Short-Term Effectiveness, Safety, and Potential Predictors of Response of Secukinumab in Patients with Severe Hidradenitis Suppurativa Refractory to Biologic Therapy: A Multicenter Observational Retrospective Study.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Biologic drugs have a key role in the long-term anti-inflammatory treatment of moderate to severe patients due to their immunomodulatory properties. The aim of this study is to evaluate the effectiveness and safety of secukinumab in patients with moderate to severe HS after 16 weeks of treatment, and to explore potential predictors of clinical response to the drug. METHODS: Multicenter observational retrospective study. Patients treated with secukinumab 300 mg every 2 or 4 weeks who had completed at least 16 weeks of follow-up from nine hospitals based in southern Spain (Andalusia) were included in this study. Treatment effectiveness was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR). Information about adverse events was collected, the therapeutic burden of the patients was calculated as the summation of systemic medical treatments and surgical interventions (excluding incision and drainage) experienced until the start of secukinumab treatment. RESULTS: Forty-seven patients with severe HS were included for analysis. At week 16, 48.9% (23/47) of patients achieved HiSCR. Adverse events were present in 6.4% (3/47) of the patients. The multivariate analysis showed that female sex and, to a lesser extent, lower body mass index (BMI) and a lower therapeutic burden were potentially associated with a higher probability of HiSCR achievement. CONCLUSIONS: Favorable short-term effectiveness and safety of secukinumab in the treatment of severe HS patients were observed. Female sex, lower BMI and a lower therapeutic burden may be associated with a higher probability of achieving HiSCR.

Long-term efficacy of photodynamic therapy with methyl aminolevulinate in treating Bowen's disease in clinical practice: A retrospective cohort study (2006-2017).

BACKGROUND: Photodynamic treatment with methyl aminolevulinate (MAL-PDT) is considered an effective and highly recommended treatment for Bowen's disease. However, its long-term efficacy remains to be established, as significant differences have been reported in this respect. OBJECTIVE: The aim of the present study was to describe the results of a retrospective analysis of patients with Bowen's disease treated with MAL-PDT during the period 2006-17 at the Costa del Sol Hospital (Marbella, Spain). MATERIAL AND METHODS: This study is based on a retrospective descriptive analysis of the clinical records of patients treated with MAL-PDT from June 2006 to September 2017. The analysis was based on calculating the mean and standard deviation values for the quantitative variables, and frequency distributions for the qualitative ones. The survival curves were plotted by the Kaplan-Meier method, and the log-rank test was used to assess differences in survival between groups. A cox regression analysis was performed to clarify the significant prognostic factors. RESULTS: A total of 537 tumours with histologically confirmed Bowen's disease were treated with MAL-PDT. Recurrence-free survival at one year was 88%, and at 5 years, 71%. Tumour size >300 mm2 (≥21 mm in diameter P = 0.019), its location in the upper extremities (P = 0.029) and patient's age <70 years (P = 0.028) were all associated with an increased risk of recurrence. LIMITATIONS: Given the retrospective design of our study, the possible existence of information bias cannot be ruled out. CONCLUSIONS: Although it is an appropriate treatment option for patients with Bowen's disease, MAL-PDT presents a risk of recurrence of almost 30% at 5 years. Larger lesions (>300 mm2 ; ≥21 mm in diameter) are more likely to recur than smaller ones. Therefore, appropriate selection is needed of the tumour to be treated, and prolonged follow-up should be provided.

Topical treatment with oleocanthal extract in reducing inflammatory reactions after photodynamic therapy: a prospective quasi-experimental pilot study.

