An overview of Personalized Medicine landscape and policies in the European Union.

BACKGROUND: The spread of Personalized Medicine (PM) over the last decade defined a revolution in healthcare systems. PM is among the priorities of the European Commission's research agenda, which funded the IC2PerMed international project aiming to integrate China into the International Consortium of PM (ICPerMed). In the context of this project, we mapped the existing policies related to PM in the European Union (EU) and at the EU Member States (EU-MS) level. METHODS: PubMed, Google Scholar, Google, Microsoft and national and international institutions' official repositories were searched in order to identify documents on PM-related policies, programmes and action plans at the EU and EU-MS level, published up to December 2020. RESULTS: We identified 28 policies in the EU aimed at improving public health promoting and fostering PM implementation, through some actions including the standardization of good medical practice, use of big data and digital innovation, data sharing and cross-border interoperability, healthcare sustainability, disease prevention and patients'/citizens' engagement. We identified 23 policies at EU-MS level which, notwithstanding national differences, have a common focus, such as patient-tailored treatment and targeted prevention, education of healthcare workers, research and innovation, big data harmonization and healthcare system sustainability. CONCLUSIONS: The definition of an integrated regulatory framework is essential to turn PM into an opportunity for citizens and patients with the involvement of all the stakeholders. This work can provide a valuable tool for decision-makers to define common approaches, priorities for research, development and increase international collaboration, which could overcome the fragmented European scenario and align the future direction on PM.

Optimizing the number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma: A propensity-score matching analysis.

OBJECTIVE: Neoadjuvant chemotherapy and interval debulking surgery are now widely offered in ovarian cancer patients unsuitable for surgery; the number of preoperative NACT cycles to be given is still an issue. Our aim was to compare survival outcomes of patients with advanced ovarian cancer treated with ≤4 or more NACT cycles. METHODS: A cohort of AEOC patients with stage III-IV epithelial OC who underwent NACT followed by IDS was identified. Patients were classified in group A (≤4 cycles) and group B (>4 cycles). Selection bias from the heterogeneity of demographic and clinical characteristics was avoided using propensity score matching (2:1 ratio). RESULTS: 140 (group A) and 70 (group B) patients were included. After the propensity score matching, there were no imbalances in baseline characteristics. BRCA status was associated to improved OS (HR = 0.41; 95%CI 0.18.0.92, p = 0.032) and residual tumor to decreased OS (HR = 1.93; 95%CI 1.08-3.46, p = 0.026). Statistically significant differences were not observed in OS (2-year OS 82.4% for group A versus 77.1% for group B, p = 0.109) and PFS (2-year PFS 29.7% for group A versus 20.0% for group A, p = 0.875). In group B, the administration of >4 cycles was related to an additional chance of achieving complete (12.9%) and partial (34.3%) responses compared to responses after 3-4 cycles. CONCLUSIONS: Receiving more than 4 cycles of NACT is no detrimental in terms of OS and PFS in advanced ovarian cancer. Response rates can increase following further cycles administration.

Gemelli decision tree Algorithm to Predict the need for home monitoring or hospitalization of confirmed and unconfirmed COVID-19 patients (GAP-Covid19): preliminary results from a retrospective cohort study.

OBJECTIVE: To develop a deep learning-based decision tree for the primary care setting, to stratify adult patients with confirmed and unconfirmed coronavirus disease 2019 (COVID-19), and to predict the need for hospitalization or home monitoring. PATIENTS AND METHODS: We performed a retrospective cohort study on data from patients admitted to a COVID hospital in Rome, Italy, between 5 March 2020 and 5 June 2020. A confirmed case was defined as a patient with a positive nasopharyngeal RT-PCR test result, while an unconfirmed case had negative results on repeated swabs. Patients' medical history and clinical, laboratory and radiological findings were collected, and the dataset was used to train a predictive model for COVID-19 severity. RESULTS: Data of 198 patients were included in the study. Twenty-eight (14.14%) had mild disease, 62 (31.31%) had moderate disease, 64 (32.32%) had severe disease, and 44 (22.22%) had critical disease. The G2 value assessed the contribution of each collected value to decision tree building. On this basis, SpO2 (%) with a cut point at 92 was chosen for the optimal first split. Therefore, the decision tree was built using values maximizing G2 and LogWorth. After the tree was built, the correspondence between inputs and outcomes was validated. CONCLUSIONS: We developed a machine learning-based tool that is easy to understand and apply. It provides good discrimination in stratifying confirmed and unconfirmed COVID-19 patients with different prognoses in every context. Our tool might allow general practitioners visiting patients at home to decide whether the patient needs to be hospitalized.

