Prevalence of SARS-CoV-2, Verona, Italy, April-May 2020.

We used random sampling to estimate the prevalence of severe acute respiratory syndrome coronavirus 2 infection in Verona, Italy. Of 1,515 participants, 2.6% tested positive by serologic assay and 0.7% by reverse transcription PCR. We used latent class analysis to estimate a 3.0% probability of infection and 2.0% death rate.

Enhancer of zeste 2 polycomb repressive complex 2 subunit polymorphisms in melanoma skin cancer risk.

Melanoma is the most deadly skin cancer, and its incidence is growing. EZH2, a member of the Polycomb Group (PcGs) proteins family, plays an important biological role in the occurrence and development of melanoma. EZH2 germline genetic polymorphisms have not been yet evaluated in melanoma predisposition. Three hundred thirty sporadic Italian melanoma patients and 333 healthy volunteers were genotyped to analyse the association between EZH2 variants rs6950683, rs2302427, rs3757441, rs2072408 and melanoma risk. The functionality of rs6950683 alleles was investigated in keratinocytes (HaCat), melanoma cells (A375) and human embryonic kidney cells (HEK293), using promoter-reporter assays. Genotype distribution of SNPs showed that rs6950683T and rs3757441C alleles were positively associated with melanoma risk (P = .003 and .004, respectively). Haplotype analysis revealed that TCCA and CCCG haplotypes were associated with a higher risk of melanoma (P = .02 and .04, respectively). Functional assays demonstrated that allele rs6950683T reduce promoter activity in the three cell lines analysed compared to C allele. rs6950683T and rs3757441C alleles in the EZH2 gene appear positively associated with melanoma risk in the analysed population. In addition, we demonstrated for the first time the functional role of rs6950683 upstream polymorphism on EZH2 gene expression regulation.

Pro: Vascular access surveillance in mature fistulas: is it worthwhile?

Guidelines recommend regular screening of mature arteriovenous fistulas (AVFs) for preemptive repair of significant stenosis (≥50% lumen reduction) at high risk of thrombosis, identifiable from clinical signs of access dysfunction (monitoring) or by measuring access blood flow (Qa surveillance), which also enables stenosis detection in functional accesses. To compare the value of Qa surveillance versus monitoring, a meta-analysis was performed on the randomized controlled trials (RCTs) comparing the two screening strategies. It emerged that correcting stenosis identified by Qa surveillance significantly halved the risk of thrombosis [relative risk (RR) = 0.51, 95% confidence interval (CI) 0.35-0.73] and access loss (RR = 0.47, 95% CI 0.28-0.80) in comparison with intervention prompted by clinical signs of access dysfunction. One small RCT aiming to identify an optimal Qa threshold showed that stenosis repair at Qa >500 mL/min produced a significant 3-fold reduction in the risk of thrombosis (RR = 0.37, 95% CI 0.12-0.97) and access loss (RR = 0.36, 95% CI 0.09-0.99) in comparison with intervening when Qa dropped to <400 mL/min as per guidelines. To test the real-world benefits of Qa surveillance, the expected RCT-based thrombosis and access loss rates with Qa surveillance were compared with the rates with monitoring reported in observational studies: the expected thrombosis and access loss rates with surveillance were only lower than with monitoring when a Qa >500 mL/min was considered (2.4, 95% CI 1.0-4.6 and 2.2, 95% CI 0.7-5.0 versus 9.4, 95% CI 7.4-11.3 and 10.3, 95% CI 7.7-13.4 events per 100 AVFs-year, P ≤ 0.024), suggesting that in clinical practice adopting Qa surveillance may only be worthwhile at centres with high thrombosis and access loss rates associated with monitoring, and adopting Qa thresholds >500 mL/min for elective stenosis repair.

Knowledge and use of e-cigarettes among nursing students: results from a cross-sectional survey in north-eastern Italy.