OBJECTIVE: Photodynamic therapy (PDT) is an effective treatment against skin field cancerization. Its main side effect is local inflammation in the treated area. The phenolic compound oleocanthal (decarboxy methyl ligstroside aglycone), which is present in extra virgin olive oil (EVOO), has anti-inflammatory properties. The purpose of this study was to evaluate the topical efficacy of an oily fluid enriched with oleocanthal (OC) extract, in comparison with a conventional oily fluid, in reducing the degree of inflammatory reaction after conventional PDT. METHODS: Quasi-experimental pilot study, before-after with a control group, performed with a cohort of consecutive patients diagnosed with actinic keratosis/field cancerization (AK/FC) in the forehead and/or scalp, treated by PDT. The study was carried out from April 2016 to November 2017 at a speciality hospital in southern Spain. A group of 24 consecutive patients received the topical application, three times daily for one week, of an emollient oily fluid in the area treated with PDT. Subsequently, another group, of 23 consecutive patients, received the same treatment pattern with an oily fluid enriched with OC extract. The post-PDT inflammatory reaction was measured by an independent member of the hospital's dermatology department, using the following visual scale of erythema (from 0 to 4).The assessment was conducted at 30 min and at 48 h post-PDT. RESULTS: In the assessment at 48 h after treatment, the inflammation had improved more among the patients treated with OC (median: 25%, 95%CI: -5.3 to 28.5) than in the non-OC group (median: 0%; 95%CI: -45.2 to -6.2). The difference was statistically significant (p<0.01), and the Cohen's d value was 0.89 (large effect). At three months after PDT, a complete response had been obtained by 60.9% of the patients treated with OC compared to 29.2% of the non-OC group, and the difference was close to statistical significance (p=0.059). CONCLUSIONS: The topical application of an oily fluid enriched with OC extract achieved a greater reduction in post-PDT cutaneous inflammation and a better treatment response, in comparison with the application of a conventional oily fluid.

Comparison of clinical outcomes regarding the use of titanium-nitride-oxide-coated stents (Titan) versus zotarolimus-eluting stents (Endeavor) in patients with ST-segment elevation myocardial infarction (STEMI): An experience from a Cardiac Center-Third care level / Comparación de los resultados clínicos con respecto al uso de stents recubiertos de óxido de titanio (Titan) versus stents liberadores de zotarolimus (Endeavor) en pacientes con infarto de miocardio por elevación del segmento ST (STEMI): Una experiencia de un centro cardiaco de Tercer nivel de atención

Abstract: Introduction: Internationally, the Titan bioactive stent efficacy and safety have been evaluated against second-generation drug-eluting stents (DES) in patients with acute coronary syndrome. In our field, however, there is not enough information about its short-term or one-year follow-up outcomes when compared with a second-generation drug-eluting stent in ST-segment elevation myocardial infarction (STEMI). Objective: To evaluate and compare immediate, in-hospital and one-year use clinical outcomes of the Titan stent versus Endeavor stent in patients with ST-segment elevation myocardial infarction. Material and methods: A descriptive, comparative, longitudinal, retrospective, observational study was performed in patients with ST-segment elevation myocardial infarction type acute coronary syndrome who were subjected to primary, pharmacoinvasive and rescue angioplasties, using a Titan stent against Endeavor stent. Primary points: major adverse cardiac events (MACEs), death, myocardial infarction, need for target lesion revascularization (TLR), target vessel revascularization (TVR), cerebrovascular event (CVE) and stent thrombosis. Secondary points: Dual antiplatelet therapy (DAPT) usage time. Results: 256 patients with ST-segment elevation myocardial infarction were examined from January 2011 to December 2014. They were treated with a Titan bioactive stent (135 patients) or Endeavor stent (121 patients). There were no significant differences related to major adverse cardiac events, death, myocardial infarction, stent thrombosis or cerebrovascular event, either in-hospital or one-year follow-up. More patients were observed in the Killip-Kimball 3-4 classification in Endeavor stent group versus patients in Titan stent group (62.2% versus 42.2%, respectively, p = 0.010). A greater pre-PTCA (Percutaneous Transluminal Coronary Angioplasty) TIMI (Thrombolysis in Myocardial Infarction) 0-1 flow rate was also observed (90.9% in Endeavor stent group versus 79.3% in Titan stent group, p = 0.010). However, the Titan stent was considerably more used in elderly patients (62.36 ± 12.95 years old versus 57.59 ± 10.42 years old in Endeavor stent group, p = 0.001); in more complex type C lesions (62.4% in Titan stent group versus 40.5% in Endeavor stent group, p = 0.010); and small vessels (28.9% in Titan stent group versus 18.2% in Endeavor stent group, p = 0.045). Target lesion revascularization and target vessel revascularization rates were similar: 0% versus 2.5%, p = 0.066 and 0% versus 0.8%, p = 0.290, in Titan stent and Endeavor stent groups, respectively. There were no significant differences on the major adverse cardiac events-free survival analysis (Log-rank Mantel-Cox 0.764 test). There were significant differences on dual antiplatelet therapy usage time (6.46 ± 4.11 months in Titan stent group versus 10.98 ± 2.51 months in Endeavor stent group, p ≤ 0.0001). Conclusions: There was no superiority registered in use of a second-generation drug-eluting stent such as the Endeavor stent versus Titan bioactive stent (titanium-nitride-oxide-coated stent) in patients with ST-segment elevation myocardial infarction regarding immediate, in-hospital and one-year follow-up clinical outcomes. The Titan stent seems to be a good choice for this kind of ST-segment elevation acute coronary syndrome in both efficacy and safety against new drug-eluting stents, and it could be used in elderly patients and/or patients with high bleeding risk requiring less time of dual antiplatelet therapy.(AU)

