Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience. / [Artículo traducido] Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Simulating intervertebral disc cell behaviour within 3D multifactorial environments.

MOTIVATION: Low back pain is responsible for more global disability than any other condition. Its incidence is closely related to intervertebral disc (IVD) failure, which is likely caused by an accumulation of microtrauma within the IVD. Crucial factors in microtrauma development are not entirely known yet, probably because their exploration in vivo or in vitro remains tremendously challenging. In silico modelling is, therefore, definitively appealing, and shall include approaches to integrate influences of multiple cell stimuli at the microscale. Accordingly, this study introduces a hybrid Agent-based (AB) model in IVD research and exploits network modelling solutions in systems biology to mimic the cellular behaviour of Nucleus Pulposus cells exposed to a 3D multifactorial biochemical environment, based on mathematical integrations of existing experimental knowledge. Cellular activity reflected by mRNA expression of Aggrecan, Collagen type I, Collagen type II, MMP-3 and ADAMTS were calculated for inflamed and non-inflamed cells. mRNA expression over long periods of time is additionally determined including cell viability estimations. Model predictions were eventually validated with independent experimental data. RESULTS: As it combines experimental data to simulate cell behaviour exposed to a multifactorial environment, the present methodology was able to reproduce cell death within 3 days under glucose deprivation and a 50% decrease in cell viability after 7 days in an acidic environment. Cellular mRNA expression under non-inflamed conditions simulated a quantifiable catabolic shift under an adverse cell environment, and model predictions of mRNA expression of inflamed cells provide new explanation possibilities for unexpected results achieved in experimental research. AVAILABILITYAND IMPLEMENTATION: The AB model as well as used mathematical functions were built with open source software. Final functions implemented in the AB model and complete AB model parameters are provided as Supplementary Material. Experimental input and validation data were provided through referenced, published papers. The code corresponding to the model can be shared upon request and shall be reused after proper training. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Informed consent in dentistry and medicine in Spain: Practical considerations and legality.

BACKGROUND: The healthcare practice of dentistry, as well as medicine, is framed within a legal environment. Patients have the right to know all the information related to any action performed on them and dental or medical doctors are obliged to obtain their patient's prior written informed consent (IC) before undertaking any healthcare procedures. MATERIAL AND METHODS: Here we reviewed the legality and jurisprudence in Spain regarding IC. We also used INFLESZ text readability analysis software to analyse a sample of official Spanish informed consent documents (ICDs) from different surgical and interventional procedures related to dentistry and oral cavity interventions. RESULTS: It is a mistake to confound IC with ICDs. This error prevents physicians from considering the former as a care process in which the patient's authorisation signature is the last link in a chain formed, almost in its entirety, by the informative process and deliberation alongside the patient. Multiple factors can influence communication between practitioners and their patients. Importantly, treatment adherence is greater when patients feel involved and autonomous in shared decision-making and when the circumstances of their lives are adequately considered. We concluded that although the ICDs we analysed conformed to the requirements set out in international law, they were somewhat difficult to read according to the reading habits of the general Spanish population. CONCLUSIONS: Knowledge about the legality of IC helps professionals to understand the problems that may arise from their non-compliance. This is because the omission or defective fulfilment of IC obligations is the origin of legal responsibility for medical practitioners. In this sense, to date, there have been more convictions for defective ICs than for malpractice. The information provided in ICs should include the risks, benefits, and treatment alternatives and must be tailored to the needs and capabilities of the patient to enable autonomous decision-making.

Prognostic Value and Risk Factors of Peritoneal Carcinomatosis Recurrence for Patients with Endometrial Cancer: A Multicenter Study from the FRANCOGYN Group.

BACKGROUND: The prognosis for patients with endometrial cancer (EC) peritoneal carcinomatosis (PC) recurrence has received little study. This study aimed to determine specific risk factors and prognosis of EC with PC recurrence (PCR) versus no PC recurrence (NPCR). METHODS: Data of all patients with EC who received primary surgical treatment between January 2000 and February 2017 were abstracted from the French FRANCOGYN Research Group database. Clinical and pathologic variables were compared between the two groups (PCR vs. NPCR). Multivariate analysis was performed to define prognostic factors for peritoneal recurrence. Overall survivals (OS) of patients after recurrence were compared using the Kaplan-Meier method. RESULTS: The study analyzed 1466 patients, and 257 of these patients (17.5%) had recurrence. At presentation, 63 of these patients had PC. International Federation of Gynecology and Obstetrics (FIGO) stages 3 and 4 disease were significantly associated with PCR versus NPCR (odds ratio 2.24; 95% confidence interval 1.23-4.07; p = 0.008). The death rate for the patients with PC was 47.6%, with a median survival of 12 months after diagnosis of recurrence. According to the histologic subtype, OS was 29 months (Q1-Q3, 13-NA) for endometrioid carcinomas, 7.5 months (Q1-Q3, 4-15) for serous carcinomas, and 10 months (Q1-Q3, 5-15) for clear cell carcinomas. Chemotherapy for treatment of PCR was associated with improved OS after recurrence (OSAR; p = 0.0025). CONCLUSION: An initial advanced stage of EC is a risk factor for PCR. For women with PCR, a diagnosis of type 1 EC recurrence more than 12 months after the initial treatment and management of PCR with chemotherapy is associated with improved OSAR. Prospective studies are needed to determine the precise optimal management required in this clinical situation and to assess the relevance of biomarkers to predict the risk of PCR for EC patients.

Genome-wide association study for feed efficiency in collective cage-raised rabbits under full and restricted feeding.

Feed efficiency (FE) is one of the most economically and environmentally relevant traits in the animal production sector. The objective of this study was to gain knowledge about the genetic control of FE in rabbits. To this end, GWASs were conducted for individual growth under two feeding regimes (full feeding and restricted) and FE traits collected from cage groups, using 114 604 autosome SNPs segregating in 438 rabbits. Two different models were implemented: (1) an animal model with a linear regression on each SNP allele for growth trait; and (2) a two-trait animal model, jointly fitting the performance trait and each SNP allele content, for FE traits. This last modeling strategy is a new tool applied to GWAS and allows information to be considered from non-genotyped individuals whose contribution is relevant in the group average traits. A total of 189 SNPs in 17 chromosomal regions were declared to be significantly associated with any of the five analyzed traits at a chromosome-wide level. In 12 of these regions, 20 candidate genes were proposed to explain the variation of the analyzed traits, including genes such as FTO, NDUFAF6 and CEBPA previously associated with growth and FE traits in monogastric species. Candidate genes associated with behavioral patterns were also identified. Overall, our results can be considered as the foundation for future functional research to unravel the actual causal mutations regulating growth and FE in rabbits.

Three-dimensional regional bi-ventricular shape remodeling is associated with exercise capacity in endurance athletes.

AIMS: Endurance athletes develop cardiac remodeling to cope with increased cardiac output during exercise. This remodeling is both anatomical and functional and shows large interindividual variability. In this study, we quantify local geometric ventricular remodeling related to long-standing endurance training and assess its relationship with cardiovascular performance during exercise. METHODS: We extracted 3D models of the biventricular shape from end-diastolic cine magnetic resonance images acquired from a cohort of 89 triathlon athletes and 77 healthy sedentary subjects. Additionally, the athletes underwent cardio-pulmonary exercise testing, together with an echocardiographic study at baseline and few minutes after maximal exercise. We used statistical shape analysis to identify regional bi-ventricular shape differences between athletes and non-athletes. RESULTS: The ventricular shape was significantly different between athletes and controls (p < 1e-6). The observed regional remodeling in the right heart was mainly a shift of the right ventricle (RV) volume distribution towards the right ventricular infundibulum, increasing the overall right ventricular volume. In the left heart, there was an increment of left ventricular mass and a dilation of the left ventricle. Within athletes, the amount of such remodeling was independently associated to higher peak oxygen pulse (p < 0.001) and weakly with greater post-exercise RV free wall longitudinal strain (p = 0.03). CONCLUSIONS: We were able to identify specific bi-ventricular regional remodeling induced by long-lasting endurance training. The amount of remodeling was associated with better cardiopulmonary performance during an exercise test.

Microgravity effects on frozen human sperm samples.