BACKGROUND: Data on electronic cigarette (e-cigarette) use among health professional students, who can play a central role in promoting healthy habits and smoking cessation, are sparse. Moreover, the association between e-cigarettes and smoking habits is still debated. The present study aimed to investigate the diffusion of e-cigarette use among nursing students in north-eastern Italy and explore its association with tobacco smoking. METHODS: In 2015, a questionnaire focused on e-cigarette use and tobacco smoking habits was anonymously administered to 2020 students attending nursing courses held by Verona University in 5 different centres. Of these students, 1463 (72.4%) answered the questionnaire. The influence of e-cigarette ever use on both tobacco smoking initiation in all subjects and smoking cessation among ever smokers was investigated by multivariable logistic models. RESULTS: Most responders were female (77.1%), and the mean (SD) age was 23.2 (4.2) years. Nearly all students (94.7%) had heard about e-cigarettes. Approximately one-third (30.3, 95% CI 27.9-32.7%) had ever used e-cigarettes, but only 2.1% (1.5-3.0%) had used e-cigarettes in the last month. Very few (2.1%) of those responders who had never used e-cigarettes were willing to try them. Prevalence values were much higher for tobacco smoking: 40.9% of responders reported being current tobacco smokers, and 10.1% reported being past smokers. Ever use and current use of e-cigarettes were reported by 57.2 and 4.4% of current tobacco smokers and by 12.0 and 0.6% of never or past smokers, respectively (p < 0.001). In multivariable analysis, students who ever used e-cigarettes had 13 times greater odds of being an ever tobacco smoker than never users, whereas they had three times lower odds of being a former smoker. Only 26 students were currently using both electronic and tobacco cigarettes, and most declared that they used e-cigarettes to stop or reduce tobacco smoking. Of note, only three students reported that they had completely stopped smoking thanks to e-cigarette use. CONCLUSION: Use of e-cigarettes seemed to be rather rare among Italian nursing students and was mainly restricted to current smokers. E-cigarette use was not associated with smoking cessation in nursing students.

Reducing interruptions during medication preparation and administration.

PURPOSE: According to literature, interruptions during drug administration lead to a significant proportion of medication errors. Evidence on the effectiveness of interventions to reduce interruption is still limited. The purpose of this paper is to explore main reasons for interruptions during drug administration rounds in a geriatric ward of an Italian secondary hospital and test the effectiveness of a combined intervention. DESIGN/METHODOLOGY/APPROACH: This is a pre and post-intervention observational study based on direct observation. All nurse staff (24) participated to the study that lead to observe a total of 44 drug dispensing rounds with 945 drugs administered to 491 patients in T0 and 994 drugs to 506 patients in T1. FINDINGS: A significant reduction of raw number of interruptions (mean per round from 17.31 in T0 to 9.09 in T1, p<0.01), interruptions/patient rate (from 0.78 in T0 to 0.40 in T1, p<0.01) and interruptions/drugs rate (from 0.44 in T0 to 0.22 in T1, p<0.01) were observed. Needs for further improvements were elicited (e.g. a greater involvement of support staff). PRACTICAL IMPLICATIONS: Nurse staff should be adequately trained on the risks related to interruptions during drug administration since routine activity is at high risk of distractions due to its repetitive and skill-based nature. ORIGINALITY/VALUE: A strong involvement of both MB and leadership, together with the frontline staff, helped to raise staff motivation and guide a bottom-up approach, able to identify tailored interventions and serve concurrently as training instrument tool.

A comparison between quantitative PCR and droplet digital PCR technologies for circulating microRNA quantification in human lung cancer.

BACKGROUND: Selected microRNAs (miRNAs) that are abnormally expressed in the serum of patients with lung cancer have recently been proposed as biomarkers of this disease. The measurement of circulating miRNAs, however, requires a highly reliable quantification method. Quantitative real-time PCR (qPCR) is the most commonly used method, but it lacks reliable endogenous reference miRNAs for normalization of results in biofluids. When used in absolute quantification, it must rely on the use of external calibrators. Droplet digital PCR (ddPCR) is a recently introduced technology that overcomes the normalization issue and may facilitate miRNA measurement. Here we compared the performance of absolute qPCR and ddPCR techniques for quantifying selected miRNAs in the serum. RESULTS: In the first experiment, three miRNAs, proposed in the literature as lung cancer biomarkers (miR-21, miR-126 and let-7a), were analyzed in a set of 15 human serum samples. Four independent qPCR and four independent ddPCR amplifications were done on the same samples and used to estimate the precision and correlation of miRNA measurements obtained with the two techniques. The precision of the two methods was evaluated by calculating the Coefficient of Variation (CV) of the four independent measurements obtained with each technique. The CV was similar or smaller in ddPCR than in qPCR for all miRNAs tested, and was significantly smaller for let-7a (p = 0.028). Linear regression analysis of the miRNA values obtained with qPCR and ddPCR showed strong correlation (p < 0.001). To validate the correlation obtained with the two techniques in the first experiment, in a second experiment the same miRNAs were measured in a larger cohort (70 human serum samples) by both qPCR and ddPCR. The correlation of miRNA analyses with the two methods was significant for all three miRNAs. Moreover, in our experiments the ddPCR technique had higher throughput than qPCR, at a similar cost-per-sample. CONCLUSIONS: Analyses of serum miRNAs performed with qPCR and ddPCR were largely concordant. Both qPCR and ddPCR can reliably be used to quantify circulating miRNAs, however, ddPCR revealed similar or greater precision and higher throughput of analysis.

Is chest X-ray screening for lung cancer in smokers cost-effective? Evidence from a population-based study in Italy.

BACKGROUND: After implementation of the PREDICA annual chest X-ray (CXR) screening program in smokers in the general practice setting of Varese-Italy a significant reduction in lung cancer-specific mortality (18 %) was observed. The objective of this study covering July 1997 through December 2006 was to estimate the cost-effectiveness of this intervention. METHODS: We examined detailed information on lung cancer (LC) cases that occurred among smokers invited to be screened in the PREDICA study (Invitation-to-screening Group, n = 5815 subjects) to estimate costs and quality-adjusted life-years (QALYs) from LC diagnosis until death. The control group consisted of 156 screening-eligible smokers from the same area, uninvited and unscreened, who developed LC and were treated by usual care. We calculated the incremental net monetary benefit (INMB) by comparing LC management in screening participants (n = 1244 subjects) and in the Invitation-to-screening group versus control group. RESULTS: The average number of QALYs since LC diagnosis was 1.7, 1.49 and 1.07, respectively, in screening participants, the invitation-to-screening group, and the control group. The average total cost (screening + management) per LC case was higher in screening participants (€17,516) and the Invitation-to-screening Group (€16,167) than in the control group (€15,503). Assuming a maximum willingness to pay of €30,000/QALY, we found that the intervention was cost-effective with high probability: 79 % for screening participation (screening participants vs. control group) and 95 % for invitation-to-screening (invitation-to-screening group vs. control group). CONCLUSIONS: Based on the PREDICA study, annual CXR screening of high-risk smokers in a general practice setting has high probability of being cost-effective with a maximum willingness to pay of €30,000/QALY.

How has peritoneal dialysis changed over the last 30 years: experience of the Verona dialysis center.

BACKGROUND: The last decade has witnessed considerable improvement in dialysis technology and changes in clinical management of patients in peritoneal dialysis (PD) with a significant impact on long term clinical outcomes. However, the identification of factors involved in this process is still not complete. METHODS: Therefore, to assess this objective, we retrospectively analyzed clinical records of 260 adult patients who started PD treatment from 1983 to 2012 in our renal unit. For the analysis, we divided them into three groups according to the time of starting dialysis: GROUP A (n: 62, 1983-1992), GROUP B (n: 66, 1993-2002) and GROUP C (n: 132, 2003 to 2012). RESULTS: Statistical analysis revealed that patients included in the GROUP C showed a reduction in mean patients' age (p = 0.03), smoking habit (p = 0.001), mean systolic blood pressure (p < 0.0001) and an increment in hemoglobin levels (p < 0.0001) and residual diuresis (p = 0.016) compared to the other two study groups. Additionally, patients included in GROUP C, mainly treated with automated peritoneal dialysis, showed a reduced risk of all-causes mortality and a decreased risk to develop acute myocardial infarction and cerebrovascular disease. Patients' age, diabetes mellitus and smoking habit were all positively associated with a significant increased risk of mortality in our PD patients, while serum albumin levels and residual diuresis were negatively correlated. CONCLUSIONS: Therefore, the present study, revealed that in the last decade there has been a growth of our PD program with a concomitant modification of our patients' characteristics. These changes, together with the evident technical advances, have caused a significant improvement of patients' survival and a decrement of the rate of hospitalization. Moreover, it reveals that our pre-dialysis care, modifying the above-mentioned factors, has been a major cause of these clinical improvements.

