Venous thromboembolism in Cushing syndrome: results from an EuRRECa and Endo-ERN survey.

Background: Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE). Objective: The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis. Design and methods: A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG's) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022. Results: Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3-30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Conclusion: Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed. Significance statement: The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.

Electronic reporting of rare endocrine conditions within a clinical network: results from the EuRRECa project.

Objective: The European Registries for Rare Endocrine Conditions (EuRRECa, eurreb.eu) includes an e-reporting registry (e-REC) used to perform surveillance of conditions within the European Reference Network (ERN) for rare endocrine conditions (Endo-ERN). The aim of this study was to report the experience of e-REC over the 3.5 years since its launch in 2018. Methods: Electronic reporting capturing new encounters of Endo-ERN conditions was performed monthly through a bespoke platform by clinicians registered to participate in e-REC from July 2018 to December 2021. Results: The number of centres reporting on e-REC increased to a total of 61 centres from 22 countries. A median of 29 (range 11, 45) paediatric and 32 (14, 51) adult centres had reported cases monthly. A total of 9715 and 4243 new cases were reported in adults (age ≥18 years) and children, respectively. In children, sex development conditions comprised 40% of all reported conditions and transgender cases were most frequently reported, comprising 58% of sex development conditions. The median number of sex development cases reported per centre per month was 0.6 (0, 38). Amongst adults, pituitary conditions comprised 44% of reported conditions and pituitary adenomas (69% of cases) were most commonly reported. The median number of pituitary cases reported per centre per month was 4 (0.4, 33). Conclusions: e-REC has gained increasing acceptability over the last 3.5 years for capturing brief information on new encounters of rare conditions and shows wide variations in the rate of presentation of these conditions to centres within a reference network. Significance statement Endocrinology includes a very wide range of rare conditions and their occurrence is often difficult to measure. By using an electronic platform that allowed monthly reporting of new clinical encounters of several rare endocrine conditions within a defined network that consisted of several reference centres in Europe, the EuRRECa project shows that a programme of e-surveillance is feasible and acceptable. The data that have been collected by the e-reporting of rare endocrine conditions (e-REC) can allow the continuous monitoring of rare conditions and may be used for clinical benchmarking, designing new studies or recruiting to clinical trials.

Niveles séricos de PAPP-A y beta-hCG en el primer trimestre del embarazo como predictores de resultados obstétricos desfavorables en el Hospital Universitario Nuestra Señora de Candelaria / Serum levels of PAPP-A and beta-hCG in the first trimester of pregnancy as predictors of unfavourable obstetric outcomes at Hospital Universitario Nuestra Señora de Candelaria

Muchos estudios han documentado la asociación entre valores bajos de PAPP-A y β-hCG en el suero materno durante el primer trimestre, así como efectos materno-fetales adversos.Para valorar dicha relación, en nuestro medio se llevó a cabo un análisis retrospectivo de casos y controles anidado en una cohorte de pacientes con embarazo único en quienes se realizó el cribado del primer trimestre entre 2017 y 2018. Se consideraron casos aquellas pacientes con niveles de MoM PAPP-A y/o β-hCG iguales o inferiores al percentil 5, y como controles a una muestra aleatorizada de pacientes con niveles séricos por encima de dicho percentil.El análisis de nuestros resultados demostró que en los grupos con niveles bajos de MoM PAPP-A y MoM β-hCG se observó un mayor riesgo de desarrollar crecimiento intrauterino restringido que en el grupo control (OR: 2,7 y 3,17, respectivamente). En el grupo MoM PAPP-A≤p5 también se obtuvo un riesgo 3,8 veces superior de estados hipertensivos del embarazo (IC: 1,94-7,83) y 7,9 veces mayor de muerte fetal anteparto (IC:1,09-217,4). Estas dos variables no resultaron estadísticamente significativas en el grupo MoM β-hCG ≤p5.Nuestros hallazgos confirmaron que los niveles bajos de PAPP-A y β-hCG en el suero de las gestantes se asoció con un riesgo elevado de desarrollar complicaciones obstétricas, por lo que podrían utilizarse para la detección precoz de las mismas y prevención de malos resultados obstétricos.

