The comparative efficacy and safety of biologics and small molecules for treating patients with ulcerative colitis in Portugal: a systematic literature review and network meta-analysis.

OBJECTIVE: The use of biological drugs to treat ulcerative colitis (UC) represents a clear added value; nevertheless, many patients do not have a sustained response to these drugs. Small molecules were recently approved for the treatment of UC in Portugal. This network meta-analysis aimed to compare the efficacy and safety of the different therapies, including biological and small molecules, in patients prior exposed to biological treatment. MATERIALS AND METHODS: A systematic review of the literature was performed on January 6, 2022, identifying all the relevant reports about the efficacy and safety of biologics (adalimumab, golimumab, infliximab, vedolizumab, ustekinumab) and small molecules (upadacitinib, filgotinib, tofacitinib) in the treatment of UC in Portugal. Network meta-analysis (NMA) was conducted using Bayesian Markov Chain Monte Carlo simulations. Results were presented in median Odds Ratio and Surface Under the Cumulative RAnking (SUCRA) score for each treatment. RESULTS: Treatment of UC is divided into two phases: induction and maintenance. Upadacitinib 45 mg was the most efficacious therapy in achieving clinical remission and response and endoscopic improvement in the induction phase. Concerning the maintenance phase, upadacitinib 30 mg performed better than ustekinumab formulations in clinical remission and response, and endoscopic improvement. Regarding safety, there were no significant differences between all the drugs included in the analysis. CONCLUSIONS: This network meta-analysis showed that upadacitinib reflects better efficacy compared to the available treatments for bio-exposed patients with moderate to severe UC. The safety profile is comparable to the other drugs.

Dynamic microbial response under ethanol stress to monitor Saccharomyces cerevisiae activity in different initial physiological states.

Dynamic Saccharomyces cerevisiae responses to increasing ethanol stresses were investigated to monitor yeast viability and to optimize bioprocess performance when gradients occurred due to the specific configuration of multi-stage bioreactors with cell recycling or of large volume industrial bioreactors inducing chemical heterogeneities. Twelve fed-batch cultures were carried out with initial ethanol concentrations (P(in)) ranging from 5 g l(-1) to 110 g l(-1) with three different inoculums in different physiological states in terms of viability and quantity of ethanol produced (P(o)). For a given initial cell viability of 50%, the time to reach the maximum growth rate and maximum ethanol production rate was dependent on the difference P(in) - P(o). Whatever the initial physiological state, when the initial ethanol concentration P(in) reached 100 g l(-1), the yeasts died. Experimental results showed that the initial physiological state of the yeast was the major parameter to determine, the microorganisms' capacities to adapt and resist environmental changes.

Estudio videopolisomnográfico en un paciente con sospecha de insomnio familiar fatal / Video-polisomnografic monitoring in a fatal familial insomnia clinical suspect case

Objetivo. Demostrar las alteraciones neurofisiológicas y del comportamiento del ciclo vigilia-sueño características del insomnio familiar fatal (IFF), en un paciente con sospecha clínica y posterior diagnóstico genético. Paciente y método. Varón de 39 años. Presenta historia familiar compatible con IFF. En el curso de 5 meses manifiesta impotencia, insomnio progresivo y episodios diurnos de sueño con apneas, mioclonías, automatismos y gesticulaciones. Al ingreso, presenta diplopía, hipertensión arterial e hiperhidrosis. Se realizó una monitorización videopolisomnográfica durante 24 h. Cada segundo de registro fue clasificado según los criterios de Sforza (1995). Resultados. Vigilia: ojos cerrados, actividad motora en miembros inferiores. Ritmo alfa posterior reactivo a 8-9 Hz. Sueño: breves episodios de sueño no REM y REM, de características atípicas, con ausencia de sueño profundo y disminución de actividad spindle, en asociación con mioclonías, gesticulaciones y apneas. Insomnio de conciliación. Tras indicar alprazolam (1 mg por vía oral y 0,5 mg sublingual), presentó patrón no REM durante 3,5 h, sin actividad motora y sin apneas. Discusión y conclusiones. Los hallazgos polisomnográficos se caracterizaron por grave alteración de la organización cíclica del sueño, disminución del tiempo total de sueño y patrones no REM y REM atípicos. La administración de alprazolam permitió aumentar el sueño nocturno, con desaparición de las sacudidas motoras y las apneas (AU)