PURPOSE: Microgravity has severe effects on cellular and molecular structures as well as on metabolic interactions. The aim of this study is to investigate the effects of microgravity (µg) exposure on human frozen sperm samples. METHODS: Sibling samples from 15 normozoospermic healthy donors were frozen using glycerol as cryoprotectant and analyzed under microgravity and ground conditions. Microgravity was obtained by parabolic flights using a CAP10B plane. The plane executed 20 parabolic maneuvers with a mean of 8.5 s of microgravity for each parabola. RESULTS: Frozen sperm samples preserved in cryostraws and stored in a secure and specific nitrogen vapor cryoshipper do not suffer significant alterations after µg exposure. Comparing the study group (µg) and the control group (1 g), similar results were obtained in the main parameters studied: sperm motility (M/ml) 13.72 ± 12.57 vs 13.03 ± 12.13 (- 0.69 95% CI [- 2.9; 1.52]), progressive a + b sperm motility (%) 21.83 ± 11.69 vs 22.54 ± 12.83 (0.03 95% CI [- 0.08; 0.15]), sperm vitality (%) 46.42 ± 10.81 vs 44.62 ± 9.34 (- 0.04 95% CI [- 0.13; 0.05]), morphologically normal spermatozoa (%) 7.03 ± 2.61 vs 8.09 ± 3.61 (0.12 95% CI [0.01; 0.24]), DNA sperm fragmentation by SCD (%) 13.33 ± 5.12 vs 13.88 ± 6.14 (0.03 95% CI [- 0.09; 0.16]), and apoptotic spermatozoa by MACS (%) 15.47 ± 15.04 vs 23.80 ± 23.63 (- 0.20 95% CI [- 0.66; 1.05]). CONCLUSION: The lack of differences obtained between frozen samples exposed to µg and those maintained in ground conditions provides the possibility of considering the safe transport of human male gametes to space. Nevertheless, further research is needed to validate the results and to consider the possibility of creating a human sperm bank outside the Earth. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03760783.

Discrimination of osteoporosis-related vertebral fractures by DXA-derived 3D measurements: a retrospective case-control study.

A retrospective case-control study assessing the association of DXA-derived 3D measurements with osteoporosis-related vertebral fractures was performed. Trabecular volumetric bone mineral density was the measurement that best discriminates between fracture and control groups. INTRODUCTION: The aim of the present study was to evaluate the association of DXA-derived 3D measurements at the lumbar spine with osteoporosis-related vertebral fractures. METHODS: We retrospectively analyzed a database of 74 postmenopausal women: 37 subjects with incident vertebral fractures and 37 age-matched controls without any type of fracture. DXA scans at the lumbar spine were acquired at baseline (i.e., before the fracture event for subjects in the fracture group), and areal bone mineral density (aBMD) was measured. DXA-derived 3D measurements, such as volumetric BMD (vBMD), were assessed using a DXA-based 3D modeling software (3D-SHAPER). vBMD was computed at the trabecular, cortical, and integral bone. Cortical thickness and cortical surface BMD were also measured. Differences in DXA-derived measurements between fracture and control groups were evaluated using unpaired t test. Odds ratio (OR) and area under the receiver operating curve (AUC) were also computed. Subgroup analyses according to fractured vertebra were performed. RESULTS: aBMD of fracture group was 9.3% lower compared with control group (p < 0.01); a higher difference was found for trabecular vBMD in the vertebral body (- 16.1%, p < 0.001). Trabecular vBMD was the measurement that best discriminates between fracture and control groups, with an AUC of 0.733, against 0.682 for aBMD. Overall, similar findings were observed within the subgroup analyses. The L1 vertebral fractures subgroup had the highest AUC at trabecular vBMD (0.827), against aBMD (0.758). CONCLUSION: This study showed the ability of cortical and trabecular measurements from DXA-derived 3D models to discriminate between fracture and control groups. Large cohorts need to be analyzed to determine if these measurements could improve fracture risk prediction in clinical practice.

Impact and risk factors of non-adherence to 5-aminosalicylates in quiescent ulcerative colitis evaluated by an electronic management system.

BACKGROUND AND OBJECTIVE: To determine the impact of non-adherence to 5-Aminosalicylates (5-ASA) on the risk of flares and to identify risk factors of non-adherence. METHODS: Observational, cohort study of ulcerative colitis (UC) patients in clinical remission at least 6 months on 5-ASA monotherapy maintenance prescribed by an electronic management program. Adherence was considered when 80% of the prescribed 5-ASA had been dispensed at the pharmacy. The study analyzed the existence and degree of 5-ASA adherence, disease course, UC phenotypic expression, and 5-ASA dose and regimen, and consumption of non-UC chronic drugs during 2-year follow-up. RESULTS: The study included 274 patients, 49% males with a median age of 38 (27-49) years old. Overall, 41% of patients were non-adherent to 5-ASA. Risk of flares was reduced in the adherent group (36% vs 54%; OR = 0,484; p = 0,004), mainly the mild ones (26% vs 38%; OR = 0,559; p = 0,031). Non-adherence was associated with younger age at diagnosis (32 (26-45) vs 41.5 (21-50), p = 0.000) and no-consumption of other chronic treatments (1.1 vs 2.1; OR = 1709; p = 0,048). CONCLUSION: Non-adherence to 5-ASA evaluated by the pharmaceutical management system was at 41% with a higher risk of relapse. Younger patients and patients who do not receive non-UC chronic treatments showed lower adherence rate.

