Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

CDK9 inhibition as an effective therapy for small cell lung cancer.

Treatment-naïve small cell lung cancer (SCLC) is typically susceptible to standard-of-care chemotherapy consisting of cisplatin and etoposide recently combined with PD-L1 inhibitors. Yet, in most cases, SCLC patients develop resistance to first-line therapy and alternative therapies are urgently required to overcome this resistance. In this study, we tested the efficacy of dinaciclib, an FDA-orphan drug and inhibitor of the cyclin-dependent kinase (CDK) 9, among other CDKs, in SCLC. Furthermore, we report on a newly developed, highly specific CDK9 inhibitor, VC-1, with tumour-killing activity in SCLC. CDK9 inhibition displayed high killing potential in a panel of mouse and human SCLC cell lines. Mechanistically, CDK9 inhibition led to a reduction in MCL-1 and cFLIP anti-apoptotic proteins and killed cells, almost exclusively, by intrinsic apoptosis. While CDK9 inhibition did not synergise with chemotherapy, it displayed high efficacy in chemotherapy-resistant cells. In vivo, CDK9 inhibition effectively reduced tumour growth and improved survival in both autochthonous and syngeneic SCLC models. Together, this study shows that CDK9 inhibition is a promising therapeutic agent against SCLC and could be applied to chemo-refractory or resistant SCLC.

Evaluación prospectiva del perfil emético y la eficacia analgésica del ibuprofeno y el metamizol intravenososen el postoperatorio inmediato de la apendicitis agudapediátrica / Prospective evaluation of the emetogenic profile and analgesic efficacy of intravenous ibuprofen and metamizole in the immediate postoperative period of pediatric acute appendicitis

Introducción: En la literatura existen pocas referencias que comparen las distintas alternativas disponibles para controlar el dolor enel postoperatorio inmediato de la apendicitis aguda pediátrica (AAP).Material y métodos: Comparación prospectiva del perfil anal-gésico y emético del ibuprofeno y el metamizol intravenosos en elpostoperatorio inmediato de la AAP, para lo cual se recurre a unamuestra de pacientes operados en 2021 en nuestro centro. Los participantes fueron reclutados a su llegada a Urgencias, obteniéndoseconfirmación histopatológica del diagnóstico en todos ellos. La evaluación del dolor se llevó a cabo cada 8 horas tras la cirugía medianteescalas analógicas visuales validadas, con valoraciones entre los 0 ylos 10 puntos. Se realizó un ANOVA de las medidas repetidas entrelos dos grupos para comparar la evolución del dolor en las 48 horasposteriores a la cirugía.Resultados: La muestra estaba compuesta por un total de 95 pacientes (65% de ellos varones) con una edad media de 9,7 años (DT:3,14). 41 pacientes fueron tratados con ibuprofeno (grupo 1) y 54 conmetamizol (grupo 2). No se hallaron diferencias significativas en lo querespecta al dolor, ni en las comparaciones de las mediciones puntuales,ni en su evolución en las 48 horas posteriores a la cirugía (p= 0,58). Unavez realizado el ajuste correspondiente a la terapia de fluidos recibida,los niños del grupo metamizol tuvieron significativamente más episodioseméticos y necesitaron significativamente más dosis de ondansetrón.Conclusiones: En nuestra cohorte, el ibuprofeno tuvo una eficaciaanalgésica similar y un mejor perfil emético que el metamizol en elpostoperatorio inmediato de la AAP. Se hacen necesarios nuevos estudiosprospectivos, adecuadamente controlados y con mayor tamaño muestralque validen estos hallazgos.(AU)

Background: Literature comparing different alternatives for paincontrol in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce.Materials and methods: We prospectively compared the analgesicand emetogenic profile of intravenous ibuprofen and metamizole in theimmediate postoperative period of PAA. For this purpose, we used asample of patients operated on in 2021 in our center. Participants wererecruited on arrival at the Emergency Department and histopathologi-cal confirmation of the diagnosis was obtained in all of them. Pain wasevaluated every 8 hours after the surgery with validated visual analogscales ranging from 0 to 10 points. Repeated measures ANOVA wasused to compare the evolution of pain in the 48 hours after surgerybetween the two groups. Results: The sample included 95 patients (65% males) with a meanage of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen(group 1) and 54 with metamizole (group 2). No significant differ-ences were found in the level of pain either in the comparisons of pointmeasurements or in its evolution in the 48 hours after surgery (p= 0.58).After adjusting for the received fluid therapy, children in the metamizolegroup had significantly more emetic episodes and needed significantlymore doses of ondansetron. Conclusions: In our cohort, ibuprofen had a similar analgesic ef-ficacy and a better emetogenic profile than metamizole in the immediatepostoperative period of PAA. Future prospective, adequately controlledstudies with larger sample sizes are needed to validate these findings.(AU)

Prospective evaluation of the emetogenic profile and analgesic efficacy of intravenous ibuprofen and metamizole in the immediate postoperative period of pediatric acute appendicitis. / Evaluación prospectiva del perfil emético y la eficacia analgésica del ibuprofeno y el metamizol intravenosos en el postoperatorio inmediato de la apendicitis aguda pediátrica.

