Fine particulate matter and sleep-disordered breathing severity in a large Italian cohort.

BACKGROUND: Air pollution and obstructive sleep apnea (OSA) are both linked with cardiovascular co-morbidities and share similar pathophysiological mechanisms. A causal association between the two has been postulated. However, the results of the studies on this topic are conflicting mainly because of the lack of adjustment for important confounders such as seasonality and temperature. We aimed to evaluate if such an association exists in a highly polluted area like Lombardy region (Italy) when accounting for all confounders. METHODS: Data of adult patients seen at the Sleep Disorder Centre in Milan from 2010 to 2020 were analysed and the main polygraphic data were retrieved. Air pollutant concentrations of the following pollutants NO2, O3, PM2.5, and PM10 were collected through monitoring stations. RESULTS: A total of 3493 patients were included: males (2358, 67.5%) mean age 60.1 (SD = 14.3) years, BMI 29.2 (6.2) kg/m2, mean AHI 16.5 (18.1) events/h. After adjusting for all confounders, in the multivariable analysis, the only associations that remained significant were long-term exposure to O3 with indexes of OSA severity (AHI and ODI) but only in spring. Furthermore, a positive association was seen between long-term exposure to PM10 and ODI but in springtime only. CONCLUSION: The findings of the current study does not support an association between fine particulate matter and OSA severity.

Maternal exposure to air pollutants, PCSK9 levels, fetal growth and gestational age - An Italian cohort.

OBJECTIVE: Exposure to airborne pollutants during pregnancy appears to be associated with uterine growth restriction and adverse neonatal outcome. Proprotein convertase subtilisin/kexin type (PCSK9), the key modulator of low-density lipoprotein (LDL) metabolism, increases following particulate matter (PM10) exposure. Because maternal cholesterol is required for fetal growth, PCSK9 levels could be used to evaluate the potential impact of airborne pollutants on fetal growth. DESIGN: A cohort of 134 healthy women during early pregnancy (11-12 weeks of gestational age) was studied. RESULTS: A significant association between circulating PCSK9 levels and three tested air pollutants (PM10, PM2.5, nitric oxide (NO2)) was found. Of importance, gestational age at birth was reduced by approximately 1 week for each 100 ng/mL rise in circulating PCSK9 levels, an effect that became more significant at the highest quartile of PM2.5 (with a 1.8 week advance in delivery date for every 100 ng/mL rise in circulating PCSK9; p for interaction = 0.026). This finding was supported by an elevation of the odds ratio for urgent cesarean delivery for each 100 ng/mL rise in PCSK9 (2.99, 95% CI, 1.22-6.57), similar trends being obtained for PM10 and NO2. CONCLUSIONS: The association between exposure to air pollutants during pregnancy and elevation in PCSK9 advances our understanding of the unforeseen influences of environmental exposure in terms of pregnancy associated disorders.

Early oral versus "traditional" postoperative feeding in gynecologic oncology patients undergoing intestinal resection: a randomized controlled trial.

BACKGROUND: A randomized controlled trial was performed to assess the outcome of early oral postoperative feeding (EOF) compared with traditional oral feeding (TOF) in gynecologic oncology patients undergoing laparotomy with associated intestinal resection. METHODS: Patients aged 18-75 years, undergoing elective laparotomy, and with preoperative diagnosis of gynecologic malignancy, were eligible. Exclusion criteria included infectious conditions, intestinal obstruction, severe malnutrition, American Society of Anesthesiologists (ASA) score > or =4, and postoperative stay in the intensive care unit lasting >24 h. Patients allocated to EOF received liquid diet in the first postoperative day and then regular diet. Patients received traditional feeding scheme until resolution of postoperative ileus to start liquid diet. The primary end-point of the trial was length of hospital stay. RESULTS: Between January 1st, 2007 and March 15th, 2008, 40 patients were randomized to receive either EOF or TOF. Hospital stay in patients who received EOF (n = 18) was 6.9 days versus 9.1 days in the TOF group (n = 22) (P = 0.022). Requirements for analgesic and antiemetic drugs, intensity of pain, intestinal function recovery, mean levels of postoperative satisfaction, postoperative complications, and quality-of-life scores did not differ between the two groups. CONCLUSION: Early resumption of oral intake is feasible and safe in gynecologic oncology patients undergoing intestinal resection as part of a planned surgical procedure. Moreover, significant reduction in length of hospital stay was demonstrated.

