Prevalence of risk factors associated with development of capsular contracture after placement of breast implants.

Objective: To determinate the prevalence of the main risk factors associated with development of capsular contracture after placement of breast implants in a referral center.

Method: Retrospect study on 210 patients where sociodemographic variables, Baker's clinical scale and histopathological results were recorded.

Results: Statistical analysis of 210 patients was performed; 98.

An ensemble reconstruction of global monthly sea surface temperature and sea ice concentration 1000-1849.

This paper describes a global monthly gridded Sea Surface Temperature (SST) and Sea Ice Concentration (SIC) dataset for the period 1000-1849, which can be used as boundary conditions for atmospheric model simulations. The reconstruction is based on existing coarse-resolution annual temperature ensemble reconstructions, which are then augmented with intra-annual and sub-grid scale variability. The intra-annual component of HadISST.

Intraspecific Genetic Diversity of L. and Evolutionary Relationships to L. (Cistaceae): Meeting of the Generations?

(Cistaceae) comprises a number of white- and purple-flowering shrub species widely distributed in the Mediterranean basin. Within genus many taxa are subject to various taxonomic uncertainties. , a prominent member of the purple-flowered clade, is a prime case of the current taxonomic troubles.

No evidence for globally coherent warm and cold periods over the preindustrial Common Era.

Earth's climate history is often understood by breaking it down into constituent climatic epochs. Over the Common Era (the past 2,000 years) these epochs, such as the Little Ice Age, have been characterized as having occurred at the same time across extensive spatial scales. Although the rapid global warming seen in observations over the past 150 years does show nearly global coherence, the spatiotemporal coherence of climate epochs earlier in the Common Era has yet to be robustly tested.

Population Pharmacokinetic Modeling and Exposure-Response Assessment for the Antibody-Drug Conjugate Brentuximab Vedotin in Hodgkin's Lymphoma in the Phase III ECHELON-1 Study.

The efficacy of the CD30-directed antibody-drug conjugate (ADC) brentuximab vedotin was established in combination with chemotherapy as frontline treatment for advanced classical Hodgkin's lymphoma in the randomized phase III ECHELON-1 study. Population pharmacokinetic (PK) and exposure-response models were developed to quantify sources of PK variability and relationships between exposure and safety/efficacy end points in ECHELON-1. The influence of patient-specific factors on the PK of the ADC and the microtubule-disrupting payload monomethyl auristatin E (MMAE) was investigated; none of the significant covariates had a clinically relevant impact.

Perspectives of regional paleoclimate modeling.

Regional climate modeling bridges the gap between the coarse resolution of current global climate models and the regional-to-local scales, where the impacts of climate change are of primary interest. Here, we present a review of the added value of the regional climate modeling approach within the scope of paleoclimate research and discuss the current major challenges and perspectives. Two time periods serve as an example: the Holocene, including the Last Millennium, and the Last Glacial Maximum.

From global circulation to local flood loss: Coupling models across the scales.

Comprehensive flood risk modeling is crucial for understanding, assessing, and mitigating flood risk. Modeling extreme events is a well-established practice in the atmospheric and hydrological sciences and in the insurance industry. Several specialized models are used to research extreme events including atmospheric circulation models, hydrological models, hydrodynamic models, and damage and loss models.

[Archibald Cochrane: evidence, effectiveness and decision-making in health].

Nowadays, Evidence-Based Medicine plays a fundamental role while making medical decisions, considering that through the methods of science, it attempts to justify the variety of alternatives that may be offered to patients. In order to understand the historical evolution of this way of practicing medicine, it is necessary to review the contribution of one of the main participants in this cultural movement: Archibald Leman Cochrane, who helped to define the theoretical framework that has allowed the integration of science into the practice of medicine. Since he insisted in the need of integrating scientific evidence into clinical experience, his role became a fundamental and decisive element in the development of a new discipline: Evidence-Based Medicine.

Surgical Site Infection Rate Drops to 0% Using a Vacuum-Assisted Closure in Contaminated/Dirty Infected Laparotomy Wounds.

Wound site infections increase costs, hospital stay, morbidity, and mortality. Techniques used for wounds management after laparotomy are primary, delayed primary, and vacuum-assisted closures. The objective of this study is to compare infection rates between those techniques in contaminated and dirty/infected wounds.

Bromine soil/sediment enrichment in tidal salt marshes as a potential indicator of climate changes driven by solar activity: New insights from W coast Portuguese estuaries.

This paper aims at providing insight about bromine (Br) cycle in four Portuguese estuaries: Minho, Lima (in the NW coast) and Sado, Mira (in the SW coast). The focus is on their tidal marsh environments, quite distinct with regard to key biophysicochemical attributes. Regardless of the primary bromide (Br) common natural source, i.

A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing a simplified interventional mapping system (SIMS) that merges knowledge about existent drugs and their impact on the hallmarks of cancer.

Natural killer T cells in advanced melanoma patients treated with tremelimumab.

A significant barrier to effective immune clearance of cancer is loss of antitumor cytotoxic T cell activity. Antibodies to block pro-apoptotic/downmodulatory signals to T cells are currently being tested. Because invariant natural killer T cells (iNKT) can regulate the balance of Th1/Th2 cellular immune responses, we characterized the frequencies of circulating iNKT cell subsets in 21 patients with melanoma who received the anti-CTLA4 monoclonal antibody tremelimumab alone and 8 patients who received the antibody in combination with MART-126-35 peptide-pulsed dendritic cells (MART-1/DC).

Phase I study of tremelimumab (CP-675 206) plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours.

Background: Tremelimumab, a fully human cytotoxic T-lymphocyte antigen 4 monoclonal antibody, and PF-3512676, a Toll-like receptor-9 agonist, are targeted immune modulators that elicit durable single-agent antitumour activity in advanced cancer.

Methods: To determine the maximum tolerated dose (MTD) of these agents combined during this phase I study, patients received intravenous tremelimumab (6.0, 10.

Screening for polyphenols, antioxidant and antimicrobial activitiesof extracts from eleven Helianthemum taxa (Cistaceae) used in folk medicine in south-eastern Spain.

Ethnopharmacological Relevance: The Helianthemum genus contains approximately one hundred taxa. Some of them are important medicinal plants used in several countries for many different purposes. However, studies addressing the phytochemistry of many of these species or their biological activities are currently nonexistent.

Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

Purpose: In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy.

Patients And Methods: Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine).

Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion.

Background: CTLA4 blocking monoclonal antibodies provide a low frequency but durable tumor responses in patients with metastatic melanoma, which led to the regulatory approval of ipilimumab based on two randomized clinical trials with overall survival advantage. The similarly fully human anti-CTLA4 antibody tremelimumab had been developed in the clinic at a fixed rate infusion, resulting in very prolonged infusion times. A new formulation of tremelimumab allowed testing a shorter infusion time.

CTLA4 blockade induces frequent tumor infiltration by activated lymphocytes regardless of clinical responses in humans.

Background: CTLA4 blocking monoclonal antibodies provide durable clinical benefit in a subset of patients with advanced melanoma mediated by intratumoral lymphocytic infiltrates. A key question is defining whether the intratumoral infiltration (ITI) is a differentiating factor between patients with and without tumor responses.

Methods: Paired baseline and postdosing tumor biopsy specimens were prospectively collected from 19 patients with metastatic melanoma, including 3 patients with an objective tumor response, receiving the anti-CTLA4 antibody tremelimumab within a clinical trial with primary endpoint of quantitating CD8(+) cytotoxic T-lymphocyte (CTL) infiltration in tumors.

Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma.

Background: The effects on cell signalling networks upon blockade of cytotoxic T lymphocyte-associated antigen-4 (CTLA4) using the monoclonal antibody tremelimumab were studied in peripheral blood mononuclear cell (PBMC) samples from patients with metastatic melanoma.

Methodology/principal: Findings Intracellular flow cytometry was used to detect phosphorylated (p) signaling molecules downstream of the T cell receptor (TCR) and cytokine receptors. PBMC from tremelimumab-treated patients were characterized by increase in pp38, pSTAT1 and pSTAT3, and decrease in pLck, pERK1/2 and pSTAT5 levels.

Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer.

Purpose: Safety and efficacy of tremelimumab (CP-675,206), a fully human anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) monoclonal antibody, were assessed in patients with treatment-refractory colorectal cancer.

Patients And Methods: A single-arm, multicenter, phase II trial was conducted in patients with Eastern Cooperative Oncology Group performance status View Article and Find Full Text PDF

Imaging of CTLA4 blockade-induced cell replication with (18)F-FLT PET in patients with advanced melanoma treated with tremelimumab.

Unlabelled: Preclinical models predict that blockade of the coinhibitory molecule cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on lymphocytes results in the release of a cell cycle inhibitory checkpoint, allowing lymphocyte proliferation, tumor targeting, and regression. However, there is a paucity of data demonstrating that lymphocyte proliferation does occur in humans treated with CTLA4-blocking antibodies.

Methods: We tested the role of whole-body molecular imaging in patients with advanced melanoma receiving the CTLA4-blocking antibody tremelimumab, allowing the analysis of changes in glucose metabolism using the PET probe (18)F-FDG and cell replication with the PET probe 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT).

Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma.

Purpose: This phase II study assessed the antitumor activity of tremelimumab, a fully human, anti-CTL-associated antigen 4 monoclonal antibody, in patients with melanoma.

Experimental Design: Patients with refractory/relapsed melanoma received 15 mg/kg tremelimumab every 90 days. After 4 doses, patients with tumor response or stable disease were eligible to receive < or =4 additional doses.

Dendritic cell vaccination combined with CTLA4 blockade in patients with metastatic melanoma.

Purpose: Tumor antigen-loaded dendritic cells (DC) are believed to activate antitumor immunity by stimulating T cells, and CTL-associated antigen 4 (CTLA4)-blocking antibodies should release a key negative regulatory pathway on T cells. The combination was tested in a phase I clinical trial in patients with advanced melanoma.

Experimental Design: Autologous DC were pulsed with MART-1(26-35) peptide and administered with a dose escalation of the CTLA4-blocking antibody tremelimumab.

Phase I/II trial of tremelimumab in patients with metastatic melanoma.

Purpose: Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with tremelimumab (CP-675,206), a fully human anti-CTLA4 monoclonal antibody, was tolerated and demonstrated antitumor activity in a single dose, dose-escalation phase I trial in patients with solid tumors. This phase I/II trial was conducted to examine safety of multiple doses of tremelimumab, to further assess efficacy, and to identify an appropriate dosing regimen for further development.

Patients And Methods: Twenty-eight patients with metastatic melanoma received monthly intravenous infusions of tremelimumab at 3, 6, or 10 mg/kg for up to 1 year to determine recommended monthly phase II dose.

Intratumoral immune cell infiltrates, FoxP3, and indoleamine 2,3-dioxygenase in patients with melanoma undergoing CTLA4 blockade.

Purpose: CTL-associated antigen 4 (CTLA4)-blocking monoclonal antibodies induce long-term regression of metastatic melanoma in some patients, but the exact mechanism is unknown. In this study, biopsies of selected accessible tumor lesions from patients treated with tremelimumab were examined to further elucidate the mechanism of its antitumor activity.

Experimental Design: Fifteen tumor biopsies from 7 patients who had been treated with tremelimumab (CP-675,206) were collected.