Long-term outcomes of total hip arthroplasty in patients younger than 55 years: a systematic review of the contemporary literature

Background: Total hip arthroplasty (THA) is increasingly performed in younger patients despite the lack of comprehensive assessment of long-term outcomes. We systematically reviewed the contemporary literature to assess the 1) indications, 2) implant selection and long-term survivorship, 3) complication and reoperation rates and 4) radiographic and functional outcomes of primary THA in patients younger than 55 years. Methods: We searched the Embase and MEDLINE databases for English-language articles published between 2000 and 2018 that reported outcomes of primary THA in patients younger than 55 years with a minimum follow-up duration of 10 years. Results: Thirty-two studies reporting on 3219 THA procedures performed in 2434 patients met our inclusion criteria. The most common preoperative diagnoses were avascular necrosis (1044 [32.4%]), osteoarthritis (870 [27.0%]) and developmental dysplasia of the hip (627 [19.5%]). Modular implants (3001 [93.2%]), cementless fixation (2214 [68.8%]) and metal-on-polyethylene bearings (1792 [55.7%]) were frequently used. The mean 5- and 10-year survival rates were 98.7% and 94.6%, respectively. Data on survival beyond 10 years were heterogeneous, with values of 27%­99.5% at 10­14 years, 59%­84% at 15­19 years, 70%­77% at 20­24 years and 60% at 25­30 years. Rates of dislocation, deep infection and reoperation for any reason were 2.4%, 1.2% and 16.3%, respectively. The mean Harris Hip Score improved from 43.6/100 to 91.0/100. Conclusion: Total hip arthroplasty in patients younger than 55 years provides reliable outcomes at up to 10 years. Future studies should evaluate the outcomes of THA in this population at 15­20 years' follow-up.

Contexte: On effectue de plus en plus d'arthroplasties totales de la hanche (ATH) chez des patients qui ne sont pas âgés, malgré l'absence d'évaluation exhaustive des issues à long terme. Nous avons procédé à une revue systématique de la littérature récente pour analyser 1) les indications, 2) la sélection des implants et la survie à long terme, 3) les taux de complications et de réintervention, et 4) les résultats radiographiques et fonctionnels des ATH primaires chez les patients de moins de 55 ans. Méthodes: Nous avons interrogé les bases de données Embase et MEDLINE pour recenser les articles de langue anglaise publiés entre 2000 et 2018 qui faisaient état des issues d'ATH primaires chez des patients de moins de 55 ans suivis pendant au moins 10 ans. Résultats: Trente-deux études portant sur 3219 ATH effectuées chez 2434 patients répondaient à nos critères d'inclusion. Les diagnostics préopératoires les plus fréquents étaient la nécrose avasculaire (1044 [32,4 %]), l'arthrose (870 [27,0 %]) et la dysplasie développementale de la hanche (627 [19,5 %]). Les implants modulaires (3001 [93,2 %]), la fixation non cimentée (2214 [68,8 %]) et le couple métal­polyéthylène (1792 [55,7 %]) ont été fréquemment utilisés. Les taux de survie moyens à 5 et à 10 ans étaient de 98,7 % et de 94,6 %, respectivement. Les données sur la survie au-delà de 10 ans étaient hétérogènes, allant de 27 % à 99,5 % après 10 à 14 ans, de 59 % à 84 % après 15 à 19 ans, de 70 % à 77 % après 20 à 24 ans et de 60 % après 25 à 30 ans. Les taux de dislocation, d'infection profonde et de réintervention, toutes causes confondues, étaient de 2,4 %, de 1,2 % et de 16,3 %, respectivement. Le score de Harris moyen s'est amélioré, passant de 43,6/100 à 91,0/100. Conclusion: L'arthroplastie totale de la hanche chez les patients de moins de 55 ans donne des résultats fiables pour les 10 premières années après l'intervention. Les prochaines études devraient évaluer les issues de l'arthroplastie de la hanche dans cette population après 15 à 20 ans de suivi.

