Persistence and effectiveness of guselkumab treatment in patients with moderate-to-severe plaque psoriasis in a non-interventional real-world setting: The SPRING study.

BACKGROUND: Guselkumab is a monoclonal antibody that blocks the IL-23 pathway with proven efficacy and tolerability in the treatment of moderate-to-severe plaque psoriasis. OBJECTIVES: To assess the persistence, effectiveness and safety of guselkumab in patients with moderate-to-severe psoriasis in real clinical practice in Spain. METHODS: SPRING was a Phase IV, retrospective and non-interventional study analysing patients with moderate-to-severe plaque psoriasis who had initiated guselkumab under clinical practice conditions at least 12 months before inclusion in the study. The primary endpoint was persistence (non-persistence: discontinuation or interruption ≥90 days). Effectiveness was assessed using the Psoriasis Area Severity Index (PASI) and Investigator Global Assessment (IGA). Dermatology Life Quality Index (DLQI) and safety were also evaluated. RESULTS: A total of 284 patients were included between September 2020 and June 2021. The 1-year probability of persistence was 89.6% (86.1%-93.3%). The 1-year probability of persistence was also calculated according to prior biologic treatment, being 90.3% for biologic-naïve patients and 89.5% for patients who received one or more biologic therapies before guselkumab. Additionally, patients were also classified based on the frequency of the administration of guselkumab treatment; the 1-year probability of persistence was 91.9% in patients receiving guselkumab according to the Summary of Product Characteristics and 89.3% in patients with lengthened intervals of administration. After 1 year, PASI 90 was achieved by 56.4% of patients, IGA 0/1 response and BSA <3% were achieved by 65.5% and 77.8% of patients, respectively, and 65.8% achieved a minimal clinically significant difference (>4-point reduction) in the DLQI score at 1 year. Twenty-six adverse reactions (4 of them serious) were reported in 16 patients. CONCLUSIONS: This study suggests that guselkumab has high persistence in real clinical practice in Spain, independently of the previous biologic treatments and changes in the frequency of treatment. Effectiveness and safety are consistent with previously published data.

Beaming in the Charcot foot: A case series with 12-month minimum follow-up.

BACKGROUND: Charcot neuropathic arthropathy is a progressive degeneration of the weightbearing joints of the foot induced by denervation and disturbance of sensorial perception. This entity clinically behaves as a destructive fast-progressive arthropathy, resulting in loss of independent walking and often requiring amputation of the leg. This study analyzes our experience with midfoot realignment arthrodesis and stabilization by intramedullary beaming in patients with Charcot diabetic foot as a limb-sparing procedure. METHODS: Patients with Charcot foot treated in our Foot and Ankle unit between January 2018 and December 2019 were analyzed. In all of the patients beaming technique was performed: open reduction and stabilization by a midfoot medial fusion beam and a lateral fusion bolt. Demographical, clinical and radiological pre and post-surgery data were assessed. The primary outcome measure was defined as an autonomous ambulation through an ulcer-free plantigrade foot. A minimum follow-up of 12 months was performed. RESULTS: A total of 5 patients were treated. Median age 64 years, mean follow-up 25 months (12-31). An ulcer-free plantigrade foot was obtained in 80% of the patients. Complications were observed in 80% of patients: 1 deep infection, 2 hardware failure, 3 Charcot foot progression. Rate of reoperation 40%, including 1 amputation. Significant improvement in all radiographic angles was observed. CONCLUSION: Beaming the medial and lateral columns of the foot in patients with Charcot foot enabled the restoration of a functional plantigrade foot and an ulcer-free autonomous ambulation, despite a relatively high complication rate. LEVEL OF EVIDENCE: IV, prospective case series.

Desmontaje por efecto cut-out en el enclavado de fracturas pertrocantéreas de fémur: ¿cuál es el tratamiento de rescate de elección? / Removal due to cut-out effect in pertrochanteric femoral fractures: what is the rescue treatment of choice?

