Nutritional management of a patient with chronic intestinal failure and hemodialysis receiving teduglutide: A case report.

We present the case of a 35-y-old woman with short bowel syndrome secondary to extensive intestinal resection with associated chronic kidney disease who was undergoing hemodialysis. This patient required permanent supplementation with intradialytic parenteral nutrition because of a high-output end-jejunostomy. The patient was a candidate for treatment with teduglutide, a glucagon-like peptide 2 analog, intending to increase intestinal absorption. A complete nutritional assessment was performed using bioelectrical impedance vector analysis. Teduglutide treatment was successful, and after a 1-y follow-up, the patient had considerably reduced end-jejunostomy output (reduction of 6 L/d) and an improved nutritional status (9.1 kg weight gain, 1.4 kg fat-free mass gain, and a 2.2-degree increase in bioimpedance phase angle). However, we have been unable to reduce intradialytic parenteral nutrition, which the patient requires thrice weekly. No significant secondary effects have occurred because of teduglutide administration. This may be the first reported use of teduglutide in a patient with short bowel syndrome undergoing hemodialysis who was monitored using bioelectrical impedance data during follow-up.

Identification of a Human SOCS1 Polymorphism That Predicts Rheumatoid Arthritis Severity.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an autoimmune response in the joints and an exacerbation of cytokine responses. A minority of patients with RA experience spontaneous remission, but most will show moderate/high disease activity, with aggressive joint damage and multiple systemic manifestations. There is thus is a great need to identify prognostic biomarkers for disease risk to improve diagnosis and prognosis, and to inform on the most appropriate therapy. Here we focused on suppressor of cytokine signaling 1 (SOCS1), a physiological negative regulator of cytokines that modulates cell activation. Using four independent cohorts of patients with arthritis, we characterized the correlation between SOCS1 mRNA levels and clinical outcome. We found a significant inverse correlation between SOCS1 mRNA expression and disease activity throughout the follow-up of patients with RA. Lower baseline SOCS1 levels were associated with poorer disease control in response to methotrexate and other conventional synthetic disease-modifying anti-rheumatic drugs in early arthritis, and to rituximab in established (active) RA. Moreover, we identified several single nucleotide polymorphisms in the SOCS1 gene that correlated with SOCS1 mRNA expression, and that might identify those patients with early arthritis that fulfill RA classification criteria. One of them, rs4780355, is in linkage disequilibrium with a microsatellite (TTTTC)3-5, mapped 0.9 kb downstream of the SNP, and correlated with reduced SOCS1 expression in vitro. Overall, our data support the association between SOCS1 expression and disease progression, disease severity and response to treatment in RA. These observations underlie the relevance of SOCS1 mRNA levels for stratifying patients prognostically and guiding therapeutic decisions.

Growth Hormone Reprograms Macrophages toward an Anti-Inflammatory and Reparative Profile in an MAFB-Dependent Manner.

Growth hormone (GH), a pleiotropic hormone secreted by the pituitary gland, regulates immune and inflammatory responses. In this study, we show that GH regulates the phenotypic and functional plasticity of macrophages both in vitro and in vivo. Specifically, GH treatment of GM-CSF-primed monocyte-derived macrophages promotes a significant enrichment of anti-inflammatory genes and dampens the proinflammatory cytokine profile through PI3K-mediated downregulation of activin A and upregulation of MAFB, a critical transcription factor for anti-inflammatory polarization of human macrophages. These in vitro data correlate with improved remission of inflammation and mucosal repair during recovery in the acute dextran sodium sulfate-induced colitis model in GH-overexpressing mice. In this model, in addition to the GH-mediated effects on other immune cells, we observed that macrophages from inflamed gut acquire an anti-inflammatory/reparative profile. Overall, these data indicate that GH reprograms inflammatory macrophages to an anti-inflammatory phenotype and improves resolution during pathologic inflammatory responses.

A multi-proxy approach to Late Holocene fluctuations of Tungnahryggsjökull glaciers in the Tröllaskagi peninsula (northern Iceland).

The Tröllaskagi Peninsula in northern Iceland hosts more than a hundred small glaciers that have left a rich terrestrial record of Holocene climatic fluctuations in their forelands. Traditionally, it has been assumed that most of the Tröllaskagi glaciers reached their Late Holocene maximum extent during the Little Ice Age (LIA). However, there is evidence of slightly more advanced pre-LIA positions. LIA moraines from Iceland have been primary dated mostly through lichenometric dating, but the limitations of this technique do not allow dating of glacial advances prior to the 18th or 19th centuries. The application of 36Cl Cosmic-Ray Exposure (CRE) dating to Tungnahryggsjökull moraine sequences in Vesturdalur and Austurdalur (central Tröllaskagi) has revealed a number of pre-LIA glacial advances at ~400 and ~700 CE, and a number of LIA advances in the 15th and 17th centuries, the earliest LIA advances dated so far in Tröllaskagi. This technique hence shows that the LIA chronology in Tröllaskagi agrees with that of other European areas such as the Alps or the Mediterranean mountains. The combined use of lichenometric dating, aerial photographs, satellite images and fieldwork shows that the regional colonization lag of the commonly used lichen species Rhizocarpon geographicum is longer than previously assumed. For exploratory purposes, an alternative lichen species (Porpidia soredizodes) has been tested for lichenometric dating, estimating a tentative growth rate of 0.737 mm yr-1.