Regional long-term analysis of dietary isotopes in Neolithic southeastern Italy: new patterns and research directions.

Isotopic analyses of prehistoric diet have only recently reached the threshold of going beyond site-focused reports to provide regional syntheses showing larger trends. In this work we present the first regional analysis for Neolithic southeastern Italy as a whole, including both substantial original data and a review of the available published data. The results show that dietary isotopes can shed new light on a number of traditional and important questions about Neolithic foodways. First, we observe regional variations in the distribution of stable isotope values across the area, suggesting variability in the Neolithic diet. Secondly, we show that, although the plant food calorific intake was primary for these communities, animal products were also important, representing on average 40% of the total calories. Third, we note that marine fish was only minorly consumed, but that this could be an underestimation, and we observe some variability in the regions considered, suggesting differences in local human-environment interactions. People in different regions of southeastern Italy may have consumed different versions of a common Neolithic diet. Regional synthesis also allows us to take stock of gaps and new directions in the field, suggesting an agenda for Neolithic isotopic research for the 2020s.

Regional point prevalence study of healthcare-associated infections and antimicrobial use in acute care hospitals in Liguria, Italy.

BACKGROUND: Given the importance of monitoring healthcare-associated infections (HCAIs) and the consumption of antibiotics, a regional point prevalence survey was conducted in Liguria between March and April 2016. AIM: To measure the overall prevalence of HCAI and describe the use of antibiotics in all public hospitals. METHODS: Data on risk factors and use of antibiotics were collected for each hospitalized patient. To define the variables significantly associated with HCAI, univariate and multivariate analyses were conducted. Standardized infection ratio and standardized antimicrobial use ratio were measured for each participating hospital. FINDINGS: A total of 3647 patients were enrolled. In all, 429 HCAIs were diagnosed in 376 patients, giving a prevalence of HCAI of 10.3%. Respiratory tract (21.7%) and urinary tract (20%) were the most frequent sites of infection. High rates of meticillin-resistant Staphylococcus aureus (47.4%) and Enterobacteriaceae resistant to carbapenems (26.3%) were isolated. Forty-six percent of patients received at least one antibiotic. Combinations of penicillins including ß-lactamase inhibitors (24.1%) were the most widely used; the main indication (46.7%) was the treatment of a community-acquired infection. CONCLUSION: There was an increase in HCAI prevalence compared to a similar survey conducted in 2007; however, the performance of overlapping investigations will enable more reliable considerations. Nevertheless, data on antimicrobial resistance and use of antibiotics are consistent with the national trend. Despite methodological limitations, prevalence studies are useful to monitor HCAI over time and encourage greater awareness of the problem by all stakeholders.

Epidemiology and biomolecular characterization of carbapenem-resistant klebsiella pneumoniae in an Italian hospital.

OBJECTIVE: To describe the occurrence of CRKP infections in a tertiary care hospital and to analyse the allelic profiles of the clinical strains involved and the most frequent carbapenemases. DESIGN: The study analyzed cases of infection due to CRKP in the period 2013-2014; 147 cases were recorded, most of which (82.31%) were in-hospital infections. SETTING: A hospital in northern Italy. METHODS: We retrospectively collected: data on patient characteristics and the microbiological characteristics of CRKP. Isolates from 72 of the in-hospital cases underwent molecular typing (MLST); in addition, in each isolate, a procedure for the detection of the blaKPC gene was carried out. RESULTS: The in-hospital death rate was 24.0% in 2013 and 37.5% in 2014. However, the difference between these two values did not prove statistically significant (P > .05). Analysis of mortality revealed that bloodstream infections were more frequently associated with death than other infections (χ2 = 14.57, P < .001). The age-adjusted Cox proportional hazard model revealed that the patients with bacteremia due to CRKP had a 3-fold higher risk of death (HR 3.11; 95% CI 1.66 - 5.84, P< .001) than those with infections of other sites. MLST revealed that the prevalent allelic profile was ST 512 (79.62%); the most frequent carbapenemase was KPC-3 (83.8%). CONCLUSIONS: Our results are in line with those of recent studies, which have shown that the spread of CRKP in Italy is a matter of concern and that further efforts have to be made to prevent the potential dissemination of carbapenemase-producing clones of K. pneumoniae, whenever possible.

Pathological spectrum in recurrences of glioblastoma multiforme.

INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant brain tumour. Despite advances in treatment its prognosis remains poor. Histological features of GBM are well known. On the contrary histological description of recurrences is still not available. The aim of this study was to describe the morphological, immunohistochemical and molecular features of recurrent GBMs. METHODS: 25 recurrent GBMs, diagnosed after 2005, were collected. All patients had undergone an adjuvant treatment regimen (temozolomide and/or radiotherapy). All cases were immunostained using anti-GFAP, Olig2 and Nogo-A antisera. MGMT and IDH1 status was reassessed. Features of the recurrences were compared with those of primary GBMs, time of recurrence and survival. RESULTS: Recurrences were divided morphologically into three groups: 1) recurrences displaying the same features of primary GBM, were highly cellular, had the fastest progression and the worst prognosis; 2) recurrences changing dramatically morphological appearance, had a slightly longer survival, 3) poorly cellular recurrences, with sparse neoplastic cells intermingled with reactive and necrotic tissue, displayed the slowest progression and longer survival. MGMT and IDH1 status remained unchanged between primary tumours and recurrences. DISCUSSION: GBM histological subtypes display different reactions to adjuvant treatments, offering a possible role in predicting different recurrence and survival time.

Effects of redox conditions on the control of arsenic mobility in shallow alluvial aquifers on the Venetian Plain (Italy).

The Venetian Plain is known for the occurrence of areas with high concentrations of arsenic in groundwater (greater than 400 µg/L). The study area represents the typical residential, industrial and agricultural features of most Western countries and is devoid of hydrothermal, volcanic or anthropogenic sources of arsenic. The aim of the study is to model the arsenic mobilization and the water-rock interaction by a complete hydrogeochemical investigation (analyses of filtered and unfiltered groundwater sediment mineralogy and geochemistry). The groundwater arsenic contamination and redox conditions are highly variable. Groundwaters with oxidizing and strongly reducing potentials have much lower arsenic concentrations than do mildly reducing waters. The grain size of the aquifer sediments includes gravels, sands and silty-clays. A continuous range of organic material concentrations is observed (from zero to 40%). The amount of sedimentary organic matter is highly correlated with the arsenic content of the sediments (up to 300 mg/kg), whereas no relationships are detectable between arsenic and other chemical parameters. The occurrence of arsenic minerals was observed as a peculiar feature under the scanning electron microscope. Arsenic and sulfur are the sole constituents of small tufts or thin crystals concentrated in small masses. These arsenic minerals were clearly observed in the peat sediments, in agreement with the geochemical modeling that requires very reducing conditions for their precipitation from the groundwater. The modeling suggests that, under oxidizing conditions, arsenic is adsorbed; moreover, a continuous decrease in the redox potential causes increasing desorption of arsenic. If the reducing conditions become more intense, the formation of As-S minerals would explain the lower concentration of arsenic measured in the strongly reducing groundwater. Even if As-sulfides are rare under low-temperature conditions, the anomalous abundance of reductants (organic matter) can locally stabilize As-S minerals, which can scavenge large quantities of groundwater arsenic.

Acne: a new model of immune-mediated chronic inflammatory skin disease.

Acne is a chronic inflammatory disease of the sebaceous-pilosebaceous unit. Interestingly, inflammation can be detected by histopathological examination and immuohistochemical analysis even in the apparently non-inflammatory acneic lesions, such as comedones. In the last years, it has been clearly demonstrated that acne development is linked to the combination of predisposing genetic factors and environmental triggers, among which a prominent role is played by the follicular colonization by Propionibacterium acnes (P. acnes). P. acnes displays several activities able to promote the development of acne skin lesions, including the promotion of follicular hyperkeratinisation, the induction of sebogenesis, and the stimulation of an inflammatory response by the secretion of proinflammatory molecules and by the activation of innate immunity, that is followed by a P. acnes-specific adaptive immune response. In addition, P. acnes-independent inflammation mediated by androgens or by a neurogenic activation, followed by the secretion in the skin of pro-inflammatory neuropeptides, can occur in acne lesions. In conclusion, acne can be considered as a model of immune-mediated chronic inflammatory skin disease, characterized by an innate immune response that is not able to control P. acnes followed by a Th1-mediated adaptive immune response, that becomes self-maintaining independently from P. acnes itself.

Drug-induced cutaneous vasculitides.

Cutaneous vasculitides (CV) can be idiopathic or secondary to several triggers, including drugs, which account for up to 30% of all the cases of CV. Several drugs can induce CV, including some medications commonly used in dermatology, including minocycline, and several new drugs, such as anti-TNF agents. Different pathomecanisms are involved in the development of drug-induced CV, including the formation and deposition of immune complexes, the induction of neutrophil apoptosis, the formation of neoantigens between the drugs and proteins from the host, the shift of the immune response, and others. Although the diagnosis is difficult, because the clinical picture of drug-induced CV is in general indistinguishable from that of other forms of CV, it is important to recognize such entities in order to correctly manage the patient. Anamnesis, diagnostic algorithms to assess the likelihood of the association between a drug and a cutaneous reaction, skin biopsy and laboratory testing (including the search for antineutrophil cytoplasmic antibodies) are useful tools to make a diagnosis of drug-induced CV. About the therapy, while in idiopathic vasculitides the treatment is usually more aggressive and long-lasting, very often requiring a maintenance therapy with immunosuppressive drugs, in drug-induced CV the discontinuation of the suspected drug alone is usually enough to achieve complete remission, making the prognosis usually very good.

