Behrensholmgaard9110

In addition, IH significantly increased cardiac interstitial fibrosis and cardiac contractility. In the HFD group, IH did not exert any additional effect, nor on insulin/Akt signaling, nor on cardiac remodeling and function.

Our study suggests that, despite systemic insulin resistance, IH exposure mediates an adaptive cardiac response in lean but not in obese mice. Further studies are needed to investigate which specific mechanisms are involved and to determine the long-term evolution of cardiac responses to IH.

Our study suggests that, despite systemic insulin resistance, IH exposure mediates an adaptive cardiac response in lean but not in obese mice. Further studies are needed to investigate which specific mechanisms are involved and to determine the long-term evolution of cardiac responses to IH.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that are associated with cancer predisposition syndromes in up to 80% of affected children. PPGLs can be divided into molecularly defined groups with comparable pathogenesis and biology (1) pseudohypoxic, (2) kinase signaling, and (3) Wnt-altered.

We report the data of children and adolescents diagnosed with PPGL who have been registered with the German GPOH-MET registry since 1997.

By December 2019, a total of 88 patients with PPGL were reported. Pheochromocytoma occurred in 56%, paraganglioma in 35%, and synchronous PPGLs in 9.1%. A total of 16% of patients presented with lymph node (5.7%) and distant metastases (10%). Median follow-up was 4.2years (range 0-17.1). Overall and disease-free survival (DFS) were 98.6% and 54.0%, respectively. Local relapses, metastases, and subsequent PPGLs occurred in 11%, 4.5%, and 15% of patients. Germline mutations were detected in 83% of patients (51% in VHL, 21% in SDHB, 7.8% in SDHD, and one patient each in RET and NF1). One patient was diagnosed with Pacak-Zhuang syndrome. A total of 96% of patients presented with PPGL of the pseudohypoxic subgroup (34% TCA cycle-related, 66% VHL/EPAS1-related). In multivariate analyses, extent of tumor resection was a significant prognostic factor for DFS.

Most pediatric PPGLs belong to the pseudohypoxia subgroup, which is associated with a high risk of subsequent PPGL events and metastatic disease. Comprehensive molecular profiling of children and adolescents with newly diagnosed PPGLs will open new avenues for personalized diagnosis, treatment, and surveillance.

Most pediatric PPGLs belong to the pseudohypoxia subgroup, which is associated with a high risk of subsequent PPGL events and metastatic disease. Comprehensive molecular profiling of children and adolescents with newly diagnosed PPGLs will open new avenues for personalized diagnosis, treatment, and surveillance.In many solid tumors including triple-negative breast cancer (TNBC), upregulation of the interleukin-4 receptor (IL-4R) has been shown to promote cancer cell proliferation, apoptotic resistance, metastatic potential, and a Th2 response in the tumor microenvironment (TME). Since immunosuppressive cells in the TME and spleen including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) also express the IL-4R, we hypothesized that selective depletion of IL-4R-bearing cells in TNBC would result in the direct killing of tumor cells and the depletion of immunosuppressive cells and lead to an enhanced antitumor response. To selectively target IL-4R+ cells, we employed DABIL-4, a fusion protein toxin consisting of the catalytic and translocation domains of diphtheria toxin fused to murine IL-4. As anticipated, DABIL-4 has potent cytotoxic activity against TNBC cells both in vitro and in vivo. We demonstrate in the murine 4T1 TNBC model that DABIL-4 significantly reduces tumor growth, splenomegaly, and lung metastases. Importantly, we also show that the administration of DABIL-4 results in the selective depletion of MDSCs, TAMs, and regulatory T cells in treated mice, with a concomitant increase in IFN-γ+ CD8 effector T cells in the TME. Since the 4T1 antitumor activity of DABIL-4 was largely diminished in IL-4R knockout mice, we postulate that DABIL-4 functions primarily as an immunotherapeutic by the depletion of MDSCs, TAMs, and regulatory T cells. NanoString analysis of control and treated tumors confirmed and extended these observations by showing a marked decline of mRNA transcripts that are associated with tumorigenesis and metastasis. In conclusion, we demonstrate that DABIL-4 targeting of both tumor and immunosuppressive host cells likely represents a novel and effective treatment strategy for 4T1 TNBC and warrants further study.

An under-recognized complication of gelatin-based haemostatic agents is their potential to cause anaphylactic reactions. This review aims to collate and analyse case in the literature of intraoperative anaphylaxis secondary to locally applied haemostatic agents.

An electronic search was performed on databases Medline, Embase, Pubmed and ProQuest. A total of 7671 articles were reviewed from title and abstract. After exclusion criteria and duplicates removed, 19 articles with 21 cases were included for analysis. Data extracted from each of the articles included patient demographics, haemostatic agent used, surgery type, known allergies and any objective evidence of hypersensitivity post anaphylactic episode, that is tryptase levels, IgE levels, skin prick testing.

Fifty-seven percent of cases involved patients <18 years of age; 57% of cases involved spinal surgery; 100% of cases displayed objective evidence of hypersensitivity (tryptase levels, bovine or porcine IgE levels, or skin prick testing). Thirive patient history and post-event patient investigation that could assist anaesthetists and surgeons in the prevention of future events.Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) are an established risk factor for cystic fibrosis (CF) and chronic pancreatitis. Whereas patients with CF usually develop complete exocrine pancreatic insufficiency, pancreatitis patients with CFTR mutations have mostly preserved exocrine pancreatic function. We therefore used a strain of transgenic mice with significant residual CFTR function (CFTRtm1HGU ) to induce pancreatitis experimentally by serial caerulein injections. Protease activation and necrosis were investigated in isolated acini, disease severity over 24h, pancreatic function by MRI, isolated duct stimulation and faecal chymotrypsin, and leucocyte function by ex vivo lipopolysaccharide (LPS) stimulation. Pancreatic and lung injury were more severe in CFTRtm1HGU but intrapancreatic trypsin and serum enzyme activities higher than in wild-type controls only at 8h, a time interval previously attributed to leucocyte infiltration. Ivacaftor purchase CCK-induced trypsin activation and necrosis in acini from CFTRtm1HGU did not differ from controls.