Longitudinal observation of anxiety and depression among palliative care cancer patients.

BACKGROUND: Anxiety and depressive symptoms are commonly reported to have a high prevalence in advanced cancer patients. However, whether the severity of the symptoms change during a stay in a palliative care unit (PCU) and after discharge home has not been studied thus far. This prospective, longitudinal, single-center study screened for anxiety and depression as measured on the German version of Hospital Anxiety and Depression Scale (HADS-D) in a palliative care (PC) cancer cohort at three different time points. METHODS: Consecutive patients (N=206) admitted to a PCU were evaluated of whom N=102 could be enrolled. Patients were screened for anxiety and depression using the HADS-D questionnaire: 24 h after admittance (P1), within 24 h before discharge (P2) and 2 weeks after discharge (P3). Longitudinal changes and influencing factors were determined. RESULTS: Nearly 80% of all patients had at least at one time point a HADS score ≥8 indicating a clinically meaningful symptom burden. The P1 mean scores were 7.1±3.3 (anxiety) and 8.9±4.6 (depression). Depression was associated with underlying cancer type (P<0.05). Anxiety and depression stabilized during hospitalization (P2). However, a significant deterioration after discharge (P3) was observed (anxiety P=0.046; depression P=0.003), in particular in older patients (>65 years) and higher ECOG status (≥3). Patients with a short time since first diagnosis (<1 year) had significantly higher symptom burden compared to patients with a longer disease course. Participation was 50% emphasizing the difficulty to study PC patients. Most patients had advanced cancers (99%). Underlying cancer types consisted of a broad variety of solid tumors including 15% hematological cases. Median survival was 1.1 months. CONCLUSIONS: The high prevalence of anxiety and depressive symptoms points to the need for psychological support. All PC patients should be screened for psychological distress to identify those in need of further assessment and treatment. The deterioration at home suggests the need for improved outpatient management, including home-based psychological support. Caregivers should be aware of the psychological vulnerability of newly diagnosed cancer patients, patients with lower functional status and higher age.

Longitudinal [18F]FDG-PET/CT analysis of the glucose metabolism in ApoE-deficient mice.

BACKGROUND: Strong line of evidence suggests that the increased risk to develop AD may at least be partly mediated by cholesterol metabolism. A key regulator of cholesterol transport is the Apolipoprotein E4 (ApoE4), which plays a fundamental role in neuronal maintenance and repair. Impaired function of ApoE4 may contribute to altered cerebral metabolism leading to higher susceptibility to neurodegeneration. METHODS: To determine a possible link between ApoE function and alterations in AD in the brain of Apolipoprotein E-deficient mice (ApoE-/-) in a longitudinal manner metabolic and neurochemical parameters were analyzed. Cortical metabolism was measured by 2-deoxy-2-[18F]fluoroglucose ([18F]FDG)-PET/CT and proton magnetic resonance spectroscopy (1H-MRS) served to record neurochemical status. RESULTS: By using [18F]FDG-PET/CT, we showed that brain metabolism declined significantly stronger with age in ApoE-/- versus wild type (wt) mice. This difference was particularly evident at the age of 41 weeks in almost each analyzed brain region. In contrast, the 1H-MRS-measured N-acetylaspartate to creatine ratio, a marker of neuronal viability, did not decline with age and did not differ between ApoE-/- and wt mice. CONCLUSION: In summary, this longitudinal in vivo study shows for the first time that ApoE-/- mice depict cerebral hypometabolism without neurochemical alterations.

Stem cell registry programme for patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting: what benefits does it derive?

