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PubMed | Pharma Mar S.A., Instituto Universitario Dexeus, Hospital Germans Trias I Pujol and Montefiore Medical Center
Type: Clinical Trial, Phase I | Journal: Investigational new drugs | Year: 2016

To determine the recommended dose for phase II trials of elisidepsin (PM02734, Irvalec) in combination with erlotinib in patients with advanced malignant solid tumors.Open-label, dose-escalating, phase I study of intravenous elisidepsin administered weekly (days 1, 8 and 15) over 3 h as a flat dose (FD) and daily oral erlotinib, every 3 weeks. A pharmacokinetic analysis was done on blood samples collected around the first elisidepsin infusion.Thirty patients were treated across six different dose levels (DLs) ranging from elisidepsin 0.33-2.25 mg/erlotinib 100-150 mg. Two patients had dose-limiting toxicities: grade 3 bilirubin increase (DL3: 0.75 mg/150 mg) and a dose omission for>2 weeks due to grade 3 alanine aminotransferase increase (DL6: 2.25 mg/100 mg). The daily erlotinib dose was escalated to 150 mg at DL2-DL5, but decreased to 100 mg at DL6, as most grade 3 toxicities were related to this agent only. The most frequent toxicities were transaminase increases (related to elisidepsin), and rash, pruritus and diarrhea (related to erlotinib). No objective responses were observed. Despite no overlapping toxicities, the combination was declared unfeasible due to frequent elisidepsin dose delays. The pharmacokinetics of elisidepsin/erlotinib was not significantly different from that of each agent alone.The difficulty in combining elisidepsin with the standard dose of erlotinib (150 mg), together with the lack of antitumor activity, made the combination unattractive for further development. The trial was closed without having determined a recommended dose.


Ladermann A.,University of Geneva | Ladermann A.,La Tour Hospital | Lubbeke A.,University of Geneva | Stern R.,University of Geneva | And 4 more authors.
International Orthopaedics | Year: 2013

Purpose: The purpose of this study was to analyse the long-term incidence of dislocation arthropathy after a modified Latarjet procedure for glenohumeral instability. Methods: Long-term follow-up information was obtained from a consecutive series of patients who had undergone a modified Latarjet procedure by one surgeon between 1986 and 1999. Multivariable regression analysis was performed to examine the relation between the development of a dislocation arthropathy and patients and surgery-related factors. Results: There were 117 patients (117 shoulders) for evaluation, (35 women and 82 men) with a mean age 28.4 ± 8.5 (range, 16-55). The mean follow-up was 16.2 years (range, ten to 22.2 years). Signs of dislocation arthropathy were found in 36 % of patients, graded as Samilson 1 in 30 %, Samilson 2 in 3 %, and 3 % Samilson 3 in 3 % of patients. Risk factors for dislocation arthropathy included surgery in patients older than 40 years of age (64.3 vs. 34.4 %; adjusted RR 2.2, 95 % CI 1.7-2.9) and lateral positioning of the transferred coracoid process in relation to the glenoid rim (82.4 vs. 30.4 %; adjusted RR 2.3, 95 % CI 1.7-3.2). Patients with hyperlaxity developed less dislocation arthropathy (15 vs. 42.5 %; adjusted RR 0.4, 95 % CI 0.1-0.95). Conclusion: The development of dislocation arthropathy after the Latarjet procedure remains a source of concern in the long term. It correlates with surgery after the age of 40 and lateral coracoid transfer in relation to the glenoid rim. On the other hand, hyperlaxity seems to have a protective effect on the development of dislocation arthropathy. © 2013 Springer-Verlag Berlin Heidelberg.


Teixido C.,University of Barcelona | Arguelaguet E.,University of Barcelona | Pons B.,University of Barcelona | Aracil M.,Pharmamar | And 6 more authors.
International Journal of Oncology | Year: 2012

