Nuclear factor-κB activation by transforming growth factor-ß1 drives tumour microenvironment-mediated drug resistance in neuroblastoma.

BACKGROUND: Intrinsic and extrinsic factors in the tumour microenvironment (TME) contribute to therapeutic resistance. Here we demonstrate that transforming growth factor (TGF)-ß1 produced in the TME increased drug resistance of neuroblastoma (NB) cells. METHODS: Human NB cell lines were tested in vitro for their sensitivity to Doxorubicin (DOX) and Etoposide (ETOP) in the presence of tumour-associated macrophages (TAM) and mesenchymal stromal cells/cancer-associated fibroblasts (MSC/CAF). These experiments were validated in xenotransplanted and primary tumour samples. RESULTS: Drug resistance was associated with an increased expression of efflux transporter and anti-apoptotic proteins. Upregulation was dependent on activation of nuclear factor (NF)-κB by TGF-ß-activated kinase (TAK1) and SMAD2. Resistance was reversed upon pharmacologic and genetic inhibitions of NF-κB, and TAK1/SMAD2. Interleukin-6, leukaemia inhibitory factor and oncostatin M were upregulated by this TGF-ß/TAK1/NF-κB/SMAD2 signalling pathway contributing to drug resistance via an autocrine loop activating STAT3. An analysis of xenotransplanted NB tumours revealed an increased presence of phospho (p)-NF-κB in tumours co-injected with MSC/CAF and TAM, and these tumours failed to respond to Etoposide but responded if treated with a TGF-ßR1/ALK5 inhibitor. Nuclear p-NF-κB was increased in patient-derived tumours rich in TME cells. CONCLUSIONS: The data provides a novel insight into a targetable mechanism of environment-mediated drug resistance.

Is unicentric familial papillary thyroid microcarcinoma different from multicentric?

BACKGROUND: Familial papillary thyroid microcarcinoma (FPTMC) appears to be more aggressive than sporadic papillary thyroid microcarcinoma (SPTMC). However, there are authors who indicate that unicentric FPTMC has a similar prognosis to SPTMC. The objective is to analyze whether unicentric FPTMC has a better prognosis than multicentric FPTMC. DESIGN AND METHODS: Type of study: National multicenter longitudinal analytical observational study. STUDY POPULATION: Patients with FPTMC. STUDY GROUPS: Two groups were compared: Group A (unicentric FPTMC) vs. Group B (multicentric FPTMC). STUDY VARIABLES: It is analyzed whether between the groups there are: a) differentiating characteristics; and b) prognostic differences. STATISTICAL ANALYSIS: Cox regression analysis and survival analysis. RESULTS: Ninety-four patients were included, 44% (n = 41) with unicentric FPTMC and 56% (n = 53) with multicentric FPTMC. No differences were observed between the groups according to socio-familial, clinical or histological variables. In the group B a more aggressive treatment was performed, with higher frequency of total thyroidectomy (99 vs. 78%; p = 0.003), lymph node dissection (41 vs. 15%; p = 0.005) and therapy with radioactive iodine (96 vs. 73%; p = 0.002). Tumor stage was similar in both groups (p = 0.237), with a higher number of T3 cases in the group B (24 vs. 5%; p = 0.009). After a mean follow-up of 90 ± 68.95 months, the oncological results were similar, with a similar disease persistence rate (9 vs. 5%; p = 0.337), disease recurrence rate (21 vs. 8%; p = 0.159) and disease-free survival (p = 0.075). CONCLUSIONS: Unicentric FPTMC should not be considered as a SPTMC due to its prognosis is similar to multicentric FPTMC.

Fibroblasts and macrophages cooperate to create a pro-tumorigenic and immune resistant environment via activation of TGF-ß/IL-6 pathway in neuroblastoma.

