Staggered bilateral total knee arthroplasty during a single hospitalization: is it still an option? a systematic review.

BACKGROUND: Bilateral knee osteoarthritis requiring total knee arthroplasty (TKA) can be addressed simultaneously in one surgical setting, staggered a few days apart during a single hospitalization, or staged several weeks to months apart. Several studies have reported on the complications and clinical outcomes of staggered bilateral TKA (BTKA) in a single hospitalization. However, there is no consensus regarding the safety and efficacy of this practice. MATERIALS AND METHODS: We performed a systematic review of the literature, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and identifying articles that reported the clinical outcomes and postoperative complications following staggered BTKA. RESULTS: Overall, six articles were included for analysis, including 43,892 patients in total. Females (n = 25,931; 59% of all patients) outnumbered males (n = 17,961; 40.1% of all patients), and most patients were middle-aged or elderly (mean age: 68.0 years). The majority of studies (83%) used a 1-week interval as the maximum time for single-hospitalization staggered BTKA. Five studies (83%) reported no difference in mortality rates between staggered, simultaneous, or staged BTKA. Compared to staged BTKA, staggered BTKA conferred an increased rate of blood transfusions. There was no consensus that staggered BTKA led to reduced complications rates, compared to simultaneous or staged BTKA. CONCLUSIONS: Single-hospitalization staggered BTKA does not appear to be safer than the well-established simultaneous or staged procedures. Overall, the data suggest that staggered BTKA will continue to decline in utilization, as staggered BTKA does not appear to yield clinical advantage over simultaneous BTKA in a medically appropriate patient. LEVEL OF EVIDENCE III: systematic review (lowest level of studies included).

Diluted povidone-iodine irrigation prior to wound closure in primary and revision total joint arthroplasty of hip and knee: a review of the evidence.

Periprosthetic Joint Infection (PJI) of the Hip and of the Knee is a tremendous complication associated with high patient morbidity, cost, and increased health care resource utilization. Over the last few years, several perioperative strategies have been developed in the hopes of reducing the risk of early superficial and deep surgical site infection (SSI). One of the most performed intraoperative treatments to reduce the risk of SSI in total joint arthroplasty is the use of dilute povidone-iodine (DPI) irrigation prior to wound closure. For this reason, we believed a systematic review of the literature was needed to better understand the current literature on the efficacy of dilute betadine in reducing PJI. The search terms for this systematic review was performed for keywords "betadine", "povidone-iodine", "lavage", "irrigation" and "arthroplasty". A total of six studies were included, four of these reported the outcome of primary total joint arthroplasty, and two of these reported the outcome of revision total joint arthroplasty. Some studies reported that the use of DPI is effective to reduce the incidence of infective complications, meanwhile other studies did not find differences when DPI was used. More studies must be addressed to provide the efficacy of DPI irrigation.

The use of dual-mobility bearings in patients at high risk of dislocation.

AIMS: Instability continues to be a troublesome complication after total hip arthroplasty (THA). Patient-related risk factors associated with a higher dislocation risk include the preoperative diagnosis, an age of 75 years or older, high body mass index (BMI), a history of alcohol abuse, and neurodegenerative diseases. The goal of this study was to assess the dislocation rate, radiographic outcomes, and complications of patients stratified as high-risk for dislocation who received a dual mobility (DM) bearing in a primary THA at a minimum follow-up of two years. MATERIALS AND METHODS: We performed a retrospective review of a consecutive series of DM THA performed between 2010 and 2014 at our institution (Hospital for Special Surgery, New York, New York) by a single, high-volume orthopaedic surgeon employing a single prosthesis design (Anatomic Dual Mobility (ADM) Stryker, Mahwah, New Jersey). Patient medical records and radiographs were reviewed to confirm the type of implant used, to identify any preoperative risk factors for dislocation, and any complications. Radiographic analysis was performed to assess for signs of osteolysis or remodelling of the acetabulum. RESULTS: There were 151 patients who met the classification of high-risk according to the inclusion criteria and received DM THA during the study period. Mean age was 82 years old (73 to 95) and 114 patients (77.5%) were female. Mean follow-up was 3.6 years (1.9 to 6.1), with five patients lost to follow-up and one patient who died (for a reason unrelated to the index procedure). One patient (0.66%) sustained an intraprosthetic dislocation; there were no other dislocations. CONCLUSION: At mid-term follow-up, the use of a DM bearing for primary THA in patients at high risk of dislocation provided a stable reconstruction option with excellent radiographic results. Longer follow-up is needed to confirm the durability of these reconstructions.

Dislocation following total hip arthroplasty using dual mobility acetabular components: a systematic review.

AIMS: The aim of this systematic review was to report the rate of dislocation following the use of dual mobility (DM) acetabular components in primary and revision total hip arthroplasty (THA). MATERIALS AND METHODS: A systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines was performed. A comprehensive search of Pubmed/Medline, Cochrane Library and Embase (Scopus) was conducted for English articles between January 1974 and March 2016 using various combinations of the keywords "dual mobility", "dual-mobility", "tripolar", "double-mobility", "double mobility", "hip", "cup", "socket". The following data were extracted by two investigators independently: demographics, whether the operation was a primary or revision THA, length of follow-up, the design of the components, diameter of the femoral head, and type of fixation of the acetabular component. RESULTS: In all, 59 articles met our inclusion criteria. These included a total of 17 908 THAs which were divided into two groups: studies dealing with DM components in primary THA and those dealing with these components in revision THA. The mean rate of dislocation was 0.9% in the primary THA group, and 3.0% in the revision THA group. The mean rate of intraprosthetic dislocation was 0.7% in primary and 1.3% in revision THAs. CONCLUSION: Based on the current data, the use of DM acetabular components are effective in minimising the risk of instability after both primary and revision THA. This benefit must be balanced against continuing concerns about the additional modularity, and the new mode of failure of intraprosthetic dislocation. Longer term studies are needed to assess the function of these newer materials compared with previous generations. Cite this article: Bone Joint J 2017;99-B(1 Supple A):18-24.

The Synergy cementless femoral stem in primary total hip arthroplasty at a minimum follow-up of 15 years.

AIMS: We report on the outcome of the Synergy cementless femoral stem with a minimum follow-up of 15 years (15 to 17). PATIENTS AND METHODS: A retrospective review was undertaken of a consecutive series of 112 routine primary cementless total hip arthroplasties (THAs) in 102 patients (112 hips). There were 60 female and 42 male patients with a mean age of 61 years (18 to 82) at the time of surgery. A total of 78 hips in the 69 patients remain in situ; nine hips in eight patients died before 15 years, and 16 hips in 16 patients were revised. Clinical outcome scores and radiographs were available for 94 hips in 85 patients. RESULTS: In all, four stems were revised. One stem was revised for aseptic loosening; two stems because of deep infection; and one because of periprosthetic femoral fracture. There was a significant improvement in all components of the Western Ontario and McMaster Universities Osteoarthritis Index score at the final follow-up (total: p < 0.001, pain: p < 0.001, stiffness: p < 0.001, function: p < 0.001). The mean Harris Hip Scores improved from 47 points (27 to 59) pre-operatively to 89 points (65 to 100) at the latest follow-up (p < 0.001). Kaplan-Meier survivorship, with stem revision for aseptic loosening as the endpoint, was 98.9% at 15 years (95% confidence interval (CI) 96.9 to 100, number at risk at 15 years: 90) and with stem revision for any reason was 95.7% (95% CI 91.7 to 99.8, number at risk at 15 years: 90). CONCLUSION: The Synergy cementless femoral stem demonstrates excellent survivorship and functional outcomes at 15 years. Cite this article: Bone Joint J 2017;99-B:29-36.

Downregulation of HMGA-targeting microRNAs has a critical role in human pituitary tumorigenesis.

Previous studies have demonstrated that high mobility group A proteins have a critical role on the onset of human pituitary adenomas. Indeed, both high mobility group A (HMGA) genes are overexpressed in pituitary adenomas, and consistently transgenic mice overexpressing either the Hmga1 or the Hmga2 gene develop mixed growth hormone/prolactin (GH-PRL)-secreting pituitary adenomas. Trisomy of chromosome 12, where HMGA2 is located, and/or amplification of the HMGA2 gene locus account for the HMGA2 overexpression in most human prolactinomas. Conversely, HMGA1 overexpression is not associated to any rearrangement or amplification of the HMGA1 locus. We have first identified micro RNAs (miRNAs) able to target both HMGA1 and HMGA2 messenger RNAs. Then, all of these miRNAs have been found downregulated in pituitary adenomas of different histotypes, compared with normal pituitary. Interestingly, their downregulation was also observed in nonfunctioning pituitary adenomas where HMGA2 overexpression is not associated to any alteration of the HMGA2 locus. Functional studies show that all these HMGA-targeting miRNAs inhibit the proliferation of the rat pituitary adenoma cell line GH3. Therefore, these results indicate that the downregulation of the miRNAs able to target the HMGA genes could contribute to increase HMGA protein levels in human pituitary adenomas, and then to pituitary tumorigenesis.

HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents.

DNA-damaging therapies represent a keystone in cancer treatment. Unfortunately, many tumors often relapse because of a group of cancer cells, which are resistant to conventional therapies. High-mobility group A (HMGA) proteins has a key role in cell transformation, and their overexpression is a common feature of human malignant neoplasias, representing a poor prognostic index often correlated to anti-cancer drug resistance. Our previous results demonstrated that HMGA1 is a substrate of ataxia-telangiectasia mutated (ATM), the main cellular sensor of genotoxic stress. Here we also report thatHMGA2, the other member of the HMGA family, is a novel substrate of ATM. Interestingly, we found that HMGA proteins positively regulate ATM gene expression. Moreover, induction of ATM kinase activity by DNA-damaging agents enhances HMGA-dependent transcriptional activation of ATM promoter, suggesting that ATM expression is modulated by a DNA-damage- and HMGA-dependent positive feedback loop. Finally, inhibition of HMGA expression in mouse embryonic fibroblasts and in cancer cells strongly reduces ATM protein levels, impairing the cellular DNA-damage response and enhancing the sensitivity to DNA-damaging agents. These findings indicate this novel HMGA-ATM pathway as a new potential target to improve the effectiveness of conventional anti-neoplastic treatments on the genotoxic-drug resistant cancer cells.

Regulation of microRNA expression by HMGA1 proteins.

The High Mobility Group proteins HMGA1 are nuclear architectural factors that play a critical role in a wide range of biological processes. Since recent studies have identified the microRNAs (miRNAs) as important regulators of gene expression, modulating critical cellular functions such as proliferation, apoptosis and differentiation, the aim of our work was to identify the miRNAs that are physiologically regulated by HMGA1 proteins. To this purpose, we have analysed the miRNA expression profile of mouse embryonic fibroblasts (MEFs) carrying two, one or no Hmga1 functional alleles using a microarray (miRNA microarray). By this approach, we found a miRNA expression profile that differentiates Hmga1-null MEFs from the wild-type ones. In particular, a significant decrease in miR-196a-2, miR-101b, miR-331 and miR-29a was detected in homozygous Hmga1-knockout MEFs in comparison with wild-type cells. Consistently, these miRNAs are downregulated in most of the analysed tissues of Hmga1-null mice in comparison with the wild-type mice. ChIP assay shows that HMGA1 is able to bind regions upstream of these miRNAs. Moreover, we identified the HMGA2 gene product as a putative target of miR-196a-2, suggesting that HMGA1 proteins are able to downregulate the expression of the other member of the HMGA family through the regulation of the miR-196a-2 expression. Finally, ATXN1 and STC1 gene products have been identified as targets of miR-101b. Therefore, it is reasonable to hypothesize that HMGA1 proteins are involved in several functions by regulating miRNA expression.

HAND1 gene expression is negatively regulated by the High Mobility Group A1 proteins and is drastically reduced in human thyroid carcinomas.

HMGA1 proteins exert their major physiological function during embryonic development and play a critical role in neoplastic transformation. Here, we show that Hand1 gene, which codes for a transcription factor crucial for differentiation of trophoblast giant cells and heart development, is upregulated in hmga1 minus embryonic stem cells. We demonstrate that HMGA1 proteins bind directly to Hand1 promoter both in vitro and in vivo and inhibit Hand1 promoter activity. We have also investigated HAND1 expression in human thyroid carcinoma cell lines and tissues, in which HMGA proteins are overexpressed, with respect to normal thyroid; an inverse correlation between HMGA1 and HAND1 expression was found in all thyroid tumor histotypes. A correlation between HAND1 gene repression and promoter hypermethylation was found in anaplastic carcinomas but not in other thyroid tumor histotypes. Therefore, we can hypothesize that HMGA1 overexpression plays a key role on HAND1 silencing in differentiated thyroid carcinomas and that promoter hypermethylation occurs in later stages of thyroid tumor progression. Finally, the restoration of the HAND1 gene expression reduces the clonogenic ability of two human thyroid carcinoma-derived cell lines, suggesting that HAND1 downregulation may have a role in the process of thyroid carcinogenesis.

B-RAF mutations are a rare event in pituitary adenomas.

Pituitary tumors are a relatively common neoplasia whose pathogenesis is still largely unknown. Recent studies have revealed frequent activating mutations of the gene for B-RAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies, including melanoma, thyroid, colorectal and ovarian cancer. However, analyses of B-RAF mutations in pituitary tumors have not been reported so far. Therefore, in the present study we have investigated the presence of the B-RAF mutations, by polymerase chain reaction (PCR) amplification of the hot spot exons 11 and 15, followed by direct sequencing, in 50 human pituitary adenomas, including 25 NFPA and 25 secreting adenomas (10 GH, 5 PRL, 6 LH and/or FSH, 4 GH/PRL). We found only one V600E mutation in a NFPA sample, suggesting that B-RAF mutations are a rare event in pituitary tumorigenesis.