AIMS: Standardization of stem cell therapy requires application of appropriate methods to evaluate safety and efficacy, including long-term pharmacovigilance. To accomplish this objective, a long-term registry programme was installed. METHODS AND RESULTS: We analysed 150 patients with ischemic cardiomyopathy, who received intramyocardial CD133+ bone marrow mononuclear stem cell treatment combined with coronary artery bypass grafting (CABG) or CABG alone. The mortality rate, major adverse cerebral and cardiac events, and functional outcome parameters were evaluated for the time period up to 14 years follow-up. As a result, we have stratified the patient population (96 patients) into responders and non-responders. Furthermore, the analysis of relevant predictors of good response to CD133+ bone marrow mononuclear stem cell treatment was performed. Several positive tendencies related to stem cells transplantation were demonstrated. First, no significant difference in major adverse cardiovascular and cerebral events was observed between stem cell and control group up to 14 years follow-up. Second, an improvement of left ventricle ejection fraction (LVEF) in stem cell group retained for 5 years in contrast with CABG-only group, where no significant changes in LVEF after 2 years were observed. In addition, LVEF under 30% and left ventricle end diastolic diameter above 60 mm were independent predictors of functional response to CD133+ cell therapy. CONCLUSIONS: Participants with overt heart failure benefit most from CABG combined with intramyocardial injection of CD133+ bone marrow mononuclear cell within the group. An improvement LVEF in stem cell group remained for 5 years in contrast with the CABG-only group. The patients, in whom the improvement of both LVEF and LVED was observed, have benefited by increased life expectancy.

Biomechanics of the osteoporotic spine, pain, and principles of training.

INTRODUCTION: A fracture is a clinical manifestation of osteoporosis and is one of the main causes of functional limitations and chronic pain in patients with osteoporosis. Muscle and coordination training are recommended to the patients as general measures. We inquired whether sling training is better than traditional physiotherapy in relieving pain and improving abilities of daily living. METHODS: Fifty patients with osteoporosis were divided into two groups. Group A performed conventional physiotherapy, while Group B performed sling training exercises. Data were collected before and after the intervention and after 3 months. The registered parameters were stamina, posture, and pain. Posture, torques, and the associated strength of spinal muscles were studied in a biomechanical model in order to estimate the forces acting on the spine. Furthermore, the factors that exerted a positive impact on the success of therapy were registered. RESULTS: Forty-four patients (88%) completed the study. Positive effects of the training were noted in both groups, but significantly better effects were observed in the group that performed sling training. A reduction of pain independent of the number of fractures, significantly reduced torques, and reduced muscle strength were registered. CONCLUSIONS: Specific training programs helped to increase muscle strength and straightening the back thereby reducing the force needed on a permanent basis and decreasing torque in the spine. Sling training was more effective in that than traditional physiotherapy.

Screening for Gram-negative bacteria: Impact of preanalytical parameters.

Screening recommendations for multidrug-resistant Gram-negative bacteria comprise microbiological analyses from rectal swabs. However, essential specifications of the preanalytic steps of such screenings, i.e. the sampling technique, sampling devices and sampling site, are lacking. For standardized and optimum screening conditions these parameters are indispensable. Here, the optimum parameters were examined irrespective of the antibiotic resistance patterns of the target bacteria in order to establish a general basis for this type of screening. Swabs with rayon, polyurethane-cellular-foam and nylon-flocked tips were tested. Different sampling locations were evaluated, i.e. perianal, intraanal and deep intraanal. Subjects were swabbed and quantities of E. coli, K. pneumoniae, P. aeruginosa and A. baumannii were assessed. Overall prevalences of E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii were 94%, 16%, 12%, and 2%, respectively. Bacterial recovery rates were independent from the sampling-timepoint during hospital stay. Polyurethane-cellular-foam or nylon-flocked swabs recovered significantly more bacteria as compared to rayon swabs. Intraanal swabbing resulted in significantly higher bacterial quantities as compared to perianal swabbing. In contrast, for the detection of A. baumannii, perianal swabbing seems more suitable than intraanal swabbing. Gender-related differences in bacterial recovery could be detected from perianal but not from intraanal swabs.

Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.