BACKGROUND: Literature comparing different alternatives for pain control in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce. MATERIALS AND METHODS: We prospectively compared the analgesic and emetogenic profile of intravenous ibuprofen and metamizole in the immediate postoperative period of PAA. For this purpose, we used a sample of patients operated on in 2021 in our center. Participants were recruited on arrival at the Emergency Department and histopathological confirmation of the diagnosis was obtained in all of them. Pain was evaluated every 8 hours after the surgery with validated visual analog scales ranging from 0 to 10 points. Repeated measures ANOVA was used to compare the evolution of pain in the 48 hours after surgery between the two groups. RESULTS: The sample included 95 patients (65% males) with a mean age of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen (group 1) and 54 with metamizole (group 2). No significant differences were found in the level of pain either in the comparisons of point measurements or in its evolution in the 48 hours after surgery (p= 0.58). After adjusting for the received fluid therapy, children in the metamizole group had significantly more emetic episodes and needed significantly more doses of ondansetron. CONCLUSIONS: In our cohort, ibuprofen had a similar analgesic efficacy and a better emetogenic profile than metamizole in the immediate postoperative period of PAA. Future prospective, adequately controlled studies with larger sample sizes are needed to validate these findings.

INTRODUCCION: En la literatura existen pocas referencias que comparen las distintas alternativas disponibles para controlar el dolor en el postoperatorio inmediato de la apendicitis aguda pediátrica (AAP). MATERIAL Y METODOS: Comparación prospectiva del perfil analgésico y emético del ibuprofeno y el metamizol intravenosos en el postoperatorio inmediato de la AAP, para lo cual se recurre a una muestra de pacientes operados en 2021 en nuestro centro. Los participantes fueron reclutados a su llegada a Urgencias, obteniéndose confirmación histopatológica del diagnóstico en todos ellos. La evaluación del dolor se llevó a cabo cada 8 horas tras la cirugía mediante escalas analógicas visuales validadas, con valoraciones entre los 0 y los 10 puntos. Se realizó un ANOVA de las medidas repetidas entre los dos grupos para comparar la evolución del dolor en las 48 horas posteriores a la cirugía. RESULTADOS: La muestra estaba compuesta por un total de 95 pacientes (65% de ellos varones) con una edad media de 9,7 años (DT: 3,14). 41 pacientes fueron tratados con ibuprofeno (grupo 1) y 54 con metamizol (grupo 2). No se hallaron diferencias significativas en lo que respecta al dolor, ni en las comparaciones de las mediciones puntuales, ni en su evolución en las 48 horas posteriores a la cirugía (p= 0,58). Una vez realizado el ajuste correspondiente a la terapia de fluidos recibida, los niños del grupo metamizol tuvieron significativamente más episodios eméticos y necesitaron significativamente más dosis de ondansetrón. CONCLUSIONES: En nuestra cohorte, el ibuprofeno tuvo una eficacia analgésica similar y un mejor perfil emético que el metamizol en el postoperatorio inmediato de la AAP. Se hacen necesarios nuevos estudios prospectivos, adecuadamente controlados y con mayor tamaño muestral que validen estos hallazgos.

Encuesta nacional sobre cambios en las políticas de comunicación, visitas y cuidados al final de la vida en las unidades de cuidados intensivos durante las diferentes olas de la pandemia de COVID-19 (estudio COVIFAUCI) / National survey on changes in visitation, communication and end-of-life care policies in intensive care units through the different COVID-19 pandemic's waves (COVIFAUCI study)

Introducción La pandemia derivada de la infección por SARS-CoV-2 propició cambios en los cuidados tanto a familiares como a pacientes de cuidados intensivos durante las diferentes olas de incidencia del virus. La línea de humanización seguida por la mayoría de los hospitales se vio gravemente afectada por las restricciones aplicadas. Como objetivo, planteamos conocer las modificaciones experimentadas durante las diferentes olas de la pandemia por SARS-CoV-2 en España respecto a la política de visitas a los pacientes en UCI, el acompañamiento al final de la vida, y el uso de las nuevas tecnologías de la comunicación entre familiares, pacientes y profesionales. Métodos Estudio descriptivo transversal multicéntrico mediante encuesta a las UCI españolas desde febrero a abril de 2022. Se realizaron métodos de análisis estadísticos a los resultados según lo apropiado. El estudio fue avalado por la Sociedad Española de Enfermería Intensiva y Unidades Coronarias. Resultados Respondieron un 29% de las unidades contactadas. Los minutos de visita diarios de los familiares se redujeron drásticamente de 135 (87,5-255) a 45 (25-60) en el 21,2% de las unidades que permitían su acceso, mejorando levemente con el paso de las olas. En el caso de duelo, la permisividad fue mayor, aumentando el uso de las nuevas tecnologías para la comunicación paciente-familia en el caso del 96,5% de las unidades. Conclusiones Las familias de los pacientes ingresados en UCI durante las diferentes olas de la pandemia por COVID-19 han experimentado restricciones en las visitas y cambio de la presencialidad por técnicas virtuales de comunicación. Los tiempos de acceso se redujeron a niveles mínimos durante la primera ola, recuperándose con el avance de la pandemia pero sin llegar nunca a los niveles iniciales... (AU)

