Thicker polyethylene inserts (≥ 13 mm) increase the risk for early failure after primary cruciate-retaining total knee arthroplasty (TKA) : a single-centre study of 7643 TKAs

PURPOSE: This study investigates whether thicker (PE) inserts lead to a greater risk for revision after TKA. The differences between the TKA designs of three manufacturers (NexGen, PFC Sigma, Triathlon) are also compared. METHODS: A total of 7643 primary TKA surgeries were included. PE inserts were divided into two groups-"thick PE inserts" with a thickness of 13 mm (mm) or more and "standard PE inserts" with a thickness of less than 13 mm. Three cruciate-retaining (CR) TKA designs (NexGen, PFC Sigma, Triathlon) were included in the study. The differences in failure rates between groups were investigated using Kaplan-Meier survival curves and Cox regression model with hazard ratios (HR). Failure rates were investigated short-term ( 2 years; HR 1.6, CI 1.1 to 2.3) follow-up. The highest revision rate was observed in patients who received the Triathlon TKA with a thicker PE insert (HR 2.6, CI 1.2 to 5.7). CONCLUSION: The results indicate that thicker PE inserts are associated with increased risk for revision in primary TKA. Further research is required to ascertain whether more conformed PE inserts or constrained knee designs instead of thick CR inserts will ultimately lead to better clinical outcomes. LEVEL OF EVIDENCE: III.publishedVersionPeer reviewe

Nitrogen Balance after the Administration of a Prolonged-Release Protein Substitute for Phenylketonuria as a Single Dose in Healthy Volunteers

Nitrogen balance is the difference between nitrogen excreted as urea and nitrogen ingested, mainly in proteins. Increased circulating concentrations of amino acids (AA) in the bloodstream are usually associated with proportional increases in the production and excretion of urea. Previously, we reported results from a randomized, controlled, single-dose, crossover trial in healthy adult volunteers (n = 30) (Trial Registration: ISRCTN11016729), in which a Test product (prolonged-release AA mixture formulated with Physiomimic Technology (TM) (PT (TM))) significantly slowed down the release and reduced the peak plasma concentrations of essential AAs compared with a free AA mixture (Reference product) while maintaining essential AA bioavailability. Here, we report an assessment of the nitrogen balance from the same study. The amount of nitrogen contained in plasma AAs, levels of blood urea nitrogen (BUN) (p < 0.0001) and changes in BUN (p < 0.0001) were smaller after the Test product compared with the Reference product. These findings suggest that the production of urea in proportion to systemic AA availability was significantly smaller after the administration of the Test product compared with the Reference product and that the test product conferred the increased utilization of AAs for protein synthesis and reduced their oxidation and conversion to urea. In the clinical setting, it is possible that the effects of PT (TM) observed on the disposition of free AAs in this study may translate to health benefits in terms of physiological body composition and growth if used for the treatment of subjects with phenylketonuria (PKU). Further investigation in patients with PKU is warranted

Amino Acid Plasma Profiles from a Prolonged-Release Protein Substitute for Phenylketonuria: A Randomized, Single-Dose, Four-Way Crossover Trial in Healthy Volunteers

Several disorders of amino acid (AA) metabolism are treated with a protein-restricted diet supplemented with specific AA mixtures. Delivery kinetics impacts AA absorption and plasma concentration profiles. We assessed plasma profiles after ingestion of an AA mixture engineered to prolong AA absorption with Physiomimic Technology(TM)(Test) in a randomized, single-dose, four-way crossover trial in healthy volunteers (Trial Registration: ISRCTN11016729). In a two-step hypothesis, the primary endpoints were (i) significant reduction in peak plasma concentrations (C-max) of essential amino acids (EAAs) while (ii) maintaining EAA bioavailability (AUC(0-300 min)) compared to a free AA mixture (Reference). Secondary endpoints included effects on plasma profiles of other AA groups and effects on several metabolic markers. Thirty subjects completed the study. Both co-primary endpoints were met: C(max)for EAAs was 27% lower with the Test product compared to the Reference product (ratio, 0.726,p< 0.0001); overall plasma EAA levels from the two AA mixtures was within the pre-specified bioequivalence range (AUC(0-300min)ratio, 0.890 (95% CI: 0.865, 0.915)). These findings were supported by the results of secondary endpoints. Prolongation of AA absorption was associated with modulation of several metabolic markers. It will be important to understand whether this can improve the long-term management of disorders of AA metabolism

