Survival of current production tumor endoprostheses: complications, functional results, and a comparative statistical analysis.

BACKGROUND AND OBJECTIVES: Retrospectively analyze outcomes of current-generation Global Modular Replacement System (GMRS) modular tumor endoprosthesis for the lower limb in primary and secondary implantation procedures. METHODS: Two hundred ninety five prostheses were implanted, 197 were primary implants, 98 were for revision surgery; revision procedures included 84 failed tumor reconstructions and 14 failed non-tumor reconstructions. Anatomic sites included: distal femur 199; proximal tibia 60; proximal femur 32;total femur 4. Endoprosthesis failures were classified as soft-tissue failures (Type 1), aseptic loosening (Type 2), structural fracture (Type 3), infection (Type 4), and tumor recurrence (Type 5). MSTS functional scores were measured. RESULTS: The overall failure rate was 28.8% and failure occurred at a median of 1.7 years (range, 1 month to 7 years). At a mean oncologic follow up of 4.2 years (range, 2-8 years), 195 patients are continuously NED, 43 NED after treatment of relapse, 10 AWD, 33 DWD. There was a significant difference in implant survival of all modes of failure between primary and revision implants (P = 0.03). No prosthetic fracture occurred. The average functional score was 81.6% (24.5). CONCLUSIONS: Mid-term results with GMRS are promising, with good functional results and low incidence of complications for primary implants. LEVEL OF EVIDENCE: Therapeutic study, level IV-1 (case series).

Cemented versus cementless endoprostheses for lower limb salvage surgery.

PURPOSE: To determine the survival and failures of cemented vs cementless endoprostheses. METHODS: We retrospectively studied 232 patients treated with lower limb salvage surgery and reconstruction using cementless and cemented endoprostheses from 2002 to 2007. We compared survival and failures of the endoprostheses regarding age, gender, body mass index (BMI), diagnosis, site of reconstruction, radiation therapy, chemotherapy, and stem fixation. RESULTS: The mean patient follow-up was 28 months (median 24; range 12-84). The overall survival of cemented and cementless endoprostheses at 60 months was 64 and 78%, respectively (p=0.0078). Survival at 60 months of cemented and cementless endoprostheses to infection was 68 and 82%, respectively (p=0.0248). Survival of cemented and cementless endoprostheses to aseptic loosening at 60 months was 94 and 96%, respectively (p=0.1493). The only significant univariate and multivariate predictor of survival was the cementless type of stem fixation. CONCLUSION: Cementless endoprostheses have higher overall survival and survival to infection compared to cemented endoprostheses. Survival to aseptic loosening is not different. Stem fixation is the only significant variable for survival.

Surgical Site Infection in Patients Managed with an Endoprosthesis for the Treatment of Cancer: Evaluation of Patient, Disease, and Index Surgical Factors.

BACKGROUND: Surgical site infection (SSI) after segmental endoprosthetic reconstruction in patients treated for oncologic conditions remains both a devastating and a common complication. The goal of the present study was to identify variables associated with the success or failure of treatment of early SSI following the treatment of a primary bone tumor with use of a segmental endoprosthesis. METHODS: The present study used the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) data set to identify patients who had been diagnosed with an SSI after undergoing endoprosthetic reconstruction of a lower extremity primary bone tumor. The primary outcome of interest in the present study was a dichotomous variable: the success or failure of infection treatment. We defined failure as the inability to eradicate the infection, which we considered as an outcome of amputation or limb retention with chronic antibiotic suppression (>90 days or ongoing therapy at the conclusion of the study). Multivariable models were created with covariates of interest for each of the following: surgery characteristics, cancer treatment-related characteristics, and tumor characteristics. Multivariable testing included variables selected on the basis of known associations with infection or results of the univariable tests. RESULTS: Of the 96 patients who were diagnosed with an SSI, 27 (28%) had successful eradication of the infection and 69 had treatment failure. Baseline and index procedure variables showing significant association with SSI treatment outcome were moderate/large amounts of fascial excision ≥1 cm2) (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.001), use of local muscle/skin graft (OR,11.88 [95% CI, 1.83 to 245.83]; p = 0.031), and use of a deep Hemovac (OR, 0.24 [95% CI, 0.05 to 0.85]; p = 0.041). In the final multivariable model, excision of fascia during primary tumor resection was the only variable with a significant association with treatment outcome (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.018). CONCLUSIONS: The results of this secondary analysis of the PARITY trial data provide further insight into the patient-, disease-, and treatment-specific associations with SSI treatment outcomes, which may help to inform decision-making and management of SSI in patients who have undergone segmental bone reconstruction of the femur or tibia for oncologic indications. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Telomeres--what's new at the end?

Telomeres are specialized chromatin domains located at the ends of chromosomes. They are involved in chromosome replication, stability and localization in the nucleus. In addition to these functions, recent work suggests that telomeres are involved in such superficially diverse cellular phenomena as ageing, cancer, nuclear architecture and nuclear/cellular division.

An overhanging 3' terminus is a conserved feature of telomeres.

The reactivity of single-stranded thymidines with osmium tetraoxide was used to demonstrate the existence of a terminal overhang of the G-rich strand of telomeres from two distantly related eucaryotes, the ciliated protozoan Tetrahymena spp. and the acellular slime mold Didymium spp. Conservation of a G-strand overhang at the molecular terminus of telomeres is consistent with our suggestion that an unusual DNA structure formed by the G-strand overhang is important for telomere function (E. Henderson, C. C. Hardin, S. K. Wolk, I. Tinoco Jr., and E. H. Blackburn, Cell 51:899-908, 1987).

The stability of the hip after the use of a proximal femoral endoprosthesis for oncological indications: analysis of variables relating to the patient and the surgical technique.

AIMS: Instability of the hip is the most common mode of failure after reconstruction with a proximal femoral arthroplasty (PFA) using an endoprosthesis after excision of a tumour. Small studies report improved stability with capsular repair of the hip and other techniques, but these have not been investigated in a large series of patients. The aim of this study was to evaluate variables associated with the patient and the operation that affect post-operative stability. We hypothesised an association between capsular repair and stability. PATIENTS AND METHODS: In a retrospective cohort study, we identified 527 adult patients who were treated with a PFA for tumours. Our data included demographics, the pathological diagnosis, the amount of resection of the abductor muscles, the techniques of reconstruction and the characteristics of the implant. We used regression analysis to compare patients with and without post-operative instability. RESULTS: A total of 20 patients out of 527 (4%) had instability which presented at a mean of 35 days (3 to 131) post-operatively. Capsular repair was not associated with a reduced rate of instability. Bivariate analysis showed that a posterolateral surgical approach (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.02 to 0.86) and the type of implant (p = 0.046) had a significant association with reduced instability; age > 60 years predicted instability (OR 3.17, 95% CI 1.00 to 9.98). Multivariate analysis showed age > 60 years (OR 5.09, 95% CI 1.23 to 21.07), female gender (OR 1.73, 95% CI 1.04 to 2.89), a malignant primary bone tumour (OR 2.04, 95% CI 1.06 to 3.95), and benign condition (OR 5.56, 95% CI 1.35 to 22.90), but not metastatic disease or soft-tissue tumours, predicted instability, while a posterolateral approach (OR 0.09, 95% CI 0.01 to 0.53) was protective against instability. No instability occurred when a synthetic graft was used in 70 patients. CONCLUSION: Stability of the hip after PFA is influenced by variables associated with the patient, the pathology, the surgical technique and the implant. We did not find an association between capsular repair and improved stability. Extension of the tumour often dictates surgical technique; however, our results indicate that PFA using a posterolateral approach with a hemiarthroplasty and synthetic augment for soft-tissue repair confers the lowest risk of instability. Patients who are elderly, female, or with a primary benign or malignant bone tumour should be counselled about an increased risk of instability. Cite this article: Bone Joint J 2017;99-B:531-7.

Comparison of postoperative complications in healthy dogs undergoing open and closed orchidectomy.

OBJECTIVE: To compare closed and open orchidectomy in dogs and the associated complications. METHODS: A randomised controlled blinded prospective clinical study of 73 cases was undertaken involving the recording of all complications during and in the 10 days following orchidectomy of dogs fulfilling the standardised inclusion criteria. The active variable was the surgical technique of either open or closed orchidectomy. RESULTS: Dogs undergoing open orchidectomy experienced significantly more complication events than the dogs undergoing closed orchidectomy [24 of 34 (70%) versus 18 of 39 (46%), P = 0 · 04]. Dogs undergoing open orchidectomy were statistically more likely to develop scrotal complications (21 of 34, 61%) compared with dogs undergoing closed orchidectomy (13 of 39, 33%; P = 0 · 02). CLINICAL SIGNIFICANCE: Open orchidectomy is associated with a higher overall complication rate in the first 10 days after surgery than closed orchidectomy. Open orchidectomy is also associated with increased scrotal complications including swelling, bruising and pain compared with closed orchidectomy.

The impact of demographic, social, and environmental factors on the development of steroid-responsive meningitis-arteritis (SRMA) in the United Kingdom.

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is an inflammatory disease of dogs that is suspected to be immune-mediated. The development of other immune-mediated diseases has been linked to vaccinations, time of the year, geographic location, sex, neuter status, and breed. HYPOTHESIS/OBJECTIVES: To identify if the development of SRMA is associated with time of year, vaccination, geographic location, sex, neuter status, and breed. ANIMALS: Sixty SRMA cases and 180 controls, all ≤24 months of age and matched for year of presentation, from a referral hospital population in the United Kingdom. METHODS: Retrospective case-control study with unconditional logistic regression analysis. RESULTS: Beagles (P = .001), Border Collies (P = .001), Boxers (P = .032), Jack Russell Terriers (P = .001), Weimaraners (P = .048), and Whippets (P < .001) had significantly greater odds of developing SRMA in this population of dogs. Vaccination, time of year, geographic category, sex, and neuter status did not increase the odds of developing SRMA. CONCLUSIONS AND CLINICAL IMPORTANCE: Only breed increased the odds of developing SRMA. It would be prudent to investigate the genetics of the identified breeds to help elucidate the etiopathogenesis of SRMA.

Classification of failure of limb salvage after reconstructive surgery for bone tumours : a modified system Including biological and expandable reconstructions.

Previous classification systems of failure of limb salvage focused primarily on endoprosthetic failures and lacked sufficient depth for the effective study of the causes of failure. In order to address these inadequacies, the International Society of Limb Salvage (ISOLS) formed a committee to recommend revisions of the previous systems. The purpose of this study was to report on their recommendations. The modifications were prepared using an earlier, evidence-based model with subclassification based on the existing medical literature. Subclassification for all five primary types of failure of limb salvage following endoprosthetic reconstruction were formulated and a complementary system was derived for the failure of biological reconstruction. An additional classification of failure in paediatric patients was also described. Limb salvage surgery presents a complex array of potential mechanisms of failure, and a complete and precise classification of types of failure is required. Earlier classification systems lacked specificity, and the evidence-based system outlined here is designed to correct these weaknesses and to provide a means of reporting failures of limb salvage in order to allow the interpretation of outcome following reconstructive surgery.

Cell viability and probe-cell membrane interactions of XR1 glial cells imaged by atomic force microscopy.

As atomic force microscopy (AFM) imaging of live specimens becomes more commonplace, at least two important questions arise: 1) do live specimens remain viable during and after AFM, and 2) is there transfer of membrane components from the cell to the AFM probe during probe-membrane interactions? We imaged live XR1 glial cells in culture by single- or dual-pass contact or tapping-mode AFM, examined cell viability at various postimaging times, and report that AFM-imaged live XR1 cells remained viable up to 48 h postimaging and that cell death rates did not increase. To determine if nonlethal, transient interactions between the AFM probe and cell membrane led to transfer of XR1 cell membrane phospholipid components on the probe, we treated the scanned probes with the lipid-binding fluorophore FM 1-43. Confocal microscopy revealed that phospholipid membrane components did accumulate on the probe, and to a generally greater extent during contact-mode imaging than during tapping-mode imaging. Moreover, membrane accumulations on the probe were greater when live XR1 cells were damaged or perturbed, yet membrane did not accumulate in fluorescently detectable quantities during repeated "force curves" during control experiments. Taken together, our data indicate that although AFM imaging of live cells in culture does not affect long-term cell viability, there are substantial probe-membrane interactions that lead to transfer of membrane components to the probe.

Identification of the telomeric sequence of the acellular slime molds Didymium iridis and Physarum polycephalum.

We have determined the telomeric DNA sequence of the acellular slime molds Didymium iridis and Physarum polycephalum. In both organisms the telomeres consist of tandem repeats of the hexamer 5'(TTAGGG)3'. This sequence was determined by cloning and sequencing the telomeric fragment of the linear extrachromosomal ribosomal DNA from Didymium, as well as direct end labeling and sequencing the rDNA from both organisms. Interestingly, this sequence is identical to the telomeric DNA sequence of the flagellated protozoan Trypanosoma brucei, and suggests that despite the diversity of telomeric sequences previously determined in lower eukaryotes, the necessity to create functional telomeres has led to constraints on these sequences.

Telomere G-strand structure and function analyzed by chemical protection, base analogue substitution, and utilization by telomerase in vitro.

Eukaryotic telomeres have a 12-16 nucleotide long deoxyguanosine (dG) rich single-stranded overhang at their molecular termini. Some of the unique features of telomeres are probably attributable to a specialized structure formed by this overhang. In the ciliated protozoan Tetrahymena thermophila, the dG-rich overhang is comprised of approximately two repeats of the sequence d(TTGGGG). Previous work has shown that the synthetic oligonucleotide d(TTGGGG)4 can form an unusual non-Watson-Crick base-paired structure (the "G-strand structure") containing G-G base pairs and syn-guanines. We have tested the susceptibility of various dGs in this structure to methylation by DMS. At 0-10 degrees C one dG residue is hypersensitive to methylation while others are particularly resistant. By systematically substituting deoxyinosine (dI) for dG in d(TTGGGG)4 we identify N2 groups of guanine essential for formation of the G-strand structure. We show that dI-substituted molecules that cannot form the G-strand structure nonetheless function as substrates for telomere repeat addition in vitro by the telomere lengthening enzyme, telomerase. The implications of these data are discussed.