Tumor-associated macrophages (TAM) and cancer-associated fibroblasts (CAF) and their precursor mesenchymal stromal cells (MSC) are often detected together in tumors, but how they cooperate is not well understood. Here, we show that TAM and CAF are the most abundant nonmalignant cells and are present together in untreated human neuroblastoma (NB) tumors that are also poorly infiltrated with T and natural killer (NK) cells. We then show that MSC and CAF-MSC harvested from NB tumors protected human monocytes (MN) from spontaneous apoptosis in an interleukin (IL)-6 dependent mechanism. The interactions of MN and MSC with NB cells resulted in a significant induction or increase in the expression of several pro-tumorigenic cytokines/chemokines (TGF-ß1, MCP-1, IL-6, IL-8, and IL-4) but not of anti-tumorigenic cytokines (TNF-α, IL-12) by MN or MSC, while also inducing cytokine expression in quiescent NB cells. We then identified a TGF-ß1/IL-6 pathway where TGF-ß1 stimulated the expression of IL-6 in NB cells and MSC, promoting TAM survival. Evidence for the contribution of TAM and MSC to the activation of this pathway was then provided in xenotransplanted NB tumors and patients with primary tumors by demonstrating a direct correlation between the presence of CAF and p-SMAD2 and p-STAT3. The data highlight a new mechanism of interaction between TAM and CAF supporting their pro-tumorigenic function in cancer.

Biological behavior of familial papillary thyroid microcarcinoma: Spanish multicenter study.

PURPOSE: Familial papillary thyroid microcarcinoma (FPTMC) can present a more aggressive behavior than the sporadic microcarcinoma. However, few studies have analyzed this situation. The objective is to analyze the recurrence rate of FPTMC and the prognostic factors which determine that recurrence in Spain. METHODS: Spanish multicenter longitudinal analytical observational study was conducted. Patients with FPTMC received treatment with curative intent and presented cure criteria 6 months after treatment. Recurrence rate and disease-free survival (DFS) were analyzed. Two groups were analyzed: group A (no tumor recurrence) vs. group B (tumor recurrence). RESULTS: Ninety-four patients were analyzed. During a mean follow-up of 73.3 ± 59.3 months, 13 recurrences of FPTMC (13.83%) were detected and mean DFS was 207.9 ± 11.5 months. There were multifocality in 56%, bilateral thyroid involvement in 30%, and vascular invasion in 7.5%; that is to say, they are tumors with histological factors of poor prognosis in a high percentage of cases. The main risk factors for recurrence obtained in the multivariate analysis were the tumor size (OR: 2.574, 95% CI 1.210-5.473; p = 0.014) and the assessment of the risk of recurrence of the American Thyroid Association (ATA), both intermediate risk versus low risk (OR: 125, 95% CI 10.638-1000; p < 0.001) and high risk versus low risk (OR: 45.454, 95% CI 5.405-333.333; p < 0.001). CONCLUSION: FPTMC has a recurrence rate higher than sporadic cases. Poor prognosis is mainly associated with the tumor size and the risk of recurrence of the ATA.

An immature, dedifferentiated, and lineage-deconstrained cone precursor origin of N-Myc-initiated retinoblastoma.

Most retinoblastomas develop from maturing cone precursors in response to biallelic RB1 loss and are dependent on cone maturation-related signaling. Additionally, ∼2% lack RB1 mutations but have MYCN amplification (MYCNA), N-Myc protein overexpression, and more rapid and invasive growth, yet the MYCNA retinoblastoma cell of origin and basis for its responses to deregulated N-Myc are unknown. Here, using explanted cultured retinae, we show that ectopic N-Myc induces cell cycle entry in cells expressing markers of several retinal types yet induces continuous proliferation and tumorigenesis only in cone precursors. Unlike the response to RB1 loss, both immature cone arrestin-negative (ARR3-) and maturing ARR3+ cone precursors proliferate, and maturing cone precursors rapidly dedifferentiate, losing ARR3 as well as L/M-opsin expression. N-Myc-overexpressing retinal cells also lose cell lineage constraints, occasionally coexpressing the cone-specific RXRγ with the rod-specific NRL or amacrine-specific AP2α and widely coexpressing RXRγ with the progenitor and Müller cell-specific SOX9 and retinal ganglion cell-specific BRN3 and GAP43. Mechanistically, N-Myc induced Cyclin D2 and CDK4 overexpression, pRB phosphorylation, and SOX9-dependent proliferation without a retinoma-like stage that characterizes pRB-deficient retinoblastoma, despite continuous p16INK4A expression. Orthotopic xenografts of N-Myc-overexpressing retinal cells formed tumors with retinal cell marker expression similar to those in MYCN-transduced retinae and MYCNA retinoblastomas in patients. These findings demonstrate the MYCNA retinoblastoma origin from immature and lineage-deconstrained cone precursors, reveal their opportunistic use of an undifferentiated retinal progenitor cell feature, and illustrate that different cancer-initiating mutations cooperate with distinct developmental stage-specific cell signaling circuitries to drive retinoblastoma tumorigenesis.

