Hyperglycemia and microRNAs in prostate cancer.

BACKGROUND: Hyperglycemia can promote the development of prostate cancer (PCa). Differential expression levels of miRNAs between PCa patients and controls were also reported. Therefore, we examined the relationship between hyperglycemia and miRNA levels in PCa. METHODS: Relative expression of urinary miR-574-3p, miR-375, miR-205-5p, miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p were investigated in 105 PCa patients and 138 noncancer controls by Real-Time quantitative PCR. Fasting plasma glucose measurements were retrieved from clinical records. The differential miRNA expressions among groups were compared using non-parametric tests. Correlations with glucose and prostate-specific antigen (PSA) were tested using Pearson correlation coefficient. RESULTS: When we analyzed miRNA expression according to glycemic state, significant down-regulations were found for miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p in noncancer controls with high glucose. The lowest down-regulations were observed for miR-187-3p, miR-182-5p, and miR-100-5p. Subsequently, when hyperglycemia was considered in PCa, significant dysregulations of selected miRNAs were found in hyperglycemic PCa patients than in controls with high glucose. In particular, miR-375 and miR-182-5p showed a 3-FC in hyperglycemic PCa patients than controls who left hyperglycemia untreated. Conversely, only a down-regulation of miR-574-3p was observed in PCa patients regardless of glycemic status and only modest down-regulation of miR-574-3p, miR-200b-3p, miR-187-3p and miR-182-5p were found in normoglycemic PCa patients. Next, significant correlations between miRNAs and glucose (miR-200b-3p, miR-100-5p) and PSA (miR-205-5p and miR-187-3p) were detected in controls. Similarly, miR-205-5p and miR-187-3p were correlated with glucose in PCa patients, while miR-574-3p and miR-375 showed inverse relationships. CONCLUSIONS: miRNA dysregulations can occur in hyperglycemic PCa patients as compared to noncancer controls who left hyperglycemia untreated. Hyperglycemia can consistently promote the expression of miR-375 and miR-182-5p. Uncontrolled hyperglycemic state could contribute to the creation of a suitable microenvironment for later PCa development by promoting gene expression.

Diagnosis of Respiratory Syncytial Virus (RSV) infection in children by Respiratory Panel utilized during the COVID-19 pandemic.

BACKGROUND: In the months of October and November 2021, there was throughout Italy and in our specific case in the area of Lucca and Versilia, a disturbing increase of SARS-CoV-2 infections and cases of Respiratory Syncytial Virus (RSV) in new-borns. The aim of this paper is to compare the cases of RSV infection diagnosed in recent years to the cases recorded during the SARS-CoV-2 pandemic to November 2022. MATERIALS AND METHODS: The study consisted of evaluating the results of requests for RSV diagnosis from 2015 to November 2022, using molecular biology techniques. RESULTS: The data obtained show that the number of cases of RSV infection in children during the winter season had a constant trend from 2015 to 2019. From November 2020 to February 2021 there were no cases of RSV respiratory infections. Starting from September 2021, on the other hand, there was a resumption of cases of RSV infections in conjunction with an increase in the number of children affected by COVID-19. From January 2022, after a peak in cases of SARS-CoV-2 infection, there has been a decrease in RSV infections. From September 2022 to November 2022, there was no increase of cases of RSV infections in new-borns but on the contrary, there was a trend in respiratory infections comparable to the pre-pandemic period. CONCLUSION: The data that emerged from the study conducted, show the onset of an outbreak of RSV in new-borns. This incidence is linked to the implementation of rigorous non-pharmacological public health interventions in 2020, aimed at combating COVID-19 infection. The use of the molecular panel made it possible to identifying the responsible agent and highlighting the most suitable clinical and therapeutic path.

Identification of Amoxicillin Crystals in Urine: a Case Report.