Fertility outcomes in women experiencing severe complications after surgery for colorectal endometriosis.

STUDY QUESTION: What are the fertility outcomes in women wishing to conceive after experiencing a severe complication from surgical removal of colorectal endometriosis? SUMMARY ANSWER: The pregnancy rate (PR) among women who wished to conceive after a severe complication of surgery for colorectal endometriosis was 41.2% (spontaneously for 80%, after ART procedure for 20%). WHAT IS KNOWN ALREADY: While the long-term benefit of surgery on pain and quality of life is well documented for women with colorectal endometriosis, it exposes women to the risk of severe complications. However, little is known about fertility outcomes in women experiencing such severe postoperative complications. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included women who experienced a severe complication after surgery for colorectal endometriosis between January 2004 and June 2014, and who wished to conceive. A total of 53 patients met the inclusion criteria. The fertility outcome was available for 48 women, who were therefore included in the analysis. The median follow-up was 5 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: All the women underwent complete removal of colorectal endometriosis. Postoperative severe complications were defined as grades III-IV of the Clavien-Dindo classification. Fertility outcomes, PR and cumulative pregnancy rate (CPR), were estimated. MAIN RESULTS AND THE ROLE OF CHANCE: Most women experienced a grade IIIb complication (83.3%). Of 48 women, 20 became pregnant (overall PR: 41.2%); spontaneously for 16 (80%) and after ART procedure for 4 (20%). The median interval between surgery and first pregnancy was 3 years. The live birth rate was 14/48 (29.2%). The 5-year CPR was 46%. A lower CPR was found for women who experienced anastomotic leakage (with or without rectovaginal fistula) (P = 0.02) or deep pelvic abscess (with or without anastomotic leakage) (P = 0.04). LIMITATIONS REASONS FOR CAUTION: Due to a lack of information, no sub-analysis was done to investigate other parameters potentially impacting fertility outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The PR for our population was slightly lower to that observed in the literature for women who experience such surgery without consideration for the occurrence of complications. However, 'severe complications' covers a range of conditions which are likely to have a very different impacts on fertility. Even if the PR and CPR appear satisfactory, septic complications can negatively impact fertility outcomes. Rapid ART may be a good option for these patients. STUDY FUNDING/COMPETING INTEREST(S): No funding was required for the current study. Pr H. Roman reported personal fees from Plasma Surgical Inc. (Roswell, GA, USA) for participating in a symposium and a masterclass, in which he presented his experience in the use of PlasmaJet®. None of the other authors declared any conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Maternal and neonatal outcomes in women with colorectal endometriosis.

OBJECTIVE: To evaluate delivery and neonatal outcomes in women with resected or in situ bowel endometriosis. DESIGN: Retrospective cohort study. SETTING: France. POPULATION AND SAMPLE: Analysis of 72 pregnancies from 67 women followed for colorectal endometriosis from 2001 to 2014 in six centres including two university expert centres for endometriosis. METHODS: Univariate analysis of maternal and neonatal outcomes. MAIN OUTCOME MEASURES: Routes for delivery and rate of complications. RESULTS: The colorectal surgery group comprised 41 women and the in situ colorectal group, 26 women. Overall, half of the women underwent caesarean section. A high incidence of postoperative complications (39%) was observed after caesarean section with no difference between the groups. Surgical difficulties at newborn extraction (22%) and postoperative complications (39%) occurred more often in women with anterior deep infiltrating endometriosis (respectively 63 versus 11%, P = 0.007 and 67% versus 26%, P = 0.046) independently of prior surgery for endometriosis. In the remaining half, vaginal delivery required an operative procedure in 28% of the women with a significant increase in postpartum complications compared with those who did not require a procedure (P = 0.001). Overall, the incidence of postpartum complications was lower after vaginal delivery (14%) than after caesarean section (39%) (P = 0.03). CONCLUSION: Pregnant women with colorectal endometriosis, irrespective of prior surgery, should be informed of the high risk of delivery by caesarean section. Vaginal delivery is preferrable in this setting because of the lower incidence of postpartum complications. TWEETABLE ABSTRACT: Due to the incidence of postpartum complications whatever the route of delivery, women should receive level III maternal care.