PURPOSE: Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT). PROCEDURES: We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used. RESULTS: The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C]CHO. The T/M ratio as well as the T/B ratio for [(18)F]Bombesin were significantly higher compared to those for [(11)C]CHO (p < 0.001, respectively). Kidney and liver uptake was statistically significantly lower for [(18)F]Bombesin (K/B 3.41 ± 0.81, L/B 1.99 ± 0.38) compared to [(11)C]CHO [K/B 7.91 ± 1.85 (p < 0.001), L/B 6.27 ± 1.99 (p < 0.001)]. The magnitudes of the time course of T/M and T/B ratios (T/M and T/Bdyn ratios) were statistically significantly different (showing a higher uptake of [(18)F]Bombesin compared to [(11)C]CHO); additionally, also the change of the T/M and T/B ratios over time was significantly different between both tracers in the dynamic analysis (p < 0.001, respectively). Furthermore, there was a statistically significantly different change of the K/B and L/B ratios over time between the two tracers in the dynamic analysis (p = 0.026 and p < 0.001, respectively). CONCLUSIONS: [(18)F]Bombesin (BAY 86-4367) visually and semi-quantitatively outperforms [(11)C]CHO in the PC-3 prostate cancer xenograft model. [(18)F]Bombesin tumor uptake was significantly higher compared to [(11)C]CHO. [(18)F]Bombesin showed better imaging properties compared to the clinically utilized [(11)C]CHO due to a higher tumor uptake as well as a lower liver and kidney uptake.

Evaluation of the physical activity of German soldiers depending on rank, term of enlistment, and task area.

Physical fitness of soldiers plays an important role during combat operations and training for deployment. The aim of this study was to collect data on the physical activity of soldiers of all rank categories and to identify task areas in which inactivity and the resulting health problems such as obesity, cardiovascular disease, and musculoskeletal problems pose a special risk. For this purpose, the physical activity of 169 German soldiers of different ranks and task areas was measured. These soldiers wore accelerometer-based physical activity monitors for a period of 7 days. Their activities were also documented in standardized forms. The results showed that officers (541 steps/h) had the lowest level of physical activity during their duties (compared to noncommissioned officers): 600 steps/h, and junior enlisted personnel: 724 steps/h). With respect to term of enlistment, conscripts and temporary-career volunteers showed a higher level of physical activity than regulars (751 and 640 vs. 539 steps/h). With respect to different task areas, drivers showed the highest activity level, whereas staff personnel showed the lowest. High-ranking personnel and soldiers in staff positions were shown to have the lowest physical activity level. In these groups, possible health problems caused by physical inactivity could be alleviated.

Diabetic foot syndrome and corneal subbasal nerve plexus changes in congolese patients with type 2 diabetes.

BACKGROUND: To study the severity of diabetic neuropathy, diabetic retinopathy and grades of diabetic foot syndrome for correlations with corneal subbasal nerve plexus (SBP) changes in Congolese patients with type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-eight type 2 diabetes patients with diabetes-related foot ulceration were recruited in a diabetic care unit in Kinshasa, Democratic Republic of Congo. Corneal SBP was investigated by confocal laser-scanning microscopy to analyse nerve fibre density (NFD) [µm/ µm²], number of branches [n] and number of connectivity points [n]. Foot ulceration was graded using the Wagner ulcer classification. Corneal sensitivity (Cochet-Bonnet), Neuropathy Symptom Score (NSS), Neuropathy Disability Score (NDS), ankle-brachial index (ABI) and ophthalmological status were evaluated. Foot ulceration was ranked as mild (Wagner 0-1: 13 patients/46.4%), moderate (Wagner 2-3: 10 patients/35.7%) and severe (Wagner 4-5: 5 patients/17.9%). The correlation between Wagner Score and NFD (p=0.017, r = - 0,454), NDS and NFD (p=0,039, r = - 0.400) as well as Wagner Score and HbA1c (p=0,007, r = - 0.477) was stated. Significant differences in confocal SBP parameters were observed between Wagner 0-1 and Wagner 4 5 (number of branches (p=0.012), number of connectivity points (p=0.001), nerve fibre density (p=0.033)) and ABI (p=0.030), and between Wagner 2-3 and Wagner 4-5 (number of branches (p=0.003), number of connectivity points (p=0.005) and nerve fibre density (p=0.014)). Differences in NDS (p=0.001) and corneal sensation (p=0.032) were significant between Wagner 0-1 and Wagner 2-3. Patients with diabetic retinopathy had significantly longer diabetes duration (p=0.03) and higher NDS (p=0.01), but showed no differences in SBP morphology or corneal sensation. CONCLUSIONS/SIGNIFICANCE: While confirming the diabetic aetiology of foot ulceration due to medial arterial calcification, this study indicates that the grade of diabetic foot syndrome correlates with corneal SBP changes and corneal sensation in patients in sub-Saharan Africa.