Sustainable and personalized nutrition: From earth health to public health.

Sustainable nutrition, equaling earth health, involves a personalized approach designed in terms of precision and avoidance of still cogent but unjustified dogmas, equaling public health. For instance, current dietary recommendations continue to dwell on the need to limit as much as possible the intake of saturated fatty acids (SFA), notwithstanding the mounting evidence that the effects of food on health cannot be predicted from the content of single nutrients without considering the overall macronutrient composition and the role of the food matrix. The traditional recommendation to restrict SFA ignores that their effects on health depend on the interaction between naturally occurring food components and those introduced by food processing. It is warranted to modify the still widely promoted dietary guidelines based upon such single nutrients as SFA and instead personalize dietary habits on the basis of the whole pattern of the food matrix. Accordingly, the double edge of malnutrition, that involves deficiency as well as excess and materializes in many individuals throughout their life course, might be tackled by implementing sustainability, with the additional effect of overcoming global inequalities. Within this context SFA may regain their position of tasty and cheap sources of energy to be adapted to each individual lifestyle.

Mediterranean diet and the prevention of non-alcoholic fatty liver disease: results from a case-control study.

OBJECTIVE: Few studies report that Mediterranean dietary (MD) pattern has a beneficial role in the progression of non-alcoholic fatty liver disease (NAFLD). Evidence on its potential effect on the onset of disease are, however, scanty. With our study, we evaluated whether MD affects the risk of NAFLD with a large case-control study performed in Italy. PATIENTS AND METHODS: Three hundred and seventy-one cases of NAFLD and 444 controls were questioned on the demographic data and their dietary habits before diagnosis. Additionally, information about lifestyles and other related diseases, such as hypertension and diabetes mellitus were collected. The MD adherence was assessed using a pre-defined Mediterranean Diet Score (MDS). Odds ratios (OR) and 95% confidence intervals (CI) were obtained using a multiple logistic regression model. RESULTS: A high adherence to the MD is significantly associated with decreased risk of NAFLD (OR: 0.83 95% CI: 0.71-0.98). When the different MD components were examined separately, higher legumes consumption (OR: 0.62 95% CI: 0.38-0.99) and high fish consumption (OR 0.38 95% CI: 0.17-0.85) were reported to be protective against NAFLD. CONCLUSIONS: Our study shows that a high adherence to the MD decreases the risk of NAFLD.

Rapid molecular tests for detection of antimicrobial resistance determinants in Gram-negative organisms from positive blood cultures: a systematic review and meta-analysis.

BACKGROUND: Timely detection of antimicrobial (cephalosporin/carbapenem) resistance (AMR) determinants is crucial to the clinical management of bloodstream infections caused by Gram-negative bacteria (GNB). OBJECTIVES: To review and meta-analyse the evidence for using commercially available molecular tests for the direct detection of AMR determinants in GNB-positive blood cultures (PBCs). DATA SOURCES: PubMed, Scopus and ISI Web of Knowledge. STUDY ELIGIBILITY CRITERIA: Clinical studies evaluating the performance of two major commercial systems, namely the Verigene® and FilmArray® systems, for rapid testing of GNB-PBCs, in comparison with the phenotypic or genotypic methods performed on GNB-PBC isolates. METHODS: Literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria and, for meta-analysis of sensitivity and specificity of both systems, bivariate random-effects model. RESULTS: Twenty studies were identified (3310 isolates) from 2006 to 2019. Nine studies were conducted in East Asia. In 15 studies using phenotypic comparators (1930 isolates), 1014 (52.5%) isolates were Escherichia coli, and 287 (14.9%) of all the isolates displayed AMR phenotypes. In five studies using genotypic comparators (1380 isolates), 585 (42.4%) were E. coli, and 100 (7.2%) of all the isolates displayed AMR genotypes. Pooled sensitivity and specificity estimates for detection of AMR determinants by the Verigene (i.e. CTX-M, IMP, KPC, NDM, OXA and VIM) and/or FilmArray (i.e. KPC) systems were 85.3% (95% CI 79.9%-89.4%) and 99.1% (95% CI 98.2%-99.5%), respectively, across the 15 studies, and 95.5% (95% CI 89.2%-98.2%) and 99.7% (95% CI 99.1%-99.9%), respectively, across the five studies. CONCLUSIONS: Our findings show that the Verigene and FilmArray systems may be a valid adjunct to the conventional microbiology (phenotypic or genotypic) methods used to identify AMR in GNBs. The FilmArray system detects only one AMR genotype, namely KPC, limiting its use. Both Verigene and FilmArray systems can miss important cephalosporin/carbapenem resistance phenotypes in a minority of cases. However, the sensitivity and specificity of both systems render them valuable clinical tools in timely identification of resistant isolates. Further studies will establish the prominence of such rapid diagnostics as standard of care in individuals with bloodstream infections.

