Safety of treatment with ulipristal acetate on the mammary gland: A pilot prospective study / Seguridad del tratamiento con acetato de ulipristal en la glándula mamaria: un estudio piloto prospectivo

IntroductionHeavy menstrual bleeding is the major complaint in women with symptomatic fibroids. Ulipristal acetate (UPA) is a “selective progesterone receptor modulator” in which mixed agonist and antagonist activity appears to offer a novel approach to medical management of symptomatic uterine fibroids. There are currently no studies that have assessed its effect on the mammary gland in humans.MethodsProspective observational study conducted in a tertiary hospital, in which 14 consecutive patients diagnosed with uterine fibroids by transvaginal ultrasound were included. The patients received two cycles of UPA 5mg/day for 3 months each, with a rest period of two months between both cycles. To assess the safety on the mammary gland, 3 mammary ultrasounds were performed at three different points: prior to the first cycle of UPA, between the two cycles and at the end of the second cycle.ResultsOf the 14 recruited patients, 9 completed the study period. Breast ultrasound reports were normal in all patients. In 4 patients (44.4%), the 3 breast ultrasounds were classified as BI-RADS 2. In 2 patients (22.2%) the 3 breast ultrasounds were classified as BI_RADS1; and in 3 patients (33.3%), the first breast ultrasound was classified as BI-RADS 3 and the last two as BI-RADS 2.ConclusionIn conclusion, our study showed that 2 cycles of treatment with UPA in patients with symptomatic uterine fibroids is safe for normal breast tissue with an acceptable adverse effects profile. Nonetheless, further research is required to confirm our findings.

IntroducciónEl sangrado menstrual abundante es el principal síntoma en mujeres con miomas uterinos. Acetato de ulipristal (AUP) es un «modulador selectivo del receptor de progesterona» que parece ofrecer una nueva opción al manejo médico de los miomas debido a su acción mixta agonista y antagonista. Actualmente no hay estudios que evalúen su efecto en la glándula mamaria en humanos.MétodosEs un estudio prospectivo observacional realizado en un hospital terciario, en el cual se incluyeron 14 mujeres con diagnóstico de miomas uterinos mediante ecografía transvaginal. Las pacientes recibieron 2 ciclos de AUP 5mg/día durante 3 meses cada ciclo, con un período de descanso de 2 meses entre ambos ciclos. Para evaluar el impacto en la glándula mamaria se realizaron 3 ecografías mamarias en 3 momentos diferentes: previo al inicio del primer ciclo, entre los 2 ciclos y al terminar el segundo ciclo.ResultadosDe las 14 pacientes reclutadas, 9 completaron el período de estudio. Las ecografías mamarias en todas las pacientes fueron normales. En 4 pacientes (44,4%), las 3 ecografías mamarias fueron catalogadas como BI-RADS® 2. En 2 pacientes (22,2%) las 3 ecografías fueron catalogadas como BI-RADS® 1, y en 3 pacientes (33,3%), la primera ecografía mamaria fue catalogada como BI-RADS® 3 y las 2 últimas BI-RADS® 2.ConclusiónEn conclusión, nuestro estudio muestra que 2 ciclos de tratamiento con AUP en pacientes con miomas uterinos sintomáticos es seguro para el tejido mamario sano con efectos adversos aceptables. Sin embargo, hacen falta más estudios para confirmar nuestros resultados.

Adenomiosis. Una gran desconocida: ¿Qué debemos saber? / Adenomyosis. A great unknown: What should we know?

La adenomiosis es una enfermedad ginecológica benigna que afecta entre el 20-35% de las mujeres en edad fértil. Sus síntomas incluyen sangrado uterino anormal, dolor pélvico e infertilidad, los cuales generan una disminución en la calidad de vida de las pacientes. El objetivo de esta revisión es actualizar «el conocimiento» que existe sobre la enfermedad, hasta ahora poco conocida, haciendo énfasis en la etiopatogenia, el diagnóstico y el manejo. Como conclusión, la adenomiosis está recibiendo más atención en las últimas décadas. Actualmente, gracias a la introducción de técnicas de imagen precisas, se ha convertido en una entidad clínica con la posibilidad de un diagnóstico prequirúrgico. El impacto de la adenomiosis en el dolor, sangrado e infertilidad, y su consecuente disminución en la calidad de vida de estas pacientes hace necesario el desarrollo de pautas de diagnóstico temprano y manejo multidisciplinar.(AU)

Adenomyosis is a benign gynaecological disease that affects between 20-35% of women of reproductive age. Its symptoms include abnormal uterine bleeding, pelvic pain, and infertility, and can lead to a decrease in the quality of life of these patients. The objective of this review is to update «the knowledge» that exists about the disease, until now little known, with emphasis on its etiopathogenesis, diagnosis, and management. In conclusion, adenomyosis is receiving more attention in recent decades. Nowadays, thanks to the introduction of precise imaging techniques, it has become a clinical entity with the possibility of a pre-surgical diagnosis. The impact of adenomyosis on pain, bleeding and infertility, and its consequent decrease in quality of life of these patients makes it necessary to develop guidelines for early diagnosis and multidisciplinary management.(AU)

Mixtures of chelating agents to enhance photo-Fenton process at natural pH: Influence of wastewater matrix on micropollutant removal and bacterial inactivation.

Three organic fertilizers (EDTA (Ethylenedinitrilotetraacetic acid), EDDS (Ethylenediamine-N, N'-disuccinic acid) and DTPA (Diethylene triamine pentaacetic acid)) were tested as Fe-complexes in photo-Fenton process at natural pH for micropollutants (MPs) abatement and simultaneous E.coli inactivation. Less stable Fe-complexes show high iron precipitation, stopping MPs degradation. On the contrary, stable Fe-complexes imply low kinetic rates for MPs removal. To solve these inconveniences, three mixtures of organic fertilizers were also tested, trying to improve the kinetic rates of micropollutants oxidation and overcome iron precipitation. Three different pollutants (propranolol (PROP), acetamiprid (ACMP) and sulfamethoxazole (SMX)) were used as the target compounds. As the iron release is, in part, linked to the hardness of water, two water matrices from two different secondary wastewaters (Membrane Bioreactor (MBR) and Conventional Activated Sludge (CAS)) were tested. The best performance in micropollutant degradation and E.coli inactivation was achieved with the combination of EDDS + EDTA, accomplishing a good equilibrium between iron precipitation and rate of MPs removal. For instance, total removal of propranolol was achieved at 45 min in MBR, while it was only 85.7% in CAS, being an improvement of the process comparing with that obtained using single organic fertilizers. At the end of the treatment, 2.1 log-inactivation for E.coli was reached in CAS. The differences observed between both wastewaters were related to CAS' higher DOC, turbidity, and hardness. Finally, from the physicochemical characterization conducted, including Biochemical Oxygen Demand at 5 days and phytotoxicity, it is possible to highlight the suitability of these treated effluents for its reuse in irrigation, as long as in CAS matrix the final values of E. coli are within the legal limit.

Evaluation of the intraoperative human papillomavirus test as a marker of early cure at 12 months after electrosurgical excision procedure in women with cervical high-grade squamous intraepithelial lesion: a prospective cohort study.

OBJECTIVE: To evaluate if the intraoperative human papillomavirus (IOP-HPV) test has the same prognostic value as the HPV test performed at 6 months after treatment of high-grade squamous intraepithelial lesion (HSIL) to predict treatment failure. DESIGN: Prospective cohort study. SETTING: Barcelona, Spain. POPULATION: A cohort of 216 women diagnosed with HSIL and treated with loop electrosurgical excision procedure (LEEP). METHODS: After LEEP, an HPV test was performed using the Hybrid Capture 2 system. If this was positive, genotyping was performed with the CLART HPV2 technique. The IOP-HPV test was compared with HPV test at 6 months and with surgical margins. MAIN OUTCOME MEASURE: Treatment failure. RESULTS: Recurrence rate of HSIL was 6%. There was a strong association between a positive IOP-HPV test, a positive 6-month HPV test, positive HPV 16 genotype, positive surgical margins and HSIL recurrence. Sensitivity, specificity, and positive and negative predictive values of the IOP-HPV test were 85.7, 80.8,24.0 and 98.8% and of the HPV test at 6 months were 76.9, 75.8, 17.2 and 98.0%. CONCLUSION: Intraoperative HPV test accurately predicts treatment failure in women with cervical intraepithelial neoplasia grade 2/3. This new approach may allow early identification of patients with recurrent disease, which will not delay the treatment. Genotyping could be useful in detecting high-risk patients. TWEETABLE ABSTRACT: IOP-HPV test accurately predicts treatment failure in women with CIN 2/3.

Trombosis del seno cavernoso en gestantes: a propósito de un caso / Thrombosis of the cavernous sinus in pregnant women: case report

La trombosis de senos venosos cerebrales es una entidad poco frecuente. Puede presentarse con clínica de cefalea, nauseas, vómitos, fiebre, déficits neurológicos focales y incluso el coma. La etiología es multifactorial siendo uno de los factores causantes los estados de hipercoagulabilidad. El embarazo y el puerperio, fisiológicamente, son estados procoagulantes. Presentamos el caso de una gestante de 32 años de 9 semanas que fue ingresada por un cuadro de nausea acompañado de una intensa cefalea, por lo que fue remitida al Servicio de Neurología. La resonancia magnética con angiografía reveló una trombosis de senos venosos cerebrales. Fue tratada con infusión bomba de heparina no fraccionada con mejoría en los síntomas. Tras el parto, prosiguió el tratamiento anticoagulante con heparina de bajo peso molecular a dosis profilácticas durante 6 semanas. En conclusión, resulta muy importante que se produzca un correcto y precoz diagnóstico para el pronóstico de esta enfermedad por lo que debe considerarse esta entidad dentro del diagnóstico diferencial de cefalea intensa en pacientes gestantes

