Comparison of recent pivotal recommendations for the diagnosis and treatment of late-onset Pompe disease using diagnostic nodes—the Pompe disease burden scale

Abstract

Pompe disease is a rare autosomal-recessive disorder characterised by limb-girdle myopathy and respiratory weakness in the late-onset form (LOPD). Various mutations in the acid alpha-glucosidase gene lead to toxic lysosomal and extra-lysosomal glycogen accumulation in all organs due to ineffective glycogen clearance by the encoded enzyme. Only one randomized trial demonstrated beneficial effects of respiratory function and meters walked in the 6-min walking test with enzyme replacement therapy (ERT). These results were confirmed in several retrospective and prospective observations and in meta-analyses. Due to a potential lifelong therapy, moderate efficacy and high treatment costs time of ERT initiation and cessation is an ongoing matter of debate. So far, several national and international recommendations have been published with different criteria concerning diagnosis, initiation and cessation of ERT in LOPD. We therefore formally analysed recent published recommendations and consensus statements of LOPD using diagnostic nodes (DODES) as a special software tool. With DODES, an objective analysis becomes possible if the content of the recommendations is represented as algorithms using cross-compatible elements. This analysis formally disclosed both, areas of great heterogeneity and concordance for the diagnosis and management of LOPD and paved the way for a Pompe disease burden scale focussing on ERT initiation. According to this investigation further clinical research should concentrate on ERT in pre-symptomatic and severely affected LOPD patients and on cessation criteria for ERT as these issues are areas of international uncertainty and discordance.

Stage III N2 non-small cell lung cancer treatment: decision-making among surgeons and radiation oncologists

“…The recommendations were reduced to the options of: a definitive surgical approach (with neoadjuvant or adjuvant CTx/CRT), definitive CRT approach or "patient preference" (no specific recommendation for either RT or surgery; both being options). Decision criteria collected were converted into decision trees, analysed and standardized if their meaning was not changed as described previously (12)(13)(14). For better comparison, universal criteria the disease was resectable, even in multilevel N2.…”

International guidelines on stage III N2 nonsmall cell lung cancer: surgery or radiotherapy?

“…The recommendations on stage III N2 NSCLC within the guidelines were reduced to recommendations towards a definitive surgical approach (with neoadjuvant or adjuvant Ch/CRT), a definitive CRT approach or no preference (no specific recommendation for either RT or surgery and both being options). Decision criteria implemented were analysed and standardised if their meaning was not changed, as described by PANJE et al [25][26][27]. Universal criteria such as the ability to give informed consent were not included in this analysis.…”

Newborn Screening for Pompe Disease

“…Starting ERT even a few days earlier may lead to better patient outcomes [28]. Starting ERT early is effective in patients with LOPD as well; however, early ERT before presentation of signs or symptoms in patients with LOPD is generally not recommended [29]. Administration of ERT in the absence of symptoms of LOPD, even when blood CK and urine HEX4 are elevated, is avoided.…”