Nasal screening for Staphylococcus aureus--daily routine with improvement potentials.

OBJECTIVES: Staphylococcus aureus causes purulent bacterial infections with a considerable number of life-threatening complications and thus, is a serious cost factor in public health. Up to 50% of a given population could asymptomatically carry Staphylococcus aureus in their nares, thereby serving as a source for contact transmissions and endogenous infections. Nasal swab-based screening techniques are widely used to identify suchcarriers. This study investigated the skill of medical professionals in taking nasal swabs and the effect of teaching on improving bacterial recovery rates. METHODS: 364 persons with different medical educational background participated in this study. A novel anatomically correct artificial nose model was implemented and inoculated with a numerically defined mixture of Staphylococcus aureus and Staphylococcus epidermidis bacteria. Utilizing regular clinical swabs, participants performed screening of the inoculated nose models before and after standardized theoretical, visual, and practical teaching. Recovery of bacteria was measured by standard viable count techniques. Data were analyzed statistically by nonparametric tests. RESULTS: It could be demonstrated that combined theoretical and practical teaching improved bacterial recovery rates. Even experienced medical professionals increased their detection levels after training. Recovery rates of bacteria varied significantly between trained (158.1 CFU) and untrained (47.5 CFU) participants (Wilcoxon test, p<0.001; Kolmogorov-Smirnov test, p<0.001). CONCLUSIONS: Swabs are commonly used to detect nasal carriage of Staphylococcus aureus in patients. The present teaching algorithm combined with the novel nose model offers an excellent precondition to improve knowledge and performance of this technique. Increased detection rates may prevent from contact transmission due to suboptimum hygienic patient handling. Consecutively, this effect could reduce costs for patient care. This study highlights the tremendous potential of combined theoretical, visual, and practical teaching methods in this field--and uncovers its actual necessity. Therefore, this training method can be recommended for all medical institutions.

Total knee replacement system with a ceramic femoral component versus two traditional metallic designs: a prospective short-term study.

PURPOSE: To compare the short-term outcome of the Multigen Plus system using a symmetric ceramic femoral component with that of 2 metallic total knee replacement (TKR) systems. METHODS: 60 patients (62 knees) with osteoarthritis or rheumatoid arthritis underwent primary TKR using the Genia system (n=20), the Multigen Plus system (n=17), and the Multigen Plus system with a ceramic femoral component (n=25). Outcome was evaluated pre- and post-operatively (at 3, 12, and 24 months) using the Hospital for Special Surgery (HSS) score, the Western Ontario and McMaster Universities (WOMAC) score, and the Short-Form 36 (SF-36) score. RESULTS: The 3 groups did not differ significantly at all 4 time points in terms of the HSS score, WOMAC score, and SF-36 score. The range of motion was significantly less in patients treated with the Genia system. Postoperatively, the HSS and WOMAC scores improved significantly in all 3 groups, whereas the SF-36 score improved significantly (at 12 and 24 months) only in patients treated with the Multigen Plus system with a ceramic femoral component. The implant position in most patients was optimal. All radiolucent lines were within 1 mm and did not progress. CONCLUSION: The short-term outcome of the 3 TKR systems was comparable. Ceramic femoral components performed comparably to traditional metallic designs.

Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) represents a therapeutic concept for type B aortic dissection. Long-term outcomes and morphology after TEVAR for uncomplicated dissection are unknown. METHODS AND RESULTS: A total of 140 patients with stable type B aortic dissection previously randomized to optimal medical treatment and TEVAR (n=72) versus optimal medical treatment alone (n=68) were analyzed retrospectively for aorta-specific, all-cause outcomes, and disease progression using landmark statistical analysis of years 2 to 5 after index procedure. Cox regression was used to compare outcomes between groups; all analyses are based on intention to treat. The risk of all-cause mortality (11.1% versus 19.3%; P=0.13), aorta-specific mortality (6.9% versus 19.3%; P=0.04), and progression (27.0% versus 46.1%; P=0.04) after 5 years was lower with TEVAR than with optimal medical treatment alone. Landmark analysis suggested a benefit of TEVAR for all end points between 2 and 5 years; for example, for all-cause mortality (0% versus 16.9%; P=0.0003), aorta-specific mortality (0% versus 16.9%; P=0.0005), and for progression (4.1% versus 28.1%; P=0.004); Landmarking at 1 year and 1 month revealed consistent findings. Both improved survival and less progression of disease at 5 years after elective TEVAR were associated with stent graft induced false lumen thrombosis in 90.6% of cases (P<0.0001). CONCLUSIONS: In this study of survivors of type B aortic dissection, TEVAR in addition to optimal medical treatment is associated with improved 5-year aorta-specific survival and delayed disease progression. In stable type B dissection with suitable anatomy, preemptive TEVAR should be considered to improve late outcome. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01415804.

The role of hydroxyethyl starch in preventing surgical-site infections and nipple necrosis in patients undergoing reduction mammaplasty: a prospective case-control study of 334 patients.

BACKGROUND: Surgical-site infections after reduction mammaplasty are associated with poor cosmetic results. This study investigated the postoperative antiinflammatory influence of hydroxyethyl starch and its effect on surgical-site infections after breast reduction. METHODS: In this prospective case-control study, 334 patients undergoing reduction mammaplasty were prospectively assigned in a 2:1 ratio to receive either 2 × 250 ml of hydroxyethyl starch 6 % or saline solution 0.9 % for 3 days postoperatively. Patient follow-up evaluation was at least 1 month. Using uni- and multivariate analyses, this study aimed to identify risk factors for surgical-site infections and nipple necrosis. RESULTS: Surgical-site infections occurred in 6.6 % of the hydroxyethyl starch group and in 3.6 % of the control group (p = 0.704). Hydroxyethyl starch had no effect of reducing surgical-site infections [p = 0.212; odds ratio (OR), 0.317; confidence interval (CI), 0.052-1.925]. According to univariate analyses, hydroxyethyl starch reduced the occurrence of postoperative fever (p = 0.085; OR 0.608; CI 0.345-1.072), and fever was associated with increased infection rates (p = 0.033; OR 2.335; CI 1.071-5.089). Additional risk factors for postoperative infections were diabetes (p = 0.051; OR 4.051; CI 0.997-16.463) and obesity (normal weight vs grade ≥2: p = 0.003; OR 7.612; CI 2.031-28.529). Multivariate analysis showed no independent predictors for surgical-site infections. Nipple necrosis were equally observed in the two groups (p = 0.458; OR 1.643; CI 0.443-6.097). CONCLUSION: The antiinflammatory approach of hydroxyethyl starch did not lead to a decrease in infections or nipple necrosis. No difference in surgical-site infections was observed between aesthetic and oncologic procedures. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Impact of treatment planning target volumen (PTV) size on radiation induced diarrhoea following selenium supplementation in gynecologic radiation oncology--a subgroup analysis of a multicenter, phase III trial.

BACKGROUND: In a previous analysis (Int J Radiat Oncol Biol Phys 70:828-835,2010), we assessed whether an adjuvant supplementation with selenium (Se) improves Se status and reduces the radiation-induced side-effects of patients treated by adjuvant radiotherapy (RT) for cervical and uterine cancer. Now, a potential relation between the planning target volume (PTV) of the RT and the Se effect concerning radiation induced diarrhoea was evaluated in detail. METHODS: Whole blood Se concentrations had been measured in patients with cervical (n=11) and uterine cancer (n=70) after surgical treatment, during, and at the end of RT. Patients with initial Se concentrations of less than 84 µg/l were categorized as Se-deficient and randomized before RT to receive Se (as sodium selenite) per os on the days of RT, or to receive no supplement during RT. Diarrhoea was graded according to the Common Toxicity Criteria system (CTC, Version 2a). The evaluation of the PTV of the RT was ascertained with the help of a specialised computer-assisted treatment planning software used for radiation planning procedure. RESULTS: A total of 81 patients had been randomized for the initial supplementation study, 39 of which received Se [selenium group, SeG] and 42 serving as controls [control group, CG]. Mean Se levels did not differ between SeG and CG upon study initiation, but were significantly higher in the SeG compared to the CG at the end of RT. The actuarial incidence of at least CTC 2 radiation induced diarrhoea in the SeG was 20.5% compared to 44.5% in the CG (p=0.04). The median PTV in both groups was 1302 ml (916-4608). With a PTV of <= 1302 ml (n=41) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 22.3% (4 of 18 patients) compared to 34.8% (8 of 23 patients) in the CG (p=0.50). In patients with a PTV of > 1302 ml (n=40) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 19.1% (4 of 21 patients) versus 52.6% (10 of 19 patients) in the CG (p=0.046). CONCLUSIONS: Se supplementation during RT was effective to improve blood Se status in Se-deficient cervical and uterine cancer patients, and reduces episodes and severity of RT-induced diarrhoea. This effect was most pronounced and significant in patients with large PTV (> 1302 ml).

