With a biomechanical treatment in knee osteoarthritis, less knee pain did not correlate with synovitis reduction

© 2017 The Author(s). Background: Braces are used to treat pain in patellofemoral joint osteoarthritis (PFJOA). In a trial, we previously reported pain improvement after 6-weeks brace use. The pain reduction did not correlate with changes in Magnetic Resonance Imaging (MRI) assessed Bone Marrow Lesion volume or static synovial volume. Studies show that changes in the synovium on dynamic contrast enhanced (DCE) MRI are more closely associated with symptom change than static synovial volume changes. We hypothesised change in synovitis assessed using dynamic imaging could explain the reduction in pain. Method: One hundred twenty-six men and women aged 40-70 years with painful radiographically confirmed PFJOA were randomised to either brace wearing or no brace for 6-weeks. Pain assessment and DCE-MRI were performed at baseline and 6 weeks. DCE data was analysed using Tofts's equation. Pain measures included a VAS of pain on nominated aggravating activity (VAS NA ), and the KOOS pain subscale. Paired t-tests were used to determine within person change in outcome measures and Spearman's correlation coefficients were used to determine the correlation between change in pain and change in the DCE parameters. Results: Mean age of subjects was 55.5 years (SD = 7.5) and 57% were female. There was clear pain improvement in the brace users compared to controls (VAS NA - 16.87 mm, p = < 0.001). There was no significant change to the dynamic synovitis parameters among brace users nor was pain change correlated with change in dynamic synovitis parameters. Conclusion: The reduction in knee pain following brace wearing in patients with PFJOA is not explained by changes in synovitis. Trial registration: Trial registration number UK. ISRCTN50380458 /Registered 21.5.2010

Evaluation of 17-mm St. Jude Medical Regent prosthetic aortic heart valves by rest and dobutamine stress echocardiography

BACKGROUND: The prosthesis used for aortic valve replacement in patients with small aortic root can be too small in relation to body size, thus showing high transvalvular gradients at rest and/or under stress conditions. This study was carried out to evaluate rest and Dobutamine stress echocardiography (DSE) hemodynamic response of 17-mm St. Jude Medical Regent (SJMR-17 mm) in relatively aged patients at mean 24 months follow-up. METHODS AND RESULTS: The study population consisted of 19 patients (2 men, 17 women, mean age 69.2 ± 7.3 years). All patients underwent rest Doppler echocardiography before and after surgery and basal and DSE at follow up (infused at rate of 5 micrg/Kg/min and increased by 5 microg/Kg/min at 5 min intervals up to 40 microg/Kg/min). The following parameters were evaluated at rest and/or under DSE: heart rate (HR), ejection fraction (EF), cardiac output (CO), peak and mean velocity and pressure gradients (MxV, MnV, MxPG, MnPG), effective orifice area (EOA), indexed EOA (EOAi), left ventricular mass (LVM), indexed LVM (LVMi), Velocity Time Integral at left ventricular outflow tract (VTI LVOT) and transvalvular (Aortic VTI), Doppler velocity index (DVI). At rest MxPG and MnPG were 29.2 ± 7.1 and 16.6 ± 5.8mmHg, respectively; EOA and EOAi resulted 1.14 ± 0.3 cm(2) and 0.76 ± 0.2 cm(2)/m(2); DVI was normal (0.50 ± 0.1). At follow-up LVM and LVMi decreased significantly from pre-operative value of 258 ± 43g and 157.4 ± 27.7g/m(2) to 191 ± 23.8g and 114.5 ± 10.6g/m(2), respectively. DSE increased significantly HR, CO, EF, MxGP (up to 83.4 ± 2 1.9mmHg), MnPG (up to 43.2 ± 12.7mmHg). EOA, EOAi, DVI increased insignificantly (from baseline up to 1.2 ± 0.4 cm(2), 0.75 ± 0.3cm(2)/m(2) and 0.48 ± 0.1 respectively). Two patients developed significant intraventricular gradients. CONCLUSION: These data show that SJMR 17-mm prostheses can be safely implanted in aortic position in relatively aged patients, offering a satisfactory hemodynamic performance at rest and under DSE, with full utilization of its available orifice, suggesting that a possible mild prosthesis-patient mismatch is not an issue of clinical relevance when this small prosthesis is used. Rest and Dobutamine stress echocardiography is a useful and effective means for evaluating prosthesis hemodynamics and for monitoring the expected LVH regression

Cutaneous lesions of the nose

Skin diseases on the nose are seen in a variety of medical disciplines. Dermatologists, otorhinolaryngologists, general practitioners and general plastic and dermatologic surgeons are regularly consulted regarding cutaneous lesions on the nose. This article is the second part of a review series dealing with cutaneous lesions on the head and face, which are frequently seen in daily practice by a dermatologic surgeon. In this review, we focus on those skin diseases on the nose where surgery or laser therapy is considered a possible treatment option or that can be surgically evaluated

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

Autosomal recessive cerebellar ataxias

Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Calcium Channel Blockers and Hypertension.

Effective treatment of high blood pressure (BP) represents a key strategy for reducing the burden of hypertension-related cardiovascular and renal diseases. In spite of these well-established concepts, hypertension remains poorly controlled worldwide. In order to improve BP control in patients with hypertension, several interventions have been proposed, among which (1) preferred use of more effective, sustained, and well-tolerated antihypertensive drug aimed to ensure adherence to prescribed medications and (2) extensive use of rational, integrated, and synergistic combination therapies, even as first-line strategy, aimed to achieve the recommended BP targets. Within the possible antihypertensive drug classes currently available for the clinical management of hypertension, both in monotherapy and in combination therapy, drugs inhibiting the renin-angiotensin system and calcium channel blockers (CCBs) have demonstrated to be effective and safe in lowering BP levels and achieving the recommended BP targets with a good tolerability profile. In particular, CCBs have been one of the most widely used classes of antihypertensive agents in the last 20 years, based on their effectiveness in reducing BP levels, good tolerability, and abundant evidence on reducing cardiovascular and renal consequences of hypertension. This article provides an updated overview of the evidence supporting the use of CCBs-based antihypertensive regimen, both in monotherapy and in combination therapies with different classes of antihypertensive drugs