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Objective A large number of studies have highlighted the important role of the gut microbiota in the pathophysiology of neurological disorders, suggesting that its manipulation might serve as a treatment strategy. We hypothesized that the gut microbiota participates in absence seizure development and maintenance in the WAG/Rij rat model and tested this hypothesis by evaluating potential gut microbiota and intestinal alterations in the model, as well as measuring the impact of microbiota manipulation using fecal microbiota transplantation (FMT). Methods Initially, gut microbiota composition and intestinal histology of WAG/Rij rats (a well-recognized genetic model of absence epilepsy) were studied at 1, 4, and 8 months of age in comparison to nonepileptic Wistar rats. Subsequently, in a second set of experiments, at 6 months of age, untreated Wistar or WAG/Rij rats treated with ethosuximide (ETH) were used as gut microbiota donors for FMT in WAG/Rij rats, and electroencephalographic (EEG) recordings were obtained over 4 weeks. At the end of FMT, stool and gut samples were collected, absence seizures were measured on EEG recordings, and microbiota analysis and histopathological examinations were performed. Results Gut microbiota analysis showed differences in beta diversity and specific phylotypes at all ages considered and significant variances in the Bacteroidetes/Firmicutes ratio between Wistar and WAG/Rij rats. FMT, from both Wistar and ETH-treated WAG/Rij donors to WAG/Rij rats, significantly decreased the number and duration of seizures. Histological results indicated that WAG/Rij rats were characterized by intestinal villi disruption and inflammatory infiltrates already at 1 month of age, before seizure occurrence; FMT partially restored intestinal morphology while also significantly modifying gut microbiota and concomitantly reducing absence seizures. Significance Our results demonstrate for the first time that the gut microbiota is modified and contributes to seizure occurrence in a genetic animal model of absence epilepsy and that its manipulation may be a suitable therapeutic target for absence seizure management.

Introduction Post-marketing surveillance activities (namely pharmacovigilance) are crucial to favor the early detection of unexpected adverse events (AEs) and/or serious adverse reactions (SAEs). Indeed, spontaneous reporting of AEs has been demonstrated to underestimate the number of events in different clinical settings. Aim of the present study is to report the preliminary data of a Regional (Calabria, Italy) Pharmacovigilance Program (CBPP) aimed at improving AEs’ reporting associated with biologics use in rheumatology. Materials and methods We developed a simple, cost-effective pharmacovigilance program based on regular training sessions for physicians (stimulated reporting), periodical phone calls by a clinical pharmacologist aimed at identifying new events and stimulating self-awareness and encouraging reporting to the physician during the subsequent follow-up visit for minor AEs. To test this approach, all consecutive patients undergoing treatment with one biologic agent at eight rheumatology centers during a two-years period were invited to participate. Collected AEs were compared to the number of AEs spontaneously reported for the same molecules in the same centers before starting the protocol. Results During the study period, 399 patients (245 females; mean age: 58 ± 11 years) were started on treatment with biologics for active RA (n = 211, 52.9%), PsA (n = 119, 29.8%) or AS (n = 69, 17.3%) at eight rheumatology centers. A total of 125 AEs (31.3%) and 9 SAEs (2.3%) were reported during the two-years study period. In the control cohort (comprising 368 consecutive patients started on treatment with bDMARDs during a two-years period before CBPP study) only 42 (11.4%) AEs and no SAEs were reported (p < 0.0001). The most common AEs were injection site reactions and skin disorders. Conclusions In conclusion, our study provides further evidence of a critical role of active pharmacovigilance in detection, reporting and analysis of AEs in rheumatology.