Hair cortisol in polycystic ovary syndrome.

The aim of the study was to evaluate adrenal axis hyperactivation measuring hair cortisol levels, and its influence on the relationship among metabolic parameters, inflammation markers and androgens in adult women with PCOS. 44 women (18-34 years) with PCOS diagnosis and a control group of 49 healthy women (19-35 years) were included. In both gropus body mass index (BMI) was calculated and waist circumference (WC) was measured. Hair cortisol, total serum testosterone (TT), serum cortisol, 25 OH vitamin D (25OHD), insulin, high sensitivity C-reactive protein (hsCRP), triglycerides (TG), HDL cholesterol (HDL), glucose and leptin were measured. Bioavailable testosterone (bioT) was calculated. Hair cortisol concentration was higher and significantly different in PCOS patients compared to the control group (130 vs 63 pg/mg of hair, p < 0.001). Subsequently, patients with PCOS were divided into two groups according to hair cortisol levels: group 1 with normal hair cortisol concentration and group 2 with levels above the upper limit of the reference values (128 pg/mg of hair). In group 2, TT significantly correlated with 25OHD, hsCRP, TG/HDL index, BMI, WC, insulin and HOMA (p < 0.05); bioT correlated with hsCRP and leptin (p < 0.05). Finally, 25OHD was inversely correlated with leptin and with TG/HDL index (p < 0.05). High hair cortisol concentration in patients with PCOS confirmed hyperactivation of the HPA axis. The associations observed were only found in patients with PCOS with high hair cortisol levels (> 128 pg/mg of hair), showing a possible effect of HPA axis in these associations.

Simultaneous electrochemical immunosensing of relevant cytokines to diagnose and track cancer and autoimmune diseases.

This work reports the first dual magnetic beads (MBs) assisted immunoplatform for the simultaneous determination of BAFF (B cell activation factor) and APRIL (a proliferation-induced ligand), two cytokines related to immunity and tumour invasion, growth and metastasis. The electrochemical immunoplatform involves sandwich-type immunoassays implemented on magnetic microparticles functionalized with neutravidin (NA-MBs) or carboxylic groups (HOOC-MBs), and amperometric detection (Eapp =  - 0.20 V vs. Ag pseudo-reference electrode) at screen-printed dual carbon electrodes (SPdCE) using the H2O2/hydroquinone (HQ) system. The developed immunosensors provide improved sensitivity, with LOD values of 0.33 and 16.4 pg mL-1 for BAFF and APRIL, respectively, and much shorter assay time that those claimed for ELISA kits and allow their simultaneous determination. The dual immunosensor permits discrimination between healthy individuals and patients diagnosed with Systemic Lupus Erythematosus (SLE) or colorectal cancer (CRC) through the determination of both cytokines in 100-times diluted human sera with results in agreement with those provided by the individual ELISA methodologies.

Recommendations on the use of intravesical hyaluronic acid instillations in bladder pain syndrome.

INTRODUCTION: Bladder pain syndrome (BPS) is a complex syndrome, without a clearly defined etiology that encompasses different entities, such as interstitial cystitis. This leads to difficulties in establishing a precise definition, obtaining accurate prevalence data, and defining diagnostic criteria and standardized assessment methods. Moreover, there is no consensus regarding the treatment of BPS. Intravesical instillations with hyaluronic acid (HA) are an option, although no specific recommendations have been made yet. OBJECTIVE: To synthesize the scientific evidence on the therapeutic options available for BPS and to establish a work plan and recommendations for the use of intravesical instillations with HA. The Spanish Association of Urology, through the Functional, Female, and Urodynamic Urology Group, created a commission of experts. This commission was in charge of reviewing literature (evidence), agreeing on the work plan, and proposing recommendations. RESULTS: There is great variability in literature on the treatment of BPS, without a standard regimen of intravesical instillation with HA (frequency and duration of initial and maintenance treatment). CONCLUSIONS: Intravesical HA instillations (usual dose of 40 mg) are effective and safe. They can be combined with other options, with efficacy still to be determined in some cases. Treatment is divided into several initial weekly sessions, followed by maintenance treatment, usually monthly (unestablished duration of cycles). Recommendations on the management of BPS were agreed, with diagnostic criteria and guidelines for treatment with intravesical HA (initiation, reassessment, and follow-up).

Plitidepsin as a successful rescue treatment for prolonged viral SARS-CoV-2 replication in a patient with previous anti-CD20 monoclonal antibody-mediated B cell depletion and chronic lymphocytic leukemia.

