Transcutaneous Osseointegrated Prosthesis Systems (TOPS) for Rehabilitation After Lower Limb Loss: Surgical Pearls.

Background: The biology of osseointegration of any intramedullary implant depends on the design, the press-fit anchoring, and the loading history of the endoprosthesis. In particular, the material and surface of the endoprosthetic stem are designed to stimulate on- and in-growth of bone as the prerequisite for stable and long-lasting integration1-8. Relative movement between a metal stem and the bone wall may stimulate the formation of a connective-tissue interface, thereby increasing the risk of peri-implant infections and implant loss9-12. The maximum achievable press-fit (i.e., the force closure between the implant and bone wall) depends on the diameter and length of the residual bone and thus on the amputation level. Beyond this, the skin-penetrating connector creates specific medical and biological challenges, especially the risk of ascending intramedullary infections. On the one hand, bacterial colonization of the skin-penetrating area (i.e., the stoma) with a gram-positive taxon is obligatory and almost impossible to avoid9,10. On the other hand, a direct structural and functional connection between the osseous tissue and the implant, without intervening connective tissue, has been shown to be a key for infection-free osseointegration11,12. Description: We present a 2-step implantation process for the standard Endo-Fix Stem (ESKA Orthopaedic Handels) into the residual femur and describe the osseointegration of the prosthesis13. In addition, we demonstrate the single-step implantation of a custom-made short femoral implant and a custom-made humeral BADAL X implant (OTN Implants) in a patient who experienced a high-voltage injury with the loss of both arms and the left thigh. Apart from the standard preparation procedures (e.g., marking the lines for skin incisions, preparation of the distal part of the residual bone), special attention must be paid when performing the operative steps that are crucial for successful osseointegration and utilization of the prosthesis. These include shortening of the residual bone to the desired length, preparation of the intramedullary cavity for hosting of the prosthetic stem, precise trimming of the soft tissue, and wound closure. Finally, we discuss the similarities and differences between the Endo-Fix Stem and the BADAL X implant in terms of their properties, intramedullary positioning, and the mechanisms leading to successful osseointegration. Alternatives: Socket prostheses for transfemoral or transtibial amputees have been the gold standard for decades. However, such patients face many challenges to recover autonomous mobility, and an estimated 30% of all amputees report unsatisfactory rehabilitation and 10% cannot use a socket prosthesis at all. Rationale: Transcutaneous osseointegrated prosthetic systems especially benefit patients who are unable to tolerate socket suspension systems, such as those with short residual limbs and/or bilateral limb loss. The use of a firmly integrated endoprosthetic stem allows patients and surgeons to avoid many of the limitations associated with conventional socket prostheses, such as the need to continually fit and refit the socket to match an ever-changing stump6,14-19. Discussion between patients who are considering an osseointegrated prosthesis and those who have already received one ("peer patients") has proven to be a powerful tool to prevent unrealistic expectations. Patients with a transhumeral amputation especially benefit from the stable connection between the residual limb and exoprosthesis. Motion of the affected and even the contralateral shoulder is no longer impaired, as straps and belts are dispensable. Furthermore, transmission of myoelectric signals from surrounding muscles to the prosthesis is fundamentally improved. However, comorbidities such as diabetes mellitus or peripheral arterial disease require careful counseling, even if these conditions were not responsible for the loss of the limb. Transcutaneous osseointegrated prosthetic systems for replacement of an upper or lower limb might not be an option in patients who are unable, for any reason, to take adequate care of the stoma. Expected Outcomes: Despite subtle differences between the systems utilized for the intramedullary anchoring of the prosthetic stem, all data indicate that mobility and quality of life significantly increase while the frequency of stoma infections is remarkably low as long as the patient is able to follow simple postoperative care protocols2-5,9,10,13-19. Important Tips: The impaction pressure of the implant depends on the diameter of the implant and the quality of the residual bone (i.e., the time interval between the amputation and the implantation of the prosthetic stem). The extent of reaming of the inner cortex of the residual bone must be adapted to these conditions. The standard Endo-Fix Stem and BADAL X implant are both slightly curved to adapt to the physiological shape of the femur. Thus, the surgeon must be sure to insert the implant in the right position and at the correct rotational alignment. When preparing a short femoral stump, carefully identify the exact transection level in order to obtain enough bone stock to anchor the implant in the correct intramedullary position for an additional locking screw into the femoral neck and head. Depending on the residual length of the humerus and the press-fit stability of the implant, the utilization of locking screws is optional, as a notch at the distal end of the implant guarantees primary rotational stability. Acronyms and Abbreviations: TOPS = transcutaneous osseointegrated prosthesis systemsEEP = endo-exo prosthesisMRSA = methicillin-resistant staphylococcus aureusa.p. = anteroposteriorK-wire = Kirschner wireCT = computed tomographyDCA = double conus adapterOFP = osseointegrated femur prosthesis.

Pharmacokinetics and penetration of moxifloxacin into infected diabetic foot tissue in a large diabetic patient cohort.