Hormone replacement therapy after prophylactic risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A meta-analysis.

BACKGROUND: Hormone replacement therapy (HRT) has been tested in women with BRCA1 and BRCA2 mutations who underwent risk-reducing salpingo-oophorectomy (RRSO), but its effect on breast cancer (BC) risk has never been appraised using meta-analysis comparison. We performed the first meta-analysis aimed to clarify whether HRT after RRSO could negatively impact on BC risk in women carriers of BRCA1 and BRCA2 mutations. METHODS AND MATERIAL: Pubmed and Scopus databases were searched to retrieve articles written in the English language. Trials comparing RRSO with or without HRT were identified and only those trials with available BC events were included. BC risk was the main endpoint. RESULTS: Three trials with 1100 patients were included. There was not a significantly higher BC risk in BRCA1 and BRCA2 mutation carriers receiving HRT after RRSO (HR = 0.98; 95% CI 0.63-1.52). There was a slightly but not significantly, benefit in BC risk reduction in favor of estrogen alone HRT versus estrogen plus progesterone HRT formulation (OR = 0.53; 95% CI 0.25-1.15). CONCLUSION: HRT use after RRSO in BRCA 1 and BRCA2 mutation carries does not affect BC risk. Comparison of the different HRT types suggests that estrogen alone should be related to lowest BC risk.

Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutated patients: An evidence-based approach on what women should know.

This review is focused on the ovarian cancer risk reduction management in BRCA mutation carriers and is intended to assist with clinical decision-making. Obviously, treatment decisions must be based on the available evidence. Despite risk-reducing salpingo-oophorectomy is firmly recommended, several separate questions can be raised to address the variety of intense controversy of this approach. A special emphasis lies in the effective preventive surgical measure against ovarian cancer risk, in an attempt to detect the optimal timing and mitigate the impact on patients. The long term implications of risk-reducing salpingo-oophorectomy as well as hormone replacement therapy are also actively debated. This is expected to represent an opportunity for improved management modelling of BRCA mutated patients.

Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. PATIENTS AND METHODS: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. RESULTS: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. CONCLUSIONS: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.

Sustainability of Endovenous Iron Deficiency Anaemia Treatment: Hospital-Based Health Technology Assessment in IBD Patients.

Iron deficiency anaemia (IDA) is the main extraintestinal manifestation affecting patients with inflammatory bowel disease (IBD). The Health Technology Assessment approach was applied to evaluate the sustainability of intravenous (IV) iron formulations in the Italian hospital setting, with particular focus on ferric carboxymaltose. Data on the epidemiology of IBD and associated IDA, in addition to the efficacy and safety of IV iron formulations currently used in Italy, were retrieved from scientific literature. A hospital-based cost-analysis of the outpatient delivery of IV iron treatments was performed. Organizational and ethical implications were discussed. IDA prevalence in IBD patients varies markedly from 9 to 73%. IV iron preparations were proven to have good efficacy and safety profiles, and ferric carboxymaltose provided a fast correction of haemoglobin and serum ferritin levels in iron-deficient patients. Despite a higher price, ferric carboxymaltose would confer a beneficial effect to the hospital, in terms of reduced cost related to individual patient management and additionally to the patient by reducing the number of infusions and admissions to healthcare facilities. Ethically, the evaluation is appropriate due to its efficacy and compliance. This assessment supports the introduction of ferric carboxymaltose in the Italian outpatient setting.

Prognostic factors in head and neck cancer: a 10-year retrospective analysis in a single-institution in Italy.