Non-bridging external fixation employing multiplanar K-wires versus volar locked plating for dorsally displaced fractures of the distal radius.

BACKGROUND: The aim of this study was to compare non-bridging external fixation to palmar angular stable plating with respect to radiological outcome, wrist function, and quality of life. METHODS: One hundred and two consecutive patients (mean age: 63 years) were enrolled in the study. Fifty-two patients were randomized for plate osteosynthesis (2.4 mm, Synthes), 50 patients received non-bridging external fixation (AO small fixator). Objective (range of motion, grip strength), patient rated outcomes (quality of life, pain), and radiological outcome were assessed 8 weeks, 6 months, and 1 year after surgery. RESULTS: Loss of radial length of more than 3 mm was not detected in any group. Volar tilt was better restored by external fixation (7.2°) than by volar plating (0.1°). Wrist function was good in both groups. The external fixator was tolerated very well, and the quality of life assessment revealed comparable results in both groups. Osteoporosis was found in 54 % of patients and had no influence on radiological and functional outcome. CONCLUSION: Non-bridging external fixation employing multiplanar K-wires is a suitable treatment option in intra- and extra-articular fractures of the distal radius even in osteoporotic bone.

Imaging and quantification of subbasal nerve plexus in healthy volunteers and diabetic patients with or without retinopathy.

BACKGROUND: The alterations of subbasal nerve plexus (SBP) innervation and corneal sensation were estimated non-invasively and compared with the values in healthy volunteers. Additionally, this study addressed the relation of SBP changes to the retinal status, glycemic control and diabetes duration. METHODOLOGY/PRINCIPAL FINDINGS: Eighteen eyes of diabetic patients with peripheral diabetic neuropathy aged 68.8±8.8 years and twenty eyes of healthy volunteers aged 66.3±13.3 yrs. were investigated with in vivo confocal laser-scanning microscopy (CLSM). An adapted algorithm for image analysis was used to quantify the morphological and topological properties of SBP. These properties were correlated to incidence of diabetic retinopathy (DR) and corneal sensation (Cochet-Bonnet esthesiometer). The developed algorithm allows a fully automated analysis of pre-segmented SBP structures. Altogether, 10 parameters were analysed, and all of them revealed significant differences between diabetic patients and healthy volunteers. The nerve fibre density, total fibre length and nerve branches were found to be significantly lower in patients with diabetes than those of control subjects (nerve fibre density 0.006±0.002 vs. 0.020±0.007 mm/mm(2); total fibre length 6223±2419 vs. 19961±6553 µm; nerve branches 25.3±28.6 vs. 141.9±85.7 in healthy volunteers). Also the corneal sensation was significantly lower in diabetic group when compared to controls (43±11 vs. 59±18 mm). There was found no difference in SBP morphology or corneal sensation in the subgroups with (DR) or without (NDR) diabetic retinopathy. CONCLUSIONS/SIGNIFICANCE: SBP parameters were significantly reduced in diabetic patients, compared to control group. Interestingly, the SBP impairment could be shown even in the diabetic patients without DR. Although automatic adapted image analysis simplifies the evaluation of in vivo CLSM data, image acquisition and quantitative analysis should be optimised for the everyday clinical practice.