Resumen: Introducción: A nivel internacional, la eficacia y la seguridad de los stents bioactivos Titan se han evaluado en comparación con los stents liberadores de fármacos (su sigla en inglés es DES) de segunda generación en pacientes con síndrome coronario agudo. Sin embargo, en nuestro campo, no hay suficiente información acerca de sus resultados de seguimiento a corto plazo o de un año cuando se compara con una endoprótesis liberadora de fármacos de segunda generación en el infarto de miocardio por elevación del segmento ST (STEMI). Objetivo: Evaluar y comparar los resultados clínicos inmediatos, en el hospital y a un año de uso del stent Titan frente a stent Endeavor en pacientes con infarto de miocardio por elevación del segmento ST. Material y métodos: Se realizó un estudio observacional descriptivo, comparativo, longitudinal, retrospectivo y observacional en pacientes con el síndrome coronario agudo de infarto de miocardio por elevación del segmento ST que fueron sometidos a angioplastias primarias, farmacoinvasivas y de rescate, utilizando un stent Titan contra el stent Endeavor. Puntos primarios: eventos cardiacos adversos mayores (MACE), muerte, infarto de miocardio, necesidad de revascularización de la lesión objetivo (TLR). Revascularización del vaso objetivo (TVR), evento cerebrovascular (CVE) y trombosis del stent. Puntos secundarios: Tiempo de uso de la terapia antiplaquetaria dual (DAPT). Resultados: De enero de 2011 a diciembre de 2014 se examinaron 256 pacientes con infarto de miocardio por elevación del segmento ST. Fueron tratados con un stent bioactivo de Titan (135 pacientes) o un stent de Endeavor (121 pacientes). No hubo diferencias significativas relacionadas con los eventos cardiacos adversos mayores, muerte, infarto de miocardio, trombosis de stent o evento cerebrovascular, ni en el hospital ni en el seguimiento de un año. Se observaron más pacientes en la clasificación Killip-Kimball 3-4 en el grupo de stent Endeavor versus pacientes en el grupo de stent Titan (62.2% versus 42.2%, respectivamente, p = 0.010). También se observó una mayor tasa de flujo 0-1 antes de la PTCA (angioplastia coronaria transluminal percutánea) TIMI (trombólisis en el infarto de miocardio) (90.9% en el grupo de stent Endeavor frente a 79.3% en el grupo de stent Titan, p = 0.010). Sin embargo, la endoprótesis Titan se utilizó considerablemente más en pacientes de edad avanzada (62.36 ± 12.95 años frente a 57.59 ± 10.42 años en el grupo de endoprótesis Endeavor, p = 0.001); en las lesiones tipo C más complejas (62.4% en el grupo de stent Titan versus 40.5% en el grupo de stent Endeavor, p = 0.010); y en pequeños vasos (28.9% en el grupo de stent Titan versus 18.2% en el grupo de stent Endeavor, p = 0.045). La revascularización de las lesiones objetivo y las tasas de revascularización de los vasos objetivo fueron similares: 0% versus 2.5%, p = 0.066 y 0% versus 0.8%, p = 0.290, en los grupos de stent Titan y stent Endeavor, respectivamente. No hubo diferencias significativas en el análisis de supervivencia sin eventos cardiacos adversos mayores (ensayo de Mantel-Cox 0.764 del rango de logos). Hubo diferencias significativas en el tiempo de uso del tratamiento antiplaquetario dual (6.46 ± 4.11 meses en el grupo con stent Titan versus 10.98 ± 2.51 meses en el grupo con stent Endeavor, p ≤ 0.0001). Conclusiones: No se registró una superioridad en el uso de un stent liberador de fármacos de segunda generación como el stent Endeavor versus el stent bioactivo Titan (stent recubierto de titanio-nitrurado) en pacientes con infarto de miocardio por elevación del segmento ST con respecto a los resultados clínicos de seguimiento inmediato, hospitalario y de un año. El stent Titan parece ser una buena opción para este tipo de síndrome coronario agudo por elevación del segmento ST, tanto en eficacia como en seguridad frente a nuevos stents liberadores de fármacos, y podría utilizarse en pacientes ancianos y/o pacientes con alto riesgo de hemorragia que requieran menos tiempo de tratamiento antiplaquetario dual.(AU)

