Phase 2 study of anastrozole in rare cohorts of patients with estrogen receptor/progesterone receptor positive leiomyosarcomas and carcinosarcomas of the uterine corpus: The PARAGON trial (ANZGOG 0903).

BACKGROUND: Aromatase inhibitors have been used empirically to treat a subset of patients with hormone receptor positive uterine leiomyosarcomas(LMS) and carcinosarcomas (UCS) mainly supported by retrospective data. We evaluated the activity of anastrozole in two rare cohorts; patients with recurrent/metastatic LMS and UCS enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER+)/progesterone receptor positive (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER &/or PR + ve LMS or UCS with measurable disease, treated until progression or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 39 eligible patients were enrolled, 32 with LMS and 7 with UCS. For the LMS cohort CBR at 3 months was 35% (95% CI: 21-53%) with a median duration of clinical benefit of 5.8 months. Best response was a partial response in one patient. Two patients remained on treatment for more than one year. The median progression-free survival was 2.8 months (95% CI: 2.6-4.9). For the UCS cohort CBR at 3 months was 43% (95% CI: 16-75%) with a median duration of clinical benefit of 5.6 months. Stable disease was seen in 3 patients but no objective responses were seen. The median progression-free survival was 2.7 months (95% CI, 1.1-8.2). Safety was acceptable with 5/39 evaluable patients showing grade 3 toxicities. CONCLUSION: Whilst objective response rates with anastrozole are low, the clinical benefit rate and good tolerance suggests that aromatase inhibitor therapy may have a role in a subset of patients with metastatic LMS and UCS.

Phase 2 study of anastrozole in patients with estrogen receptor/progesterone receptor positive recurrent low-grade endometrial stromal sarcomas: The PARAGON trial (ANZGOG 0903).

BACKGROUND: Aromatase inhibitors are standard of care for low-grade endometrial stromal sarcomas (LGESS), based on very high response rates reported in retrospective studies. We evaluated the activity of anastrozole in recurrent/metastatic LGESS patients enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER±)/progesterone receptor (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER ± PR + ve LGESS with measurable disease, treated until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 15 eligible patients were enrolled. CBR at 3 months was 73% (95% CI: 48-89.1%); unchanged at 6 months. Best response was 26.7%, including complete response in one (6.7%; 95% CI 1.2-29.8%), partial response in three (20%, 95% CI 7.1-45.2%) and stable disease in seven (46.7%). Four patients ceased treatment by 3 months due to progression. Median PFS was not reached (25th percentile: 2.9 months (95% CI: 1.2-NR)). PFS was 73.3%, 73.3% and 66% at 6, 12, and 18 months, respectively. Six patients remained on treatment for an average of 44.2 months (range 34.5-63.6) up until data cut. Toxicity was as expected, with 3 patients stopping due to adverse effects. CONCLUSION: The 26.7% objective response rate with anastrozole is lower than reported in retrospective series, but the CBR was high and durable. The results underscore the importance of prospective trials in rare cancers.

Droplet digital PCR quantification suggests that higher viral load correlates with improved survival in HPV-positive oropharyngeal tumours.

BACKGROUND: Although HPV-positive oropharyngeal cancer (OPC) patients have improved prognosis compared to HPV negative patients; there remains an HPV-positive group who have poor outcomes. Biomarkers to stratify discrete patient outcomes are thus desirable. Our objective was to analyse viral load (VL) by droplet digital PCR (ddPCR), in HPV-positive patients with OPC on whom clinical outcome data were available. METHODS: In a cohort of patients that had previously tested HPV positive via conventional PCR, VL was determined using ddPCR assays for HPV16 L1 and E6 genes. VL was classed as "medium/high" if more than 5.57 copies or 8.68 copies of the HPV 16 L1 or E6 gene were detected respectively. Effect of VL on overall survival and hazard of death & disease progression was performed with adjustments made for sex, age, deprivation, smoking, alcohol consumption and stage. RESULTS: L1 VL ranged from 0.0014-304 gene copies per cell with a mean of 30.9; comparatively E6 VL ranged from 0.0012-356 copies per cell with a mean of 37.9. Univariate analysis showed those with a medium/high VL had a lower hazard of death; this was significant for L1 (p = 0.02) but not for E6 (p = 0.67). The ratio of E6 to L1 deviated from n = 1 in most samples but had no influence on clinical outcomes. CONCLUSIONS: HPV viral load may be informative for the further stratification of clinical outcomes in HPV positive OPC patients.

