Constrained condylar knee without stem extensions for difficult primary total knee arthroplasty

Two hundred forty-eight constrained condylar total knee arthroplasties consecutively implanted without the use of diaphyseal stem extensions were studied in 180 patients. Preoperative deformity was severe (82% Ahlb?ck grade 4-5). One hundred ninety-two knees (148 patients) were reviewed at mean 47-month follow-up (range: 24-72 months). Knee Society score improved from 36 to 89 points, and function score improved from 42 to 76 points. Failure rate was 2.5% (2 infections, 1 aseptic loosening, 1 supracondylar femoral fracture, and 1 tibial post fracture). Five (2.5%) knees had patellofemoral complications. Nonprogressive radiolucent lines were present in 16% of cases. Use of a nonmodular constrained condylar knee for primary severely damaged knees demonstrated reliable short- to mid-term results with a low complication rate and questioned the routine use of intramedullary stem extensions in all such cases.     

Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects

Besides the use of autologous bone grafting several osteoconductive and osteoinductive methods have been reported to improve bone healing. However, persistent non‐union occurs in a considerable number of cases and compromised angiogenesis is suspected to impede bone regeneration. Hyperbaric oxygen therapy (HBO) improves angiogenesis. This study evaluates the effects of HBO on bone defects treated with autologous bone grafting in a bone defect model in rabbits. Twenty‐four New‐Zealand White Rabbits were subjected to a unilateral critical sized diaphyseal radius bone defect and treated with autologous cancellous bone transplantation. The study groups were exposed to an additional HBO treatment regimen. Bone regeneration was evaluated radiologically and histologically at 3 and 6 weeks, angiogenesis was assessed by immunohistochemistry at three and six weeks. The additional administration of HBO resulted in a significantly increased new bone formation and angiogenesis compared to the sole treatment with autologous bone grafting. These results were apparent after three and six weeks of treatment. The addition of HBO therapy to autologous bone grafts leads to significantly improved bone regeneration. The increase in angiogenesis observed could play a crucial role for the results observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:513–520, 2015.     

Endovascular revascularization of renal artery stenosis in the solitary functioning kidney

The treatment of renal artery stenosis by angioplasty and stenting is an effective and accepted alternative to surgery for the treatment of renovascular hypertension and preservation of renal function. We report the technical and clinical outcomes of renal artery stenting in patients with a solitary functioning kidney and renal artery stenosis. From October 1993 to November 1999, 30 stents were placed in the renal arteries of 27 patients (mean age 72 ± 8 years) with a solitary functioning kidney and azotemia. The mean diameter renal artery stenosis was 86 ± 14%. The mean preprocedure serum creatinine (Cr) level was 3.0 ± 1.5 mg/dL (range 1.5–7.5 mg/dL), arterial blood pressure was 171 ± 29/85 ± 13 mmHg, and the number of antihypertensive drugs was 2.9 ± 1.1. Indications for stenting were suboptimal balloon dilation (n = 16), intimai dissection (n = 6), and restenosis following angioplasty (n = 5). Atherosclerotic ostial lesions were present in 25 (93%) of 27 renal arteries. This represents the largest series of renal artery stenting in patients with a solitary functioning kidney, and demonstrates this treatment modality to be a relatively safe alternative to conventional surgery in this high-risk patient group. Most (74%) of the patients in this series had improved or stabilized renal function. Further efforts to define preprocedural indicators of success are necessary to identify the patients who may benefit from revascularization of their solitary kidney. Presented at the Twenty-fifth Annual Meeting of the Peripheral Vascular Surgery Society, Toronto, Ontario, Canada, June 10, 2000.     

COL1A1 Sp1 polymorphism predicts perimenopausal and early postmenopausal spinal bone loss.

Genetic factors play an important role in the pathogenesis of osteoporosis but the genes that determine susceptibility to poor bone health are defined incompletely. Previous work has shown that a polymorphism that affects an Spl binding site in the COLIA1 gene is associated with reduced bone mineral density (BMD) and an increased risk of osteoporotic fracture in several populations. Data from cross-sectional studies have indicated that COLIA1 Sp1 alleles also may be associated with increased rates of bone loss with age, but longitudinal studies, which have examined bone loss in relation to COLIA1 genotype, have yielded conflicting results. In this study, we examined the relationship between COLIA1 Sp1 alleles and early postmenopausal bone loss measured by dual-energy X-ray absorptiometry (DXA) in a population-based cohort of 734 Scottish women who were followed up over a 5- to 7-year period. The distribution of genotypes was as expected in a white population with 484 "SS" homozygotes (65.9%); 225 "Ss" heterozygotes (30.7%), and 25 "ss" homozygotes (3.4%). Women taking hormone-replacement therapy (HRT; n = 239) had considerably reduced rates of bone loss at the spine (-0.40 +/- 0.06%/year) and hip (-0.56 +/- 0.06%/year) when compared with non-HRT users (n = 352; spine, -1.36 +/- 0.06%/year; hip, -1.21 +/- 0.05%/year; p < 0.001 for both sites). There was no significant difference in baseline BMD values at the lumbar spine (LS) or femoral neck (FN) between genotypes or in the rates of bone loss between genotypes in HRT users. However, in non-HRT users (n = 352), we found that ss homozygotes (n = 12) lost significantly more bone at the lumbar site than the other genotype groups in which ss = -2.26 +/- 0.31%/year compared with SS = -1.38 +/- 0.07%/year and Ss = -1.22 +/- 0.10%/year (p = 0.004; analysis of variance [ANOVA]) and a similar trend was observed at the FN in which ss = -1.78 +/- 0.19%/year compared with SS = -1.21 +/- 0.06%/year and Ss = -1.16 +/- 0.08%/year (p = 0.06; ANOVA). The differences in spine BMD loss remained significant after correcting for confounding factors. Stepwise multiple regression analysis showed that COLIA1 genotype independently accounted for a further 3.0% of the variation in spine BMD change after age (4.0%), weight (5.0%), and baseline BMD (2.8%). We conclude that women homozygous for the Sp1 polymorphism are at significantly increased risk of excess rates of bone loss at the spine, but this effect may be nullified by the use of HRT.     

Targeted Next-generation Sequencing of Advanced Prostate Cancer Identifies Potential Therapeutic Targets and Disease Heterogeneity

Background

Most personalized cancer care strategies involving DNA sequencing are highly reliant on acquiring sufficient fresh or frozen tissue. It has been challenging to comprehensively evaluate the genome of advanced prostate cancer (PCa) because of limited access to metastatic tissue.

Objective

To demonstrate the feasibility of a novel next-generation sequencing (NGS)–based platform that can be used with archival formalin-fixed paraffin-embedded (FFPE) biopsy tissue to evaluate the spectrum of DNA alterations seen in advanced PCa.

Design, setting, and participants

FFPE samples (including archival prostatectomies and prostate needle biopsies) were obtained from 45 patients representing the spectrum of disease: localized PCa, metastatic hormone-naive PCa, and metastatic castration-resistant PCa (CRPC). We also assessed paired primaries and metastases to understand disease heterogeneity and disease progression.

Intervention

At least 50 ng of tumor DNA was extracted from FFPE samples and used for hybridization capture and NGS using the Illumina HiSeq 2000 platform.

Outcome measurements and statistical analysis

A total of 3320 exons of 182 cancer-associated genes and 37 introns of 14 commonly rearranged genes were evaluated for genomic alterations.

Results and limitations

We obtained an average sequencing depth of >900X. Overall, 44% of CRPCs harbored genomic alterations involving the androgen receptor gene (AR), including AR copy number gain (24% of CRPCs) or AR point mutation (20% of CRPCs). Other recurrent mutations included transmembrane protease, serine 2 gene (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) gene (ERG) fusion (44%); phosphatase and tensin homolog gene (PTEN) loss (44%); tumor protein p53 gene (TP53) mutation (40%); retinoblastoma gene (RB) loss (28%); v-myc myelocytomatosis viral oncogene homolog (avian) gene (MYC) gain (12%); and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α gene (PIK3CA) mutation (4%). There was a high incidence of genomic alterations involving key genes important for DNA repair, including breast cancer 2, early onset gene (BRCA2) loss (12%) and ataxia telangiectasia mutated gene (ATM) mutations (8%); these alterations are potentially targetable with poly(adenosine diphosphate-ribose)polymerase inhibitors. A novel and actionable rearrangement involving the v-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) was also detected.

Conclusions

This first-in-principle study demonstrates the feasibility of performing in-depth DNA analyses using FFPE tissue and brings new insight toward understanding the genomic landscape within advanced PCa.     

The Fate of the Remaining Knee(s) or Hip(s) in Osteoarthritic Patients Undergoing a Primary TKA or THA

The purpose of this study was to determine the fate of the remaining hip(s) and knee(s) following an initial total hip or knee arthroplasty in 5352 patients with idiopathic osteoarthritis who were followed for a minimum ten years (mean 17.8 ± 5.7 years). Following an initial primary TKA, 46.0% of patients had a contralateral TKA, 2.3% had an ipsilateral THA and 1.3% had a contralateral THA. Following an initial primary THA, 30.5% of patients had a contralateral THA, 6.8% had an ipsilateral TKA and 2.9% had a contralateral TKA. Cox regression analysis demonstrated that BMI was the sole risk factor for a second THA, but both age less than sixty years and a higher BMI were significant factors for patients requiring an additional primary TKA.     

Sham feed or sham? A meta-analysis of randomized clinical trials assessing the effect of gum chewing on gut function after elective colorectal surgery

Purpose  Enhanced recovery programs aim to expedite gut function after elective colorectal surgery. Early oral feeding simulates gut function but is not always feasible. Gum chewing, a form of sham feed, is an alternative. We assessed current evidence for gum chewing and gut function. Study design  All randomized controlled trials (RCTs) between 1990 and 2008 comparing gum chewing with controls/placebo were analyzed irrespective of language, blinding, or publication bias. The Jadad scale was used to assess study quality. Endpoints were time to flatus/feces, postoperative complications, and hospital stay. Random and fixed models were employed to aggregate study endpoints and assess heterogeneity. Results  Six RCTs containing 256 patients were included. Significant heterogeneity was identified and random effects model was employed. Heterogeneity may be explained through variations in delivery of surgical care. Significant reductions in the time to flatus and time to feces were identified but no significant difference in hospital or in-hospital postoperative complications were found. Conclusions  Gum chewing significantly reduced time to flatus and feces; however, hospital stay and postoperative complications were not reduced. Significant study heterogeneity means that these results should be interpreted with caution. Presentation to European Society of Coloproctology Annual Scientific Meeting Malta September 2007 Presentation to West of Scotland Surgical Association Annual Scientific Meeting October 2007