One-year follow-up data from the German Cartilage Registry (KnorpelRegister DGOU) in the treatment of chondral and osteochondral defects of the talus.

INTRODUCTION: Chondral and osteochondral lesions of the talus (OLTs) remain a challenging issue with numerous operative treatments proposed to date. The aim of this study was to evaluate 1-year follow-up data in the German Cartilage Registry (KnorpelRegister DGOU). METHODS: Among 401 patients in the database, 114 patients with a complete 1-year Foot and Ankle Outcome (FAOS) score for subscale Pain as the primary variable were included. A total of 12 different surgical treatments were performed. However, 8 techniques were carried out in negligible numbers of patients (n = 1-3), leaving 89 patients treated with the following techniques: arthroscopic antegrade bone marrow stimulation (group A; n = 32), autologous chondrocyte implantation with autologous cancellous bone grafting (group B; n = 9), matrix-augmented bone marrow stimulation (group C; n = 22), and matrix-augmented bone marrow stimulation with autologous cancellous bone grafting (group D; n = 26). Group differences and possible influencing variables such as age and sex were evaluated. Level of significance was set at p < 0.05 for all statistical tests. RESULTS: All four treatment groups showed significant improvement of the FAOS scores at 1 year postoperatively compared with their preoperative scores. No significant differences were found with respect to score changes among the groups. A positive correlation between FAOS subscale Pain improvement and defect size volume and negative correlations between increasing age and FAOS subscales Sports/Rec and QoL were found. Concomitant ankle stabilization led to greater improvement in FAOS subscales Symptoms and ADL than in patients with no stabilization. FAOS subscale Pain showed greater improvement in women than in men. CONCLUSION: All analyzed treatment options were effective for treatment of OLTs. In particular, large defects appeared to benefit from treatment. In the presence of concomitant ankle instability, a stabilizing procedure appeared to have a positive impact on the outcome.

[Surgical procedures for the correction and stabilization of pes planovalgus]. / Stabilisierung und Korrektur der medialen Säule im Rahmen der operativen Pes-planovalgus-Therapie.

The medial column of the foot is a relevant factor of the pathogenesis of pes planovalgus. Crucial anatomic structures are the tibiocalcaneonavicular ligament complex, the naviculocuneiform joints, including the ossa cuneiformia, and the first tarsometatarsal joint. A combination of bony and soft tissue reconstructive techniques must, therefore, be taken into account when treating pes planovalgus. The present article presents stabilizing and correcting surgical procedures for the medial column of the foot, including basic anatomy and biomechanics.

Subjective outcome following neurostimulator implantation as drop foot therapy due to lesions in the central nervous system-midterm results.

BACKGROUND: Drop foot can be caused by many conditions. Stroke is one of the major causes of drop foot and 5% of stroke survivors suffer from hemiplegia, which in some cases, can manifest as drop foot. The abnormal gait resulting from the lack of innervation of the extensor muscles may result in a secondary malposition of the foot and lead to a steppage gait. Among the several therapy options for the treatment of drop foot, functional electrostimulation (FES) with a transcutaneous peroneal nerve stimulator (tPNS) or an implantable peroneal nerve stimulator (iPNS) represents the two recent approaches. OBJECTIVE: Although therapy with an iPNS has been proven to be effective, a subjective patient assessment has not yet been executed. The aim of this study was to assess the patient's satisfaction with the therapy by using two established surveys. METHODS: The Rivermead Mobility Index (RMI) and the Reintegration to Normal Life Index (RNLI) were used for this retrospective study. The RMI includes 15 questions which are to be answered as either "yes" or "no" and given a value of 1 or 0, respectively, with a maximum of 15 points possible. The RNLI includes 11 questions which are to be answered with the use of a visual analog scale (VAS, 0 to 10 cm). In this case, a maximum adjusted score of 100 points is possible. RESULTS: The total study cohort involved 56 patients treated with an iPNS. Thirty-five complete data sets for the RMI and 29 for the RNLI could be achieved. A significant difference in the total score of both surveys was observed between the deactivated and the activated iPNS (RMI: p = 0.02; RNL: p = 0.01). CONCLUSION: A significant improvement in patient satisfaction was detected with the use of an activated iPNS after a mean time span of 4 years. Due to the marked mobility, an increase in the social satisfaction and integration could be achieved. Both aspects represent essential components for the recovery and quality of life of the patients.