Objetivo. Comparar los resultados funcionales de las distintas opciones terapéuticas, y analizar los factores técnicos asociados al cut-out. Material y método. Estudio de cohortes retrospectivo de 56 pacientes diagnosticados de cut-out entre 2000-2010, divididos en dos grupos en función del tratamiento de rescate: artroplastia frente a conservar la cabeza femoral (alternativo). Se analizaron datos demográficos, características de la fractura y osteosíntesis, tip to apex distance (TAD), seguimiento, complicaciones y capacidad funcional final. Resultados. Grupo artroplastia 36 pacientes (64,28%) y 20 (35,72%) grupo alternativo. Comparables en parámetros demográficos, comorbilidades, patrón de fractura y características de la osteosíntesis. Se observó poca variabilidad interobservador (k = 0,83; IC 95%: 0,78-0,88) en el análisis radiográfico; con un TAD medio de 28,66 mm (p = 0,01) y un déficit de reducción en el 39,3% (p = 0,001). La mediana de cut-out fue de 60 días (artroplastia 90, alternativo 18; p = 0,001). Seguimiento mínimo 12 meses, con tasa de complicaciones similar en ambos grupos (p = 0,16) y de reintervención del 3,57% (p = 0,01). La capacidad funcional final fue mayor en el grupo de artroplastia (p = 0,004). Conclusión. El tratamiento de rescate con artroplastia ofrece mejores resultados funcionales, considerándolo el tratamiento de elección en pacientes ancianos, aunque la tasa de reintervención es mayor. Recomendamos nuevo enclavado antes que artroplastia en los casos de cut-out temprano (< 4 semanas) en aquellos casos que se mantenga la integridad de la cabeza femoral. Un déficit de reducción de la fractura es el principal factor predictor de fallo a corto plazo; un TAD por encima de 20 mm lo es a medio-largo plazo (AU)

Objective. The goal of the study was to compare functional results in different treament options in cutting-out, and analize factors associated to failure. Material and methods. Retrospective cohort study in 56 patients diagnosed with cutting-out between 2000-2010. Groups were based on rescue treatment: arthroplasty versus alternative treatment. Demographics, fracture characteristics, osteosynthesis, tip to apex distance (TAD), follow-up, complications, and final functional capacity were analyzed. Results. Rescue treatment: 36 (64.28%) hip replacement (arthroplasty group), and 20 (35.72%) alternative treatment preserving femoral head (alternative group). Groups comparable on demographic parameters, fracture pattern and osteosynthesis characteristics. Radiography analysis: low inter-observer variability (k = 0.83, 95% CI 0.78-0.88), mean TAD 28.66 mm (arthroplasty group 32.9 mm, 21.5 mm control group; p = 0.01), insufficient fracture reduction 39.3% (p = 0.001). Cutting-out diagnosis median 60 days (arthroplasty group 90 days, 18 days alternative group; p = 0.001). Follow up at least 12 months from rescue treatment. Similar complications rate in both groups (p = 0.16). Re-operation rate 3.57% (11.7% arthroplasty group, alternative group 0%; p = 0.01). Better final functional capacity in arthroplasty group (p = 0.004). Discussion. Hip arthroplasty offers better results, being considered the gold standard in geriatric patients, although re-operation rate is higher. We recommend new nailing before arthroplasty in early failure (4 weeks) in patients with femoral head integrity. An insufficient fracture reduction is the main short term factor predicting failure; and TAD higher than 20 mm is a middle-long term one (AU)

[Removal due to cut-out effect in pertrochanteric femoral fractures: what is the rescue treatment of choice?]. / Desmontaje por efecto cut-out en el enclavado de fracturas pertrocantéreas de fémur: ¿cuál es el tratamiento de rescate de elección?

OBJECTIVE: The goal of the study was to compare functional results in different treament options in cutting-out, and analize factors associated to failure. MATERIAL AND METHODS: Retrospective cohort study in 56 patients diagnosed with cutting-out between 2000-2010. Groups were based on rescue treatment: arthroplasty versus alternative treatment. Demographics, fracture characteristics, osteosynthesis, tip to apex distance (TAD), follow-up, complications, and final functional capacity were analyzed. RESULTS: Rescue treatment: 36 (64.28%) hip replacement (arthroplasty group), and 20 (35.72%) alternative treatment preserving femoral head (alternative group). Groups comparable on demographic parameters, fracture pattern and osteosynthesis characteristics. Radiography analysis: low inter-observer variability (k=0.83, 95% CI 0.78-0.88), mean TAD 28.66mm (arthroplasty group 32.9mm, 21.5mm control group; p=0.01), insufficient fracture reduction 39.3% (p=0.001). Cutting-out diagnosis median 60 days (arthroplasty group 90 days, 18 days alternative group; p=0.001). Follow up at least 12 months from rescue treatment. Similar complications rate in both groups (p=0.16). Re-operation rate 3.57% (11.7% arthroplasty group, alternative group 0%; p=0.01). Better final functional capacity in arthroplasty group (p=0.004). DISCUSSION: Hip arthroplasty offers better results, being considered the gold standard in geriatric patients, although re-operation rate is higher. We recommend new nailing before arthroplasty in early failure (4 weeks) in patients with femoral head integrity. An insufficient fracture reduction is the main short term factor predicting failure; and TAD higher than 20mm is a middle-long term one.