Cerebral venous sinus thrombosis is a rare entity. It can present with symptoms of headache, nausea, vomiting, fever, focal neurological deficits and even coma. The etiology is multifactorial, being one of the factors causing hypercoagulability states. Pregnancy and the puerperium, physiologically, are procoagulant states. We present the case of a pregnant woman of 32 years of 9 weeks who was admitted for a nausea episode accompanied by an intense headache, for which she was referred to the Neurology Service. Magnetic resonance imaging with angiography revealed a cerebral venous sinus thrombosis. It was treated with infusion of unfractionated heparin pump with improvement in symptoms. After delivery, the anticoagulant treatment with low molecular weight heparin at prophylactic doses during 6 weeks. In conclusion, it is very important that there is a correct and early diagnosis for the prognosis of this disease so this entity should be considered within the differential diagnosis of severe headache in patients pregnant women

Sepsis urinaria tras tratamiento endourológico de la litiasis por ureterorrenoscopia / Urinary sepsis after endourological ureterorenoscopy for the treatment of lithiasis

Objetivo: Evaluar la incidencia, presentación clínica y factores asociados al desarrollo de sepsis urinaria tras la realización de una ureterorrenoscopia. Material y métodos: Estudio retrospectivo de los pacientes intervenidos mediante ureterorrenoscopia para el tratamiento de la litiasis entre julio de 2015 y octubre de 2017. Se identificaron aquellos pacientes que desarrollaron sepsis urinaria en los primeros 30 días tras la intervención. Se recogieron antecedentes personales, clínicos, quirúrgicos y microbiológicos. Se realizó análisis estadístico mediante chi2 (o test exacto de Fisher), t de Student (o U de Mann-Whitney) o regresión logística según procediese. Resultados: Se realizaron 246 ureterorrenoscopias, 184 (74,8%) sobre litiasis ureterales y 62 (25,2%) sobre litiasis renales, con una edad media de 52 (44,5-59,5) años. Tras el procedimiento, 18 (7,3%) pacientes desarrollaron sepsis urinaria, 10 de ellos (55,5%) en las primeras 24h. El urocultivo mostró enterobacterias (61,1%) y enterococos (38,9%). El antibiograma mostró mayor sensibilidad a nitrofurantoínas (100%) y a quinolonas (72%). El análisis estadístico mostró que el sexo femenino, el inicio clínico de la litiasis en forma de sepsis urinaria, haber recibido antibiótico o haber precisado derivación urinaria mediante doble J en el inicio, el urocultivo prequirúrgico positivo y la persistencia de restos litiásicos tras la cirugía se asociaron de forma significativa (p<0,05) al desarrollo de sepsis urinaria tras la ureterorrenoscopia. Conclusión: La sepsis urinaria es una complicación que aparece tras la realización de una ureterorrenoscopia, especialmente en pacientes de sexo femenino, con antecedente de sepsis urinaria, antibioterapia, doble J, urocultivo previo positivo o presencia de restos litiásicos tras el procedimiento

Objective: To evaluate the incidence, clinical presentation and factors associated with the development of urinary sepsis after performing ureterorenoscopy. Material and methods: Retrospective study of patients undergoing ureterorenoscopy for the treatment of lithiasis between July 2015 and October 2017. Patients who developed urinary sepsis during the 30 days following the intervention were identified. Personal, clinical, surgical and microbiological backgrounds were collected. Statistical analysis was performed with the Chi squared test (or Fisher's exact test), Student's t (or U Mann-Whitney) or logistic regression as appropriate. Results: 246 ureterorenoscopies were performed, 184 (74.8%) on ureteral stones and 62 (25.2%) on kidney stones, with a mean age of 52 (44.5-59.5) years. After procedure, 18 (7.3%) patients developed urinary sepsis, 10 of them (55.5%) occurred in the first 24h. The urine culture showed enterobacteria (61.1%) and enterococci (38.9%). The antibiogram showed greater sensitivity to nitrofurantoins (100%) and quinolones (72%). The statistical analysis showed that female sex, the clinical debut of urolithiasis as urinary sepsis, having received antibiotic or having required urinary diversion by a double J during debut, positive presurgical uroculture and the persistence of residual lithiasis after surgery were significantly associated (p < 0.05) with the development of urinary sepsis after ureterorenoscopy. Conclusion: Urinary sepsis is a complication that appears after performing ureterorenoscopy, especially in female patients with a history of urinary sepsis, antibiotic therapy, double J, previous positive urine culture or residual lithiasis after the procedure

Synergies, radiation and kinetics in photo-Fenton process with UVA-LEDs.