Many studies have documented the association between low PAPP-A and β-hCG values in maternal serum during the first trimester and adverse maternal-foetal effects.To assess this relationship a retrospective analysis of cases and controls was carried out, based on a cohort of patients with a single pregnancy who underwent first-trimester screening between 2017 and 2018. For the group of cases, patients with MoM levels PAPP-A and/or β-hCG equal to or below the 5th percentile were selected. The control group was obtained by making a randomized selection of all patients with MoM PAPP-A levels and/or β-hCG above that percentile.The analysis of our results showed that in groups with low levels of MoM PAPP-A and MoM β- hCG, we observed a higher risk of developing restricted intrauterine growth than in the control group (OR: 2.7 and 3.17, respectively). In the MoM PAPP-A ≤p5 group we also obtained a 3.8-foldhigher risk of global hypertensive states of pregnancy (CI: 1.94-7.83) and 7.9-fold higher risk of antepartum foetal death (CI: 1.09- 217.4). These two variables were not statistically significant in the MoM β-hCG ≤p5 group.Our findings confirmed that low levels of PAPP-A and β-hCG in the serum of pregnant women are associated with a high risk of developing obstetric complications, so they could be used for their early detection and the prevention of poor obstetric results.

Differentiation of Trichuris species using a morphometric approach.

Trichuris trichiura is a nematode considered as the whipworm present in humans and primates. The systematics of the genus Trichuris is complex. Morphological studies of Trichuris isolated from primates and humans conclude that the species infecting these hosts is the same. Furthermore, numerous molecular studies have been carried out so far to discriminate parasite species from humans and Non-Human Primates using molecular techniques, but these studies were not performed in combination with a parallel morphological study. The hypothesised existence of more species of Trichuris in primates opens the possibility to revise the zoonotic potential and host specificity of T. trichiura and other putative new species of whipworms. In the present work, a study of Trichuris Roederer, 1761 (Nematoda:Trichuridae) parasitizing C. g. kikuyensis, P. ursinus, Macaca sylvanus, Pan troglodytes, and Sus scrofa domestica has been carried out using modern morphometric techniques in order to differentiate populations of Trichuris isolated from four species of captive NHP from different geographical regions, and swine, respectively. The results obtained revealed strong support for geometrical morphometrics as a useful tool to differentiate male Trichuris populations. Therefore, morphometrics in combination with other techniques, such as molecular biology analyses, ought to be applied to further the differentiation of male populations. On the other hand, morphometrics applied to female Trichuris species does not seem to contribute new information as all the measurements combinations of obtained from females always showed similar results.

Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with second-line VEGFR-TKI after first-line immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are being increasingly utilised in the front-line (1L) setting of metastatic clear-cell renal cell carcinoma (mccRCC). Limited data exist on responses and survival on second-line (2L) vascular endothelial growth factor-receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy after 1L ICI therapy. PATIENTS AND METHODS: This is a retrospective study of mccRCC patients treated with 2L VEGFR-TKI after progressive disease (PD) with 1L ICI. Patients were treated at MD Anderson Cancer Center or Memorial Sloan Kettering Cancer Center between December 2015 and February 2018. Objective response was assessed by blinded radiologists' review using Response Evaluation Criteria in Solid Tumours v1.1. Descriptive statistics and Kaplan-Meier method were used. RESULTS: Seventy patients were included in the analysis. Median age at mccRCC diagnosis was 59 years; 8 patients (11%) had international metastatic database consortium favourable-risk disease, 48 (69%) had intermediate-risk disease and 14 (20%) had poor-risk disease. As 1L therapy, 12 patients (17%) received anti-programmed death ligand-1 (PD-(L)1) monotherapy with nivolumab or atezolizumab, 33 (47%) received nivolumab plus ipilimumab and 25 (36%) received combination anti-PD-(L)1 plus bevacizumab. 2L TKI therapies included pazopanib, sunitinib, axitinib and cabozantinib. On 2L TKI therapy, one patient (1.5%) achieved a complete response, 27 patients (39.7%) a partial response and 36 patients (52.9%) stable disease. Median progression-free survival (mPFS) was 13.2 months (95% confidence interval: 10.1, NA). Forty-five percent of subjects required a dose reduction, and twenty-seven percent of patients discontinued treatment because of toxicity. CONCLUSIONS: In this retrospective study of patients with mccRCC receiving 2L TKI monotherapy after 1L ICI, we observed 2L antitumour activity and tolerance comparable to historical data for 1L TKI.

