Inferior outcome after hip resurfacing arthroplasty than after conventional arthroplasty: Evidence from the Nordic Arthroplasty Register Association (NARA) database, 1995 to 2007

Today, total hip arthroplasty (THA) is one of the safest and most efficient surgical treatments. New materials, surgical techniques and design concepts intended to improve THA have not always been successful. Thorough preclinical and early clinical investigations can detect some aspects of under-performing, while continuing surveillance is recommended to detect and analyze reasons for any later appearing flaws. In this thesis, several ways to monitor and assess THA performance are explored and carried out, using survival analysis in registry studies, radiostereometry (RSA), radiology and clinical outcome. In Paper I, a study using the Nordic Arthroplasty Register Association (NARA) registry shows that HRA had an almost 3-fold increased early non-septic revision risk and that risk factors were found to be female sex, certain HRA designs and units having performed few HRA procedures. Papers II and III contain comparisons of highly cross-linked polyethylene (XLPE) and conventional polyethylene (PE). XLPE had a considerably lower wear rate up to 10 years but showed no obvious improvements regarding implant fixation, BMD or clinical outcome. In the NARA registry, in 2 of 4 studied cup designs the XLPE version had a lower risk of revision for aseptic loosening compared to the PE version. Paper IV describes that stem subsidence and retrotorsion measured with RSA at 2 years predicted later aseptic stem failure in an unfavorably altered, previously well-functioning cemented femoral stem. In Paper V and VI, a novel approach to measure articulation wear with RSA in radiodense hip arthroplasty articulations was presented and evaluated. Subsequently, a comparison between ceramic-on-ceramic (COC) and metal-on-conventional PE uncemented THA displayed a considerably lower wear rate, smaller periacetabular bone lesions and a relatively high squeaking rate, the latter with unknown long-term consequences, in the COC hips. Implant fixation, heterotopic ossification and clinical outcome did not differ between articulation types. In conclusion, it was confirmed that implant surveillance can be done with RSA, also in radiodense THA. Early migration predicts later aseptic implant failure. Prolonged surveillance can confirm long-term material and design performance, verify or contradict anticipated advantages as well as detect unanticipated long-term complications

The natural history of classic galactosemia: lessons from the GalNet registry

BACKGROUND: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. METHODS: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. RESULTS: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. CONCLUSION: This study describes the natural history of classic galactosemia based on the hitherto largest data set.status: publishe