BACKGROUND: The case concerns a 30-year-old woman in the 24th week of pregnancy presenting to the medical emergency room with fever and abdominal pain. Urine sediment microscopy revealed the presence of unknown needle-shaped crystals. METHODS: Crystals identification was performed by Fourier-Transform Infrared Spectroscopy coupled to Attenuated Total Reflectance (FTIR-ATR). RESULTS: Amoxicillin crystals were verified with semiquantitative results of 87.7%. CONCLUSIONS: Drug-induced crystalluria is a frequent finding in urine examination and it may be asymptomatic. FTIR spectroscopy is a rapid and specific tool in identification of crystals and could be useful supporting renal disease diagnosis and monitoring drug therapy.

Faecal haemoglobin concentration among subjects with negative FIT results is associated with the detection rate of neoplasia at subsequent rounds: a prospective study in the context of population based screening programmes in Italy.

OBJECTIVE: To estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer-CRC-or advanced adenoma). DESIGN: Prospective cohort of subjects aged 50-69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy. METHODS: All programmes adopted the same analytical procedure (OC Sensor, Eiken Japan), performed every 2 years, on a single sample, with the same positivity cut-off (20 µg Hb/g faeces). We assessed the AN risk at subsequent exams, the cumulative AN detection rate (DR) over the 4-year period following the second FIT and the interval CRC (IC) risk following two negative FITs by cumulative amount of f-Hb concentration over two consecutive negative FITs, using multivariable logistic regression models and the Kaplan-Meier method. RESULTS: The cumulative probability of a positive FIT result over the subsequent two rounds ranged between 7.8% (95% CI 7.5 to 8.2) for subjects with undetectable f-Hb at the initial two tests (50% of the screenees) and 48.4% (95% CI 44.0 to 53.0) among those (0.7% of the screenees) with a cumulative f-Hb concentration ≥20 µg/g faeces. The corresponding figures for cumulative DR were: 1.4% (95% CI 1.3 to 1.6) and 25.5% (95% CI 21.4 to 30.2) for AN; 0.17% (95% CI 0.12 to 0.23) and 4.5% (95% CI 2.8 to 7.1) for CRC. IC risk was also associated with cumulative f-Hb levels. CONCLUSION: The association of cumulative f-Hb concentration with subsequent AN and IC risk may allow to design tailored strategies to optimise the utilisation of endoscopy resources: subjects with cumulative f-Hb concentration ≥20 µg/g faeces over two negative tests could be referred immediately for total colonoscopy (TC), while screening interval might be extended for those with undetectable f-Hb.

Appropriate use of laboratory test requests in the emergency department: a multilevel intervention.

OBJECTIVE: Laboratory test requests in the emergency department (ED) are increasing worldwide. We evaluated whether a multilevel intervention on the basis of the optimization of test profiles and educational meetings with physicians could reduce the number of tests ordered. PATIENTS AND METHODS: In a single-center before and after study design, the 8-month intervention period was compared with the 8-month preintervention period. Laboratory test profiles were reduced from 6 to 2 and the number of tests in each profile was reduced by 50%. All physicians received education about the costs and appropriate use of the tests. Primary outcomes were the number of laboratory blood tests and their costs, with a focus on high-cost tests. Secondary outcomes were ED and laboratory performances (patients' waiting time, number of deaths in ED, re-entry, laboratory turn-around time, and add-on tests). RESULTS: Overall, 61 976 and 61 154 patients were evaluated, respectively, during the intervention and the preintervention period. Laboratory blood test requests were decreased by 207 637 (-36.3%) in the intervention period (P < 0.05), which corresponds to a reduction of 337.3 tests/100 patients. Costs were decreased by 608 079&OV0556; ( - 29.6%, P < 0.05), leading to a cost reduction of 981.2&OV0556;/100 patients. High-cost test requests decreased by 11 457 ( - 27.3%) and contributed toward the overall reduction in costs with 197 206&OV0556; ( - 30.5%). No significant differences were found in ED and laboratory performances between intervention and preintervention periods. CONCLUSIONS: Optimization of test profiles and education on the costs and appropriate use of the tests significantly reduced laboratory test ordering and costs without affecting ED and laboratory performances.

Daily urinary sodium and potassium excretion in Chinese first-generation migrants in Italy.

BACKGROUND: China has one of the highest salt intake levels in the world, and Chinese people form one of the largest foreign-born communities now living in Europe. The present study was performed to assess 24-hour urinary sodium and potassium excretion in Chinese migrants in Italy and to explore possible associations with hypertension, hypertension awareness, and length of residence in Italy. METHODS: A cross-sectional evaluation was conducted on 319 first-generation Chinese migrants (154 women and 165 men) aged 18-70 years. Subjects were asked to do a 24-hour urine collection and the relationships of urinary sodium and potassium and arterial blood pressure, hypertension (BP ≥ 140/90 mmHg or anti-hypertensive drug use), hypertension awareness, and years of residence in Italy were investigated with linear or logistic regression analysis. RESULTS: Sodium excretion was 145.2 mmol/day (95%CI 138.0-152.3) in men, and 134.7 (95%CI 127.6-141.8) in women corresponding to a dietary salt intake of 9.4 g/day (95%CI 9.0-9.9) and 8.8 (95%CI 8.3-9.2) respectively. Potassium excretion was 35.1 mmol/day (95%CI 33.6-36.5), with no significant difference by gender. At multivariable adjusted linear regression analysis body mass index, low education level, and hypertension were positive predictors of sodium urinary excretion; gender (women), and body mass index were positive predictors of potassium excretion. Sodium and potassium excretion were unaffected by hypertension awareness or years of residence in Italy. CONCLUSIONS: Sodium excretion in Chinese workers is higher than recommended and in line with high salt intake in Italy. Potassium consumption remains low.

Seasonal blood pressure variation: implications for cardiovascular risk stratification.

Long-term blood pressure variations contribute to an increased risk of cardiovascular events during cold season, requiring personalized management of antihypertensive medications in a single patient, and can influence the results of clinical trials and epidemiological surveys in population studies. In addition to blood pressure values, which guide the stratification of cardiovascular risk, other cardiovascular risk factor levels also tend to be higher in the winter months and lower in the summer months. The resultant estimation of individual cardiovascular risk may thus vary depending on the season. At the patient level, only a low value in the winter should thus be considered a true measure of low cardiovascular risk, whereas low values measured in the summer do not indicate a low risk in the winter. Likewise, estimations of cardiovascular risk in population studies may vary according to the period of the year. Efforts should thus be directed at considering the potential influence of seasonal variations in establishing "normal" and "high-risk" assessment at both the patient and population levels, integrating such data into clinical practice.

Guidance for faecal occult blood testing: quantitative immunochemical method (FIT-HB) in colorectal cancer screening programmes. / Guida per la determinazione del sangue occulto fecale: metodo immunochimico quantitativo (FIT-HB) nei programmi di screening per il carcinoma colorettale

BACKGROUND: in Italy, colorectal cancer screening is included as part of the Italian National Health Service - SSN (Servizio Sanitario Nazionale) Essential Levels of Care - LEA (Livelli Essenziali Assistenziali) and the European Guidelines, which specify quantitative FIT-Hb testing as the best strategy for organised screening programmes. To ensure consistent operating standards in Member States, European regulations require the implementation of certification and accreditation requirements for diagnostic and care-related processes. The requirement, based on ISO 17021 accreditation standards, includes ISO 9001 certification for systems and ISO 15189:2012 accreditation for laboratories. METHODOLOGY: various phases of the analytical process (pre-test, test, post-test) were evaluated in detail and provided operational guidelines for adjusting analytical and managerial procedures using: (a) feedback from members of GISCoR screening labs; (b) performance data obtained via a systematic review of the literature and the Osservatorio Nazionale Screening (ONS) Survey; (c) recommendations for laboratory practice issued by the World Endoscopy Organization "FIT for Screening" Working Group; (d) selected guidelines from the National Guidelines Clearinghouse database; and (e) Canadian, Australian and European screening programme websites. With respect to ISO 15189:2012 standards for accreditation of medical laboratories, GISCoR's guidance has been re-evaluated and revised by auditors from the Italian certification body (ACCREDIA) to assess its compliance and completeness with the aim of finalising operating procedures. CONCLUSIONS: the implementation and maintenance of operational standards required by complex systems (e.g. screening programmes) involving constant interaction between facilities and the supporting organisational structure are not easy to achieve. The guide aims to provide laboratories with the necessary guidance for proper process management.