Irvalec® (elisidepsin trifluoroacetate, PM02734) is a novel marine-derived cyclic peptide belonging to the Kahaladide family of compounds, currently in clinical trials with preliminary evidence of antitumor activity. Previous studies have shown a correlation between elisidepsin sensitivity and expression of the ErbB3 receptor in a panel of NSCLC cell lines. We have studied the effect of elisidepsin on the ErbB3 pathway, characterizing the expression of all members of the ErbB (HER) family of receptors and their main downstream signaling effectors, such as Akt and MAPK. Interestingly, we observed a downregulation of ErbB3 upon elisidepsin treatment that correlates with a reduction in the Akt phosphorylation levels in the most sensitive cell lines, whereas ErbB3 levels are not affected in the less sensitive ones. Also, we observed that the basal levels of ErbB3 protein expression show a significant correlation with cell viability response against elisidepsin treatment in 14 different cell lines. Furthermore, we analyzed the combination of elisidepsin with different chemotherapeutics agents, such as cisplatin, paclitaxel and gemcitabine, in a panel of different breast (MDA-MB-435, MDA-MB-231 and MCF7), lung (HOP62, DV90 and A549) and colorectal cancer cell lines (DLD1 and HT29). IC50 values for the different drugs were tested. We observed a synergistic effect in all cell lines tested with any chemotherapeutic agent. More importantly, the two in vitro elisidepsin-resistant cell lines (MDA-MB-231 and HOP62) presented a synergistic effect in combination with cisplatin and paclitaxel, respectively. These results provide a rationale for further development of these combinations in an ongoing clinical trial.


Guerriero S.,University of Cagliari | Alcazar J.L.,University of Navarra | Pascual M.A.,Instituto Universitario Dexeus | Ajossa S.,University of Cagliari | And 2 more authors.
Ultrasound in Obstetrics and Gynecology | Year: 2012

Objective To describe the gray-scale and color Doppler ultrasound features as well as some clinical and biochemical features of metastatic ovarian tumors according to the origin of the primary tumor in a large study population, Methods This was a retrospective analysis of 116 masses in 92 patients (mean age, 51 years) evaluated and treated at three European university centers for a metastatic tumor in the ovary. All patients had undergone transvaginal color Doppler ultrasound according to a standardized protocol prior to surgery and tumor removal. Ultrasound features analyzed were bilaterality, tumor volume, morphologic gray-scale appearance and color score. CA 125 was also recorded. Results Primary tumor histological diagnosis was as follows: colon-sigmoid (n = 32), stomach (n = 28), breast (n = 20), uterus (n = 17), lymphoma (n = 4), liver-pancreas-biliary tract (n = 4) and miscellaneous (n = 11). There were no differences in age, menopausal status or CA 125 values according to origin of primary tumor. Bilaterality was significantly more frequent in stomach metastases (56%) in comparison with colon-sigmoid and liver-pancreas-biliary tract metastases (18.5% and 0%, respectively, P < 0.05). Median tumor volume was significantly lower in breast metastases (33.5 mL) compared with other metastases (P < 0.05) except stomach metastases and metastatic tumors from the miscellaneous group. Ovarian metastases from breast cancers were significantly more frequently solid in comparison to stomach, colorectal and uterine cancer metastases (95.0% vs. 60.8%, 46.8% and 70.6%, respectively, P < 0.05), and tended to appear moderately or highly vascularized. There were no differences in color score among all groups, although the percentage of masses with abundant color was high (50-82%). Conclusions Ovarian metastases derived from breast cancers tend to be small, solid and vascularized; they seem to be the only ovarian metastases whose primary tumor origin can be suspected by ultrasonography preoperatively. Color score does not seem to help suspect the origin of the primary tumor. Copyright © 2012 ISUOG.


Curell Aguila N.,Instituto Universitario Dexeus
Pediatria Integral | Year: 2013

Clinicians need to be aware of evidence-based norms for pubertal development and menstrual function and consider menstrual bleeding as a "vital sign". The menstrual cycle is defined as the number of days that elapse from the beginning of one menstrual period through the beginning of the next. A certain degree of variability from cycle to cycle is absolutely normal, but the range is wider in adolescents than in adults. The average age of menarche (first menstruation) is 12.6 years. Menstrual cycles usually last between 21 and 45 days, with an average of 32 days. A normal duration of menstruation can range from 2 to 7-8 days, with fewer than 6 full pads or tampons per day. More than 50% of the first years' cycles are anovulatory. The onset of menarche is influenced by socio-economic level, geographic location, body mass index, genetic influences, psychological factors, chemical exposure and physical exercise.


