Prediction of peritoneal soiling in acute appendicitis with simple clinical and laboratory data. Prospective, multicenter, cohort study of 2,645 adult patients nationwide.

BACKGROUND AND AIMS: In order to facilitate the preoperative prediction of complicated appendicitis, we propose a complementary approach by selecting an endpoint defined by the intraoperative finding of peritoneal soiling (PS). METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending emergency general surgery patients on a 24-h, 7-days a week basis, enrolled consecutive adult patients requiring appendectomy. Patients were stratified according to the absence or the finding of PS during the surgical procedure. RESULTS: A total of 2645 patients were included; median age (IQR) was 35 (22-51) years, 44.3% were female. The laparoscopic approach was used in 70.8% of appendectomies. In a third of patients (31.7%), there was PS with pus around the appendix, or bowel contents, free pus, or blood in the peritoneal cavity. To develop the prediction model, 1764 patients were randomly selected for the derivation cohort and the remaining 881 patients were assigned to the validation cohort. On multivariable logistic regression analysis of all patients, two clinical variables (age, and pulse) and three laboratory variables (serum urea, serum sodium, and white blood cell count) were individually associated (P < .05) with a greater probability of having PS (Hosmer-Lemeshow chi, 1.63; P = .99; C-statistic, 0.7). Based on the multivariable regression model, both static and dynamic nomograms were developed for the prediction of PS in patients with acute appendicitis. CONCLUSIONS: The entry of simple clinical and laboratory variables in the dynamic nomogram may be useful in guiding the initial management of patients with acute appendicitis in resource-limited settings.

Simplified risk-prediction for benchmarking and quality improvement in emergency general surgery. Prospective, multicenter, observational cohort study.

BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.

Prevalence and risk factors for acute stress disorder in female victims of sexual assault.

Sexual assault is one of the most traumatic events a person can experience. Despite this, information regarding the risk factors associated with the development of Acute Stress Disorder (ASD) in sexual assault victims is scarce. A follow-up prospective cohort study was designed to examine the prevalence and risk factors of ASD in women exposed to a recent sexual assault. A total of 156 women were treated at the Emergency Department of a university general hospital shortly after sexual assault. Sociodemographic, clinical and sexual assault-related variables were collected. The Acute Stress Disorder Interview was used to estimate the prevalence of ASD at three weeks post-SA. From the 156 victims, 66.6% (N = 104) met ASD diagnosis using DSM-5 criteria, whereas 59.6% (N = 93) met ASD diagnosis using DSM-IV criteria. The risk factors associated with the development of ASD were nationality, psychiatric history, peritraumatic dissociation and type of assault. In conclusion, the prevalence of ASD in female victims of recent sexual assault was high, affecting approximately two thirds of them. The recognition of the risk factors associated with ASD development, like peritraumatic dissociation or type of assault, may aid in the prompt detection of vulnerable women that require early and specific interventions shortly after trauma.

Sperm donation: an alternative to improve post-ICSI live birth rates in advanced maternal age patients.

STUDY QUESTION: Can sperm donation increase live birth rates following ICSI in advanced maternal age (AMA) patients? SUMMARY ANSWER: Sperm donation increases the live birth rate in AMA ICSI cycles. WHAT IS KNOWN ALREADY: In ICSI practice, sperm donation has been predominantly applied to overcome male infertility. The involvement of paternal age and lower sperm quality in the severe reduction in fertility observed in AMA patients remains to be clarified. STUDY DESIGN, SIZE, DURATION: Retrospective multicenter cohort study including data generated between 2015 and 2019 from 755 ICSI cycles achieving a fresh embryo transfer, of which 337 were first homologous cycles (normozoospermic partner sperm and homologous oocytes) and 418 were first sperm donation cycles (donor sperm and homologous oocytes). The association of sperm origin (partner vs donor) with live birth was assessed by multivariate analysis in non-AMA (<37 years, n = 278) and AMA (≥37 years, n = 477) patients, separately, including in the model all variables previously found to be associated with live birth in a univariate analysis (number of MII oocytes recovered, number of embryos transferred, and maternal age). ICSI outcomes were compared between sperm donation and homologous cycles in overall, non-AMA and AMA patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted in three fertility clinics and included 755 Caucasian patients aged 24-42 years undergoing their first homologous or sperm donation ICSI cycle achieving a fresh embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: The multivariate analysis revealed that sperm donation was positively associated with the likelihood of a live birth independently of all other variables tested in AMA (P = 0.02), but not in non-AMA patients. Live birth, delivery, and miscarriage rates differed substantially between sperm donation and homologous AMA cycles; live birth and delivery rates were 70-75% higher (25.4% vs 14.5% and 22.5% vs 13.5%, respectively; P < 0.01), while miscarriage occurrence was less than half (18.0% vs 39.5%; P < 0.01) in sperm donation compared to homologous AMA cycles. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective nature, differences in patients profiles between sperm donation and homologous-control groups and varying proportion of donor cycles between fertility centers, although these variations have been controlled for in the statistical analysis. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest that sperm donation increases live birth rates while reducing miscarriage occurrence in AMA patients, and thus may be a valid strategy to improve ICSI outcomes in this growing and challenging patient group. STUDY FUNDING/COMPETING INTEREST(S): N/A. TRIAL REGISTRATION NUMBER: N/A.