This study was undertaken to evaluate the association between demographics, lifestyle habits, and clinical data and overall survival (OS), recurrence and second primary cancer (SPC) in patients with first primary head and neck cancer (HNC). We retrospectively reviewed data from 482 patients treated at the "Agostino Gemelli" Teaching Hospital, Rome, between 2002-2012 for primary HNC. Individual parameters were evaluated for association with specific outcomes such as OS, cancer recurrence and second primary cancer (SPC) appearance using hazard ratios (HR) and 95% confidence intervals (CIs). Five-year OS was 60.6% for all HNC cases, 49.0% for oral cavity, 54.8% for oropharynx, 50.0% for hypopharynx and 63.4% for larynx. Predictors of OS were older age (HR = 1.04; 95% CI: 1.02-1.05) and advanced tumour stage (HR = 2.00; 95% CI: 1.41-2.84). The risk of recurrence was associated with drinking 8-14 drinks per week (HR = 1.73; 95% CI: 1.00-2.97). The risk of developing SPC increased with advanced tumour stage (HR = 2.75; 95% CI: 1.39-5.44) and with smoking for more than 40 years (HR = 3.68; 95% CI: 1.10-12.30). OS differed among HNC sites. Increasing age was an unfavourable predictor of HNC OS. Tumour stage was a prognostic factor both for OS and for risk of developing SPC. Alcohol and tobacco consumption were prognostic factors for recurrence and SPC, respectively.

Current state of genomic policies in healthcare among EU member states: results of a survey of chief medical officers.

Background: A need for a governance of genomics in healthcare among European Union (EU) countries arose during an international meeting of experts on public health genomics (PHG). We have conducted a survey on existing national genomic policies in healthcare among Chief Medical Officers (CMOs) of the 28 EU member states, plus Norway. Methods: A questionnaire was sent to CMOs after a meeting on the policy implications of PHG held during the Italian presidency of the Council of EU in 2014. The survey was closed in November 2015. Results: CMOs response rate was 65.5% (19/29). Twelve (63.2%) reported that their countries had a policy for genomics in healthcare in place, and 15 (78.9%) reported that public funding existed. Public research facilities for the development of such policies were documented in 13 (68.4%) countries, and 15 (83.3%) had working groups devoted to policy development. National agencies carrying out Health Technology Assessment of genomic-based technologies were present in nine countries (50%). Sixteen (88.9%) countries reported having agencies dealing with ethical issues related to genomic technologies. About 55% of countries disclosed the lack of information campaigns aimed at citizens, and 44.4% reported they had a legal framework for direct-to-consumer genetic tests. Conclusion: Belgium, France, Italy, Spain and UK documented the presence of a policy on genomics in healthcare. While many caveats are necessary because of the methodology, results suggest a need for a co-ordinated effort to foster development and harmonization of dedicated policies across EU to responsibly integrate genomics policies into existing health systems.

Fatty acids profiling reveals potential candidate markers of semen quality.

Previous reports showed altered fatty acid content in subjects with altered sperm parameters compared to normozoospermic individuals. However, these studies focused on a limited number of fatty acids, included a short number of subjects and results varied widely. We conducted a case-control study involving 155 patients allocated into four groups, including normozoospermia (n = 33), oligoasthenoteratozoospermia (n = 32), asthenozoospermia (n = 25), and varicocoele (n = 44). Fatty acid profiling, including 30 species, was analyzed by a validated gas chromatography (GC) method on the whole seminal fluid sample. Multinomial logistic regression modeling was used to identify the associations between fatty acids and the four groups. Specimens from 15 normozoospermic subjects were also analyzed for fatty acids content in the seminal plasma and spermatozoa to study the distribution in the two compartments. Fatty acids lipidome varied markedly between the four groups. Multinomial logistic regression modeling revealed that high levels of palmitic acid, behenic acid, oleic acid, and docosahexaenoic acid (DHA) confer a low risk to stay out of the normozoospermic group. In the whole population, seminal fluid stearic acid was negatively correlated (r = -0.53), and DHA was positively correlated (r = 0.65) with sperm motility. Some fatty acids were preferentially accumulated in spermatozoa and the highest difference was observed for DHA, which was 6.2 times higher in spermatozoa than in seminal plasma. The results of this study highlight complete fatty acids profile in patients with different semen parameters. Given the easy-to-follow and rapid method of analysis, fatty acid profiling by GC method can be used for therapeutic purposes and to measure compliance in infertility trials using fatty acids supplements.

Risk factors for neuroendocrine neoplasms: a systematic review and meta-analysis.