Paediatric reference values for the C-terminal fragment of fibroblast-growth factor-23, sclerostin, bone-specific alkaline phosphatase and isoform 5b of tartrate-resistant acid phosphatase.

BACKGROUND: Paediatric reference values for novel markers of phosphate homeostasis, bone formation and resorption and their putative relationship to growth are lacking. METHODS: A total of 424 healthy children, adolescents and young adults (221 males) aged 0.1-21 y, were enrolled in this cross-sectional study. Height, weight and height velocity were assessed. Plasma/serum samples for determination of C-terminal fragment of fibroblast growth factor-23 (cFGF-23), sclerostin, bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRAP5b) were available from 222, 264, 352 and 338 individuals, respectively. Calculation of cross-sectional centiles and z-scores was based on median (M), standard coefficient of variation (S) and the Box-Cox power (L) of transformation (LMS method) per age cohort. Correlations between variables as well as with growth were assessed. RESULTS: cFGF-23, BAP and TRAP5b were significantly correlated with age (each P < 0.01), with highest values during infancy and adolescence. Serum levels of BAP and TRAP5b were significantly higher in adolescent boys compared with girls (each P < 0.01). In contrast, sclerostin levels were independent of age and gender. BAP and TRAP5b were strongly correlated and both were significantly associated with cFGF-23 and sclerostin as well (each P < 0.01). cFGF-23 was positively correlated with serum phosphate and renal phosphate threshold concentration (each P < 0.01). Height, weight, body mass index and height velocity were weakly correlated with BAP and TRAP5b (each P < 0.05). CONCLUSIONS: This study provides age- and gender-related centile charts and z-scores for cFGF-23, BAP, TRAP5b and sclerostin and highlights the link between phosphate homeostasis and markers of bone metabolism during growth.

Effects of physical therapy on quality of life in osteoporosis patients - a randomized clinical trial.

SUMMARY: The aim of this prospective randomized single-center study was to investigate whether sling exercise therapy is superior to conventional exercises in osteoporosis patients. BACKGROUND: Patients with osteoporosis frequently experience fractures of the vertebral body, which may cause chronic back pain and other symptoms. These, in turn, may lead to immobilization, muscular atrophy, and restrictions in activities of daily living. The situation can be improved with specific medication and physiotherapy. We explored the effects of a variety of physical treatments on activities of daily living in patients with osteoporosis. METHOD: Fifty patients were randomly allocated to two treatment groups. Group A received traditional physiotherapy (PT) while group B underwent sling exercise therapy (ST). Both treatments were given twice a week for three months. The results of the treatment were registered on the quality of life questionnaire (Qualeffo-41) devised by the International Osteoporosis Foundation. After a further three months with no specific exercise treatment, we again tested all patients in order to draw conclusions about the long-term effects of both types of exercise. RESULTS: Forty-four patients (88%) completed the study. Patients were assigned to small groups (a maximum of 5 patients in each group) and thus received individual attention and motivation. Quality of life was improved in both groups; a significantly greater improvement was registered in patients who performed sling exercises (Global score Qualeffo: p = 0.002). CONCLUSION: The test results confirm the known positive effects of physical therapy on the quality of life of osteoporosis patients, as well as the fact that sling exercises are a sound alternative treatment for this condition.

Validating intramyocardial bone marrow stem cell therapy in combination with coronary artery bypass grafting, the PERFECT Phase III randomized multicenter trial: study protocol for a randomized controlled trial.

BACKGROUND: For the last decade continuous efforts have been made to translate regenerative cell therapy protocols in the cardiovascular field from 'bench to bedside'. Successful clinical introduction, supporting safety, and feasibility of this new therapeutic approach, led to the initiation of the German, Phase III, multicenter trial - termed the PERFECT trial (ClinicalTrials.gov Identifier: NCT00950274), in order to evaluate the efficacy of surgical cardiac cell therapy on left ventricular function. METHODS/DESIGN: The PERFECT trial has been designed as a prospective, randomized, double-blind, placebo controlled, multicenter trial, analyzing the effect of intramyocardial CD 133(+) bone marrow stem cell injection in combination with coronary artery bypass grafting on postoperative left ventricular function. The trial includes patients aged between 18 and 79 years presenting with a coronary disease with indication for surgical revascularization and reduced global left ventricular ejection fraction as assessed by cardiac magnet resonance imaging. The included patients are treated in the chronic phase of ischemic cardiomyopathy after previous myocardial infarction. DISCUSSION: Patients undergoing coronary artery bypass grafting in combination with intramyocardial CD133+ cell injection will have a higher LV ejection fraction than patient who undergo CABG alone, measured 6 months after the operation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00950274.