OBJECTIVES: Physiological changes occurring in patients with diabetes may affect the pharmacokinetics and penetration of antimicrobial agents into peripheral tissue. We examined the pharmacokinetics and the penetration of moxifloxacin into perinecrotic tissue of diabetic foot lesions in patients with diabetic foot infections (DFI). PATIENTS AND METHODS: Adult patients suffering from type 2 diabetes mellitus and hospitalized for DFI (Texas classification of at least B2) were treated with 400 mg moxifloxacin intravenously (IV) or orally (PO) once daily. The pharmacokinetics of moxifloxacin and its concentration 3 h after administration in samples of perinecrotic tissue resected from infected diabetic foot wounds were determined at steady state (days 4-8). RESULTS: A total of 53 patients with diabetes mellitus type 2 (mean age 69.4 ± 10.8 years) were included in the study, of whom 28 received PO and 25 IV moxifloxacin therapy for a median of 8 days. In the PO and IV subgroups, the mean maximum observed plasma concentration (C (max)) in plasma was 2.69 and 4.77 mg/l at a median of 2 [time to reach C (max) (T (max)) range 1.0-8.0 h] and 1 h after administration, respectively. A mean area under the plasma concentration-time curve from time 0 until the last quantifiable plasma concentration (AUC(0-24 h)) of 29.36 mg h/l (PO) and 27.09 mg h/l (IV) was achieved. Mean moxifloxacin concentrations in perinecrotic tissue of infected diabetic foot wounds following PO or IV administration were 1.79 ± 0.82 and 2.20 ± 1.54 µg/g, thus exceeding the MIC(90) (minimum inhibitory concentration required to inhibit growth of 90% of organisms) for Staphylococcus aureus (0.25 mg/l) by seven- and eightfold and the MIC(90) for Escherichia coli (0.06 mg/l) by 29-fold and 36-fold, respectively. The mean tissue-to-plasma ratios of moxifloxacin concentration 3 h after administration were 1.01 ± 0.57 (PO) and 1.09 ± 0.69 (IV). Significant differences between the routes of administration were observed for T (max) and C (max) (P < 0.01), but not for other clinically relevant parameters (AUC(0-24); moxifloxacin DFI tissue concentration). CONCLUSIONS: The plasma concentration-time curve of moxifloxacin in diabetic patients is similar to that of healthy volunteers. We also observed a good penetration of moxifloxacin into inflamed DFI tissue which taken together with the possibility of sequential IV/PO therapy suggest that moxifloxacin 400 mg once daily is a therapeutic option in the treatment of DFI caused by susceptible organisms.

In vitro and in vivo degradation studies for development of a biodegradable patch based on poly(3-hydroxybutyrate).

For the development of a resorbable gastrointestinal patch, the in vitro degradation of solution-cast films of poly(3-hydroxybutyrate) (PHB), modifications of PHB expected to influence its degradation time, as well a poly(L-lactide) (PLLA) was examined. The molecular weight of pure PHB decreased by one-half after 1 year in buffer solution (pH 7.4, 37 degrees C). Acceleration in molecular weight decrease was observed by blending with atactic PHB, whereas no influence was found with low-molecular weight PHB. Leaching of a water-soluble additive led to a slight acceleration of PHB degradability. In contrast, a deceleration in degradation rate was observed with the addition of a hydrophobic plasticizer. In vitro tests indicated an accelerating effect of pancreatin on PHB degradation, whereas PLLA degradation remained essentially uninfluenced. In comparison to simple hydrolysis, the degradation rate of PHB was accelerated about threefold. From the in vitro results, a PHB/atactic PHB blend was selected for repair of a bowel defect in Wistar rats. A patch film was fabricated by a dipping/leaching method. Twenty-six weeks post-implantation, material remnants were found in only one of four animals. The bowel defects were closed in all cases. It could be assessed that the patch material resists the intestinal secretions for a sufficiently long time but that it finally degrades completely.

Biomaterial implants induce the inflammation marker CRP at the site of implantation.

Following implantation of biomaterial patches into the gastrointestinal tract, we analyzed the host's response towards the foreign material. Asymmetric patches of polydioxanone covered Vicryl or poly-3-hydroxybutyrate were sutured onto the rat stomach. Tissue samples were generated at distinct time intervals after surgery, and RNA profiles were compared by Differential Display. RT-PCR analysis of gene candidates that seemed differentially expressed showed that vitamin D binding protein mRNA was induced in stomach tissue after implantation of the biomaterial patches. In parallel, the amount of C-reactive protein mRNA was found to be increased transiently as well. Implants induce a tissue response that is specific for a given material.

Biomaterial patches sutured onto the rat stomach induce a set of genes encoding pancreatic enzymes.

Asymmetric patches of polyhydroxybutyric acid with one smooth and one rough surface were produced by a dipping procedure. These patches were implanted into the rat gastrointestine and tissue samples were generated at distinct time intervals after surgery. The host's response towards the foreign material was analyzed by Differential Display and RNA profiles were compared to each other. One to two weeks after surgery a group of mRNAs encoding pancreatic enzymes was transiently present after biomaterial implantation.