arthroplasty Registry (DSR) was established in 2004. Data are reported electronically by the surgeons. Patient-reported outcome is collected 10–14 months postoperatively using the Western Ontario osteoarthritis of the shoulder index (WOOS). 2,137 primary shoulder arthroplasties (70% women) were reported to the registry between January 2006 and December 2008. Mean age at surgery was 69 years (SD 12). The most common indications were a displaced proximal humeral fracture (54%) or osteoarthritis (30%). 61% were stemmed hemiarthroplasties, 28% resurfacing hemiarthroplasties, 8% reverse shoulder arthroplasties, and 3% total arthroplasties. Median WOOS was 59% (IQR: 37–82). 5% had been revised by the end of June 2010. The most frequent indications for revision were dislocation or glenoid attrition

Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression:implications for atherosclerosis research

Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE−/− mice, their M1/M2 phenotype, inflammatory status, and lipid metabolism signatures were compared. oxLDL accumulation was similar in PEMs and BMDMs. On protein expression level, BMDMs showed an M2-like CD206(high)CD11c(low) profile, while cholesterol loading led to enhanced CD11c expression and reduced MCP-1 secretion. In contrast, PEMs expressed low levels of CD206 and CD11c, and responded to cholesterol loading by increasing CD11c expression and MCP-1 secretion. mRNA expression of M1/M2 markers was higher in PEMS than BMDMs, while lipid metabolism genes were similarly expressed. Whole aorta flow cytometry showed an accumulation of M2-like CD206(high)CD11c(low) macrophages in advanced versus early atherosclerotic disease in ApoE−/− mice. In isolated lesions, mRNA levels of the M2 markers Socs2, CD206, Retnla, and IL4 were downregulated with increasing disease severity. Likewise, mRNA expression of lipid metabolism genes (SREBP2, ACSL1, SRB1, DGAT1, and cpt1a) was decreased in advanced versus early lesions. In conclusion, PEMs and BMDMs are phenotypically distinct and differ from macrophages in lesions with respect to expression of M1/M2 markers and lipid metabolism genes

Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

Background Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes and tubular epithelial cells. We have previously shown that α-Gal A is delivered to these cells by different pathways involving different receptors. This study investigated the long-term changes in albuminuria, estimated glomerular filtration rate (eGFR) and urinary markers of both glomerular and tubular dysfunction in women with Fabry disease treated with ERT. Methods A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile, including the glomerular marker IgG, the tubular markers α1-microglobulin and retinol-binding protein (RBP), and the shared tubular and glomerular markers albumin and transferrin. Results ERT was associated with a significant reduction in albuminuria and a relatively stable eGFR. The decrease in albuminuria was paralleled by a decrease in both glomerular and tubular urine protein markers. Conclusions The data indicate that long-term ERT is associated with a reduction in albuminuria and glomerular and tubular urinary protein markers in women with Fabry disease and mild renal manifestation

Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata - seasonal variation and impact of environmental factors

Fucoidans are sulphated fucose-rich polysaccharides predominantly found in the cell walls of brown algae. The bioactive properties of fucoidans attract increasing interest from the medico-pharmaceutical industries and may drive an increase in demand of brown algae biomass. In nature, the biochemical composition of brown algae displays a seasonal fluctuation driven by environmental factors and endogenous rhythms. To cultivate and harvest kelps with high yields of fucoidans, knowledge is needed on seasonal variation and impact of environmental conditions on the fucoidan content of brown algae. The relations between the fucoidan content and key environmental factors (irradiance, nutrient availability, salinity and exposure) were examined by sampling natural populations of the common North Atlantic kelps, Saccharina latissima and Laminaria digitata, over a full year at Hanstholm in the North Sea and Aarhus in the Kattegat. In addition, laboratory experiments were carried out isolating the effects of the single factors. The results demonstrated that (1) seasonal variation alters the fucoidan content by a factor of 2–2.6; (2) interspecific differences exist in the concentrations of crude fucoidan (% of dry matter): L. digitata (11%) > S. latissima (6%); and (3) the effects of single environmental factors were not consistent between species or between different conspecific populations. The ambiguous response to single environmental factors complicates prospective directions for manipulating an increased content of fucoidan in a cultivation scenario and emphasizes the need for knowledge on performance of local kelp ecotypes.This study was carried out as part of the MacroAlgae Biorefinery (MAB3), the MacroAlgae Biorefinery 4 (MAB4) and the Macrofuels projects, funded by The Danish Council for Strategic Research, the Innovation Fund Denmark and the European Union's Horizon 2020 research and innovation programme under grant agreement no. 654010, respectively

Ice-core data used for the construction of the Greenland Ice-Core Chronology 2005 and 2021 (GICC05 and GICC21)

We here describe, document, and make available a wide range of data sets used for annual-layer identification in ice cores from DYE-3, GRIP, NGRIP, NEEM, and EGRIP. The data stem from detailed measurements performed both on the main deep cores and shallow cores over more than 40 years using many different setups developed by research groups in several countries and comprise both discrete measurements from cut ice samples and continuous-flow analysis data. The data series were used for counting annual layers 60 000 years back in time during the construction of the Greenland Ice-Core Chronology 2005 (GICC05) and/or the revised GICC21, which currently only reaches 3800 years back. Now that the underlying data are made available (listed in Table 1) we also release the individual annual-layer positions of the GICC05 timescale which are based on these data sets. We hope that the release of the data sets will stimulate further studies of the past climate taking advantage of these highly resolved data series covering a large part of the interior of the Greenland ice sheet