[Autologous concentrated bone marrow graft in the treatment of femoral head avascular necrosis: clinical outcome after two years of follow up in a non-controlled prospective study]. / Implante de concentrado de médula ósea autógeno en el tratamiento de la necrosis isquémica de cabeza femoral: evolución clínica al segundo año de seguimiento de un estudio prospectivo no controlado.

OBJECTIVE: To assess the efficacy of implanting concentrated bone marrow rich in mesenchymal stem cells (MSC) for the treatment of femoral head avascular necrosis (AVN) to prevent or delay total hip replacement (THR). MATERIAL AND METHODS: A single-centre, prospective, non-controlled clinical study was conducted on patients with a diagnosis of AVN. The parameters assessed were, patient demographics, Harris Hip Score (HHS), imaging test (X-ray and NMR), and staging using the Arlet-Ficat scale. The patients were followed up for 1, 6, 12 and 24 months. The bone marrow was aspirated from the iliac crest, concentrated with the Harvest SmartPReP 2 system, and infused into the necrotic area by means of core decompression. RESULTS: A total of 22 hips in 17 patients were recruited between the years 2006 to 2012, with a minimum follow-up of 2 years. A mean of 119.5 mL of aspirate was extracted, with 15.25 ml of MSC being implanted. During the first 2 years of the infusion, 5 hips (24.7%) required THR, with no differences in the baseline Arlet-Ficat stage, and 4 of these (80%) had femoral head involvement equal to or higher than 30%. A significant increase of 14.27 (P=.026) in the HHS and a 0.98 (P=.089) decrease in the VAS was observed two years after the infusion in the remaining 17 hips. The results suggest that the infusion of concentrated bone marrow rich in MSC, combined with surgical decompression of the nucleus, improves hip function (HHS), and avoids THR in 75.3% of patients with AVN treated during the first 2 years.

Implante de concentrado de médula ósea autógeno en el tratamiento de la necrosis isquémica de cabeza femoral: evolución clínica al segundo año de seguimiento de un estudio prospectivo no controlado / Autologous concentrated bone marrow graft in the treatment of femoral head avascular necrosis: Clinical outcome after two years of follow up in a non-controlled prospective study

Objetivo. Evaluar la utilidad del aporte de concentrado de médula ósea rico en células troncales mesenquimales (MSC) como tratamiento de la necrosis avascular de cabeza femoral (NAV) para evitar o retrasar la artroplastia total de cadera (ATC). Material y métodos. Estudio clínico unicéntrico, prospectivo, no controlado, de pacientes con diagnóstico de NAV. Evaluación de parámetros demográficos, Harris Hip Score (HHS), pruebas de imagen (radiografía y RMN); estadificación mediante escala de Arlet-Ficat. Seguimiento a 1, 6, 12 y 24 meses. Aspirado de médula ósea de cresta ilíaca, concentrado con sistema Harvest SmartPReP 2, e infusión en zona de necrosis mediante forages. Resultados. Veintidós caderas en 17 pacientes fueron reclutados entre los años 2006-2012, seguimiento mínimo 2 años. Extracción media de 119,5ml de aspirado, implantándose 15,25ml de concentrado de MSC. Durante los primeros 2 años de la infusión 5 caderas (24,7%) precisaron ATC, sin diferencias en estadio de Ficat basal, y 4 (80%) de ellas presentaban afectación de cabeza femoral igual o superior al 30%. En las 17 caderas restantes, se observó a los 2 años de la infusión un aumento significativo del HHS (14,27) (p=0,026) y disminución del dolor (0,98) en la EVA (p=0,089). Nuestros resultados sugieren que la infusión de concentrado de médula ósea rico en MSC asociado a descompresión quirúrgica del núcleo mejora significativamente la funcionalidad de la cadera (HHS) y evita la ATC en el 75,3% de los pacientes con NAV tratados durante los primeros 2 años (AU)