The deubiquitinating enzyme USP19 modulates adipogenesis and potentiates high-fat-diet-induced obesity and glucose intolerance in mice.

AIMS/HYPOTHESIS: Elucidating the molecular mechanisms of fat accumulation and its metabolic consequences is crucial to understanding and treating obesity, an epidemic disease. We have previously observed that Usp19 deubiquitinating enzyme-null mice (Usp19-/-) have significantly lower fat mass than wild-type (WT) mice. Thus, this study aimed to provide further understanding of the role of ubiquitin-specific peptidase 19 (USP19) in fat development, obesity and diabetes. METHODS: In this study, the metabolic phenotypes of WT and Usp19-/- mice were compared. The stromal vascular fractions (SVFs) of inguinal fat pads from WT and Usp19-/- mice were isolated and cells were differentiated into adipocytes in culture to assess their adipogenic capacity. Mice were fed a high-fat diet (HFD) for 18 weeks. Body composition, glucose metabolism and metabolic variables were assessed. In addition, following insulin injection, signalling activity was analysed in the muscle, liver and adipose tissue. Finally, the correlation between the expression of Usp19 mRNA and adipocyte function genes in human adipose tissue was analysed. RESULT: Upon adipogenic differentiation, SVF cells from Usp19-/- failed to accumulate lipid and upregulate adipogenic genes, unlike cells from WT mice. Usp19-/- mice were also found to have smaller fat pads throughout the lifespan and a higher percentage of lean mass, compared with WT mice. When fed an HFD, Usp19-/- mice were more glucose tolerant, pyruvate tolerant and insulin sensitive than WT mice. Moreover, HFD-fed Usp19-/- mice had enhanced insulin signalling in the muscle and the liver, but not in adipose tissue. Finally, USP19 mRNA expression in human adipose tissue was positively correlated with the expression of important adipocyte genes in abdominal fat depots, but not subcutaneous fat depots. CONCLUSIONS/INTERPRETATION: USP19 is an important regulator of fat development. Its inactivation in mice exerts effects on multiple tissues, which may protect against the negative metabolic effects of high-fat feeding. These findings suggest that inhibition of USP19 could have therapeutic potential to protect from the deleterious consequences of obesity and diabetes.

Fixation Options Following Greater Trochanteric Osteotomies and Fractures in Total Hip Arthroplasty: A Systematic Review.

BACKGROUND: The optimal system for greater trochanteric fixation following osteotomy or fracture remains unknown. This systematic review aims to synthesize the available English-language literature on 5 commonly reported trochanteric fixation methods to quantify and compare rates of complications and reoperation. METHODS: A comprehensive search of MEDLINE and Embase databases from January 1946 to June 2017 was performed for articles in English describing fixation of trochanteric osteotomies and fractures using wires, cables, cable-plate devices, claw or locking plates, and trochanteric bolts. Pooled mean rates of complications and reoperation with 95% confidence intervals (CIs) were analyzed using a random-effects model. RESULTS: Fifty-seven studies involving 10,956 hips were eligible for inclusion. Five studies had Level-III evidence and 52 had Level-IV evidence. The pooled mean rate of nonunion was 4.17% (95% CI, 3.21% to 5.13%; I = 79%) for wires, 5.07% (95% CI, 0.37% to 9.77%; I = 74%) for cables, 16.11% (95% CI, 10.85% to 21.37%; I = 89%) for cable-plate systems, 9.60% (95% CI, 2.23% to 16.97%; I = 59%) for claw or locking plates, and 12.42% (95% CI, 3.41% to 21.43%; I = 75%) for trochanteric bolts. Substantial heterogeneity in the data precluded formal statistical comparison of outcomes and complications between implants. CONCLUSIONS: Available literature on the various trochanteric fixation implants is heterogeneous and consists primarily of retrospective case series. Based on the current literature, it is difficult to support the use of one implant over another. Despite superior mechanical properties, rates of complication and reoperation following cable-plate fixation remains suboptimal, especially in complex revision scenarios. Additional rigorous prospective randomized and cohort studies are needed to make definitive recommendations regarding the most reliable method of trochanteric fixation. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Decreased 11ß-Hydroxysteroid Dehydrogenase 1 Level and Activity in Murine Pancreatic Islets Caused by Insulin-Like Growth Factor I Overexpression.

We have reported a high expression of IGF-I in pancreatic islet ß-cells of transgenic mice under the metallothionein promoter. cDNA microarray analysis of the islets revealed that the expression of 82 genes was significantly altered compared to wild-type mice. Of these, 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1), which is responsible for the conversion of inert cortisone (11-dehydrocorticosterone, DHC in rodents) to active cortisol (corticosterone) in the liver and adipose tissues, has not been identified previously as an IGF-I target in pancreatic islets. We characterized the changes in its protein level, enzyme activity and glucose-stimulated insulin secretion. In freshly isolated islets, the level of 11ß-HSD1 protein was significantly lower in MT-IGF mice. Using dual-labeled immunofluorescence, 11ß-HSD1 was observed exclusively in glucagon-producing, islet α-cells but at a lower level in transgenic vs. wild-type animals. MT-IGF islets also exhibited reduced enzymatic activities. Dexamethasone (DEX) and DHC inhibited glucose-stimulated insulin secretion from freshly isolated islets of wild-type mice. In the islets of MT-IGF mice, 48-h pre-incubation of DEX caused a significant decrease in insulin release, while the effect of DHC was largely blunted consistent with diminished 11ß-HSD1 activity. In order to establish the function of intracrine glucocorticoids, we overexpressed 11ß-HSD1 cDNA in MIN6 insulinoma cells, which together with DHC caused apoptosis and a significant decrease in proliferation. Both effects were abolished with the treatment of an 11ß-HSD1 inhibitor. Our results demonstrate an inhibitory effect of IGF-I on 11ß-HSD1 expression and activity within the pancreatic islets, which may mediate part of the IGF-I effects on cell proliferation, survival and insulin secretion.

IGF-I stimulates CCN5/WISP2 gene expression in pancreatic ß-cells, which promotes cell proliferation and survival against streptozotocin.

IGF-I is normally produced from hepatocytes and other sources, stimulates protein synthesis, cell survival, and proliferation through receptor-mediated activation of phosphatidylinositol 3-kinase and MAPK, and targets specific molecules within the pancreatic islet cells. The current study was designed to identify novel targets that may mediate its pro-islet actions. Whole-genome cDNA microarray analysis in IGF-I-overexpressing islets identified 82 genes specifically up- or down-regulated. Prominent among them was CCN5/WISP2 whose expression was increased 3- and 2-fold at the mRNA and protein levels. Dual-labeled immunofluorescence revealed that CCN5 expression was low in the ß-cells of wild-type islets but was significantly induced in response to IGF-I overexpression. In vitro treatment of mouse islets with IGF-I increased both CCN5 mRNA and protein levels significantly. To define the role of CCN5 in islet cell biology, we stably overexpressed its cDNA in insulinoma MIN6 cells and detected a 2-fold increase in the proliferation of MIN6-CCN5 compared with that in control cells, which correlated with significant elevations in the levels of cyclin D1 and the phosphorylation of Akt and Erk2. Moreover, MIN6-CCN5 cells were found to be resistant to streptozotocin-induced cell death. Using confocal microscopy and subcellular fractionation, we found that overexpressed CCN5 exhibited cytoplasmic accumulation upon stimulation by high glucose. Our results indicate that CCN5, which is minimally expressed in islet ß-cells, is strongly and directly induced by IGF-I. CCN5 overexpression stimulates the proliferation of insulinoma cells, activates Akt kinase, and inhibits streptozotocin-induced apoptosis, suggesting that increased CCN5 expression contributes to IGF-I-stimulated islet cell growth and/or survival.