BACKGROUND: There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies. CASE PRESENTATION: Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+ B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved. CONCLUSIONS: Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.

Mastitis granulomatosa: caso clínico y revisión de la literatura / Granulomatous mastitis: case report and literature review

OBJETIVO: La mastitis granulomatosa es una patología mamaria benigna y crónica de baja incidencia, cuyo diagnóstico es complejo y su tratamiento no está del todo establecido. Se presenta un caso clínico con el objetivo de hacer una revisión de la bibliografía sobre esta patología, su diagnóstico y tratamiento. MATERIAL Y MÉTODOS: Se presenta el caso de una paciente de 30 años con una mastitis refractaria a tratamiento antibiótico a la que finalmente se diagnosticó una mastitis granulomatosa idiopática gracias a la biopsia excisional. El tratamiento con corticoides a dosis altas tuvo buenos resultados en este caso. Se realizó una búsqueda bibliográfica en las bases de datos Medline vía PubMed, EMBASE y SciELO y también en libros de texto en papel. RESULTADOS: Se hallaron 598 referencias, la mayoría de ellas revisiones sistemáticas y casos clínicos. CONCLUSIONES: La mastitis granulomatosa es una patología poco frecuente cuyo diagnóstico se logra mediante estudio histológico de la misma. No hay consenso sobre cuál es el tratamiento óptimo, pero la tendencia actual es el tratamiento conservador con corticoides a altas dosis. Cada vez es más frecuente el uso de metotrexato cuando no hay buena respuesta con el tratamiento con corticoides.

OBJECTIVE: Granulomatous mastitis is a benign and chronic breast pathology with a low incidence, whose diagnosis is complex and its treatment is not fully established. A case report is presented with the aim of reviewing the literature on this pathology, its diagnosis and its treatment. MATERIAL AND METHODS: The patient is a 30-year-old woman with a mastitis refractory to antibiotic treatment. Finally, idiopathic granulomatous mastitis was diagnosed through excisional biopsy. Treatment with high-dose corticosteroids had good results in this patient. A literature search was performed in the Medline databases via PubMed, EMBASE and SciELO and also in paper textbooks. RESULTS: 598 references were found, most of them systematic reviews and case reports. CONCLUSIONS: Granulomatous mastitis is an uncommon pathology whose definitive diagnosis is achieved by histological study. Treatment is not fully established, but conservative treatment with high-dose corticosteroids is the current trend. The use of methotrexate has risen when there is no good evolution with corticosteroid treatment.

Combined immune checkpoint blockade increases CD8+CD28+PD-1+ effector T cells and provides a therapeutic strategy for patients with neuroblastoma.

Immune checkpoint therapy has resulted in minimal clinical response in many pediatric cancers. We sought to understand the influence of immune checkpoint inhibition using anti-PD-1 and anti-CTLA-4 antibodies individually, in combination, and after chemotherapy on immune responses in minimal and established murine neuroblastoma models. We also sought to understand the role of the tumor microenvironment (TME) and PD-L1 expression and their alteration post-chemotherapy in our models and human tissues. PD-L1 expression was enriched in human tumor-associated macrophages and up-regulated after chemotherapy. In a murine minimal disease model, single and dual immune checkpoint blockade promoted tumor rejection, improved survival, and established immune memory with long-term anti-tumor immunity against re-challenge. In an established tumor model, only dual immune checkpoint blockade showed efficacy. Interestingly, dual immune checkpoint therapy distinctly influenced adaptive and innate immune responses, with significant increase in CD8+CD28+PD-1+ T cells and inflammatory macrophages (CD11bhiCD11c-F4/80+Ly6Chi) in tumor-draining lymph nodes. Adding chemotherapy before immunotherapy provided significant survival benefit for mice with established tumors receiving anti-PD-1 or dual immune checkpoint blockade. Our findings demonstrate anti-PD-1 and anti-CTLA-4 therapy induces a novel subset of effector T cells, and support administration of induction chemotherapy immediately prior to immune checkpoint blockade in children with high-risk neuroblastoma.

Impact of cadaveric practices on arthroscopic knee training for Orthopaedic Surgery and Traumatology residents. / Impacto de las prácticas cadavéricas en la formación artroscópica de rodilla de los residentes de Cirugía Ortopédica y Traumatología.