[Alzemon: a prospective follow-up study of eslicarbazepine acetate monotherapy in patients with newly diagnosed epilepsy]. / Alzemon: estudio de seguimiento prospectivo del acetato de eslicarbacepina en monoterapia en pacientes con epilepsia de diagnóstico reciente.

INTRODUCTION: Eslicarbazepine acetate is a novel sodium channel blocker for use in the treatment of focal onset seizures. Prospective studies on its effectiveness in monotherapy in patients with newly diagnosed partial epilepsy in routine clinical practice are scarce. AIM: To evaluate the effectiveness of eslicarbazepine as initial monotherapy in patients with newly diagnosed partial epilepsy in routine clinical practice. PATIENTS AND METHODS: A prospective, multicentre, post-authorisation study. Patients with newly diagnosed partial epilepsy aged 18 years or older without previous treatment were included. The efficacy variables were: percentage of seizure-free patients, responders and reduction in monthly frequency of seizures. The safety variables analyse the 12-month retention rate and the occurrence of adverse effects. RESULTS: Fifty-three patients were included. The retention rate was 77.4%. At the end of the observation period, 83% of patients were seizure-free and 92.5% had reduced their baseline frequency by 50% or more. In addition, 68% of the patients reported some adverse effect and 7.5% of them dropped out of the study for this reason. The effectiveness analysis of the subgroup of patients aged 65 years or more showed no differences with respect to the overall population. CONCLUSION: Eslicarbazepine monotherapy in patients with newly diagnosed partial epilepsy, both in the general population and in the population over 65 years old, is effective and safe in routine clinical practice.

TITLE: Alzemon: estudio de seguimiento prospectivo del acetato de eslicarbacepina en monoterapia en pacientes con epilepsia de diagnóstico reciente.Introducción. El acetato de eslicarbacepina es un nuevo bloqueante de los canales de sodio en el tratamiento de las crisis de inicio focal. Los estudios prospectivos sobre su efectividad en monoterapia en pacientes con epilepsia parcial de reciente diagnóstico en la práctica clínica habitual son escasos. Objetivo. Evaluar la efectividad de la eslicarbacepina en monoterapia de inicio en pacientes con epilepsia parcial de reciente diagnóstico en la práctica clínica habitual. Pacientes y métodos. Estudio postautorización prospectivo y multicéntrico. Se incluyó a pacientes con epilepsia parcial de reciente diagnóstico de 18 años o más sin tratamiento previo. Las variables de eficacia fueron: porcentaje de pacientes libres de crisis, respondedores y reducción en la frecuencia mensual de crisis. Las variables de seguridad analizan la tasa de retención a los 12 meses y la aparición de efectos adversos. Resultados. Se incluyó a 53 pacientes. La tasa de retención fue del 77,4%. Al final del período de observación, el 83% de los pacientes se encontraba libre de crisis y el 92,5% había reducido en un 50% o más su frecuencia basal. El 68% de los pacientes notificó algún efecto adverso y el 7,5% de ellos abandonó el estudio por este motivo. El análisis de efectividad del subgrupo de 65 años o más no mostró diferencias respecto a la población global. Conclusión. La eslicarbacepina en monoterapia en pacientes con epilepsia parcial de reciente diagnóstico, tanto en la población general como en la población de más de 65 años, es eficaz y segura en la práctica clínica habitual.