Should current criteria for detecting and repairing arteriovenous fistula stenosis be reconsidered? Interim analysis of a randomized controlled trial.

BACKGROUND: The vascular access guidelines recommend that arteriovenous fistulas (AVFs) with access dysfunction and an access blood flow (Qa) <300-500 mL/min be referred for stenosis imaging and treatment. Significant (>50%) stenosis, however, may be detected in a well-functioning AVF with a Qa > 500 mL/min, too, but whether it is worth correcting or not remains to be seen. METHODS: In October 2006, we began an open randomized controlled trial enrolling patients with an AVF with subclinical stenosis and Qa > 500 mL/min, to see how elective stenosis repair [treatment group (TX)] influenced access failure (thrombosis or impending thrombosis requiring access revision), or loss and the related cost compared with stenosis correction according to the guidelines, i.e. after the onset of access dysfunction or a Qa < 400 mL/min [control group (C)]. An interim analysis was performed in July 2012, by which time the trial had enrolled 58 patients (30 C and 28 TX). RESULTS: TX led to a relative risk of 0.47 [95% confidence interval (CI): 0.17-1.15] for access failure (P = 0.090), 0.37 [95% CI: 0.12-0.97] for thrombosis (P = 0.033) and 0.36 [95% CI: 0.09-0.99] for access loss (P = 0.041). In the setting of our study (in which all surgery was performed as in patient procedure) no significant differences in costs emerged between the two strategies. The mean incremental cost-effectiveness ratio for TX was €282 or €321 to avoid one episode of thrombosis or access loss, respectively. CONCLUSIONS: Our interim analysis showed that elective repair of subclinical stenosis in AVFs with Qa > 500 mL/min cost-effectively reduces the risk of thrombosis and access loss in comparison with the approach of the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, raising the question of whether the currently recommended criteria for assessing and treating stenosis should be reconsidered.

The rise and fall of access blood flow surveillance in arteriovenous fistulas.

Vascular access blood flow (Qa) surveillance has been described as a typical false paradigm, an example of how new tests are sometimes adopted even without good-quality evidence of their benefits. This may be true for grafts, but not necessarily for arteriovenous fistulas. We reviewed the literature on Qa surveillance in fistulas to see whether it complies with the World Health Organization's criteria for screening tests. Measuring Qa has a fairly good reproducibility. Qa shows an excellent-to-good accuracy for stenosis being the only bedside screening test that achieves a very high sensitivity while retaining a fair-to-good positive predictive value for Qa thresholds of 600 ml/minute or higher associated with a >25% drop in Qa, or findings suggesting stenosis on physical examination. The accuracy of Qa in predicting thrombosis is hard to establish because of the heterogeneity of published studies, though a Qa of 300 ml/minute seems the most reliable cutoff. Qa surveillance affords a significant 2- to 3-fold reduction in the risk of thrombosis by comparison with clinical monitoring alone when Qa criteria highly sensitive to stenosis are considered, regardless of the study design (randomized controlled trials, cohort studies with concurrent or historic controls). Using highly sensitive Qa screening criteria also halves the risk of access loss, although this effect is not statistically significant. Our analysis strongly suggests that Qa surveillance is an effective method for screening mature fistulas, though further, appropriately designed studies are needed to fully elucidate its benefits and cost effectiveness.

A population-based cohort study of chest x-ray screening in smokers: lung cancer detection findings and follow-up.

