Citations

ABSTRACT Travel distance, growing disability, and uneven distribution of doctors limit access to care for most Parkinson's disease (PD) patients worldwide. Telemedicine, the use of telecommunications technology to deliver care at a distance, can help overcome these barriers. In this report, we describe the past, present, and likely future applications of telemedicine to PD. Historically, telemedicine has relied on expensive equipment to connect single patients to a specialist in pilot programs in wealthy nations. As the cost of video conferencing has plummeted, these efforts have expanded in scale and scope, now reaching larger parts of the world and extending the focus from care to training of remote providers. Policy, especially limited reimbursement, currently hinders the growth and adoption of these new care models. As these policies change and technology advances and spreads, the following will likely develop: integrated care networks that connect patients to a wide range of providers; education programs that support patients and health care providers; and new research applications that include remote monitoring and remote visits. Together, these developments will enable more individuals with PD to connect to care, increase access to expertise for patients and providers, and allow more‐extensive, less‐expensive participation in research. © 2014 International Parkinson and Movement Disorder Society

Objective To highlight a specific under‐recognized radiological feature of spondylotic myelopathy often resulting in misdiagnosis. Methods Patients evaluated between January 1, 1996 and December 31, 2012 who met the following criteria were included: (1) spondylotic myelopathy was suspected, (2) gadolinium enhancement was detected, and (3) spinal surgery was performed. Results Fifty‐six patients (70% men) whose median age was 53.5 years (range = 24–80) were included. Spinal cord magnetic resonance imaging (cervical in 52; thoracic in 4) revealed longitudinal spindle‐shaped T2‐signal hyperintensity (100%) and cord enlargement (79%) accompanied by a characteristic pancakelike transverse band of gadolinium enhancement in 41 (73%), typically immediately caudal to the site of maximal spinal stenosis. Forty (71%) patients were initially diagnosed with neoplastic or inflammatory myelopathies, and decompressive surgery was delayed by a median of 11 months (range = 1–64). Spinal cord biopsy in 6 did not reveal any alternative diagnosis. Ninety‐five percent were stable or improved. Gadolinium enhancement persisted in 75% at 12 months, raising concern about the accuracy of the initial diagnosis. Twenty patients required a gait aid (36%) at last follow‐up (median = 60 months, range = 10–172). The need for a gait aid preoperatively ( p = 0.005), but not delay of surgery, predicted the need for gait aid at final follow‐up. Interpretation Transverse pancakelike gadolinium enhancement associated with and just caudal to the site of maximal stenosis and at the rostrocaudal midpoint of a spindle‐shaped T2 hyperintensity suggests that spondylosis is the cause of the myelopathy. Persistent enhancement for months to years following decompressive surgery is common. Recognition is important to prevent inappropriate interventions or delay in consideration of a potentially beneficial decompressive surgery. Ann Neurol 2014;76:54–65

ABSTRACT We describe a case of chronic tenosynovitis in the hand of a 58-year-old cattle farmer. Surgical biopsy specimens grew Mycobacterium arupense . The patient responded to surgery and antimicrobial therapy based on in vitro susceptibility testing. The antimicrobial susceptibility profiles of the isolate from this patient and 39 additional clinical isolates are presented.

Abstract Rationale Daily azithromycin decreases acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but long-term side effects are unknown. Objectives To identify the types of exacerbations most likely to be reduced and clinical subgroups most likely to benefit from azithromycin, 250 mg daily, added to usual care. Methods Enrollment criteria included irreversible airflow limitation and AECOPD requiring corticosteroids, emergency department visit, or hospitalization in the prior year or use of supplemental oxygen. Recurrent events and cumulative incidence analyses compared treatment received for AECOPD by randomization group, stratified by subgroups of interest. Cox proportional hazards models estimated treatment effects in subgroups adjusted for age, sex, smoking status, FEV1% predicted, concomitant COPD medications, and oxygen use. Measurements and Main Results Azithromycin was most effective in reducing AECOPD requiring both antibiotic and steroid treatment (n = 1,113; cumulative incidence analysis, P = 0.0002; recurrent events analysis, P = 0.002). No difference in treatment response by sex (P = 0.75), presence of chronic bronchitis (P = 0.19), concomitant inhaled therapy (P = 0.29), or supplemental oxygen use (P = 0.23) was observed. Older age and milder Global Initiative for Chronic Obstructive Lung Disease stage were associated with better treatment response (P = 0.02 and 0.04, respectively). A significant interaction between treatment and current smoking was seen (P = 0.03) and azithromycin did not reduce exacerbations in current smokers (hazard ratio, 0.99; 95% confidence interval, 0.71–1.38; P = 0.95). Conclusions Azithromycin is most effective in preventing AECOPD requiring both antibiotic and steroid treatment. Adjusting for confounders, we saw no difference in efficacy by sex, history of chronic bronchitis, oxygen use, or concomitant COPD therapy. Greater efficacy was seen in older patients and milder Global Initiative for Chronic Obstructive Lung Disease stages. We found little evidence of treatment effect among current smokers. Clinical trial registered with www.clinicaltrials.gov (NCT0011986 and NCT00325897).

Abstract Oncolytic viruses can exert their antitumor activity via direct oncolysis or activation of antitumor immunity. Although reovirus is currently under clinical investigation for the treatment of localized or disseminated cancer, any potential immune contribution to its efficacy has not been addressed. This is the first study to investigate the ability of reovirus to activate human dendritic cells (DC), key regulators of both innate and adaptive immune responses. Reovirus induced DC maturation and stimulated the production of the proinflammatory cytokines IFN-α, TNF-α, IL-12p70, and IL-6. Activation of DC by reovirus was not dependent on viral replication, while cytokine production (but not phenotypic maturation) was inhibited by blockade of PKR and NF-κB signaling. Upon coculture with autologous NK cells, reovirus-activated DC up-regulated IFN-γ production and increased NK cytolytic activity. Moreover, short-term coculture of reovirus-activated DC with autologous T cells also enhanced T cell cytokine secretion (IL-2 and IFN-γ) and induced non-Ag restricted tumor cell killing. These data demonstrate for the first time that reovirus directly activates human DC and that reovirus-activated DC stimulate innate killing by not only NK cells, but also T cells, suggesting a novel potential role for T cells in oncolytic virus-induced local tumor cell death. Hence reovirus recognition by DC may trigger innate effector mechanisms to complement the virus’s direct cytotoxicity, potentially enhancing the efficacy of reovirus as a therapeutic agent.

Abstract Under optimal Ag stimulation, CTL become functional effector and memory T cells. Professional APCs (pAPC) are considered essential for the activation of CTL, due to their unique capacity to provide costimulation and present exogenous Ags through MHC class I molecules. In this study, we report a novel means by which Th lymphocytes acquire and present MHC class I determinants to naive CTL. Although previous studies have looked at T cell Ag presentation to activated T cells, this study presents the first example of Ag presentation by Th cells to naive CTL. We report that activated Th cells can function as effective pAPC for CTL. Our results show that: 1) In addition to acquisition of cell surface molecules, including MHC class I/peptide complexes, from pAPC, Th cells can acquire and present MHC class I-binding peptides through TCR-MHC class II interactions with pAPC; 2) the acquired Ag can be functionally presented to CTL; and 3) Ag presentation by Th cells induces naive CTL to proliferate and preferentially differentiate into cells that phenotypically and functionally resemble central memory T cells. These findings suggest a novel role of Th cells as pAPC for the development of memory immune responses.