Filgotinib for the treatment of rheumatoid arthritis

Introduction: Biologics were the first targeted therapies for rheumatoid arthritis (RA), having in common high clinical efficacy. Being proteins, they are administered parenterally. The first oral targeted small molecules approved for RA are competitive inhibitors of the Janus kinase (JAK) enzyme family which mediate signalling for a cytokine subset important in RA pathogenesis.

Areas covered: Several JAK inhibitors have been developed with differing selectivity for the four JAK enzymes with a view to generating oral, multi-cytokine inhibitors. Here we review the pharmacology and clinical trial data for efficacy and safety of filgotinib, an investigational selective JAK1 inhibitor. We contextualise the contemporary approach to RA management and substantial unmet needs that remain.

Expert opinion: The selectivity of filgotinib for JAK1 may have theoretical advantages in terms of limiting toxicity. However, establishing whether this is so before larger numbers of patients are exposed in phase III and beyond in the real word setting, will be difficult. Filgotinib clinical trial data to date has been encouraging with rapid, sustained efficacy with promising safety and tolerability. We are likely to see an expanding choice of approved JAK inhibitors in the clinic but it may not be straightforward to distinguish safety and efficacy differences.     

New antimicrobial flavonoids and chalcone from <Emphasis Type="Italic">Colutea armata</Emphasis>

Colucins A (1) and B (2), new flavonoids and colucone (3), the new chalcone derivative, have been isolated from the CHCl₃-soluble fraction of the whole plant of Colutea armata along with luteolin (4), luteolin 7-O-β-D-glucoside (5), isoliquiritigenin (6), trans-caffeic acid (7) and stigmasterol (8) reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS and 2D-NMR spectroscopy. Compounds 1 and 2 showed significant antimicrobial activity against two Gram positive and three Gram negative bacterial strains while 3 was moderately active.     

18F-FDG positron emission tomography/computed tomography and the "underground map" appearance in imaging Horton's arteritis

A majority of the clinical use of positron emission tomography (PET)-computed tomography (CT) is related to cancer management. Its application in evaluating inflammatory diseases and pyrexia of unknown origin is becoming popular. We reviewed the fluorine-18-fluorodeoxyglucose PET-CT findings of an 80-year-old woman with nonspecific clinical presentation consisting of generalised malaise, moderately high fever and weight loss. Prior CT and magnetic resonance imaging were not helpful in providing a clinical diagnosis. The diagnosis was Horton's arteritis, and the patient responded well to high-dose steroids.     

Cardiac metastasis in malignant fibrous histiocytoma

Malignant fibrous histiocytoma MFH is an aggressive spindle cell cancer and is the most common soft tissue tumor in the elderly, primarily affecting the extremities. It has high metastatic potential and can spread to various viscera including liver, lung, bone, and brain; however, cardiac metastasis is an extreme rarity. Here, we present a 50-year-old male, diagnosed as pleiomorhphic storiform MFH a of right arm who developed parenchymal pulmonary metastases and a mass lesion in left atrium. Patient had a downhill course and eventually succumbed.     

Dishevelled proteins are significantly upregulated in chronic lymphocytic leukaemia

Tumor Biology - Dishevelled (DVL) proteins are components of the Wnt signalling pathways, and increased expression is associated with various malignancies. Information on DVLs in chronic lymphatic...     

Long-term local control and survival after preoperative radiochemotherapy in combination with deep regional hyperthermia in locally advanced rectal cancer

Purpose: The aim of this study was to evaluate the impact of deep regional hyperthermia on long-term local control and survival in locally advanced non-metastatic rectal cancer. Methods: In total 103 patients with locally advanced non-metastatic rectal cancer were treated preoperatively with either neoadjuvant radiochemotherapy alone (n?=?43) or the same treatment with additional deep regional hyperthermia (n?=?60). The two groups were compared with respect to local control, overall survival (OS), disease-free survival (DFS), and distant metastases-free survival (DMFS). Results: Patients receiving additional hyperthermia had excellent long-term local control with a 5-year Kaplan-Meier estimate of 98% compared with 87% in the radiochemotherapy only group (p?=?0.09). Five-year rates for OS (88% versus 76%, p?=?0.08), DFS (77% versus 73%, p?=?n.s.) and DMFS (75% versus 77%, p?=?n.s.) were not statistically different between the two groups. Conclusion: Radiochemotherapy combined with hyperthermia results in excellent long-term local control.     

Comparison of clinical characteristics of opium-induced and independent major depressive disorder

Psychiatric disorders and among them depression are common in substance dependent patients. The aim of this study is to compare the clinical characteristics of those that appear to have substance-induced depression and those that have independent major depression. One-hundred eighty-four independent and 187 opium-induced (OID) depressed male patients that met the DSM-IV criteria for major depressive disorder were randomly selected. Standard demographic data, including age, marital, employment and education status, were collected. The primary measure of depressive signs and symptoms was Hamilton Depression Scale (HAMD-21). The two groups were compared with each other for the HAMD total and subscales scores. The two groups were matched regarding age, educational level and marital status. Opium-induced depressed patients were more severely depressed and motor retarded and also they had more social and occupational problems. Gastrointestinal, sexual and somatic complaints were more common among them too. MDD patients had better insight than the other group. The results demonstrate that it is possible to differentiate between substance-induced and independent depression. Such differentiation might be important for establishing prognosis and optimal treatment.