Particulate Air Pollution, Blood Mitochondrial DNA Copy Number, and Telomere Length in Mothers in the First Trimester of Pregnancy: Effects on Fetal Growth.

Growing evidences have shown that particulate matter (PM) exposures during pregnancy are associated with impaired fetal development and adverse birth outcomes, possibly as a result of an exaggerated systemic oxidative stress and inflammation. Telomere length (TL) is strongly linked to biological age and is impacted by oxidative stress. We hypothesized that PM exposure during different time windows in the first trimester of pregnancy influences both mitochondrial DNA copy number (mtDNAcn), an established biomarker for oxidative stress, and TL. Maternal blood TL and mtDNAcn were analysed in 199 healthy pregnant women recruited at the 11th week of pregnancy by quantitative polymerase chain reaction. We also examined whether maternal mtDNAcn and TL were associated with fetal growth outcomes measured at the end of the first trimester of pregnancy (fetal heart rate, FHR; crown-rump length, CRL; and nuchal translucency, NT) and at delivery (birth weight, length, head circumference). The possible modifying effect of prepregnancy maternal body mass index was evaluated. PM10 exposure during the first pregnancy trimester was associated with an increased maternal mtDNAcn and a reduced TL. As regards ultrasound fetal outcomes, both FHR and CRL were positively associated with PM2.5, whereas the association with FHR was confirmed only when examining PM10 exposure. PM10 was also associated with a reduced birth weight. While no association was found between mtDNAcn and CRL, we found a negative relationship between mtDNAcn and fetal CRL only in overweight women, whereas normal-weight women exhibited a positive, albeit nonsignificant, association. As abnormalities of growth in utero have been associated with postnatal childhood and adulthood onset diseases and as PM is a widespread pollutant relevant to the large majority of the human population and obesity a rising risk factor, our results, if confirmed in a larger population, might represent an important contribution towards the development of more targeted public health strategies.

Urinary chromium is associated with changes in leukocyte miRNA expression in obese subjects.

BACKGROUND/OBJECTIVES: Epidemiological studies suggest a link between chromium (Cr) status and cardiovascular disease. Increased urinary excretion of Cr was reported in subjects with diabetes compared with non-diabetic controls and those with non-diabetic insulin resistance. Epigenetic alterations have been linked to the presence of Cr, and microRNA (miRNA) expression has been implicated in the pathogenesis of metabolic diseases and cardiovascular diseases (CVDs). We investigated the association between Cr excretion and miRNA expression in leukocytes from obese subjects. We also examined the relationship between altered miRNA expression and selected clinical parameters to further investigate mechanisms linking Cr to metabolic diseases and CVDs. SUBJECTS/METHODS: We analyzed urinary Cr in 90 Italian subjects using inductively coupled plasma-mass spectrometry. Peripheral blood miRNA levels were screened with TaqMan Low-Density Array Human MicroRNA A. Cr level-associated expression of miRNAs was detected with multivariate regression analyses, and the top 10 candidate miRNAs were selected for validation. We also used multivariate regression analyses to assess possible associations between validated miRNAs and glycated hemoglobin (A1c) and blood pressure (BP). The validated miRNAs were further investigated by functional analysis with Ingenuity Pathway Analysis software. RESULTS: Urinary Cr levels (mean: 0.35 µg/l; s.d.=0.24) ranged from 0.05 to 1.27 µg/l. In the screening phase, 43 miRNAs were negatively associated with Cr. Of the top 10 miRNAs selected for validation, nine (miR-451, miR-301, miR-15b, miR-21, miR-26a, miR-362-3p, miR-182, miR-183 and miR-486-3p) were downregulated in association with Cr (P-false discovery rate (FDR)<0.10). miR-451 expression was associated with A1c (ß=-0.06; P=0.0416), whereas miR-486-3p expression was associated both with diastolic (ß=2.1; P=0.004) and systolic BP (ß=3.3; P=0.003). CONCLUSIONS: These results indicate that miR-451 and miR-486-3p are involved in the link between Cr levels and metabolic diseases and CVDs.

Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis.