Introduction The pandemic derived from the SARS-CoV-2 infection led to changes in care for both relatives and intensive care patients during the different waves of incidence of the virus. The line of humanization followed by the majority of the hospitals was seriously affected by the restrictions applied. As an objective, we propose to know the modifications suffered during the different waves of the SARS-CoV-2 pandemic in Spain regarding the policy of visits to patients in the ICU, monitoring at the end of life, and the use of new technologies of communication between family members, patients and professionals. Methods Multicenter cross-sectional descriptive study through a survey of Spanish ICUs from February to April 2022. Statistical analysis methods were performed on the results as appropriate. The study was endorsed by the Spanish Society of Intensive Nursing and Coronary Units. Results Twenty-nine percent of the units contacted responded. The daily visiting minutes of relatives dropped drastically from 135 (87.5-255) to 45 (25-60) in the 21.2% of units that allowed their access, improving slightly with the passing of the waves. In the case of bereavement, the permissiveness was greater, increasing the use of new technologies for patient-family communication in the case of 96.5% of the units. Conclusions The family of patients admitted to the ICU during the different waves of the COVID-19 pandemic have suffered restrictions on visits and a change from face-to-face to virtual communication techniques. Access times were reduced to minimum levels during the first wave, recovering with the advance of the pandemic but never reaching initial levels. Despite the implemented solutions and virtual communication, efforts should be directed towards improving the protocols for the humanization of healthcare that allow caring for families and patients whatever the healthcare context. (AU)

Encuesta nacional sobre cambios en las políticas de comunicación, visitas y cuidados al final de la vida en las unidades de cuidados intensivos durante las diferentes olas de la pandemia de COVID-19 (estudio COVIFAUCI) / National survey on changes in visitation, communication and end-of-life care policies in intensive care units through the different COVID-19 pandemic's waves (COVIFAUCI study)

Introducción La pandemia derivada de la infección por SARS-CoV-2 propició cambios en los cuidados tanto a familiares como a pacientes de cuidados intensivos durante las diferentes olas de incidencia del virus. La línea de humanización seguida por la mayoría de los hospitales se vio gravemente afectada por las restricciones aplicadas. Como objetivo, planteamos conocer las modificaciones experimentadas durante las diferentes olas de la pandemia por SARS-CoV-2 en España respecto a la política de visitas a los pacientes en UCI, el acompañamiento al final de la vida, y el uso de las nuevas tecnologías de la comunicación entre familiares, pacientes y profesionales. Métodos Estudio descriptivo transversal multicéntrico mediante encuesta a las UCI españolas desde febrero a abril de 2022. Se realizaron métodos de análisis estadísticos a los resultados según lo apropiado. El estudio fue avalado por la Sociedad Española de Enfermería Intensiva y Unidades Coronarias. Resultados Respondieron un 29% de las unidades contactadas. Los minutos de visita diarios de los familiares se redujeron drásticamente de 135 (87,5-255) a 45 (25-60) en el 21,2% de las unidades que permitían su acceso, mejorando levemente con el paso de las olas. En el caso de duelo, la permisividad fue mayor, aumentando el uso de las nuevas tecnologías para la comunicación paciente-familia en el caso del 96,5% de las unidades. Conclusiones Las familias de los pacientes ingresados en UCI durante las diferentes olas de la pandemia por COVID-19 han experimentado restricciones en las visitas y cambio de la presencialidad por técnicas virtuales de comunicación. Los tiempos de acceso se redujeron a niveles mínimos durante la primera ola, recuperándose con el avance de la pandemia pero sin llegar nunca a los niveles iniciales... (AU)

Introduction The pandemic derived from the SARS-CoV-2 infection led to changes in care for both relatives and intensive care patients during the different waves of incidence of the virus. The line of humanization followed by the majority of the hospitals was seriously affected by the restrictions applied. As an objective, we propose to know the modifications suffered during the different waves of the SARS-CoV-2 pandemic in Spain regarding the policy of visits to patients in the ICU, monitoring at the end of life, and the use of new technologies of communication between family members, patients and professionals. Methods Multicenter cross-sectional descriptive study through a survey of Spanish ICUs from February to April 2022. Statistical analysis methods were performed on the results as appropriate. The study was endorsed by the Spanish Society of Intensive Nursing and Coronary Units. Results Twenty-nine percent of the units contacted responded. The daily visiting minutes of relatives dropped drastically from 135 (87.5-255) to 45 (25-60) in the 21.2% of units that allowed their access, improving slightly with the passing of the waves. In the case of bereavement, the permissiveness was greater, increasing the use of new technologies for patient-family communication in the case of 96.5% of the units. Conclusions The family of patients admitted to the ICU during the different waves of the COVID-19 pandemic have suffered restrictions on visits and a change from face-to-face to virtual communication techniques. Access times were reduced to minimum levels during the first wave, recovering with the advance of the pandemic but never reaching initial levels. Despite the implemented solutions and virtual communication, efforts should be directed towards improving the protocols for the humanization of healthcare that allow caring for families and patients whatever the healthcare context. (AU)