Origin, evolution, phylogeny and taxonomy of Pulex irritans.

The human flea Pulex irritans Linnaeus, 1758 (Siphonaptera: Pulicidae) is one of the most studied species together with the cat flea Ctenocephalides felis Bouché, 1835, because they have a cosmopolitan distribution and are closely related to humans. The present study aimed to carry out a comparative morphometric and molecular study of two different populations of P. irritans (Spain and Argentina). Accordingly, internal transcribed spacer (ITS)1 and ITS2 of rDNA and the partial cytochrome c oxidase subunit 1 (cox1) and cytochrome b (cytb) mtDNA genes of these taxa were sequenced. Furthermore, the taxonomy, origin, evolution and phylogeny of P. irritans was assessed. The morphometric data obtained did not show significant differences between P. irritans specimens from Spain and Argentina, even when these two populations were collected from different hosts; however, there was a considerable degree of molecular divergence between both populations based on nuclear and mitochondrial markers. Thus, it is proposed that P. irritans, in contrast with other generalist fleas, maintains a certain degree of morphological similarity, at least between Western Palearctic and Neotropical areas. Furthermore, two well defined geographical genetic lineages within the P. irritans species are indicated, suggesting the existence of two cryptic species that could be discriminated by a polymerase chain reaction-linked restriction fragment length polymorphism.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry as a useful tool for the rapid identification of wild flea vectors preserved in alcohol.

Flea identification is a significant issue because some species are considered as important vectors of several human pathogens that have emerged or re-emerged recently, such as Bartonella henselae (Rhizobiales: Bartonellaceae) and Rickettsia felis (Rickettsiales: Rickettsiaceae). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been evaluated in recent years for the identification of multicellular organisms, including arthropods. A preliminary study corroborated the usefulness of this technique for the rapid identification of fleas, creating a preliminary database containing the spectra of five species of flea. However, longterm flea preservation in ethanol did not appear to be an adequate method of storage in the context of specimen identification by MALDI-TOF MS profiling. The goal of the present work was to assess the performance of MALDI-TOF MS in the identification of seven flea species [Ctenocephalides felis (Siphonaptera: Pulicidae), Ctenocephalides canis, Pulex irritans (Siphonaptera: Pulicidae), Archaeopsylla erinacei (Siphonaptera: Pulicidae), Leptopsylla taschenbergi (Siphonaptera: Ceratophyllidae), Stenoponia tripectinata (Siphonaptera: Stenoponiidae) and Nosopsyllus fasciatus (Siphonaptera: Ceratophyllidae)] collected in the field and stored in ethanol for different periods of time. The results confirmed that MALDI-TOF MS can be used for the identification of wild fleas stored in ethanol. Furthermore, this technique was able to discriminate not only different flea genera, but also the two congeneric species C. felis and C. canis.

Hipertensión arterial no controlable en el primer trimestre de la gestación. Hiperparatiroidismo primario, a propósito de un caso / Uncontrollable hypertension in the first trimester of pregnancy. Primary hyperparathyroidism; a case report

Mujer de 28 años. Sin antecedentes médico-quirúrgicos de interés. Gestación actual gemelar bicorial-biamniótica espontánea. Ingresa con 9 semanas por vómitos incoercibles con diagnóstico de hiperemesis gravídica. Las tensiones arteriales se mantienen elevadas. Se inicia estudio de enfermedad hipertensiva y tratamiento, sin mejoría. En las analíticas destacan una calcemia y PTH muy elevada con fosforemia baja. Se completa estudio con ecografía de cuello informada como presencia de lesión hipoecoica inferior al lóbulo tiroideo derecho sugestiva de adenoma paratiroideo. Se confirma diagnóstico de hipercalcemia severa secundaria a hiperparatiroidismo primario por adenoma de paratiroides. Se decide realizar paratiroidectomía en segundo trimestre, tras la cual se produce descenso de la calcemia y control de la tensión arterial y del resto de clínica. Aunque es la causa más frecuente de hipercalcemia en la población general, se trata de una enfermedad poco frecuente en mujeres en edad fértil. Su incidencia aproximada durante el embarazo es de 8/10.000. Durante el embarazo se produce una transferencia de calcio y fósforo materno al feto, lo que provoca la supresión de la secreción de PTH fetal y el incremento de los valores de calcitonina. Se asocia a una alta morbimortalidad materno-fetal, con riesgo de nefrolitiasis, hiperemesis, HTA, gran morbilidad con aumento de riesgo de preeclampsia y de afección renal. Como complicaciones obstétricas destacan el aumento del riesgo de aborto, amenaza de parto pretérmino y el desarrollo de fetos con retraso del crecimiento intrauterino. Entre las medidas conservadoras de tratamiento se recomienda mantener una buena hidratación oral, limitar la ingesta de calcio y tratar los síntomas asociados. La paratiroidectomía es el tratamiento definitivo y se debe realizar en el segundo trimestre

