The treatment and outcome of peri-prosthetic infection of the ankle: a single cohort-centre experience of 34 cases

The treatment of peri-prosthetic joint infection (PJI) of the ankle is not standardised. It is not clear whether an algorithm developed for hip and knee PJI can be used in the management of PJI of the ankle. We evaluated the outcome, at two or more years post-operatively, in 34 patients with PJI of the ankle, identified from a cohort of 511 patients who had undergone total ankle replacement. Their median age was 62.1 years (53.3 to 68.2), and 20 patients were women. Infection was exogenous in 28 (82.4%) and haematogenous in six (17.6%); 19 (55.9%) were acute infections and 15 (44.1%) chronic. Staphylococci were the cause of 24 infections (70.6%). Surgery with retention of one or both components was undertaken in 21 patients (61.8%), both components were replaced in ten (29.4%), and arthrodesis was undertaken in three (8.8%). An infection-free outcome with satisfactory function of the ankle was obtained in 23 patients (67.6%). The best rate of cure followed the exchange of both components (9/10, 90%). In the 21 patients in whom one or both components were retained, four had a relapse of the same infecting organism and three had an infection with another organism. Hence the rate of cure was 66.7% (14 of 21). In these 21 patients, we compared the treatment given to an algorithm developed for the treatment of PJI of the knee and hip. In 17 (80.9%) patients, treatment was not according to the algorithm. Most (11 of 17) had only one criterion against retention of one or both components. In all, ten of 11 patients with severe soft-tissue compromise as a single criterion had a relapse-free survival. We propose that the treatment concept for PJI of the ankle requires adaptation of the grading of quality of the soft tissues. Cite this article: Bone Joint J 2014;96-B:772-7.

Mandibular implant overdentures followed for over 10 years: patient compliance and prosthetic maintenance

PURPOSE: The mandibular implant overdenture is a popular treatment modality and is well documented in the literature. Follow-up studies with a long observation period are difficult to perform due to the increasing age of patients. The present data summarize a long-term clinical observation of patients with implant overdentures. MATERIALS AND METHODS: Between 1984 and 1997, edentulous patients were consecutively admitted for treatment with an implant overdenture. The dentures were connected to the implants by means of bars or ball anchors. Regular maintenance was provided with at least one or two scheduled visits per year. Recall attendance and reasons for dropout were analyzed based on the specific history of the patient. Denture maintenance service, relining, repair, and fabrication of new dentures were identified, and complications with the retention devices specified separately. RESULTS: In the time period from 1984 to 2008, 147 patients with a total of 314 implants had completed a follow-up period of >10 years. One hundred one patients were still available in 2008, while 46 patients were not reexamined for various reasons. Compliance was high, with a regular recall attendance of >90%. More than 80% of dentures remained in continuous service. Although major prosthetic maintenance was rather low in relation to the long observation period, visits to a dental hygienist and dentist resulted in an annual visit rate of 1.5 and 2.4, respectively. If new dentures became necessary, these were made in student courses, which increased the treatment time and number of appointments needed. Complications with the retention devices consisted mostly of the mounting of new female retainers, the repair of bars, and the changing of ball anchors. The average number of events and the rate of prosthetic service with ball anchors were significantly higher than those with bars. Twenty-two patients changed from ball anchors to bars; 9 patients switched from a clip bar to a rigid U-shaped bar. CONCLUSIONS: This long-term follow-up study demonstrates that implant overdentures are a favorable solution for edentulous patients with regular maintenance. In spite of specific circumstances in an aging population, it is possible to provide long-term care, resulting in a good prognosis and low risk for this treatment modality. For various reasons the dropout rate can be considerable in elderly patients and prosthetic service must be provided regularly.

Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers

Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes.

Local targeting of malignant gliomas by the diffusible peptidic vector 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid-substance p

PURPOSE: Malignant glial brain tumors consistently overexpress neurokinin type 1 receptors. In classic seed-based brachytherapy, one to several rigid (125)I seeds are inserted, mainly for the treatment of small low-grade gliomas. The complex geometry of rapidly proliferating high-grade gliomas requires a diffusible system targeting tumor-associated surface structures to saturate the tumor, including its margins. EXPERIMENTAL DESIGN: We developed a new targeting vector by conjugating the chelator 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid to Arg(1) of substance P, generating a radiopharmaceutical with a molecular weight of 1,806 Da and an IC(50) of 0.88 +/- 0.34 nmol/L. Cell biological studies were done with glioblastoma cell lines. neurokinin type-1 receptor (NK1R) autoradiography was done with 58 tumor biopsies. For labeling, (90)Y was mostly used. To reduce the "cross-fire effect" in critically located tumors, (177)Lut and (213)Bi were used instead. In a pilot study, we assessed feasibility, biodistribution, and early and long-term toxicity following i.t. injection of radiolabeled 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid substance P in 14 glioblastoma and six glioma patients of WHO grades 2 to 3. RESULTS: Autoradiography disclosed overexpression of NK1R in 55 of 58 gliomas of WHO grades 2 to 4. Internalization of the peptidic vector was found to be specific. Clinically, the radiopharmeutical was distributed according to tumor geometry. Only transient toxicity was seen as symptomatic radiogenic edema in one patient (observation period, 7-66 months). Disease stabilization and/or improved neurologic status was observed in 13 of 20 patients. Secondary resection disclosed widespread radiation necrosis with improved demarcation. CONCLUSIONS: Targeted radiotherapy using diffusible peptidic vectors represents an innovative strategy for local control of malignant gliomas, which will be further assessed as a neoadjuvant approach.

