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Prosthetic joint infections are a major challenge in total joint arthroplasty, especially in times of accumulating drug resistancies. Even though predictive risk classifications are a widely accepted tool to define a suitable treatment protocol a classification is still missing considering the difficulty in treating the -causative pathogen antibiotically. In this study, we present and evaluate a new predictive risk stratification for prosthetic joint infections in 120 cases, treated with a two-stage exchange. Treatment outcomes in 120 patients with proven prosthetic joint infections in hip and knee prostheses were regressed on time of infection, systemic risk factors, local risk factors and the difficulty in treating the causing pathogen. The main outcome variable was "definitely free of infection" after two years as published. Age, gender, and BMI were included as covariables and analyzed in a logistic regression model. 66 male and 54 female patients, with a mean age at surgery of 68.3 years±12.0 and a mean BMI of 26.05±6.21 were included in our survey and followed for 29.0±11.3 months. We found a significant association (p<0.001) between our score and the outcome parameters evaluated. Age, gender and BMI did not show a significant association with the outcome. These results show that our score is an independent and reliable predictor for the cure rate in prosthetic joint infections in hip and knee prostheses treated within a two-stage exchange protocol. Our score illustrates, that there is a statistically significant, sizable decrease in cure rate with an increase in score. In patients with prosthetic joint infections the validation of a risk score may help to identify patients with local and systemic risk factors or with infectious organisms identified as "difficult to treat" prior to the treatment or the decision about the treatment concept. Thus, appropriate extra care should be considered and provided.

Introduction: Fractures in persons with haemophilia (PWH) are not uncommon and require an interdisciplinary approach to maintain haemostasis during surgical treatment., Aim: The aim of this study was to evaluate the perioperative management and outcome in PWH following fracture fixation compared to a matched non-haemophilic control group., Methods: A cohort of 44 PWH who underwent 46 surgical fracture fixations was retrospectively compared to 46 non-haemophilic patients (matched-pair controls). Patients were classified according to the fracture localization: (i) proximal upper extremity (PrUEx; n = 7), (ii) distal upper extremity (DiUEx; n = 12), (iii) proximal lower extremity (PrLEx; n = 13) and (iv) distal lower extremity (DiLEx; n = 14). Both groups were assessed for length of hospital stay, duration of surgery, drainage use and complication rates., Results: There was no significant difference regarding the duration of the preoperative hospital stay between PWH and controls. Only PWH who were operated at the DiUEx stayed significantly longer in hospital (4.8 ± 3.7 days) than controls (2.2 ± 2.3 days; P = 0.039). Operation time was significantly longer in PWH with fractures treated at the DiLEx (64.9 ± 26.6 min) compared to the controls (49.8 ± 37.9 min; P = 0.035). Neither frequency nor duration of surgical drainage placement differed significantly between the two groups. The overall complication rate in both groups was low without a statistically significant difference., Conclusion: An optimal interdisciplinary perioperative management provided the surgical treatment of fractures in PWH can be performed safely with a low complication rate., (© 2015 John Wiley & Sons Ltd.)

Introduction: Total knee arthroplasty (TKA) is an effective treatment option for patients with end-stage haemophilic arthropathy of the knee. However, the procedure is technically challenging, as knee motion is often restricted before the operation and complication rates are then thought to be higher than for patients with a normal range of motion (ROM). There is very limited information on the outcome of TKA in haemophilic patients presenting with stiff knees. The objective of the present study was to retrospectively analyse and compare the clinical results after TKA in haemophiliacs with stiff and non-stiff knees., Patients and Methods: The results of 50 TKA procedures in 41 haemophilic patients were retrospectively evaluated at a mean follow-up of 7.2 ± 4.9 years (range 2-25 years). 20 patients presenting with 23 stiff knees - defined by a preoperative ROM of 50° or less - were compared with 21 patients with 27 non-stiff knees. Knee motion (ROM, flexion, extension), Knee Society Score (KSS/KSS function), pain status (visual analogue scale, VAS), number of bleedings and patient satisfaction were evaluated., Results: The complication rate was 12 %, including two haematomas, one aseptic loosening, and three periprosthetic infections. The overall mean ROM increased from 58.6 ± 34.2° (range 0-120°) preoperatively to 85.9 ± 23.4 (35-130°) postoperatively (p < 0.005). Mean KSS and KSS function improved from 30.6 ± 11.0 points (range 10-49) and 43.4 ± 9.3 points (range 15-65) to 79.3 ± 9.6 points (range 49-95) and 68.9 ± 11.0 points (45-90), respectively (p < 0.005). The mean VAS score decreased significantly from 7.9 ± 0.8 points (range 6-9) to 1.8 ± 1.1 points (range 0-4; p < 0.005). In comparison to the non-stiff group, patients with stiff knees showed a significantly greater mean improvement in ROM (46.3 ± 21.8° [range - 10-85°] vs. 9.4 ± 16.9° [range - 30-35°]), flexion (32.8 ± 19.6° [range - 10-85°] vs. 5.2 ± 16.2° [range - 40-35°]), and flexion contracture (13.5 ± 9.6° [range 5-30°] vs. 5.9 ± 6.7° [range 5-20°]). Both KSS and KSS function were significantly inferior in stiff knees than with non-stiff knees. Nine patients with knee stiffness who underwent additional v-y quadricepsplasty to lengthen the extensor mechanism developed a mean extensor lag of 7-0° ± 4-8° (range 5-15°). At final follow-up, 37/41 patients were satisfied or very satisfied with the surgical result., Conclusion: TKA in haemophilic patients presenting with haemophilic arthropathy of the knee results in significant improvements in function and reduced pain. Although the ultimate clinical outcome in stiff knees is inferior to that with non-stiff knees, joint replacement surgery can be successfully performed in patients with restricted preoperative range of motion. Vy-quadricepsplasty for to facilitate exposure is associated with the development of a postoperative extensor lag and should therefore be performed restrictively. Patient satisfaction after TKA was equally high in the two groups., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: The Charlson comorbidity index (CCI) was developed to quantify the influence of comorbidities on survival. The age-related CCI respects patients' age as an additional risk factor. There are several studies available based on administrative data regarding functional outcome, implant survival, resource use and length of hospital stay in patients undergoing primary total hip arthroplasty (THA). To date, there is a lack of knowledge regarding the correlation of the CCI and the age-related CCI in case of revision total hip arthroplasty (RTHA)., Objective: Our objective was to validate the influence of the CCI and age-related CCI in patients undergoing RTHA regarding complication rate, resource use implant survival and mortality rate., Methods: Between October 2007 and November 2012, 142 consecutive patients undergoing RTHA were included in this retrospective study. Routine clinical data were collected and analysed as anonymized aggregated data. In accordance to CCI and age-related CCI the rate of complications (internal medical and surgical complications), the length of hospital stay and the need for ICU treatment and the mortality rate was evaluated. Kaplan-Meier survivorship was used to determine implant survival., Results: Twenty-one patients (15%) had a low risk CCI, 59 patients (41%) a moderate risk CCI and 62 patients (44%) a high risk CCI. The mean follow-up was 27 months (range 24-70 months). In total, we recorded 57 complications (40%), of which 45 were surgical (79%) and 12 were internal medical complications (21%). Twenty-four patients (17%) had to undergo revision surgery. CCI and age-related CCI had no influence regarding implant survival. We recorded a significant influence of the age-related CCI in regard to the necessity of postoperative intensive care unit stay and the length of total hospital stay. Further we recorded a significant influence of the CCI and the age-related CCI regarding postoperative complications and internal complications, postoperative dislocation and the need for surgical revision., Conclusion: In summary, we conclude that the CCI and the age-related CCI are strong predictors regarding complication rate in patients undergoing RTHA. In a short- to mid-term follow-up, no influence on implant survival is detectable.

Introduction: Advanced haemophilic arthropathy of the knee is associated with progressive joint stiffness. Results after total knee arthroplasty (TKA) in stiff knees are considered to be inferior compared to those with less restricted preoperative range of motion (ROM). There is only very limited data on the results of primary TKA in haemophilic patients with stiff knees., Aim: The purpose of this retrospective study was to evaluate the clinical outcome after TKA performed in haemophilic patients with preoperative ROM of 50° or less., Methods: Twenty one patients (23 knees) undergoing TKA with stiff knees were retrospectively evaluated. Mean follow-up was 8.3 years (range, 2-25). Clinical assessment included ROM, degree of flexion contracture and complication rate. Functional evaluation and pain status were assessed using the Knee Society's Scoring System (KSS)., Results: Range of motion improved from 26.7° preoperatively to 73.0° postoperatively. Flexion contracture decreased from 21.7° to 8.3°. KSS increased from 22.9 to 72.9 points. Evaluation of pain revealed a decrease from 8.4 points preoperatively to 2.1 points postoperatively. All these differences were statistically significant (P < 0.005). The complication rate was 8.7% including one late periprosthetic infection, and one aseptic implant loosening. Nine patients who required VY-quadricepsplasty for knee exposure developed a mean postoperative extensor lag of 7°., Conclusion: Total knee arthroplasty in haemophilic patients presenting with stiff knees results in significant improvement of function and reduction in pain. Although the clinical outcome is inferior compared to nonstiff knees reported in the literature, joint replacement surgery can be successfully performed in this particular group of patients., (© 2015 John Wiley & Sons Ltd.)

Purpose: Revision of failed total hip arthroplasty with severe acetabular bone loss represents a rare but challenging problem. Anatomic reconstruction with biological defect augmentation as solid bone transplants or cancellous bone restores bone stock while providing good component stability. The objective of this study was to present short- to mid-term results of revision total hip arthroplasty with a modular ring system in a consecutive series of patients with severe acetabular bone loss., Methods: We retrospectively reviewed 39 consecutive patients (39 hips) with severe acetabular bone loss (Paprosky type 3 A and 3 B) reconstructed with revision total hip arthroplasty using the cementless modular ring system MRS-Titan®. The MRS-Titan® consists of independent ring systems that are adapted modularly to the defect situation. Combined with acetabular defect reconstruction by using cancellous bone in impaction grafting technique, the MRS-Titan® system offers a cement-free revision system that enables defect-adapted customization to individual anatomic matters, bridging of the acetabular bone defect and reconstruction of the centre of rotation. Initial stability of the implant was obtained by screw fixation. Harris hip score and sequential radiographs were used to evaluate clinical and radiographic results., Results: At an average follow up of 31 months (range 12-69 months) 33 of 39 (84.6 %) of the implants were considered radiographically stable without signs of acetabular migration of more than 2 mm in the horizontal or vertical direction, implant rotation or screw breakage. Complications included six implant failures (15 %). We recorded one aseptic loosening of the MRS prosthesis after 20 months. Five patients (12.8 %) had to undergo revision surgery because of periprosthetic joint infection. Two patients had a dislocation postoperatively. The mean Harris hip score improved from 27 ± 14 points preoperatively to 76 ± 15 points at the time of last follow up., Conclusion: By achieving stable implant fixation and providing potential for biological fixation, treatment of severe acetabular bone loss in revision total hip arthroplasty with the modular ring system MRS-Titan provides a durable solution with good clinical and radiographic results and allows us to accomplish major goals of reconstruction.

Background: Radiofrequency ablation (RFA), with or without endoscopic mucosal resection (EMR), has been validated as a safe, effective and durable treatment option for dysplastic Barrett's esophagus. Its durability in eradicating Barrett's-associated intramucosal carcinoma (IMC), however, is unclear. We set out to assess the long-term safety and efficacy of RFA for IMC., Methods: Retrospective review of two tertiary care facility records for patients undergoing RFA, with or without EMR, for biopsy-proven IMC. Our primary outcome of interest was to quantify the rate of durable complete eradication for intestinal metaplasia and for IMC and associated dysplasia. A multi-variate regression analysis was performed to identify features which correlate with durable eradication of IMC/dysplasia. Our secondary outcome of interest was treatment-related complications., Results: 36 patients (26 male; mean age 64 ± 12 years), with a mean Barrett's length of 3.5 ± 2.5 cm, underwent RFA for biopsy-proven IMC. EMR was performed in 31 (86%) prior to or during RFA. Complete eradication of IMC/dysplasia was achieved in 32/36 (89%) and patients required a mean of 1 ± 1 EMR and 2 ± 1 RFA sessions to achieve eradication. During a mean follow-up period of 24 ± 19 months, durable complete eradication of IMC/dysplasia was achieved in 29/36 (81%) patients. On multi-variate regression analysis, undergoing an EMR prior to RFA was associated with an increased likelihood of maintaining durable eradication of IMC/dysplasia (p = 0.03). Treatment-related complications included: bleeding (3%) and stricture formation (19%)., Conclusion: RFA is an effective and durable treatment option for Barrett's-associated IMC. Greater than 80% of patients will achieve and maintain complete eradication of IMC at a mean of 2 years follow-up.

Despite reliable results of ankle fusion for advanced haemophilic arthropathy, total ankle replacement (TAR) may be functionally advantageous. There is only very limited literature data available on TAR in patients with haemophilia. The objective of this study is to evaluate the short- and mid-term results after TAR in patients with end-stage haemophilic ankle arthropathy and concomitant virus infections. In a retrospective study, results after eleven TAR in 10 patients with severe (n = 8) and moderate (n = 2) haemophilia (mean age: 49 ± 7 years, range, 37-59) were evaluated at a mean follow-up of 3.0 years (range, 1.2-5.4). Nine patients were positive for hepatitis C, five were HIV-positive. Range of motion (ROM), AOFAS-hindfoot-score, pain status (visual analogue scale, VAS) as well as patient satisfaction were evaluated. In two cases deep prosthesis infection occurred leading to the removal of the implant. In the remaining eight patients the mean AOFAS score improved significantly from 21.5 to 68.0 points (P < 0.0005), the VAS score decreased significantly from 7.6 to 1.9 points (P < 0.0005). ROM increased from 23.2 to 25.0 degrees (P = 0.51). At final follow-up all patients without any complications were satisfied with the postoperative results. Radiographic examination did not reveal any signs of prosthetic loosening. TAR is a viable surgical treatment option in patients with end-stage ankle osteoarthritis due to haemophilia. It provides significant pain relieve and high patient satisfaction. However, due to the increased risk of infection and lack of long-term results, TAR particularly in patients with severe haemophilia and virus infections should be indicated carefully., (© 2014 John Wiley & Sons Ltd.)

Chronic fatigue syndrome (CFS) remains an incompletely characterized illness, in part due to controversy regarding its definition, biological basis and diagnosis. Biomarkers are objective measures that may lead to improvements in our understanding of CFS by providing a more coherent and consistent approach to study, diagnosis and treatment of the illness. Such metrics may allow us to distinguish between CFS subtypes - each defined by characteristic biomarkers - currently conflated under the single, heterogeneous condition of CFS. These delineations, in turn, may guide more granular, focused, and targeted treatment strategies based on more precise characterizations of the illness. Here, we review potential CFS biomarkers related to neurological and immunological components of the illness, and discuss how these biomarkers may be used to move the field of CFS forward, emphasizing clinical utility and potential routes of future research.

Unlabelled: Total knee arthroplasty (TKA) provides significant pain relief and better function in patients with end-stage haemophilic knee arthropathy. Peri- and postoperative care tends to be more complex than in non-haemophilic patients undergoing TKA and requires a multidisciplinary team approach., Aim: The implementation of standardized clinical pathways in non-haemophilic patients undergoing TKA has been shown to increase quality of care and to reduce postoperative complication rates. Consequently, the use of clinical pathways in haemophilic patients undergoing TKA may be beneficial to this particular subpopulation of patients., Methods: A clinical pathway for TKA for haemophilic patients was designed in a consensus process involving all participating departments., Results: We propose a specifically adjusted clinical pathway for TKA for haemophilic patients to show that standardization of elective orthopaedic surgery in haemophilia is feasible., Conclusion: The authors emphasize that there are limitations on categorizing haemophilic patients and stress that individual interdisciplinary treatment should take precedence over a standardized approach.

Unlabelled: After ankle and knee, the elbow is the most frequent joint affected by haemophilic arthropathy. The objective of this retrospective single centre study is to evaluate the results of treatment of elbow arthropathy after failed conservative therapy., Patients, Methods: In 21 consecutive patients, 11 radiosynoviortheses (RSO), four arthroscopic and six open synovectomies were performed, among them four with additional resection of the radial head. The mean duration of follow-up was 4.8 (RSO) and 5.3 years (surgery), respectively. Pain status (visual analogue scale, VAS), bleeding frequency, range of motion (ROM) as well as patient satisfaction were evaluated., Results: Both, RSO and surgical synovectomy, achieved a significant reduction of pain and bleeding frequency (p < 0.05). Surgical synovectomies were associated with a marked yet not statistically significant increase of postoperative ROM. Radial head resection improved forearm rotation in all cases. No complications occurred. 20 out of 21 patients were satisfied or highly satisfied with the result of the treatment and would undergo the respective procedure again., Conclusion: Due to the effectiveness and safety RSO is considered to be the primary treatment option in haemophilic arthropathy of the elbow after failed conservative therapy. Arthroscopic synovectomy should be considered if RSO shows inadequate effect or in the presence of contraindications. Open synovectomy with resection of the radial head yields good results in the case of advanced arthropathy with radial head impingement.

A 44-year-old man is presented here with 14 years of chronic purulent sinusitis, a chronic fungal rash of the scrotum, and chronic pelvic pain. Treatment with antifungal therapy resulted in symptom improvement, however he was unable to establish an effective long-term treatment regimen, resulting in debilitating symptoms. He had undergone extensive work-up without identifying a clear underlying etiology, although Candida species were cultured from the prostatic fluid. 100 genes involved in the cellular immune response were sequenced and a missense mutation was identified in the Ras-binding domain of PI3Kγ. PI3Kγ is a crucial signaling element in leukotaxis and other leukocyte functions. We hypothesize that his mutation led to his chronic infections and pelvic pain.

Imatinib mesylate (IM) induces remission in chronic myelogenous leukemia (CML) patients but does not eliminate leukemia stem cells (LSCs), which remain a potential source of relapse. Here we investigated the ability of HDAC inhibitors (HDACis) to target CML stem cells. Treatment with HDACis combined with IM effectively induced apoptosis in quiescent CML progenitors resistant to elimination by IM alone, and eliminated CML stem cells capable of engrafting immunodeficient mice. In vivo administration of HDACis with IM markedly diminished LSCs in a transgenic mouse model of CML. The interaction of IM and HDACis inhibited genes regulating hematopoietic stem cell maintenance and survival. HDACi treatment represents an effective strategy to target LSCs in CML patients receiving tyrosine kinase inhibitors., ((c) 2010 Elsevier Inc. All rights reserved.)

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition among men of a wide age range, with detrimental effects on quality of life. The etiology, pathogenesis, and optimal treatment of CP/CPPS remain unknown, although progress has been made in these domains in recent years. A wide variety of pharmacologic and nonpharmacologic therapies have been studied in clinical trials, but most have shown limited efficacy in symptom alleviation. CP/CPPS is increasingly viewed as a condition that involves variable degrees of neuropathic pain. Medications such as gabapentin, pregabalin, memantine, and tricyclic antidepressants are often used in other neuropathic pain conditions and, therefore, are considered potential treatments for CP/CPPS. Few studies of these agents in patients with CP/CPPS have been reported, but future clinical trials should help to determine their utility and to characterize the pathogenetic mechanisms of pain in CP/CPPS. Combining treatment trials with biomarker, genomic, and imaging studies, in addition to epidemiologic and symptom-based assessments, will maximize the ability to probe disease etiology and pathogenesis, as well as identify effective treatment.

Advances, over the past 20 years, in the genetic manipulation of mammalian cells form the scientific basis of gene therapy. A number of strategies are presently being used to replace or augment a dysfunctional gene with a correct copy of itself. Now, a novel approach to correct the dysfunctional gene in the chromosome is being developed. Data obtained from biochemical, cell-based and animal studies suggest that the era of gene repair is dawning. It is now conceivable that inherited and non-inherited disorders might be treated with a small molecular tool designed to fix the mutation directly. Here, the conceptualization of the technique and its barriers to success are discussed.