BACKGROUND: Case-control studies of mass screening for lung cancer (LC) by chest x-rays (CXR) performed in the 1990s in scarcely defined Japanese target populations indicated significant mortality reductions, but these results are yet to be confirmed in western countries. To ascertain whether CXR screening decreases LC mortality at community level, we studied a clearly defined population-based cohort of smokers invited to screening. We present here the LC detection results and the 10-year survival rates. METHODS: The cohort of all smokers of > 10 pack-years resident in 50 communities of Varese, screening-eligible (n = 5,815), in July 1997 was invited to nonrandomized CXR screening. Self-selected participants (21% of cohort) underwent screening in addition to usual care; nonparticipants received usual care. The cohort was followed-up until December 2010. Kaplan-Meier LC-specific survival was estimated in participants, in nonparticipants, in the whole cohort, and in an uninvited, unscreened population (control group). RESULTS: Over the initial 9.5 years of study, 67 LCs were diagnosed in screening participants (51% were screen-detected) and 178 in nonparticipants. The rates of stage I LC, resectability and 5-year survival were nearly twice as high in participants (32% stage I; 48% resected; 30.5% 5-year survival) as in nonparticipants (17% stage I; 27% resected; 13.5% 5-year survival). There were no bronchioloalveolar carcinomas among screen-detected cancers, and median volume doubling time of incidence screen-detected LCs was 80 days (range, 44-318), suggesting that screening overdiagnosis was minimal. The 10-year LC-specific survival was greater in screening participants than in nonparticipants (log-rank, p = 0.005), and greater in the whole cohort invited to screening than in the control group (log-rank, p = 0.001). This favourable long-term effect was independently related to CXR screening exposure. CONCLUSION: In the setting of CXR screening offered to a population-based cohort of smokers, screening participants who were diagnosed with LC had more frequently early-stage resectable disease and significantly enhanced long-term LC survival. These results translated into enhanced 10-year LC survival, independently related to CXR screening exposure, in the entire population-based cohort. Whether increased long-term LC-specific survival in the cohort corresponds to mortality reduction remains to be evaluated. TRIAL REGISTRATION NUMBER: ISRCTN90639073.

Acetate-free biofiltration reduces intradialytic hypotension: a European multicenter randomized controlled trial.

BACKGROUND: Intradialytic hypotension (IH) is a common complication of bicarbonate hemodialysis (BD) and contributes to the intolerance of dialysis and the high cardiovascular morbidity and mortality among dialysis patients, the risk of which can be contained by convective therapies. AIMS/METHODS: To assess whether acetate-free biofiltration (AFB), a hemodiafiltration technique found to improve intradialytic cardiovascular stability in short-term studies, can influence long-term IH rates, predialysis systolic blood pressure (SBP), cardiovascular morbidity and mortality by comparison with BD, we analyzed data from a randomized controlled trial enrolling 371 new-to-dialysis patients, 194 on BD and 177 on AFB. RESULTS: During a 3-year follow-up, AFB carried a significantly lower risk of IH (incidence rate ratio 0.60 (95% CI 0.53-0.68), p < 0.0001). SBP dropped on AFB (p = 0.01), while it did not change on BD. Cardiovascular morbidity and mortality were similar between AFB and BD. CONCLUSION: AFB carries a lower long-term IH rate and reduces SBP by comparison with BD.

Clinical response to biologicals for severe asthma: any relevance for sex in different age ranges?

Background: Whether sex can influence the clinical response to biological treatment in patients with severe asthma has not been fully addressed. Aims and methods: The aim of this study was to investigate in patients with severe asthma undergoing biological treatment the individual evolution of lung function measurements and patient-reported asthma control scores over a 12-month follow-up period, in relation to patients' sex, in different age ranges. Second, the change in the administered dose of oral corticosteroids (OCS) before and after 12 months of treatment was investigated. Results: 64 patients (58% female and 42% male) with a median age of 52 years were enrolled in the study. There were no relevant differences between sexes in terms of lung function, patient-reported asthma control, exacerbation rate and daily OCS dose within the study timeframe. A separate sub-analysis by biological treatment confirmed the same finding. Stratifying individuals by age, we showed that older men had lower lung function parameter values (forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity index) than older women, whereas an opposite trend was observed in terms of Asthma Control Test score. No other relevant differences were detected after age stratification. Conclusion: According to our findings, sex does not act as a determinant of treatment response to biologicals in people with severe asthma. Although to be confirmed in larger studies, our data suggest that neither sex nor age should limit biological treatment prescription, once the eligibility criteria for that therapy are satisfied.

A molecular case-control study of the Merkel cell polyomavirus in colon cancer.