National survey on changes in visitation, communication and end-of-life care policies in intensive care units through the different COVID-19 pandemic's waves (COVIFAUCI study).

INTRODUCTION: The pandemic derived from the SARS-CoV-2 infection led to changes in care for both relatives and intensive care patients during the different waves of incidence of the virus. The line of humanization followed by the majority of the hospitals was seriously affected by the restrictions applied. As an objective, we propose to know the modifications suffered during the different waves of the SARS-CoV-2 pandemic in Spain regarding the policy of visits to patients in the ICU, monitoring at the end of life, and the use of new technologies. of communication between family members, patients and professionals. METHODS: Multicenter cross-sectional descriptive study through a survey of Spanish ICUs from February to April 2022. Statistical analysis methods were performed on the results as appropriate. The study was endorsed by the Spanish Society of Intensive Nursing and Coronary Units. RESULTS: 29% of the units contacted responded. The daily visiting minutes of relatives dropped drastically from 135 (87.5-255) to 45 (25-60) in the 21.2% of units that allowed their access, improving slightly with the passing of the waves. In the case of bereavement, the permissiveness was greater, increasing the use of new technologies for patient-family communication in the case of 96.5% of the units. CONCLUSIONS: The family of patients admitted to the ICU during the different waves of the COVID-19 pandemic have suffered restrictions on visits and a change from face-to-face to virtual communication techniques. Access times were reduced to minimum levels during the first wave, recovering with the advance of the pandemic but never reaching initial levels. Despite the implemented solutions and virtual communication, efforts should be directed towards improving the protocols for the humanization of healthcare that allow caring for families and patients whatever the healthcare context.

El déficit de lipasa ácida lisosomal como paradigma de enfermedad de depósito multisistémica / Lysosomal acid lipase deficiency as a paradigm of multisystemic storage disease

Las enfermedades de depósito lisosomal son un grupo de enfermedades que ha cambiado su pronóstico y manejo clínico en los últimos 15 años gracias a la aparición de tratamientos enzimáticos sustitutivos. La mayoría de las formas clínicas diagnosticadas eran síndromes clásicos graves; el avance de los métodos diagnósticos de función enzimática hace que se hayan diagnosticado e identificado formas más leves que han pasado desapercibidas, pero que a pesar de ello asocian una elevada morbimortalidad, y en las cuales el tratamiento es incluso más efectivo que en las formas graves. El déficit de lipasa ácida lisosomal es una de estas enfermedades lisosomales por depósito de ésteres de colesterol y triglicéridos que cumplen con todas estas características. El tratamiento enzimático sustitutivo con la enzima recombinante sebelipasa ha cambiado el pronóstico infausto de las formas graves. Los métodos diagnósticos de análisis enzimático en gota seca están identificando formas más leves en la infancia tardía y la vida adulta en pacientes con hipercolesterolemia y afectación hepática que estaban sin diagnóstico o mal diagnosticados.(AU)

Lysosomal storage diseases are a group of diseases whose prognosis and clinical management have changed in the last 15 years thanks to the appearance of enzyme replacement treatments. Most of the diagnosed clinical forms were severe classic syndromes; the advance of diagnostic methods of enzymatic function has meant that milder forms that had previously gone unnoticed have been diagnosed and identified. However, in spite of this they are associated with high morbidity and mortality, and in which treatment is even more effective than in severe forms. The lysosomal acid lipase deficit is one of these lysosomal diseases due to the deposition of cholesterol esters and triglycerides that fulfill all these characteristics. Enzyme replacement treatment with the recombinant enzyme sebelipase has changed the poor prognosis of the severe forms. Diagnostic methods of dry smear enzyme analysis are identifying milder forms in late childhood and adult life in patients with hypercholesterolemia and liver involvement who were undiagnosed or misdiagnosed.(AU)

Cirugía radioguiada de tumores mesenquimales con semilla de 125I / Radioguided surgery of mesenchymal tumors with 125I seeds

