Booster hepatitis B vaccination not necessary for long-term protection in children immunised with hexavalent vaccines

Editoria

Cost-effectiveness of direct acting oral anticoagulants in the prevention of thromboembolic complications : limits and concerns of economic evaluations

Economic evaluations have a widespread application in many areas of clinical research and play a key role in the clinical decision-making process. However, economic analyses have been sometimes used to produce new 'evidence' that is not adequately tested in the target population. This is the case of data arising from a systematic review of clinical trials evaluating the use of direct acting oral anticoagulants for the prevention of stroke in patients with atrial fibrillation. Taking into account this example, here we discuss the concerns raised by the improper interpretation of the results. Our conclusions are three-fold. Data from economic analyses should not be shifted to a clinical recommendation. Simulation models should not be used to generate new 'evidence' that is not supported by experimental data and is misleading. Clinical judgment is therefore pivotal to interpret results emerging from economic analyses

Does Living in Previously Exposed Malaria or Warm Areas is Associated with a Lower Risk of Severe COVID-19 Infection in Italy?

Incidence of Covid-19 positivity (21/2/2020-28/3/2020) in provinces of 4 Italian regions whose territory was described as previously exposed to Malaria was compared with those of other provinces of the same regions. The climate of such provinces was compared with the climate of the other provinces in some regions. Previously malarial areas show a lower risk than other provinces of the same regions: Mantua (Lombardy) RR=0.94 (CI95%0.89-0.99); Venice-Rovigo (Veneto) RR=0.61 (CI95%0.58-0.65); Ferrara-Ravenna (Emilia-Romagna) RR=0.37 (CI95%0.35-0.41); Cagliari Oristano-South Sardinia (Sardinia) RR=0.25 (0.17-0.31). The maximum temperature in March 2020 in those provinces was higher in mean 1.5° for other provinces. The lower frequency of COVID-19 in the provinces previously exposed to Malaria of four Italian regions does not reveal a causal link. The phenomenon has emerged independently in all the regions investigated. People born between the 1920s and 1950s were those most exposed to malaria years ago and today are the most exposed to the severest forms of COVID-19. A warmer climate seems to be associated with a lower risk of COVID, in line with the evidence highlighted in equatorial states where a lower lethality of the virus has emerged, however this regardless of the presence of Malaria. This may suggest that climate and not Malaria is the real risk factor, though further studies need to determine the role of the association climate / COVID

Silencing of Keratinocyte Growth Factor Receptor Restores 5-Fluorouracil and Tamoxifen Efficacy on Responsive Cancer Cells

BACKGROUND: Keratinocyte growth factor receptor (KGFR) is a splice variant of the FGFR2 gene expressed in epithelial cells. Activation of KGFR is a key factor in the regulation of physiological processes in epithelial cells such as proliferation, differentiation and wound healing. Alterations of KGFR signaling have been linked to the pathogenesis of different epithelial tumors. It has been also hypothesized that its specific ligand, KGF, might contribute to the development of resistance to 5-fluorouracil (5-FU) in epithelial cancers and tamoxifen in estrogen-positive breast cancers. METHODOLOGY/PRINCIPAL FINDINGS: Small interfering RNA was transfected into a human keratinocyte cell line (HaCaT), a breast cancer derived cell line (MCF-7) and a keratinocyte primary culture (KCs) to induce selective downregulation of KGFR expression. A strong and highly specific reduction of KGFR expression was observed at both RNA (reduction = 75.7%, P = 0.009) and protein level. KGFR silenced cells showed a reduced responsiveness to KGF treatment as assessed by measuring proliferation rate (14.2% versus 39.0% of the control cells, P<0.001) and cell migration (24.6% versus 96.4% of the control cells, P = 0.009). In mock-transfected MCF-7 cells, KGF counteracts the capacity of 5-FU to inhibit cell proliferation, whereas in KGFR silenced cells KGF weakly interferes with 5-FU antiproliferative effect (11.2% versus 28.4% of the control cells, P = 0.002). The capacity of 5-FU to induce cell death is abrogated by co-treatment with KGF, whereas in KGFR silenced cells 5-FU efficiently induces cell death even combined to KGF, as determined by evaluating cell viability. Similarly, the capacity of tamoxifen to inhibit MCF-7 and KCs proliferation is highly reduced by KGF treatment and is completely restored in KGFR silenced cells (12.3% versus 45.5% of the control cells, P<0.001). CONCLUSIONS/SIGNIFICANCE: These findings suggest that selective inhibition of the KGF/KGFR pathway may provide a useful tool to ameliorate the efficacy of the therapeutic strategies for certain epithelial tumors

Neuropilin 1mediates keratinocyte growth factor signaling in adipose-derived stem cells: potential involvement in adipogenesis

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs

Permissive role for mGlu1 metabotropic glutamate receptors in excitotoxic retinal degeneration

Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3g/kg), which caused the death of >70% of Brn-3a+ RGCs. Systemic administration of the mGlu1 receptor negative allosteric modulator (NAM), JNJ16259685 (2.5mg/kg, s.c.), was largely protective against MSG-induced RGC death. This treatment did not cause changes in motor behavior in the pups. We also injected MSG to crv4 mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in crv4 mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration

Prevalence of sexually transmitted infections and enteric protozoa among homosexual men in western Sicily (south Italy)

Introduction. In recent years an increase in the number of sexu- ally transmitted infections (STIs) in men who have sex with men (MSM) has been reported in different industrialised countries. Because few epidemiological data on the STIs/MSM population in Sicily are available, a survey was conducted to assess the preva- lence of STIs/enteric protozoa and risky sexual behaviours among MSM in western Sicily. Methods. In 2010, 74 MSM with median age of 30 years old, were recruited via networks. All participants to the study were interviewed by anonymous self-administered questionnaire in order to collect social/demographic information, clinic data and STI-related risky sexual behaviours. After completing the ques- tionnaire, blood samples were collected to determine HIV, HCV, HHV8 and Treponema pallidum antibodies; presence of Giardia duodenalis and Cryptosporidium parvum was also investigated in faecal samples by immunofluorescence assay. Results. HIV, HHV8, T. pallidum and Giardia prevalence were 8.1%, 16.2%, 21.6% and 16.4% respectively; all patients were negative for HCV and Cryptosporidium infections. The median values of sexual anal intercourse and oral sex per week were 2 and 1, respectively. 7% of participants always had unprotected anal sex, 50.7% sometimes used condom during sexual anal inter- course and 42.3% always had protected anal sex. All MSM-HIV+ and 7 (43.7%) syphilis seropositives were unaware of their own infection. Discussion. MSM in western Sicily are a high risk group for important STIs. It seems necessary that continuous interventions for preventing HIV/AIDS and other STIs and for improving the level of knowledge of symptoms are needed

A proposal for an evidence-based model of the screening for the colorectal carcinoma in an Italian setting

Introduction. The aim of this paper is to improve the feasibility perception of policymakers, health care workers and target population about the cost-effectiveness of the implementation of colorectal screening as Public Health strategy. Methods. Retrospective study by application of a three-step model designed for a local setting in Sicily (Palermo and its Province) in order to distribute Fecal Occult Blood Tests (FOBTs), offer colonoscopy and surgery, by district allocation of pharmacies, public digestive endoscopic centres and oncologic and general surgery units. Mean adherence to consolidated colorectal screening programs in Italy was applied in order to evaluate the feasibility of an operative model in our area. Results. Applying the model to the target population (269,368 individuals of both sexes), it can be expected a mean percentage of 79% delivered invitation and a mean participation rate of 46.3% accounting for a total of 213,070 invited individuals and 98,651 participating in the first round of the program. Furthermore, considering the national mean of 6% positive FOBT, 82% of colonscopy adhesion and 7% CRC detection rate, it can be scheduled a burden for health care structures involved in the program accounting for 49,325 FOBTs, 2,338 colonscopies and 141 surgeries for each year. Discussion. This work demonstrates the feasibility of a colorectal screening project in our area, showing a sustainable impact for local health care involved structures. Furthermore, this program may be spread as an applicative model to other areas, adapting the project to the needs of the local setting in which the colorectal screening will be organized

Genetic predictors of response to treatment of chronic hepatitis C virus infection in patients from southern Italy

Various clinical and genetic factors affect response to antiviral treatment of chronic hepatitis C virus (HCV) infection. The IL28B single-nucleotide polymorphism (SNP) rs12979860 is associated with a sustained viral response (SVR), and the suppressor cytokine signaling 3 (SOCS3) gene is over-expressed in HCV-1b non-responders. The aim of this study was to look for correlations between genetic, clinical and viral factors implicated in response to antiviral treatment in chronic HCV infection. We evaluated 190 controls and 148 HCV-infected patients (102 HCV-1 and 46 HCV-2). Demographic, metabolic and histological features related to antiviral treatment were recorded. Univariate and multivariate analyses were used to identify correlations between the genetic and non-genetic features examined and response to antiviral treatment. IL28B expression was higher in CC SNPs versus other alleles in controls (P=0.01) and this difference was associated with viral infection (HCV vs controls P=0.006), particularly in HCV-2 patients (P=0.003). SOCS3 and IL28B expression was correlated with controls (P=0.011), whereas there was an inverse correlation between the expression of the two genes in HCV patients and HCV-1b non-responders (P=0.014 and P=0.03, respectively). Multivariate analysis showed that the only independent SVR predictive factor was rapid virological response. The frequency of IL28B rs12979860 SNP alleles in controls (C allele=71.1% and T allele= 28.9%) was comparable to that of the HCV population (C allele=66.6% and T allele=33.4%). Rapid virological response seems to be the only significant independent predictor of an SVR to antiviral treatment. The inverse correlation between SOCS3 and IL28B expression in genotype 1b non-responders suggests that SOCS3 may affect IL28B expression thereby influencing response to antiviral therapy