Objective. To demonstrate the neurophysiologic and behavior disorders in the wake-sleep cycle typical of fatal familial insomnia (IFF), in a case with clinical suspect and latter genetic diagnostic. Patient and method. Male 39 year old. Family history of an IFF syndrome. Within 5 months he developed impotence, progressive insomnia and episodes of daytime somnolence associated with apneas, myoclonus and anormal motor behavior. He was hospitalized with diplopia, high blood pressure and hyperhidrosis. We carried out a video-polisomnografic long-term monitoring during 24 hours. Each second of the record was classified according to the de Sforza criterium (1995). Results. Waking: closed eyes, restless movements of legs. Responsive posterior alpha rhythm at 8-9 Hz. Sleep: brief episodes of "NREM" and "REM" sleep of atipical features, such as absence of slow wave sleep and marked reduction of spindle frequency activity, with myoclonus, gesturing and apneas. At night, impossibility in falling asleep. After alprazolam, "NREM" sleep during 3,5 hours, without motor activity nor apneas. Discussion and conclusions. The polisomnografic findings characterized by severe alteration of the cyclic sleep organization, reduction in total sleep time and atipical patterns of "NREM" and "REM" sleep. Administration of alprazolam (1 mg orally and 0.5 mg sublingually) allowed increasing night-time sleep, dissapearing jerks and apneas (AU)

[Disorders affecting the digestive system during sleep]. / Alteraciones del sistema digestivo durante el sueño.

AIMS: In this work we review the major publications dealing with disorders that affect the digestive system and how they are related to sleep. Development. Sleep disorders occur in 12-25% of the general population and a large percentage of these pathologies are related to disorders of the digestive system. We review the different pathologies and symptoms linked to the digestive tract that give rise to sleep disorders. The study first examined the upper digestive tract, that is, the teeth and teeth grinding, and we then went on to look at gastroesophageal reflux, esophageal motility disorders, peptic ulcer disease, cholelithiasis, gastric ulcer, irritable bowel, proctalgia, the extent to which the disorders are related to pregnancy, disorders at the paediatric age and eating disorders. CONCLUSIONS: Digestive pains during sleep form a heterogeneous clinical picture that disrupts patients' sleep and exerts an influence on their quality of daily living, which in turn may affect sleep and favour the appearance of pains. To date these symptoms have received relatively little attention, but in the few studies that have been carried out, it has not been possible to establish with any degree of accuracy whether sleep and the digestive system share common control mechanisms or not. Research into this type of disorders could help to prevent the appearance of the complications that appear in these clinical pictures.

Alteraciones del sistema digestivo durante el sueño / Disorders affecting the digestive system during sleep

Objetivo. En el presente trabajo se revisan las principales publicaciones que tratan sobre alteraciones del sistema digestivo y su relación con el sueño. Desarrollo. Los trastornos del sueño se dan en el 12-25 por ciento de la población general; una gran parte de esta patología tiene relación con alteraciones del sistema digestivo; realizamos una revisión de las distintas patologías digestivas y los cuadros relacionados con el tubo digestivo que acarrean trastornos de sueño. Comenzamos por el sistema digestivo superior, en los dientes, con el bruxismo, y continuamos con la enfermedad por reflujo gastroesofágico, los trastornos de la motilidad esofágica, la enfermedad ulcerosa péptica, la colelitiasis, la úlcera gástrica, el intestino irritable, la proctalgia, la relación de los trastornos con el embarazo, las alteraciones en la edad pediátrica y los trastornos de la alimentación. Conclusiones. Los dolores digestivos durante el sueño forman un cuadro heterogéneo de patologías que interrumpen el sueño del paciente e influyen sobre su calidad de vida diurna; ésta, a su vez, puede influir sobre el sueño y favorecer la aparición de dolores. Estos cuadros se han estudiado hasta ahora relativamente poco; cuando sí se han estudiado, no se ha llegado a establecer con precisión si existen mecanismos de control comunes entre el sueño y el aparato digestivo. La investigación de este tipo de trastornos podría llevar a evitar muchas de las complicaciones que aparecen en estos cuadros (AU)

Aims. In this work we review the major publications dealing with disorders that affect the digestive system and how they are related to sleep. Development. Sleep disorders occur in 12-25% of the general population and a large percentage of these pathologies are related to disorders of the digestive system. We review the different pathologies and symptoms linked to the digestive tract that give rise to sleep disorders. The study first examined the upper digestive tract, that is, the teeth and teeth grinding, and we then went on to look at gastroesophageal reflux, esophageal motility disorders, peptic ulcer disease, cholelithiasis, gastric ulcer, irritable bowel, proctalgia, the extent to which the disorders are related to pregnancy, disorders at the paediatric age and eating disorders. Conclusions. Digestive pains during sleep form a heterogeneous clinical picture that disrupts patients’ sleep and exerts an influence on their quality of daily living, which in turn may affect sleep and favour the appearance of pains. To date these symptoms have received relatively little attention, but in the few studies that have been carried out, it has not been possible to establish with any degree of accuracy whether sleep and the digestive system share common control mechanisms or not. Research into this type of disorders could help to prevent the appearance of the complications that appear in these clinical pictures (AU)

[Lipid peroxidation in adult epileptic patients treated with valproic acid]. / Peroxidación lipídica en pacientes epilépticos adultos tratados con ácido valproico.