Introducción La cirugía radioguiada emplea fuentes radioactivas para identificar y extirpar lesiones de difícil localización. Los tumores mesenquimales constituyen un grupo heterogéneo de neoplasias derivados del mesodermo, incluyendo lesiones benignas y sarcomas malignos. El objetivo de este estudio fue evaluar la capacidad de la semilla radioactiva de 125I para guiar la localización intraoperatoria de tumores mesenquimales, analizando sus tasas de complicación y evaluando los márgenes de las piezas quirúrgicas recuperadas. Métodos Estudio observacional retrospectivo de todos los pacientes consecutivos sometidos a cirugía radioguiada de un tumor mesenquimal con semilla radioactiva de 125I desde enero de 2012 hasta enero de 2020 en un centro de referencia terciario en España. La semilla fue insertada mediante punción percutánea guiada con ecografía o tomografía computarizada de forma ambulatoria. Resultados Se extirparon 15 lesiones en 11 cirugías a 11 pacientes, recuperando todas las lesiones marcadas (100%) con semilla de 125I. Las lesiones incluyeron áreas de fibrosis benigna (26,7%), angiofibroma celular (6,7%), tumor desmoide (20%), tumor fibroso solitario (13,3%), condrosarcoma (6,7%) y sarcoma pleomórfico (26,7%), con una tasa elevada de tumores recurrentes (60%). Solo hubo una complicación (6,7%) por caída de la semilla dentro del lecho quirúrgico. Según la clasificación de la Union for International Cancer Control de tumor residual, el 80% de las lesiones resultaron en una resección R0, el 6,7% fueron una resección R1 y el 13,3% fueron una resección R2. Conclusión La cirugía radioguiada fue una técnica precisa para la extirpación de tumores mesenquimales de difícil localización (AU)

Introduction Radioguided surgery uses radioactive substances to identify and remove hard-to-locate lesions. Mesenchymal tumors constitute a heterogeneous group of neoplasms derived from the mesoderm, including benign lesions and malignant sarcomas. The aim of this study was to evaluate the ability of the 125I radioactive seed to guide intraoperative localization of mesenchymal tumors, analyzing its complication rates and evaluating the margins of the surgical specimens retrieved. Methods Retrospective observational study of all consecutive patients undergoing radioguided surgery of a mesenchymal tumor with a 125I radioactive seed from January 2012 to January 2020 at a tertiary referral center in Spain. The seed was inserted percutaneously guided by ultrasound or computed tomography on an outpatient setting. Results Fifteen lesions were removed in 11 surgeries on 11 patients, recovering all marked lesions (100%) with a 125I seed. The lesions included areas of benign fibrosis (26.7%), cellular angiofibroma (6.7%), desmoid tumor (20%), solitary fibrous tumor (13.3%), chondrosarcoma (6.7%), and pleomorphic sarcoma (26.7%), with a high rate of recurrent tumors (60%). There was only one complication (6.7%) due to the seed falling within the surgical bed. According to the UICC classification of residual tumor, 80% of the lesions resulted in an R0 resection, 6.7% were an R1 resection, and 13.3% were an R2 resection. Conclusion Radioguided surgery was a precise technique for the removal of hard-to-locate mesenchymal tumors (AU)

Técnica del acceso apical con injerto simultáneo de tejido conectivo subepitelial para el tratamiento de una fenestración del tejido blando peri-implantario: descripción de la técnica y presentación de un caso clínico / Apical access technique with simultaneous grafting of subepithelial connective tissue for the treatment of peri-implant soft tissue fenestration: description of the technique and presentation of a clinical case

Cuando hablamos de defectos sobre implantes y tejidos blandos lo asociamos principalmente a dehiscencias del tejido blando. Generalmente estamos cada vez más acostumbrados a tratar este tipo de patologías. Sin embargo, en la practica clínica diaria encontramos otras preocupaciones estéticas sobre el tejido blando que requieren estudio y tratamiento. Desde este punto de vista, este informe de caso clínico tuvo como objetivo describir un abordaje quirúrgico mediante la técnica del acceso apical para el tratamiento de una fenestración estética sobre los tejidos blandos periimplantarios. La selección de la técnica bilaminar mediante un acceso apical con injerto de tejido conectivo simultaneo, parece ofrecer resultados prometedores para el tratamiento de deformidades del tejido blando periimplantario. (AU)

When we talk about implant and soft tissue defects we mainly associate them with soft tissue dehiscence. Generally, we are more and more accustomed to treating this type of pathology. However, in daily clinical practice we find other aesthetic concerns about soft tissue that require study and treatment. From this point of view, the aim of this clinical case report was to describe a surgical approach using the apical access technique for the treatment of an aesthetic fenestration on the peri-implant soft tissues. The selection of the bilaminar technique using an apical access with simultaneous connective tissue grafting seems to offer promising results for the treatment of peri-implant soft tissue deformities. (AU)

Severe penile fibrotic reaction secondary to a non-absorbable suture: a case report. / Reacción fibrótica peneana severa secundaria a una sutura no absorbible: reporte de un caso.