To explore the putative role of the Merkel cell polyomavirus in human colon cancer, a prospective molecular case-control study was undertaken in patients and their relatives enrolled during a screening program. Fresh tissue samples from 64 cases of colon cancer (mean age 69.9 ± 11.0 years; 40 males) and fresh biopsies from 80 relatives (mean age 53.7 ± 8.6 years; 43 male; 55 son/daughter, 23 brother/sister, 2 parents) were analyzed by PCR and sequencing. Pre-cancerous lesions, namely adenomas and polyps, were detected in 15 (18.8%) and 9 (11.2%) of the controls, respectively. In addition, 144 blood samples were examined. Merkel cell polyomavirus DNA was detected in 6.3% of cases and 8.8% of controls. This difference was not statistically significant in the logistic regression analysis, after adjustment for age. Whereas blood samples from both cases and controls tested negative, the DNA Merkel cell polyomavirus was identified in 12.5% of adenoma/polyp tissues. No statistically significant difference was found when prevalence rates of Merkel cell polyomavirus in normal, pre-cancerous and cancer tissues were compared. Sequence analysis of the viral LT3 and VP1 regions showed high homology (>99%) with those of strains circulating worldwide, especially with genotypes detected in France. The findings of this survey are consistent with the hypothesis that the Merkel cell polyomavirus, in addition to other human polyomaviruses, can be recovered frequently from the gastrointestinal tract, because it is transmitted throughout the fecal-oral route. Moreover, the study does not indicate a role for Merkel cell polyomavirus in the genesis of colon cancer.

Volunteer effect and compromised randomization in the Mayo Project of screening for lung cancer.

It has been confirmed recently that the volunteer effect in lung cancer screening is characterized by higher lung cancer mortality risk in self-selected screening participants. The Mayo Lung Project, the most influential trial of screening for lung cancer ever completed, was conducted in nonvolunteer Mayo Clinic outpatients, with a peculiar study design that rendered the randomization vulnerable to the volunteer effect. Of all nonvolunteers randomized in the Mayo Lung Project, only those allocated in the screened group were asked consent to participate in the trial. The final Mayo Lung Project report stated that 655 randomized nonvolunteers refused screening and were excluded from the study, thus documenting violation of the rule that no selection should occur after randomization. The long-term follow-up of the Mayo Lung Project showed an enigmatic result which has never been explained: the lung cancer mortality was 13% higher in the screening intervention group than in the control group [4.4 (95% CI 3.9-4.9) vs. 3.9 (95% CI 3.5-4.4) per 1,000 person-years; P = 0.09]. Such overrepresented mortality is consistent with the volunteer effect and supports the concept that the Mayo Lung Project randomization was compromised by the post-randomization self-selection of participant nonvolunteers.

Patient Safety in the Eyes of Aspiring Healthcare Professionals: A Systematic Review of Their Attitudes.

A culture of safety is important for the delivery of safe, high-quality care, as well as for healthcare providers' wellbeing. This systematic review aimed to describe and synthesize the literature on patient safety attitudes of the next generation of healthcare workers (health professional students, new graduates, newly registered health professionals, resident trainees) and assess potential differences in this population related to years of study, specialties, and gender. We screened four electronic databases up to 20 February 2020 and additional sources, including weekly e-mailed search alerts up to 18 October 2020. Two independent reviewers conducted the search, study selection, quality rating, data extraction, and formal narrative synthesis, involving a third reviewer in case of dissent. We retrieved 6606 records, assessed 188 full-texts, and included 31 studies. Across articles, healthcare students and young professionals showed overwhelmingly positive patient safety attitudes in some areas (e.g., teamwork climate, error inevitability) but more negative perceptions in other domains (e.g., safety climate, disclosure responsibility). Women tend to report more positive attitudes. To improve safety culture in medical settings, health professions educators and institutions should ensure education and training on patient safety.

Detection of SV40 in colon cancer: a molecular case-control study from northeast Italy.