Prospective, randomized comparison of the use of FloShield Air System® versus the reference technique (water + povidone-iodine solution) during gynecologic endoscopic surgery to evaluate the operative lens vision quality.

BACKGROUND: The FloShield Air System® is a new device for laparoscopic surgery that utilizes a continuous dry CO2 gas flow over the scope to defog the lens and protect it from condensation, debris and smoke. We set out to compare the performance and efficiency of the device in terms of operative lens vision quality (OLVQ) with the reference technique (water + povidone-iodine (PVI) solution) during gynecologic laparoscopic surgery. MATERIALS AND METHODS: We conducted a single-center randomized prospective study between March and June 2016 (Trials Database Registration NCT02702531) including 53 patients undergoing gynecologic laparoscopic surgery with water + PVI solution and 51 patients who underwent surgical procedures with the FloShield Air System. The primary outcome measure was the number of laparoscope removals during surgery. Secondary outcome measures were the time to clean, assessment of the quality of vision, the correlation between the laparoscopic surgical complexity and outcomes, and cost effectiveness. RESULTS: Overall, the mean patient age was 43.2 years (range 22-86) and body mass index 24.8 (range 16.8-42.7). The mean number of endoscope removals during surgery was 7.0 (range 0-37) in the water + PVI solution arm and 2.8 (range 0-12) in the FloShield Air System® arm. The number of removals was significantly lower in the FloShield arm (p < 0.001). No difference in time to clean, quality of vision, level of laparoscopic procedure complexity, or cost was observed between the groups. CONSLUSIONS: The FloShield Air System® resulted in fewer laparoscopic lens removals than the water + PVI solution solution, but that there was no difference in quality of vision, cleaning time or cost, especially for the more complex surgery.

Call for Surgical Nodal Staging in Women with ESMO/ESGO/ESTRO High-Intermediate Risk Endometrial Cancer: A Multicentre Cohort Analysis from the FRANCOGYN Study Group.

BACKGROUND: The European Society of Medical Oncology (ESMO)/European Society of Gynaecological Oncology (ESGO)/European Society for Radiotherapy & Oncology (ESTRO) classification for endometrial cancer (EC) now includes a high-intermediate risk (HIR) group of recurrence due to the adverse prognostic role of lymphovascular space involvement (LVSI) and grade 3 for women at intermediate risk. However, optimal surgical staging, and especially the place of lymphadenectomy, remains to be elucidated. We aimed to establish whether systematic nodal staging should be part of surgical staging for women with HIR EC. METHODS: We abstracted from a prospectively maintained multicentre database the data of 181 women with HIR EC based on uterine factors (endometrioid type 1, grade 1-2 tumors with deep (≥50%) myometrial invasion and unequivocally positive LVSI, and those with grade 3 tumors with <50% myometrial invasion regardless of LVSI status), who received primary surgical treatment between January 2001 and December 2013. We recorded frequency of lymph node (LN) metastases in those who underwent nodal staging. The secondary outcomes were overall survival and recurrence patterns. RESULTS: Overall, 145 (80.1%) women underwent nodal staging consisting of at least pelvic lymphadenectomy. Of these, 62 (42.7%) had LN disease (9.7% with micrometastases). The respective 5-year overall survival rates according to LN status were 85.0% (95% confidence interval [CI] 76.5-91.4), 71.8% (95% CI 61.9-80.4) and 36.0% (95% CI 26.6-46.2) for women with negative LN, positive LN, and unstaged (p = 0.047). Unstaged women were more likely to experience nodal recurrence than surgically staged/LN negative women (p = 0.05). CONCLUSIONS: Systematic nodal staging should be part of surgical staging for women with apparent ESMO/ESGO/ESTRO HIR EC. Sentinel LN biopsy (SLNB) could be an option in this specific setting that may possibly substitute comprehensive staging, for the identification of patients with lymphatic dissemination.

Improving the clinical management of women with borderline tumours: a recurrence risk scoring system from a French multicentre study.

