The Effects of ESC/ESH-Based Written Generic Lifestyle Advice and a Nutraceutical on 24-Hour Blood Pressure in Patients with High-Normal Office Blood Pressure and Low-Moderate Cardiovascular Risk.

(1) Background: Lifestyle changes, eventually coupled with a nutraceutical, are recommended strategies for managing high-normal blood pressure (BP) patients with low-moderate cardiovascular (CV) risk. In a real-life clinical setting, we evaluated the effects of generic written lifestyle advice, extrapolated from the 2018 ESC/ESH guidelines, and a beetroot-based nutraceutical on 24 h BP in a population with a high-normal office BP and low-moderate CV risk. (2) Methods: A longitudinal observational study was conducted in two ESH Hypertension Excellence Centres on 43 consecutive subjects with high-normal BP according to repeated office BP (OBP) measurements and a low-moderate CV risk based on SCORE2/SCORE2-OP. Additionally, 24 h ambulatory BP monitoring (ABPM) was carried out at baseline and three months after lifestyle changes, according to generic written advice from the 2018 ESC/ESH guidelines, coupled with a nutraceutical containing 500 mg of dry beetroot extract. (3) Results: The mean age was 50 ± 11 years, with male prevalence (54%). The prevalence of overweight/obesity was 58%. The mean OBP was 135 ± 3/85 ± 3 mmHg. At baseline, the mean 24 h BP, daytime BP, and night-time BP were 127 ± 7/80 ± 6 mmHg, 131 ± 8/83 ± 6 mmHg, and 118 ± 8/70 ± 5 mmHg, respectively, BP profiles compatible with hypertension status in some subjects. After a median follow-up of 98 (92-121) days, all BPs, except night-time diastolic BP, were significantly decreased: -3 ± 6/-2 ± 4 mmHg for 24 h BP, -3.9 ± 6.0/-3.0 ± 4.0 mmHg for daytime BP, and -3.3 ± 7.4/-1.3 ± 4.7 mmHg for night-time BP, respectively. No significant clinical changes in body weight were detected. BP decreased independently of baseline BP levels, sex, smoking status, and body mass index, while a more substantial BP decrease was observed in older patients. (4) Conclusions: Our exploratory study shows, for the first time, that written generic lifestyle advice taken from the ESC/ESH hypertension guidelines coupled with a beetroot-based nutraceutical may represent a valid initial non-pharmacological approach in subjects with a high-normal office BP and low-moderate CV risk, even without personalized diet interventions.

Upper Gastrointestinal Endoscopy Quality in Italy: A Nationwide Study.

BACKGROUND AND AIMS: International guidelines advise improving esophagogastroduodenoscopy (EGD) quality in Western countries, where gastric cancer is still diagnosed in advanced stages. This nationwide study investigated some indicators for the quality of EGD performed in endoscopic centers in Italy. METHODS: Clinical, endoscopic, and procedural data of consecutive EGDs performed in one month in the participating centers were reviewed and collected in a specific database. Some quality indicators before and during endoscopic procedures were evaluated. RESULTS: A total of 3,219 EGDs performed by 172 endoscopists in 28 centers were reviewed. Data found that some relevant information (family history for GI cancer, smoking habit, use of proton pump inhibitors) were not collected before endoscopy in 58.5-80.7% of patients. Pre-endoscopic preparation for gastric cleaning was routinely performed in only 2 (7.1%) centers. Regarding the procedure, sedation was not performed in 17.6% of patients, and virtual chromoendoscopy was frequently (>75%) used in only one (3.6%) center. An adequate sampling of the gastric mucosa (i.e., antral and gastric body specimens) was heterogeneously performed, and it was routinely performed only by 23% of endoscopists, and in 14.3% centers. CONCLUSIONS: Our analysis showed that the quality of EGD performed in clinical practice in Italy deserves to be urgently improved in different aspects.

[Death certification of pleural malignant mesothelioma from the Italian National Institute of Statistics: a comparison on 269 clinical diagnosis confirmed at autopsy (1997-2016)]. / La certificazione Istat di decesso per mesotelioma maligno pleurico: comparazione con 269 diagnosi cliniche confermate all'autopsia (1997-2016).

OBJECTIVES: To evaluate the agreement between pleural malignant mesothelioma diagnosis in life, with diagnoses confirmed at autopsy, and the certification of the cause of death in the form of the Italian National Institute of Statistics (Istat). DESIGN: comparison between autopsic cases and cases from Istat. SETTING AND PARTICIPANTS: two series of autopsy diagnoses of pleural malignant mesothelioma placed from 1997 to 2016; 185 in shipyard workers and 90 in Brescia province inhabitants, for whom the Istat death form was acquired for 180 and 89 subjects, respectively. RESULTS: the general agreement between pleural malignant mesothelioma clinical diagnosis in life and death certification was about 91% for the first group and 92% for the second one. In the first group, the age at diagnosis does not affect the accuracy of the death certification, which instead increased over time to become total in the period 2010-2016. CONCLUSIONS: the study suggests that the agreement between pleural malignant mesothelioma clinical diagnosis and certification of the cause of death appears to be very high.

Pleural mesothelioma in doll manufacture: possible asbestos exposure. / Mesoteliomi pleurici in addette alla fabbricazione di bambole: esposizione ad amianto?

BACKGROUND: The occurrence of malignant mesothelioma is almost always causally associated to asbestos exposure but, considering women occurrences, this association is often difficult to demonstrate and consequently the asbestos exposure is defined as 'unknown'. OBJECTIVES: To describe the working activity and to give occupational asbestos exposure probability estimation related to an uncommon and poorly investigated productive sector: doll manufacture. METHODS: From the Province of Brescia Mesothelioma Registry, established in 1993 on population-based criteria, we have extracted the certified mesothelioma diagnosis cases, related to patients who were employed for some time in doll manufacture. RESULTS: Among the 757 total cases of malignant mesothelioma registered and studied up to 2016, we found 3 cases of pleural epithelial mesothelioma histologically diagnosed in young women who had worked in two doll manufacturing companies and whose asbestos exposure had been initially defined as 'unknown', because an environmental, family or extra-professional asbestos exposure was considered unlikely. However, the judicial autopsy performed on one of the 3 women had allowed examining lung tissue samples with Scanning Electron Microscopy. This technique showed a concentration of amphiboles fibers of about 12,000,000 per gram of dry lung tissue, with a consequent re-classification of asbestos exposure from 'unknown' to 'occupational certified'. DISCUSSION: Mesotheliomas in women with no apparent occupational asbestos exposure are normally referred to life or family environmental exposure. Moreover, it is known that occupational asbestos exposure in women is difficult to recognize. Previously, only one publication had reported two cases of mesothelioma in cloth doll manufacture. The occurrence of two mesothelioma cases in the same company out of the three here presented was suggesting an occupational exposure. The finding of a high amphibole fibers lung concentration confirmed the previous hypothesis, despite the impossibility to determine the circumstances with good evidence. CONCLUSION: The three cases of mesothelioma in doll production workers suggest that also in this restricted manufacturing sector had occurred an occupational asbestos exposure, which is up to now unknown and isn't due only to the use of sewing or ironing machines. The lung asbestos fibers burden analysis is confirmed to be a decisive factor in the assessment of mesothelioma cases with 'unknown' exposure.

Oxidative stress and metabolic syndrome: Effects of a natural antioxidants enriched diet on insulin resistance.

BACKGROUND & AIMS: Oxidative stress (OS) could play a role in metabolic syndrome-related manifestations contributing to insulin resistance (IR). The aim of the present study was to gain insight the relationships between OS, IR and other hormones involved in caloric balance, explaining the effects of a natural antioxidant-enriched diet in patients affected by metabolic syndrome. METHODS: We investigated the effects of dietary antioxidants on IR, studying 53 obese (20 males and 33 females, 18-66 years old, BMI 36.3 ± 5.5 kg/m2), with IR evaluated by Homeostasis Model Assessment (HOMA)-index, comparing 4 treatments: hypocaloric diet alone (group A) or plus metformin 1000 mg/daily (group B), natural antioxidants-enriched hypocaloric diet alone (group C) or plus metformin (group D). A personalized program, with calculated antioxidant intake of 800-1000 mg/daily, from fruit and vegetables, was administered to group C and D. The glycemic and insulinemic response to oral glucose load, and concentrations of total-, LDL- and HDL-cholesterol, triglycerides, uric acid, C reactive protein, fT3, fT4, TSH, insulin-like growth factor 1 were evaluated before and after 3-months. Plasma Total antioxidant capacity was determined by H2O2-metmyoglobin system, which interacting with the chromogen ABTS generates a radical with latency time (LAG) proportional to antioxidant content. RESULTS: Despite a similar BMI decrease, we found a significant decrease of HOMA and insulin peak only in group B and D. Insulin response (AUC) showed the greatest decrease in group D (25.60  ±  8.96%) and was significantly lower in group D vs B. No differences were observed in glucose response, lipid metabolism and TAC (expressed as LAG values). TSH values were significantly suppressed in group D vs B. CONCLUSIONS: These data suggest that dietary antioxidants ameliorate insulin-sensitivity in obese subjects with IR by enhancing the effect of insulin-sensitizing drugs albeit with molecular mechanisms which remain yet to be elucidated.

Anti-inflammatory effect of ubiquinol-10 on young and senescent endothelial cells via miR-146a modulation.