BACKGROUND: Neuroendocrine neoplasms (NENs) are rare cancers mainly of lung and digestive tract. Little is known on risk factors. The aim of this work is to define the risk factors for NEN development by extensive review and meta-analysis of published data. METHODS: The search was conducted on Medline, Scopus, and Web of Science following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Newcastle-Ottawa scale was used for study quality. Meta-analyses were conducted by primary site. Odds ratio (OR), hazard ratio, risk ratio, standardized incidence ratio, and associated 95% confidence intervals (CIs) were abstracted. Data were combined and analyses carried out for risk factors considered by at least two studies. Random-effects model was adopted for study variation. RESULTS: Of 1535 extracted articles, 24 were enrolled. Meta-analyses were possible for pancreas, small intestine, and rectum. Risk for NEN associated with: (i) family history of cancer at all investigated sites (lung, stomach, pancreas, small intestine, appendix, and colon; OR 2.12 [95% CI 1.40-3.22, I(2) = 0.0%, P = 0.681] at meta-analysis in pancreas); (ii) body mass index (BMI) or diabetes (stomach, pancreas, and small intestine; OR of 2.76 [95% CI 1.65-4.64, I(2) = 58.5%, P = 0.090] for diabetes at meta-analysis in pancreas); (iii) cigarette smoking (lung, stomach, pancreas, and small intestine; OR of 1.34 [95% CI 1.10-1.63, I(2) = 0.0%, P = 0.780] and of 1.59 [95% CI 1.07-2.37, I(2) = 32.9%, P = 0.225] for smokers versus never-smokers at meta-analysis for pancreas and small intestine); (iv) alcohol consumption (pancreas and rectum; OR of 2.44 [95% CI 1.07-5.59, I(2) = 65.8%, P = 0.054] and of 1.53 [95% CI 0.99-2.35, I(2) = 0.0%, P = 0.630] for heavy drinkers versus never-drinkers at meta-analysis for pancreas and rectum). CONCLUSIONS: Family history of cancer is the most relevant risk factor for NEN development at all investigated sites, followed by BMI and diabetes. Cigarette smoking and alcohol consumption are potential risk factors for selected anatomical sites.

Prognostic factors and outcomes in Italian patients undergoing curative gastric cancer surgery.

BACKGROUND: Survival of patients after curative surgical resection for gastric cancer (GC) remains poor, thus emphasizing the need for better definition of prognostic factors to improve the long-term course of disease. METHODS: From 1999 to 2009, 110 patients had curative-intent gastrectomy for adenocarcinoma. Clinicopathological features, Helicobacter pylori infection, dietary habits and lifestyle, and the presence of proinflammatory gene polymorphisms were evaluated. RESULTS: At the end of follow-up, 55 deaths had occurred, 48 of them due to GC, whereas the median overall survival (OS) and disease-free survival (DFS) were 62 and 51 months, respectively. From the Kaplan-Meier analysis and log-rank test, statistically significant differences in OS and DFS were found for tumor site (only for DFS), tumor size, lymph node metastasis ratio (NR), and tumor-node-metastasis stage, but not for age, comorbidity, H. pylori infection, cigarette smoking, and IL1B or TNFA polymorphisms. Multivariable Cox regression analysis revealed NR was an independent prognostic factor for OS and DFS. Cardia tumor and patient age 65 years or older were also independent prognostic factors for OS and DFS. CONCLUSIONS: Tumor-related factors remain strongest predictors of survival in GC patients after surgery. Particularly, NR was an effective feature in identifying patients at high risk for adverse outcome.

Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

BACKGROUND: The objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. PATIENTS AND METHODS: We conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. RESULTS: Ninety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. CONCLUSION: We report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.

A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes, cell cycle control and alcohol metabolism.

The purpose of this report is to review the relationship between genetic polymorphisms involved in carcinogen metabolism, alcohol metabolism and cell-cycle control with the risk of head and neck cancer. The review was performed on available studies on genetic polymorphisms and head and neck cancer (HNC) published in PubMed up to September 2011. 246 primary articles and 7 meta-analyses were published. Among these, a statistically significant association was reported for glutathione S-transferases (GSTM1), glutathione S-transferases (GSTT1) and human microsomal epoxide hydrolase (EPHX1) genes. An increased risk for HNC was also associated reported for P53 codon 72 Pro/Pro, ALDH2 and three variants of the ADH gene: ADH1B (rs1229984), ADH7 (rs1573496) and ADH1C (rs698).

Could antispasmodic drug reduce pain during hysterosalpingo-contrast sonography (HyCoSy) in infertile patients? A randomized double-blind clinical trial.