Objective. To assess the efficacy of implanting concentrated bone marrow rich in mesenchymal stem cells (MSC) for the treatment of femoral head avascular necrosis (AVN) to prevent or delay total hip replacement (THR). Material and methods. A single-centre, prospective, non-controlled clinical study was conducted on patients with a diagnosis of AVN. The parameters assessed were, patient demographics, Harris Hip Score (HHS), imaging test (X-ray and NMR), and staging using the Arlet-Ficat scale. The patients were followed up for 1, 6, 12 and 24 months. The bone marrow was aspirated from the iliac crest, concentrated with the Harvest SmartPReP 2 system, and infused into the necrotic area by means of core decompression. Results. A total of 22 hips in 17 patients were recruited between the years 2006 to 2012, with a minimum follow-up of 2 years. A mean of 119.5mL of aspirate was extracted, with 15.25ml of MSC being implanted. During the first 2 years of the infusion, 5 hips (24.7%) required THR, with no differences in the baseline Arlet-Ficat stage, and 4 of these (80%) had femoral head involvement equal to or higher than 30%. A significant increase of 14.27 (P=.026) in the HHS and a 0.98 (P=.089) decrease in the VAS was observed two years after the infusion in the remaining 17 hips. The results suggest that the infusion of concentrated bone marrow rich in MSC, combined with surgical decompression of the nucleus, improves hip function (HHS), and avoids THR in 75.3% of patients with AVN treated during the first 2 years (AU)

Posible validez de medicamentos termolábiles fuera de las condiciones de conservación recomendadas por el fabricante / No disponible

El farmacéutico de hospital, según Ley 25/1990, de 20 de diciembre del Medicamento, debe garantizar la correcta conservación de los medicamentos tanto en el servicio de farmacia comoen los stocks del hospital. El almacenado y conservación de los medicamentos termolábiles en las condiciones establecidas por el fabricante, garantiza la estabilidad y condiciones óptimas de utilización hasta la fecha de caducidad. La rotura de la cadena de frío puede condicionar significativamente la actividad y toxicidad de estos medicamentos. El farmacéutico debe tomar decisiones rápidas en situaciones donde se haya producido alguna eventualidad en la cadena del frío, de ahí la importancia de disponer de datos actualizados de su estabilidad a temperaturas distintas a las recomendadas. Se ha realizado una revisión de la información disponible sobre estabilidad de los medicamentos que requieren conservación en frigorífico de uso más frecuente en el medio hospitalario (AU)

Hospital pharmacists, according to the Ley del Medicamento25/1990 of 20th December, should ensure appropriate drug preservation within the Pharmacy Department and in hospital stocks.The storage and preservation of thermolabile drugs according to manufacturer recommendations guarantees stability and optimaluse conditions until the expiry date. Cold chain disruption may significantly affect the activity and toxicity of these drugs. Pharmacists should make quick decisions in case of cold chain-relatedevents, hence the relevance of up-to-date information on stability under temperatures differing from those recommended. A review of the information available on the stability of drugs commonly used in the hospital setting that require a fridge for storage has been carried out (AU)

[The action of 5-fluorouracil in DMH-induced carcinogenesis in rats]. / Acción del 5-fluorouracilo en la carcinogénesis inducida con DMH en ratas.

An experimental model to observe the action of 5-fluorouracil on rats with DMH-induced cancer of colon was designed. Ten Wistar rats were injected weekly with 25 subcutaneous doses (21 mg/kg) of DMH, and another ten, coinciding with the last 10 doses of the former, received intraperitoneally 10 mg/kg of the cytostatic agent. The animals were sacrificed 7 days after the last injection and samples of the colon processed by the "Swiss roll" technique. Differences in the weight of the animals and in the localization, size and macro and microscopic type of the tumours encountered, as well as the localization and grade of the dysplasias are studied.

Submucosal plexus of terminal ileum: a study of the cholinergic and noradrenergic nerves in rats with streptozotocin-induced diabetes.

In order to study the type and degree of the alterations in the innervation of the intestine in experimental diabetes, a histochemical study on the cholinergic and noradrenergic nerves of the submucosal plexus of terminal ileum from rats with streptozotocin-induced diabetes was performed. The results obtained suggest that the diabetic animals keep the cholinergic activity undamaged 20 weeks after the induction of the illness, while the number of the catecholaminergic nerves appears to be markedly reduced.

Effects of experimental diabetes in the noradrenergic and cholinergic nerves of the rat small intestine.

An histochemical research on cholinergic and noradrenergic fibres of the adventitia layer and of the myenteric plexus of the terminal ileum from rats with streptozotocin-induced diabetes, after 20 weeks of evolution of the illness, was carried out to study changes in the innervation of the gut. The cholinergic nerves, revealed through their acetylcholinesterase activity, did not present alterations, but an evident reduction in number of the noradrenergic nerves and swollen intensely fluorescent varicosities, were observed, both in the perivascular and myenteric plexus of terminal ileum from diabetic animals.