Can we use baseline characteristics to assess which men with moderately symptomatic benign prostatic hyperplasia at risk of progression will benefit from treatment? A post hoc analysis of data from the 2-year CONDUCT study.

PURPOSE: To investigate (in a post hoc analysis of the 2-year CONDUCT study) the characteristics and clinical outcomes of men with moderately symptomatic benign prostatic hyperplasia (BPH) at risk of progression who benefitted from lifestyle changes alone. METHODS: Patients were given lifestyle advice and randomized to a fixed-dose combination (FDC) of dutasteride and tamsulosin or watchful waiting (WW) and followed for 24 months. Patients in the WW group were escalated to tamsulosin if any follow-up International Prostate Symptom Score (IPSS) was equal or greater than the baseline value. Improvements in symptoms (change in IPSS) and quality of life [measured by BPH Impact Index (BII) and question 8 of the IPSS (IPSS-Q8)] were analysed in the FDC group, men who initiated tamsulosin (WW-TAM) and men who received no medical intervention (WW-no treatment) and the impact of baseline variables on IPSS determined. RESULTS: The adjusted mean decrease in IPSS, BII and IPSS-Q8 at each post-baseline visit over 24 months appeared greater in the FDC (n = 369) and WW-no treatment groups (n = 144) than in the WW-TAM group (n = 229). IPSS improvements appeared similar in the FDC group and WW-no treatment subgroup, except in patients with the greatest degree of bother at baseline (BII 7-13). CONCLUSION: BII at baseline may be a more relevant indicator than symptom severity as to whether a patient with moderate symptoms should receive medical therapy or not.

Tratamiento de la neoplasia vulvar intraepitelial con cidofovir tópico: presentación de un caso y revisión de la literatura / Treatment of vulvar intraepithelial neoplasia with topical cidofovir: a case report and literature review

La neoplasia vulvar intraepitelial (VIN) es una precursora del carcinoma vulvar invasivo. Aunque la cirugía es el tratamiento estándar, se están investigando nuevas terapias médicas con el fi n de mantener la anatomía y función sexual de la vulva. Nuestro objetivo es describir la utilidad del cidofovir tópico en la VIN. Presentamos una paciente con una VIN resistente a terapia fotodinámica e imiquimod tópico, que fue tratada con cidofovir tópico con respuesta completa a nivel vulvar y respuesta parcial a nivel perineal y perianal. El cidofovir puede ser una opción terapéutica en el manejo de la VIN. Se necesitan más ensayos futuros para investigar la eficacia y la posología más recomendada (AU)

Vulvar intraepithelial neoplasia (VIN) is a precursor of invasive vulvar carcinoma. Although the standard treatment is surgery, new medical therapies are under investigation to maintain the sexual anatomy and function of the vulva. Our objective was to describe the usefulness of topical cidofovir in VIN. We report a case of VIN resistant to photodynamic therapy and topical imiquimod, which was treated with topical cidofovir with complete response in the vulvar area and partial response in the perineal and perianal area. Cidofovir may be a therapeutic option in the management of VIN. Future trials are needed to investigate its efficacy and recommended dosage (AU)

Efficacy and safety of a fixed-dose combination of dutasteride and tamsulosin treatment (Duodart(®) ) compared with watchful waiting with initiation of tamsulosin therapy if symptoms do not improve, both provided with lifestyle advice, in the management of treatment-naïve men with moderately symptomatic benign prostatic hyperplasia: 2-year CONDUCT study results.