Exploring the pros and cons of new approaches for gamete cross-border donation based on fresh and vitrified oocytes.

As highlighted by European statistics, the employment of donor oocytes is a growing option for women who cannot make use of their own gametes. As the potential recipients are continuously increasing in number, a donor programme which satisfies this demand is mandatory. Improvements in cryopreservation techniques, like oocyte and embryo vitrification, have led to the overcoming of the sequence of stimulation-retrieval-transfer both from a spatial and a temporal point of view, with the development of cryobanks of oocytes permitting crossborder donation. However, while some studies report comparable success when using vitrified and fresh oocytes we still need to investigate whether the use of fresh oocytes give higher live birth rate than cryopreserved ones, when the same number of oocytes are given. The performance of embryo cryopreservation, conversely, seems to be more reliable. A novel approach based on the shipment of frozen sperm from the recipient's country to the oocyte donor's one, where fresh oocytes are inseminated and the resulting embryos frozen and transported back to the referring IVF centre to perform a frozen embryo transfer may be a good strategy. We believe that the use of frozen embryos from fresh oocytes could be associated with a higher cumulative live birth rate per cycle, while favouring personalised oocyte recipient care with a flexible number of oocytes assigned and limiting the burden of travelling abroad.

Surveillance for pancreatic cancer in high-risk individuals.

Background: Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods: A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results: Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion: A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC.

Antecedentes: Se podrían obtener mejores resultados con el seguimiento de individuos de alto riesgo para adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) y lesiones precursoras. El objetivo de este estudio fue determinar la prevalencia y los resultados del PDAC y de las lesiones precursoras de alto riesgo neoplásico en pacientes que participaron en programas de seguimiento. Métodos: Se llevó a cabo un estudio multicéntrico a través del registro internacional del consorcio CAPS (Common Automotive Platform Standard) para identificar a las personas de alto riesgo que se habían sometido a una resección pancreática o habían progresado a PDAC avanzado mientras estaban en seguimiento. Se definieron como lesiones neoplásicas precursoras de alto riesgo la neoplasia intraepitelial pancreática de tipo 3 (PanIN­3), la neoplasia papilar mucinosa intraductal (intraductal papillary mucinous neoplasia, IPMN) con displasia de alto grado y los tumores neuroendocrinos pancreáticos (pancreatic neuroendocrine tumours, PanNET) de ≥ 2 cm de diámetro. Resultados: De 76 individuos con lesiones de alto riesgo identificados en 11 programas de seguimiento, 71 fueron tratados quirúrgicamente y 5 fueron diagnosticados de un PDAC inoperable. De las 71 resecciones, 32 (45%) tenían PDAC o una lesión precursora de alto riesgo (19 PDAC, 4 IPMN de conducto principal, 4 IPMN de rama secundaria y 5 PanIN­3). Los otros 39 pacientes tenían lesiones que se consideraron asociadas con un menor riesgo de progresión neoplásica. La edad ≥ 65 años, el sexo femenino, el ser portador de una mutación genética y la localización de la lesión en la cabeza/proceso uncinado fueron factores asociados a las lesiones precursoras de alto riesgo o al PDAC. No hubo diferencias en la supervivencia de individuos de alto riesgo con lesiones neoplásicas de bajo riesgo frente a aquellos que presentaron lesiones precursoras de alto riesgo. La supervivencia fue peor en los pacientes con PDAC. No hubo mortalidad relacionada con la cirugía. Conclusión: Un elevado porcentaje de individuos de alto riesgo que se sometieron a resección quirúrgica tras la detección de lesiones pancreáticas en el seguimiento tenían una lesión precursora neoplásica de alto riesgo o un PDAC. La supervivencia fue mejor en individuos de alto riesgo que tenían lesiones precursoras neoplásicas de bajo o alto riesgo en comparación con aquellos pacientes que habían desarrollado un PDAC.

A novel transnational fresh oocyte donation (TOD) program based on transport of frozen sperm and embryos.

STUDY QUESTION: What is the clinical efficacy of an oocyte donation program based on the transportation of frozen semen and embryos between two countries? SUMMARY ANSWER: The transnational oocyte donation program is efficient and reliable and it could provide a first-line strategy to overcome the lack of donors in some countries. WHAT IS KNOWN ALREADY: While there is increasing need for donated oocytes, in many countries the availability of donors is still insufficient to cover the therapeutic demands, and patients are referred abroad for treatment. Since embryo cryopreservation is reliable and efficient, we propose a strategy based on frozen embryos instead of frozen oocytes to satisfy the increasing demand for cross border oocyte donation. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study including 630 patients treated from December 2015 to July 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women were treated with elective vitrified-thawed embryo shipping and embryo transfer (ET) between two IVF clinics, one in Spain and one in Italy. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 2617 embryos were created for the 630 patients and the survival rate after warming was 98.5%. After the first ET the live birth rate (LBR) was 30.6%. In 476 patients (75.5%), embryos were transferred at the cleavage stage (Day 2 or 3) and the LBR was 29.2%. Vitrified blastocysts were available for 154 patients (24.5%) and the LBR was 35%. Among patients who did not achieve a pregnancy after the first frozen ET (FET), 92.5% had at least one frozen embryo for successive procedures. 213 patients underwent a second FET. The LBR at the second FET was 30%. The cumulative LBR at the end of the observation period was 39.3%. LIMITATIONS, REASONS FOR CAUTION: The study design was retrospective. A direct comparison with vitrified oocyte donors cycle and subsequent fresh ET would have permitted to compare this strategy versus the current standard based on vitrified gametes. WIDER IMPLICATIONS OF THE FINDINGS: The LBR found in our study is more than acceptable and seems to be higher than what reported with vitrified oocytes. The transnational fresh oocyte donation program may have several advantages over the shipment of vitrified oocytes: similarly to the fresh oocyte donation program it allows for personalized care in oocyte recipient, which is provided by assigning a flexible number of oocytes, and at the same time it maintains the benefit of a frozen ART program permitting scheduling flexibility. The TOD program is efficient and may be proposed as a first-line strategy for distance and inter-countries oocyte donation programs. STUDY FUNDING, COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: NA.

Characterization of the miRNA regulators of the human ovulatory cascade.

Ovarian follicular development and ovulation are complex and tightly regulated processes that involve regulation by microRNAs (miRNAs). We previously identified differentially expressed mRNAs between human cumulus granulosa cells (CGCs) from immature early antral follicles (germinal vesicle - GV) and mature preovulatory follicles (metaphase II - M2). In this study, we performed an integrated analysis of the transcriptome and miRNome in CGCs obtained from the GV cumulus-oocyte complex (COC) obtained from IVM and M2 COC obtained from IVF. A total of 43 differentially expressed miRNAs were identified. Using Ingenuity IPA analysis, we identified 7288 potential miRNA-regulated target genes. Two hundred thirty-four of these target genes were also found in our previously generated ovulatory gene library while exhibiting anti-correlated expression to the identified miRNAs. IPA pathway analysis suggested that miR-21 and FOXM1 cooperatively inhibit CDC25A, TOP2A and PRC1. We identified a mechanism for the temporary inhibition of VEGF during ovulation by TGFB1, miR-16-5p and miR-34a-5p. The linkage bioinformatics analysis between the libraries of the coding genes from our preliminary study with the newly generated library of regulatory miRNAs provides us a comprehensive, integrated overview of the miRNA-mRNA co-regulatory networks that may play a key role in controlling post-transcriptomic regulation of the ovulatory process.

Association of sporadic and familial Barrett's esophagus with breast cancer.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Based on striking aggregation of breast cancer and BE/EAC within families as well as shared risk factors and molecular mechanisms of carcinogenesis, we hypothesized that BE may be associated with breast cancer. Pedigree analysis of families identified prospectively at multiple academic centers as part of the Familial Barrett's Esophagus Consortium (FBEC) was reviewed and families with aggregation of BE/EAC and breast cancer are reported. Additionally, using a matched case-control study design, we compared newly diagnosed BE cases in Caucasian females with breast cancer (cases) to Caucasian females without breast cancer (controls) who had undergone upper endoscopy (EGD). Two familial pedigrees, meeting a stringent inclusion criterion, manifested familial aggregation of BE/EAC and breast cancer in an autosomal dominant inheritance pattern with incomplete penetrance. From January 2008 to October 2016, 2812 breast cancer patient charts were identified, of which 213 were Caucasian females who underwent EGD. Six of 213 (2.82%) patients with breast cancer had pathology-confirmed BE, compared to 1 of 241 (0.41%) controls (P-value < 0.05). Selected families with BE/EAC show segregation of breast cancer. A breast cancer diagnosis is marginally associated with BE. We postulate a common susceptibility between BE/EAC and breast cancer.