A Prospective Cohort Study of Human Papillomavirus-Driven Oropharyngeal Cancers: Implications for Prognosis and Immunisation.

AIMS: Oropharyngeal cancer (OPC) is increasing on a global scale, including the component driven by high-risk human papillomavirus (HR-HPV); contemporary data that provides insight into the prognosis of this disease in addition to the fraction attributable to HR-HPV are essential to inform primary and secondary disease management strategies. MATERIALS AND METHODS: A population-based cohort of 235 patients diagnosed with OPC between 2013 and 2015 in Scotland was assessed for HPV status using molecular genotyping. Associations between HR-HPV status and key clinical and demographic variables were estimated using the Pearson chi-squared test. Rates of overall survival and progression-free survival were estimated and visualised using Kaplan-Meier curves. RESULTS: HPV DNA (largely HPV 16) was identified in 60% of cases. After adjustment for age, gender, deprivation, smoking, alcohol consumption and tumour stage, patients with HR-HPV-positive OPC had an 89% reduction in the risk of death (hazard ratio = 0.11, 95% confidence interval 0.05-0.25) and an 85% reduction in the risk of disease progression (hazard ratio = 0.15, 95% confidence interval 0.07-0.30). HPV positivity was not associated with age, deprivation or smoking status, whereas those who reported excess alcohol consumption were less likely to be positive for HR-HPV. CONCLUSIONS: The prevalence of HR-HPV-associated OPC is high in Scotland and strongly associated with dramatically improved clinical outcomes, including survival. Demographic/behavioural variables did not reliably predict HPV positivity in this cohort, which underlines the importance of laboratory confirmation. Finally, the dominance of HPV 16 in OPC indicates the significant impact of prophylactic immunisation on this disease.

The Occipital Emissary Vein: A Possible Marker for Pseudotumor Cerebri.

BACKGROUND AND PURPOSE: Transverse sinus stenosis can lead to pseudotumor cerebri syndrome by elevating the cerebral venous pressure. The occipital emissary vein is an inconstant emissary vein that connects the torcular herophili with the suboccipital veins of the external vertebral plexus. This retrospective study compares the prevalence and size of the occipital emissary vein in patients with pseudotumor cerebri syndrome with those in healthy control subjects to determine whether the occipital emissary vein could represent a marker of pseudotumor cerebri syndrome. MATERIALS AND METHODS: The cranial venous system of 46 adult patients with pseudotumor cerebri syndrome (group 1) was studied on CT venography images and compared with a group of 92 consecutive adult patients without pseudotumor cerebri syndrome who underwent venous assessment with gadolinium-enhanced 3D-T1 MPRAGE sequences (group 2). The presence of an occipital emissary vein was assessed, and its proximal (intraosseous) and distal (extracranial) maximum diameters were measured and compared between the 2 groups. Seventeen patients who underwent transverse sinus stent placement had their occipital emissary vein diameters measured before and after stent placement. RESULTS: Thirty of 46 (65%) patients in group 1 versus 29/92 (31.5%) patients in group 2 had an occipital emissary vein (P < .001). The average proximal and distal occipital emissary vein maximum diameters were significantly larger in group 1 (2.3 versus 1.6 mm, P <.005 and 3.3 versus 2.3 mm, P < .001). The average maximum diameters of the occipital emissary vein for patients who underwent transverse sinus stent placement were larger before stent placement than after stent placement: 2.6 versus 1.8 mm proximally (P < .06) and 3.7 versus 2.6 mm distally (P < .005). CONCLUSIONS: Occipital emissary veins are more frequent and larger in patients with pseudotumor cerebri syndrome than in healthy subjects, a finding consistent with their role as collateral venous pathway in transverse sinus stenosis. A prominent occipital emissary vein is an imaging sign that should raise the suspicion of pseudotumor cerebri syndrome.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): clinical trial design for rare ovarian tumours.

