Unusual case of traumatic neuroma of the orbit

Traumatic or amputation neuromas are neoformations developing after damage to a peripheral nerve. They are not proper tumors but rather a reactive process or a frustrated attempt of nerve regeneration. Traumatic neuromas are potentially found in every sensory peripheral nerve and often at the site of past surgical intervention, including orbital surgery. A 29-year-old Northern African migrant presented progressive exophthalmos and progressive loss of acuity in left eye, which had started about 6 months before after a cranio-facial trauma caused by a violent assault. MRI of the orbits showed a massive intra-orbital, intra-conical lesion, clearly compressing and dislocating the optic nerve and extending posteriorly to the orbital apex. Surgery was performed through lateral approach of Kroenlein and led to complete excision of the lesion. Histology revealed fibrotic, adipose and striated muscle tissues, a disordered, non-neoplastic overgrowth of small and large fascicles of nerves, inflammatory infiltrates, and fibrosis with sparse calcifications were diffusely observed in a background of fat, scar and striated muscle tissued. Patient was discharged on the fifth day in good health condition, without deficit of eye motion but without recovery of visual acuity. In conclusion, this case demonstrates that traumatic neuromas may arise in the orbit in patients with minor direct trauma to nerves and without previous surgical treatment.     

BRCA-mutant pancreatic ductal adenocarcinoma

Despite continued research, pancreatic ductal adenocarcinoma (PDAC) remains one of the main causes of cancer death. Interest is growing in the role of the tumour suppressors breast cancer 1 (BRCA1) and BRCA2—typically associated with breast and ovarian cancer—in the pathogenesis of PDAC. Indeed, both germline and sporadic mutations in BRCA1/2 have been found to play a role in the development of PDAC. However, data regarding BRCA1/2-mutant PDAC are lacking. In this review, we aim to outline the specific landscape of BRCA-mutant PDAC, focusing on heritability, clinical features, differences between BRCA1 and 2 mutations and between germline and sporadic alterations, as well as established therapeutic strategies and those that are still under evaluation.Subject terms: Gastrointestinal cancer, Cancer genetics     

What is semantic in semantic dementia? The decay of knowledge of physical entities but not of verbs,numbers and body parts

Background: Conceptual knowledge does not decay randomly in patients with cerebral damage, suggesting that dedicated neural substrates may support different categories of knowledge. Semantic dementia is an optimal natural model for studying the organization of semantic memory. Nevertheless, in a pathology primarily characterized by a semantic memory disorder categorical- and modality- specific effects are not obvious findings. In fact, there is no clear evidence of categorical effects, at least concerning two broad categories of knowledge, that is, natural items and artifacts. Furthermore, transmodal deficits do not seem to be the rule in SD. Also quite robust is the observation that some conceptual domains are relatively spared in this pathology, that is, numerical knowledge, abstract words, and action verbs.

Aims: To explore category specific and modality specific deficit in SD and to support the evidence that semantic degradation in SD primarily involves knowledge of the objects in the real world, whereas categories of knowledge whose items can be less easily identified by surface attributes, such as verbs, numbers and body parts, are more preserved.

Methods and Procedures: We investigated the semantic impairment in 8 patients with Semantic Dementia (SD). Voxel-based morphometry (VBM) in each patient was also obtained

Outcomes and Results: In some patients manmade objects were significantly more preserved than natural items, verbs more preserved than nouns and the number system entirely preserved; the body parts category was the least impaired in all subjects; finally, in three patients visual semantic knowledge was significantly more preserved than verbal semantic knowledge. VBM showed that atrophy of the anterior inferior temporal regions was insufficient to impair knowledge about verbs, numbers and body parts, whose impairment was associated with more widespread atrophy. In subjects whose verbal semantic knowledge was significantly more impaired than visual semantic knowledge, atrophy was principally distributed in the left hemisphere. In patients with significant impairment for natural items compared to manmade objects, atrophy was not confine in the temporal lobes.

Conclusion: We conclude that in SD semantic decay primarily involves the real-world items whose knowledge is processed by surface sensorifunctional features and that this is the type of knowledge stored in the temporal lobes. Our data support a model that associates a semantic hub with modality/category specific neural substrates.     

The dopaminergic system in peripheral blood lymphocytes: from physiology to pharmacology and potential applications to neuropsychiatric disorders

Besides its action on the nervous system, dopamine (DA) plays a role on neural-immune interactions. Here we review the current evidence on the dopaminergic system in human peripheral blood lymphocytes (PBL). PBL synthesize DA through the tyrosine-hydroxylase/DOPA-decarboxylase pathway, and express DA receptors and DA transporter (DAT) on their plasma membrane. Stimulation of DA receptors on PBL membrane contributes to modulate the development and initiation of immune responses under physiological conditions and in immune system pathologies such as autoimmunity or immunodeficiency.The characterization of DA system in PBL gave rise to a further line of research investigating the feasibility of PBL as a cellular model for studying DA derangement in neuropsychiatric disorders. Several reports showed changes of the expression of DAT and/or DA receptors in PBL from patients suffering from several neuropsychiatric disorders, in particular parkinsonian syndromes, schizophrenia and drug- or alcohol-abuse. Despite some methodological and theoretical limitations, these findings suggest that PBL may prove a cellular tool with which to identify the derangement of DA transmission in neuropsychiatric diseases, as well as to monitor the effects of pharmacological treatments.     