Effects of fecal sampling on preanalytical and analytical phases in quantitative fecal immunochemical tests for hemoglobin.

BACKGROUND: Information on preanalytical variability is mandatory to bring laboratories up to ISO 15189 requirements. Fecal sampling is greatly affected by lack of harmonization in laboratory medicine. The aims of this study were to obtain information on the devices used for fecal sampling and to explore the effect of different amounts of feces on the results from the fecal immunochemical test for hemoglobin (FIT-Hb). METHODS: Four commercial sample collection devices for quantitative FIT-Hb measurements were investigated. The volume of interest (VOI) of the probes was measured from diameter and geometry. Quantitative measurements of the mass of feces were carried out by gravimetry. The effects of an increased amount of feces on the analytical environment were investigated measuring the Hb values with a single analytical method. RESULTS: VOI was 8.22, 7.1 and 9.44 mm3 for probes that collected a target of 10 mg of feces, and 3.08 mm3 for one probe that targeted 2 mg of feces. The ratio between recovered and target amounts of devices ranged from 56% to 121%. Different changes in the measured Hb values were observed, in adding increasing amounts of feces in commercial buffers. CONCLUSIONS: The amounts of collected materials are related to the design of probes. Three out 4 manufacturers declare the same target amount using different sampling volumes and obtaining different amounts of collected materials. The introduction of a standard probes to reduce preanalytical variability could be an useful step for fecal test harmonization and to fulfill the ISO 15189 requirements.

Impact of a new sampling buffer on faecal haemoglobin stability in a colorectal cancer screening programme by the faecal immunochemical test.

Haemoglobin (Hb) stability in faecal samples is an important issue in colorectal cancer screening by the faecal immunochemical test (FIT) for Hb. This study evaluated the performance of the FIT-Hb (OC-Sensor Eiken) used in the Florence screening programme by comparing two different formulations of the buffer, both in an analytical and in a clinical setting. In the laboratory simulation, six faecal pools (three in each buffer type) were stored at different temperatures and analysed eight times in 10 replicates over 21 days. In the clinical setting, 7695 screenees returned two samples, using both the old and the new specimen collection device (SCD). In the laboratory simulation, 5 days from sample preparation with the buffer of the old SCD, the Hb concentration decreased by 40% at room temperature (25°C, range 22-28°C) and up to 60% at outside temperature (29°C, range 16-39°C), whereas with the new one, Hb concentration decreased by 10%. In the clinical setting, a higher mean Hb concentration with the new SCD compared with the old one was found (6.3 vs. 5.0 µg Hb/g faeces, respectively, P<0.001); no statistically significant difference was found in the probability of having a positive result in the two SCDs. Better Hb stability was observed with the new buffer under laboratory conditions, but no difference was found in the clinical performance. In our study, only marginal advantages arise from the new buffer. Improvements in sample stability represent a significant target in the screening setting.

Panethnic Differences in Blood Pressure in Europe: A Systematic Review and Meta-Analysis.

BACKGROUND: People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU. METHODS AND FINDINGS: We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to 7.66). SA had lower SBP than EU(-4.57 mmHg, 95% CI -6.20 to -2.93; -2.97 mmHg, 95% CI -5.45 to -0.49) but similar DBP values. Meta-analysis by subgroup showed that SA originating from countries where Islam is the main religion had lower SBP and DBP values than EU. In multivariate meta-regression analyses, SBP difference between minorities and EU populations, was influenced by panethnicity and diabetes prevalence. CONCLUSIONS: 1) The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe;2) The lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension;3) The additive effect of diabetes, emphasizes the need of new strategies for the control of hypertension in groups at high prevalence of diabetes.

