Improving Conversations about Parkinson's Dementia.

BACKGROUND: People with Parkinson's disease (PD) have an increased risk of dementia, yet patients and clinicians frequently avoid talking about it due to associated stigma, and the perception that "nothing can be done about it". However, open conversations about PD dementia may allow people with the condition to access treatment and support, and may increase participation in research aimed at understanding PD dementia. OBJECTIVES: To co-produce information resources for patients and healthcare professionals to improve conversations about PD dementia. METHODS: We worked with people with PD, engagement experts, artists, and a PD charity to open up these conversations. 34 participants (16 PD; 6 PD dementia; 1 Parkinsonism, 11 caregivers) attended creative workshops to examine fears about PD dementia and develop information resources. 25 PD experts contributed to the resources. RESULTS: While most people with PD (70%) and caregivers (81%) shared worries about cognitive changes prior to the workshops, only 38% and 30%, respectively, had raised these concerns with a healthcare professional. 91% of people with PD and 73% of caregivers agreed that PD clinicians should ask about cognitive changes routinely through direct questions and perform cognitive tests at clinic appointments. We used insights from the creative workshops, and input from a network of PD experts to co-develop two open-access resources: one for people with PD and their families, and one for healthcare professionals. CONCLUSION: Using artistic and creative workshops, co-learning and striving for diverse voices, we co-produced relevant resources for a wider audience to improve conversations about PD dementia.

Practical application of Alzheimer's Disease Neuroimaging Initiative plasma P-tau181 reference data to support diagnosis of Alzheimer's disease.

OBJECTIVES: To assess plasma phosphorylated tau181 (p-tau181) levels in Alzheimer's disease (AD), cognitively impaired non-AD participants (CI non-AD) and Control participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset that could potentially act as reference data for clinic diagnoses of AD. METHODS: Data from 1558 participants (649 AD participants, 445 CI non-AD participants and 464 controls) were examined, comparing p-tau181 levels between Controls, AD and other dementias, stratified by age. RESULTS: There were significant differences in plasma p-tau181 values between Controls and those with AD at all ages up to 85 years. There were also significant differences between AD and CI non-AD participants up to the age of 85 years. CONCLUSIONS: Plasma P-tau181 may be a useful tool in the diagnosis of AD in those clinical settings where biomarkers have traditionally been less used. P-tau181 may be less useful as an aid to diagnosis in the very oldest-old. Further work is needed to establish the feasibility and utility of this biomarker within dementia diagnosis services not led by Neurologists, such as UK National Health Service Memory Services.

Comment on: Conservative management of an infected laparoscopic hernia mesh: A case study.

INTRODUCTION: We recently published an article in this journal describing the successful conservative treatment of a patient with an infected laparoscopically inserted hernia mesh using gentamycin flushes via a pig-tail drain and long term oral antibiotics. This prevented the need for major reconstructive surgery. However, 3 months after we published our report, the patient re-presented with symptoms of a recurrence of infection. PRESENTATION OF CASE: Seven months after stopping oral antibiotics, our patient represented with fever and swelling and redness over his left sided inguinal hernia mesh. This mesh had to be surgically removed. The procedure was laparoscopic and showed infection confined to the central 5cm of the mesh. Microbiology culture results were the same as on initial presentation. DISCUSSION: The microbiology results suggest that it is likely that the infection was never fully eradicated and that our intervention merely kept the infection at bay. Once long term antibiotics were stopped it is likely that the infection was able to eventually recur. CONCLUSION: Consequently, we have been unable to show that our method of conservative management of infected hernia meshes is effective to prevent long term recurrence of infection.

Conservative management of an infected laparoscopic hernia mesh: A case study.

INTRODUCTION: A dreaded complication of laparoscopic hernia repair is infection of the mesh. Traditionally mesh infection is managed by surgical removal of the mesh, an extensive procedure resulting in high re-herniation rates. A technique to treat such infections whilst salvaging the mesh is sorely needed. We describe a case in which a laparoscopic mesh infection was treated solely with drainage, parenteral antibiotics and antibiotic irrigation of the mesh. PRESENTATION OF CASE: A 65 year old gentleman presented 11 months post laparoscopic repair of an inguinal hernia with malaise and an uncomfortable groin swelling. Computed tomography scanning revealed a collection surrounding the mesh which was drained and cultured to show heavy growth of Staphylococcus aureus. A pigtail drain on continuous drainage was inserted and kept in situ for 7 weeks. The patient received one week of intravenous flucloxacillin and two gentamycin irrigations through the drain as an inpatient. He then received 6 weeks of oral flucloxacillin and bi-weekly saline flushes through the drain in the community. By 12 weeks an ultrasound scan showed resolution of the collection. At 7 months he remains clinically free from recurrence. DISCUSSION: Here we report a novel conservative method used to treat a hernia mesh infection, preserve the mesh and avoid major surgery. Other reports exist suggesting variations in conservative methods to treat mesh infections, however ours is by far the most conservative. CONCLUSION: Clearly, further research is required to identify which method is most effective and in which patients it is likely to be successful.

Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production.

To identify genes and mechanisms involved in humoral immunity, we did a mouse genetic screen for mutations that do not affect the first wave of antibody to immunization but disrupt response maturation and persistence. The first two mutants identified had loss-of-function mutations in the gene encoding a previously obscure member of a family of Rho-Rac GTP-exchange factors, DOCK8. DOCK8-mutant B cells were unable to form marginal zone B cells or to persist in germinal centers and undergo affinity maturation. Dock8 mutations disrupted accumulation of the integrin ligand ICAM-1 in the B cell immunological synapse but did not alter other aspects of B cell antigen receptor signaling. Humoral immunodeficiency due to Dock8 mutation provides evidence that organization of the immunological synapse is critical for signaling the survival of B cell subsets required for long-lasting immunity.