OBJECTIVE: To investigate whether a fixed-dose combination (FDC) of 0.5 mg dutasteride and 0.4 mg tamsulosin is more effective than watchful waiting with protocol-defined initiation of tamsulosin therapy if symptoms did not improve (WW-All) in treatment-naïve men with moderately symptomatic benign prostatic hyperplasia (BPH) at risk of progression. PATIENTS AND METHODS: This was a multicentre, randomised, open-label, parallel-group study (NCT01294592) in 742 men with an International Prostate Symptom Score (IPSS) of 8-19, prostate volume ≥30 mL and total serum PSA level of ≥1.5 ng/mL. Patients were randomised to FDC (369 patients) or WW-All (373) and followed for 24 months. All patients were given lifestyle advice. The primary endpoint was symptomatic improvement from baseline to 24 months, measured by the IPSS. Secondary outcomes included BPH clinical progression, impact on quality of life (QoL), and safety. RESULTS: The change in IPSS at 24 months was significantly greater for FDC than WW-All (-5.4 vs -3.6 points, P < 0.001). With FDC, the risk of BPH progression was reduced by 43.1% (P < 0.001); 29% and 18% of men in the WW-All and FDC groups had clinical progression, respectively, comprising symptomatic progression in most patients. Improvements in QoL (BPH Impact Index and question 8 of the IPSS) were seen in both groups but were significantly greater with FDC (P < 0.001). The safety profile of FDC was consistent with established profiles of dutasteride and tamsulosin. CONCLUSION: FDC therapy with dutasteride and tamsulosin, plus lifestyle advice, resulted in rapid and sustained improvements in men with moderate BPH symptoms at risk of progression with significantly greater symptom and QoL improvements and a significantly reduced risk of BPH progression compared with WW plus initiation of tamsulosin as per protocol.

Burden of Illness in Prostate Cancer Patients with a Low-to-Moderate Risk of Progression: A One-Year, Pan-European Observational Study.

Objective. To assess the impact of low-to-moderate risk prostate cancer on patients' quality of life (QoL) at diagnosis and within the first year of treatment. Subjects and Methods. Men (n = 672) aged 50-75 years with prostate cancer (Gleason score ≤7, PSA ≤20 ng/mL and clinical staging T1c-T2b) were enrolled in five European countries. Patients completed five questionnaires, including EORTC Quality of Life Questionnaire-Prostate Cancer 25 (QLQ-PR25) and EORTC Quality of Life Questionnaire-Cancer 30 (QLQ-C30). Questionnaires were completed at baseline, at 3 months and 12 months after starting treatment. The primary endpoint was the change in QLQ-PR25 urinary symptoms subscale score from baseline to the assessment at 3 months. Results. Mean (SD) age was 65.0 (5.7) years and 400 (66%) men had Gleason score ≤6 prostate cancer. The most frequently used initial treatment was radical prostatectomy (71% of patients). QLQ-PR25 urinary symptoms subscale score was significantly increased at 3 months (P < 0.001), indicating that urinary symptoms worsened after treatment. The score was lower at 12 months than at 3 months, but it was still significantly higher than at baseline (P < 0.001). Hormonal treatment-related symptoms, sexual functioning, and sexual activity scores significantly worsened at 3 and 12 months (all P < 0.001). For the QLQ-C30 questionnaire, global health status/QoL score significantly decreased at month 3 but was not different from baseline by month 12. Scales for physical, role, and social functioning, and fatigue, showed significant deterioration at 3 and 12 months. Conclusions. Low-to-moderate risk prostate cancer may have a substantial effect on patients' QoL within one year following treatment.