Cancer incidence and cause-specific mortality in patients with metal-on-metal hip replacements in Finland : A population-based study with a mean follow-up of 4.6 (1–11) years

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Effect of femoral head size on risk of revision for dislocation after total hip arthroplasty A population-based analysis of 42,379 primary procedures from the Finnish Arthroplasty Register

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High intratumoral dihydrotestosterone is associated with antiandrogen resistance in VCaP prostate cancer xenografts in castrated mice

Antiandrogen treatment resistance is a major clinical concern in castration-resistant prostate cancer (CRPC) treatment. Using xenografts of VCaP cells we showed that growth of antiandrogen resistant CRPC tumors were characterized by a higher intratumor dihydrotestosterone (DHT) concentration than that of treatment responsive tumors. Furthermore, the slow tumor growth after adrenalectomy was associated with a low intratumor DHT concentration. Reactivation of androgen signaling in enzalutamide-resistant tumors was further shown by the expression of several androgen-dependent genes. The data indicate that intratumor DHT concentration and expression of several androgen-dependent genes in CRPC lesions is an indication of enzalutamide treatment resistance and an indication of the need for further androgen blockade. The presence of an androgen synthesis, independent of CYP17A1 activity, has been shown to exist in prostate cancer cells, and thus, novel androgen synthesis inhibitors are needed for the treatment of enzalutamide-resistant CRPC tumors that do not respond to abiraterone.Peer reviewe

Implant survival of the most common cemented total hip devices from the Nordic Arthroplasty Register Association database

Background and purpose According to previous Nordic Arthroplasty Register Association (NARA) data, the 10-year implant survival of cemented total hip arthroplasties (THAs) is 94% in patients aged 65-74 and 96% in patients aged 75 or more. Here we report a brand-level comparison of cemented THA based on the NARA database, which has not been done previously.Patients and methods We determined the rate of implant survival of the 9 most common cemented THAs in the NARA database. We used Kaplan-Meier analysis with 95% CI to study implant survival at 10 and 15 years, and Cox multiple regression to assess survival and hazard ratios (HRs), with revision for any reason as endpoint and with adjustment for age, sex, diagnosis, and femoral head material.Results Spectron EF THA (89.9% (CI: 89.3-90.5)) and Elite THA (89.8% (CI: 89.0-90.6)) had the lowest 10-year survivorship. Lubinus (95.7% survival, CI: 95.5-95.9), MS 30 (96.6%, CI: 95.8-97.4), and C-stem THA (95.8%, CI: 94.8-96.8) had a 10-year survivorship of at least 95%. Lubinus (revision risk (RR)=0.77, CI: 0.73-0.81), Muller (RR =0.83, CI: 0.70-0.99), MS-30 (RR =0.73, CI: 0.63-0.86), C-stem (RR =0.70, CI: 0.55-0.90), and Exeter Duration THA (RR =0.84, CI: 0.77-0.90) had a lower risk of revision than Charnley THA, the reference implant.Interpretation The Spectron EF THA and the Elite THA had a lower implant survival than the Charnley, Exeter, and Lubinus THAs. Implant survival of the Muller, MS 30, CPT, and C-stem THAs was above the acceptable limit for 10-year survival.Peer reviewe

A multi-centre randomized controlled trial comparing arthroscopic osteochondroplasty and lavage with arthroscopic lavage alone on patient important outcomes and quality of life in the treatment of young adult (18-50) Femoroacetabular impingement