Focused time-lapse analysis reveals novel aspects of human fertilization and suggests new parameters of embryo viability.

STUDY QUESTION: Can focused application of time-lapse microscopy (TLM) lead to a more detailed map of the morphokinetics of human fertilization, revealing novel or neglected aspects of this process? SUMMARY ANSWER: Intensive harnessing of TLM reveals novel or previously poorly characterised phenomena of fertilization, such as a cytoplasmic wave (CW) preceding pronuclear formation and kinetics of pronuclear chromatin polarization, thereby suggesting novel non-invasive biomarkers of embryo quality. WHAT IS KNOWN ALREADY: In recent years, human preimplantation development has been the object of TLM studies with the intent to develop morphokinetic algorithms able to predict blastocyst formation and implantation. Regardless, our appreciation of the morphokinetics of fertilization remains rather scarce, currently including only times of polar body II (PBII) emission, pronuclear appearance and fading, and first cleavage. This is not consistent with the complexity and importance of this process, calling for further TLM studies aimed at describing previously unrecognized or undetected morphokinetic events and identifying novel developmental biomarkers. STUDY DESIGN, SIZE, DURATION: The study involved a retrospective observation by TLM of the fertilization process in 500 oocytes utilized in consecutive ICSI cycles carried out in 2016. A maximum of five fertilized oocytes per patients were included in the analysis to reduce possible patient-specific biases. Oocytes of patients with different diagnoses of infertility where included in the analysis, while cases involving cryopreserved gametes or surgically retrieved sperm were excluded. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Microinjected oocytes where assessed by a combined TLM-culture system (Embryoscope). Oocytes that were not amenable to TLM assessment, due to excess of residual corona cells or inadequate orientation for the observation of PBII emission, were not analysed. We identified and monitored 28 parameters relevant to meiotic resumption, pronuclear dynamics, chromatin organization, and cytoplasmic/cortical modifications. Times (T) were expressed as mean ± SD hours post-insemination (p.i.) and analysed, where appropriate, by Paired T Student or Fisher's exact tests. MAIN RESULTS AND ROLE OF CHANCE: PBII emission was occasionally followed (4.3% of cases) by the transient appearance of a protrusion of the cell surface, the fertilization cone (FC), probably resulting from interaction of the male chromatin with the oocyte cortex. Pronuclear formation was always preceded by a radial CW originating from the initial position of the male pronucleus (PN) and extending towards the oocyte periphery. The appearance of the CW followed a precise sequence, occurring always 2-3 h after PBII emission and shortly before PN appearance. Male and female PN appeared virtually simultaneously at approximately 6.2 h p.i. However, while the female PN always formed cortically and near the site of emission of the PBII, the initial position of the male PN was cortical, intermediate, or central (15.2%, 31.2% and 53.6%, respectively). PN juxtaposition involved rapid and straight movement of the female PN towards the male PN. In addition, the initial position of male PN formation was predictive of the position of PN juxtaposition. It was also observed that nucleolar precursor bodies (NPBs) aligned along the juxtaposition area and this happened considerably earlier for the female PN (8.2 ± 2.6 vs.11.2 ± 4.1 h, P = 0.0001). Although it occurred rarely, displacement of juxtaposed PN to the cortex was strongly associated (P < 0.0001) with direct cleavage into three blastomeres at the first cell division. The times of PN breakdown and first cleavage showed a very consistent trend, occurring earlier or progressively later depending on whether initial male PN positioning was central, intermediate or cortical, respectively. Finally, time intervals between discrete fertilization events were strongly associated with embryo quality on Day 3. For example, longer intervals between disappearance of the cytoplasmic halo and PN breakdown were highly predictive of reduced blastomere number and increased fragmentation (P = 0.0001). LARGE SCALE DATA: N/A. LIMITATIONS, REASON FOR CAUTION: Some of the morphokinetic parameters assessed in this study may require better definition to reduce inter-operator annotation variability. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, overall, these data represent the most detailed morphokinetic description of human fertilization. Many of the illustrated parameters are novel and may be amenable to further elaboration into algorithms able to predict embryo quality, as suggested by the findings presented in this study. STUDY FUNDING/COMPETING INTERESTS: None.