The interactions of cell division protein FtsZ with guanine nucleotides.

Prokaryotic cell division protein FtsZ, an assembling GTPase, directs the formation of the septosome between daughter cells. FtsZ is an attractive target for the development of new antibiotics. Assembly dynamics of FtsZ is regulated by the binding, hydrolysis, and exchange of GTP. We have determined the energetics of nucleotide binding to model apoFtsZ from Methanococcus jannaschii and studied the kinetics of 2'/3'-O-(N-methylanthraniloyl) (mant)-nucleotide binding and dissociation from FtsZ polymers, employing calorimetric, fluorescence, and stopped-flow methods. FtsZ binds GTP and GDP with K(b) values ranging from 20 to 300 microm(-1) under various conditions. GTP.Mg(2+) and GDP.Mg(2+) bind with slightly reduced affinity. Bound GTP and the coordinated Mg(2+) ion play a minor structural role in FtsZ monomers, but Mg(2+)-assisted GTP hydrolysis triggers polymer disassembly. Mant-GTP binds and dissociates quickly from FtsZ monomers, with approximately 10-fold lower affinity than GTP. Mant-GTP displacement measured by fluorescence anisotropy provides a method to test the binding of any competing molecules to the FtsZ nucleotide site. Mant-GTP is very slowly hydrolyzed and remains exchangeable in FtsZ polymers, but it becomes kinetically stabilized, with a 30-fold slower k(+) and approximately 500-fold slower k(-) than in monomers. The mant-GTP dissociation rate from FtsZ polymers is comparable with the GTP hydrolysis turnover and with the reported subunit turnover in Escherichia coli FtsZ polymers. Although FtsZ polymers can exchange nucleotide, unlike its eukaryotic structural homologue tubulin, GDP dissociation may be slow enough for polymer disassembly to take place first, resulting in FtsZ polymers cycling with GTP hydrolysis similarly to microtubules.

Tratamiento de la estenosis mitral severa mediante comisurotomía transvenosa percutánea / Treatment of severe mitral stenosis by balloon catheter percutaneous transvenous commissurotomy

Seleccionamos 110 pacientes adultos, 87.1 por ciento mujeres, (edad promedio 38.2 años, límites 16 a 72) con estenosis mitral (EM) severa sintomática, candidatos a valvotomía quirúrgica, para tratamiento alternativo mediante dilatación mitral transversa percutánea (CMTP). Se utilizó el catéter de Inoue en 80 casos (72.7 por ciento) y doble catéter-globo en 30 (27.3 por ciento). El procedimiento se realizó con éxito en 102 pacientes (92.7 por ciento, 2do. intento en 5), con resultados óptimo en 96 (87.3 por ciento); fracasó en un paciente (0.9 por ciento) por dificultad técnica; se complicó en 3 (2.7 por ciento) por perforación de cámara cardíaca, en 4/106 pacientes (3.8 por ciento) insuficiencia mitral severa. El área valvular mitral se incrementó de 1.09 ñ 0.27 a 2.6 ñ 0.87 cm² (p<0.0001); el gradiente transvalvular mitral disminuyó del 18.9 ñ 5.9 a 3.6 ñ 2.8 mmHg (p<0.0001); igualmente descendieron la presión media auricular izquierda de 26 ñ 6.5 a 12.5 ñ 4.2 mmHg (p<0.0001), y la presión arterial pulmonar media de 38 ñ 17 a 26.2 ñ 10.4 mmHg (p<0.0005). En 12/106 pacientes (11.3 por ciento) apareció insuficiencia mitral, o se incrementó la preexistente en más de un grado, y en 86 (81.1 por ciento) no fue detectable. Durante el seguimiento promedio (100 casos) de 10.8 meses (límites 5 a 24), todos los pacientes mejoraron su clase funcional (83.1 por ciento asintomáticos) y conservaron su área valvular mitral según valoración ecocardiográfica. En conclusión, la CMTP es el tratamiento de elección para casos seleccionados de EM adquirida sintomática, con resultados funcionales inmediatos y tardíos comparables a la comisurotomía quirúrgica