The role of registries in hematological disorders.

Hematopoietic cell transplantation (HCT) was developed more than 65 years ago to treat malignant blood disorders and irreversible bone marrow failures, with the aim of replacing a diseased hematopoietic system with a healthy one (allogeneic HCT). Decades later, the procedure was adapted to apply maximal chemotherapy or radiotherapy, which would result in bone marrow failure, but could be remedied by an infusion of a patient's own cryopreserved bone marrow (autologous HCT). Both treatments are high-risk and complex, especially during the initial phases. However, concerted efforts, vision, and collaboration between physicians and centers worldwide have resulted in HCT becoming a standard of care for many hematological disorders with progressive improvements in outcomes. Registries and the collaboration of societies worldwide have enabled the delivery of this curative therapy to many patients with fatal hematological diseases. More than 1.5 million HCT were performed between 1957 and 2019, and activity is continuously increasing worldwide.

Global characteristics and outcomes of autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma: A study of the worldwide network for blood and marrow transplantation (WBMT).

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.

Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors.

Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (6 World Health Organization regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT numbers increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA-identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/10 million population was observed for autologous HCT (correlation coefficient [r]=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation was detected from related donors (r=0.48 for HLA-identical sibling; r=0.45 for other). The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.

[INTERPOLAR-prospective, interventional studies as part of the Medical Informatics Initiative to improve medication therapy safety in healthcare]. / INTERPOLAR ­ prospektive, interventionelle Studien im Rahmen der Medizininformatik-Initiative zur Verbesserung der Arzneimitteltherapiesicherheit in der Krankenversorgung.

Medication analyses by ward pharmacists are an important measure of drug therapy safety (DTS). Medication-related problems (MRPs) are identified and resolved with the attending clinicians. However, staff resources for extended medication analyses and complete documentation are often limited. Until now, data required for the identification of risk patients and for an extended medication analysis often had to be collected from various parts of the institution's internal electronic medical record (EMR). This error-prone and time-consuming process is to be improved in the INTERPOLAR (INTERventional POLypharmacy-Drug interActions-Risks) project using an IT tool provided by the data integration centers (DIC).INTERPOLAR is a use case of the Medical Informatics Initiative (MII) that focuses on the topic of DTS. The planning phase took place in 2023, with routine implementation planned from 2024. DTS-relevant data from the EMR is to be presented and the documentation of MRPs in routine care is to be facilitated. The prospective multicenter, cluster-randomized INTERPOLAR­1 study serves to evaluate the benefits of IT support in routine care. The aim is to show that more MRPs can be detected and resolved with the help of IT support. For this purpose, six normal wards will be selected at each of eight university hospitals, so that 48 clusters (with a total of at least 70,000 cases) are available for randomization.

The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking.

Epithelial-mesenchymal transition (EMT) plays important roles in tumour progression and is orchestrated by dynamic changes in gene expression. While it is well established that post-transcriptional regulation plays a significant role in EMT, the extent of alternative polyadenylation (APA) during EMT has not yet been explored. Using 3' end anchored RNA sequencing, we mapped the alternative polyadenylation (APA) landscape following Transforming Growth Factor (TGF)-ß-mediated induction of EMT in human mammary epithelial cells and found APA generally causes 3'UTR lengthening during this cell state transition. Investigation of potential mediators of APA indicated the RNA-binding protein Quaking (QKI), a splicing factor induced during EMT, regulates a subset of events including the length of its own transcript. Analysis of QKI crosslinked immunoprecipitation (CLIP)-sequencing data identified the binding of QKI within 3' untranslated regions (UTRs) was enriched near cleavage and polyadenylation sites. Following QKI knockdown, APA of many transcripts is altered to produce predominantly shorter 3'UTRs associated with reduced gene expression. These findings reveal the changes in APA that occur during EMT and identify a potential role for QKI in this process.

Copper chelation suppresses epithelial-mesenchymal transition by inhibition of canonical and non-canonical TGF-ß signaling pathways in cancer.