Spontaneous dichorionic-diamniotic twin pregnancy. Patient is admitted at 9weeks pregnant due to uncontrollable vomiting and is diagnosed with hyperemesis gravidarum. Blood pressure remains high. Study of hypertensive disease and treatment initiated without improvement. Blood tests showed a very high serum calcium and PTH with low phosphoremia. Study is completed with neck ultrasound revealing a lower hypoechoic lesion of the right thyroid lobe suggestive of parathyroid adenoma. Diagnosis of severe hypercalcemia secondary to primary hyperparathyroidism due to parathyroid adenoma was confirmed. It was decided to perform a parathyroidectomy in the second trimester after which a decrease in serum calcium, control blood pressure and other symptoms was found. Although it is the most common cause of hypercalcemia in the general population, it is a rare condition in women of childbearing age. Its approximate incidence during pregnancy is 8/10,000. During pregnancy, maternal calcium and phosphorus is transferred to the fetus, which results in suppression of fetal PTH secretion and increased fetal calcitonin values. It is associated with high maternal and fetal morbidity and mortality and risk of nephrolithiasis, hyperemesis, hypertension, high morbidity with increased risk of preeclampsia and kidney disease. In the fetus, there is an increased risk of spontaneous abortion, intrauterine growth retardation and preterm birth. Among conservative treatment measures, it is recommended to maintain good oral hydration, limit calcium intake and treat associated symptoms. Parathyroidectomy is the definitive treatment and should be performed in the second trimester

Morphological, biometrical and molecular characterization of Archaeopsylla erinacei (Bouché, 1835).

In the present work, we carried out a morphological, biometrical and molecular study of the species Archaeopsylla erinacei (Bouché, 1835) and their subspecies: Archaeopsylla erinacei erinacei (Bouché, 1835) and Archaeopsylla erinacei maura (Jordan & Rothschild, 1912) isolated from hedgehogs (Erinaceus europaeus) from different geographical regions (Seville and Corse). We have found morphological differences in females of A. erinacei from the same geographical origin that did not correspond with molecular differences. We suggest that some morphological characters traditionally used to discriminate females of both subspecies should be revised as well as we set the total length of the spermatheca as a valid criterion in order to discriminate between both subspecies. The Internal Transcribed Spacers 1 and 2 (ITS1, ITS2) and partial 18S rRNA gene, and partial cytochrome c-oxidase 1 (cox1) and cytochrome b (cytb) mtDNA gene sequences were determined to clarify the taxonomic status of these taxa and to assess intra-specific and intra-population similarity. In addition, a phylogenetic analysis with other species of fleas using Bayesian and Maximum Likelihood analysis was performed. All molecular markers used, except 18S, showed molecular differences between populations corresponding with geographical origins. Thus, based on the phylogenetic and molecular study of two nuclear markers (ITS1, ITS2) and two mitochondrial markers (cox1 and cytb), as well as concatenated sequences of both subspecies, we reported the existence of two geographical genetic lineages in A. erinacei corresponding with two different subspecies: A. e. erinacei (Corse, France) and A. e. maura (Seville, Spain), that could be discriminated by polymerase chain reaction-linked random-fragment-length polymorphism.

Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma.