OBJECTIVE: To develop a risk scoring system (RSS) for predicting recurrence in women with borderline ovarian tumours (BOTs). DESIGN: Cohort study of women with BOTs. SETTING: French multicentre tertiary care centres. POPULATION: A cohort of 360 women with BOTs who received primary surgical treatment between January 2000 and December 2013. METHODS: Clinical and pathological factors affecting recurrence in women with BOTs. MAIN OUTCOME MEASURE: The development of a model for the prediction of recurrence in women with BOTs. RESULTS: Overall the recurrence rate was 20.0% (72/360). Recurrence was associated with five variables: age < 45 years; preoperative serum tumour marker CA125 > 150 IU/mL; a serous histological subtype; International Federation of Gynecology and Obstetrics (FIGO) stage other than IA; and ovarian surgery other than bilateral salpingo-oophorectomy (BSO; i.e. cystectomy and unilateral salpingo-oophorectomy). These variables were included in the RSS and assigned scores ranging from 0 to 6. The discrimination of the RSS was 0.82 (95% confidence interval, 95% CI 0.79-0.85). A total score of 8 points corresponded to the optimal threshold of the RSS, with a rate of recurrence of 11.8% (35/297) and 58.7% (37/63) for women at low risk (<8 points) and women at high risk (≥8 points), respectively. The diagnostic accuracy was 85.0%. CONCLUSIONS: This study shows that the risk of BOT recurrence can be accurately predicted so that women at high risk can benefit from adapted surgical treatment. TWEETABLE ABSTRACT: Our RSS permitted women with BOTs at low risk to be distinguished from women with BOTs at high risk of recurrence.

Evaluation of antigen-induced synovitis in a porcine model: Immunological, arthroscopic and kinetic studies.

BACKGROUND: Synovitis is an inflammation-related disease linked to rheumatoid arthritis, osteoarthritis, infections and trauma. This inflammation is accompanied by immune cells infiltration which initiates an inflammatory response causing pain, discomfort and affecting the normal joint function. The treatment of synovitis is based on the administration of anti-inflammatory drugs or biological agents such as platelet rich plasma and mesenchymal stem cells. However, the evaluation and validation of more effective therapies of synovitis requires the establishment of clinically relevant animal models. RESULTS: In this study, Large White pigs were pre-immunized to evaluate an antigen-induced synovitis. The immune monitoring of synovial fluids in this model allowed us the identification of IL-12p40 and T cell subsets as immune biomarkers. Moreover, the evolution of synovitis was performed by arthroscopic procedures and kinetic analysis. In summary, this paper describes an animal model of antigen-induced synovitis to be used in the evaluation of anti-inflammatory therapies. CONCLUSIONS: The novelty of this paper lies in the development of a clinically relevant model of synovitis which permits the simultaneous evaluation of synovitis from an immunological, surgical and kinetic point of view.

Association of genetic variants and expression levels of porcine FABP4 and FABP5 genes.

The FABP4 and FABP5 genes, coding for fatty acid transport proteins, have long been studied as positional candidate genes for SSC4 QTL affecting fat deposition and composition traits in pigs. Polymorphisms in these genes, FABP4:g.2634_2635insC and FABP5:g.3000T>G, have previously been associated with fatness traits in an Iberian by Landrace cross (IBMAP). The aim of the present work was to evaluate the functional implication of these genetic variants. For this purpose, FABP4 and FABP5 mRNA expression levels in 114 BC1_LD animals (25% Iberian × 75% Landrace) were analyzed using real-time quantitative PCR in backfat and muscle. FABP4 gene expression in backfat, but not in muscle, was associated with FABP4:g.2634_2635insC. In contrast, FABP5:g.3000T>G was not associated with gene expression levels. An expression-based genome-wide association study highlighted the FABP4:g.2634_2635insC polymorphism as the polymorphism most associated with FABP4 gene expression in backfat. Furthermore, other genomic regions associated in trans with the mRNA expression of FABP4 in backfat and FABP5 in muscle were also identified. Finally, two putative transcription binding sites for PPARG and NR4A2 may be affected by the FABP4:g.2634_2635insC polymorphism, modifying FABP4 gene expression. Our results reinforce FABP4 as a candidate gene for fatness traits on SSC4.

[Detecting and measuring functional and organic disease in general population: Development and validation of TOPYPS clinical scale]. / Detección y medición de la enfermedad funcional y orgánica en población general: desarrollo y validación de la escala clínica TOPYPS.