INTRODUCTION: Circumcision is one of the most frequent urological surgical procedures in the pediatric population globally. Complications, although rare, can be severe. CLINICAL CASE: We present the case of a Senegalese 10-year-old male patient who had undergone ritual circumcision in his early childhood and developed a progressive circumferential tumor in the penile body with no further associated symptoms. Surgical exploration was carried out. A fibrotic-looking penile ring, which was interpreted as an injury secondary to the non-absorbable suturing material used in the previous surgery, was identified. The tissue involved was removed, and on-demand preputioplasty was conducted. Due to technical limitations, the resected tissue could not be analyzed, which means diagnosis could not be histopathologically confirmed. The patient had a favorable progression. CONCLUSIONS: This case demonstrates that the medical personnel in charge of performing circumcisions should be adequately trained in order to prevent severe complications.

INTRODUCCION: La circuncisión es uno de los procedimientos quirúrgicos urológicos más frecuentemente realizados en la población pediátrica en todo el mundo. Las complicaciones, aunque infrecuentes, pueden ser graves. CASO CLINICO: Presentamos el caso de un paciente varón senegalés de 10 años que fue sometido a una circuncisión ritual en la primera infancia y que desarrolló una tumoración circunferencial progresiva en el cuerpo del pene sin otra sintomatología asociada. Se realizó una exploración quirúrgica y se identificó un rodete peneano de aspecto fibrótico que se interpretó como lesión secundaria al material de sutura no absorbible utilizado en la cirugía anterior. Se realizó una exéresis del tejido afecto y una prepucioplastia a demanda. Por limitaciones técnicas, no se pudo analizar el tejido resecado y por tanto no se pudo confirmar histopatológicamente el diagnóstico. El paciente evolucionó favorablemente. CONCLUSIONES: Este caso pone de manifiesto la necesidad de formar adecuadamente al personal que realiza la circuncisión para evitar complicaciones severas.

Reacción fibrótica peneana severa secundaria a una sutura no absorbible: reporte de un caso / 144J. Arredondo M ontero et al. CIRUGÍA PEDIÁTRICA Resumen Introducción. La circuncisión es uno de los procedimientos qui- rúrgicos urológicos más frecuentemente realizados en la población pe- diátrica en todo el mundo. Las complicaciones, aunque infrecuentes, pueden ser graves. Caso clínico. Presentamos el caso de un paciente varón senegalés de 10 años que fue sometido a una circuncisión ritual en la primera infancia y que desarrolló una tumoración circunferencial progresiva en el cuerpo del pene sin otra sintomatología asociada. Se realizó una exploración quirúrgica y se identificó un rodete peneano de aspecto fibrótico que se interpretó como lesión secundaria al material de sutura no absorbible utilizado en la cirugía anterior. Se realizó una exéresis del tejido afecto y una prepucioplastia a demanda. Por limitaciones técnicas, no se pudo analizar el tejido resecado y por tanto no se pudo confirmar histopa- tológicamente el diagnóstico. El paciente evolucionó favorablemente. Conclusiones. Este caso pone de manifiesto la necesidad de for- mar adecuadamente al personal que realiza la circuncisión para evitar complicaciones severas. Palabras Clave: Fimosis; Circuncisión, Varón; Fibrosis. Severe penile fibrotic reaction secondary to a non- absorbable suture: a case report

Introducción: La circuncisión es uno de los procedimientos quirúrgicos urológicos más frecuentemente realizados en la población pediátrica en todo el mundo. Las complicaciones, aunque infrecuentes,pueden ser graves. Caso clínico: Presentamos el caso de un paciente varón senegalés de10 años que fue sometido a una circuncisión ritual en la primera infanciay que desarrolló una tumoración circunferencial progresiva en el cuerpodel pene sin otra sintomatología asociada. Se realizó una exploraciónquirúrgica y se identificó un rodete peneano de aspecto fibrótico que seinterpretó como lesión secundaria al material de sutura no absorbibleutilizado en la cirugía anterior. Se realizó una exéresis del tejido afectoy una prepucioplastia a demanda. Por limitaciones técnicas, no se pudoanalizar el tejido resecado y por tanto no se pudo confirmar histopatológicamente el diagnóstico. El paciente evolucionó favorablemente. Conclusiones: Este caso pone de manifiesto la necesidad de formar adecuadamente al personal que realiza la circuncisión para evitarcomplicaciones severas.(AU)

Introduction: Circumcision is one of the most frequent urologicalsurgical procedures in the pediatric population globally. Complications,although rare, can be severe.Clinical case: We present the case of a Senegalese 10-year-oldmale patient who had undergone ritual circumcision in his early childhood and developed a progressive circumferential tumor in the penilebody with no further associated symptoms. Surgical exploration was carried out. A fibrotic-looking penile ring, which was interpreted asan injury secondary to the non-absorbable suturing material used inthe previous surgery, was identified. The tissue involved was removed,and on-demand preputioplasty was conducted. Due to technical limitations, the resected tissue could not be analyzed, which means diagnosiscould not be histopathologically confirmed. The patient had a favorableprogression. Conclusions: This case demonstrates that the medical personnelin charge of performing circumcisions should be adequately trained inorder to prevent severe complications.(AU)

Clozapine but not lithium reverses aberrant tyrosine uptake in patients with bipolar disorder.