Nylon sutures versus skin staples in foot and ankle surgery: is there a clinical difference?

BACKGROUND: Staple sutures have already been proven as a good alternative to nylon sutures for wound closure in hip and knee surgeries. One such advantage to using staple sutures is the significant decrease in surgical time. In foot surgeries, staple sutures are still considered critical and are only used sporadically. OBJECTIVE: The aim of this retrospective study was to compare nylon sutures and skin staples for wound closure in foot and ankle surgeries with respect to complications and patient satisfaction. METHODS: A total of 61 patients underwent different operations in the fore-, mid-, and hindfoot areas, which were performed by a single surgeon. Twenty-nine patients received staple wound closures, while 32 patients received nylon suture closures using the Donati back-and-forth technique. Incision length, surgery time, in-patient stay, and wound complications were recorded. Furthermore, a patient survey using the verbal numeric rating scale (VNRS) for subjective pain and cosmetic results at the time of stitch removal (14 days) and after a 6-week follow-up was conducted. RESULTS: A significant between-group difference was found for surgery time (p = .041) and VNRS for pain (p < .001), with better results seen for staple sutures. Four patients with staple sutures and five with nylon sutures experienced wound dehiscence 14 days postoperatively. However, all patients had completely healed wounds at their 6-week follow-up. No revisional surgeries were necessary. CONCLUSION: The present results indicate that a skin staple wound closure is a considerable alternative to the nylon suture closure in foot and ankle surgeries. Nevertheless, further prospective randomized trials must cement these insights.

[Rupture of the tendon of the tibialis anterior muscle : Etiology, clinical symptoms and treatment]. / Ruptur der Musculus-tibialis-anterior-Sehne : Ätiologie, klinische Symptome und Therapie.

Ruptures of the tendon of the tibialis anterior muscle tend to occur in the context of degenerative impairments. This mainly affects the distal avascular portion of the tendon. Owing to the good compensation through the extensor hallucis longus and extensor digitorum muscles, diagnosis is often delayed. In addition to the clinical examination, magnetic resonance inaging (MRI) diagnostics are of particular importance, although damage or rupture of the tendon can also be demonstrated sonographically. Therapeutic measures include conservative or operative measures, depending on the clinical symptoms. Conservative stabilization of the ankle can be achieved by avoiding plantar flexion using a peroneal orthosis or an ankle-foot orthosis. Subsequent problems, such as metatarsalgia or overloading of the medial foot edge can be addressed by insoles or a corresponding shoe adjustment. An operative procedure is indicated when there is corresponding suffering due to pressure and functional impairment. The direct end-to-end reconstruction of the tendon is only rarely possible in cases of delayed diagnosis due to the degenerative situation and the retraction of the tendon stumps. Depending on the defect size and the tendon quality, various operative techniques, such as rotationplasty, free transplants or tendon transfer can be used.

[Foot drop treatment by implantation of a neuroprosthesis (ActiGait®)]. / Behandlung des Fallfußes durch Implantation einer Neuroprothese (ActiGait®).