This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the fifth Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian cancers (eOC), sex-cord stromal tumours (SCST) and germ cell tumours (GCT)): (i) What are the research and trial issues that are unique to rare ovarian tumours? There is a lack of randomised phase III data defining standards of care which makes it difficult to define control arms, but identifies unmet needs that merit investigation. Internationally agreed upon diagnostic criteria, expert pathological review and translational research are crucial. (ii) What should be investigated in rare eOC, GCT and SCST? Trials dedicated to each rare ovarian tumour should be encouraged. Nonetheless, where the question is relevant, rare eOC can be included in eOC trials but with rigorous stratification. Although there is emerging evidence suggesting that rare eOC have different molecular profiles, trials are needed to define new type-specific standards for each rare eOC (clear cell, low grade serous and mucinous). For GCTs, a priority is reducing toxicities from treatment while maintaining cure rates. Both a robust prognostic scoring system and more effective treatments for de novo poor prognosis and relapsed GCTs are needed. For SCSTs, validated prognostic markers as well as alternatives to the current standard of bleomycin/etoposide/cisplatin (BEP) should be identified. (iii) Are randomised trials feasible? Randomised controlled trials (RCT) should be feasible in any of the rare tumours through international collaboration. Ongoing trials have already demonstrated the feasibility of RCT in rare eOC and SCST. Mucinous OC may be considered for inclusion, stratified, into RCTs of non-gynaecological mucinous tumours, while RCTs in high risk or relapsed GCT may be carried out as a subset of male and/or paediatric germ cell studies.

Ascending and Descending Thoracic Vertebral Arteries.

Thoracic vertebral arteries are anastomotic chains similar to cervical vertebral arteries but found at the thoracic level. Descending thoracic vertebral arteries originate from the pretransverse segment of the cervical vertebral artery and curve caudally to pass into the last transverse foramen or the first costotransverse space. Ascending thoracic vertebral arteries originate from the aorta, pass through at least 1 costotransverse space, and continue cranially as the cervical vertebral artery. This report describes the angiographic anatomy and clinical significance of 9 cases of descending and 2 cases of ascending thoracic vertebral arteries. Being located within the upper costotransverse spaces, ascending and descending thoracic vertebral arteries can have important implications during spine interventional or surgical procedures. Because they frequently provide radiculomedullary or bronchial branches, they can also be involved in spinal cord ischemia, supply vascular malformations, or be an elusive source of hemoptysis.

Methanol-based fixation is superior to buffered formalin for next-generation sequencing of DNA from clinical cancer samples.

BACKGROUND: Next-generation sequencing (NGS) of tumour samples is a critical component of personalised cancer treatment, but it requires high-quality DNA samples. Routine neutral-buffered formalin (NBF) fixation has detrimental effects on nucleic acids, causing low yields, as well as fragmentation and DNA base changes, leading to significant artefacts. PATIENTS AND METHODS: We have carried out a detailed comparison of DNA quality from matched samples isolated from high-grade serous ovarian cancers from 16 patients fixed in methanol and NBF. These experiments use tumour fragments and mock biopsies to simulate routine practice, ensuring that results are applicable to standard clinical biopsies. RESULTS: Using matched snap-frozen tissue as gold standard comparator, we show that methanol-based fixation has significant benefits over NBF, with greater DNA yield, longer fragment size and more accurate copy-number calling using shallow whole-genome sequencing (WGS). These data also provide a new approach to understand and quantify artefactual effects of fixation using non-negative matrix factorisation to analyse mutational spectra from targeted and WGS data. CONCLUSION: We strongly recommend the adoption of methanol fixation for sample collection strategies in new clinical trials. This approach is immediately available, is logistically simple and can offer cheaper and more reliable mutation calling than traditional NBF fixation.

Preclinical evaluation of collagen type I scaffolds, including gelatin-collagen microparticles and loaded with a hydroglycolic Calendula officinalis extract in a lagomorph model of full-thickness skin wound.

