Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer.

BACKGROUND: The immune contexture predicts prognosis in human colorectal cancer (CRC). Whereas tumour-infiltrating CD8+ T cells and myeloid CD16+ myeloperoxidase (MPO)+ cells are associated with favourable clinical outcome, interleukin (IL)-17-producing cells have been reported to correlate with severe prognosis. However, their phenotypes and functions continue to be debated. OBJECTIVE: To investigate clinical relevance, phenotypes and functional features of CRC-infiltrating, IL-17-producing cells. METHODS: IL-17 staining was performed by immunohistochemistry on a tissue microarray including 1148 CRCs. Phenotypes of IL-17-producing cells were evaluated by flow cytometry on cell suspensions obtained by enzymatic digestion of clinical specimens. Functions of CRC-isolated, IL-17-producing cells were assessed by in vitro and in vivo experiments. RESULTS: IL-17+ infiltrates were not themselves predictive of an unfavourable clinical outcome, but correlated with infiltration by CD8+ T cells and CD16+ MPO+ neutrophils. Ex vivo analysis showed that tumour-infiltrating IL-17+ cells mostly consist of CD4+ T helper 17 (Th17) cells with multifaceted properties. Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release. Consistent with these findings, the presence of intraepithelial, but not of stromal Th17 cells, positively correlated with improved survival. CONCLUSIONS: Our study shows the dual role played by tumour-infiltrating Th17 in CRC, thus advising caution when developing new IL-17/Th17 targeted treatments.

Patient-reported outcomes (PROs): the significance of using humanistic measures in clinical trial and clinical practice.

Patient-reported outcome (PRO) is an "umbrella term" that covers a whole range of potential types of measurement but it is used specifically to refer to all measures quantifying the state of health through the evaluation of outcomes reported by the patient himself/herself. PROs are increasingly seen as complementary to biomedical measures and they are being incorporated more frequently into clinical trials and clinical practice. After considering the cultural background of PROs - that is the well known patient-centered model of medicine -, their historical profile (since 1914, the year of the first outcome measure) and typologies, the paper aims at debating their methodological complexity and implementation into practice. Some clinical trials and therapeutic managements utilizing patient-centered measures will be also analyzed.

[Patient-reported outcomes (PRO): historical profile, definitions, classifications and problems]. / Patient-reported outcomes (PRO): profilo storico, definizioni, classificazioni e criticità.

This contribution deals with the use, within healthcare systems, of patient-reported outcomes (PROs), i.e., all measures aimed at quantifying the state of health through the evaluation of outcomes reported by the patient himself. A survey of their cultural background, identified in the patient-centered model of medicine, is followed by a delineation of their historical profile (from 1914, the year of the first outcome measure, to the more recent examples of their use in clinical trial and practice), a classification based on the size they wish to detect and the reconstruction of the main lines of debate around their use in health care.

Analysis of extracellular superoxide dismutase in fibroblasts from patients with systemic sclerosis.

Systemic sclerosis (SSc) is a chronic disease of connective tissue characterized by vascular damage, autoantibody production and extensive fibrosis of skin, skeletal muscles, vessels and visceral organs. Fibrosis is a biological process involving inflammatory response and reactive oxygen species (ROS) accumulation leading to fibroblast activation. Extracellular superoxide dismutase (SOD3), a copper and zinc superoxide dismutase, which is expressed in selected tissues, is secreted into the extracellular space and catalyzes the dismutation of superoxide radical to hydrogen peroxide and molecular oxygen. Moreover, SOD3 is associated to inflammatory responses in some experimental models. In this paper we analysed, by RT-PCR and immunofluorescence, SOD3 expression and intracellular localization in dermal fibroblasts from both healthy donors and patients affected by diffuse form of SSc. Moreover, we determined SOD3 enzymatic activity in fibroblast culture medium with the xanthine/xanthine oxidase method. Increased expression of SOD3 mRNA was detected in systemic sclerosis fibroblasts (SScF), as compared to control healthy fibroblasts (HF), and SOD3 immunofluorescence staining displayed a characteristic pattern of secretory proteins in both HF and SScF. Superoxide dismutase assay demonstrated that SOD3 enzymatic activity in SScF culture medium is four times more than in HF culture medium. These data suggest that an alteration in SOD3 expression and activity could be associated to SSc fibrosis.

Role for the families in child involving research.

In a clinical research which involves disabled children, family plays a fundamental role for the stipulation of consent - according to international ethical guidelines - as well as it has to be considered one of the main caregivers in this context. Therefore this fundamental role has to be recognized when considering the development of pediatric research programs, in which the family should be involved. In fact, therapeutic alliance between families and researchers should be considered, not only as a fundamental basis for children health and well-being, but also as an important resource for better outcomes in terms of research, health care and efficacy.

Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer.

BACKGROUND: The aim of this study was to elucidate the prognostic impact of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and aldehyde dehydrogenase-1 (ALDH1) in colorectal cancer. METHODS: A tissue microarray of 1420 primary colorectal cancers and 57 normal mucosa samples was immunostained for CD133, CD166, CD44s, EpCAM, and ALDH1 in addition to 101 corresponding whole tissue sections. Invasive potential of three colorectal cancer cell lines was tested. RESULTS: Differences between normal tissue and cancer were observed for all markers (P<0.001). Loss of membranous CD166 and CD44s were linked to higher pT (P=0.002, P=0.014), pN (P=0.004, P=0.002), an infiltrating growth pattern (P<0.001, P=0.002), and worse survival (P=0.015, P=0.019) in univariate analysis only. Loss of membranous EpCAM expression was also linked to higher pN (P=0.023) and infiltrating growth pattern (P=0.005). The CD44s, CD166, and EpCAM expression were lost towards the invasive front. The CD44-/CD166- cells from three colorectal cancer cell lines exhibited significantly higher invasive potential in vitro than their positive counterparts. CONCLUSIONS: Loss, rather than overexpression, of membranous CD44s, CD166, and EpCAM is linked to tumour progression. This supports the notion that the membranous evaluation of these proteins assessed by immunohistochemistry may be representative of their cell adhesion rather than their intra-cellular functions.

