Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial.

Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule.

Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.

In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at the time of second vaccination and 4 weeks later, with values reported in standardized World Health Organization international units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy.

Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial.

Background: In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection.

Methods: Through case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80).

Efficacy and Safety of Inhaled Glycopyrronium Bromide in COPD: A Randomized, Parallel Group, Dose-Ranging Study (GLIMMER).

This Phase II, randomized, parallel group study was conducted as part of US regulatory requirements to identify the most appropriate dose of the long-acting muscarinic antagonist glycopyrronium bromide (GB) for use in a single-inhaler triple-therapy combination with the inhaled corticosteroid beclomethasone dipropionate plus the long-acting β-agonist formoterol fumarate. Eligible subjects were adults with COPD and post-bronchodilator forced expiratory volume in 1 s (FEV) 40-80% predicted. Subjects were randomized to receive inhaled double-blind GB 6.

International Delphi Expert Consensus on Safe Return to Surgical and Endoscopic Practice: From the Coronavirus Global Surgical Collaborative.

Objective: The aim of this work is to formulate recommendations based on global expert consensus to guide the surgical community on the safe resumption of surgical and endoscopic activities.

Background: The COVID-19 pandemic has caused marked disruptions in the delivery of surgical care worldwide. A thoughtful, structured approach to resuming surgical services is necessary as the impact of COVID-19 becomes better controlled.

Peripheral Vascular Trauma in Pediatrics: A Case Report and Literature Review.

Vascular lesions constitute an important cause of morbidity and mortality, including functional disability. Their poor documentation in the literature suggests a low frequency in the pediatric age range. Herein, we describe the case of an 11-year-old-boy with an isolated radial artery injury.

[Pancreatoblastoma in a pediatric patient: a case report].

Pancreoblastoma is a very rare tumor that originates from the exocrine epithelial cells of the pancreas. However, it is the most frequent pancreatic tumor in children. It usually appears in the first decade of life with an average of 5 years old.

Physiological responses in horses, donkeys and mules sold at livestock markets.

The horse welfare at markets includes fatigue, fear, fasting, dehydration and injuries. However, the scientific literature contains no readily-available information on the physiology responses of equids sold in livestock markets. The objective of the present study was to evaluate the effect of holding in livestock markets on gas exchange, the acid-base balance, energy metabolism, and the mineral and water balance in 4 types of horses (), donkeys () and mules (( × ).

Impact of treatment in long-term survival patients with follicular lymphoma: A Spanish Lymphoma Oncology Group registry.

Background: Follicular lymphoma is the second most common non-Hodgkin lymphoma in the United States and Europe. However, most of the prospective randomized studies have very little follow-up compared to the long natural history of the disease. The primary aim of this study was to investigate the long-term survival of our series of patients with follicular lymphoma.

Sam68 Mediates the Activation of Insulin and Leptin Signalling in Breast Cancer Cells.

Obesity is a well-known risk factor for breast cancer development in postmenopausal women. High insulin and leptin levels seem to have a role modulating the growth of these tumours. Sam68 is an RNA-binding protein with signalling functions that has been found to be overexpressed in breast cancer.

Effectiveness of chemotherapy in advanced differentiated thyroid cancer: a systematic review.

In differentiated thyroid carcinoma refractory to radioactive iodine (CDT-RTI), chemotherapy has been considered for decades to be the only systemic therapy with palliative purpose. Phase II studies assessing the efficacy of different chemotherapy outlines have been published. Nevertheless, phase III studies in these tumours have not been performed.

Altered expression of CKs 14/20 is an early event in a rat model of multistep bladder carcinogenesis.

Cytokeratins (CKs) 14 and 20 are promising markers for diagnosing urothelial lesions and for studying their prognosis and histogenesis. This work aimed to study the immunohistochemical staining patterns of CK14/20 during multistep carcinogenesis leading to papillary bladder cancer in a rat model. Thirty female Fischer 344 rats were divided into three groups: group 1 (control); group 2, which received N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 20 weeks plus 1 week without treatment; and group 3, which received BBN for 20 weeks plus 8 weeks without treatment.

Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group.

Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included.

Are there any significant variations in the clinical or histological presentation of lymphoid pathologies over the course of time in Spain?

Introduction: Little data is available concerning variations in the clinical characteristics of lymphoid neoplasms at presentation. We decided to investigate whether any variations in these characteristics had occurred in Spain during the last few years.

Materials And Methods: The GOTEL group database is an archive of all new lymphoma cases, regardless of their histological subtype, diagnosed in the hospitals within the group.

Raman spectroscopy for the process analysis of the manufacturing of a suspension metered dose inhaler.

The purpose of this research was to demonstrate the utility of Raman spectroscopy for process analysis of a suspension metered dose inhaler manufacturing process. Chemometric models were constructed for the quantification of ethanol and active pharmaceutical ingredient such that both could be monitored in real-time during the compounding and filling operations via tank measurements and recirculation line flow-cell measurements. Different spectral preprocessing techniques were used to delineate the effects of mixing speed and temperature changes from actual concentration effects.

The effects of sirolimus on urothelial lesions chemically induced in ICR mice by BBN.

Background: Sirolimus was originally used as an immunosuppressant drug but recent reports have indicated that it may have other potential biological effects as an anticancer drug. The chemopreventive efficacy of sirolimus was evaluated in an experimental model of invasive urinary bladder cancer.

Materials And Methods: ICR mice received N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water for a period of twelve weeks.

Correction of nasojugal groove with tunnelled fat graft.

Background: Pronounced nasojugal sulcus (tear trough deformity) is a frequent and distressing symptom in aesthetic palpebral surgery. The sliding fat technique using the transcutaneous or transconjunctival approach has proven to be considerably useful in patients with clinically evident fat bags. In the absence of fat bags, commonly used techniques can lead to unpredictable (and frequently less than optimal) results.

How many polysomnograms must sleep fellows score before becoming proficient at scoring sleep?

Objectives: In the field of sleep medicine, there is a paucity of evidence-based curriculum development strategies in the literature. We chose to determine the number of polysomnograms (PSG) necessary to be scored by sleep fellows in order to reasonably approximate sleep scoring by a Diplomate of the American Board of Sleep Medicine (DABSM).

Design: The fifth PSG scored by two sleep fellows during the 12 consecutive months of training was chosen for analysis.

DNA content analysis, expression of Ki-67 and p53 in rat urothelial lesions induced by N-butyl-N-(4-hydroxybutyl) nitrosamine and treated with mitomycin C and bacillus Calmette-Guérin.

N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urothelial carcinogenesis is a useful model for studying urothelial carcinogenesis. Here, the DNA content and the expression of Ki-67 and p53 in urothelial lesions induced by BBN and treated with mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) were investigated. Female Fisher 344 rats were distributed into five groups treated with 0.

Mastopexy utilizing a dermoglandular hammock flap.

Background: Many procedures have been described in the search for the ideal mastopexy technique, ranging from simple cutaneous reduction, with or without glandular remodelling, to the use of dermal flaps fixed to the pectoral fascia, or even the use of silicone mesh or sheets.

Objective: We describe a technique that uses a dermoglandular hammock flap to achieve optimal position and shape of the breast; well located, good quality scars that are as short as possible; and satisfactory early- and long-term results.

Methods: A superior pedicle dermoglandular flap was raised from the lower pole of the breast and transposed to the upper pole.

Rapid sevoflurane induction compared with thiopental.

Study Objectives: To examine whether the speed of induction of anesthesia with sevoflurane/nitrous oxide (N2O) utilizing a 10-second vital capacity rapid inhalation induction (VCRII) followed by tidal breathing was similar or faster than cautious intravenous (i.v.V) thiopental induction with inhaled N2O.