Paoli Hospital

Evidence on the impact of dimethyl fumarate (DMF) during pregnancy in women with multiple sclerosis (MS) is limited. To investigate disease activity and pregnancy outcomes in a retrospective cohort of women exposed to DMF in early pregnancy. Women discontinuing DMF after pregnancy confirmation were identified from 29 Italian MS Centers. Disease activity 12 months before conception, during pregnancy, and 12 months postpartum were recorded, exploring reactivation predictors. Pregnancy and fetal outcomes were assessed. The study analyzed 137 pregnancies (12 pregnancy losses, 125 live births) from 137 women (mean age 32.9 ± 4.7 years), discontinuing DMF within a median (interquartile range (IQR)) interval of 4.9 (3.7-5.7) weeks from conception. In live birth pregnancies, annualized relapse rate (ARR) significantly decreased during pregnancy (ARR = 0.07, 95% confidence interval (CI): 0.03-0.14, p = 0.021) compared to pre-conception (ARR = 0.21 (95% CI: 0.14-0.30)) and increased postpartum ((ARR = 0.22 (95% CI: 0.15-0.32), p = 0.006). Median time to first relapse (TTFR) was 3.16 (IQR: 1:87-5.42) months. Higher pre-conception relapse number (hazard ratio (HR) = 2.33, 95% CI: 1.08-5.02) and Expanded Disability Status Scale (EDSS; HR = 1.81, 95% CI: 1.17-2.74) were associated with shorter TTFR, while treatment resumption with longer TTFR (HR = 0.29, 95% CI: 0.11-0.74). Fetal outcomes were unaffected by DMF exposure. DMF discontinuation does not increase relapse risk during pregnancy. Early therapy restart prevents postpartum relapses. Early DMF exposure shows no adverse fetal outcomes.

To design slow resorption patient-specific bone graft whose properties of bone regeneration are increased by its geometry and composition and to assess it in in-vitro and in-vivo models.A graft composed by hydroxyapatite (HA) and β-TCP was designed as a cylinder with 3D gyroid porosities and 7 mm medullary space based on swine's anatomy. It was produced using a stereolithography 3D-printing machine (V6000, Prodways).Sterile bone grafts impregnated with or without a 10µg/mL porcine BMP-2 (pBMP-2) solution were implanted into porcine femurs in a bone loss model. Bone defect was bi-weekly evaluated by X-ray during 3 months. After sacrifice, microscanner and non-decalcified histology analysis were conducted on biopsies.Finally, osteoblasts were cultured inside the bone graft or in monolayer underneath the bone graft. Cell viability, proliferation, and gene expression were assessed after 7 and 14 days of cell culture (n=3 patients).3D scaffolds were successfully manufactured with a composition of 80% HA and 20% β-TCP ±5% with indentation compressive strength of 4.14 MPa and bending strength of 11.8MPa.In vivo study showed that bone regeneration was highly improved in presence of pBMP-2. Micro-CT shows a filling of the gyroid sinuses of the implant (Figure 1).In vitro, the presence of BMP2 did not influence the viability of the osteoblasts and the mortality remained below 3%. After 7 days, the presence of BMP2 in the scaffold significantly increased by 85 and 65% the COL1A1 expression and by 8 and 33-fold the TNAP expression by osteoblasts in the monolayer or in the scaffold, respectively. This BMP2 effect was transient in monolayer and did not modify gene expression at day 14.BMP2-impregnated bone graft is a promising patient-personalized 3D-printed solution for bone defect regeneration, by promoting neighboring host cells recruitment and solid new bone formation.For any figures and tables, please contact the authors directly.

Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) could be determined by the presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters can be identified in EGPA. This study used standardized data of 15 European centers for patients with EGPA fulfilling widely accepted classification criteria. We used multiple correspondence analysis, hierarchical cluster analysis, and a decision tree model. The main model included 10 clinical variables (musculoskeletal [MSK], mucocutaneous, ophthalmological, ENT, cardiovascular, pulmonary, gastrointestinal, renal, central, or peripheral neurological involvement); a second model also included ANCA results. The analyses included 489 patients diagnosed between 1984 and 2015. ANCA were detected in 37.2% of patients, mostly perinuclear ANCA (85.4%) and/or antimyeloperoxidase (87%). Compared with ANCA-negative patients, those with ANCA had more renal (P < 0.001) and peripheral neurological involvement (P = 0.04), fewer cardiovascular signs (P < 0.001), and fewer biopsies with eosinophilic tissue infiltrates (P = 0.001). The cluster analyses generated 4 (model without ANCA) and 5 clusters (model with ANCA). Both models identified 3 identical clusters of 34, 39, and 40 patients according to the presence or absence of ENT, central nervous system, and ophthalmological involvement. Peripheral neurological and cardiovascular involvement were not predictive characteristics. Although reinforcing the known association of ANCA status with clinical manifestations, cluster analysis does not support a complete separation of EGPA in ANCA-positive and -negative subsets. Collectively, these data indicate that EGPA should be regarded as a phenotypic spectrum rather than a dichotomous disease.

Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA), and osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated with bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis, thus controlling the balance of bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.

In the treatment of trauma survivors, analysts often find themselves befuddled and disturbed by their clients’ unpredictable and self-destructive behavior. One or more dissociated self-states, initially hidden behind the patient’s high-functioning presentation, may eventually make themselves known in the treatment. The analyst is then challenged to find ways to forge a healing alliance with a disavowed part of the patient’s personality that has previously existed only in the context of a perpetually abusive internalized object relationship. Not only must the multiple self-states learn to communicate with each other, but the unformulated components of the trauma survivor’s childhood experience must be formulated with the analyst in the interpersonal field. At the same time, the analyst’s dissociated self-states and unformulated experience are interwoven in the therapy, creating their own confusion and blind spots. A case study illustrates how the client’s and analyst’s vulnerabilities intersect in the shared unconscious of their work. Psychoanalytic theories on multiple self-states, dissociation, transference-countertransference configurations and unformulated experience all combine to shed light on the difficulties faced by wounded healers treating traumatized patients. The analyst’s countertransference dream is pivotal in exposing her previously inaccessible reactions to her patient.

A smart city is providing a intelligent way for the communication between infrastructure, capital, behaviours and cultures. Smart city provides smart environment technologies which improves the living and work standard of the citizens. Intelligent transportation system is one of the major domains in smart city. Intelligent transportation system is used to monitor and control the vehicular traffic in smart way by using the different communication modes and networks i.e VANET. Presently VANET already monitors and controls the vehicular traffic but if it comes under smart city environment, it gives multi fold benefit for individual and other to plan smartly their travel plan. This paper focuses on the Quality of Service of VANET in case of failure in communication particularly with infrastructure i.e. road side unit (RSU).