Previously, we have developed collagen type I scaffolds including microparticles of gelatin-collagen type I (SGC) that are able to control the release of a hydroglycolic extract of the Calendula officinalis flower. The main goal of the present work was to carry out the preclinical evaluation of SGC alone or loaded with the C. officinalis extract (SGC-E) in a lagomorph model of full-thickness skin wound. A total of 39 rabbits were distributed in three groups, of 13 animals each. The first group was used to compare wound healing by secondary intention (control) with wound healing observed when wounds were grafted with SGC alone. Comparison of control wounds with wounds grafted with SGC-E was performed in the second group, and comparison of wounds grafted with SGC with wounds grafted with SGC-E was performed in the third group. Clinical follow-ups were carried in all animals after surgery, and histological and histomorphometric analyses were performed on tissues taken from the healed area and healthy surrounding tissue. Histological and histomorphometric results indicate that grafting of SGC alone favors wound healing and brings a better clinical outcome than grafting SGC-E. In vitro collagenase digestion data suggested that the association of the C. officinalis extract to SGC increased the SGC-E cross-linking, making it difficult to degrade and affecting its biocompatibility.

¿Son válidos los criterios quirúrgicos actuales del hiperparatiroidismo primario asintomático? / Are the current surgical criteria for asymptomatic primary hyperparathyroidism valid?

El HPTP es una patología muy frecuente que a menudo cursa de manera asintomática. Siendo la intervención quirúrgica el único tratamiento curativo de la enfermedad, existen unos criterios de indicación de cirugía que no siempre se ajustan a la realidad del paciente, pues se basan en la existencia de complicaciones clínicas (osteoporosis, insuficiencia renal, urolitiasis, fracturas por fragilidad). Presentamos el caso clínico de una paciente que no cumplía ninguno de los requisitos para ser intervenida quirúrgicamente según los documentos de posición, y que fue operada tras demostrarse la existencia de un deterioro de la estructura trabecular ósea, determinada por la técnica TBS (trabecular bone score), y localizarse el adenoma por gammagrafía. Se discute la posible utilidad de estas técnicas, no observadas en los documentos de posición, como complemento de la decisión de cirugía (AU)

HPTP is a very frequent pathology which often develops asymptomatically. Surgical intervention being the only curative treatment for this disease there are some criteria for the indication of surgery, but these do not always fit the reality of the patient since they are based on clinical complications (osteoporosis, renal insufficiency, urolithiasis, fragility fractures). We present the clinical case of a patient who did not meet any of the requirements for having surgical intervention according to the position documents, and who was operated on after the existence was shown of a deterioration of the trabecular bone structure, determined by the TBS (trabecular bone score) technique, and located in the adenoma using gammagraphy. The possible use of these techniques, not seen in the position documents, to complement the decision regarding surgery, is discusse (AU)

Relationships between surface free energy, surface texture parameters and controlled drug release in hydrophilic matrices.

The study of controlled release and drug release devices has been dominated by considerations of the bulk or average properties of material or devices. Yet the outermost surface atoms play a central role in their performance. The objective of this article has been to characterize the surface of hydrophilic matrix tablets using the contact angle (CA) method to ascertain the surface free energy, and atomic force microscopy (AFM) and confocal microscopy (CM) for the physical characterization of the surface of the hydrophilic matrix. The surface free energy results obtained show that hydroxypropylmethylcellulose K15M hinders the spreading of water on the surface of the tablet, such that the concentration of HPMC K15M increases the reaction rate of the hydrophobic interactions between the chains of HPMC K15M which increases with respect to the rate of penetration of water into the tablet. In this study, we developed a new method to characterize the swelling of the tablets and established a relationship between the new method based on microswelling and the swelling ratio parameter. The surface texture parameters have been determined and the morphology of the tablets of the different formulations and the evolution of the surface morphology after interacting with the water, swelling and forming a gel layer were characterized. This work represents significant progress in the characterization of matrix tablets.

Quality by Design approach to understand the physicochemical phenomena involved in controlled release of captopril SR matrix tablets.

