RESUMEN
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma that is incurable with existing therapies, and therefore presents a significant unmet clinical need. The ability of this disease to overcome therapy, including those that target the B cell receptor pathway which has a pathogenic role in MCL, highlights the need to develop new treatment strategies. Herein, we demonstrate that a distinguishing feature of lymph node resident MCL cells is the expression of phosphatidylinositol 3-kinase γ (PI3Kγ), a PI3K isoform that is not highly expressed in other B cells or B-cell malignancies. By exploring the role of PI3K in MCL using different PI3K isoform inhibitors, we provide evidence that duvelisib, a dual PI3Kδ/γ inhibitor, has a greater effect than PI3Kδ- and PI3Kγ-selective inhibitors in blocking the proliferation of primary MCL cells and MCL cell lines, and in inhibiting tumour growth in a mouse xenograft model. In addition, we demonstrated that PI3Kδ/γ signalling is critical for migration of primary MCL cells and cell lines. Our data indicates that aberrant expression of PI3Kγ is a critical feature of MCL pathogenesis. Thus, we suggest that the dual PI3Kδ/γ duvelisib would be effective for the treatment of mantle cell lymphoma.
Asunto(s)
Linfoma de Células del Manto , Inhibidores de las Quinasa Fosfoinosítidos-3 , Animales , Humanos , Ratones , Proliferación Celular , Modelos Animales de Enfermedad , Linfoma de Células del Manto/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacologíaRESUMEN
AIMS: Revision knee replacement is an increasingly common procedure, however, information on patient-focused outcomes is limited. This systematic review and meta-analysis aimed to investigate the medium-term patient reported outcomes following a revision knee replacement. METHODS: We performed a systematic review of MEDLINE and EMBASE (from inception to 1st March 2021) for articles reporting five year or greater patient reported outcome measures (PROMs) following revision knee replacement. A meta-analysis of PROMs data was undertaken using the Standardised Mean Difference (SMD). Quality of methodology was assessed using Wylde's non-summative four-point system. The study was registered with PROPSERO (CRD42021199289). RESULTS: A total of 23 studies met the inclusion criteria containing 2414 patients at a mean minimum follow-up of 74 months (60-122). The reporting of PROMs were poorly standardised with several PROMs being used. The most commonly reported patient reported outcome was the Knee Society Score reported in 65% of studies (15/23). A meta-analysis of 629 eligible patients undergoing revision knee replacement revealed a significant improvement in pre-operative state with a SMD 2·05 95% CI 0.87, 3.23. CONCLUSION: This systematic review has found a significant and sustained improvement in patient-reported outcomes following a revision knee arthroplasty beyond five years. We found a variation in the usage and administration of PROMs which hinders a clear synthesis of results. Furthermore, the PROMs have not been robustly tested for validity in the context of a revision knee replacement.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Artroplastia de Reemplazo de Rodilla/métodos , Humanos , Articulación de la Rodilla/cirugía , Medición de Resultados Informados por el PacienteRESUMEN
Luxatio erecta is the rarest form of shoulder dislocation, accounting for 0.5% of all glenohumeral dislocations. Bilateral cases are rarer still with only 12 accounts described in medical literature. We describe an unusual case and its management.
Asunto(s)
Luxación del Hombro/diagnóstico por imagen , Femenino , Humanos , Manipulación Ortopédica/métodos , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Radiografía , Luxación del Hombro/terapia , Resultado del TratamientoAsunto(s)
Disentimientos y Disputas , Tutores Legales/legislación & jurisprudencia , Cuidados para Prolongación de la Vida/legislación & jurisprudencia , Privación de Tratamiento/legislación & jurisprudencia , Directivas Anticipadas , Daño Encefálico Crónico , Toma de Decisiones , Nutrición Enteral , Familia/psicología , Florida , Humanos , Apoyo Nutricional , Padres , Estado Vegetativo Persistente , Esposos/legislación & jurisprudencia , Estados UnidosRESUMEN
OBJECTIVE: To assess the degree of debilitation and the treatment views of individuals with headache presenting to a community pharmacy. BACKGROUND: Migraine and chronic daily headache are common poorly managed illnesses. Pharmacists recommend an over-the-counter "headache product" to customers more than 53 000 times daily, thus they are well positioned to help those with headache. DESIGN: Pilot project of 22 self-administered surveys of individuals presenting to a community pharmacy with a complaint of headache. RESULTS: Thirteen persons had Migraine Disability Assessment scores of grade III or grade IV. Of the sample population, a substantial minority (41%) did not believe their headaches could be effectively managed with over-the-counter medications, 72% did not feel over-the-counter agents were safer than prescription products, 96% did not indicate that over-the-counter drugs were more effective than prescription drugs, and 50% disagreed that a physician's evaluation was not necessary. Only half of the population was satisfied with their current therapy, and individuals overwhelmingly (91%) wished they could prevent their headaches. CONCLUSIONS: The majority of individuals with headache presenting to a community pharmacy had high levels of morbidity and were in need of education regarding the proper role of over-the-counter medications, the advantages of prescription agents, and the benefits of a physician's referral. These preliminary results indicate that community pharmacies are potentially important locations for identification, education, and referral of individuals with headache.