BACKGROUND: In two clinical trials of the vascular endothelial growth factor (VEGF) receptor inhibitor pazopanib in advanced renal cell carcinoma (mRCC), we found interleukin-6 as predictive of pazopanib benefit. We evaluated the prognostic significance of candidate cytokines and angiogenic factors (CAFs) identified in that work relative to accepted clinical parameters. METHODS: Seven preselected plasma CAFs (interleukin-6, interleukin-8, osteopontin, VEGF, hepatocyte growth factor, tissue inhibitor of metalloproteinases (TIMP-1), and E-selectin) were measured using multiplex ELISA in plasma collected pretreatment from 343 mRCC patients participating in the phase 3 registration trial of pazopanib vs placebo (NCT00334282). Tumour burden (per sum of longest diameters (SLD)) and 10 other clinical factors were also analysed for association with overall survival (OS; based on initial treatment assignment). RESULTS: Osteopontin, interleukin-6, and TIMP-1 were independently associated with OS in multivariable analysis. A model combining the three CAFs and five clinical variables (including SLD) had higher prognostic accuracy than the International Metastatic Renal Cell Carcinoma Database Consortium criteria (concordance-index 0.75 vs 0.67, respectively), and distinguished two groups of patients within the original intermediate risk category. CONCLUSIONS: A prognostic model incorporating osteopontin, interleukin-6, TIMP-1, tumour burden, and selected clinical criteria increased prognostic accuracy for OS determination in mRCC patients.

Dose painting by means of Monte Carlo treatment planning at the voxel level.

PURPOSE: To develop a new optimization algorithm to carry out true dose painting by numbers (DPBN) planning based on full Monte Carlo (MC) calculation. METHODS: Four configurations with different clustering of the voxel values from PET data were proposed. An optimization method at the voxel level under Lineal Programming (LP) formulation was used for an inverse planning and implemented in CARMEN, an in-house Monte Carlo treatment planning system. RESULTS: Beamlet solutions fulfilled the objectives and did not show significant differences between the different configurations. More differences were observed between the segment solutions. The plan for the dose prescription map without clustering was the better solution. CONCLUSIONS: LP optimization at voxel level without dose-volume restrictions can carry out true DPBN planning with the MC accuracy.

A randomized phase 2 study of MK-2206 versus everolimus in refractory renal cell carcinoma.

Background: Activation of the phosphoinisitide-3 kinase (PI3K) pathway through mutation and constitutive upregulation has been described in renal cell carcinoma (RCC), making it an attractive target for therapeutic intervention. We performed a randomized phase II study in vascular endothelial growth factor (VEGF) therapy refractory patients to determine whether MK-2206, an allosteric inhibitor of AKT, was more efficacious than the mammalian target of rapamycin inhibitor everolimus. Patients and methods: A total of 43 patients were randomized in a 2:1 distribution, with 29 patients assigned to the MK-2206 arm and 14 to the everolimus arm. Progression-free survival (PFS) was the primary endpoint. Results: The trial was closed at the first futility analysis with an observed PFS of 3.68 months in the MK-2206 arm and 5.98 months in the everolimus arm. Dichotomous response rate profiles were seen in the MK-2206 arm with one complete response and three partial responses in the MK-2206 arm versus none in the everolimus arm. On the other hand, progressive disease was best response in 44.8% of MK2206 versus 14.3% of everolimus-treated patients. MK-2206 induced significantly more rash and pruritis than everolimus, and dose reduction occurred in 37.9% of MK-2206 versus 21.4% of everolimus-treated patients. Genomic analysis revealed that 57.1% of the patients in the PD group had either deleterious TP53 mutations or ATM mutations or deletions. In contrast, none of the patients in the non-PD group had TP53 or ATM defects. No predictive marker for response was observed in this small dataset. Conclusions: Dichotomous outcomes are observed when VEGF therapy refractory patients are treated with MK-2206, and MK-2206 does not demonstrate superiority to everolimus. Additionally, mutations in DNA repair genes are associated with early disease progression, indicating that dysregulation of DNA repair is associated with a more aggressive tumor phenotype in RCC.

Tuberculosis diseminada en anciano de edad avanzada / Disseminated tuberculosis in elderly patients

No disponible

Molecular study of Stenoponia tripectinata tripectinata (Siphonaptera: Ctenophthalmidae: Stenoponiinae) from the Canary Islands: taxonomy and phylogeny.