The aim of this study is to obtain swelling controlled release matrix tablets of captopril using the Quality by Design methodology (ICH Q8) and to know the transport mechanisms involved in captopril release. To obtain the area of knowledge, the design of experiments studying the effect of two components (HPMC K15M and ethylcellulose) at different levels has been applied, with the captopril dissolution profile as the product's most important critical quality attribute (CQA). Different dissolution profiles have been obtained with the design of experiments performed, which is a key factor in the development of controlled release matrix tablets. Kinetic analysis according to the equations of Higuchi and Korsmeyer-Peppas demonstrates that the release mechanism is a mechanism of erosion when the whole percentage of the polymer is ethylcellulose, and a diffusion mechanism when the whole percentage of the polymer is HPMC K15M. The physico-chemical characteristics of the gel layer determine the release rate of captopril. The thickness of the gel layer, the porosity which is formed in the matrix upon contact with water, pore size, the swelling rate, the erosion rate of the matrix, and the physico-chemical characteristics of captopril, are factors related to the kinetic equations described and that allow us to predict the release mechanism of captopril. A new relationship of the kinetic equations governing the in vitro behavior with the physical characteristics of the gel layer of the different formulations has been established. This study shows that the size of water-filled pores and the degree of crosslinking between the chains of HPMC K15M of the matrix are related to the exponent n of the Korsmeyer-Peppas equation and the type of transport of the captopril from within the matrix to the dissolution medium, that is, if the transport is only through water-filled pores, or if a combination of diffusion occurs through water-filled pores with a transport through continuous polymeric networks.

[Benefits of Decumanum Phlebodium intake on the muscle damage in the response to intense physical exercise in sedentary subjects]. / Beneficios de la ingesta del phlebodium decumanum sobre el daño muscular al efectuar ejercicio físico intenso en sujetos sedentarios.

INTRODUCTION: Intense physical exercise provoke muscle damage, that in sedentary people can increase cardiovascular risk. Phlebodium decumanum (PD) has shown to have immunomodulator effects in models of moderate intense physical activities in well conditioned groups. To evaluate the PD effects during eccentric exercise, as a model of muscle inflammation protocol, on a sedentary population with cardiovascular risk. METHODS: This is an experimental, double-blind, multigroup randomized study. Experimental Group 1 (n = 17)received PD, 9 doses of 400 mg (total amount 3.6 g) every 8 hours during 3 days, and Control Group 2 (n = 16)received a placebo. All the subjects performed two treadmill ergoespirometry tests: first, a modified Bruce protocol to discard ischemic responses during exercise and to evaluate VO2max before the experimental phase;and second, with an eccentric protocol (14% descending ramp test) during 10 minutes in stable state at 70-80%VO2max, as experimental inflammatory protocol.We compared intra and inter groups to evaluate differences in the pre and post-test differences results on blood muscle damage variables. RESULTS: The study shown statistically significant differences in all pre-post intra-groups results in muscle damage variables (CK, LDH and Myoglobin, but not in Cardiac Troponin), and in functional lower-limb test (SJand CMJ). The comparison of inter-group results shown less muscle damage and less functional lower-limb deterioration in Group 1 compared with Control group, with statistical significance in both cases. Differences in handgrip dynamometry were no statistically significant. CONCLUSIONS: The eccentric exercise protocol in that study has proven to be a good model to induce muscle and functional damage in sedentary people. Short PD treatment has shown to reduce muscle and functional acute damages compared with placebo control group in this specific population.

Introducción: El ejercicio intenso provoca un daño muscular inflamatorio que, en sujetos sedentarios provoca un aumento del riesgo cardiovascular. El Phlebodium decumanum (PD) ha evidenciado efectos inmunomoduladores protectores frente a ese daño en los deportistas. Para conocer los efectos del PD en una población sedentaria frente al ejercicio excéntrico, y como modelo del daño muscular inflamatorio. Metodología: Se llevó a cabo un estudio experimental, doble ciego, multigrupo, randomizado, con un grupo experimental (n = 17) al que se le administró una formulación de PD (3,6 g/sujeto distribuidos en 9 dosis de 400 mg desde el 3.er día pretest), y un grupo control (n = 16) que tomó sustancia placebo. Se realizaron dos ergoespirometrías en tapiz rodante a cada participante: una previa al estudio (protocolo de Bruce modificado) para descartar signos de isquemia durante el esfuerzo y valorar el VO2max; la segunda, aplicando un protocolo excéntrico (14% de desnivel descendente), durante 10 minutos en estado estable a una intensidad entre 70-80% del VO2max individual, como protocolo experimental. Se efectuaron comparaciones intragrupo e intergrupo del porcentaje de cambio pre-postesfuerzo en variables sanguíneas y de funcionalidad muscular. Resultados: El estudio evidencia aumentos significativos de enzimas musculares MG, CPK y LDH en los dos grupos de estudio, sin cambios para la TncI, siendo significativamente menores en el grupo al que se le administró PD. Se observaron reducciones significativas de los test funcionales SJ, CMJ en ambos grupos, lo que mostró un apreciable menor descenso en el grupo PD. Se apreció una reducción del índice elástico y de la dinamomentría manual solo en el grupo control, aunque las diferencias con el grupo PD no alcanzaron una significación estadística. Conclusiones: El protocolo del ejercicio excéntrico en el presente estudio ha inducido daños musculoesqueléticos y en la funcionalidad muscular, que han resultado significativamente menores en el grupo PD, al mostrar los efectos protectores del Phlebodium Decumanum en tratamientos cortos, frente al daño muscular también en el esfuerzo agudo.

