Antibacterial Bioactive Glass, S53P4, for Chronic Bone Infections - A Multinational Study

Correction: Volume: 971 Pages: 115-116 DOI: 10.1007/5584_2017_13 Published: 2017 WOS:000446017300010Osteomyelitis is an infectious process in bone that occasionally leads to bone destruction. Traditionally, the surgical treatment procedure is performed in combination with systemic and local antibiotics as a two-stage procedure that uses autograft or allograft bone for filling of the cavitary defect. Bioactive glass (BAG-S53P4) is a bone substitute with proven antibacterial and bone bonding properties. One hundred and sixteen patients who had verified chronic osteomyelitis was treated using BAG-S53P4 as part of the treatment. Most of the patients had previously undergone numerous procedures, sometimes for decades. A register of patient data obtained from 11 centers from Finland, Italy, the Netherlands, Germany, Azerbaijan and Poland was set-up and continuously maintained at Helsinki University Central Hospital. The location of the osteomyelitis was mainly in the tibia followed by the femur and then the calcaneus. The median age of the patients was 48 years (15-87). The patients were either treated according to a one-stage procedure without local antibiotics (85 %) or by a two-stage procedure using antibiotic beads in the first procedure (15 %). The minimum follow-up was 1 year (12-95 months, median 31). The cure rate was 104/116, the total success rate 90 % and most of the patients showed a rapid recovery. The study shows that (BAG-S53P4) can be used in a one-stage procedure in treatment of osteomyelitis with excellent results.Peer reviewe

Ceftriaxone bone penetration in patients with septic non-union of the tibia

SummaryObjectivesA main determinant of clinical response to antibiotic treatment is drug concentration at the infected site. Data on ceftriaxone (CFX) bone penetration are lacking. We measured CFX concentrations in infected bone to verify their relationship with pharmacodynamic microbiological markers.MethodsEleven patients undergoing debridement for septic non-union of the tibia and receiving intravenous CFX were studied. Plasma and bone specimens were collected intraoperatively at a variable interval after CFX administration. Drug concentrations were measured by high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method.ResultsBone samples were extracted at a mean of 3.3h (range 1.5–8.0h) since the start of CFX infusion. The mean±standard deviation intraoperative CFX plasma concentration was 128.4±30.8mg/l; the corresponding bone concentrations were 9.6±3.4mg/l (7.8%) in the cortical compartment and 30.8±8.6mg/l (24.3%) in the cancellous compartment. The mean 24-h area under the concentration–time curve (AUC24) values were 176.8±62.2 h*mg/l in cortical bone and 461.5±106.8 h*mg/l in cancellous bone. The time above the minimum inhibitory concentration (T>MIC) was 24h in all compartments. The estimated mean free AUC/MIC ratios and T>MIC were 140 and 24.4h, respectively, in cancellous bone and 42.4 and 21h, respectively, in cortical bone.ConclusionsCFX bone penetration was poor (<15%) in the cortical compartment and satisfactory in the more vascularized cancellous bone. The T>MIC and AUC/MIC ratios suggest that CFX achieves a satisfactory pharmacokinetic exposure in cancellous bone as far as pathogens with a MIC of <0.5 are concerned. However, considering free drug concentrations, pharmacokinetic/pharmacodynamic targets may not be fully achieved in cortical bone. As antibiotic exposure can be suboptimal in the infected cortical compartment, and drug penetration may be impaired into necrotic bone and sequesters, a radical surgical removal of purulent and necrotic tissues appears essential to shorten treatment duration and to prevent treatment failures

Can Clinical and Surgical Parameters Be Combined to Predict How Long It Will Take a Tibia Fracture to Heal? A Prospective Multicentre Observational Study: The FRACTING Study

Background. Healing of tibia fractures occurs over a wide time range of months, with a number of risk factors contributing to prolonged healing. In this prospective, multicentre, observational study, we investigated the capability of FRACTING (tibia FRACTure prediction healING days) score, calculated soon after tibia fracture treatment, to predict healing time. Methods. The study included 363 patients. Information on patient health, fracture morphology, and surgical treatment adopted were combined to calculate the FRACTING score. Fractures were considered healed when the patient was able to fully weight-bear without pain. Results. 319 fractures (88%) healed within 12 months from treatment. Forty-four fractures healed after 12 months or underwent a second surgery. FRACTING score positively correlated with days to healing: r = 0.63 (p &lt; 0.0001). Average score value was 7.3 \ub1 2.5; ROC analysis showed strong reliability of the score in separating patients healing before versus after 6 months: AUC = 0.823. Conclusions. This study shows that the FRACTING score can be employed both to predict months needed for fracture healing and to identify immediately after treatment patients at risk of prolonged healing. In patients with high score values, new pharmacological and nonpharmacological treatments to enhance osteogenesis could be tested selectively, which may finally result in reduced disability time and health cost savings