In the present work, we carried out a comparative molecular study of Stenoponia tripectinata tripectinata isolated from Mus musculus from the Canary Islands, Spain. The Internal Transcribed Spacers 1 and 2 (ITS1, ITS2) and 18S ribosomal RNA partial gene and cytochrome c-oxidase 1 (cox1) mitochondrial DNA partial gene sequences of this subspecies were determined to clarify the taxonomic status of this subspecies and to assess inter-population variation and inter-specific sequence differences. In addition, we have carried out a comparative phylogenetic study with other species of fleas using Bayesian, Maximum Parsimony, Maximum Likelihood and Neighbor-Joining analysis. A geographical signal was detected between the cox1 partial gene sequences of S. t. tripectinata isolated from M. musculus from different islands and those isolated from Apodemus sylvaticus from the Iberian Peninsula. Our results assess the monophyletic origin of Stenoponiinae and a different genetic lineage from Ctenophthalmidae. Thus, the elevation of subfamily Stenoponiinae to family level (Stenoponiidae) is suggested.

Integrating chemohormonal therapy and surgery in known or suspected lymph node metastatic prostate cancer.

BACKGROUND: Prostate cancer persisting in the primary site after systemic therapy may contribute to emergence of resistance and progression. We previously demonstrated molecular characteristics of lethal cancer in the prostatectomy specimens of patients presenting with lymph node metastasis after chemohormonal treatment. Here we report the post-treatment outcomes of these patients and assess whether a link exists between surgery and treatment-free/cancer-free survival. METHODS: Patients with either clinically detected lymph node metastasis or primaries at high risk for nodal dissemination were treated with androgen ablation and docetaxel. Those responding with PSA concentration <1 ng ml(-1) were recommended surgery 1 year from enrollment. ADT was withheld postoperatively. The rate of survival without biochemical progression 1 year after surgery was measured to screen for efficacy. RESULTS: Forty patients were enrolled and 39 were evaluable. Three patients (7.7%) declined surgery. Of the remaining 36, 4 patients experienced disease progression during treatment and 4 more did not reach PSA <1. Twenty-six patients (67%) completed surgery, and 13 (33%) were also progression-free 1 year postoperatively (8 with undetectable PSA). With a median follow-up of 61 months, time to treatment failure was 27 months in the patients undergoing surgery. The most frequent patterns of first disease recurrence were biochemical (10 patients) and systemic (5). CONCLUSIONS: Half of the patients undergoing surgery were off treatment and progression-free 1 year following completion of all therapy. These results suggest that integration of surgery is feasible and may be superior to systemic therapy alone for selected prostate cancer patients presenting with nodal metastasis.

Taxonomy and phylogeny of Trichuris globulosa Von Linstow, 1901 from camels. A review of Trichuris species parasitizing herbivorous.

At the present work, we carried out a morph-biometrical and molecular study of Trichuris species isolated from Camelus dromedarius from Iran and from Ovis aries from South Africa comparatively with other species of Trichuris from different herbivorous hosts and geographical regions. The population from camels from Iran was identified as Trichuris globulosa. Two different morphometrically populations of Trichuris sp. from sheep from South Africa were identified: Trichuris ovis and Trichuris skrjabini. Ribosomal data did not reveal significate differences in the ITS2 sequences between T. ovis and T. globulosa to assess a specific determination. The mitochondrial data suggest that T. globulosa constitute a different genetic lineage to T. ovis. Cytochrome c-oxidase and cytochrome b partial gene sequences corroborated the existence of a different genetic lineage of T. ovis from sheep of South Africa that would be closely related to the populations of T. globulosa from camels from Iran. The cytochrome c-oxidase and cytochrome b partial gene sequences of T. globulosa have been reported for the first time.

Atención en el parto en la mujer inmigrante; características sociodemográficas y de comportamiento en función de la procedencia de la paciente / Antenatal care among immigrant women: Sociodemografic characteristics and behavior depending on the patient's geographical origin

