Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Erratum: Phase Equilibrium In Aqueous Two-phase Systems Containing Ethylene Oxide-propylene Oxide Block Copolymers And Dextran (fluid Phase Equilibria (2004) 218 (221-228) Doi: 10.1016/j.fluid.2004.01.001)

[No abstract available]231225025

Nipple-sparing mastectomy for breast cancer and risk-reducing surgery : the memorial sloan-kettering cancer center experience

Background: Nipple-sparing mastectomy (NSM) has been gathering increased recognition as an alternative to more traditional mastectomy approaches. Initially, questions concerning its oncologic safety limited the use of NSM. Nevertheless, mounting evidence supporting the practice of NSM for both prophylactic and oncologic purposes is leading to its more widespread use and broadened indications. Methods: Using a prospectively maintained database, we reviewed our experience of 353 NSM procedures performed in 200 patients over the past 10 years. Results: The indications for surgery were:196 prophylactic risk-reduction (55.5%), 74 ductal carcinoma in situ (DCIS) (20.8%), 82 invasive cancer (23.2%), and 1 phyllodes tumor (0.5%). The nipple areolar complex (NAC) was entirely preserved in 341 mastectomies (96.7%). There were 11 patients (3.1%) who were found to have cancer at the nipple margin, warranting further excision. A total of 69 breasts (19.5%) had some degree of skin desquamation or necrosis, but only 12 (3.3%) required operative debridement, of which 3 breasts (1%) necessitated removal of a breast implant. Also, 6 patients (2%) were treated for infection. Of the 196 prophylactic NSMs, 11 specimens (5.6%) were found to harbor occult cancer (8 DCIS and 3 invasive cancers). One patient who underwent NSM for invasive ductal carcinoma in 2006 developed metastatic disease to her brain. No other recurrences are attributable to the 353 NSMs. Conclusions: The trends demonstrate the increasing acceptance of NSM as a prophylactic procedure as well as for therapeutic purposes. Although NSM is not standard, our experience supports the selective use of NSM in both prophylactic and malignant settings

Precipitation Of Porcine Insulin With Carbon Dioxide

Recent works have pointed to the use of volatile electrolytes such as carbon dioxide (CO2) dissolved in aqueous solutions as a promising alternative to the precipitating agents conventionally used for protein recovery in the food and pharmaceutical industries. In this work we investigated experimental and theoretical aspects of the precipitation of porcine insulin, a biomolecule of pharmaceutical interest, using CO2 as an acid-precipitating agent. The solubility of porcine insulin in NaHCO3 solutions in pressurized CO2 was determined as a function of temperature and pressure, with a minimum being observed close to the protein isoelectric point. A thermodynamic model was developed and successfully utilized to correlate the experimental data. Insulin was considered a polyelectrolyte in the model and its self-association reactions were also taken into account. 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Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-03-06T13:02:43Z No. of bitstreams: 1 Daltro PS Therapy with mesenchymal stromal....pdf: 2220259 bytes, checksum: 0d8b877260e733ab651cf93ee12e0276 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-03-06T13:39:29Z (GMT) No. of bitstreams: 1 Daltro PS Therapy with mesenchymal stromal....pdf: 2220259 bytes, checksum: 0d8b877260e733ab651cf93ee12e0276 (MD5)Made available in DSpace on 2018-03-06T13:39:29Z (GMT). No. of bitstreams: 1 Daltro PS Therapy with mesenchymal stromal....pdf: 2220259 bytes, checksum: 0d8b877260e733ab651cf93ee12e0276 (MD5) Previous issue date: 2017Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), by Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) and Financiadora de Estudos e Projetos (FINEP).Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Federal University of Bahia. Multicentric Program in Biochemistry and Molecular Biology. Salvador, BA, BrazilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Federal University of Bahia. Faculty of Biology. Salvador, BA, BrazilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFederal University of Bahia. Faculty of Pharmacy. Salvador, BA, BrazilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilHospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil / Federal University of Bahia. Institute of Health Sciences. Department of Biochemistry and Biophysics. Salvador, BA, BrazilObesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity.Methods. After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed using electrocardiography, echocardiography and treadmill test. Body weight and biochemical parameters were evaluated. Cardiac tissue was used for real time (RT)-polymerase chain reaction (PCR) and histopathologic analysis. Results/ Discussion. Characterization of CM by protein array showed the presence of different cytokines and growth factors, including chemokines, osteopontin, cystatin C, Serpin E1 and Gas 6. HFD-fed mice presented cardiac arrhythmias, altered cardiac gene expression and fibrosis reflected in physical exercise incapacity associated with obesity and diabetes. Administration of MSCs or CM improved arrhythmias and exercise capacity. This functional improvement correlated with normalization of GATA4 gene expression in the hearts of MSC- or CM-treated mice. The gene expression of connexin 43, troponin I, adiponectin, transforming growth factor (TGF) β, peroxisome proliferator activated receptor gamma (PPARγ), insulin-like growth factor 1 (IGF-1), matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) were significantly reduced in MSCs, but not in CM-treated mice. Moreover, MSC or CM administration reduced the intensity of cardiac fibrosis. Conclusion. Our results suggest that MSCs and CM have a recovery effect on cardiac disturbances due to obesity and corroborate to the paracrine action of MSCs in heart disease models