OBJECTIVE: Gait improvement by restoring dorsiflexion using a neuroprosthesis implant. INDICATIONS: Foot drop with damage to the 1st motor neuron; passive mobility in ankle is possible; adult patients. CONTRAINDICATIONS: Foot drop with peripheral damage and injury to the peroneal nerve; already implanted stimulators (e.g., defibrillator, pacemaker, or pain stimulator); severe anesthesia risks in multimorbid patients. SURGICAL TECHNIQUE: Surgery in lateral position. Searching for the peroneal nerve after dorsal incision in the popliteal fossa, using the medial edge of the biceps femoris as anatomic landmark. After identification of the motor branch of the peroneal nerve by positive dorsiflexion after using electrostimulation apply the electrode cuff on the nerve. Epifascial implantation of stimulation body lateral at the middle third of the thigh over the tractus iliotibialis. POSTOPERATIVE MANAGEMENT: Pain-adapted full weight bearing, no knee flexion more than 90° for 4-6 weeks, activation of neuroprosthesis 3 weeks after surgery, physiotherapy with gait training is required. RESULTS: Between 2013 and 2015, implantation of the neuroprosthesis was performed in 21 patients (13 men/8 women) with chronic foot drop due to a central lesion. Significant improvement in walking speed measured with the 10 meter walk test (11.8 ± 5.4 s to 7.9 s ± 3.4; p = 0.007), in gait endurance with 6 min walk test (212.2 ± 75.5 m to 306.4 ± 96.4 m; p ≤ 0.001), and in gait performance using the Emory Functional Ambulation Profile (105.9 ± 49.7 s to 63.2 ± 31. 3 s; p ≤ 0.001). No patient required surgical revision. Postoperative bleeding was recorded in one case (4%). Patient satisfaction and improvement in mobility and quality of life could be achieved (95% and 90%, respectively).

[Lapidus arthrodesis]. / Lapidus-Arthrodese.

The tarso-metatarsal 1 joint (TMT-I) arthrodesis is a treatment option or moderate to severe hallux valgus (HV) deformities. Instability of the TMT1 joint is still a debatable indication. Using stable osteosynthesis techniques allows early postoperative weight bearing. Plantar plating combined with a lag screw is the biomechanical most stable construct. An additional intermetatarsal screw can improve the horizontal stability. Clinical results are good and radiological parameters stay constant, even in the long term.

[Distal osteotomy for the treatment of hallux valgus (Chevron osteotomy)]. / Distale Korrekturosteotomie zur Behandlung des Hallux valgus (Chevron-Osteotomie).

Distal osteotomies, like the Chevron osteotomy, is indicated for mild to moderate hallux valgus deformities. Splayfoot, painful pseudoexostosis, and transfer metatasalgia are observed in the clinical examination. Radiographic examination should be done with weight bearing in two planes. Preoperatively the intermetatarsal (IM), hallux valgus, and distal metatarsal articular (DMAA) angles should be measured. The operative technique is based on soft tissue and bony correction. Modifications of the osteotomy allow a shortening, lengthening, or neutral correction of the first metatarsal. With a modified Chevron osteotomy, an increased DMAA can be also corrected.

[Functional electrostimulation for drop foot treatment : Clinical outcome]. / Funktionelle Elektrostimulation zur Therapie des neurogenen Fallfußes : Klinisches Outcome.

INTRODUCTION: Neurologic paralysis of the foot due to damage to the central nervous system is primarily caused by a cerebral insult. The ankle-foot orthosis (AFO), which is the classical conservative treatment option, is associated with drawbacks, e.g., increased contractures, limited mobilization from the sitting position, and cosmetic aspects. METHODS: Functional external electrostimulation (FES) is an suitable treatment method for patients with a central lesion and intact peroneal nerve. Based on this method, the neuroprosthesis is a dynamic therapy option in the form of an implantable nerve stimulator (ActiGait® system, Otto Bock, Duderstadt, Germany) which is placed directly on the motor branch of the peroneus nerve and results in active foot lifting. The aim of the present study is to evaluate the clinical effect of the ActiGait® system with regard to its suitability for everyday use by means of gait tests with an emphasis on time-distance parameters and to compare it with the current literature. RESULTS AND CONCLUSION: In this retrospective study, the clinical results after implantation of the ActiGait® system are presented and evaluated. In summary, the implantation of a neuroprosthesis in patients with stroke-related drop foot represents a sensible and promising therapy option.

Restoring mobility after stroke: first kinematic results from a pilot study with a hybrid drop foot stimulator.