To explore the involvement of the simian polyomavirus SV40 in human colon cancer, a molecular case-control study was undertaken in patients and in their relatives living in an area where the spread of SV40 has already been documented. From 2006 to 2008, 94 colon cancer patients (age: 37-90 years) and 91 subjects (age: 32-70 years) relatives of each index case were enrolled. A blood sample and a specimen of cancer tissue or biopsy were collected, from each patient or control, respectively. Samples were analyzed twice for Polyomavirus (i.e., SV40, JCV, and BKV) by PCR and by quantitative real-time PCR (RT-qPCR) with reproducible results. No BKV/JCV was detected either in normal or pathological tissues. SV40 was not present in control subjects, either normal tissue or in biopsies from adenomas or polyps. All blood samples were negative. Conversely, six adenocarcinoma specimens were positive for SV40 sequences (overall prevalence 6.4%, P = 0.03 in comparison with controls). Nevertheless, the SV40-associated colon cancer risk proved statistically not significant (OR = 3.91; P = 0.115) when adjusted for age. Quantitation of SV40 DNA performed by RT-qPCR showed a low viral load ranging from 6.2 x 10(1) to 9 x 10(3) copies per reaction. This molecular case-control survey showed, for the first time in fresh samples and by RT-qPCR, that SV40 can be detected in colon cancer tissue. However, the finding was not statistically significant when compared with a well-structured community control group. Thus, the role of SV40 and other polyomavirus in colon cancer genesis deserves further investigation.

Evaluation of hepcidin isoforms in hemodialysis patients by a proteomic approach based on SELDI-TOF MS.

The hepatic iron regulator hormone hepcidin consists, in its mature form, of 25 amino acids, but two other isoforms, hepcidin-20 and hepcidin-22, have been reported, whose biological meaning remains poorly understood. We evaluated hepcidin isoforms in sera from 57 control and 54 chronic haemodialysis patients using a quantitative proteomic approach based on SELDI-TOF-MS. Patients had elevated serum levels of both hepcidin-25 and hepcidin-20 as compared to controls (geometric means: 7.52 versus 4.69 nM, and 4.06 versus 1.76 nM, resp., P < .05 for both). The clearance effects of a single dialysis session by different dialysis techniques and membranes were also investigated, showing an average reduction by 51.3% +/- 29.2% for hepcidin-25 and 34.2% +/- 28.4% for hepcidin-20 but only minor differences among the different dialysis modalities. Measurement of hepcidin isoforms through MS-based techniques can be a useful tool for better understanding of their biological role in hemodialysis patients and other clinical conditions.

Hepcidin is not useful as a biomarker for iron needs in haemodialysis patients on maintenance erythropoiesis-stimulating agents.

BACKGROUND: It has been suggested that hepcidin may be useful as a tool for managing iron therapy in haemodialysis (HD) patients on erythropoiesis-stimulating agents (ESA). METHODS: We used SELDI-TOF mass spectrometry assay to measure serum hepcidin-25 (Hep-25) and hepcidin-20 (Hep-20) in 56 adult HD patients on maintenance ESA to assess their ability to predict haemoglobin (Hb) response after 1 g intravenous iron (62.5 mg ferric gluconate at 16 consecutive dialysis sessions) and their relationship with markers of iron status, inflammation and erythropoietic activity. RESULTS: At multivariate analysis (in a model that also included Hb, reticulocyte, ESA dose, HFE genotype, soluble transferrin receptor [sTfR] and C-reactive protein), Hep-25 independently correlated with ferritin (ß = 0.03, P = 0.01) and the percentage of hypochromic red blood cells [%Hypo] (ß = 1.84, P = 0.01), suggesting that Hep-25 may be a useful biomarker for iron stores and bone marrow iron availability. Hep-20 correlated independently with Hep-25 (ß = 0.159, P < 0.001) and ferritin (ß = 0.006, P = 0.05), suggesting that it may be a useful additional biomarker for iron stores. On receiver operating characteristics curve analysis, neither Hep-25 nor Hep-20 significantly predicted who will increase their Hb after iron loading (AUC = 0.52 ± 0.09 and 0.54 ± 0.08, P = 0.612), and the same applied to ferritin and transferrin saturation (AUC = 0.55 ± 0.08 and 0.59 ± 0.08, P = 0.250), whereas %Hypo and reticulocyte Hb content were significant predictors (AUC = 0.84 ± 0.05 and 0.70 ± 0.08, P < 0.01). At multivariate logistic regression analysis, %Hypo was the only biomarker independently associated with iron responsiveness. CONCLUSIONS: Although our study suggests an important role for hepcidin in regulating iron homeostasis in HD patients on ESA, our findings do not support its utility as a predictor of iron needs, offering no advantage over established markers of iron status.