Classification and clinical diagnosis of cutaneous vasculitides.

The definition, diagnostic criteria and classification of systemic vasculitides, of which cutaneous vasculitides (CV) are a part, have long been discussed by the medical scientific world. The most significant contribution is due to the consensus-based criteria specifically derived by the combination of judgments from groups of experts, after accurate literature reviews and developed using consensus techniques. First of them came from the American College of Rheumatology (ACR) in 1990. In 1994 the Chapel Hill International Consensus Conference (CHCC) produced the Consensus-based Criteria essentially providing proper nomenclature for systemic vasculitis, which has been modified in 2012 by the CHCC2012. Moreover, in 2006 European League against Rheumatism and Pediatric Rheumatology European Society produced consensus criteria for the classification of childhood vasculitis. In CHCC2012 CV, affecting small vessels with a predominant skin involvement, have been included in both small vessel vasculitis and single organ vasculitis. The general characteristics of so-called CV have been described (epidemiology, clinical features, histopathology and etiopathogenesis) and, finally, the major characteristics of each clinical type of CV as well as their diagnostic criteria currently available in the literature have been reported.

Regulatory T cells in skin lesions and blood of patients with bullous pemphigoid.

BACKGROUND: Although regulatory T cells (Tregs) are affected in several autoimmune skin diseases, only two studies have been performed in patients with bullous pemphigoid (BP) with contrasting results. OBJECTIVE: To characterize Tregs and to determine the serum levels of regulatory cytokines in patients with BP. METHODS: In BP lesional skin, immunohistochemistry and confocal microscopy were performed for CD4(+) , CD25(+) , forkhead/winged helix transcription factor (FOXP3)(+) , transforming growth factor (TGF)-ß(+) and interleukin (IL)-10(+) cells. In addition, the number of CD4(+) CD25(++) FOXP3(+) Tregs in peripheral blood was assessed by flow cytometry, and the levels of TGF-ß and IL-10 were determined in serum samples by enzyme-linked immunosorbent assay before and after steroid therapy. Controls included patients with psoriasis, atopic dermatitis (AD) and healthy donors. RESULTS: The frequency of FOXP3(+) cells was significantly reduced in skin lesions from patients with BP (P < 0.001) compared with psoriasis and AD. Moreover, the number of IL-10(+) cells was lower in BP than in psoriasis (P < 0.001) and AD (P = 0.002), while no differences were observed in the number of TGF-ß(+) cells. CD4(+) CD25(++) FOXP3(+) Treg in the peripheral blood of patients with BP was significantly reduced compared with healthy controls (P < 0.001), and augmented significantly after steroid therapy (P = 0.001). Finally, TGF-ß and IL-10 serum levels were similar in patients with BP compared with healthy controls. However, after therapy, BP patients showed significantly higher IL-10 serum levels than before therapy (P = 0.01). CONCLUSIONS: These data suggest that the depletion of Tregs and of IL-10 in patients with BP may be an important factor in the pathogenesis of the disease.

Treatment of cutaneous lichen planus: an evidence based analysis of efficacy by the Italian Group for Cutaneous Immunopathology.

Cutaneous lichen planus (LP) is an inflammatory papulo-squamous disorder presenting with violaceous, polygonal, flat-topped papules and plaques on the skin that shows a chronic-relapsing course. However, in most cases, the disease spontaneously regresses 1 month to 7 years after onset; for this reason, it is very difficult to evaluate the effectiveness of the therapeutic strategies for cutaneous LP. This study reviewed the more recent status of systemic therapies for cutaneous LP. No level A trials on the medical or physical treatment of cutaneous LP were found in the literature. Moreover, only three trials were found with acceptable methods including more than 20 patients (one on the use of acitretin, one on the use of phototherapy and the other one on the use of sulfasalazine, respectively). Among the new drugs, although few evidences could be provided, alitretinoin may represent a novel effective and well-tolerated treatment option for refractory cutaneous LP. By contrast, no trials were found about the treatment of specific LP variants (including inverse, hypertrophic or ulcerative LP), but only treatment reports of single cases. Finally, basing on the careful revision of the whole Literature and on the personal experience of the Authors, the therapeutic recommendations for cutaneous LP proposed by the Italian Group for Cutaneous Immunopathology were reported.

Clinical and immunopathological features of 159 patients with dermatitis herpetiformis: an Italian experience.