RATIONALE: Availability of the dopamine and noradrenaline precursor tyrosine is critical for normal functioning, and deficit in tyrosine transport across cell membrane and the blood-brain barrier has been reported in bipolar disorder and schizophrenia. Clozapine and lithium are two psychoactive agents used to treat psychosis, mood disorders and suicidal behavior, but their mechanism of action remains largely unknown. OBJECTIVE: To characterize immediate and delayed differences in tyrosine uptake between healthy controls (HC) and bipolar patients (BP) and see if these differences could be normalized by either clozapine, lithium or both. A second objective was to see if clozapine and lithium have additive, antagonistic or synergistic effects in this. METHOD: Fibroblasts from five HC and five BP were incubated for 5 min or 6 h with clozapine, lithium, or combination of both. Radioactive labelled tyrosine was used to quantify tyrosine membrane transport. RESULTS: There was significantly reduced tyrosine uptake at baseline in BP compared to HC, a deficit that grew with increasing incubation time. Clozapine selectively increased tyrosine uptake in BP and abolished the deficit seen under baseline conditions, while lithium had no such effect. Combination treatment with clozapine and lithium was less effective than when clozapine was used alone. CONCLUSIONS: There was significant deficit in tyrosine transport in BP compared to HC that was reversed by clozapine but not lithium. Clozapine was more effective when used alone than when added together with lithium. Potential clinical implications of this will be discussed.

Targeted Electromyographic Biofeedback With Endoanal Electrostimulation for Anal Incontinence.

Purpose. Anal incontinence (AI) is a disabling condition with a variable response to conservative physical therapies. We assess the utility of combining electromyographic biofeedback with endoanal electrostimulation targeted to the weakest areas of the pelvic floor using the MAPLe® probe (Multiple Array Probe Leiden Novuqare). Methods. Patients with AI unresponsive to conservative measures were assessed before and after treatment with anorectal manometry (ARM), electromyography (EMG), Wexner Continence Scoring, Visual Analog Scoring (VAS), FIQL and SF-12 quality of life determination. Results. Of 29 patients in the final analysis, there was an improvement in the mean Wexner continence score from 13.59 to 8.03 and a concomitant improvement in the reported VAS from 3.45 to 6.72. Both Wexner continence and VAS scores were maintained during follow-up. Maximum voluntary manometric contraction significantly improved from 91.76 mmHg to 110.33 mmHg with no changes in resting pressure. The EMG values ​​(µV) that significantly improved included the average and peak resistance, the average general voluntary contraction, and the average and peak voluntary contraction for both the external anal sphincter and the puborectalis. In the FIQL, behavior, depression and shame domains improved after treatment and during follow-up with lifestyle improvements detected at 6 and 12 months. Physical and mental components of the SF-12 improved at 6 and 12 months. Conclusions. Targeted electromyographic biofeedback and endoanal electrostimulation using MAPLe® probe in AI patients sustainably improves objective ARM and EMG parameters along with subjective reporting of continence severity, VAS, and quality of life.

Tratamiento de infecciones graves por Acinetobacter baumannii / Treatment of Acinetobacter baumannii severe infections

El Acinetobacter baumannii es un patógeno gramnegativo, multirresistente (MR) que causa infecciones nosocomiales, especialmente en las unidades de cuidados intensivos (UCI) y en los pacientes inmunocomprometidos. El A. baumannii ha desarrollado una resistencia antibiótica de amplio espectro, asociada con alta tasa de mortalidad entre los pacientes infectados comparada con las otras especies de Acinetobacter no baumannii. En relación con el impacto clínico, las cepas resistentes están asociadas con incremento de la estadía hospitalaria y de la mortalidad. El A. baumannii puede causar diferentes infecciones, especialmente neumonía asociada a la ventilación mecánica, bacteriemia, e infección de piel y partes blandas, entre otras. Los factores de riesgo más frecuentes para la adquisición de A. baumannii MR son el uso previo de antibióticos, la asistencia respiratoria mecánica, la estadía en la UCI y en el hospital, la severidad de la enfermedad y el uso de dispositivos médicos. Los esfuerzos actuales están focalizados en determinar todos los mecanismos de resistencia descritos en el A. baumannii, con el objetivo de identificar esquemas terapéuticos más efectivos (AU)

Acinetobacter baumannii is a Gram-negative, multidrug-resistant (MDR) pathogen that causes nosocomial infections, especially in intensive care units (ICUs) and immunocompromised patients. A. baumannii has developed a broad spectrum of antimicrobial resistance, associated with a higher mortality rate among infected patients compared with other non-baumannii species. In terms of clinical impact, resistant strains are associated with increases in both in-hospital length of stay and mortality. A. baumannii can cause a variety of infections, especially ventilator-associated pneumonia, bacteremia, and skin wound infections, among others. The most common risk factors for the acquisition of MDR A. baumannii are previous antibiotic use, mechanical ventilation, length of ICU and hospital stay, severity of illness, and use of medical devices. Current efforts are focused on addressing all the antimicrobial resistance mechanisms described in A. baumannii, with the objective of identifying the most promising therapeutic scheme (AU)

Determinants of mortality in cancer patients with unscheduled admission to the Intensive Care Unit: A prospective multicenter study.

