Total Joint Replacement in the Past Does Not Relate to a Deteriorated Functional Level and Health Status in the Oldest Old

Total hip or knee replacement is effective in improving joint function, quality of life, and pain reduction. The oldest old population with joint replacements (TJR) is underrepresented in current literature. We compared health-related and functional characteristics of oldest olds with and without TJR. Participants (aged 85 years) were divided into a group with and without TJR. Comorbidity, physical and joint functioning, daily living activities, quality of life, and mortality were recorded. Thirty-eight of 599 participants (6.3%) received a TJR in the past. Participants with a TJR had slightly less comorbidities, walked slower (P = 0.006), and complained more about hip-pain (P = 0.007). Mortality of those with a TJR was lower during the first 8-year followup (P = 0.04). All other characteristics were comparable between groups. We conclude that subjects with a TJR performed equally well, besides showing a lower gait speed and a higher frequency of hip-pain. Except for the lower gaitspeed, having a TJR is not associated with poorer health

Total ankle prostheses in rheumatoid arthropathy: Outcome in 52 patients followed for 1–9 years

Background and purpose The first generations of total ankle replacements (TARs) showed a high rate of early failure. In the last decades, much progress has been made in the development of TARs, with the newer generation showing better results. We evaluated TARs implanted with rheumatoid arthritis (RA) or juvenile inflammatory arthritis (JIA) as indication

Shallow-water hydrothermal venting linked to the Palaeocene–Eocene Thermal Maximum

The Palaeocene–Eocene Thermal Maximum (PETM) was a global warming event of 5–6 °C around 56 million years ago caused by input of carbon into the ocean and atmosphere. Hydrothermal venting of greenhouse gases produced in contact aureoles surrounding magmatic intrusions in the North Atlantic Igneous Province have been proposed to play a key role in the PETM carbon-cycle perturbation, but the precise timing, magnitude and climatic impact of such venting remains uncertain. Here we present seismic data and the results of a five-borehole transect sampling the crater of a hydrothermal vent complex in the Northeast Atlantic. Stable carbon isotope stratigraphy and dinoflagellate cyst biostratigraphy reveal a negative carbon isotope excursion coincident with the appearance of the index taxon Apectodinium augustum in the vent crater, firmly tying the infill to the PETM. The shape of the crater and stratified sediments suggests large-scale explosive gas release during the initial phase of vent formation followed by rapid, but largely undisturbed, diatomite-rich infill. Moreover, we show that these vents erupted in very shallow water across the North Atlantic Igneous Province, such that volatile emissions would have entered the atmosphere almost directly without oxidation to CO2 and at the onset of the PETM

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

Irreversible renal damage after transient renin-angiotensin system stimulation:involvement of an AT1-receptor mediated immune response

Transient activation of the renin-angiotensin system (RAS) induces irreversible renal damage causing sustained elevation in blood pressure (BP) in Cyp1a1-Ren2 transgenic rats. In our current study we hypothesized that activation of the AT1-receptor (AT1R) leads to a T-cell response causing irreversible impairment of renal function and hypertension. Cyp1a1-Ren2 rats harbor a construct for activation of the RAS by indole-3-carbinol (I3C). Rats were fed a I3C diet between 4-8 weeks of age to induce hypertension. Next, I3C was withdrawn and rats were followed-up for another 12 weeks. Additional groups received losartan (20 mg/kg/day) or hydralazine (100 mg/kg/day) treatment between 4-8 weeks. Rats were placed for 24h in metabolic cages before determining BP at week 8, 12 and 20. At these ages, subsets of animals were sacrificed and the presence of kidney T-cell subpopulations was investigated by immunohistochemistry and molecular marker analysis. The development of sustained hypertension was completely prevented by losartan, whereas hydralazine only caused a partial decrease in BP. Markers of renal damage: KIM-1 and osteopontin were highly expressed in urine and kidney samples of I3C-treated rats, even until 20 weeks of age. Additionally, renal expression of regulatory-T cells (Tregs) was highly increased in I3C-treated rats, whereas the expression of T-helper 1 (Th1) cells demonstrated a strong decrease. Losartan prevented these effects completely, whereas hydralazine was unable to affect these changes. In young Cyp1a1-Ren2 rats AT1R activation leads to induction of an immune response, causing a shift from Th1-cells to Tregs, contributing to the development of irreversible renal damage and hypertension

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe