Immunomodulation in psoriatic arthritis: Focus on cellular and molecular pathways

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis. Pathogenesis is incompletely understood and pathophysiological role of synovium is just beginning to be elucidated. PsA could be considered an enthesal disease and this hypothesis is the link between mechanical stress (entheses) and immunologically active tissue (synovium). Histologically, PsA is characterized by lining layer hyperplasia, diffuse infiltrate of B, T, macrophages and dendritic cells associated with neutrophils' proliferation and angiogenesis. T cells are present, and oligoclonal T-cell expansions have been demonstrated in both skin and synovium. Histological findings are associated with monocyte-derived cytokines expression, as Myeloid-related protein (S100A8/A9). They play an important role in intracellular functions and cytoskeleton–membrane interactions. S100A8/A9 has a role in the propagation and perpetuation of the inflammatory process in patients with psoriasis and PsA, because of an activated monocyte/macrophage system that involve, distal to the skin, the “enthesal-complex.” Complement system can be considered part of the acute phase response as demonstrated by higher plasma levels of C3 and C4 complement components in PsA patients compared with healthy subjects. These abnormal levels are then reverted by anti-TNF drugs. Evidences of efficacy of anti-TNF are expressed by reduction of vascularity and immune cells in synovial tissue. Therefore, innate response generates high concentrations of inflammatory cytokines which promote effector functions of a variety of tissue cells and sustain the characteristic chronicity of synovitis. The challenge will be the development of molecules affecting the balance between innate and adaptive immunity without affecting beneficial functions of the perfect concert of immunological process.     

Donor compatibility and performance status affect outcome of allogeneic haematopoietic stem cell transplant in patients with relapsed or refractory acute myeloid leukaemia

We retrospectively analysed 78 patients with relapsed (n?=?38), primary refractory (n?=?34) or untreated (n?=?6) acute myeloid leukaemia (AML) who underwent allogeneic HSCT at our Institution between 2002 and 2011, to verify outcome and to identify factors that can affect long-term outcome. Myeloablative conditioning regimens were used in 48 patients (24 siblings, 24 matched unrelated donor (MUD)), while 30 patients (18 siblings, 12 MUD) received reduced-intensity conditioning. Acute graft versus host disease (GVHD) developed in 37 (47?%) patients, while chronic GVHD occurred in 19 of the 65 evaluable patients (29?%). With a median follow-up time of 5?years, 13 of 78 patients (17?%) are alive and in complete remission (CR), while 64 have died. Cause of death was disease recurrence in 37 patients (58?%), infection in ten patients (16?%) and GVHD in six (9?%). One-year non-relapse mortality was 35?%. In multivariate analysis, performance status ≥80?% WHO and a full-matched donor were associated with a better outcome: these two variables allowed for risk stratification, identifying three groups with significantly different survival after transplant (P?=?0.0001). Considering post-transplant variables, only CR at recovery and development of cGVHD were correlated with a longer survival. Our data confirm the capacity of allogeneic transplant to prolong survival in a significant proportion of extremely high-risk AML patients.     

What is the probability of being too old for salvage transplantation after hepatocellular carcinoma resection?

BackgroundThe strategy of salvage transplantation for patients with hepatocellular carcinoma is based on the premise that tumour recurrence will be still transplantable at the time of recurrence. However, patients can not only present non-transplantable recurrence but can also be over the age limit accepted for transplantation.AimsTo measure the risk of being too old for salvage transplantation of patients resected for hepatocellular carcinoma within Milan criteria.MethodsA Markov simulation model was developed on the basis of published literature.ResultsThe risk of being too old for salvage transplantation depends on the time-span between age at hepatic resection and age limit, and the expected median waiting-time. Patients resected at an age 2 or 3 years below the age limit carry a risk of being too old that overcomes the probability of receiving transplantation. Salvage strategy can cause harm that depends on the tumour characteristics and degree of portal hypertension, becoming maximal for patients with multiple tumours, clinical signs of portal hypertension and increased bilirubin levels.ConclusionsThe best strategy to adopt should be balanced between the risk of being too old and the expected transplant benefit, but salvage strategy could be pursued if it did not turn into significant harm in comparison to primary transplantation.     

Iatrogenic collapse of the nasal valve after aesthetic rhinoplasty

We present our experience of reconstruction of the nasal valve after iatrogenic collapse, and evaluate the feasibility and outcome of composite grafts. We selected all collapsed nasal valves that occurred after primary aesthetic rhinoplasties of the total number done at the University Tor Vergata in Rome. We excluded collapses that followed septoplasty for nasal deviation, reconstructions, and rhinoplasties for trauma. We selected 15 patients of 1252 who presented from January 1998 to December 2003. Eleven patients who had collapse of both the external and internal valve were treated with a composite graft (septum plus retroauricular) inserted by an “open tip” technique. Four patients (1 with both internal and external valve collapse, 3 with only internal) were treated with a section and opening of the upper lateral cartilages, transposition and repositioning of mucocartilaginous flaps. Good functional and aesthetic results were achieved in almost all patients without complications. Composite cartilaginous grafts are an easy and safe technique for the treatment of iatrogenic collapse of the nasal valve.     

Adult-onset leukodystrophies from respiratory chain disorders: do they exist?

Respiratory chain disorders (RCDs) have been included in the differential diagnosis of adult-onset leukodystrophies. Here, we first report a 32-year-old female with an atypical, adult-onset, non-syndromic RCD due to a mitochondrial DNA deletion and manifesting as complicated ataxia. A ‘leukodystrophic’ pattern was found on brain MRI, but it was neither isolated nor predominant because of the presence of overt basal ganglia and infratentorial lesions, which led us to the proper diagnosis. Subsequently, we evaluated our series of patients with RCDs in order to verify whether a ‘leukodystrophic’ pattern with little or no involvement of deep grey structures and brainstem may be found in adult-onset RCDs, as reported in children. Among 52 patients with adult-onset RCDs, no case with a ‘leukodystrophic’ pattern was found, apart from three cases with a classical phenotype of mitochondrial neurogastrointestinal encephalopathy. In addition, no case of RCDs was found among six cases of adult-onset leukodystrophy of unknown origin and at least one feature suggestive of mitochondrial disease. The review of the literature was in agreement with these findings. Thus, we provide evidence that, unlike in children, RCDs should not be included in the differential diagnosis of adult-onset leukodystrophies, except when there are additional MRI findings or clinical features which unequivocally point towards a mitochondrial disorder.