The photo-Fenton process, with UV-A LED (λ = 380-390, 390-400 and 380-400 nm) has demonstrated to be effective in the abatement of a target micropollutant, such as diphenhydramine hydrochloride (DPH). Different concentrations of iron (Fe2+) and H2O2 were tested and monitored, and the best results in DPH removal were obtained for the highest concentrations of both iron (II) and H2O2 (10 mg Fe2+/L - 150 mg H2O2/L). The evolution of iron and peroxide concentration was also monitored. Kinetic studies showed that dark Fenton process prevails at the beginning of the experiment, when Fe2+ concentration is higher. However, after these initial moments, the prevailing process is photo-Fenton and, in addition, wavelength radiation plays an important role. Concerning the effect of radiation, four LEDs (4.2 W total power) were used, emitting radiation in the wavelength range between 380-390 or 390-400 nm. Similar results were obtained in both cases in DPH removal by photo-Fenton (30 min for total elimination). However, a synergistic effect was observed when two LEDs of 380-390 nm and two LEDs of 390-400 nm were used. Total power was the same (4.2 W) in each experimental condition, but the increase in the wavelength range to 20 nm (380-400 nm) produces an increase in the rate of DPH removal, achieving its total elimination at 15 min. This fact, with the use of a simple radiation model, reveals the important role that radiation plays in the photo-Fenton process. Finally, the formed intermediates were determined and some reaction pathways were proposed.

Urinary sepsis after endourological ureterorenoscopy for the treatment of lithiasis. / Sepsis urinaria tras tratamiento endourológico de la litiasis por ureterorrenoscopia.

OBJECTIVE: To evaluate the incidence, clinical presentation and factors associated with the development of urinary sepsis after performing ureterorenoscopy. MATERIAL AND METHODS: Retrospective study of patients undergoing ureterorenoscopy for the treatment of lithiasis between July 2015 and October 2017. Patients who developed urinary sepsis during the 30 days following the intervention were identified. Personal, clinical, surgical and microbiological backgrounds were collected. Statistical analysis was performed with the Chi squared test (or Fisher's exact test), Student's t (or U Mann-Whitney) or logistic regression as appropriate. RESULTS: 246 ureterorenoscopies were performed, 184 (74.8%) on ureteral stones and 62 (25.2%) on kidney stones, with a mean age of 52 (44.5-59.5) years. After procedure, 18 (7.3%) patients developed urinary sepsis, 10 of them (55.5%) occurred in the first 24h. The urine culture showed enterobacteria (61.1%) and enterococci (38.9%). The antibiogram showed greater sensitivity to nitrofurantoins (100%) and quinolones (72%). The statistical analysis showed that female sex, the clinical debut of urolithiasis as urinary sepsis, having received antibiotic or having required urinary diversion by a double J during debut, positive presurgical uroculture and the persistence of residual lithiasis after surgery were significantly associated (P<.05) with the development of urinary sepsis after ureterorenoscopy. CONCLUSION: Urinary sepsis is a complication that appears after performing ureterorenoscopy, especially in female patients with a history of urinary sepsis, antibiotic therapy, double J, previous positive urine culture or residual lithiasis after the procedure.

Experience With Hypothermic Machine Perfusion in Expanded Criteria Donors: Functional Outcomes.

Hypothermic machine perfusion (HMP) decreases delayed graft function (DGF) and improves 1-year graft survival in expanded criteria donors (ECDs). Time of HMP could be associated with incidence of DGF. OBJECTIVE: To analyze functional outcomes of ECD grafts preserved totally (local grafts) or partially (imported grafts) with HMP. MATERIALS AND METHODS: We analyzed prospectively collected data from a cohort of first ECD graft receptors, with a minimum follow-up of 6 months. A total of 119 imported and 74 local grafts were included. Local ECD kidneys were preserved with HMP after retrieval. Imported ECD kidneys were preserved with simple cold storage and HMP. Vascular thrombosis, acute rejection, DGF, 1-year glomerular filtration rate, and 1-year graft survival were assessed. Univariate and estimative multivariate logistic regression was applied for analysis of DGF. A Cox proportional hazards model was applied to estimate graft survival. RESULTS: DGF occurred in 14 recipients of local grafts and in 33 recipients of imported grafts (28.0 vs 18.1%, P = .13); 1-year graft survival was better in the group of local grafts (80.3 vs 91.9%, P = .03). No differences in vascular thrombosis (5.9 vs 5.4%, P = .88), acute rejection (12.3 vs 9.8%, P = .91), or 1-year glomerular filtration rate (41.2 vs 40.5 mL/m/1.73m2, P = .87) were observed. In multivariate analysis, adjusted odds ratio for DGF was 1.20 (P = .79) and adjusted hazard ratio for graft survival was 1.93 (P = .31). CONCLUSIONS: There is a trend that complete HMP reduces the risk of DGF and improves 1-year graft survival in ECD kidneys.