OBJECTIVE: The objective was to obtain first insights into the kinematic and kinetic walking patterns resulting from an implanted functional electrical stimulation system in subjects with a drop foot caused by stroke. METHODS: Four subjects who experienced a stroke were chosen due to a comparatively long/short time after surgery and young/old at the stroke event were examined retrospectively with gait analysis. Kinematics and kinetics of normal walking were assessed in comparison with and without activated drop foot stimulation. RESULTS: In general, an improvement regarding spatiotemporal parameters as a result of the stimulation could be observed. Walking speed was increased by 45 % and stride length by 22 % after a mean usage of 7 (2-14) months, whereas both younger subjects improved significantly more. Dorsiflexion increased in all subjects on average from 1.3° to 11.6° during initial contact as well as from 11.3° to 17.0° during mid-swing and therefore implies an advantage of around 5.5 inch foot clearance. Pathologic elements like knee hyperextension during loading response and mid-stance, leg circumduction during swing or the increased hip flexion of the contralateral leg during mid-stance could be in general adjusted with stimulation. CONCLUSION: An implantable functional electrical stimulation system seems to be a promising treatment of drop feet following strokes. Further clinical investigations are necessary to confirm these first insights.

Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours.

The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®, Pfizer Animal Health, Madison, NJ, USA) in select solid tumours in dogs. Cases in which toceranib was used to treat dogs with apocrine gland anal sac adenocarcinoma (AGASACA), metastatic osteosarcoma (OSA), thyroid carcinoma, head and neck carcinoma and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 AGASACA [8 partial response (PR), 20 stable disease (SD)], 11/23 OSAs (1 PR and 10 SD), 12/15 thyroid carcinomas (4 PR and 8 SD), 7/8 head and neck carcinomas [1 complete response (CR), 5 PR and 1 SD] and 5/7 (1 CR and 4 SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg kg(-1) , 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis and 47/63 (74.6%) were treated 4 months or longer. Although these data provide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumours, future prospective studies are necessary to define its true activity.

Heat shock protein 27 confers resistance to androgen ablation and chemotherapy in prostate cancer cells through eIF4E.

One strategy to improve therapies in advanced prostate cancer (PC) involves targeting genes that are activated by androgen withdrawal to delay the emergence of the androgen-independent (AI) phenotype. Heat shock protein 27 (Hsp27) expression becomes highly upregulated in PC cells after androgen withdrawal or chemotherapy, in which it functions as a cytoprotective chaperone to confer broad-spectrum treatment resistance. The purpose of this study is to elucidate anti-apoptotic pathways regulated by Hsp27 that are activated during PC progression. Using two-hybrid experiment, we found that Hsp27 was having a major role in the protein translational initiation process. Furthermore, using complementary DNA (cDNA) microarray analysis, 4E binding protein 1 was identified as being proportionately and highly regulated by Hsp27. These data led us to analyze the protein synthesis initiation pathway, which is a prerequisite for cell growth and proliferation. Using northern and western blot analysis, we found that Hsp27 downregulation decreased eukaryotic translation initiation factor 4E (eIF4E) expression at the protein, but not mRNA, level. The cytoprotection afforded by Hsp27 overexpression was attenuated by eIF4E knockdown using specific eIF4E short interfering RNA (siRNA). Co-immunoprecipitation and co-immunofluorescence confirmed that Hsp27 colocalizes and interacts directly with eIF4E. Hsp27-eIF4E interaction decreases eIF4E ubiquitination and proteasomal degradation. By chaperoning eIF4E, Hsp27 seems to protect the protein synthesis initiation process to enhance cell survival during cell stress induced by castration or chemotherapy. Forced overexpression of eIF4E induces resistance to androgen-withdrawal and paclitaxel treatment in the prostate LNCaP cells in vitro. These findings identify Hsp27 as a modulator of eIF4E and establish a potential mechanism for the eIF4E-regulated apoptosis after androgen ablation and chemotherapy. Targeting Hsp27-eIF4E interaction may serve as a therapeutic target in advanced PC.

Enhanced sensitivity to androgen withdrawal due to overexpression of interleukin-6 in androgen-dependent human prostate cancer LNCaP cells.

