The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT ...in a cohort of patients with severe Pompe disease.
We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT. Patients' medical records were collected and reviewed and respiratory and motor functions, before ERT initiation and upon last evaluation were compared.
Twelve patients (7 males) were identified. Median age at symptom onset was 24years IQR=15.5; 36.0. At baseline ventilation was invasive in 11 patients and noninvasive in one, with a median ventilation time of 24h IQR=21.88; 24.00 (min 20; max 24). ERT was initiated at a median age of 52.5years IQR=35.75; 66.50. Median treatment duration was 55months IQR=39.5; 81.0. During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90min and two increased their assisted walking distance, by 80 and 20m.
Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk. ERT can be initiated in these patients in order to retain their current level of independence and ability to perform daily life activities.
•The efficacy of ERT in patients at an advanced stage of Pompe disease, confined in a wheelchair and ventilator dependent, has not been proven in a randomized trial.•We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT.•During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90minutes and two increased their assisted walking distance, by 80 and 20meters.•Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk.
Immunogenicity of recombinant human acid-alpha glucosidase (rhGAA) in enzyme replacement therapy (ERT) is a safety and efficacy concern in the management of late-onset Pompe disease (LOPD). However, ...long-term effects of ERT on humoral and cellular responses to rhGAA are still poorly understood. To better understand the impact of immunogenicity of rhGAA on the efficacy of ERT, clinical data and blood samples from LOPD patients undergoing ERT for >4 years (n = 28) or untreated (n = 10) were collected and analyzed. In treated LOPD patients, anti-rhGAA antibodies peaked within the first 1000 days of ERT, while long-term exposure to rhGAA resulted in clearance of antibodies with residual production of non-neutralizing IgG. Analysis of T cell responses to rhGAA showed detectable T cell reactivity only after in vitro restimulation. Upregulation of several cytokines and chemokines was detectable in both treated and untreated LOPD subjects, while IL2 secretion was detectable only in subjects who received ERT. These results indicate that long-term ERT in LOPD patients results in a decrease in antibody titers and residual production of non-inhibitory IgGs. Immune responses to GAA following long-term ERT do not seem to affect efficacy of ERT and are consistent with an immunomodulatory effect possibly mediated by regulatory T cells.
Institutional claims of university-community engagement in support of the public good and planning for teaching, learning, and research have largely remained in the realm of rhetoric. This thesis ...analyzes the 2019-2021 Trent University Lands and Nature Areas Plan and public consultation process, which at times was marked by the complete absence of consultation and at other times, wholly inadequate consultation with regards to developments affecting its on-campus food growing system and correlate pedagogy. Using methods from Institutional Ethnography, Participatory Action Learning and Action Research, and the BIAS FREE Framework, I explore how Trent University manages its approach to land-use planning and public consultation, revealing that it is ultimately working at cross-purposes with its foundational principles. I advise that Trent University’s current land-use planning model, lacking critical examination and intervention, puts the institution’s academic reputation, campus ecological functions, and university-community relations at risk. If perpetuated, this model will be detrimental to the university’s capacity to generate new knowledge for teaching, learning, and research, as well as context-specific solutions for its land-use planning. My findings define a new concept of fait accompli planning to describe how and why Trent’s public consultation process fell significantly short of both its institutional mandate and claims of robust and comprehensive engagement. I conclude that post-secondary institutions (and beyond) need to implement dialogic approaches to planning that abandon predetermined outcomes and instead foster genuine dialogue toward a collaborative milieu of shared, informed, and deliberate planning practices.
Polynomial regression is a proven method to calculate person-environment (PE) interest fit between the RIASEC (realistic, investigative, artistic, social, enterprising and conventional) interests of ...a student and the RIASEC profile of a study program. The method has shown much larger effects of PE interest fit on academic achievement than earlier approaches in literature. However, the polynomial regression method in its current form only focuses on establishing the regressed interest fit (RIF) of a population of students with their study environments, in order to observe how large the general impact of PE interest fit can become on academic achievement. The present study (N = 4407 across n = 22 study programs) further validates this method towards new applications by theoretically deriving two measures of RIF that only affect a single environment like a study program. Analyses show that the use of RIF for a single study environment results in an even stronger positive relation between PE interest fit and academic achievement of r = 0.36, compared to r = 0.25 for the original polynomial regression method. Analyses also show that RIF for one environment can be used to generate interpretable and reliable RIASEC environment profiles. In sum, RIF for a single (study) environment is a promising operationalization of PE interest fit which facilitates both empirical research as well as the practical application of interest fit in counseling settings.
•New methods of regressed interest fit (RIF) calculate the interest fit between a student and a specific study program.•RIF12 shows a stronger positive relation between interest fit and academic achievement than previously found.•RIF6 uses regression to extract specific RIASEC program profiles from the variance in student RIASEC data.•The presented RIF can facilitate both empirical research and study counseling.
Discussion on the impact of microenvironments on macrophage permissiveness to influenza virus infection and to the innate immune responses elicited by such infection.
PDF