INTRODUCTION: Free radicals play an important role as regulatory mediators in cellular signalling processes; however, when overproduced or when antioxidant defence systems are weakened, they are cause of cellular damage. Excessive amount of free radical production has been related with a variety conditions, like aging, different kind of diseases, and xenobiotics biotransformation; this last process includes the metabolism of lipid soluble drugs. An increase in oxidative stress has been described in series of treated epileptic patients. OBJECTIVE: To evaluate the susceptibility to plasma lipid peroxidation in samples from epileptic patients treated with valproic acid monotherapy, studying if the formation of lipid peroxides was related with plasma drug concentration, patients' sex or the kind of epilepsy suffered. PATIENTS AND METHODS: Peroxidated lipids (LPO) were measured by spectrofluorometry before and after induction of an oxidative Fenton reaction in 76 epileptic patients and 4 healthy subjects. RESULTS: After induction of the Fenton reaction, but not in basal conditions, lipid peroxidation showed a lineal relationship with valproate plasma levels. Oxidized LPO values were also significantly higher in samples from patients with partial epilepsies than in those with generalized epilepsies. Likewise, a significant gender effect was observed, being values from epileptic women noticeably higher than those of epileptic men. CONCLUSIONS: Plasma from epileptic patients receiving valproic acid evidences an increased vulnerability to lipid peroxidation which seems to be related with drug amount in the body, subject's sex, and epilepsy type.

Peroxidación lipídica en pacientes epilépticos adultos tratados con ácido valproico / Lipid peroxidation in adult epileptic patients treated with valproic acid

Introducción. Aunque los radicales libres son mediadores importantes en la regulación de algunos procesos celulares, pueden causar citotoxicidad cuando se producen en exceso o las defensas antioxidantes disminuyen, y se han implicado en la patogenia de numerosas enfermedades. Asimismo, los fármacos, fundamentalmente a través de la producción de metabolitos intermediarios, pueden aumentar el estrés oxidativo; en este sentido, diversos autores han observado alteraciones del metabolismo oxidativo en pacientes epilépticos tratados. Objetivo. Evaluar la susceptibilidad a la peroxidación lipídica en epilépticos adultos tratados con ácido valproico (VPA), y comprobar si ésta guarda relación con la concentración plasmático del fármaco, el sexo del enfermo o el tipo de epilepsia padecido. Pacientes y métodos. Los lípidos peroxidados (LPO) se midieron mediante espectrofluorometría antes y después de la inducción de una reacción oxidativa de tipo Fenton en el plasma de 76 pacientes epilépticos y 48 sujetos sanos. Resultados. La formación de LPO tras la oxidación mostró una relación lineal positiva con las concentraciones plasmáticas de VPA. Asimismo, fue superior en los pacientes con epilepsias parciales que en aquellos con epilepsias generalizadas. Se observó también un efecto significativo del sexo, puesto que los valores de LPO se elevaron más en las mujeres que en los varones epilépticos. Conclusiones. En el plasma de los pacientes tratados con VPA se aprecia una vulnerabilidad al estrés oxidativo directamente proporcional a la concentración plasmática del fármaco, más acentuada en las mujeres que en los hombres. Ésta, por otra parte, parece ser mayor en los pacientes con epilepsias parciales (AU)

Introduction. Free radicals play an important role as regulatory mediators in cellular signalling processes; however, when overproduced or when antioxidant defence systems are weakened, they are cause of cellular damage. Excessive amount of free radical production has been related with a variety conditions, like aging, different kind of diseases, and xenobiotics biotransformation; this last process includes the metabolism of lipid soluble drugs. An increase in oxidative stress has been described in series of treated epileptic patients. Objective. To evaluate the susceptibility to plasma lipid peroxidation in samples from epileptic patients treated with valproic acid monotherapy, studying if the formation of lipid peroxides was related with plasma drug concentration, patients’ sex or the kind of epilepsy suffered. Patients and methods. Peroxidated lipids (LPO) were measured by spectrofluorometry before and after induction of an oxidative Fenton reaction in 76 epileptic patients and 4 healthy subjects. Results. After induction of the Fenton reaction, but not in basal conditions, lipid peroxidation showed a lineal relationship with valproate plasma levels. Oxidized LPO values were also significantly higher in samples from patients with partial epilepsies than in those with generalized epilepsies. Likewise, a significant gender effect was observed, being values from epileptic women noticeably higher than those of epileptic men. Conclusions. Plasma from epileptic patients receiving valproic acid evidences an increased vulnerability to lipid peroxidation which seems to be related with drug amount in the body, subject’s sex, and epilepsy type (AU)