Ceramic femoral components in total knee arthroplasty - two year follow-up results of an international prospective multi-centre study.

BACKGROUND: Total knee arthroplasty can be considered as a reliable surgical procedure with a good long-term clinical result. However, implant failure due to particle induced aseptic loosening as well as the aspect of hypersensitivity to metal ions still remains an emerging issue. METHODS: The purpose of this prospective international multi-centre study was to evaluate the clinical and radiological outcomes and the reliability of the unconstrained Multigen Plus Total Knee System with a new BIOLOX® delta ceramic femoral component. Cemented total knee arthroplasty was performed on 108 patients (110 knees) at seven hospitals in three countries. Clinical and radiological evaluations were performed preoperatively, and after 3, 12 and 24 months postoperatively using the HSS-, WOMAC-, SF-36-score and standardised X-rays. RESULTS: The mean preoperative HSS-Score amounted to 55.5 ± 11.5 points and improved significantly in all postoperative evaluations (85.7 ± 11.7 points at 24 months). Furthermore, improvements in WOMAC- and SF-36-score were evaluated as significant at all points of evaluation. Radiolucent lines around the femoral ceramic component at 24 months were found in four cases. Progression of radiolucent lines was not seen and no implant loosening was observed. During the 24 month follow-up eight patients underwent subsequent surgery due to reasons unrelated to the implant material. CONCLUSIONS: The observed clinical and radiological results are encouraging for a long-term survival of the ceramic femoral component. Therefore, ceramic implants could be a promising solution not only for patients with allergies against metallic implant materials, but also for the osteoarthritic knee joint. Long-term follow-up is necessary to draw conclusions regarding the superiority of the ceramic knee implants concerning in vivo wear and long-term survivorship.

Serum fetuin-A and vitamin D in children with mild-to-severe chronic kidney disease: a cross-sectional study.

BACKGROUND: Fetuin-A and vitamin D are significant correlates of cardiovascular morbidity in paediatric chronic kidney disease (CKD) patients. It is thus far unknown, whether or not serum fetuin-A is affected by the vitamin D status or treatment with vitamin D preparations in these patients. METHODS: In a cross-sectional study, serum concentrations of fetuin-A, 25-hydroxyvitamin D(3) (25OHD) and 1,25-dihydroxyvitamin D(3) (calcitriol) levels were determined in 112 paediatric patients with mild-to-severe CKD (Stages 1-5) and after renal transplantation. A25OHD supplementation and/or calcitriol treatment were given in 64% of the patients. RESULTS: Fetuin-A levels were clearly reduced in dialysis patients but were comparable to healthy controls in those with moderate CKD and after transplantation. Although 64 and 46% of all patients received 25OHD and/or calcitriol treatment, 48 and 20% of patients were 25OHD and/or calcitriol deficient, respectively. Within the whole patient cohort, fetuin-A correlated with serum calcium and yearly weight-related 25OHD dosage (each P < 0.01) but not with the vitamin D status per se. Multiple regression analysis revealed the need for dialysis treatment and cumulative 25OHD dosage as independent predictors of fetuin-A concentrations (model r(2) = 0.17). In dialysis patients, fetuin-A was inversely correlated with serum C-reactive protein but positively correlated with cumulative calcitriol dosage and serum parathormone (each P < 0.01). CONCLUSIONS: Fetuin-A levels are clearly reduced in children on dialysis but not in those with moderate CKD and after transplantation. Besides the degree of microinflammation, the cumulative intake of 25OHD and calcitriol are significantly correlated to fetuin-A in these patients. The impact of vitamin D treatment appears to be at least partly mediated by serum calcium.