Kinetic study of colored species formation during paracetamol removal from water in a semicontinuous ozonation contactor.

Paracetamol aqueous solutions, when ozonized, acquired a strong red coloration depending on the applied ozone dose and the initial pH of the aqueous solution. Then, this color loses intensity and turns to yellow. Color formation is favored when operating at initial pH0 = 12.0 and ozone flow-rate 4.2 mg/min. A mechanism describing color formation was proposed, being the main pathway involved an initial paracetamol hydroxylation to yield 3-hydroxyacetaminophen followed by the formation of 2-amino-5-hydroxyacetofenone. Then, these compounds are degraded to colored oxidation by-products. A model describing color evolution was also proposed, considering first-order kinetics for both color formation and degradation. The corresponding kinetic constant values were determined to be kf = 0.01 (1/min) and kd = 0.03 pH -0.055 (1/min), respectively. A relationship between aromaticity loss and color changes during the reaction has been estimated considering the parameter α=kA/kf, being α = 1.62 pH + 3.5 and the first-order rate constant for aromaticity loss given by kA = 0.0162 pH + 0.035 (1/min).

Comparison between percutaneous nephrolithotomy and flexible ureteroscopy for the treatment of 2 and 3cm renal lithiasis. / Comparación entre nefrolitotomía percutánea y ureteroscopia flexible para el tratamiento de litiasis renales de entre 2 y 3cm.

CONTEXT AND OBJECTIVES: The first-line treatment for >2cm lithiasis is percutaneous nephrolithotomy (PNL), leaving flexible ureteroscopy (fURS) as a second option. In the present review, the stone-free rate and the complications of both techniques were evaluated in the treatment of 2-3cm stones. MATERIAL AND METHODS: Systematic review of studies that compared both techniques. Studies that were not comparative, as well as those carried out in the pediatric population or with <2cm or>3cm stones, were excluded. Two researchers independently performed the investigation, obtaining 5 studies that made up a total of 815 patients: 252 belonged to the fURS group and 563 to the PNL group. Four studies were retrospective, and one was non-randomized prospective. RESULTS: Stone-free rate ranged between 47.0% and 95.0% for the fURS and between 87.0% and 100% for the PNL. The complication rate was 8.8-29.0% in the fURS and 11.9-27.0% in the PNL. fURS required a greater number of procedures, and had a lower decrease in haemoglobin and creatinine rise compared to PNL. CONCLUSIONS: The stone-free rate was higher for PNL, although the fURS could reach comparable results at the expense of performing several procedures. Both techniques have a similar frequency of complications, but the PNL has more postsurgical analytical alterations.

Exploring ozonation as treatment alternative for methiocarb and formed transformation products abatement.

Despite the high toxicity and resistance to conventional water treatments exhibited by methiocarb (MC), there are no reports regarding the degradation of this priority pesticide by means of alternative purification technologies. In this work, the removal of MC by means of ozonation was studied for the first time, employing a multi-reactor methodology and neutral pH conditions. The second-order rate constants of MC reaction with molecular ozone (O3) and formed hydroxyl radicals (OH·) were determined to be 1.7·106 and 8.2·109 M-1 s-1, respectively. During degradation experiments, direct ozone reaction was observed to effectively remove MC, but not its formed intermediates, whereas OH· could oxidize all species. The major identified TPs were methiocarb sulfoxide (MCX), methiocarb sulfoxide phenol (MCXP) and methiocarb sulfone phenol (MCNP), all of them formed through MC oxidation by O3 or OH· in combination with hydrolysis. A toxicity assessment evidenced a strong dependence on MCX concentration, even at very low values. Despite the OH· capability to degrade MC and its main metabolites, the relative resistance of TPs towards ozone attack enlarged the oxidant dosage (2.5 mg O3/mg DOC) necessary to achieve a relatively low toxicity of the medium. Even though ozonation could be a suitable technique for MC removal from water compartments, strategies aimed to further promote the indirect contribution of hydroxyl radicals during this process should be explored.

Priority pesticides abatement by advanced water technologies: The case of acetamiprid removal by ozonation.

With the aim of exploring treatment alternatives for priority insecticide acetamiprid (ACMP) abatement, the removal of this compound from water by ozonation was studied for the first time, paying special attention to the kinetic, mechanistic and toxicological aspects of the process. The second order rate constants of reactions between ACMP and both molecular ozone (O3) and hydroxyl radicals (OH) were determined to be 0.25M-1s-1 and 2.1·109M-1s-1, respectively. On the basis of kinetic results, the degradation of ACMP during ozonation could be well-explained by the reactivity of this pesticide with OH. HPLC/MS analysis of the ozonated ACMP showed ACMP-N-desmethyl, 6-chloronicotinic acid, N'cyano-N-methyl acetamidine and N'-cyano acetamidine as the major transformation products (TPs), all of them formed through amine α carbon oxidation in combination with hydrolysis. Microtox bioassays revealed an increase in the toxicity of the medium during ACMP ozonation process, followed by a decrease to relatively low values. These changes could be attributed to the synergistic effects between TPs as well as to the presence of toxic intermediate aldehydes. Even though adopting strategies to further promote ozone decomposition to hydroxyl radicals appears to be essential, ozonation can be an effective treatment process for ACMP removal and associated toxicity abatement.

