Th17 lymphocyte-dependent degradation of joint cartilage by synovial fibroblasts in a humanized mouse model of arthritis and reversal by secukinumab

How T-helper (Th) lymphocyte subpopulations identified in synovial fluid from patients with juvenile idiopathic arthritis (JIA) (Th17, classic Th1, or nonclassic Th1) drive joint damage is of great interest for the possible use of biological drugs that inhibit the specific cytokines. Our objective was to clarify the role of such Th subpopulations in the pathogenesis of articular cartilage destruction by synovial fibroblasts (SFbs), and the effect of Th17 blockage in an animal model. SFbs were isolated from healthy subjects and patients with JIA, and peripheral blood Th lymphocytes subsets were obtained from healthy subjects. Fragments of human cartilage from healthy subjects in a collagen matrix containing JIA or normal SFbs grafted underskin in SCID mice were used to measure cartilage degradation under the effects of Th supernatants. JIA SFbs overexpress MMP9 and MMP2 and Th17 induce both MMPs in normal SFbs, while nonclassic Th1 upregulate urokinase plasminogen activator (uPA) activity. In vitro invasive phenotype of normal SFbs is stimulated with conditioned medium of Th17 and nonclassic-Th1. In the in vivo “inverse wrap” model, normal SFbs stimulated with supernatants of Th17-lymphocytes and nonclassic Th1 produced a cartilage invasion and degradation similar to JIA SFbs. Secukinumab inhibits the cartilage damage triggered by factors produced by Th17.     

The Validation of Auricular Diagnosis

Background

The first attempt to validate auricular diagnosis in a blind experimental evaluation was made by Terry Oleson in 1980. Now, a new project was proposed for validating auricular diagnosis by means of three methods: Inspection of the outer ear, Pain Pressure Test (PPT), and Electric Skin Resistance Test (ESRT)

Objectives

To find an answer to the following questions:1. Were the above mentioned diagnostic methods quantitatively equivalent in unveiling the patient's problems?2. Were the different methods equivalent in diagnosing recent and old problems?3. In case of musculoskeletal disorders, were the different methods equally effective in detecting the prevalent side of pain?

Methods

A total of 506 patients were examined in a one-sided blinded trial: 371 females (average age 48.1) and 135 males (average age 46.5). Inspection at first, PPT and ESRT in a random order afterwards, were all performed after having invited every new patient to fill in a form with his old and recent symptoms and diseases in decreasing order of importance.The first assessor transcribed for each method, on different sheets of the Sectogram, all possible symptoms and diseases thought to be related with the topography of ear skin alterations or the location of the points identified with PPT and ESRT.The second assessor had the delicate task of working out the number of consistent symptoms, but was free to interpret them as best he could, also speaking to the patient. He also had to verify if there were symptoms which the patient had neglected to mention in the form.

Results

The three diagnostic methods used had different success rates for the identification of patients' symptoms. Ranging in first place was inspection with 52.2 %, followed by PPT with 33.7 % and ESRT - with 33.2 %. Interestingly, if a symptom was identified by at least one method, the success rate rose to 78.6 %.Regarding the second question, “recent” and “old” problems were defined following the categorization used by Oleson (having occurred < 6 or ≥ 6 months, respectively). The success rates in identifying these two categories of symptoms were very similar for all 3 diagnostic methods.Regarding the third question, the first assessor could, when diagnosing musculoskeletal disorders, further specify the side of pain (right, left and bilateral). If the pain was bilateral or without prevalence of side, the success rates were higher than expected (inspection 85.2 %, PPT 56.2 %, ESRT - 20.7 %), as opposed to the cases of ipsilateral (right or left) pain (inspection 51.7 %, PPT 25.3 %, ESRT - 14.6 %).

Conclusions

Inspection is an essential part of auricular diagnosis, alone or in combination with one or more detection techniques. Its superiority over the other methods confirms the importance given by Chinese authors to this procedure which has been neglected in Western countries. The combination of as many diagnostic methods as possible permits the experienced physician to achieve a relevant diagnostic versatility in detecting health disorders of various origins in his patients.     

Optimizing acitretin use in patients with plaque psoriasis

Acitretin is one of the systemic agents used for the treatment of psoriasis. Because different acitretin dosages resulted therapeutically successful, there is no general agreement on the optimal dose regimen. To report acitretin efficacy and safety in a real‐life setting, wherein patient‐tailored dose regimen is usually prescribed, a retrospective analysis evaluating charts of all plaque‐type psoriasis patients treated with acitretin from the clinic database was performed. PASI score improvement, as well as PASI 50, 75, 90, and 100 responses were assessed throughout the observational period. Overall, 52% PASI score reduction and a satisfactory safety profile were detected. PASI 50, 75, 90, and 100 response was achieved by 53%, 48%, 28%, and 14%, respectively. Treatment consisted on a mean daily acitretin dose of 25.01 mg. The initial dose was increased (51.2% of cases) or decreased (48.8%) prescribing a mean daily dose of 29.8 mg and 20.02 mg, respectively. This study proposed a dose regimen customized on clinical response and patient's needs, to optimized acitretin benefit.     

Physical Activity in Liver Transplantation: A Patient's and Physicians’ Experience

Liver transplantation has become a highly standardized, acceptable option for selected patients with end-stage liver disease and/or hepatocellular carcinoma in the setting of cirrhosis. Both conditions are associated with loss of skeletal muscle mass (sarcopenia) and physical deconditioning. Both conditions result in a dramatic decrease in the patients’ quality of life, negatively impacting on the pre- and post-transplant prognosis. In this context, awareness of the advantages of physical activity in both the pre- and post-transplant setting is key. However, the importance of regular, individualized and patient-adapted physical activity is still understudied and underestimated. This article describes a three-sided perspective on the importance of physical activity in the setting of liver transplantation, including a patient's, transplant surgeon's and hepatologist’s point of view.