Background: Several cross-sectional studies have estimated that the prevalence of femoroacetabular impingement (FAI) ranges from 14-17% among asymptomatic young adults to almost 95% among competitive athletes. With FAI, there is abnormal contact between the proximal femur and the acetabulum, resulting in abnormal mechanics with terminal motion such as hip flexion and rotation. This condition results from bony anomalies of the acetabular rim (Pincer) and or femoral head/neck junction (CAM) and typically causes hip pain and decreased hip function. The development of hip pain potentially serves as an indicator for early cartilage and labral damage that may result in hip osteoarthritis. Although surgical correction of the misshaped bony anatomy and associated intra-articular soft tissue damage of the hip is thought to improve hip pain and alter the natural history of degenerative disease, the supportive evidence is based upon low quality observational studies. The Femoroacetabular Impingement RandomiSed controlled Trial (FIRST) compares outcomes following surgical correction of the impingement morphology (arthroscopic osteochondroplasty) with/without labral repair versus arthroscopic lavage of the hip joint in adults aged 18 to 50 diagnosed with FAI. Methods and design: FIRST is a multi-centre, randomized controlled trial with a sample size of 220 patients. Exclusion criteria include the presence of hip syndromes, previous surgery or trauma to the affected hip, and significant medical comorbidities. The primary outcome is pain and the secondary outcomes include patient function, quality of life, complications, and cost-effectiveness - all within one year of follow-up. Patients are stratified based on centre and impingement sub-type. Patients, outcome assessors, data analysts, and the Steering Committee are blinded to surgical allocation. Using an intention-to-treat approach, outcome analyses will be performed using an analysis of covariance and descriptive statistics. Discussion: Symptomatic FAI is associated with chronic hip pain, functional limitations, and secondary osteoarthritis. Therefore, optimizing treatment has the potential to improve the lives millions of young, active persons who are diagnosed with this condition. Few orthopaedic surgical trials have similar potential to shift the paradigm of care dramatically towards (or away) from surgical bony and soft tissue interventions.Peer reviewe