OBJECTIVES: To analyze clinical features associated to mortality in oncological patients with unplanned admission to the Intensive Care Unit (ICU), and to determine whether such risk factors differ between patients with solid tumors and those with hematological malignancies. DESIGN: An observational study was carried out. SETTING: A total of 123 Intensive Care Units across Spain. PATIENTS: All cancer patients with unscheduled admission due to acute illness related to the background oncological disease. INTERVENTIONS: None. MAIN VARIABLES: Demographic parameters, severity scores and clinical condition were assessed, and mortality was analyzed. Multivariate binary logistic regression analysis was performed. RESULTS: A total of 482 patients were included: solid cancer (n=311) and hematological malignancy (n=171). Multivariate regression analysis showed the factors independently associated to ICU mortality to be the APACHE II score (OR 1.102; 95% CI 1.064-1.143), medical admission (OR 3.587; 95% CI 1.327-9.701), lung cancer (OR 2.98; 95% CI 1.48-5.99) and mechanical ventilation after the first 24h of ICU stay (OR 2.27; 95% CI 1.09-4.73), whereas no need for mechanical ventilation was identified as a protective factor (OR 0.15; 95% CI 0.09-0.28). In solid cancer patients, the APACHE II score, medical admission, antibiotics in the previous 48h and lung cancer were identified as independent mortality indicators, while no need for mechanical ventilation was identified as a protective factor. In the multivariate analysis, the APACHE II score and mechanical ventilation after 24h of ICU stay were independently associated to mortality in hematological cancer patients, while no need for mechanical ventilation was identified as a protective factor. Neutropenia was not identified as an independent mortality predictor in either the total cohort or in the two subgroups. CONCLUSIONS: The risk factors associated to mortality did not differ significantly between patients with solid cancers and those with hematological malignancies. Delayed intubation in patients requiring mechanical ventilation might be associated to ICU mortality.

Treatment of Acinetobacter baumannii severe infections.

Acinetobacter baumannii is a Gram-negative, multidrug-resistant (MDR) pathogen that causes nosocomial infections, especially in intensive care units (ICUs) and immunocompromised patients. A. baumannii has developed a broad spectrum of antimicrobial resistance, associated with a higher mortality rate among infected patients compared with other non-baumannii species. In terms of clinical impact, resistant strains are associated with increases in both in-hospital length of stay and mortality. A. baumannii can cause a variety of infections, especially ventilator-associated pneumonia, bacteremia, and skin wound infections, among others. The most common risk factors for the acquisition of MDR A. baumannii are previous antibiotic use, mechanical ventilation, length of ICU and hospital stay, severity of illness, and use of medical devices. Current efforts are focused on addressing all the antimicrobial resistance mechanisms described in A. baumannii, with the objective of identifying the most promising therapeutic scheme.

Cigarette smoke induces pulmonary arterial dysfunction through an imbalance in the redox status of the soluble guanylyl cyclase.

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking (CS), is one of the most common diseases globally. Some COPD patients also develop pulmonary hypertension (PH), a severe complication that leads to premature death. Evidence suggests reactive oxygen species (ROS) involvement in COPD and PH, especially regarding pulmonary artery smooth muscle cells (PASMC) dysfunction. However, the effects of CS-driven oxidative stress on the pulmonary vasculature are not completely understood. Herein we provide evidence on the effects of CS extract (CSE) exposure on PASMC regarding ROS production, antioxidant response and its consequences on vascular tone dysregulation. Our results indicate that CSE exposure promotes mitochondrial fission, mitochondrial membrane depolarization and increased mitochondrial superoxide levels. However, this superoxide increase did not parallel a counterbalancing antioxidant response in human pulmonary artery (PA) cells. Interestingly, the mitochondrial superoxide scavenger mitoTEMPO reduced mitochondrial fission and membrane potential depolarization caused by CSE. As we have previously shown, CSE reduces PA vasoconstriction and vasodilation. In this respect, mitoTEMPO prevented the impaired nitric oxide-mediated vasodilation, while vasoconstriction remained reduced. Finally, we observed a CSE-driven downregulation of the Cyb5R3 enzyme, which prevents soluble guanylyl cyclase oxidation in PASMC. This might explain the CSE-mediated decrease in PA vasodilation. These results provide evidence that there might be a connection between mitochondrial ROS and altered vasodilation responses in PH secondary to COPD, and strongly support the potential of antioxidant strategies specifically targeting mitochondria as a new therapy for these diseases.