OBJECTIVE: To develop and validate the TOPYPS scale, an instrument designed to: (i)detect with a high degree of suspicion the most frequent functional pathologies according to standard diagnostic criteria, and (ii)to assess the physical health in the general population quickly, comprehensive and reliable. DESIGN: Validation of a scale. LOCATION: Primary Care Centre, Barcelona. PARTICIPANTS: The scale was administered to 67 randomly selected adults. MEASUREMENTS: TOPYPS scale was administered to 67 adults randomly selected from a primary care setting in Barcelona, Spain. TOPYPS has six sections based on body systems, each one scored according to the degree of interference in daily activity, type of treatment received, and prognostic of the reported illnesses in each section. Test-retest reliability completions were on two separate occasions one week apart. Validity was then tested by comparing the results with the clinical examination conducted by two different specialists in general practice (gold standard). RESULTS: Repeatability (test-retest) and inter-rater agreement for each of the six sections and for the total score were satisfactory. Validity was acceptable both for content and construct, according to their correlation with the gold standard. CONCLUSIONS: TOPYPS displayed good psychometrical properties. It is a suitable tool to detect and measure functional and organic diseases in general population.

Nomogram to predict live birth rate after fertility-sparing surgery for borderline ovarian tumours.

STUDY QUESTION: Can a nomogram be used to predict the individual probability of live birth (LB) in women with borderline ovarian tumours (BOTs) receiving primary fertility-sparing surgery? SUMMARY ANSWER: A nomogram built according to the woman's age, histological subtype (serous versus mucinous), type of ovarian surgical treatment and FIGO stage can accurately predict the probability of LB in women with BOT. WHAT IS KNOWN ALREADY: Current prediction models determine the probability of pregnancy after medically assisted reproduction (MAR) and form the basis of patient counselling to guide the decision as to whether to consider in vitro fertilization but do not take into account prediction of the LB rate. STUDY DESIGN, SIZE, DURATION: This was a retrospective multi-centre study including 187 women with fertility-sparing surgery for BOT diagnosed between January 1980 and December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: A multivariate logistic regression analysis of selected factors and a nomogram to predict the subsequent LB rate was constructed. A bootstrapping technique was used for internal validation. MAIN RESULTS AND THE ROLE OF CHANCE: Fifty-one women had LB (27.3%). Taking into account multiple pregnancies, the overall LB rate was 40.1% (75/187). Federation International of Gynaecology and Obstetric (FIGO) stage, age at diagnosis, histological subtype and surgery type were included in the nomogram. The predictive model had an AUC of 0.742 (95% CI, 0.644-0.825) and 0.72 (95% CI, 0.621-0.805) before and after the 200 repetitions of bootstrap sample corrections, respectively, and showed a good calibration. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study cannot exclude all biases. Our nomogram is based on simple criteria, but did not take into account the evaluation of ovarian reserve. It demonstrates a fair relevance, but requires external validation before routine use. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians are increasingly interested in such tools to support the patient in making an informed decision about treatment options. This nomogram contributes to the decision-making by defining simple risk factors of poor LB probability that can help identify good candidates for MAR. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Analysis of the porcine APOA2 gene expression in liver, polymorphism identification and association with fatty acid composition traits.

APOA2 is a protein implicated in triglyceride, fatty acid and glucose metabolism. In pigs, the APOA2 gene is located on pig chromosome 4 (SSC4) in a QTL region affecting fatty acid composition, fatness and growth traits. In this study, we evaluated APOA2 as a candidate gene for meat quality traits in an Iberian × Landrace backcross population. The APOA2:c.131T>A polymorphism, located in exon 3 of APOA2 and determining a missense mutation, was associated with the percentage of hexadecenoic acid [C16:1(n-9)], linoleic acid [C18:2(n-6)], α-linolenic acid [C18:3(n-3)], dihomo-gamma-linolenic acid [C20:3(n-6)] and polyunsaturated fatty acids (PUFAs) in backfat. Furthermore, this SNP was associated with the global mRNA expression levels of APOA2 in liver and was used as a marker to determine allelic expression imbalance by pyrosequencing. We determined an overexpression of the T allele in heterozygous samples with a mean ratio of 2.8 (T/A), observing a high variability in the allelic expression among individuals. This result suggests that complex regulatory mechanisms, beyond a single polymorphism (e.g. epigenetic effects or multiple cis-acting polymorphisms), may be regulating APOA2 gene expression.