OBJECTIVE: To assess the effectiveness of an antispasmodic drug, hyoscine-N-butylbromide, in reducing pain during hysterosalpingo-contrast sonography (HyCoSy). METHODS: Eight hundred and sixteen patients undergoing HyCoSy were randomized to receive 10 mg hyoscine-N-butylbromide (n = 408) or placebo (n = 408) per os, 30 min before the procedure, in a double-blind randomized controlled trial. Immediately after the procedure, the patient was asked to describe any pain experienced in comparison with pain usually suffered during the menstrual cycle, and the operator assigned a pain score between 0 and 4 as follows: 0 (no reaction or discomfort), 1 (slight pain, less than menstrual pain), 2 (moderate pain, exceeding menstrual cramps but no vasovagal reaction), 3 (vasovagal reaction or pain requiring observation in a hospital) and 4 (vasovagal reaction or pain requiring resuscitation). The primary aim was to estimate the difference in pain score, considered as a categorical value, between the active arm of the trial and the control group. The secondary aim was to evaluate if pain is related to tubal patency. RESULTS: There was no difference in pain score between the hyoscine-N-butylbromide group and the placebo group (P = 0.807). There was a negative correlation between pain and tubal patency, regardless of treatment group (P < 0.0001). CONCLUSIONS: Administration of 10 mg antispasmodic drug hyoscine-N-butylbromide does not reduce pain in patients undergoing HyCoSy.

Intestinal parasites isolated in a large teaching hospital, Italy, 1 May 2006 to 31 December 2008.

Intestinal parasites account for the majority of parasitic diseases, particularly in endemic areas. Most are transmitted via contaminated food. Because of increased immigration and travel, enteric parasitoses are now distributed worldwide. Between May 2006 and December 2008, we examined stool specimens from 5,351 patients (4,695 Italians, 656 non-Italians) for ova and parasites using microscopy, culture techniques, and molecular methods. Stools from 594 patients (11.1%) were contaminated and for all patients samples combined, a total of 700 intestinal parasites were counted. Ninety of the 594 infected patients had more than one parasite in their stools. Parasites causing intestinal disease occurred in 8.8% of patients. The prevalence was over twice as high among non-Italians (26.8% vs 8.9% in Italians, p<0.001) and higher in males (13.0% vs 9.5% in females, p=0.003). Most isolates were pathogenic protozoa, including in decreasing order of frequency: Blastocystis hominis, Giardia intestinalis, Entamoeba histolytica, and Cyclospora cayetanensis. The latter two species tended to be more common in Italians, although not at significant level (3.6% (15/418) vs 1.7% (3/176) in non-Italians, OR: 2.15; 95%CI: 0.60­11.70, p=0.22). Helminthes were found in 28 patients, mainly non-Italians (5.7% (10/176) vs 4.3% (18/418), OR: 1.34; 95%CI: 0.54­3.13, p=0.47). Ascaris lumbricoides and Hymenolepis nana were the most common. Strongyloides stercoralis, Enterobius vermicularis, Taenia spp. and Trichuris trichiura were also found. Intestinal parasites are a serious problem in developing countries, but should not be underestimated in industrialised countries.

Ratio of metastatic lymph nodes: impact on staging and survival of gastric cancer.

AIMS: No consensus exists on the level and number of lymph nodes to be dissected and examined for accurate staging of patients with resectable gastric cancer. The aim of this study was to examine the prognostic value and staging accuracy of the metastatic lymph nodes ratio (NR). METHODS: The postoperative survival of 247 patients with gastric cancer who underwent gastrectomy was analyzed. Lymph nodes status was assigned according to three different classifications: 6th UICC/AJCC TNM; JGCA; NR (NR0: 0%; NR1: < or =20%; NR2: >20%). Staging accuracy of the three classifications was compared according to patients survival. RESULTS: A significant difference in survival was observed in patients with NR1 versus NR2. At multivariate analysis only NR along with pT and grading were found to be independent prognostic factors. Stage migration was present in 84 cases (51%) with JGCA classification, in 30 (19%) with 6th UICC/AJCC TNM classification and in only 18 cases (11%) when NR was applied. CONCLUSIONS: Our data showed that NR is a simply reproducible and highly reliable staging system with a strong ability to predict patients' outcome. Compared to other nodal staging classifications, NR is less influenced from the number of the lymph nodes dissected and examined, reducing the stage migration phenomenon.