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.     

Mutation of Vav1 adaptor region reveals a new oncogenic activation

Vav family members function as remarkable scaffold proteins that exhibit both GDP/GTP exchange activity for Rho/Rac GTPases and numerous protein-protein interactions via three adaptor Src-homology domains. The exchange activity is under the unique regulation by phosphorylation of tyrosine residues hidden by intra-molecular interactions. Deletion of the autoinhibitory N-terminal region results in an oncogenic protein, onco-Vav, leading to a potent activation of Rac GTPases whereas the proto-oncogene barely leads to transformation. Substitution of conserved residues of the SH2-SH3 adaptor region in onco-Vav reverses oncogenicity. While a unique substitution D797N did not affect transformation induced by onco-Vav, we demonstrate that this single substitution leads to transformation in the Vav1 proto-oncogene highlighting the pivotal role of the adaptor region. Moreover, we identified the cell junction protein β-catenin as a new Vav1 interacting partner. We show that the oncogenicity of activated Vav1 proto-oncogene is associated with a non-degradative phosphorylation of β-catenin at residues important for its functions and its redistribution along the cell membrane in fibroblasts. In addition, a similar interaction is evidenced in epithelial lung cancer cells expressing ectopically Vav1. In these cells, Vav1 is also involved in the modulation of β-catenin phosphorylation. Altogether, our data highlight that only a single mutation in the proto-oncogene Vav1 enhances tumorigenicity.     

SAPHO Syndrome: Current Developments and Approaches to Clinical Treatment

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare autoimmune disease which, due to its clinical presentation and symptoms, is often misdiagnosed and unrecognized. Its main features are prominent inflammatory cutaneous and articular manifestations. Treatments with immunosuppressive drugs have been used for the management of SAPHO with variable results. To date, the use of anti-TNF-α agents has proved to be an effective alternative to conventional treatment for unresponsive or refractory SAPHO cases. TNF-α is a pro-inflammatory cytokine and pivotal regulator of other cytokines, including IL-1 β, IL-6, and IL-8, involved in inflammation, acute-phase response induction, and chemotaxis. IL-1 inhibition strategies with anakinra have shown efficacy as first and second lines of treatment. In this review, we will describe the main characteristics of biological drugs currently used for SAPHO syndrome. We also describe some of the promising therapeutic effects of ustekinumab, an antibody against the p40 subunit of IL-12 and IL-23, after failure of multiple drugs including anti-TNF-α and anakinra. We discuss the use and impact of the new anti-IL-1 antagonists involved in the IL-17 blockade, in particular for the most difficult-to-treat SAPHO cases.     

Impact on Quality of Life Following the Implantable Miniature Telescope Procedure

The purpose is to examine the impact of the Implantable Miniature Telescope procedure on the level of treatment satisfaction and quality of life of individuals with end-stage age-related macular degeneration. Six individuals who had undergone the Implantable Miniature Telescope procedure were recruited. The participants completed two survey instruments about their overall quality of life and level of treatment satisfaction post intervention. In-depth interviews were also conducted to gain a perspective of the participant’s lived experience. A moderately high quality-of-life and treatment satisfaction rating was reported by participants post intervention. Qualitative themes included loss of independence, realistic perspective about the procedure, importance of rehabilitation following the procedure, and high treatment satisfaction despite lack of improvement in visual functioning. Moderately high quality-of-life ratings and treatment satisfaction were reported despite reports of limited improvements in participants’ visual function and ability to utilize the Implantable Miniature Telescope. However, qualitative responses revealed a negative impact on quality of life in relation to their diagnosis of end-stage age-related macular degeneration, but not in direct relation to the Implantable Miniature Telescope procedure.     

An evaluation of the treatment of parapsoriasis with phototherapy

Whether parapsoriasis represents an early stage of T-cell cutaneous lymphoma is still the subject of controversy. We evaluated the efficacy of phototherapy in the treatment of parapsoriasis and its relation with TCCL. Patients diagnosed with parapsoriasis and treated with phototherapy PUVA or UVB-NB were selected. Between 1 to 8 years following treatment the evolution of their disease was evaluated. In 62 patients the cure rate was 79.3% and 17.2% showed improvement of the lesions. Only two patients developed full blown T-cell cutaneous lymphoma. Phototherapy is an excellent treatment for parapsoriasis, with high cure rates, regardless of the type of phototherapy employed. Of the 62 patients under study, parapsoriasis showed no general tendency to progress to T-cell cutaneous lymphoma.