Listeria monocytogenes Inhibits Serotonin Transporter in Human Intestinal Caco-2 Cells.

Listeria monocytogenes is a Gram-positive bacterium that can cause a serious infection. Intestinal microorganisms have been demonstrated to contribute to intestinal physiology not only through immunological responses but also by modulating the intestinal serotonergic system. Serotonin (5-HT) is a neuromodulator that is synthesized in the intestinal epithelium and regulates the whole intestinal physiology. The serotonin transporter (SERT), located in enterocytes, controls intestinal 5-HT availability and therefore serotonin's effects. Infections caused by L. monocytogenes are well described as being due to the invasion of intestinal epithelial cells; however, the effect of L. monocytogenes on the intestinal epithelium remains unknown. The main aim of this work, therefore, was to study the effect of L. monocytogenes on SERT. Caco2/TC7 cell line was used as an enterocyte-like in vitro model, and SERT functional and molecular expression assays were performed. Our results demonstrate that living L. monocytogenes inhibits serotonin uptake by reducing SERT expression at the brush border membrane. However, neither inactivated L. monocytogenes nor soluble metabolites were able to affect SERT. The results also demonstrate that L. monocytogenes yields TLR2 and TLR10 transcriptional changes in intestinal epithelial cells and suggest that TLR10 is potentially involved in the inhibitory effect observed on SERT. Therefore, L. monocytogenes, through TLR10-mediated SERT inhibition, may induce increased intestinal serotonin availability and potentially contributing to intestinal physiological changes and the initiation of the inflammatory response.

Toll-like receptors 2 and 4 exert opposite effects on the contractile response induced by serotonin in mouse colon: role of serotonin receptors.

What is the central question of this study? The action of Toll-like receptors (TLRs) 2 and 4 on the motor response to serotonin in mouse colon has not previously been reported. What is the main finding and its importance? Toll-like receptors 2 and 4 modulate the serotonin-induced contractile response in mouse colon by modifying the expression of serotonin (5-HT) receptors. Alterations in 5-HT2A and 5-HT2C receptors explain the increase of the response to serotonin in TLR2(-/-) mice. Alterations in 5-HT2C and 5-HT4 receptors explain the suppression of the response to serotonin in TLR4(-/-) mice. The microbiota, through Toll-like receptors (TLRs), may regulate gastrointestinal motility by activating neuroendocrine mechanisms. We evaluated the influence of TLR2 and TLR4 in spontaneous contractions and in the serotonin (5-HT)-induced motor response in mouse colon, and assessed the 5-HT receptors involved. Muscle contractility studies to evaluate the intestinal spontaneous motility and the response to 5-HT were performed in the colon from wild-type (WT), TLR2(-/-) , TLR4(-/-) and TLR2/4 double knockout (DKO) mice. The 5-HT receptor mRNA expression was determined by real-time PCR. The amplitude and frequency of the spontaneous contractions of the colon were smaller in TLR4(-/-) and TLR2/4 DKO mice with respect to WT mice. In WT, TLR2(-/-) and TLR2/4 DKO mice, 100 µm 5-HT evoked a contractile response. The contractile response induced by 5-HT was significantly higher in TLR2(-/-) than in WT mice. In TLR4(-/-) mice, 5-HT did not evoke any contractile response. The mRNA expression of 5-HT2A was increased in TLR2(-/-) and TLR2/4 DKO mice. The 5-HT2C and 5-HT4 mRNA expressions were increased in TLR4(-/-) and TLR2/4 DKO mice. The 5-HT2C mRNA expression was diminished in TLR2(-/-) mice. The 5-HT3 mRNA expression was increased in TLR2(-/-) , TLR4(-/-) and TLR2/4 DKO mice. The 5-HT7 mRNA expression was diminished in TLR2/4 DKO mice. In WT, TLR2(-/-) and TLR2/4 DKO mice, 5-HT2 , 5-HT3 , 5-HT4 and 5-HT7 receptor antagonists reduced or blocked the contractile response evoked by 5-HT. We postulate that TLR2 and TLR4 modulate the serotonin contractile motor response in mouse colon in an opposing manner by modifying the expression of several serotonin receptors.

Toll-like receptors 2 and 4 modulate the contractile response induced by serotonin in mouse ileum: analysis of the serotonin receptors involved.