Tendencia y distribución municipal de la incidencia de cáncer de vejiga en el área de salud de León (1996-2010) / Municipal distribution and trends in bladder cancer incidence in health area of León, Spain (1996-201

Objetivo: España presenta unas de las tasas más elevadas de incidencia y mortalidad por cáncer de vejiga del mundo. El presente estudio tiene por objeto conocer la incidencia, tendencia y distribución geográfica del cáncer de vejiga en el área de salud de León. Material y métodos: Fueron incluidos los casos nuevos de cáncer de vejiga (CIE-188) del registro hospitalario de tumores del Centro Asistencial Universitario de León, entre 1996-2010 con residencia en el ASL. Se calcularon las incidencias brutas trienales y ajustadas a población mundial y europea. Como denominador se utilizaron los datos del INE de población desagregada por sexo y grupos quinquenales de edad de residentes en municipios del ASL. Para el análisis de la distribución espacial se estimaron los riesgos relativos (RR) municipales suavizados mediante el ajuste del modelo de Besag, York y Mollié y sus probabilidades posteriores de que los RR fuesen > 1 (PP), utilizando métodos bayesianos. Resultados: Se incluyeron 1.573 casos. Las tasas estandarizadas a población europea ascendieron de 20,8 (1996-98) a 33,1 (2006-2008) casos nuevos por 100.000 hombres y de 1,9 a 5,9 en las mujeres. No se observaron diferencias de interés en la distribución municipal de las incidencias. Conclusiones: Las tasas de incidencia observadas son elevadas en el contexto europeo. Se observan tendencias ascendentes en hombres y especialmente relevantes en mujeres

Objective: Spain is a country where bladder cancer incidence and mortality rates are some of the highest in the world. The aim of this study is to know the incidence, trends and geographical distribution of bladder cancer in the health area of León. Material and methods: the new cases of bladder cancer (CIE-188) in patients residing in the health area of León and registered in the Hospital Tumor Registry of the Centro Asistencial Universitario in León (Spain) between 1996-2010 were included in this study. Triennial crude incidence and adjusted incidence rates to the worldwide and European population were calculated. Population data of the municipalities of Leon (Spain) were obtained from National Institute of Statistic of Spain (INE, Instituto Nacional de Estadística). Data were disaggregated by sex-groups and five-year age groups. Spatial distribution of smoothed municipal relative risks (RR) of bladder cancer was carried out using a Besag, York and Mollié model. Bayesian model were used to calculate the posterior probability (PP) of RR greater than one. Results: 1.573 cases were included. Incidence rates standardized to European population increased among men from 20,8/100.000 (1996-98) to 33,1/100.000 (2006-2008) and among women these rates increased from 1,9/100.000 to 5,9/100.000 for the same period of time. No relevant differences were found in the municipal distribution of the incidences. Conclusions: bladder cancer incidence rates are high in the European context. Rising trends in incidence in both sexs, particularly in women are observed

Hipofisitis linfocitaria y paquimeningitis hipertrófica: descripción de un posible caso asociado a las patologías IgG4 / Lymphocytic hypophysitis and hypertrophic pachymeningitis: description of a possible case associated to IgG4 pathologies

