Contrast medium in power Doppler ultrasound for assessment of synovial vascularity: comparison with arthroscopy

OBJECTIVE: To evaluate the reliability of contrast-unenhanced power Doppler (CUPD) and contrast-enhanced power Doppler (CEPD) ultrasound (US) assessment of synovial vascularity of knee joint synovitis by prospective comparison with the "gold standard," arthroscopy. METHODS: A total of 18 knees of 17 patients with refractory rheumatoid and psoriatic knee joint synovitis were examined by US. Recognition of PD synovial vessel flow and its spatial arrangement in relation to the pannus/cartilage interface (P/CI) or fluid/synovium interface (F/SI) were studied by CUPD- and CEPD-US after a single intravenous bolus of galactosel palmitic acid (Levovist). Arthroscopy video recordings were reanalyzed by computer image analysis to assess synovial vascular marking. CUPD and CEPD flow signal scores were compared with each other and with corresponding vascular marking scores. Using villous vascular marking as reference, CUPD and CEPD sensitivity and specificity were measured. Interobserver variability was evaluated. RESULTS: Compared with the unenhanced PD method, contrast administration increased the PD flow signal score in 13/18 knees (72.2%), allowing increased detection of F/SI PD flow signal configuration (p < 0.018) and of the coexistence of P/CI and F/SI PD imaging (p < 0.0078). With arthroscopy as reference, contrast-enhanced PD was found to be more useful than the unenhanced method, showing more reproducible PD signal scores (p = 0.05 vs p = nonsignificant), as well as higher sensitivity (80% vs 30%), but lower specificity (62% vs 87%), in the recognition of increased vascularity of synovial villi. Interobserver agreement was 100%. CONCLUSION: The prospective comparison with arthroscopy showed the reliability of the CEPD method in synovial vessel recognition and its potential clinical usefulness in assessment of knee joint synovitis.     

Prognostic relevance of microsatellite instability in pT3N0M0 colon cancer: a population-based study

Although surgery alone represents a curative approach for patients with pT3N0M0 colon cancer, about 15–20 % of these patients develop a relapse of disease. Microsatellite instability (MSI) is one of the most important molecular markers in colorectal cancer. The aim of this study was to investigate the prognostic relevance of MSI in all pT3N0M0 tumors recorded in the Cancer Registry of the Province of Modena—(Northern Italy) within the 2002–2006 period in patients who showed a relapse of disease during the 5-year period of follow-up (59 cases). They were compared to 59 controls similar in clinical and pathological features but with good prognosis. None of the subjects received adjuvant chemotherapy. MSI status was tested using BAT25, BAT26, NR24, and CAT25 fluorescent-labeled mononucleotide markers. The overall prevalence of MSI was 12.7 % (15 of 118 cases). MSI was detected mainly in mucinous adenocarcinoma (p < 0.003), in high-grade tumors (p < 0.008), in right-sided neoplasms (p < 0.005), and in patients with a better prognosis, though the difference was not statistically significant (11/59 patients ?18.6 % vs 4/59 patients ?6.7 %; OR 0.36 CI 95 % 0.11–1.15; p = 0.08). However, in multivariate analysis, MSI status becomes the strongest independent factor associated with relapse (OR 0.21, CI 95 % 0.06–0.81; p = 0.023), together with mucinous histological type (OR 0.40, CI 90 % 0.18–0.92). MSI is a relevant prognostic factor in stage pT3N0M0 colon cancer suitable to discriminate those patients with a high risk of relapse.     

Molecularly imprinted ‘traps’ for sulfonylureas prepared using polymerisable ion pairs

A novel approach towards recognition of sulfonylureas based on a polymerisable ion pair is presented. A solution association constant >10⁵ M⁻¹ between the model target glibenclamide and 4-vinylbenzyltrimethylammonium methacrylate is measured, and the formation of 1 : 1 complexes verified. Subsequently prepared stoichiometrically imprinted polymers exhibit exceptionally high affinity and binding capacity for glibenclamide, owing to synergistic binding of both the neutral and deprotonated form of the drug by the ion pair monomer. The polymers are applied to the selective extraction of glibenclamide from blood serum samples, achieving recoveries of up to 98% and demonstrating excellent long-term stability, negating the need for regular sorbent regeneration.

Polymerisable ion pair captures both neutral and anionic form of acidic sulfonylurea drug in stoichiometrically imprinted polymer.     

Quantitative assessment of the effects of 6 months of adapted physical activity on gait in people with multiple sclerosis: a randomized controlled trial

Purpose: The purpose of this study is to quantitatively assess the effect of 6 months of supervised adapted physical activity (APA i.e. physical activity designed for people with special needs) on spatio-temporal and kinematic parameters of gait in persons with Multiple Sclerosis (pwMS).