BACKGROUND: Microbiota through toll-like receptors (TLR) may regulate gastrointestinal motility by activating neuroendocrine mechanisms. We evaluated the influence of TLR2 and TLR4 in the spontaneous contractions and serotonin (5-HT)-induced motor response in mouse ileum, and the 5-HT receptors involved. METHODS: Muscle contractility studies to evaluate the spontaneous intestinal motility and the response to 5-HT were performed in the ileum from wild type (WT), TLR2(-/-), TLR4(-/-), and TLR2/4 double knockout (DKO) mice. 5-HT receptor expression was determined by real-time PCR. KEY RESULTS: The amplitude of spontaneous contractions in ileum was higher in TLR2(-/-), TLR4(-/-), and TLR2/4 DKO mice with respect to WT. 5-HT evoked concentration-dependent contractile responses in the ileum from TLR2(-/-) and TLR4(-/-) mice similar to WT. However, in ileum from TLR2/4 DKO, 5-HT did not induce any contractile response. Expression of 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT3 receptors resulted increased in ileum from TLR4(-/-) and TLR2/4 DKO. Expression of the 5-HT4 receptor was diminished in TLR2(-/-) and TLR2/4 DKO. High levels of 5-HT7 receptor expression were found in TLR2/4 DKO but not in TLR2(-/-) or TLR4(-/-). In WT and TLR4(-/-), 5-HT2, 5-HT3, 5-HT4, and 5-HT7 receptor antagonists reduced the contractile response evoked by 5-HT. In TLR2(-/-) mice, 5-HT4 antagonist did not reduce the 5-HT response. In TLR2/4 DKO mice, only 5-HT4 and 5-HT7 receptor antagonists reduced the relaxing response induced by 5-HT. CONCLUSIONS & INFERENCES: TLR2 and TLR4 signaling may modulate the spontaneous contractions and the serotonin contractile response by acting on 5-HT2, 5-HT3, 5-HT4, and 5-HT7 receptors.

Surgery improves survival in elderly with breast cancer. A study of 465 patients in a single institution.

INTRODUCTION: Breast cancer treatment in elderly patients is controversial. This single-centre study was conducted to review the treatment and outcomes for octogenarian women treated for breast cancer. METHODS: Data from all patients aged 80 years or more with primary breast cancer treated at our institution between 1995 and 2012 were included. Patients with carcinoma in-situ (stage 0) and advanced breast cancer (stage IV) were excluded. RESULTS: The study population consisted of 369 patients (median age 84 years). A total of 277 (75%) patients underwent surgical treatment (PST) and 92 (25%) received primary endocrine treatment (PET). Prognostic factors (HER-2, tumour grade, lymphovascular invasion and subsequent adjuvant therapy) were homogeneously distributed in both groups. PST and PET were stratified according to stage: 273 (66%) patients with early stage disease (I, IIA, IIB) and 96 (34%) with locally advanced disease (IIIA, IIIB, IIIC). Patients were followed-up for a median of 63 months. In patients with early stage disease, the mean breast cancer-specific survival (BCSS) was 109 months (95% CI = 101-115) in PST patients, and 50 months (95% CI = 40-60) in PET patients (P < 0.01). Conversely, for patients with locally advanced breast cancer, there was no significant difference in BCSS between the surgical and non-surgical groups. In the PST group, BCSS and disease-free survival were significantly better among patients who underwent standard surgical treatment than among those who received suboptimal treatment. There were no differences in the Charlson comorbidity index scores between the PST and PET groups. CONCLUSION: In women ≥80 years with early-stage breast cancer, standard surgical treatment was associated with a better BCSS when compared with PET.

Conservative approach versus urgent appendectomy in surgical management of acute appendicitis with abscess or phlegmon.

BACKGROUND: Surgical management of acute appendicitis with appendiceal abscess or phlegmon remains controversial. We studied the results of initial conservative treatment (antibiotics and percutaneous drainage if necessary, with or without interval appendectomy) compared with immediate surgery. METHODS: We undertook an observational, retrospective cohort study of patients with a clinical and radiological diagnosis of acute appendicitis with an abscess or phlegmon, treated in our hospital between January 1997 and March 2009. Patients younger than 14, with severe sepsis or with diffuse peritonitis were excluded. A study group of 15 patients with acute appendicitis complicated with an abscess or phlegmon underwent conservative treatment. A control group was composed of the other patients, who all underwent urgent appendectomy, matched for age and later randomized 1:1. The infectious risk stratification was established with the National Nosocomial Infections Surveillance System (NNIS) index. Dependent variables were hospital stay and surgical site infection. Analysis was with SPSS, with p < 0.05 considered significant. RESULTS: Interval appendectomy was performed in 7 study group patients. Surgical site infection episodes were more frequent in the control group (6 vs. 0, p < 0.001). A greater percentage of high risk patients (NNIS ≥ 2) was identified in the control group (80 vs. 28.7%, p < 0.03), mostly related with contaminated or dirty procedures in this group (p < 0.001). No significant difference between groups was found in hospital stay. CONCLUSION: Initial conservative treatment should be considered the best therapeutic choice for acute appendicitis with abscess or phlegmon.