Los continuos movimientos migratorios son la causa de la gran variedad de pacientes extranjeros que se atiende en algunos centros hospitalarios. Este hecho supone una dificultad añadida al cuidado de las pacientes, en nuestro caso gestantes, puesto que nos encontramos con una barrera idiomática y cultural importante que en muchos casos puede dificultar su atención y mermar su trato. Para conocer estas limitaciones se ha planteado un estudio descriptivo transversal con el fin de determinar las características sociodemográficas de las gestantes inmigrantes de la zona tropical de Granada que acuden al Hospital General Básico Santa Ana, en Motril. En este estudio se ha evidenciado que el seguimiento del embarazo en las mujeres inmigrantes es alto, pero es menor en las mujeres procedentes del Magreb y el África subsahariana. También se percibe que el número de mujeres que realiza el curso de educación maternal es muy bajo: el 37% en las mujeres latinoamericanas, pero inferior al 12% en las demás procedencias

Due to continuous migration, some hospital centers attend a wide variety of foreign patients. This increases the difficulties of attending patients -in our case pregnant women-due to language and cultural barriers that can hamper communication and patient care. With a view to characterizing these limitations, a cross-sectional descriptive study was performed to determine the sociodemographic characteristics of pregnant immigrant women from the tropical coast of Granada attending the Santa Ana Basic General Hospital in Motril, Granada. This study found that antenatal care among immigrant women was high but was lower in women from the Magreb and sub-Saharan Africa. The number of women attending pregnancy-related health education programs was very low: 37% among Latin-American women but less than 12% among women from other areas

Circulating cytokines and monocyte subpopulations as biomarkers of outcome and biological activity in sunitinib-treated patients with advanced neuroendocrine tumours.

BACKGROUND: Sunitinib is approved worldwide for treatment of advanced pancreatic neuroendocrine tumours (pNET), but no validated markers exist to predict response. This analysis explored biomarkers associated with sunitinib activity and clinical benefit in patients with pNET and carcinoid tumours in a phase II study. METHODS: Plasma was assessed for vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, interleukin (IL)-8 (n=105), and stromal cell-derived factor (SDF)-1α (n=28). Pre-treatment levels were compared between tumour types and correlated with response, progression-free (PFS), and overall survival (OS). Changes in circulating myelomonocytic and endothelial cells were also analysed. RESULTS: Stromal cell-derived factor-1α and sVEGFR-2 levels were higher in pNET than in carcinoid (P=0.003 and 0.041, respectively). High (above-median) baseline SDF-1α was associated with worse PFS, OS, and response in pNET, and high sVEGFR-2 with longer OS (P⩽0.05). For carcinoid, high IL-8, sVEGFR-3, and SDF-1α were associated with shorter PFS and OS, and high IL-8 and SDF-1α with worse response (P⩽0.05). Among circulating cell types, monocytes showed the largest on-treatment decrease, particularly CD14+ monocytes co-expressing VEGFR-1 or CXCR4. CONCLUSIONS: Interleukin-8, sVEGFR-3, and SDF-1α were identified as predictors of sunitinib clinical outcome. Putative pro-tumorigenic CXCR4+ and VEGFR-1+ monocytes represent novel candidate markers and biologically relevant targets explaining the activity of sunitinib.

Use of imipenem to detect KPC, NDM, OXA, IMP, and VIM carbapenemase activity from gram-negative rods in 75 minutes using liquid chromatography-tandem mass spectrometry.

Resistance to extended-spectrum ß-lactam antibiotics has led to a greater reliance upon carbapenems, but the expression of carbapenemases threatens to limit the utility of these drugs. Current methods to detect carbapenemase activity are suboptimal, requiring prolonged incubations during which ineffective therapy may be prescribed. We previously described a sensitive and specific assay for the detection of carbapenemase activity using ertapenem and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we assessed 402 Gram-negative rods, including both Enterobacteriaceae and non-Enterobacteriaceae expressing IMP, VIM, KPC, NDM, and/or OXA carbapenemases, by using imipenem, meropenem, and ertapenem with LC-MS/MS assays. LC-MS/MS methods for the detection of intact and hydrolyzed carbapenems from an enrichment broth were developed. No ion suppression was observed, and the limits of detection for all three drugs were below 0.04 µg/ml. The sensitivity and specificity of meropenem and ertapenem for carbapenemase activity among non-Enterobacteriaceae were low, but imipenem demonstrated a sensitivity and specificity of 96% and 95%, respectively, among all Gram-negative rods (GNR) tested, including both Enterobacteriaceae and non-Enterobacteriaceae. LC-MS/MS allows for the analysis of more complex matrices, and this LC-MS/MS assay could easily be adapted for use with primary specimens requiring growth enrichment.