Beneficios de la ingesta del Phlebodium decumanum sobre el daño muscular al efectuar ejercicio físico intenso en sujetos sedentarios / Benefits of decumanum phlebodium intake on the muscle damage in the response to intense physical exercise in sedentary subjects

Introducción: El ejercicio intenso provoca un daño muscular inflamatorio que, en sujetos sedentarios provoca un aumento del riesgo cardiovascular. El Phlebodium decumanum (PD) ha evidenciado efectos inmunomoduladores protectores frente a ese daño en los deportistas. Para conocer los efectos del PD en una población sedentaria frente al ejercicio excéntrico, y como modelo del daño muscular inflamatorio. Metodología: Se llevó a cabo un estudio experimental, doble ciego, multigrupo, randomizado, con un grupo experimental (n = 17) al que se le administró una formulación de PD (3,6 g/sujeto distribuidos en 9 dosis de 400 mg desde el 3.er día pretest), y un grupo control (n = 16) que tomó sustancia placebo. Se realizaron dos ergoespirometrías en tapiz rodante a cada participante: una previa al estudio (protocolo de Bruce modificado) para descartar signos de isquemia durante el esfuerzo y valorar el VO2max; la segunda, aplicando un protocolo excéntrico (14% de desnivel descendente), durante 10 minutos en estado estable a una intensidad entre 70-80% del VO2max individual, como protocolo experimental. Se efectuaron comparaciones intragrupo e intergrupo del porcentaje de cambio pre-postesfuerzo en variables sanguíneas y de funcionalidad muscular. Resultados: El estudio evidencia aumentos significativos de enzimas musculares MG, CPK y LDH en los dos grupos de estudio, sin cambios para la TncI, siendo significativamente menores en el grupo al que se le administró PD. Se observaron reducciones significativas de los test funcionales SJ, CMJ en ambos grupos, lo que mostró un apreciable menor descenso en el grupo PD. Se apreció una reducción del índice elástico y de la dinamomentría manual solo en el grupo control, aunque las diferencias con el grupo PD no alcanzaron una significación estadística. Conclusiones: El protocolo del ejercicio excéntrico en el presente estudio ha inducido daños musculoesqueléticos y en la funcionalidad muscular, que han resultado significativamente menores en el grupo PD, al mostrar los efectos protectores del Phlebodium Decumanum en tratamientos cortos, frente al daño muscular también en el esfuerzo agudo (AU)

Introduction: Intense physical exercise provoke muscle damage, that in sedentary people can increase cardiovascular risk. Phlebodium decumanum (PD) has shown to have immunomodulator effects in models of moderateintense physical activities in well conditioned groups. To evaluate the PD effects during eccentric exercise, as a model of muscle inflammation protocol, on a sedentary population with cardiovascular risk. Methods. This is an experimental, double-blind, multigroup randomized study. Experimental Group 1 (n = 17) received PD, 9 dosis of 400 mg (total amount 3.6 g) every 8 hours during 3 days, and Control Group 2 (n = 16) received a placebo. All the subjects performed two treadmill ergoespirometry tests: first, a modified Bruce protocol to discard ischemic responses during exercise and to evaluate VO2max before the experimental phase; and second, with an eccentric protocol (14% descending ramp test) during 10 minutes in stable state at 70-80% VO2max, as experimental inflammatory protocol. We compared intra and inter groups to evaluate differences in the pre and post-test differences results on blood muscle damage variables. Results: The study shown statistically significant differences in all pre-post intra-groups results in muscle damage variables (CK, LDH and Myoglobin, but not in Cardiac Troponin), and in functional lower-limb test (SJ and CMJ). The comparison of inter-group results shown less muscle damage and less functional lower-limb deterioration in Group 1 compared with Control group, with statistical significance in both cases. Differences in hand grip dynamometry were no statistically significant. Conclusions: The eccentric exercise protocol in that study has proven to be a good model to induce muscle and functional damage in sedentary people. Short PD treatment has shown to reduce muscle and functional acute damages compared with placebo control group in this specific population (AU)