Impact of preanalytical factors on fecal immunochemical tests: need for new strategies in comparison of methods.

BACKGROUND: Harmonization of fecal immunochemical tests for hemoglobin (FIT-Hb) is crucial to compare clinical outcomes in screening programs. The lack of reference materials and standard procedures does not allow the use of usual protocols to compare methods. We propose 2 protocols, based on artificial biological samples (ABS), to discriminate preanalytical and analytical variation and investigate clinical performances. The protocols were used to compare 2 FIT systems available on European markets: the OC-Sensor Diana (Eiken, Tokyo, Japan) and HM-JACKarc (Kyowa-Medex, Tokyo, Japan). METHODS: ABS were obtained adding Hb to Hb-free feces. In the first procedure, 35 ABS were collected for each collection device and analyzed on both systems. In the second, 188 ABS (106 positive and 82 negative) were -collected and tested on the specific systems. Passing-Bablock (PB), Pearson's correlation coefficients (R) and Bland-Altman difference analysis were used to compare data. RESULTS: PB, R and mean standard errors for Bland-Altman analysis (Diana vs. Arc) results were 0.93x-0.56: R = 0.97 and 19%; and 1.09x + 5.60: R = 0.96 and -18%; for Diana and Arc devices, respectively. No correlations and no difference in positive/negative assessment were observed with the second protocol. CONCLUSIONS: A good correlation was observed in comparing data generated using collection devices on the 2 systems. Manufacturers have developed different sample collection procedures for feces: therefore, data from different systems cannot easily be compared. Adoption of protocols to discriminate preanalytical and analytical variation would be a significant contribution to harmonization of FIT, facilitating data comparison and information acquisition for sample collection strategy and effect of buffers on systems.

How to improve the performances of Fecal Immunological Tests (FIT): Need for standardization of the sampling and pre-analytical phases and revision of the procedures for comparison of methods.

Lack of reference materials and standard procedures, on faecal tests leads to major problems in harmonisation of methods and do not allow the comparison of outcome data. In particular the absence of standardisation of pre-analytical characteristic was noted for faecal test methods for haemoglobin since different manufacturers have developed different sampling procedures and report units. Moreover the physical characteristics of the faecal specimen and the designs of specimen collection devices do not allow analysis of samples on different systems in consequence, faecal tests cannot be compared using standard evaluation protocols. To improve the harmonization of results generated using different analytical systems and the overall performances of test on faecal materials we propose the introduction of standard procedures for sampling and pre-analytical phase and the adoption of specific procedures based on the use of artificial biological samples for comparison of methods. Harmonization of sampling devices with the use of a standard design for pickers and a standard ratio between analyte and buffer for different manufacturers represent a mandatory step in the roadmap for harmonization of clinical laboratory measurement on faecal materials and can allow a significant standardisation of results generated by different devices.The creation of specific protocols for the evaluation and comparison of analytical methods for analyse of faeces could lead to a significant improvement in the performance of methods and systems.

Stability of human α-salivary amylase in aged forensic samples.

The unequivocal tissue identification in forensic casework samples is a key step for crime scene reconstruction. Just knowing the origin of a fluid can sometimes be enough to either prove or disprove a fact in court. Despite the importance of this test, very few data are available in literature concerning human saliva identification in old forensic caseworks. In this work the stability of human α-amylase activity in aged samples is described by using three different methods integrated with DNA profiling techniques. This analytical protocol was successfully applied on 26-years old samples coming from anonymous threat letters sent to prosecutors who were working on "the Monster of Florence", a case of serial murders happened around Florence (Italy) between 1968 and 1985.

Faecal haemoglobin concentrations vary with sex and age, but data are not transferable across geography for colorectal cancer screening.