Methods: Twenty-two pwMS with Expanded Disability Status Scale scores ranging from 1.5 to 5.5 were randomly assigned either to the intervention group (APA, n?=?11) or the control group (CG, n?=?11). The former underwent 6 months of APA consisting of 3 weekly 60-min sessions of aerobic and strength training, while CG participants were engaged in no structured PA program. Gait patterns were analyzed before and after the training using three-dimensional gait analysis by calculating spatio-temporal parameters and concise indexes of gait kinematics (Gait Profile Score – GPS and Gait Variable Score – GVS) as well as dynamic Range of Motion (ROM) of hip, knee, and ankle joints.

Results: The training originated significant improvements in stride length, gait speed and cadence in the APA group, while GPS and GVS scores remained practically unchanged. A trend of improvement was also observed as regard the dynamic ROM of hip, knee, and ankle joints. No significant changes were observed in the CG for any of the parameters considered.

Conclusions: The quantitative analysis of gait supplied mixed evidence about the actual impact of 6 months of APA on pwMS. Although some improvements have been observed, the substantial constancy of kinematic patterns of gait suggests that the full transferability of the administered training on the ambulation function may require more specific exercises.

• Implications for rehabilitation

• Adapted Physical Activity (APA) is effective in improving spatio-temporal parameters of gait, but not kinematics, in people with multiple sclerosis.

• Dynamic range of motion during gait is increased after APA.

• The full transferability of APA on the ambulation function may require specific exercises rather than generic lower limbs strength/flexibility training.

     

NCOA4-mediated ferritinophagy in macrophages is crucial to sustain erythropoiesis in mice

Nuclear receptor coactivator 4 (NCOA4) promotes ferritin degradation and Ncoa4-ko mice in a C57BL/6 background show microcytosis and mild anemia, aggravated by iron deficiency. To understand tissue-specific contributions of NCOA4-mediated ferritinophagy we explored the effect of Ncoa4 genetic ablation in the iron-rich Sv129/J strain. Increased body iron content protects these mice from anemia and, in basal conditions, Sv129/J Ncoa4-ko mice show only microcytosis; nevertheless, when fed a low-iron diet they develop a more severe anemia compared to that of wild-type animals. Reciprocal bone marrow (BM) transplantation from wild-type donors into Ncoa4-ko and from Ncoa4-ko into wild-type mice revealed that microcytosis and susceptibility to iron deficiency anemia depend on BM-derived cells. Reconstitution of erythropoiesis with normalization of red blood count and hemoglobin concentration occurred at the same rate in transplanted animals independently of the genotype. Importantly, NCOA4 loss did not affect terminal erythropoiesis in iron deficiency, both in total and specific BM Ncoa4-ko animals compared to controls. On the contrary, upon a low iron diet, spleen from wild-type animals with Ncoa4-ko BM displayed marked iron retention compared to (wild-type BM) controls, indicating defective macrophage iron release in the former. Thus, erythropoietin administration failed to mobilize iron from stores in Ncoa4-ko animals. Furthermore, Ncoa4 inactivation in thalassemic mice did not worsen the hematologic phenotype. Overall our data reveal a major role for NCOA4-mediated ferritinophagy in macrophages to favor iron release for erythropoiesis, especially in iron deficiency.     

Association between vitamin D deficiency and serum Homocysteine levels and its relationship with coronary artery disease

Journal of Thrombosis and Thrombolysis - Homocysteine (Hcy) elevation and vitamin D deficiency have emerged as potential markers of coronary artery disease (CAD). However, even tough...     

Evaluation of acromegaly treatment direct costs with respect to biochemical control and follow-up length

Purpose

Acromegaly is a severe chronic endocrine disease. Achieving biochemical control often needs a multimodal treatment approach, including prolonged medical treatment. Aim of the study is to evaluate the burden of treatment direct costs with respect to the different therapeutic strategies, disease control, and follow-up length.

Methods

Single center retrospective study on 73 acromegaly patients. Costs of acromegaly treatments were computed based on a detailed revision of patients’ clinical charts.

Results

Median total treatment cost/patient was €47,343 during the entire follow-up (8 years), while median treatment cost/patient/year was €6811. The majority of patients received medical therapy (71/73, 97.3%). Median cost for first-line medical treatment (first-generation somatostatin receptor ligands) was lower compared to second-line treatments (pegvisomant monotherapy or combination therapies), considering both total (€22,824 vs €76,140; p?<?0.001), and yearly cost/patient (€4927 vs €9161; p?<?0.001). Sixty patients (82.2%) reached biochemical control at last follow-up (IGF-1?≤?1 xULN). The percentage of patients treated with first- or second-line medical therapies was comparable between controlled and uncontrolled patients (p?=?1.000), and the yearly cost/patient did not significantly differ between the two groups (€6936 vs €6680; p?=?0.829). Follow-up duration was significantly longer in controlled patients compared to the uncontrolled ones (8.7 vs 3.5 years; p?=?0.019).

Conclusions

Direct costs for the management of acromegaly have a significant burden on the healthcare systems. However, more than 80% of our patients reached biochemical control using multimodal approaches. Treatment modalities and yearly costs did not significantly differ between controlled and uncontrolled patients, while follow-up length represented a major determinant of biochemical outcome.