BACKGROUND: The objective of this study was to investigate the effects of interleukin-6 (IL-6) overexpression in androgen-dependent prostate cancer LNCaP cells on their phenotype under an androgen-deprived condition. METHODS: We established IL-6-overexpressing LNCaP (LNCaP/IL-6) by introducing the expression vector containing IL-6 cDNA. Changes in the phenotype in LNCaP/IL-6 were compared with that in LNCaP transfected with control vector alone (LNCaP/Co). RESULTS: In vitro, the growth of LNCaP/IL-6 was significantly inferior to that of LNCaP/Co under an androgen-deprived condition. Similarly, LNCaP/IL-6 tumour in nude mice rapidly regressed after castration; however, LNCaP/Co tumour growth was transiently inhibited after castration and then continuously accelerated. After androgen withdrawal, expression levels of phosphorylated p44/42 mitogen-activated protein kinase (MAPK) and Akt in LNCaP/IL-6 were markedly upregulated compared with those in LNCaP/Co; however, additional treatment with specific inhibitor of the MAPK or Akt signalling pathway significantly inhibited the growth of LNCaP/IL-6 compared with that of LNCaP/Co. Furthermore, gene microarray analyses showed that androgen deprivation resulted in differential expression of genes involved in growth, apoptotsis and tumorigenesis between LNCaP/Co and LNCaP/IL-6. CONCLUSION: Excessive secretion of IL-6 by LNCaP cells in an autocrine manner may have a suppressive function in their growth and acquisition of androgen-independent phenotype under an androgen-deprived condition.

Measures of adiposity and body fat distribution in relation to serum folate levels in postmenopausal women in a feeding study.

OBJECTIVE: To assess the associations between serum folate concentration and measures of adiposity in postmenopausal women. DESIGN: This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n=51) consumed 0 g (control), 15 g (one drink) and 30 g (two drinks) alcohol (ethanol)/day for 8 weeks as part of a controlled diet. Subjects in one treatment arm were crossed-over to another arm after a 2- to 5-week washout period. Body mass index (BMI) was measured, and dual energy X-ray absorptiometry (DEXA) scan administered to the women during the control (0 g alcohol) treatment, and a blood sample from this group was collected at baseline and week 8 of each diet period and analyzed for folate, B12, homocysteine and methylmalonic acid. SETTING: This study was conducted at the Beltsville Human Nutrition Research Center, MD, USA. RESULTS: In multivariate analysis, women who were overweight had a 12% lower, and obese women had a 22% lower serum folate concentrations compared to normal weight women (P-trend=0.02). Vitamin B12 also decreased with increasing BMI (P-trend=0.08). Increased BMI, percent body fat, and absolute amounts of central and peripheral fat were all significantly associated with decreased serum folate, but were unrelated to serum B12, homocysteine or methylmalonic acid. CONCLUSIONS: Our data show that adiposity is associated with lower serum folate levels in postmenopausal women. With obesity at epidemic proportions, these data, if confirmed by prospective or randomized controlled studies, have important public health implications.

Prognostic significance of intratumoral microvessel density in canine soft-tissue sarcomas.

The prognosis of canine soft-tissue sarcomas (STS) has traditionally been based on histologic grading. We have recently demonstrated the prognostic value of cellular proliferation markers in canine STS. Another method of predicting the behavior of neoplasms is intratumoral microvessel density (IMD), which is a measure of tumor angiogenesis. The prognostic significance of IMD has been documented in many human neoplasms and in a limited number of canine and feline neoplasms. To evaluate the prognostic value of IMD in canine STS, we studied 57 STS and compared IMD with histologic features, histologic grade, cellular proliferation, metastatic propensity, and survival. Using immunohistochemistry, the STS were labeled with anti-factor VIII-related antigen (FVIII-RA) and anti-CD31 antibodies to determine 3 IMD parameters: mean microvessel density, high microvessel density, and microvessel area. Using FVIII-RA and CD31, increasing IMD was statistically associated with increasing histologic grade, necrosis scores, and mitotic scores. Higher FVIII-RA IMD values were significantly associated with higher median argyrophilic nucleolar organizing region (AgNOR) values (as previously investigated) and increased metastatic propensity. Fibrosarcomas appear to be the least vascularized of STS. There is no correlation between IMD and survival. Our results indicate that IMD is of prognostic value for histologic grade, histologic features, cellular proliferation (based on AgNOR), and metastatic propensity of canine STS, specifically when using FVIII-RA as the endothelial marker. Assessing histologic grading, cellular proliferation, and IMD of canine STS at the time of diagnosis could therefore provide better prognostic information for the veterinary clinician.