A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis

BACKGROUND: Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species. METHODS: A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10. RESULTS: Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated. CONCLUSIONS: Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.

Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors

BACKGROUND: Treatment with (90)Y- or (177)Lu-DOTATOC has recently been introduced in the palliative treatment of somatostatin receptor-expressing neuroendocrine tumors (NETs). The aim of the study was to present clinical experience with (90)Y- and (177)Lu-DOTATOC therapy in the management of NET. METHODS: To prove suitability for treatment each patient underwent scanning with (111)In-DTPAOC or (68)Ga-DOTATOC positron emission tomography/computed tomography. All patients received [(90)Y-DOTATOC] as initial treatment. In case of disease relapse the treatment was repeated. To avoid side effects of repeated [(90)Y] applications, a switch to [(177)Lu-DOTATOC] was carried out. Clinical, biochemical, and radioimaging responses were documented. RESULTS: Twenty patients with metastatic nonresectable NETs (15 pancreas NETs, 2 midgut NETs, 1 gastrinoma, 1 paraganglioma, 1 NET of unknown primary origin) were included. In 8 patients the treatment was repeated more than once (mean, 3 times; range, 2-5 times). After [(90)Y] treatment moderate toxicity was observed in 8 patients. No serious adverse events were documentable. After restaging, a partial remission was found in 5 patients, stable disease in 11 patients, and tumor progression in 4 patients. CONCLUSIONS: Peptide receptor-targeted radionuclide therapy is a promising, safe, and feasible approach in the palliative therapy of patients with NET.

[Radiation exposure in (90)Y-Zevalin therapy: results of a prospective multicentre trial]

AIM of this study was the assessment of the radiation exposure from preparation and application of (90)Y-Zevalin, the measurement of the dose rate at the patient, the exposure of family members as well as the determination of the activity concentration in urine of patients. METHODS: Overall data from 31 therapeutic administrations carried out in four institutions were evaluated. During preparation and application of (90)Y-Zevalin the finger exposures of radiochemists, technicians, and physicians were measured. The dose rate of the patient was measured immediately after radioimmunotherapy. In patients treated in a nuclear medicine therapy unit, urine was collected over a two day period and the corresponding activity was determined. Family members of outpatients were asked to wear a dosimeter over a seven day period. RESULTS: During the preparation we found a maximum skin dose of 6 mSv at the average, and during application of 3 mSv, respectively. After administration of (90)Y the dose rate was 0.4 +/- 0.1 microSv/h at 2 m distance. Urine measurements yielded a cumulated 24 h excretion of 3.9 +/- 1.4% and 4.4 +/- 1.4% within 48 h, respectively, that is equivalent to 43 +/- 18 and 50 +/- 20 MBq of (90)Y, respectively. Family members received a radiation exposure of 40 +/- 14 microSv over seven days. CONCLUSION: During preparation and application of (90)Y-Zevalin appropriate radiation shielding is necessary. For family members as well as nursing staff no additional special radiation protection measures beyond those being common for other nuclear medicine procedures are necessary.

Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis

The aim of the present study was to evaluate the potential of diagnostic tests based on interferon-gamma inducible protein (IP)-10 and monocyte chemotactic protein (MCP)-2, and compare the performance with the QuantiFERON TB Gold In-Tube (QFT-IT; Cellestis, Carnagie, Australia) test. IP-10 and MCP-2 were determined in supernatants from whole blood stimulated with Mycobacterium tuberculosis-specific antigens. Samples were obtained from 80 patients with culture- and/or PCR-proven tuberculosis (TB), and 124 unexposed healthy controls: 86 high school students and 38 high school staff. IP-10 and MCP-2 test cut-offs were established based on receiver operating characteristic curve analysis. TB patients produced significantly higher levels (median) of IP-10 (2158 pg x mL(-1)) and MCP-2 (379 pg x mL(-1)) compared with interferon (IFN)-gamma (215 pg x mL(-1)). The QFT-IT, IP-10 and MCP-2 tests detected 81, 83 and 71% of the TB patients; 0, 3 and 0% of the high school students and 0, 16 and 3% of the staff, respectively. Agreement between tests was high (>89%). By combining IP-10 and IFN-gamma tests, the detection rate increased among TB patients to 90% without a significant increase in positive responders among the students. In conclusion, interferon-gamma inducible protein-10 and monocyte chemotactic protein-2 responses to Mycobacterium tuberculosis-specific antigens could be used to diagnose infection. Combining interferon-gamma inducible protein-10 and interferon-gamma may be a simple approach to increase the detection rate of the Mycobacterium tuberculosis-specific in vitro tests.