The effectiveness and safety of TNF-alpha blockers in the treatment of early psoriatic arthritis: an Italian multicentre longitudinal observational pilot study

The objective of this study is to assess the effectiveness and safety of TNF-α blockers in a group of early psoriatic arthritis (PsA) patients with an unsatisfactory response to previous conventional treatment consecutively enrolled in five Italian centres. A 24-week open-label trial was carried out in consecutive early PsA patients classified according to the CASPAR criteria, with unsatisfactory response to previous treatments and with a DAS28 threshold as ≥3.2, seen at the outpatient clinics of each centre. Exclusion criteria were previous usage of TNF-α blockers and a disease duration >12 months. The choice of any of the three TNF-α blockers was decided by the expert’s opinion, without any restriction. Effectiveness was considered as an improvement of DAS28 at 12 and 24 weeks of treatment. Secondary endpoints were an improvement of TJC, SWJ, HAQ score and PASI score. Changes from baseline to the 12- and 24-week follow-up assessments were analysed using the Wilcoxon paired sign rank test. Twenty-nine patients (14 males, 15 females, median age 37 years, range 20–65 years) were enrolled. A statistical improvement of the DAS28 was observed at 12 and 24 weeks from baseline (p < 0.001). Secondary endpoints also confirmed the effectiveness of the TNF-α blockers in the treatment of early PsA. No severe adverse events were observed during the treatment period, and no patient withdrew from the medications. This study suggests that the TNF-α blockers can be effective in the management of early PsA. Further controlled studies will provide more data on this challenging topic

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

The reproducibility of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study

Background: Cardiovascular magnetic resonance (CMR) imaging has been used to visualise post-ablation atrial scar (PAAS), generally employing a three-dimensional (3D) late gadolinium enhancement (LGE) technique. However the reproducibility of PAAS imaging has not been determined. This cross-over study is the first to investigate the reproducibility of the technique, crucial for both future research design and clinical implementation. Methods: Forty subjects undergoing first time ablation for atrial fibrillation (AF) had detailed CMR assessment of PAAS. Following baseline pre-ablation scan, two scans (separated by 48 h) were performed at three months post-ablation. Each scan session included 3D LGE acquisition at 10, 20 and 30 min post administration of gadolinium-based contrast agent (GBCA). Subjects were allocated at second scan post-ablation to identical imaging parameters (‘Repro’, n = 10), 3 T scanner (‘3 T’, n = 10), half-slice thickness (‘Half-slice’, n = 10) or half GBCA dose (‘Half-gad’, n = 10). PAAS was compared to baseline scar and then reproducibility was assessed for two measures of thresholded scar (% left atrial (LA) occupied by PAAS (%LA PAAS) and Pulmonary Vein Encirclement (PVE)), and then four measures of non-thresholded scar (point-by-point assessment of PAAS, four normalisation methods). Thresholded measures of PAAS were evaluated against procedural outcome (AF recurrence). Results: A total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. At 20 and 30 min, inter-scan reproducibility was good to excellent (coefficient of variation at 20 min and 30 min: %LA PAAS 0.41 and 0.20; PVE 0.13 and 0.04 respectively for ‘Repro’ group). Changes in imaging parameters, especially reduced GBCA dose, reduced inter-scan reproducibility, but for most measures remained good to excellent (ICC for %LA PAAS 0.454–0.825, PVE 0.618–0.809 at 30 min). For non-thresholded scar, highest reproducibility was observed using blood pool z-score normalisation technique: inter-scan ICC 0.759 (absolute agreement, ‘Repro’ group). There was no significant relationship between indices of PAAS and AF recurrence. Conclusion: PAAS imaging is a reproducible finding. Imaging should be performed at least 20 min post-GBCA injection, and a blood pool z-score should be considered for normalisation of signal intensities. The clinical implications of these findings remain to be established in the absence of a simple correlation with arrhythmia outcome.The research was performed at King’s College London Medical Engineering Centre, funded by the Wellcome Trust and the Engineering and Physical Sciences Research Council (EPSRC). The research was also supported by the National Institute for Health Research (NIHR) Biomedical Research Centre awards to Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London, by the NIHR Healthcare Technology Co-operative for Cardiovascular Disease at Guy’s and St Thomas’ NHS Foundation Trust, and by the Cardiovascular HTC. Work upon the PVE methodology was partially funded by the Spanish Ministry of Economy and Competitiveness (DPI2015-71640-R) and by the “Fundació La Marató de TV3” (no. 20154031)

Physician’s Global Assessment in Psoriatic Arthritis: A Multicenter GRAPPA Study

Objective: Physician’s global assessment (PGA) of disease activity is a major determinant of therapeutic decision making. This study assesses the reliability of the PGA, measured by means of 0–100 mm visual analog scale (VAS), and the additional use of separate VAS scales for musculoskeletal (PhysMSK) and dermatologic (PhysSk) manifestations in patients with psoriatic arthritis (PsA). Methods: Sixteen centers from 8 countries enrolled 319 consecutive patients with PsA. PGA, PhysMSK, and PhysSk evaluation forms were administered at enrollment (W0) and after 1 week (W1). Detailed clinical data regarding musculoskeletal (MSK) manifestations, as well as dermatological assessment, were recorded. Results: Comparison of W0 and W1 scores showed no significant variation (intraclass correlation coefficients were PGA 0.87, PhysMSK 0.86, PhysSk 0.78), demonstrating the reliability of the instrument. PGA scores were dependent on PhysMSK and PhysSk (p < 0.0001) with a major effect of the MSK component (B = 0.69) compared to skin (B = 0.32). PhysMSK was correlated with the number of swollen joints, tender joints, and presence of dactylitis (p < 0.0001). PhysSk scores were correlated with the extent of skin psoriasis and by face, buttocks or intergluteal, and feet involvement (p < 0.0001). Finally, physician and patient assessments were compared showing frequent mismatch and a scattered dot plot: PGA versus patient’s global assessment (r = 0.36), PhysMSK versus patient MSK (r = 0.39), and PhysSk versus patient skin (r = 0.49). Conclusion: PGA assessed by means of VAS is a reliable tool to assess MSK and dermatological disease activity. PGA may diverge from patient self-evaluation. Because MSK and skin/nail disease activity may diverge, it is suggested that both PhysMSK and PhysSk are assessed