Mortality and Institutionalization After Percutaneous Endoscopic Gastrostomy in Parkinson's Disease and Related Conditions.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) can facilitate feeding and medication administration in dysphagic patients with Parkinson's disease and related disorders. Information on survival, institutionalization, and complications post PEG might inform feeding decisions. METHOD: A total of 93 patients with Parkinson's disease and related disorders were identified by review of PEG registers and by searching the administrative databases in 2 large UK university hospitals (2005-2017); 83 case notes were available for retrospective review. Care processes and outcomes were assessed. RESULTS: The following were the diagnoses: 58 (70%) had Parkinson's disease, 10 (12%) had progressive supranuclear palsy, 5 (6%) had multiple system atrophy, 3 (4%) had dementia with Lewy bodies, and 7 (8%) had vascular parkinsonism. The median age was 78 years (interquartile range 72-82); 29 (35%) were women. Care processes included a future care plan in place prior to admission for 18 patients (22%), and PEG was placed during emergency admission in 68 patients (82%). The outcomes included median survival at 422 days; 30-day mortality rate was 6% (5 patients); and of 56 patients admitted from home, 18 (32%) were discharged to institutions (nursing or care homes). The most common complication was aspiration pneumonia for 18 (22%) of patients. Age, sex, diagnosis, admission type, comorbidities, and place of residence did not predict survival. Discharge to own home and follow-up by the home enteral feeding team were associated with longer survival. CONCLUSION: We recommend markers of advanced disease should prompt advanced care planning. Discussions about PEG feeding should include information about post-PEG survival, complications, and risk of institutionalization. Further research is needed on quality-of-life post PEG and ways to reduce aspiration pneumonia. All PEG patients should have nutrition team follow-up.

Recurrent subacute visual loss presenting in a 52-year-old Caucasian woman with chronic relapsing inflammatory optic neuropathy: a case report.

INTRODUCTION: Chronic relapsing inflammatory optic neuropathy is a recently described form of recurrent isolated subacute optic neuropathy. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. A complete work up for demyelination, autoimmune disease and sarcoidosis must be made before considering chronic relapsing inflammatory optic neuropathy. CASE PRESENTATION: We describe the case of a 52-year-old Caucasian woman who presented with isolated subacute optic neuropathy. There was no evidence of demyelination, autoimmunity or sarcoidosis. There was an abrupt and prompt response to systemic corticosteroids and a relapse of the condition on steroid withdrawal. CONCLUSIONS: Chronic relapsing inflammatory optic neuropathy requires careful consideration and differentiation from demyelinating optic neuritis and ischemic optic neuropathy since the treatment is different and the outcome without treatment is likely to be poor. The importance of identifying these patients has considerable clinical implications as the condition is highly responsive to steroids.

Tissue-specific roles of ABCA1 influence susceptibility to atherosclerosis.

OBJECTIVE: The ATP-binding cassette transporter, subfamily A, member 1 (ABCA1) plays a key role in HDL cholesterol metabolism. However, the role of ABCA1 in modulating susceptibility to atherosclerosis is controversial. METHODS AND RESULTS: We investigated the role of ABCA1 in atherosclerosis using a combination of overexpression and selective deletion models. First, we examined the effect of transgenic overexpression of a full-length human ABCA1-containing bacterial artificial chromosome (BAC) in the presence or absence of the endogenous mouse Abca1 gene. ABCA1 overexpression in the atherosclerosis-susceptible Ldlr(-/-) background significantly reduced the development of atherosclerosis in both the presence and absence of mouse Abca1. Next, we used mice with tissue-specific inactivation of Abca1 to dissect the discrete roles of Abca1 in different tissues on susceptibility to atherosclerosis. On the Apoe(-/-) background, mice lacking hepatic Abca1 had significantly reduced HDL cholesterol and accelerated atherosclerosis, indicating that the liver is an important site at which Abca1 plays an antiatherogenic role. In contrast, mice with macrophage-specific inactivation of Abca1 on the Ldlr(-/-) background displayed no change in atherosclerotic lesion area. CONCLUSIONS: These data indicate that physiological expression of Abca1 modulates the susceptibility to atherosclerosis and establish hepatic Abca1 expression as an important site of atheroprotection. In contrast, we show that selective deletion of macrophage Abca1 does not significantly modulate atherogenesis.

Neutralizing anti-4-1BBL treatment improves cardiac function in viral myocarditis.

Coxsackievirus B3 (CVB3) is the most common causative agent of infectious myocarditis. Chronic inflammation, loss of contractile tissue, and maladaptive remodeling all contribute to dilated cardiomyopathy and heart failure. The 4-1BB receptor is a costimulatory molecule expressed by T cells and cardiomyocytes. We infected mice with CVB3 to examine if virus infection triggers 4-1BB activation and whether inhibition of this pathway will reduce inflammation and improve heart function. Echocardiography was performed on days 3, 9, 30 and at 10 weeks post-infection (pi) and ejection fraction (EF), left ventricular (LV) wall thickness, contractility, and internal cardiac dimensions were measured. At day 9, reduced rate of wall thickening (30+/-17 vs 70+/-19%), increased LV wall thickness (0.15+/-0.04 vs 0.09+/-0.01 cm in diastole and 0.19+/-0.04 vs 0.15+/-0.02 cm in systole), and reduced cardiac volume (0.013+/-0.004 vs 0.023+/-0.003 ml in diastole and 0.004+/-0.002 ml vs 0.007+/-0.001 ml in systole) were observed in infected hearts as compared with shams. At 14 days pi, CVB3-infected mice were randomly assigned to receive either anti-4-1BBL neutralizing (M522) or control antibodies (Ab) for 8 weeks. Cardiac damage, fibrosis, and inflammation were assessed by histological stains and immunohistochemistry. Polymerase chain reaction (PCR) was utilized to detect matrix metalloproteinase (MMP)-2, MMP-9, and MMP-12 expressions. At 10 weeks pi, M522 treatment improved LV wall thickening rate (-10+/-13 vs -49+/-16%, expressed as percentage change from baseline) and reduced diastolic LV posterior wall thickness (17+/-10 vs 57+/-47%, expressed as percentage change from baseline), cardiac damage as assessed by histological scores (0 vs 1.3+/-1.5), fibrosis by collagen volume fraction (3.2+/-0.6 vs 4.9+/-2.2%), overall inflammation (5.9+/-1.3 vs 8.5+/-4.1%), and T-cell infiltration (1.3+/-0.9 vs 4.3+/-3.8%) as compared to control. MMP-12 was highly increased during acute and chronic myocarditis, but was significantly decreased by M522 treatment. Thus, long-term inhibition of the 4-1BB pathway reduces cardiac damage, remodeling, and inflammation during viral myocarditis.