BACKGROUND: Metastatic cancer cells exploit Epithelial-mesenchymal-transition (EMT) to enhance their migration, invasion, and resistance to treatments. Recent studies highlight that elevated levels of copper are implicated in cancer progression and metastasis. Clinical trials using copper chelators are associated with improved patient survival; however, the molecular mechanisms by which copper depletion inhibits tumor progression and metastasis are poorly understood. This remains a major hurdle to the clinical translation of copper chelators. Here, we propose that copper chelation inhibits metastasis by reducing TGF-ß levels and EMT signaling. Given that many drugs targeting TGF-ß have failed in clinical trials, partly because of severe side effects arising in patients, we hypothesized that copper chelation therapy might be a less toxic alternative to target the TGF-ß/EMT axis. RESULTS: Our cytokine array and RNA-seq data suggested a link between copper homeostasis, TGF-ß and EMT process. To validate this hypothesis, we performed single-cell imaging, protein assays, and in vivo studies. Here, we used the copper chelating agent TEPA to block copper trafficking. Our in vivo study showed a reduction of TGF-ß levels and metastasis to the lung in the TNBC mouse model. Mechanistically, TEPA significantly downregulated canonical (TGF-ß/SMAD2&3) and non-canonical (TGF-ß/PI3K/AKT, TGF-ß/RAS/RAF/MEK/ERK, and TGF-ß/WNT/ß-catenin) TGF-ß signaling pathways. Additionally, EMT markers of MMP-9, MMP-14, Vimentin, ß-catenin, ZEB1, and p-SMAD2 were downregulated, and EMT transcription factors of SNAI1, ZEB1, and p-SMAD2 accumulated in the cytoplasm after treatment. CONCLUSIONS: Our study suggests that copper chelation therapy represents a potentially effective therapeutic approach for targeting TGF-ß and inhibiting EMT in a diverse range of cancers.

The Quaking RNA-binding proteins as regulators of cell differentiation.

The RNA-binding protein Quaking (QKI) has emerged as a potent regulator of cellular differentiation in developmental and pathological processes. The QKI gene is itself alternatively spliced to produce three major isoforms, QKI-5, QKI-6, and QKI-7, that possess very distinct functions. Here, we highlight roles of the different QKI isoforms in neuronal, vascular, muscle, and monocyte cell differentiation, and during epithelial-mesenchymal transition in cancer progression. QKI isoforms control cell differentiation through regulating alternative splicing, mRNA stability and translation, with activities in gene transcription now also becoming evident. These diverse functions of the QKI isoforms contribute to their broad influences on RNA metabolism and cellular differentiation. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Processing > Splicing Regulation/Alternative Splicing RNA in Disease and Development > RNA in Development.

Longitudinal Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging in Sheep (Ovis aries) With Quinolinic Acid Lesions of the Striatum: Time-Dependent Recovery of N-Acetylaspartate and Fractional Anisotropy.

We created an excitotoxic striatal lesion model of Huntington disease (HD) in sheep, using the N-methyl-d-aspartate receptor agonist, quinolinic acid (QA). Sixteen sheep received a bolus infusion of QA (75 µL, 180 mM) or saline, first into the left and then (4 weeks later) into the right striatum. Magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) of the striata were performed. Metabolite concentrations and fractional anisotropy (FA) were measured at baseline, acutely (1 week after each surgery) and chronically (5 weeks or greater after the surgeries). There was a significant decrease in the neuronal marker N-acetylaspartate (NAA) and in FA in acutely lesioned striata of the QA-lesioned sheep, followed by a recovery of NAA and FA in the chronically lesioned striata. NAA level changes indicate acute death and/or impairment of neurons immediately after surgery, with recovery of reversibly impaired neurons over time. The change in FA values of the QA-lesioned striata is consistent with acute structural disruption, followed by re-organization and glial cell infiltration with time. Our study demonstrates that MRS and DTI changes in QA-sheep are consistent with HD-like pathology shown in other model species and that the MR investigations can be performed in sheep using a clinically relevant human 3T MRI scanner.

AAVrh10 Vector Corrects Disease Pathology in MPS IIIA Mice and Achieves Widespread Distribution of SGSH in Large Animal Brains.

Patients with mucopolysaccharidosis type IIIA (MPS IIIA) lack the lysosomal enzyme sulfamidase (SGSH), which is responsible for the degradation of heparan sulfate (HS). Build-up of undegraded HS results in severe progressive neurodegeneration for which there is currently no treatment. The ability of the vector adeno-associated virus (AAV)rh.10-CAG-SGSH (LYS-SAF302) to correct disease pathology was evaluated in a mouse model for MPS IIIA. LYS-SAF302 was administered to 5-week-old MPS IIIA mice at three different doses (8.6E+08, 4.1E+10, and 9.0E+10 vector genomes [vg]/animal) injected into the caudate putamen/striatum and thalamus. LYS-SAF302 was able to dose-dependently correct or significantly reduce HS storage, secondary accumulation of GM2 and GM3 gangliosides, ubiquitin-reactive axonal spheroid lesions, lysosomal expansion, and neuroinflammation at 12 weeks and 25 weeks post-dosing. To study SGSH distribution in the brain of large animals, LYS-SAF302 was injected into the subcortical white matter of dogs (1.0E+12 or 2.0E+12 vg/animal) and cynomolgus monkeys (7.2E+11 vg/animal). Increases of SGSH enzyme activity of at least 20% above endogenous levels were detected in 78% (dogs 4 weeks after injection) and 97% (monkeys 6 weeks after injection) of the total brain volume. Taken together, these data validate intraparenchymal AAV administration as a promising method to achieve widespread enzyme distribution and correction of disease pathology in MPS IIIA.

miR-200/375 control epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking.

Members of the miR-200 family are critical gatekeepers of the epithelial state, restraining expression of pro-mesenchymal genes that drive epithelial-mesenchymal transition (EMT) and contribute to metastatic cancer progression. Here, we show that miR-200c and another epithelial-enriched miRNA, miR-375, exert widespread control of alternative splicing in cancer cells by suppressing the RNA-binding protein Quaking (QKI). During EMT, QKI-5 directly binds to and regulates hundreds of alternative splicing targets and exerts pleiotropic effects, such as increasing cell migration and invasion and restraining tumour growth, without appreciably affecting mRNA levels. QKI-5 is both necessary and sufficient to direct EMT-associated alternative splicing changes, and this splicing signature is broadly conserved across many epithelial-derived cancer types. Importantly, several actin cytoskeleton-associated genes are directly targeted by both QKI and miR-200c, revealing coordinated control of alternative splicing and mRNA abundance during EMT These findings demonstrate the existence of a miR-200/miR-375/QKI axis that impacts cancer-associated epithelial cell plasticity through widespread control of alternative splicing.

Regulation of splicing and circularisation of RNA in epithelial mesenchymal plasticity.

Interconversions between epithelial and mesenchymal states, often referred to as epithelial mesenchymal transition (EMT) and its reverse MET, play important roles in embryonic development and are recapitulated in various adult pathologies including cancer progression. These conversions are regulated by complex transcriptional and post-transcriptional mechanisms including programs of alternative splicing which are orchestrated by specific splicing factors. This review will focus on the latest developments in our understanding of the splicing factors regulating epithelial mesenchymal plasticity associated with cancer progression and the induction of pluripotency, including potential roles for circular RNAs (circRNAs) which have been recently implicated in these processes.

Use of high-throughput RT-qPCR to assess modulations of gene expression profiles related to genomic stability and interactions by cadmium.

Predictive test systems to assess the mode of action of chemical carcinogens are urgently required. Within the present study, we applied the Fluidigm dynamic array on the BioMark™ HD System for quantitative high-throughput RT-qPCR analysis of 95 genes and 96 samples in parallel, selecting genes crucial for maintaining genomic stability, including stress response as well as DNA repair, cell cycle control, apoptosis and mitotic signaling. The specificity of each individually designed sequence-specific primer pair and their respective target amplicons were evaluated via melting curve analysis as part of qPCR and size verification via agarose gel electrophoresis. For each gene, calibration curves displayed high efficiencies and correlation coefficients in the identified linear dynamic range as well as low intra-assay variations. Data were processed via Fluidigm real-time PCR analysis and GenEx software, and results were depicted as relative gene expression according to the ΔΔC q method. Subsequently, gene expression analyses were conducted in cadmium-treated adenocarcinoma A549 and epithelial bronchial BEAS-2B cells. They revealed distinct dose- and time-dependent and also cell-type-specific gene expression patterns, including the induction of genes coding for metallothioneins, the oxidative stress response, cell cycle control, mitotic signaling and apoptosis. Interestingly, while genes coding for the DNA damage response were induced, distinct DNA repair genes were down-regulated at the transcriptional level. Thus, this approach provided a comprehensive overview on the interaction by cadmium with distinct signaling pathways, also reflecting molecular modes of action in cadmium-induced carcinogenicity. Therefore, the test system appears to be a promising tool for toxicological risk assessment.

Use of ß-tricalcium phosphate grafts for Airway reconstruction in rabbits: A pilot study.

OBJECTIVES/HYPOTHESIS: To assess the safety and feasibility of using ß-tricalcium phosphate grafts in airway reconstruction in rabbits. STUDY DESIGN: Interventional animal study. METHODS: Ten New Zealand White rabbits underwent division of the anterior cricoid cartilage with interposition of a graft sculpted from ß-tricalcium phosphate blocks. Grafts were secured with sutures or were self-retaining. Rabbit larynges were harvested according to the following schedule: one at 1 week, one at 3 months, and two each at 2 weeks, 4 weeks, 6 months, and 1 year after graft implantation. Specimens were evaluated grossly for overall graft incorporation. Sections through the graft substance were prepared for histology. All sections were reviewed by a pathologist for evidence of vascular ingrowth, granulation tissue, inflammation, epithelialization, and graft resorption. RESULTS: There were no major postoperative complications. Gross examination revealed persistent widening of the airway at the level of graft placement. Histologic evaluation of the larynges showed growth of new blood vessels within all specimens and absence of significant granulation tissue near the airway lumen. The graft was at least partially covered by an epithelium in seven of the 10 specimens. Evidence of graft resorption was present as early as 4 weeks after implantation, with replacement of the graft substance by fibrous tissue, fatty tissue, bone, or cartilage. CONCLUSIONS: ß-tricalcium phosphate grafts can be used safely in airway reconstruction procedures in rabbits. Further research is necessary to demonstrate its safety in human airway reconstruction in addition to further clarifying the processes of graft resorption and integration. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E255-E260, 2016.

Supraglottoplasty in Infants: A Staged Approach.

OBJECTIVE: While generally well tolerated for the treatment of severe laryngomalacia, bilateral supraglottoplasty has potential complications including supraglottic stenosis and aspiration. We report a more conservative staged supraglottoplasty in infants with severe laryngomalacia. METHODS: A retrospective review was performed of our patients who underwent staged supraglottoplasty from June 2007 to June 2012. Fifteen infants were identified and scored based on stridor, retractions, oxygen saturation, and feeding quality. Outcomes were compared with those reported in the literature for conventional bilateral supraglottoplasty. RESULTS: Seventy-three percent had significant improvement or resolution of stridor following the first stage of surgery and 100% in those undergoing a second stage. Twelve patients (80%) had mild to no retractions following one procedure and 100% had resolution after a second surgery. All 6 patients with recurrent preoperative desaturations had resolution after the first stage of surgery. Of the 11 infants who had preoperative moderate-severe feeding problems, 9 of them (82%) had resolution after one surgery and the remaining 2 had resolution after a second surgery. There were no complications in any of the patients. CONCLUSIONS: Staged supraglottoplasty appears to be an effective, low-risk method to treat severe laryngomalacia. A second procedure was only required in 40% of patients.