Choroideremia (CHM), an X-linked degen- eration of the retinal pigmented epithelium (RPE), pho- toreceptors, and choroid, ultimately leads to blindness. It is caused by loss-of-function of the CHM gene prod- uct, the Rab escort protein 1 (REP1) that is involved, together with its homologue REP2, in prenylation of Rab GTPases, key regulators of intracellular vesicular traf- fic. Here, we report the molecular characterization of 20 unrelated Italian families affected by CHM. We identi- fied 19 different mutations, nine of which are new. In most cases, we analyzed the effect of the mutations at the mRNA level. Furthermore, we demonstrated, by in vitro trancription/translation assays, that the mutated mRNAs produced truncated proteins in all cases but one. In fact, we also identified a novel REP1 missense variant (c.1520A>G; p.H507R) associated to CHM. Thus far, only two other CHM-associated missense mutations have been identified, one of which was a splicing alteration. We investigated the impact of the p.H507R amino acid change on REP1 structure and function, thus providing the first experimental demonstration that correlates a mis- sense mutation in CHM with a functional impairment of REP1. Overall, our results indicate that the REP1-Rab geranyl-geranyl transferase interaction and consequently REP1-mediated Rab prenylation is essential for RPE and photoreceptor function. Hum Mutat 32:1460-1469, 2011. C 2011 Wiley Periodicals, Inc.

Background Complete rectal prolapse is a disease characterized by the complete protrusion of rectal wall through the anus. This disability affects mostly elderly women (>65 years). Several surgical techniques have been described for the treatment of this condition with both perineal and abdominal approach. Under trial condition none of them have been demonstrated to be the best choice in terms of recurrence, postoperative faecal incontinence or stipsis and cost-effectiveness. The aim of our study was to compare different surgical techniques for complete rectal prolapse in the elderly.

In making healthcare management decisions, clinicians must weigh up the benefits and the harms of alternative strategies. Guidelines are useful tools for administrators, policy makers, managers, clinical leaders and care givers to achieve this aim. Guidelines recommendations may be produced in three different ways: small panels of experts, consensus conferences and on the basis of evidence. Expert clinicians and organisations offering recommendations to the clinical community have often erred as a result of not taking sufficient account of evidence. Moreover the so-called "evidence-based guidelines" are often inconsistent in how they rate the quality of evidence and the strength of recommendation. Systems used to assess quality of evidence in guidelines were only scales that reported the study design the evidence was provided from as a letter or a number (i.e. C1, IIb, etc). This kind of evaluation gives great emphasis on RCTs and metanalysis as an "a priori" source of good evidence without a systematic evaluation of study quality. This drives to a lesser impact of observational studies, CCTs and case series of rare adverse events in guidelines. Geriatric patients are often excluded or underrepresented in trials mainly because comorbidity conditions and toxic effects of treatment are the greatest barriers to recruitment of older patients. Other studies have shown that physician refusal to enrol patients onto trials is among the top reasons for low protocol participation. Thus evidences for geriatric guidelines are, according to such a rating scheme, of low level. Since 2006 the BMJ requested in its instruction to authors, that authors should preferably use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for grading evidence when submitting a clinical guidelines article. The GRADE system separates decisions regarding the quality of evidence from strength of recommendations and allows upgrading or down grading of – level of evidence according to quality of evidence rather than to study design In order to obtain reliable and evidence-based guidelines in geriatric surgery, the GRADE system for grading evidence should be used as consolidated standard.

Results During this time period, 153 (27%) of patients with breast cancer were 60 years or older. Approximately, one third (49 patients) required or elected mastectomy as primary treatment. Of the 49 women evaluated, 17 (28%) elected delayed implant-based breast reconstruction. No patients experienced major complications at the longest follow up. Conclusion Elderly women undergoing with mastectomy should be offered breast reconstruction as part of their treatment. Physicians and patients need to be educated regarding surgical options, the minimal associated morbidity and mortality, and excellent functional and cosmetic outcomes. With extended life expectancy, breast reconstruction enhances these aspects of quality of life. Future management guidelines should include breast reconstruction in the algorithm. from XXI Annual Meeting of The Italian Society of Geriatric Surgery Terni, Italy. 4–6 December 2008