Urea as a recovery marker for quantitative assessment of tumor interstitial solutes with microdialysis.

Microdialysis is a technique that enables measurement of extracellular concentrations of unbound analytes. A small probe with a semipermeable membrane is implanted in tissue and constantly perfused. Small analytes in the interstitial fluid diffuse into the perfusate and are collected. Often, microdialysate concentrations of an analyte are only a fraction of the unbound concentrations in the extracellular space attributable to incomplete equilibration between these two compartments. Thus, it is necessary to determine the degree of equilibration between microdialysate and interstitium for each probe to accurately estimate concentrations. In this study, we investigated tissue urea as a solute to continually correct for nonequilibrium conditions. We used this method, along with relative diffusivities of urea and glucose, to monitor glucose levels before and during hyperglycemia as an example of how this method can be applied. No-net-flux experiments were performed on 10 anesthetized female rats with mammary adenocarcinomas. Microdialysis probes 1 cm in length with a molecular weight cutoff of M(r) 100,000 were used. Urea was added to the perfusate in concentrations of 0.83, 2.5, 5.0, and 13.33 mM. Microdialysate samples were collected every 15 min. For each rat, there was a linear relationship between the net urea concentration (outflow-inflow) and the urea concentration in the perfusate (inflow). Net flux should equal zero when perfusate and interstitial concentrations are equal. In an additional series of 13 rats, microdialysate samples were obtained before, during, and after administration of glucose at a dose of 1 g/kg. The interstitial tumor urea concentration was 7.8 +/- 0.3 mM compared with 6.2+/- 0.3 mM in plasma. There was a significant linear relationship between plasma urea (measured directly) and tumor urea (microdialysis measurement). Plasma urea concentrations were constant over time in all of the experiments, including those where hyperglycemia was induced. Hyperglycemia caused 7.7- and 3.6-fold increases in tumor and plasma glucose, respectively. There was no effect of hyperglycemia on tumor blood flow. Urea appears to be a useful low molecular weight relative recovery marker for tumor microdialysis. In combination with the determination of relative diffusivity between urea and the solute of interest, this calibration method may allow for quantitative measurements of tumor metabolites and unbound drugs.

Short-term 17-beta-estradiol administration does not affect metabolism in young males.

We have previously demonstrated that females oxidize more lipid and less protein and carbohydrate during endurance exercise [21]. Several studies in male rats have demonstrated similar metabolic changes after 4 d of 17-beta-estradiol (E2) administration. Our purpose was to study the effects of E2 administration upon substrate metabolism during 90min of cycle ergometry at 60% VO2peak in 11 healthy, young males. E2 was administered in a single-blind, cross-over, randomized fashion for 11 d (100 microg.d(-1) x 3.5d --> 200 microg.d(-1) x 3.5 d --> 300 microg.d(-1) x 4.0 d). Respiratory exchange ratio (RER), VO2, Ve, HR, lactate, and glucose were measured every 30 min during exercise and E2, testosterone TEST, glycerol and triglycerides were measured prior to exercise T = 0 min. Muscle biopsies were taken from the vastus lateralis before and after exercise for glycogen determination. Estradiol treatment resulted in lower plasma TEST (20.8-->7.8 nmol.L(-1), P<0.0001) and higher plasma E2 (168.1 327.3 pmol.L(-1), P < 0.002). Therewere no effects of E2 treatment upon any of the other measured variables including muscle glycogen: (E2 - PRE = 529.3 --> POST = 237.9; PL-PRE = 582.2 --> POST = 262.4 mmol.kg(-1) [dm]). We concluded that short-term E2 treatment increased plasma E2 to female follicular levels in males but had no effect upon lipid or carbohydrate metabolism.