BACKGROUND: Faecal immunochemical tests (FIT) are becoming widely used in colorectal cancer (CRC) screening. Availability of data on faecal haemoglobin concentrations (f-Hb) in three countries prompted an observational study on sex and age and the transferability of data across geography. METHODS: Single estimates of f-Hb in large groups were made in Scotland, Taiwan and Italy using quantitative automated immunoturbidimetry on the Eiken OC-Sensor. Distributions were examined for men and women overall and in four different age groups. RESULTS: The distributions of f-Hb were not Gaussian and had kurtosis and positive skewness. The distributions were different in the three countries: f-Hb varies with sex and age in all countries, being higher in men and the elderly, but the degree of variation is inconsistent across countries, f-Hb being higher in Scotland than in Taiwan than in Italy, possibly due to different lifestyles. At any cut-off concentration, more men are declared positive than women and more older people are declared positive than younger individuals. CONCLUSIONS: Our analysis supports the view that setting and using a single f-Hb cut-off in any CRC screening programme is far from ideal. We suggest that individualisation is the optimum approach with f-Hb, alone or with other important factors such as sex and age, used to determine important personal issues such as need for colonoscopy, screening interval between tests and risk of future CRC. Whether there is merit in monitoring f-Hb in individuals over time remains an interesting research question for the future.

[Design and arrangement of the CHIP (CHinese In Prato) study]. / Disegno e modalità di realizzazione dello studio CHIP (CHinese In Prato).

Following the rapid economic development, China is experiencing a progressive increase in the incidence of cardiovascular (CV) events and in the prevalence of CV risk factors. According to recent estimations, the prevalence of diabetes sharply increased from 1% in 1980 to 11% in 2013. Migration from China to Europe is now mainly concentrated in Countries of the Southern Europe, e.g., Italy and Spain. The largest Chinese community living in Italy is now settled in Prato, being also one of the largest Chinese community in Europe. Local authorities estimate a number of Chinese citizens living in Prato of over 40,000 individuals, including illegal immigrants. The availability of reliable data on the health needs of Chinese population is thus a recognised priority for the local health system. The creation of a participatory research where Chinese population directly participates in the formation of a group of citizens involved in designing and conducting the survey allows to overcome difficulties due to the lack of official demographic files. Secondly, and most important, this approach makes it possible to effectively pass a prevention message to an elusive population. The purpose of the CHIP (CHinese In Prato) survey is to investigate the prevalence of diabetes and cardiovascular risk factors among Chinese immigrants. Recruitment procedure was started on 8th July 2014.

Epidemiology of hypertension in Yemen: effects of urbanization and geographical area.

Although globalization can contribute to increased blood pressure by spreading unhealthy behaviors, it also provides powerful means to tackle hypertension. The dissemination of information about and advice on cardiovascular prevention and facilitated contact with health services are valuable resources. To investigate the effects of urbanization, geographical area, and air temperature on hypertension burden and kidney damage, a survey was performed in 2008 with a door-to-door approach among urban and rural adult dwellers of three geographic areas (capital, inland, coast) of Yemen. Subjects (n=10 242) received two visits several days apart to confirm the diagnosis of hypertension. Proteinuria (dipstick test +1) was used as a marker of kidney damage. Prevalence rates were weighted to represent the Yemen population aged 15-69 years in 2008. Rates of hypertension and proteinuria progressively increased from the capital (6.4%; 95% confidence level (CI) 5.8-7.0 and 5.1%; 4.4-5.9, respectively), to inland areas (7.9%; 7.0-8.7 and 6.1%; 5.1-7.1), to the coastal area (10.1%; 8.9-11.4 and 8.9%; 7.3-10.4). When compared with urban dwellers, rural dwellers had similar hypertension prevalence (adjusted odds ratios (ORs) 1.03; 95% CI 0.91-1.17) but higher proteinuria rates (adjusted ORs 1.55; 1.31-1.85). Overall, home temperature was associated with a lower hypertension rate (adjusted OR 0.98; 0.96-0.99). This large population study reveals that the highest burden of hypertension and kidney damage is detectable in remote areas of the country.