Resultados del tratamiento conservador inicial y de la cirugía urgente en la apendicitis aguda evolucionada / No disponible

Introducción: Existe controversia acerca del tratamiento idóneo de la apendicitis aguda evolucionada en forma de absceso o flemón. Realizamos un estudio para la evaluación de resultados del tratamiento conservador inicial (antibiótico y drenaje percutáneo si se precisa, con/sin apendicectomía diferida) y del tratamiento quirúrgico urgente. Método: Estudio observacional analítico de cohortes retrospectivas. Criterios de inclusión: pacientes con diagnóstico clínico y radiológico de apendicitis aguda evolucionada en forma de absceso o flemón, tratados en nuestro hospital entre enero 1997 y marzo 2009, excluyendo pacientes pediátricos, con sepsis grave o peritonitis difusa. En 15 pacientes con apendicitis complicada con absceso o flemón (cohorte de estudio) se indicó tratamiento conservador inicial. El grupo control se obtuvo del resto de pacientes (en todos ellos se indicó apendicectomía urgente) mediante un matching por edad y asignación aleatoria posterior (1:1). La estratificación del riesgo infeccioso se determinó mediante el índice National Nosocomial Infections Surveillance System (NNIS). Variables resultado: estancia global e infección de sitio quirúrgico. Se consideraron de relevancia estadística niveles de significación < 0,05. Resultados: En 7 pacientes del grupo de estudio se indicó apendicectomía diferida. La incidencia de episodios de infección de sitio quirúrgico fue significativamente mayor en el grupo control (6 vs. 0, p < 0,001). Un mayor porcentaje de pacientes con NNIS de alto riesgo (>= 2) se objetivó en el grupo control (80% vs. 28,7%, p < 0,03). El item determinante fue el carácter contaminado o sucio de las apendicectomías urgentes (p < 0,001). La estancia global no mostró diferencias significativas entre grupos. Conclusión: El tratamiento conservador inicial constituye la mejor alternativa terapéutica para la apendicitis aguda evolucionada(AU)

Background: Surgical management of acute appendicitis with appendiceal abscess or phlegmon remains controversial. We studied the results of initial conservative treatment (antibiotics and percutaneous drainage if necessary, with or without interval appendectomy) compared with immediate surgery. Methods: We undertook an observational, retrospective cohort study of patients with a clinical and radiological diagnosis of acute appendicitis with an abscess or phlegmon, treated in our hospital between January 1997 and March 2009. Patients younger than 14, with severe sepsis or with diffuse peritonitis were excluded. A study group of 15 patients with acute appendicitis complicated with an abscess or phlegmon underwent conservative treatment. A control group was composed of the other patients, who all underwent urgent appendectomy, matched for age and later randomized 1:1. The infectious risk stratification was established with the National Nosocomial Infections Surveillance System (NNIS) index. Dependent variables were hospital stay and surgical site infection. Analysis was with SPSS, with p < 0.05 considered significant. Results: Interval appendectomy was performed in 7 study group patients. Surgical site infection episodes were more frequent in the control group (6 vs. 0, p < 0.001). A greater percentage of high risk patients (NNIS >= 2) was identified in the control group (80 vs. 28.7%, p < 0.03), mostly related with contaminated or dirty procedures in this group (p < 0.001). No significant difference between groups was found in hospital stay. Conclusion: Initial conservative treatment should be considered the best therapeutic choice for acute appendicitis with abscess or phlegmon(AU)

Regulation of serotonin transporter activity by adenosine in intestinal epithelial cells.

Serotonin plays a critical role in the regulation of intestinal physiology. The serotonin transporter (SERT) expressed in the intestinal epithelium determines 5-HT availability and activity. The serotoninergic system and SERT activity have been described as being altered in chronic intestinal pathologies such as inflammatory diseases. Adenosine has also been shown to be involved in a variety of intestinal functions and to play a central role in the regulation of inflammatory responses of injured tissue. Since the modulation of SERT by adenosine in the intestine remains unknown, the aim of the present work was to study the effect of adenosine on SERT activity and expression and to determine the molecular mechanism involved. The study has been carried out using human enterocyte-like Caco-2 cells which endogenously express SERT. The results show that adenosine diminishes SERT activity in both the apical and basal membranes by acting in the intrinsic molecule with no alteration of either SERT mRNA or protein levels. The effect of adenosine appears to be mediated by A(2) receptors and activation of the cAMP/PKA signalling pathway. Moreover, the adenosine effect did not seem to involve the activation of AMP activated protein kinase. Adenosine effects are reached at high concentrations, which suggests that adenosine modulation of SERT may be significant under conditions of inflammation and tissue injury.