A 30-year-old woman (ASA II, obese) in her 40th week of a first pregnancy required epidural analgesia for labor. When the cervix had dilated to 5 cm, the epidural infusion was started with a 9-mL bolus of 0.2% ropivacaine and 50 pg of fentanyl, after a negative test dose. An infusion of 0.2% ropivacaine and 1 microg/mL of fentanyl was started at a rate of 8 mL/h. A cesarean section was required after insufficient progress was made during 8 hours of labor. Eight milliliters of 0.75% ropivacaine was administered to provide anesthesia to T4; cesarean delivery was completed without complications. Early during postoperative recovery, in addition to motor blockade of the legs, the patient experienced a right brachial plexus blockade and Horner syndrome on the same side. Both effects disappeared spontaneously (1 and 4 hours later, respectively).


De Benito J.,Instituto Universitario Dexeus | Sanchez K.,Instituto Universitario Dexeus
Aesthetic Plastic Surgery | Year: 2010

Breast augmentation is one of the most regularly performed interventions requiring reoperation in aesthetic surgery. For this reason, it involves a greater chance for complications. In this report, the authors aim to provide young plastic surgeons with guidelines based on their experience for responding to each of these complications, to explain the causes and ways of avoiding them, and to show how they can be treated when they occur. © 2010 The Author(s).


Hernandez A.,Hammersmith Hospital | Miranda A.,Instituto Universitario Dexeus | Parada A.,Instituto Universitario Dexeus
Revista Espanola de Anestesiologia y Reanimacion | Year: 2012

Objectives: To evaluate whether Levosimendan has any impact on peri-operative mortality in cardiac surgery. Material and methods: A literature search was performed with the main purpose of looking for mortality in cardiac surgery. Data tabulated by both the fixed effects model and the random effects model were analysed based on the method by Peto. The statistical heterogeneity and inconsistency was estimated and quantified, as well as performing a sensitivity analysis to test the influence of individual studies on the overall result. All the calculations and statistical analyses were performed using the software; "Comprehensive Meta-Analysis" V2.0 and "StatsDirect statistical software" V 2.7.8. At the same time, possible publication bias was also determined. Results: A total of 169 articles were found, from which 13 studies were finally included in the meta-analysis; 12 randomised and one of them retrospective with paired data. The global analysis showed that the use of levosimendan was associated with a significant reduction in postoperative mortality. Conclusions: The meta-analysis showed that the use of Levosimendan was associated with a reduction in mortality in patients subjected to cardiac surgery, although there is still no definitively clear evidence. Additional randomised and multicentre clinical studies, with a much larger number of patients are required, in which hospital mortality and mortality at 6 months are analysed as the primary outcomes. © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor.


The unexpected, but relative letdown of the combined preventive therapy topiramate + propranolol, and the failed drug telcagepant, can induce us to a state of pessimism about the future of the treatment of migraine. Nothing could be further from the truth. Multiple studies in phase II will provide us results in the coming years on numerous drugs aimed at new and very different therapeutic targets, as new gepants, monoclonal antibody against the CGRP receptor, nitric-oxide synthase inhibitors, 5-HT (1F) receptor agonists, gap-junctions blocker tonabersat, dopamine antagonists, TRPV1 receptor antagonists, prostanoids receptor agonists, glutamate receptor antagonists, third-generation antiepileptics, melatonin receptor agonists, and orexin receptor antagonists. To these, must be added the new studies with botulinum toxin, infiltration and stimulation of occipital nerves and the spheno-palatine ganglion, stimulation of vagus nerve, transcranial magnetic stimulation, acupuncture, manual and psychological therapies. Given such diversity, it is very likely that more than one of these ongoing studies give us new therapies in the next 5 years, mainly in preventive therapy. There is no reason for discouragement.


De Benito J.,Instituto Universitario Dexeus | Sanchez K.,Instituto Universitario Dexeus
Aesthetic Plastic Surgery | Year: 2010

Breasts represent femininity and any change of shape may affect their appearance. Breast ptosis may be caused by several factors, including significant weight loss, pregnancy, long breastfeeding periods, and involution of the postmenopausal breast tissue. Breast ptosis may be associated with breast hypoplasia; thus, in case of a mastopexy with or without the use of implants being indicated, several considerations have to be taken into account: the wishes of the patient, age of the patient, degree of ptosis, parenchymal volume, covering tissue, quality of the tissue, pocket implant, shape and content of the implant, and resulting scars. © 2010 Springer Science+Business Media, LLC and International Society of Aesthetic Plastic Surgery.

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