BACKGROUND: Women with BRCA1 or BRCA2 mutations are at increased risk of breast and ovarian cancer. Oral contraceptives (OC) use has been associated with a reduction in ovarian cancer risk and with a moderately increased breast cancer risk, which tends to level off in the few years after stopping. The association between oral contraceptive and BRCA1 or BRCA2 gene mutations carriers is unclear. METHODS: We performed a comprehensive literature search updated to March 2010 of studies on the associations between OC users and breast or ovarian cancer for ascertained BRCA1/2 carriers. We obtained summary risk estimated for ever OC users, for duration of use and time since stopping. RESULTS: A total of 2855 breast cancer cases and 1503 ovarian cancer cases, carrying an ascertained BRCA1/2 mutation, were included in our meta-analyses, based on overall 18 studies. Use of OC was associated with a significant reduced risk of ovarian cancer for BRCA1/2 carriers (summary relative risk (SRR)=0.50; 95% confidence interval (CI), 0.33-0.75). We also observed a significant 36% risk reduction for each additional 10 years of OC use (SRR: 0.64; 95% CI, 0.53-0.78; P trend<0.01). We found no evidence of a significant association between OC and breast cancer risk in carriers (SRR: 1.13; 95% CI, 0.88-1.45) and with duration of use. OC formulations used before 1975 were associated with a significant increased risk of breast cancer (SRR: 1.47; 95% 1.06, 2.04), but no evidence of a significant association was found with use of more recent formulations (SRR: 1.17; 95% 0.74, 1.86). CONCLUSIONS: OC users carrying an ascertained BRCA1/2 mutation have a reduced risk of ovarian cancer, proportional to the duration of use. There is no evidence that recent OC formulations increase breast cancer risk in carriers.

Case mix at the European Institute of Oncology: first report of the Tumour Registry, 2000-2002.

INTRODUCTION: An institutional and centralized hospital-based tumour registry (TR) is the ideal supporting tool for the organization and management of clinical data in a comprehensive cancer centre. The purpose of this paper is to describe the development of the TR at the European Institute of Oncology (IEO), Milan, Italy, from its origin to its current applications. MATERIAL AND METHODS: After a series of meetings with members of administrative, clinical, research and informatics departments, the TR was activated in March 2006 with the aim of collecting data on all the individuals referred to the institute, with or at risk of developing a tumour. It was implemented on an Oracle™-based interface. A minimum dataset of variables was defined and data collection was divided into four forms, which together gather all the relevant data on patients, tumours, treatments and subsequent events. RESULTS: After a six-month pilot period, which involved the training of the tumour registrars, adjustments to the structure of the registry, development of a data quality control procedure and finalization of the operative protocol, since September 2006 the data collection has been fully operative. Five registrars have been chronologically entering data of all individuals who visited the IEO for the first time since 1 January 2000. As of March 2009, data on 69,637 individuals and 43,567 tumours has been reviewed, recoded and registered in the TR. Twenty-two per cent of the tumours (n=9578) were first invasive primaries, diagnosed and treated in the IEO; the most common sites were breast (n=4972), lung (n=627), intestines (n=479) and prostate (n=376). CONCLUSION: The IEO TR has been proven functional and reliable in monitoring the activity of the hospital, allowing extraction of data from any subpopulation with characteristics of interest. The structured and centralized TR represents an important tool for our research-oriented institution.

Venous thromboembolic events and organ-specific occult cancers: a review and meta-analysis.

BACKGROUND: Despite a recognized association between venous thromboembolic events (VTE) and cancer, little is known about the strength and the features of this association. We performed a meta-analysis in order to clarify this issue. METHODS: We retrieved data from 40 reports published between 1982 and 2007: 12 contained cancer risk estimates for patients with either idiopathic or secondary VTE vs. subjects without VTE and 17 for patients with idiopathic vs. secondary VTE. We also pooled risk estimates from four cohort studies to assess the association between VTE and specific forms of cancer and conducted a proportional incidence study, based on the remaining 28 reports, which did not provide risk estimates. RESULTS: The pooled relative risk (RR) of cancer was 3.2 [95% confidence interval (95% CI) 2.4-4.5] for patients with any form of VTE vs. no VTE, 2.7 (95% CI 1.9-3.9) for patients with idiopathic vs. no VTE and 3.8 (95% CI 2.6-5.4) for patients with idiopathic vs. secondary VTE. In the pooled cohort studies, RRs for VTE vs. no VTE were significantly elevated for cancers of the ovary (RR 7.0), pancreas (RR 6.1), liver (RR 5.6), blood (4.2), brain (RR 3.8), kidney (RR 3.4), lung (3.1), colon (2.9), and esophagus (2.1). In the proportional incidence study, cancers of the pancreas, colon, and blood were significantly more frequently observed than in the general population. CONCLUSIONS: Overall we found a 3-fold excess risk of occult cancer in patients with VTE. The risk varies according to tumor site and is highest for cancers of the ovary, pancreas, and liver.