Thyrotropin regulation of malic enzyme in FRTL5 rat thyroid cells

TSH-induced increases in malic enzyme mRNA levels in FRTL-5 rat thyroid cells are paralleled by increases in malic enzyme activity and are mimicked by 8-bromo-cAMP. Apparent approximately 4 h after TSH challenge and maximal after 16 h, they decline by 24 h and are at basal levels by 48 h. The increase occurs in the absence of a measurable effect of TSH on DNA synthesis related to cell growth, since [3H] thymidine incorporation into DNA is still at basal levels 24 h after TSH challenge and is maximal only at 48 h. A protein(s) whose formation is inhibited by cycloheximide appears to be critical to the ability of TSH to increase malic enzyme mRNA levels. Thus, cycloheximide given 30 min before TSH prevents the hormone-induced increase in malic enzyme mRNA; also, when given 24 h after TSH, cycloheximide accelerates the loss of the TSH-induced increase in malic enzyme mRNA. In neither case does cycloheximide affect beta-actin mRNA levels. A second factor(s) whose formation is prevented by actinomycin-D appears to be important for the decrease in malic enzyme mRNA levels seen 24 and 48 h after TSH challenge. Thus, in experiments in which it is given 24 h after TSH, actinomycin-D preserves the hormone-induced increase in malic enzyme mRNA levels rather than accelerating the decrease, as does cycloheximide. In the same experiment, beta-actin mRNA levels decrease to less than 10-20% of control values over the same period; this factor also, therefore, appears to exhibit some degree of specificity

Treatment of femoral shaft fractures with monoaxial external fixation in polytrauma patients [version 1; referees: 3 approved]

Background: Femoral shaft fractures, typical in younger people, are often associated with polytrauma followed by traumatic shock. In these situations, despite intramedullary nailing being the treatment of choice, external fixation could be used as the definitive treatment. The aim of this study is to report evidence regarding definitive treatment of femoral shaft fractures with monoaxial external fixation. Methods: Between January 2006 and December 2015, 83 patients with 87 fractures were treated at the Department of Orthopaedics and Traumatology CTO of Turin, with a monoaxial external fixation device. Mean age at surgery, type of fracture, mean follow-up, time and modalities of treatment, non-weight bearing period, average healing, external fixation removal time, and complications were reported. Results: The average patient age was 31.43±15.19 years. In 37 cases (42.53%) the right femur was involved. 73 (83.91%) fractures were closed, and 14 (16.09%) were open. The average follow-up time was 61.07±21.86 weeks.  In 68 (78.16%) fractures the fixation was carried out in the first 24 hours, using a monoaxial external fixator. In the remaining 19 cases, the average delay was 6.80±4.54 days. Mean non-weight bearing time was 25.82±27.66 days (ranging from 0 to 120). The 87 fractures united at an average of 23.60±11.37 weeks (ranging from 13 to 102). The external fixator was removed after an average of 33.99±14.33 weeks (ranging from 20 to 120). Reported complications included 9.19% of delayed union, 1.15% of septic non-union, 5.75% of malunion, and 8.05% cases of loss of reduction. Conclusions: External fixation of femoral shaft fractures in polytrauma is an ideal method for definitive fracture stabilization, with minimal additional operative trauma and an acceptable complication rate

Treatment of Infected Tibial Non-Unions with Ilizarov Technique: A Case Series

Background: The Ilizarov external fixation technique has been widely used for the treatment of long-bone infected non-unions. After surgical infected bone resection, to allow filling of the remaining bone gap, biomaterials with antibacterial properties could be used. The aim of this study was to report outcomes of infected tibial non-unions treated using the Ilizarov technique and antibacterial bioactive glass. Methods: Between April 2009 and December 2014, 26 patients with infected tibial non-unions were treated with the Ilizarov technique and possible use of the bioactive glass, S53P4. The Association for the Study and Application of Methods of Ilizarov (ASAMI) criteria, a clinical and radiographic evaluating tool, was used for assessing the sample. Results: The average age at the start of treatment was 51 years. The mean follow-up time was 113 weeks. According to the ASAMI Functional Scoring System, 10 excellent (38.5%) cases and 12 good (46.1%) values were recorded. According to the ASAMI Radiological System, they were excellent in 16 (61.5%) cases and good in nine (34.6%). Conclusions: Treatment of infected tibial non-unions using the Ilizarov technique was effective in bone segment regeneration. To fill the remaining bone gap, additional bioactive glass S53P4 could be used, allowing a decrease in re-interventions and minimizing complications