BACKGROUND AND OBJECTIVES: There currently is a considerable variability in the content of training programs and courses for orthopaedic surgeons in training. Besides this, there is still no consensus regarding which is the most effective methodology for improving learning of the technique or for its qualitative evaluation. A study was carried out to assess the influence of carrying out a cadaveric practical course on the acquisition of arthroscopic technical skills in fifth-year residents. MATERIAL AND METHODS: A knee arthroscopy cadaveric course was performed in which 48 students participated. Different technical aspects during a knee arthroscopy, as well as the residents skill and the execution time were evaluated before and after the course using a specific questionnaire. RESULTS: There was a significant statistic improvement between the initial and final evaluation, increasing from 11,7 till 17,1 (maximum 20) points. Also, a significant improvement in all the parameters analysed was observed; the identification of anatomic structures (p = 0.001), the palpation of specific structures (p = 0.032), and the time necessary for the arthroscopic knee check (p = 0.015). CONCLUSIONS: A knee arthroscopy cadaveric course improves significantly the technical skills of surgeons in training.

Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

BACKGROUND: Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. METHODS: Observational retrospective multicenter study. INCLUSION CRITERIA: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. RESULTS: Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. CONCLUSION: It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here.

Obstrucción intestinal por brida postquirúrgica en gestante: a propósito de un caso / Intestinal obstruction due to postsurgical bridle in pregnant woman: on the subject of a case

RESUMEN El dolor abdominal en gestantes supone un diagnóstico complejo por el múltiple diagnóstico diferencial que existe. Es necesaria la realización de un diagnóstico precoz para reducir el número de complicaciones. Para ello, nos apoyamos no sólo en criterios clínicos si no en pruebas de imagen como la resonanacia magnética nuclear. Nuestro objetivo es la realización de una revisión bibliográfica sobre el dolor abdominal en gestantes, centrándonos en la obstrucción intestinal, a propósito de un caso de una gestante con dolor abdominal agudo a la que se le diagnosticó de isquemia intestinal secundaria a obstrucción intestinal por brida postquirúrgica. La obstrucción intestinal es una causa infrecuente y potencialmente grave de dolor abdominal agudo en gestantes, que cursa con clínica insidiosa y que precisa cirugía como tratamiento.

ABSTRACT Abdominal pain in the pregnant woman is complex to diagnose because of the multiple differential diagnosis that exists. It is necessary to perform an early diagnosis to reduce the number of complications. For this, we rely not only on clinical criteria but on imaging tests such as nuclear magnetic resonance. Our objective is to review the literature on abdominal pain in pregnant women, focusing on intestinal obstruction, and with regard to the case of a pregnant woman with acute abdominal pain who was diagnosed of intestinal ischemia due to intestinal obstruction by post-surgical bridle. Intestinal obstruction is an infrequent and potentially serious cause of acute abdominal pain in the pregnant woman, which is insidious and requires surgery as a treatment.

Anti-CD105 Antibody Eliminates Tumor Microenvironment Cells and Enhances Anti-GD2 Antibody Immunotherapy of Neuroblastoma with Activated Natural Killer Cells.

PURPOSE: We determined whether elimination of CD105+ cells in the tumor microenvironment (TME) with anti-CD105 antibodies enhanced anti-disialoganglioside (GD2) antibody dinutuximab therapy of neuroblastoma when combined with activated natural killer (aNK) cells. EXPERIMENTAL DESIGN: The effect of MSCs and monocytes on antibody-dependent cellular cytotoxicity (ADCC) mediated by dinutuximab with aNK cells against neuroblastoma cells was determined in vitro. ADCC with anti-CD105 mAb TRC105 and aNK cells against MSCs, monocytes, and endothelial cells, which express CD105, was evaluated. Anti-neuroblastoma activity in immunodeficient NSG mice of dinutuximab with aNK cells without or with anti-CD105 mAbs was determined using neuroblastoma cell lines and a patient-derived xenograft. RESULTS: ADCC mediated by dinutuximab with aNK cells against neuroblastoma cells in vitro was suppressed by addition of MSCs and monocytes, and dinutuximab with aNK cells was less effective against neuroblastomas formed with coinjected MSCs and monocytes in NSG mice than against those formed by tumor cells alone. Anti-CD105 antibody TRC105 with aNK cells mediated ADCC against MSCs, monocytes, and endothelial cells. Neuroblastomas formed in NSG mice by two neuroblastoma cell lines or a patient-derived xenograft coinjected with MSCs and monocytes were most effectively treated with dinutuximab and aNK cells when anti-human (TRC105) and anti-mouse (M1043) CD105 antibodies were added, which depleted human MSCs and murine endothelial cells and macrophages from the TME. CONCLUSIONS: Immunotherapy of neuroblastoma with anti-GD2 antibody dinutuximab and aNK cells is suppressed by CD105+ cells in the TME, but suppression is overcome by adding anti-CD105 antibodies to eliminate CD105+ cells.

