Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer

Goals of endocrine therapy for advanced breast cancer (ABC) include prolonging survival rates, maintaining the quality of life, and delaying the initiation of chemotherapy. We evaluated the effectiveness of fulvestrant as first-line in patients with estrogen receptor (ER)-positive ABC with relapse during or after adjuvant anti-estrogenic therapy in real-world settings. Retrospective, observational study involving 171 postmenopausal women with ER-positive ABC who received fulvestrant as first-line between January 2011 and May 2018 in Spanish hospitals. With a median follow-up of 31.4 months, the progression-free survival (PFS) with fulvestrant was 14.6 months. No differences were seen in the visceral metastatic (14.3 months) versus non-visceral (14.6 months) metastatic subgroup for PFS. Overall response rate and clinical benefit rate were 35.2% and 82.8%. Overall survival was 43.1 months. The duration of the clinical benefit was 19.2 months. Patients with ECOG performance status 0 at the start of treatment showed a significant greater clinical benefit rate and overall survival than with ECOG 1-2. Results in real-world settings are in concordance with randomized clinical trials. Fulvestrant continues to demonstrate clinical benefits in real-world settings and appears be well tolerated as first-line for the treatment of postmenopausal women with ER-positive ABC

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review

Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are considered a single entity with variability in the extent of the lesions, characterized by erythema multiforme that may involve mucosa. Severe cutaneous reactions secondary to medications are classified according to the area of epidermal detachment. The activation of cytotoxic T cells and macrophages is mediated mainly by IL-2 and interferon gamma secreted by Th1 lymphocytes, and the activation of eosinophils and B lymphocytes in IgE is mediated by secreted IL-4, IL-5, IL-10 and IL13 by B lymphocytes. The topography of SJS is predominantly central, affecting the trunk and sometimes a generalized dissemination is shown that affects a body surface area of less than 10%, characterized by irregular violaceous erythematous macules of target shooting, which can form confluent blisters. TEN is characterized by a skin detachment greater than 30% of the body surface, whose predominant lesion is diffuse erythema with individual macules, which give rise to detachment surfaces greater than 5 cm. The treatment is symptomatic, nonspecific, and aimed at avoiding complications, carried out in specialized intensive care units, due to ignorance of the pathogenesis. Integral management with different therapeutic alternatives can represent a crucial part in the multisystemic management of SJS and TEN

Antebrachial microvascular flap for reconstruction of the pelvic limb: case report

Complex defects in the soft tissues of the foot and ankle caused by high-energy trauma, infection, cancer or diabetes require rapid and effective treatment which decreases the risk of infection, bone healing time, hospital stay and number total of surgical approaches. Authors report a clinical case of a 23-year-old female patient who suffers high-energy trauma due to a motorcycle accident which causes exposure of the distal third of the tibia, loss of the tibial joint face, and loss of tissue throughout the region of the malleolus medial of the right pelvic extremity. Tissue transfer to the pelvic limb is performed using left contralateral radial antebrachial free flap as donor area. This case report aims to emphasize the key aspects of the high energy trauma approach by using microvascular flaps, as well as the satisfactory evolution of the patient that directly affects the prognosis for life and function

You made him be alive: Children’s perceptions of animacy in a humanoid robot

Social robots are becoming more sophisticated; in many cases they offer complex, autonomous interactions, responsive behaviors, and biomimetic appearances. These features may have significant impact on how people perceive and engage with robots; young children may be particularly influenced due to their developing ideas of agency. Young children are considered to hold naive beliefs of animacy and a tendency to mis-categorise moving objects as being alive but, with development, children can demonstrate a biological understanding of animacy. We experimentally explore the impact of children’s age and a humanoid’s movement on children’s perceptions of its animacy. Our humanoid’s behavior varied in apparent autonomy, from motionless, to manually operated, to covertly operated. Across conditions, younger children rated the robot as being significantly more person-like than older children did. We further found an interaction effect: younger children classified the robot as significantly more machine-like if they observed direct operation in contrast observing the motionless or apparently autonomous robot. Our findings replicate field results, supporting the modal model of the developmental trajectory for children’s understanding of animacy. We outline a program of research to both deepen the theoretical understanding of children’s animacy beliefs and develop robotic characters appropriate across key stages of child development

The EASEL project: Towards educational human-robot symbiotic interaction

This paper presents the EU EASEL project, which explores the potential impact and relevance of a robot in educational settings. We present the project objectives and the theorectical background on which the project builds, briefly introduce the EASEL technological developments, and end with a summary of what we have learned from the evaluation studies carried out in the project so far

Global, Regional, and National Levels and Trends in Burden of Oral Conditions from 1990 to 2017: A Systematic Analysis for the Global Burden of Disease 2017 Study

Government and nongovernmental organizations need national and global estimates on the descriptive epidemiology of common oral conditions for policy planning and evaluation. The aim of this component of the Global Burden of Disease study was to produce estimates on prevalence, incidence, and years lived with disability for oral conditions from 1990 to 2017 by sex, age, and countries. In addition, this study reports the global socioeconomic pattern in burden of oral conditions by the standard World Bank classification of economies as well as the Global Burden of Disease Socio-demographic Index. The findings show that oral conditions remain a substantial population health challenge. Globally, there were 3.5 billion cases (95% uncertainty interval [95% UI], 3.2 to 3.7 billion) of oral conditions, of which 2.3 billion (95% UI, 2.1 to 2.5 billion) had untreated caries in permanent teeth, 796 million (95% UI, 671 to 930 million) had severe periodontitis, 532 million (95% UI, 443 to 622 million) had untreated caries in deciduous teeth, 267 million (95% UI, 235 to 300 million) had total tooth loss, and 139 million (95% UI, 133 to 146 million) had other oral conditions in 2017. Several patterns emerged when the World Bank's classification of economies and the Socio-demographic Index were used as indicators of economic development. In general, more economically developed countries have the lowest burden of untreated dental caries and severe periodontitis and the highest burden of total tooth loss. The findings offer an opportunity for policy makers to identify successful oral health strategies and strengthen them; introduce and monitor different approaches where oral diseases are increasing; plan integration of oral health in the agenda for prevention of noncommunicable diseases; and estimate the cost of providing universal coverage for dental care

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin

The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor kappa B signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.Peer reviewe

Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries.

Globally, group B Streptococcus (GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation. This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations