The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy.

Direct analysis of HLA-presented antigens by mass spectrometry provides a comprehensive view on the antigenic landscape of different tissues/malignancies and enables the identification of novel, pathophysiologically relevant T-cell epitopes. Here, we present a systematic and comparative study of the HLA class I and II presented, nonmutant antigenome of multiple myeloma (MM). Quantification of HLA surface expression revealed elevated HLA molecule counts on malignant plasma cells compared with normal B cells, excluding relevant HLA downregulation in MM. Analyzing the presentation of established myeloma-associated T-cell antigens on the HLA ligandome level, we found a substantial proportion of antigens to be only infrequently presented on primary myelomas or to display suboptimal degrees of myeloma specificity. However, unsupervised analysis of our extensive HLA ligand data set delineated a panel of 58 highly specific myeloma-associated antigens (including multiple myeloma SET domain containing protein) which are characterized by frequent and exclusive presentation on myeloma samples. Functional characterization of these target antigens revealed peptide-specific, preexisting CD8(+) T-cell responses exclusively in myeloma patients, which is indicative of pathophysiological relevance. Furthermore, in vitro priming experiments revealed that peptide-specific T-cell responses can be induced in response-naive myeloma patients. Together, our results serve to guide antigen selection for T-cell-based immunotherapy of MM.

Comparative clinical study of the prophylaxis of heterotopic ossifications after total hip arthroplasty using etoricoxib or diclofenac.

PURPOSE: This study investigated whether etoricoxib (COX-II blocker) has a superior efficacy of preventing heterotopic ossification (HO) after total hip arthroplasty (THA) compared to diclofenac (non-selective NSAID). METHODS: One hundred patients were included (50 in each group) in this single centre, prospective, double-blinded, randomized, controlled trial. Etoricoxib (90 mg) was administered once and diclofenac (75 mg) twice per day for a perioperative period of nine days. The incidence of HO was evaluated on radiographs of the pelvis six months after surgery. RESULTS: Eighty nine of 100 (89 %) patients could be analysed. The overall HO incidence was 37.8 %. There was no significant difference between both study groups. Twelve patients (27.3 %) of the DIC group and 13 patients (28.9 %) of the ETO group showed Brooker grade I ossifications. Five patients (11.4 %) of the DIC and four patients of the ETO (8.9 %) group showed grade II HO formations. No class III or IV HO formations occured in both groups. Ad hoc analysis detected a negative correlation between HO incidence and limited abduction and internal rotation of the hip. CONCLUSIONS: Etoricoxib and diclofenac are equally effective for oral HO prophylaxis after primary cementless THA when given for nine peri-operative days to ensure a full recovery and high patient satisfaction.

Risk assessment of back pain in youth soccer players.

The purpose of this study is to identify several responsible parameters for back pain (BP) in youth soccer players to create a risk assessment tool for early prevention. An iPad-based survey was used to screen for parameters in a cross-sectional study. This questionnaire includes items regarding anthropometric data, training habits and sports injuries and was put into practice with 1110 athletes. Sex (odds ratio (OR): 1.84), age group (1.48) and playing surface (1.56) were significantly associated with BP. A history of injuries especially to the spine and hip/groin increased the likelihood for evolving recurrent BP (1.74/1.40). Overall 15 factors seem to influence the appearance of pain and were integrated into a feasible nomogram. The nomogram provides a practical tool to identify the risks of developing BP for youth soccer players. Although most factors we identified are non-modifiable, this method allows to rank the importance of factors and especially their prevention treatments for athletes.

Arthrodesis of the talonavicular joint using angle-stable mini-plates: a prospective study.

PURPOSE: The talonavicular joint is a central connection of the human foot. Symptomatic talonavicular arthritis can be adequately addressed by isolated talonavicular fusion. However, non-union remains a relevant clinical challenge to the orthopaedic surgeon. The aim of this study was to analyse the clinicoradiological outcome of talonavicular fusion using angle-stable mini-plates. METHODS: We performed 30 talonavicular fusions in 30 patients (12 male, 18 female) with a mean age of 58.8 years (range, 22-74) between 2005 and 2007. Osseous joint fusion was achieved using mono- and multidirectional angle-stable mini-plates. The patients followed a standardised immobilisation and weight bearing protocol. The mean postoperative follow up was 15.8 months (6.1-23.8). RESULTS: The American Orthopedic Foot and Ankle Society AOFAS score increased significantly from 31.7 (19-42) to 82.3 points (55-97) (p < 0.001). Neither age at operation nor gender influenced the score results significantly, while the aetiology of talonavicular degeneration showed a significant effect. Mean visual analogue scale (VAS) pain intensity (0-10) reduced from 8.6 to 1.7 (p < 0.001). Good or excellent results were achieved in 26 patients, while two patients reported fair and another two poor results. Complete osseous fusion was observed at a mean of 10.9 weeks (8-13) postoperatively. CONCLUSIONS: For the treatment of talonavicular arthritis, the application of mono- and multidirectional angle-stable mini-plates provided a strong fixation that led to high union rates and good to excellent overall outcome.

Clinical outcome after Chevron-Akin double osteotomy versus isolated Chevron procedure: a prospective matched group analysis.

BACKGROUND: Hallux valgus is a frequent condition of the forefoot, resulting in cosmetic deformity and pain. Chevron osteotomy (CO) is widely employed for the treatment of hallux valgus. Chevron-Akin double osteotomy (CAO) was previously described and superiority over an isolated Chevron procedure was assumed. The objective of this study was to compare the short-to-middle term outcomes of CO and CAO. PATIENTS AND METHODS: This study included 72 patients with established diagnosis of mild-to-moderate hallux valgus, treated by either isolated CO or CAO. The CO group included 46 patients (mean 51.5 years) with a mean hallux valgus angle of 27°, while the CAO group included 26 subjects (mean 53.1 years) and a mean hallux valgus angle of 32° preoperatively. All patients were reviewed by physical examination, and standardized questionnaire, and pre- and postoperative standing X-rays were performed. Matched group analysis was carried out to analyze statistical differences of both techniques. RESULTS: The patients were assessed and group matched at a mean of 1.37 years for the CO group and 1.04 years for the CAO group, postoperatively. Mean improvement of HVA (hallux valgus angle) was 10.6° in the CO group and the CAO group improved by 17.5°. DMAA (distal metatarsal articular angle) improved in the CO group by 5.4° and in the CAO by 13.7°. Mean AOFAS score improved by 27.9 (CO) and 21.5 (CAO). Patient satisfaction was high in both groups, with a tendency towards higher values within the CAO group. CONCLUSIONS: These findings indicate that Chevron-Akin double osteotomy is a save and practicable procedure for the treatment of mild-to-moderate hallux valgus. Superiority of combined Chevron-Akin procedure over an isolated Chevron osteotomy might be limited to distinct clinical settings, but should not be generally assumed.

In vitro investigation of the influence of pelvic tilt on acetabular cup alignment.

This study investigates the influence of pelvic tilt on conventional alignment of acetabular cups. Cementless cups were aligned into a synthetic replica of the pelvis 300 times at different pelvic tilts. At +10 degrees pelvic tilt, average cup inclination was 46.2 degrees (32 degrees to 65 degrees ; +/-7.0 degrees ), and average cup anteversion was 19.8 degrees (4 degrees to 37 degrees ; +/-9.1 degrees ). At neutral pelvic tilt, inclination was 44.5 degrees (28 degrees to 59 degrees ; +/-7.2 degrees ), and anteversion was 15.6 degrees (-5 degrees to 33 degrees ; +/-8.1 degrees ). At -10 degrees pelvic tilt, inclination was 42.6 degrees (25 degrees to 61 degrees ; +/-7.2 degrees ), and anteversion was 10.5 degrees (-10 degrees to 37 degrees ; +/-12.2 degrees ). Overall, 50% of the cups were positioned outside the safe zone: 46% in pelvic inclination, 42% in neutral position, and 63% in pelvic reclination (P = .007). This study shows the considerable inaccuracies of conventional cup implantation by experienced and trainee surgeons and shows the influence of pelvic tilt on acetabular cup alignment.

Leg axis correction with ConforMIS iForma (interpositional device) in unicompartmental arthritis of the knee.

Degeneration of the meniscus and the articular cartilage in unicompartmental osteoarthritis of the knee results in progressive deformity of the leg axis. It is the aim of this study to evaluate if a leg axis correction can be achieved by implanting a customised metallic interpositional device for the knee (ConforMIS iForma). Before and after implanting a ConforMIS iForma knee implant, a radiological analysis of the leg axis deviation in the frontal plane was performed prospectively in 27 patients by evaluating anteroposterior single-leg stance radiographs. We achieved a sufficient leg axis correction with an average correction of 3.8 degrees and an averaged small under-adjustment of 0.9 degrees by inserting the ConforMIS iForma interpositional knee implant. Apart from the primary treatment objective of articular surface restitution the ConforMIS iForma knee implant can be reliably used to correct axis deformity occurring with unicompartmental osteoarthritis of the knee.

Position of the acetabular cup -- accuracy of radiographic calculation compared to CT-based measurement.

OBJECTIVE: A variety of mathematical and trigonometric methods has been described for determining the position of the acetabular cups from conventional radiographs. However, these formulae are subject to unduly large inaccuracies. The aim of the study was to compare the reliability and the accuracy of radiological and CT-based determination of acetabular cup position. MATERIALS AND METHODS: The positions of acetabular cups of 31 patients were calculated in conventional plain radiographs of the hip using the method described by Widmer. Further, in all patients computed tomograms of the pelvis were performed and the cup position was measured with the aid of a CT-based computer-assisted navigation software. As reference values inclination and anteversion of the cups were calculated in 3D reconstructions of the pelvis with the aid of an image processing software. RESULTS: The radiological measurement as well as the CT-based method showed good intra- and inter-observer reliability and no significant difference in the calculation of the inclination (p=0.409). However, CT-based determination of anteversion was significantly more exact than radiological measurement (p<0.001). The calculation of the cup anteversion from the X-rays showed serious deviations from the reference method and a substantial error range (X-ray: mean deviation +1.74 degrees, range -16.6 degrees to +29.8 degrees , S.D. +/-9.32 degrees; CT-based: mean deviation -0.74 degrees, range -6.6 degrees to +5.3 degrees, S.D. +/-2.87). CONCLUSION: For any clinical problem or for clinical studies in which acetabular positions of acetabular cups have to be exactly determined, CT-based measuring methods are obviously the method of choice. Evaluations based only on conventional plain X-rays and calculation of the acetabular cup position using the formula described by Widmer must be regarded as unreliable, particularly, because of problems in measuring the anteversion.

Contaminant seeding in bone by different irrigation methods: an experimental study.

OBJECTIVE: This study was designed to investigate the effectiveness of using various devices and manual procedures for cleansing bacterially contaminated bone tissue and to assess the risk of iatrogenic bacterial seeding in deep bone layers. METHODS: In an in vitro model, human femoral heads were contaminated with Escherichia coli and then cleansed with pulsatile high-pressure lavage, pulsatile low-pressure lavage, manual rinsing with bulb syringe lavage, or manual rinsing with combined brush cleaning. The numbers of bacteria that remained or those that were introduced by the rinsing procedures were quantitatively determined at depths of 0 to 1 cm, 1 to 2 cm, and 2 to 3 cm. RESULTS: Both pulsatile high-pressure lavage and brush cleaning were more effective than pulsatile low-pressure lavage and bulb syringe lavage for the purpose of surface cleansing. The differences were highly significant (P < 0.001). There was no significant difference in the decontaminating effect between pulsatile high-pressure lavage and brush cleaning (P = 0.24). The bacterial contamination attributable to the cleansing procedure, as measured at tissue depths of 1 to 2 cm and 2 to 3 cm, was significantly higher after pulsatile high-pressure lavage and after pulsatile low-pressure lavage than it was after bulb syringe lavage or brush cleaning (P < 0.001). CONCLUSION: In this in vitro investigation of cancellous bone, the brush cleansing was just as effective for getting rid of bacterial contamination as pulsatile high-pressure lavage, and carries a significantly lesser risk of iatrogenic bacterial seeding into deeper tissue layers. In the light of these promising results obtained by the cleansing of cancellous bone contaminated with bacteria, it would be desirable to perform supplementary in vitro and in vivo investigations into brush cleansing.

An experimental comparison of different devices for pulsatile high-pressure lavage and their relevance to cement intrusion into cancellous bone.

INTRODUCTION: Some of the systems marketed for pulsatile high-pressure lavage are clearly different in their mechanical pulse characteristics. To take the matter further we set up an experimental in vitro model to determine whether these different lavage systems might produce different cementation results because of their differing pulse characteristics, and whether the systems differed significantly in terms of cement depth penetration. MATERIALS AND METHODS: A total of 48 femoral heads were obtained at operation from patients who had undergone endoprosthetic hip replacement. The specimens were subjected to manual rinsing or semiautomatic cleansing procedures with five different pulsatile lavage devices. After the cleansing procedures, polymethylmetacrylate bone cement was intruded into the cancellous bone under standardised conditions. Determination of cement penetration was done by computed tomography using an image processing software. RESULTS: Irrespective of the nature of the lavage system tested, superficial cement penetration, both up to 2 mm and up to 3 mm, was significantly better after pulsatile high-pressure lavage than it was after manual rinsing of the specimens with a bladder syringe (P < 0.001 in each case). Whereas our experimental model did not show any significant differences between the lavage systems as regards the cementation results to a depth of up to 2 mm (P = 0.996), there were significant differences at a target depth of 3 mm (P < 0.05). CONCLUSION: As compared with manual rinsing, pulsatile high-pressure lavage in vitro makes highly significant improvements in cement penetration into cancellous bone and should be regarded as an indispensable component of modern cementation techniques for endoprosthetic surgery. Up to the present we have not been able to ascertain what influence the different pulse characteristics of a pulsatile lavage system may have on the intended cementation result, whether it is impact force, pulse shape, pulse duration, flow rate or frequency. Appropriate investigations will be necessary.

Moxifloxacin superior to vancomycin for treatment of bone infections--a study in rats.

BACKGROUND: Increasing resistance rates towards conventional antibiotics necessitate investigations of the efficacy of newly developed antibiotics. Thus, in a rat study, we compared the efficacy of moxifloxacin and vancomycin in the treatment of a local Staphylococcus aureus bone infection. METHOD: The femoral medullary cavities of 36 Wistar rats were contaminated with 100 muL of an oxacillin-sensitive Staphylococcus aureus strain (ATCC 29213) at 10(8) cfu/mL. On the seventh day, antibiotic treatment with moxifloxacin (10 mg/kg twice daily i.p.) or vancomycin (15 mg/kg twice daily i.p.) was commenced in 12 animals each. 12 control animals were left untreated. After 21 days, the infected femurs were explanted and the bacterial counts (cfu/g) were determined. RESULTS: In the control group, a median of 3.42 x 10(6) cfu/g (LQ/UQ 1.09 x 10(6)/ 1.55 x 10(7)) was cultured, with a median of 2.53 x 10(6) cfu/g (LQ/UQ 1.95 x 10(6)/ 4.25 x 10(6)) in the vancomycin group and a median of 2.49 x 10(5) cfu/g (LQ/UQ 2.84 x 10(4)/ 3.75 x 10(5)) in the moxifloxacin group. The bacterial count was reduced by treatment with moxifloxacin both in comparison with the control group (p < 0.001), and in comparison with treatment with vancomycin (p < 0.001). There was no statistically significant difference between the vancomycin group and the control group (p = 0.53). INTERPRETATION: In contrast to vancomycin, moxifloxacin proved to be an effective antibiotic for the treatment of bone infections due to Staphylococcus aureus in our animal model.

No difference between two doses of diclofenac in prophylaxis of heterotopic ossifications after total hip arthroplasty.

BACKGROUND: In a monocentric, randomized, placebo-controlled double-blind study, we investigated the efficacy of two doses of diclofenac-cholestyramine for the prevention of heterotopic ossification (HO). PATIENTS: The study comprised 245 patients undergoing total hip arthroplasty (THA). RESULTS: With 150 mg cholestyramine-bound diclofenac (2 x 1 capsule Voltaren resinate) daily during a postoperative period of 14 days, 19% of patients showed slight HO (Brooker grade 1), and no patient had more severe ossifications (grades 2-4). In the group receiving 75 mg daily (1 x 1 capsule), 17% of patients showed grade 1 HO and 4% grade 2 HO. No patient had grades 3-4 HO. No differences in clinical results were seen between the two groups 6 months after THA. INTERPRETATION: Since the rate of adverse gastrointestinal events was lower (23% versus 38%, p = 0.02) in the group receiving the lower dose, we recommend it.

Dose-dependent efficacy of diclofenac-cholestyramine on pain and periarticular ossifications after total hip arthroplasty: a double-blind, prospective, randomised trial.

INTRODUCTION: To investigate the efficacy of treatment with diclofenac-cholestyramine on postoperative pain and functional outcome after total hip arthroplasty, a randomised double-blind study was conducted. MATERIALS AND METHODS: A total of 245 patients received postoperative treatment with 75 mg or 150 mg diclofenac p.o. daily for 14 days. RESULTS: Patients who received 75 mg diclofenac per day needed paracetamol as an additional analgesic significantly more often (p=0.0162) than patients who were treated with 150 mg diclofenac daily (75 mg twice a day). The incidence of adverse gastrointestinal events was significantly lower in the group receiving 75 mg diclofenac daily than in the group receiving the higher dose (23.1% vs 37.1%; p=0.025). Six months after the operation, no differences were observed between the two groups with regard to pain or functionality measured in terms of overall mobility of the hip. No patient of either group developed clinically relevant heterotopic ossifications. CONCLUSION: Treatment with a dose of 75 mg diclofenac once daily-if necessary with the additional use of paracetamol-is a favourable option for the postoperative care of THA.

Influence of acid-citrate-dextrose anticoagulant on blood quality in retransfusion systems after total knee arthroplasty.

The influence of acid-citrate-dextrose (ACD) anticoagulant on the blood quality was assessed in this prospective, randomized, controlled study. The clinical consequences with regard to retransfusion of drainage blood following total knee arthroplasty were evaluated. After total knee arthroplasty, retransfusion was performed utilizing a "SureTrans" retransfusion system in 81 patients. In 42 of them, blood was collected adding an ACD anticoagulant (group A), while in the remaining 39 patients blood was collected without any additives (group B). Blood losses were retransfused over a 6-h period after attaching the retransfusion system to the patient of either group. Blood samples of the 6-h blood collection were taken and analysed for several blood quality parameters. Significant differences were found in the platelet count (61,200+/-16,700 microl(-1) in group A versus 70,100+/-21,600 microl(-1) in group B, p=0.042), the lactate concentration (4.09+/-0.86 mmol/l vs 4.82+/-0.83 mmol/l, p<0.001), the pH (6.96+/-0.10 vs 7.18+/-0.06, p<0.001), as well as the protein content (5.44+/-0.57 g/dl vs 5.85+/-0.43 g/dl, p<0.001). These observed significant differences were, however, of no clinical relevance to the patients' treatment. Hemoglobin concentration, hematocrit, mean corpuscular volume (MCV), erythrocyte count, leukocyte count, concentration of free hemoglobin in the blood plasma (fHb), potassium concentration, lactate dehydrogenase (LDH), serotonin concentration, triglyceride concentration, free fatty acid concentration, and interleukin-6 concentration did not differ significantly. This study indicates that the blood quality in retransfusion systems is not substantially influenced by adding ACD anticoagulant.