Association of Ureaplasma diversum with reproductive disease in cattle.

Aims: To examine the association between the detection of Ureaplasma diversum in vaginal swabs from dairy cows in north western Spain with the diagnosis of granular vulvovaginitis (GVV) and reproductive performance, and the association with subclinical endometritis (SE) in slaughterhouse material. The presence of this microorganism in cases of abortion was also investigated. Methods: From 106 dairy farms in the province of Lugo, 40 herds were randomly selected. Vaginal swabs were obtained from 10 randomly selected cows per farm, then pooled for analysis to detect the presence of U. diversum by quantitative real-time PCR (qPCR). In five of these herds samples from the 10 animals were individually tested for U. diversum, and the presence of GVV lesions and their reproductive efficiency (number of inseminations to achieve pregnancy over two subsequent pregnancies) were determined. Vaginal swabs from uteri of cattle obtained at a slaughterhouse (n = 100) were tested for U. diversum and the presence of SE, defined as >5% polymorphonuclear cells in cytobrush smears, was determined. Sixteen farms with abortion problems submitted samples for culture and PCR testing including for U. diversum. Results: Of the 40 herds, 39 (98%) tested positive for U. diversum. On the five farms, 25/50 (50%) cows tested positive for U. diversum, and more cows with GGV-lesions (16/25; 64%) tested positive than cows without lesions (9/25; 36%) (p = 0.047). There were more cows with poor reproductive efficacy that tested positive (8/11; 57%) than tested negative (3/17; 18%) for U. diversum (p = 0.029). Of the 100 uteri, five tested positive for U. diversum and there were more uteri with SE that tested positive (3/19; 16%) than uteri without SE (2/81; 2%) (p = 0.036). U. diversum was also diagnosed in 4/16 farms with abortion problems and liver appeared to be the best tissue for detecting U. diversum DNA in the fetuses analysed. Conclusions and Clinical Relevance: Infection with U. diversum was present in most of herds investigated and it was statistically associated with GVV, SE and poor reproductive performance. It was also detected in abortions and the liver may also be an additional tissue to be considered in the diagnosis of U. diversum abortion by PCR. The possible association with different diseases in the same area suggests that different presentations should be considered when studying the implications of U. diversum on the reproductive diseases of cattle.

Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.

Long-term results of genital prolapse surgery with polypropylene mesh. / Resultados a largo plazo de la cirugía de prolapsos genitales con mallas de polipropileno.

INTRODUCTION AND OBJECTIVE: The risk of intervention due to urogenital prolapse in a woman's life is 11.1%. Recurrences after classic surgery reach up to 38%. With the aim of improving these results, transvaginal mesh kits are used. The purpose of the study is to describe the results of efficacy and long-term safety of vaginal prolapse surgery with polypropylene mesh, assess subjective symptoms before and after surgery and the level of satisfaction. PATIENTS AND METHODS: A descriptive, retrospective study of 58 women with symptomatic genital prolapses operated with polypropylene mesh between September / 2011-November / 2016. Mean age: 66.53 years, 98.27% menopausal women, 77.59% overweight/obesity, 29.31% with previous gynaecological surgery and 55.17% with combined prolapse. 46 Elevate anterior and 12 posterior were inserted. The mean follow-up period was 34.02 months. The PFDI questionnaire was used pre and post-surgery, as well as the satisfaction questionnaire. RESULTS: Healing rate of 91.38%. Recurrences were associated with a higher BMI and with background of recurrence of previous surgery. Mean length of stay: 2.5 days. 70.69% did not need analgesia at discharge. Clavien-Dindo complications: 1 type I (urinary retention), 5 type II (urinary tract infection) and 1 type IIIa (erosion). De novo stress urinary incontinence occurred in 3.44%, while de novo dyspareunia 14.28%. 89.36% patients improved subjective symptoms, and 95.92% were satisfied. CONCLUSION: This surgery achieves high healing rates, with few complications, improvement of subjective symptoms and high level of satisfaction of the patients.