Registers in assessing complication and revision after hip arthoplasty

Cemented low-friction arthroplasty, pioneered by Sir John Charnley, is the basis for modern total hip arthroplasty (THA). The Charnley THA is still considered as the gold standard against which new devices are compared. However, aseptic loosening was a relatively common cause for the failure of cemented THAs. Therefore, new fixation methods and bearing surfaces were developed, e.g., uncemented THAs, resurfacing arthroplasty (HRA), and metal-on-metal THAs. National arthroplasty registers were established to assess new THA devices and to detect outlier products as early as possible. The Swedish Hip Arthroplasty Register was established in 1979, the Finnish Arthroplasty Register (FAR) in 1980, the Norwegian Arthroplasty Register in 1987, and the Danish Hip Arthroplasty Register in 1995. A combined Nordic arthroplasty register (Nordic Arthroplasty Register Association, NARA) was established in 2007 with the overall aim of improving the quality of joint replacement surgery by registry-based research collaboration. The aim of this thesis was to assess risk factors and prevalence of adverse reaction to metal debris (ARMD) associated with two metal-on-metal hip devices – the Birmingham Hip Resurfacing (BHR) HRA and the Biomet ReCap Magnum THA – based on data of the joint replacement register of the Turku University Hospital. Another aim was to compare the differences in survivorship of three HRA designs with their analogous uncemented, large-diameter head metal-on-metal THAs based on FAR data. Further, survival of the most common cemented THA brands was assessed by data of the NARA. We found that hip resurfacing arthroplasty with the BHR HRA may be more dangerous than previously thought. Systematic follow-up of these patients is advised. There was a high prevalence of ARMD among ReCap-M2a-Magnum THA patients. The shortterm revision risk of large diameter head MoM hip replacements was not increased compared to similar HRAs (FAR data), but implant-related factors may contribute to this success. Several brands of cemented THAs performed well in the long term, but there are significant differences in implant survival between the best and the worst performers.Sementtikiinnitteinen lonkan tekonivelleikkaus on modernin lonkkaproteesikirurgian perusta. Muiden leikkausmenetelmien pysyvyystuloksia verrataan edelleen sementtikiinnitteisen Charnleyn proteesiin (DePuy; Johnson and Johnson, New Brunswick, NJ). Sementtikiinnitteisen proteesin uusintaleikkauksen yleisin syy on sementtikiinnityksen pettäminen, eli aseptinen irtoaminen. Uusia kiinnitysmenetelmiä ja liukupintaratkaisuja kehitettiinkin sementtiproteesien verrattain tavallisen irtoamisongelman takia. Sementitön lonkan tekonivel kiinnittyy luutumisen kautta. Perinteisen muovi-metalli liukuparin lisäksi on käytetty keraami-keraami sekä keraamimuovi liukupintavaihtoehtoja. 2000-luvulla liukupintamateriaaleina yleistyivät metallimetalliliukupinnat. Kansalliset tekonivelrekisterit on perustettu tuottamaan tietoa tekonivelten uusintaleikkauksista. Tavoitteena on havaita huonot proteesimallit mahdollisimman aikaisin, jotta uusintaleikkauksien määrä saataisiin pidettyä vähäsenä. Pohjoismaisista tekonivelrekistereistä Ruotsin lonkkaproteesirekisteri perustettiin 1979, Suomen Tekonivelrekisteri 1980, Norjan tekonivelrekisteri 1987, ja Tanskan lonkkaproteesirekisteri 1995. Yhdistetty pohjoismainen tekonivelrekisteri (The Nordic Arthroplasty Register Association, NARA) perustettiin 2007 parantamaan tekonivelkirurgian laatua Pohjoismaissa havainnoivan rekisteritutkimuksen avulla. Tämän väitöskirjatutkimuksemme tarkoituksena oli arvioida metalli-metalliliukupintaisiin lonkan tekoniveliin liittyvien metallihierrekomplikaatioiden yleisyyttä ja riskitekijöitä käytettäessä BHR- ja ReCap Magnum-lonkkaproteeseja Turun yliopistollisen sairaalan proteesirekisteriin perustuen. Tarkoituksenamme oli myös arvioida lonkan pinnoiteproteesien ja vastaavien kokotekonivelmallien pysyvyyttä lyhyen aikavälin seurannassa Suomen Tekonivelrekisteriin perustuen. Tutkimme myös sementtikiinnitteisten lonkan tekonivelten mallikohtaista pysyvyyttä Pohjoismaisessa NARA-rekisterissä. Totesimme tutkimuksessamme että BHR-pinnoitetekonivelleikkaukseen saattaa liittyä aiempaa luultua enemmän ongelmia. Suosittelemmekin näiden potilaiden systemaattista seurantaa. Metallihierrekomplikaatioiden määrä ReCap Magnumproteesia käytettäessä oli varsin korkea. Lyhyen aikavälin uusintaleikkausriski käytettäessä pinnoiteproteesia tai vastaavaa isonuppista, metalli-metalli-liukupintaista kokotekoniveltä oli samaa suuruusluokkaa. Havaitsimme lisäksi että monet sementtikiinnitteiset kokotekonivelmallit toimivat hyvin pitkällä aikavälillä. Mallien pitkäaikaispysyvyydessä oli kuitenkin merkitseviä eroja

Nitrogen Balance after the Administration of a Prolonged-Release Protein Substitute for Phenylketonuria as a Single Dose in Healthy Volunteers

Nitrogen balance is the difference between nitrogen excreted as urea and nitrogen ingested, mainly in proteins. Increased circulating concentrations of amino acids (AA) in the bloodstream are usually associated with proportional increases in the production and excretion of urea. Previously, we reported results from a randomized, controlled, single-dose, crossover trial in healthy adult volunteers (n = 30) (Trial Registration: ISRCTN11016729), in which a Test product (prolonged-release AA mixture formulated with Physiomimic Technology™ (PT™)) significantly slowed down the release and reduced the peak plasma concentrations of essential AAs compared with a free AA mixture (Reference product) while maintaining essential AA bioavailability. Here, we report an assessment of the nitrogen balance from the same study. The amount of nitrogen contained in plasma AAs, levels of blood urea nitrogen (BUN) (p &lt; 0.0001) and changes in BUN (p &lt; 0.0001) were smaller after the Test product compared with the Reference product. These findings suggest that the production of urea in proportion to systemic AA availability was significantly smaller after the administration of the Test product compared with the Reference product and that the test product conferred the increased utilization of AAs for protein synthesis and reduced their oxidation and conversion to urea. In the clinical setting, it is possible that the effects of PT™ observed on the disposition of free AAs in this study may translate to health benefits in terms of physiological body composition and growth if used for the treatment of subjects with phenylketonuria (PKU). Further investigation in patients with PKU is warranted