Introducción. Las patologías relacionadas con la infiltración de linfocitos y células inflamatorias se clasifican, según su topografía, en patología orbitaria idiopática, paquimeningitis hipertrófica idiopática, síndrome de Tolosa-Hunt e hipofisitis linfocitaria. Presentamos a una paciente que comenzó con una hipofisitis linfocitaria hace ocho años y ha presentado varios episodios de paquimeningitis hipertrófica variables en su localización. Caso clínico. Mujer de 55 años, en seguimiento por cefalea de dos meses de evolución, que ingresó por empeoramiento clínico con parálisis del III par derecho completo, lagrimeo y rinorrea. Se realizó una resonancia magnética cerebral que demostró la presencia de una lesión sellar compatible con hipofisitis linfocitaria. Se inició tratamiento con corticoides con mejoría inicial, pero, tras dos años, la paciente presentó empeoramiento clínico con cefalea y parestesias perioculares derechas. Se repitió la resonancia, donde se observaron varias lesiones extraaxiales, siendo el resto de estudios normales, por lo que se diagnosticó paquimeningitis hipertrófica idiopática y se inició tratamiento de nuevo con corticoides. En el seguimiento posterior, la paciente presentó nuevas lesiones en diferentes localizaciones y mal control álgico, por lo que se añadió tratamiento inmunomodulador. Ante la asociación de hipofisitis linfocitaria y paquimeningitis hipertrófica, se completó el estudio con determinación de la IgG4 en el suero, que resultó negativa. Conclusiones. La asociación de hipofisitis linfocitaria y paquimeningitis hipertrófica con las patologías relacionadas con la IgG4 se ha descrito recientemente. A pesar de que en nuestra paciente no se ha confirmado el diagnóstico, se debe considerar esta relación en aquellos casos idiopáticos y, sobre todo, si se asocian otras manifestaciones sistémicas

Introduction. Pathologies related to lymphocyte infiltration and inflammatory cells are classified, according to their topography, into idiopathic orbital pathology, idiopathic hypertrophic pachymeningitis, Tolosa-Hunt syndrome and lymphocytic hypophysitis. Here we review the case of a female patient who began with lymphocytic hypophysitis eight years ago and has since presented several episodes of hypertrophic pachymeningitis in a variety of locations. Case report. Our study involves a 55-year-old female, being monitored owing to a two-month history of headaches, who was admitted to hospital as the result of a deterioration of her clinical signs and symptoms with paralysis of the whole right-side third cranial nerve, watery eyes and rhinorrhea. A magnetic resonance brain scan revealed the presence of a sellar lesion consistent with lymphocytic hypophysitis. Treatment was established with corticoids with an improvement at first, but two years later the patient’s clinical features worsened, with headaches and periocular paraesthesias on the right-hand side. Another MRI scan was performed and several extra-axial lesions were observed, the results of the other studies being normal. Idiopathic hypertrophic pachymeningitis was therefore diagnosed and treatment with corticoids was started again. In the ensuing follow-up the patient presented new lesions in different locations and poor pain control, and so immunomodulator treatment was thus added. Given the association between lymphocytic hypophysitis and hypertrophic pachymeningitis, the study was completed with determination of the IgG4 in serum, which was negative. Conclusions. The association of lymphocytic hypophysitis and hypertrophic pachymeningitis with IgG4-related pathologies have recently been reported. Although the diagnosis has not been confirmed in our patient, this relationship must be taken into account in these idiopathic cases and, above all, if they are associated with other systemic manifestations

[Lymphocytic hypophysitis and hypertrophic pachymeningitis: description of a possible case associated to IgG4 pathologies]. / Hipofisitis linfocitaria y paquimeningitis hipertrófica: descripción de un posible caso asociado a las patologías IgG4.

INTRODUCTION: Pathologies related to lymphocyte infiltration and inflammatory cells are classified, according to their topography, into idiopathic orbital pathology, idiopathic hypertrophic pachymeningitis, Tolosa-Hunt syndrome and lymphocytic hypophysitis. Here we review the case of a female patient who began with lymphocytic hypophysitis eight years ago and has since presented several episodes of hypertrophic pachymeningitis in a variety of locations. CASE REPORT: Our study involves a 55-year-old female, being monitored owing to a two-month history of headaches, who was admitted to hospital as the result of a deterioration of her clinical signs and symptoms with paralysis of the whole right-side third cranial nerve, watery eyes and rhinorrhea. A magnetic resonance brain scan revealed the presence of a sellar lesion consistent with lymphocytic hypophysitis. Treatment was established with corticoids with an improvement at first, but two years later the patient's clinical features worsened, with headaches and periocular paraesthesias on the right-hand side. Another MRI scan was performed and several extra-axial lesions were observed, the results of the other studies being normal. Idiopathic hypertrophic pachymeningitis was therefore diagnosed and treatment with corticoids was started again. In the ensuing follow-up the patient presented new lesions in different locations and poor pain control, and so immunomodulator treatment was thus added. Given the association between lymphocytic hypophysitis and hypertrophic pachymeningitis, the study was completed with determination of the IgG4 in serum, which was negative. CONCLUSIONS: The association of lymphocytic hypophysitis and hypertrophic pachymeningitis with IgG4-related pathologies have recently been reported. Although the diagnosis has not been confirmed in our patient, this relationship must be taken into account in these idiopathic cases and, above all, if they are associated with other systemic manifestations.

TITLE: Hipofisitis linfocitaria y paquimeningitis hipertrofica: descripcion de un posible caso asociado a las patologias IgG4.Introduccion. Las patologias relacionadas con la infiltracion de linfocitos y celulas inflamatorias se clasifican, segun su topografia, en patologia orbitaria idiopatica, paquimeningitis hipertrofica idiopatica, sindrome de Tolosa-Hunt e hipofisitis linfocitaria. Presentamos a una paciente que comenzo con una hipofisitis linfocitaria hace ocho años y ha presentado varios episodios de paquimeningitis hipertrofica variables en su localizacion. Caso clinico. Mujer de 55 años, en seguimiento por cefalea de dos meses de evolucion, que ingreso por empeoramiento clinico con paralisis del III par derecho completo, lagrimeo y rinorrea. Se realizo una resonancia magnetica cerebral que demostro la presencia de una lesion sellar compatible con hipofisitis linfocitaria. Se inicio tratamiento con corticoides con mejoria inicial, pero, tras dos años, la paciente presento empeoramiento clinico con cefalea y parestesias perioculares derechas. Se repitio la resonancia, donde se observaron varias lesiones extraaxiales, siendo el resto de estudios normales, por lo que se diagnostico paquimeningitis hipertrofica idiopatica y se inicio tratamiento de nuevo con corticoides. En el seguimiento posterior, la paciente presento nuevas lesiones en diferentes localizaciones y mal control algico, por lo que se añadio tratamiento inmunomodulador. Ante la asociacion de hipofisitis linfocitaria y paquimeningitis hipertrofica, se completo el estudio con determinacion de la IgG4 en el suero, que resulto negativa. Conclusiones. La asociacion de hipofisitis linfocitaria y paquimeningitis hipertrofica con las patologias relacionadas con la IgG4 se ha descrito recientemente. A pesar de que en nuestra paciente no se ha confirmado el diagnostico, se debe considerar esta relacion en aquellos casos idiopaticos y, sobre todo, si se asocian otras manifestaciones sistemicas.

Selective immediate responders to amoxicillin and clavulanic acid tolerate penicillin derivative administration after confirming the diagnosis.

BACKGROUND: An increasing number of patients show immediate selective hypersensitivity reactions to clavulanic acid (CLV) and amoxicillin (AX), probably due to their increased prescription. The maintenance of this response should be established. OBJECTIVE: To assess that the immediate hypersensitivity selective response to AX or to CLV is maintained after repeated administration of penicillin G (PG)/penicillin V (PV) and AX. METHODS: Patients with proven immediate hypersensitivity to AX (Group A) or CLV (Group B) were included. Diagnosis was performed using skin tests with major and minor determinants of PG (PPL/MDM), AX and CLV and by drug provocation test (DPT) if required. Selectivity was established by confirming tolerance to PG/PV (Group A) and to PG/PV and AX (Group B). The maintenance of the selective response was verified by repeating DPT, 15 days after the initial investigation, with the same procedure. RESULTS: Of 51 patients, 78% belonged to Group A and 22% to Group B. Most had anaphylaxis. In Group A, 72% were skin test positive; 28% required DPT. In Group B, 63% were skin test positive; 37% required DPT. Only two AX-selective cases developed positive responses after re-provocation with PG/PV. No cases selective for CLV developed a positive response to PG, PV or AX. DISCUSSION: The selective response to AX appears consistent, and a response to penicillin determinants only develops in a minority of cases. For the case of CLV, the selective response appears not to be modified by exposure to penicillin determinants, meaning that patients with CLV allergy can take penicillin derivatives safely.