Revision rate of Birmingham Hip Resurfacing arthroplasty: comparison of published literature and arthroplasty register data.

PURPOSE: Hip resurfacing arthroplasty has gained popularity for treating young and active patients who have arthritis. There are two major data sources for assessing outcome and revision rate after total joint arthroplasty: sample-based clinical trials and national arthroplasty registers. The purpose of this study was to evaluate the outcome of the Birmingham Hip Resurfacing (BHR) arthroplasty in terms of revision rate as reported in clinical studies and recorded by national arthroplasty registers. METHODS: A comprehensive literature research was performed from English-language, peer-reviewed journals and annual reports from national joint arthroplasty registers worldwide. Only publications from MEDLINE-listed journals were included. The revision rate was used as the primary outcome parameter. In order to allow for direct comparison of different data sets, calculation was based on revisions per 100 observed component years. For statistical analysis, confidence intervals (CI) were calculated. RESULTS: A total of 18,708 implants, equivalent to 106,565 observed component years, were analysed in the follow-up studies. The register reports contained 9,806 primary cases corresponding to 44,294 observed component years. Statistical analysis revealed a significant difference in revisions per 100 observed component years between the development team (0.27; CI: 0.14-0.40) and register data (0.74; CI: 0.72-0.76). CONCLUSION: The BHR arthroplasty device shows good results in terms of revision rate in register data as well as in clinical studies. However, the excellent results reported by the development team are not reproducible by other surgeons. Based on the results of our study, we believe that comprehensive national arthroplasty registers are the most suitable tool for assessing hip arthroplasty revision rate.

Modified vaccinia virus Ankara delivers a robust surrogate marker for immune monitoring to sarcoma cells even if cells are being exposed to chemotherapy and heat treatment.

PURPOSE: Adding hyperthermia to chemotherapy improved the clinical outcome of patients with high risk soft tissue sarcoma. Further improvement might be possible if combined with vaccination strategies. As no sarcoma-associated antigens are known, the ectopic expression of a surrogate marker for which immune monitoring tools are available, is envisaged. We tested surrogate marker transfer into sarcoma cells in vitro using modified vaccinia virus Ankara (MVA), which has well established clinical safety. We examined its robustness against standard sarcoma treatment modalities, such as ifosfamide and hyperthermia. MATERIALS AND METHODS: We transduced sarcoma cell lines and primary tumour cells from sarcoma patients with MVA encoding the human tyrosinase gene (MVA-hTyr). Kinetics of tyrosinase expression and the potency to activate tyrosinase-specific cytotoxic T cells were assessed. In addition cells were exposed to chemotherapy and heat, imitating the clinical setting. RESULTS: Tyrosinase was ectopically expressed in sarcoma cells. Infected cells presented tyrosinase epitopes for T cell recognition even if exposed to ifosfamide/heat. CONCLUSIONS: As sarcoma patients receive surgery up front or after neoadjuvant systemic chemotherapy/hyperthermia, tumour material is generally available. Our data document that primary sarcoma cells can be infected with MVA-hTyr in vitro and antigen presentation is not affected by ifosfamide or heat treatment. Infected cells can serve as a source for vaccine preparation. MVA-hTyr infection of tumour cells lacking defined antigens is a feasible system to introduce a robust surrogate marker to provide an immune monitoring marker for assessing the induction of antigen-specific T cell activation.

Femoral shortening and cementless arthroplasty in Crowe type 4 congenital dislocation of the hip.