Endoscopic removal of alloplastic sinus graft material via a wide middle antrotomy.

The purpose of this paper is to discuss the treatment required for a patient affected by chronic maxillary sinusitis following a sinus grafting procedure with an alloplastic material. Sinusitis was not the consequence of migration of alloplastic material into the maxillary sinus, but rather the consequence of overfilling the subantral space followed by obstruction of the ostium. The treatment involved removal of the alloplastic material and correction of the ostium obstruction via a nasal endoscopic approach.

Bioethics, bridge to medical education.

INTRODUCTION: Research in education assumes that every intuition regarding the improvement of the educational process is followed by one demonstration and foundation. Creativeness and rigour with the relative implications in the context of research and difficulties are the two main elements. OBJECTIVES AND DIFFICULTIES: The knowledge that features the transition from a PHOG approach in teaching: prejudice, hunches, opinions, guess to an evidence-based education is not easy to collect, to document and to generalize. But this is still not easy to apply in a context that is very difficult to improve, to know and to check. To obtain high quality education research activity is needed, because the costs and consequences of the non quality are very high and serious and the relapsing could be very important from the assistance, social prevention and clinical research point of view. CONCLUSIONS: In the university research is done in everyone's cultural area, but it should also be done in the teaching area. This is important especially in a faculty of medicine where education depends on continuous improvements in assistance and also in the prevention to be carried out through projects aiming at education to health.

Reasons for not exercising and exercise intentions: a study of middle-aged sedentary adults.

The aims of this study were to assess why people do not participate in exercise and physical activity, and what might lead them to become active. More specifically, we focused on the hindrances to entering the phase of transition from a sedentary to a more active lifestyle by analysing the reasons 265 middle-aged Belgian adults gave for their inactivity. Their justifications were examined in relation to the conditions which they say would be needed for them to become more involved in regular physical activity. Factor analysis revealed that the reasons for inactivity referred to the adults' self-concept, to cognitive cost-benefit based processes and to negative emotions associated with exercise. The conditions reported to be necessary to begin exercising referred to a perceived decrease in health and to the appropriateness of the exercise offered. Discriminant analysis showed that 'never-exercisers' differed from 'ex-exercisers', and that within the subgroup of 'ex-exercisers' the long-term drop-outs differed from the recent drop-outs. Cluster analysis revealed three types of sedentary adults: the unconcerned, the opposed and the approachable.

Postsurgical dyskeratosis treated with topical and parenteral administration of vitamin A.

A severe case of conjunctival dyskeratosis was resolved by treatment with high doses of vitamin A administered both topically and parenterally. This result, which was confirmed by cytology, and the lack of adverse effects suggest that vitamin A administration might be a valid alternative to surgery in cases of dyskeratosis.

Quality of life and neoplastic diseases. Ethical issues.

The article analyses the concept of the quality of life comparing two different ethical approaches, that is "catholic" personalist bioethics and "lay" bioethics. As regards the oncological field, personalist bioethics defends the respect for life as an absolute value (sanctity of life), while "lay" bioethics focuses attention on the patient's autonomy. The authors think that in oncological therapies the subjective evaluation of the patient must be taken into consideration as the expression of his/her personal concept of the quality of life, always with priority of the respect of life.

Quality of life in gynaecological oncology. The personalist perspective of bioethics.

Quality of life in gynaecological neoplastic diseases assumes a specific role within the therapeutic choice. Gynaecologists must give attention to the possibility of the patient's identity crises: a woman's reconstruction of her psycho-physical identity as regards gynaecological cancer is particularly difficult. Psychological assistence acquire a relevant role in improving the patient's quality of life. Personalist bioethics proposes a concept of corporeity which considers body not only in the physical aspect but also as an expression of subjectivity and totality of the person.

Papaverine hydrochloride as an adjunct to asanguinous cardioplegia, is it beneficial?

Papaverine hydrochloride was added to a standard asanguinous cardioplegic solution to study its effect on cardioplegic distribution by evaluating coronary resistance, myocardial temperature, and postoperative enzyme changes. Seventeen patients were randomized into a control group (8 patients) and a papaverine group (9 patients). All patients received 300 cc of a standard asanguinous cardioplegic solution into the aortic root after systemic cooling to 28 degrees C and measurement of septal temperature (To). The duration of infusion (t1), root pressure (p1), and septal temperature (T1) were recorded. All patients received a subsequent infusion of 200 cc of cardioplegia to which had been added either 10 cc normal saline (control group) or 1 mg papaverine hydrochloride in 10 cc normal saline (papaverine group). Time of infusion, root pressure, and septal temperature (t2, p2, T2) were recorded. Coronary resistance was calculated. Postoperative CPK and CPK-MB were recorded and compared. Mean high CPK in the papaverine group was 163 units and 182 units in the control group. There was no statistically significant difference in any parameter between groups. This study, in contradistinction to experience with animal research models, failed to demonstrate any significant value in adding papaverine hydrochloride to standard cardioplegic solutions.