The importance of angiogenesis in ovarian cancer

Advanced stage ovarian cancer has a high rate of recurrence even after surgery followed by chemotherapy combining carboplatin and a taxane. New strategies are currently under way to combat this situation and one of the most promising ones is based on the knowledge that angiogenesis, the mechanism of formation of new blood vessels coupled with the degradation of the extracellular matrix for metalloproteinases, could be crucial in the development of this tumor. The principal molecule implicated in angiogenesis process of ovarian cancer is the vascular endothelial growth factor (VEGF). Several studies are now in progress to clarify its role as a diagnostic tool or its therapeutic implication. Presently, there is no indication for the use of VEGF in a preliminary diagnosis seeing that an increase in levels can be seen in both benign and malignant ovarian conditions. VEGF is also responsible for an increase in vascular permeability and is directly related to symptoms such as ascites and pleural effusion, both of which are frequent in ovarian cancer. Several papers have analised the role of VEGF as a prognostic factor and some of them do confirm VEGF as an independent prognostic factor in ovarian cancer. VEGF and the metalloproteinase system coupled with angiogenesis are currently being evaluated as therapeutic targets but no positive results have yet to be seen in this field.      

Characterization of erenumab and rimegepant on calcitonin gene-related peptide induced responses in Xenopus Laevis oocytes expressing the calcitonin gene-related peptide receptor and the amylin-1 receptor

BackgroundThe clinical use of calcitonin gene-related peptide receptor (CGRP-R) antagonists and monoclonal antibodies against CGRP and CGRP-R has offered new treatment possibilities for migraine patients. CGRP activates both the CGRP-R and structurally related amylin 1 receptor (AMY₁-R). The relative effect of erenumab and the small-molecule CGRP-R antagonist, rimegepant, towards the CGRP-R and AMY-R needs to be further characterized.MethodsThe effect of CGRP and two CGRP-R antagonists were examined in Xenopus laevis oocytes expressing human CGRP-R, human AMY₁-R and their subunits.ResultsCGRP administered to receptor expressing oocytes induced a concentration-dependent increase in current with the order of potency CGRP-R> > AMY₁-R > calcitonin receptor (CTR). There was no effect on single components of the CGRP-R; calcitonin receptor-like receptor and receptor activity-modifying protein 1. Amylin was only effective on AMY₁-R and CTR. Inhibition potencies (pIC₅₀ values) for erenumab on CGRP induced currents were 10.86 and 9.35 for CGRP-R and AMY₁-R, respectively. Rimegepant inhibited CGRP induced currents with pIC₅₀ values of 11.30 and 9.91 for CGRP-R and AMY₁-R, respectively.ConclusionOur results demonstrate that erenumab and rimegepant are potent antagonists of CGRP-R and AMY₁-R with 32- and 25-times preference for the CGRP-R over the AMY₁-R, respectively. It is discussed if this difference in affinity between the two receptors is the likely reason why constipation is a common and serious adverse effect during CGRP-R antagonism but less so with CGRP binding antibodies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01425-9.     

Sexual behavior and findings on laparoscopy or laparotomy in women with severe chronic pelvic pain

OBJECTIVE: To identify features of sexual behavior in women with and without chronic pelvic pain. STUDY DESIGN: A group of 41 women with chronic pelvic pain of more than 6 months' duration and scheduled to undergo laparoscopy or laparotomy were surveyed to obtain information on their sexual activity. The results were compared with a control group of 86 women of similar age and socioeconomic status who underwent planned tubal ligation for permanent contraception. RESULTS: Women with pelvic pain initiated sexual relations at a later age and had a higher rate of dyspareunia than women in the control group. There were no significant differences between groups in any other characteristics of sexual behavior. CONCLUSION: Dyspareunia, the only feature of sexual relations that differed significantly between women with and without chronic pelvic pain, should be accorded greater attention as a painful symptom and not be dismissed as simply a type of sexual dysfunction.     

Mortality for newborns of birthweight less than 1500 g in Spanish neonatal units (2002-2005)

The purpose of this study was to analyze the mortality and its prognostic factors in a Spanish cohort of very low birthweight (VLBW) infants during the period 2002 to 2005. Using the Spanish Society of Neonatology database (SEN 1500), 8942 infants with a birthweight < 1500 g were recruited. The overall mortality was 17.3%. However, this incidence underwent a significant decrease over the study period, from 19.4% in 2002 to 15.2% in 2005 ( P = 0.003). Mortality ranged from 12.4% in 25% of the participating neonatal units to 19.4% in a further 25%. Mortality was higher in outborn infants (25.8%) than in inborn infants (16.6%) ( P < 0.001). The mortality rates of these neonates are also presented by 100-g intervals (401 to 1500) and for the different hospitalization times: in the delivery room, within 24 hours and 28 days of birth, at 36 weeks of postmenstrual age, and on discharge. Of note was that mortality was greatest within 24 hours and 28 days of birth in each of the weight groups ( P < 0.001). In conclusion, in the cohort of infants < 1500 g examined, mortality in the period from 2002 to 2005 was still high, especially among newborns weighing < 1000 g. We did, however, observe a decreasing trend in mortality rates for the participating neonatal units over the 4 study years. Our findings highlight the need to promote intrauterine transport and improve neonatal transport as well as the management of these infants in the delivery room and within the first 28 days of life.     

Actualización en fascitis necrotizante

Necrotizing fasciitis is defined as a rapidly progressive infection of the skin and soft tissue that usually involves severe systemic toxicity. The incidence of this infection has increased in the last few decades and is estimated to affect one out of every 100,000 inhabitants in western European countries. This disease is the most serious form of skin and soft tissue infection, due to rapid destruction and necrosis of the fascia and subcutaneous fat, and the development of shock and multiorgan failure in about one third of patients.Although there are several predisposing factors for the development of the disease, especially for type I, or polymicrobial, necrotizing fasciitis, many patients are young and have no underlying chronic diseases, as is the case for type II, or streptococcal, necrotizing fasciitis. The diagnosis is mainly clinical, and urgent surgical consultation is required as soon as possible once suspicion is high, as the main determinant of mortality is the delay in surgical treatment. Overall mortality remains high, affecting more than 25% of patients. Surgical debridement is the mainstay of treatment, along with hemodynamic support and broad-spectrum antibiotics.     

Metatarsalgia

Metatarsalgia is a clinical syndrome characterized by pain in the forefoot. To understand the physiopathogenesis and treatment of this condition, an understanding of the anatomy and biomechanics of the foot is essential. There are a large number of causes of metatarsalgia and some, such as rheumatoid arthritis, may be highly complex. The use of ortheses should be individualized and adjusted to the diagnosis. To prevent this condition, the use of appropriate footwear is essential.