PURPOSE: In reconstruction of congenital hip dislocation by total hip arthroplasty (THA), positioning of the acetabular component in the true acetabulum is sometimes accompanied by shortening of the femur. Shortening of the femur is of importance for minimising risk of damaging neurovascular structures due to excessive limb lengthening. Furthermore, reduction of the femoral head into the true acetabulum remains challenging without shortening of the femur. METHODS: We performed a consecutive case series of cementless THA with femoral shortening and Crowe type 4 congenital dislocation. All acetabular cups were placed in their original anatomical location. In all cases a proximal diaphyseal step-cut shortening osteotomy was performed and stabilised with two to three titanium cerclage bands. RESULTS: At an average of 60 months follow-up (range 36-96), 12 patients (13 THA) were scored clinically by the Merle D'Aubigne and Harris hip scores. In ten cases good to excellent outcome scores were observed. During the follow-up period no cases of aseptic loosening, nerve palsy, nonunions or dislocations were found. CONCLUSIONS: This technique seems to be an excellent treatment option in the case of Crowe type 4 hips presenting with endstage osteoarthritis.

Two-stage cementless revision of late total hip arthroplasty infection using a premanufactured spacer.

We observed 44 patients with 2-stage revisions for septic hip prostheses. We used a uniform protocol consisting of the implantation of a preformed spacer (interval 12-26 weeks), specific systemic antibiotic therapies, and cementless total hip arthroplasty at time of reimplantation. The minimum follow-up was 36 months (mean, 67 months; range, 36-120 months). During the spacer period, we observed 4 dislocations and 2 fractures leading to a resection arthroplasty interval before reimplantation in 5 cases. In one patient, reinfection was diagnosed 12 months after reimplantation. The Harris hip score increased from a preoperative mean of 39 to 90 at a mean follow-up of 67 months after reimplantation.

Follow-up of thirty-three computed-tomography-guided percutaneous radiofrequency thermoablations of osteoid osteoma.

PURPOSE: This study aimed to determine the mid- and long-term success and complication rates of radiofrequency ablation (RFA) in treatment of osteoid osteoma (OO). Furthermore we were interested in the value of bone biopsy when using a core-drill before the radiofrequency ablation. METHODS: We retrospectively analysed data of 33 patients (33 osteoid osteomas, 22 males, 11 females) who underwent computed-tomography (CT) guided radiofrequency ablation between 1998 and 2005. The patients had a mean age of 20 years (range, five to 50 years). They were monitored for a mean follow-up of 92 months (range, 60-121 months). RESULTS: Lesions were located as follows: 11 cases in the proximal femur, five in the femoral shaft, six in the tibia, one in the calcaneus, two in the metatarsals (second and fourth metatarsals), one in the os cuneiforme mediale, six in the humeral and one in the ulnar shaft. Within the presented time frame 32 of 33 patients were successfully treated and had no more complaints. In one of 33 patients relapse occurred after 28 months and RFA was repeated. There were no complications associated with the procedure. Biopsy obtained prior to thermocoagulation with the help of a core-drill was able to prove diagnosis in all patients (100%). CONCLUSIONS: These results indicate that the presented technique of CT guided RFA combined with the use of a core-drill for biopsy prior to RFA treatment is a highly effective, efficient, minimally invasive and safe method for the treatment of OO, yielding a success rate of 97% combined with a 100% histological verification of the diagnosis after a minimum follow-up period of five years.

Management of Vancouver B2 and B3 femoral periprosthetic fractures using a modular cementless stem without allografting.

PURPOSE: We reviewed our experience with the management of B2 and B3 femoral periprosthetic fractures using a distally fixed modular femoral stem in 55 patients. METHODS: All periprosthetic fractures were managed immediately after injury without using allograft; 53 hips were available for a mean follow up of 67 months. RESULTS: All fractures united, and the mean Harris hip score at the last follow up was 72. Subsidence was noted in two patients (4%) within six months postoperatively and required revision surgery. One patient developed peroneal nerve palsy. Two hips dislocated and were managed by closed reduction. CONCLUSION: In these severe cases of periprosthetic fracture, the technique reviewed here proved to be reliable.