Comparison of fixed dose pegfilgrastim and daily filgrastim after autologous stem cell transplantation in patients with multiple myeloma autografted on a outpatient basis

Different authors have explored the feasibility of autografting patients with multiple myeloma (MM) on an outpatient basis. Peg-filgrastim (PEG), a long-acting recombinant G-CSF, has similar efficacy when compared to conventional G-CSF for chemotherapy-induced neutropenia, but little is known about its use in the autologous stem-cell transplantation (ASCT) setting, namely in patients programmed to be autografted on outpatient basis. In this study, we compared therapeutic results in terms of hematopoietic recovery, non-hematologic toxicity, duration of hospitalization and percentage of hospital readmission between patients receiving either conventional G-CSF or PEG. Thirty-eight MM patients (48 autografts) received PEG, given at a single dose of 6 mg at day +5 from stem cell infusion, while 81 (113 autografts) received G-CSF from day + 2 up to stable neutrophil recovery. The conditioning regimen was high dose melphalan in all patients. The median age and the median number of CD34 + cell infused were comparable between the two groups. Overall, a second hospital admission was required in 36 procedures out of 161 (32%). Febrile neutropenia (FN) and severe mucositis were the most frequent causes of hospitalization. There was no statistically significant difference as percentage of hospital readmission is concerned: in the PEG group readmission was needed in 6 out of 48 autografts (12%) as opposed to 30 out of 113 (26%) in the G-CSF subgroup, p: 0.06. The median time of hospital stay for readmitted patients was identical for the two subgroups (9 days vs. 9 days, p: 0.94). Finally, one case of transplant related mortality occurred in the whole patient series (0.6%). In conclusion, ASCT on an outpatient basis is feasible and safe in patients with MM, the majority of whom are manageable at home. The administration of single dose PEG results in no different outcome in terms of safety and efficacy as compared to 8 days of G-CSF.     

AAV6-mediated Systemic shRNA Delivery Reverses Disease in a Mouse Model of Facioscapulohumeral Muscular Dystrophy

Treatment of dominantly inherited muscle disorders remains a difficult task considering the need to eliminate the pathogenic gene product in a body-wide fashion. We show here that it is possible to reverse dominant muscle disease in a mouse model of facioscapulohumeral muscular dystrophy (FSHD). FSHD is a common form of muscular dystrophy associated with a complex cascade of epigenetic events following reduction in copy number of D4Z4 macrosatellite repeats located on chromosome 4q35. Several 4q35 genes have been examined for their role in disease, including FRG1. Overexpression of FRG1 causes features related to FSHD in transgenic mice and the FRG1 mouse is currently the only available mouse model of FSHD. Here we show that systemic delivery of RNA interference expression cassettes in the FRG1 mouse, after the onset of disease, led to a dose-dependent long-term FRG1 knockdown without signs of toxicity. Histological features including centrally nucleated fibers, fiber size reduction, fibrosis, adipocyte accumulation, and inflammation were all significantly improved. FRG1 mRNA knockdown resulted in a dramatic restoration of muscle function. Through RNA interference (RNAi) expression cassette redesign, our method is amenable to targeting any pathogenic gene offering a viable option for long-term, body-wide treatment of dominant muscle disease in humans.     

Addiction treatment provider attitudes on staff capacity and evidence-based clinical training: results from a national study

This national study of addiction-treatment organizations' implementation of evidence-based practices examines: (1) organizational/leadership factors associated with director (n = 212) attitudes regarding staff resistance to organizational change, and (2) organizational/staff factors associated with staff (n = 312) attitudes regarding evidence-based clinical training. Linear regression analyses, controlling for type of treatment unit, leadership/staff characteristics and organizational readiness to change, identified that directors who perceived their organization needed more guidance and had less staff cohesion and autonomy rated staff resistance to organizational change significantly higher. Staff with higher levels of education and greater agreement that their organization supported change had greater preference for evidence-based trainings. Federal addiction treatment policy should both promote education and training of treatment staff and organizational development of treatment CBOs.     

Use of donor bone marrow mesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model

Recent studies indicate that mesenchymal stem cells (MSC) exhibit a degree of immune privilege due to their ability to suppress T cell mediated responses causing tissue rejection; however, the impact of allogeneic MSC in the setting of organ transplantation has been poorly investigated so far. The aim of our study was to evaluate the effect of intravenous donor MSC infusion for clinical tolerance induction in allogeneic skin graft transplantations in rats. MSC were isolated from Wistar rats and administered in Sprague-Dawley rats receiving Wistar skin graft with or without cyclosporine A (CsA). Graft biopsies were performed at day 10 post transplantation in all experimental groups for histological and gene expression studies. Intravenous infusion with donor MSC in CsA-treated transplanted rats resulted in prolongation of skin allograft survival compared to control animals. Unexpectedly, donor MSC infusion in immunocompetent rats resulted in a faster rejection as compared to control group. Cytokine expression analysis at the site of skin graft showed that CsA treatment significantly decreased pro-inflammatory cytokines IFN-γ and IL-2 and reduced TNF-α gene expression; however, the level of TNF-α is high in MSC-treated and not immunosuppressed rats. Results of our study in a rat tissue transplantation model demonstrated a possible immunogenic role for donor (allogeneic) MSC, confirming the need of adequate preclinical experimentation before clinical use. This work was supported by a grant from a collaborative study with the Ministero della Salute and Regione Toscana (D.Lgs. 502,1992), and funding from Fondazione Marchi.