AIM: The aim of this paper to report the main clinical and immunopathological findings of our case series of 159 patients with dermatitis herpetiformis (DH). METHODS: All DH patients that were diagnosed from 1995 to 2012 at the Section of Dermatology of the University of Florence were included in the study. Clinical data were collected for each patient. Moreover, histopathological examination on both the skin and the small bowel, direct immunofluorescence on perilesional skin as well as the search for anti-endomysium and anti-tissue transglutaminsase antibodies (tTG) were performed. RESULTS: A total of 159 patients with a male predominance were enrolled. About 36% of the patients were below the age of 20. The most frequent clinical features seen in our DH patients were represented by figurate erythema, wheals, papules and scratching lesions, while the knees, elbows and buttocks were the most commonly involved sites. All the 22 patients that underwent a bowel biopsy showed the typical alterations found in celiac disease. Moreover, 100% of the patients showed granular IgA deposits at the papillary tips. Finally, anti-endomysium and anti-tTG antibodies were present in 90% and 96% of the patients, respectively. CONCLUSION: We reported one of the largest case series of patients with DH from a single center. Our study confirmed most of the data from the Literature, and in particular the association of DH to histologically proven CD in all the biopsied cases. Another interesting finding of our study is the high prevalence of DH within pediatric patients, that is usually underreported.

Multidrug-resistant Acinetobacter baumannii outbreak: an investigation of the possible routes of transmission.

OBJECTIVES: To establish the possible sources and routes of transmission of a multidrug-resistant Acinetobacter baumannii outbreak involving 22 patients. STUDY DESIGN: Descriptive, retrospective study. METHODS: An environmental investigation was undertaken, monitoring surfaces, air and water. Reconstruction of the spread of the infection took several factors into account such as intrahospital movements of patients and healthcare personnel, hospitalization of patients in the same ward and in chronologically compatible periods, and length of stay. A. baumannii clinical samples were typed using the Multilocus Sequence Typing scheme. RESULTS: The outbreak originated from a patient admitted to the sub-intensive care unit, and the infection subsequently spread to other wards. The allelic profile proved to be the same for all the clinical isolates. Environmental monitoring yielded negative results for A. baumannii. CONCLUSIONS: The results suggest that this epidemic spread through cross-transmission involving healthcare workers.

Annular subacute cutaneous lupus erythematosus lesions and polymyositis onset in a patient with primary Sjogren's syndrome: how should this unusual association be classified?

Classification of the wide variety of autoimmune diseases that can occur before or after the onset of Sjögren's syndrome (SS) is currently debated within the conventional SS criteria or as primary SS (pSS) developing autoimmune disease or as 'associated-overlap' with other systemic autoimmune diseases. There is also debate on whether or not to consider annular polycyclic subacute cutaneous lupus erythematosus (SCLE) and annular erythema associated with Sjögren's syndrome (AESS) as a spectrum linked to Ro-SSA and/or La-SSB auto-antibodies (SSA/SSB auto-ab). We present the case of a 55-year-old female patient, with pSS positive for SSA and SSB auto-ab, who developed chronic relapsing polymyositis and atypical annular non-polycyclic SCLE lesions resembling AESS, which seemed to suggest a common spectrum. While a chronic-progressive polymyositis may be generally accepted as a relatively rare myositis complicating pSS, interpretation of annular lesions of non-systemic SCLE in SS patients might actually be underestimated as pSS skin manifestation likely related to SSA/SSB auto-ab.

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients.

Bullous pemphigoid (BP) is the most frequent autoimmune bullous skin disease, characterised by auto-antibodies against the hemidesmosome complex. Recently, regulatory T cells (Tregs) have been implicated in the development of several autoimmune diseases; few data are available in BP, failing to demonstrate a role of this subset in disease pathogenesis. The aim of this study was to investigate the expression and phenotypes of different Tregs (CD4+ CD25brightFOXP3+ and CD8+ CD28- cells) in BP to clarify whether the depletion of this subset constitutes one mechanism of tolerance loss. The CD4+ CD25brightFOXP3 and CD8+ CD28- circulating subsets were determined by flow-cytometry in 26 untreated BP patients and compared with a group of age- and sex-matched healthy controls (HC, n = 30). Absolute and percentage values of the CD4+ CD25brightFOXP3+ cells were significantly reduced in BP compared with HC (median CD25brightFOXP3+ expression within CD4+ cells: 1.8 vs. 3.5%, p = 0.002); conversely, BP patients were characterised by a significant expansion of the CD25brightFOXP3- "activated" T-cell subset. CCR4 and CD62L were expressed on the majority of CD4+ CD25brightFOXP3+ cells (75.2 and 82.3%, respectively). No differences in the CD8+ CD28- subset were found between BP and HC. This is the first report showing a significant reduction of circulating CD4+ CD25brightFOXP3+ Treg frequency in BP patients.