Influence of HPV type on prognosis in patients diagnosed with invasive cervical cancer.

While much is known about the influence of HPV type on the progression of pre-invasive cervical lesions, the impact of HPV type on cervical cancer prognosis is less evidenced. Thus, we assessed the impact of HPV type on the survival of women diagnosed with cervical cancer. A total of 370 cases of cervical cancer were assessed. Univariate analysis is presented using Kaplan-Meier survival curves and log-rank statistics and multivariable Cox proportional hazard models were generated using age group, socio-economic deprivation, FIGO stage, differentiation and HPV type. HPV grouping was considered in a number of ways with particular reference to the presence or absence of HPV 16 and/or 18. In the univariate analysis, FIGO, age at diagnosis and treatment were associated with poorer survival (p < 0.0001) as was absence of HPV 16 and/or 18 (p = 0.0460). The 25% mortality time in the non-HPV 16/18 vs. HPV16/18 positive group was 615 days and 1,307 days respectively. An unadjusted Cox PH model based HPV16/18 vs. no HPV 16/18 resulted in a hazard ratio of 0.669 (0.450, 0.995). Adjusting for deprivation, FIGO and age group resulted in a hazard ratio of 0.609 (0.395, 0.941) p = 0.025. These data indicate that cancers associated with HPV 16 and/or 18 do not confer worse survival compared to cancers associated with other types, and may indicate improved survival. Consequently, although HPV vaccine is likely to reduce the incidence of cervical cancer it may not indirectly improve cervical cancer survival by reducing the burden of those cancers caused by HPV16/18.

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression.

The SeDeM diagram expert system has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril direct compression SR matrix tablets. The application of the SeDeM diagram expert system enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM diagram expert system as system responses.

A case of sebaceous carcinoma arising in a benign cystic teratoma of the ovary and review of the literature.

OBJECTIVE: To present an extremely rare case of sebaceous carcinoma arising in a mature cystic teratoma of the ovary. CLINICAL PRESENTATION AND INTERVENTION: A 66-year-old woman presented with abdominal discomfort and a pelvic mass. Abdominal and pelvic ultrasound, as well as CT scan, revealed a 27 cm complex right pelvic mass, which was diagnosed histologically as a sebaceous carcinoma arising in a mature cystic teratoma. The patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, peritoneal washings, appendicectomy and infracolic omentectomy. CONCLUSION: This case adds to the rare reports in the literature of sebaceous carcinoma occurring in a mature cystic teratoma. The clinical behaviour and optimal management of this entity are not well established. The patient has been well for 32 months following surgery with no evidence of recurrent disease clinically.

[Resistant enterobacteria: explosion of extended-spectrum beta-lactamases]. / Entérobactéries résistantes: explosion des beta-lactamases à spectre élargi.

During the past recent years, Enterobacteriaceae have supplanted Gram-positives in terms of frequent resistant bacteria seen in the outpatent setting. This change involves common opportunistic pathogens such as E. coli and K. pneumoniae. It is mainly due to the appearance and dissemination of extended-spectrum beta-lactamases (ESBL), that hydrolyse penicillins and cephalosporins. Bacteria producing these enzymes are often also resistant to quinolones and trimethoprime-sulfamethoxazole. This article, illustrated by a clinical case, presents the current epidemiology of ESBL-producing Enterobacteriaceae and the possible prevention measures and treatment options to fight the growing number of infections that they are causing.