Clinical evidence demonstrates that ubiquinol-10, the reduced active form of coenzyme Q10 (CoQ10H2), improves endothelial function through its antioxidant and probably its anti-inflammatory properties. We previously reported that a biomarker combination including miR-146a, its target protein IL-1 receptor-associated kinase (IRAK-1), and released interleukin (IL)-6, here collectively designated as MIRAKIL, indicates senescence-associated secretory phenotype (SASP) acquisition by primary human umbilical vein endothelial cells (HUVECs). We explore the ability of short- and long-term CoQ10H2 supplementation to affect MIRAKIL in HUVECs, used as a model of vascular aging, during replicative senescence in the absence/presence of lipopolysaccharide (LPS), a proinflammatory stimulus. Senescent HUVECs had the same ability as young cells to internalize CoQ10 and exhibit an improved oxidative status. LPS-induced NF-κB activation diminished after CoQ10H2 pretreatment in both young and senescent cells. However, short-term CoQ10H2 supplementation attenuated LPS-induced MIRAKIL changes in young cells; in senescent cells CoQ10H2 supplementation significantly attenuated LPS-induced miR-146a and IRAK-1 modulation but failed to curb IL-6 release. Similar results were obtained with long-term CoQ10H2 incubation. These findings provide new insights into the molecular mechanisms by which CoQ10H2 stems endothelial cell inflammatory responses and delays SASP acquisition. These phenomena may play a role in preventing the endothelial dysfunction associated with major age-related diseases.

The p53 codon 72 (Arg72Pro) polymorphism is associated with the degree of insulin resistance in type 2 diabetic subjects: a cross-sectional study.

Tumor suppressor protein p53 has been demonstrated to regulate genes involved in energy generating metabolic pathways and apoptosis. To date, a new field of research is the involvement of TP53 codon 72 (Arg72Pro) polymorphism in the diabetic disease. The aim of this study was to evaluate whether the genotype and the related genetic models of Arg72Pro polymorphism of TP53 (rs1042522) are associated with insulin resistance and its metabolic parameters in diabetic and non-diabetic subjects. We examined 335 type 2 diabetic patients (65.5 ± 8.4 years) and 367 non-diabetic subjects (60.5 ± 11.7 years). The results were validated in a validation sample consisting of 199 type 2 diabetic (66.2 ± 8.5 years) and 224 non-diabetic subjects (61.2 ± 12.7 years). In the study sample, the analysis of covariance, adjusted for the effects of age, gender and BMI, showed a significant genotype-diabetes effect on insulin resistance evaluated by HOMA-IR (p = 0.038). This result was mediated by variations in fasting plasma insulin (p = 0.027), as no TP53 genotype-diabetes effects were detected for fasting plasma glucose. In particular, in the diabetic subjects, Pro/Pro genotype was associated with lower values of HOMA-IR with respect to Arg/Arg (p = 0.013) and Arg/Pro (p = 0.006) carriers. No difference in HOMA-IR between diabetic and non-diabetic Pro/Pro carriers was found. Significant recessive model-diabetes interaction effects on fasting insulin and HOMA-IR adjusted for age, sex and BMI were found (p = 0.007 and p = 0.029, respectively). Linear regression analyses, based on the assumption of an additive genetic model adjusted for age, sex and BMI, highlight p53 gene-diabetes interaction effects on fasting insulin (ß = -1.27; p = 0.001) and HOMA-IR (ß = -0.22; p = 0.006). The results of statistical analyses on fasting insulin and HOMA-IR were all confirmed in the validation sample. Furthermore, the logistic regression models confirmed that the effect of HOMA-IR levels on diabetes was moderated by Pro/Pro genotype in both study and validation samples (OR = 0.29, p = 0.034, 95 % CI = 0.09-0.91, OR = 0.37, p = 0.035, 95 % CI = 0.15-0.93, respectively). Our findings suggest that p53 codon 72 (Arg72Pro) polymorphism influences insulin resistance in type 2 diabetic patients independently of body mass.

Evaluation of antioxidant systems (coenzyme Q10 and total antioxidant capacity) in morbid obesity before and after biliopancreatic diversion.

Biliopancreatic diversion (BPD) is a surgical procedure performed in patients with untreatable obesity and insulin resistance. The demonstrated metabolic and hormonal results of this procedure include the reversal of insulin resistance; an increase in diet-induced thermogenesis; and modifications of gut hormones, such as gastrin, enteroglucagon, neurotensin, and cholecystokinin. On the other hand, obesity is a condition of increased oxidative stress; however, few studies have investigated antioxidant systems in obese persons with BPD. To evaluate the metabolic status and antioxidant systems in such patients, we studied a group of 11 morbidly obese patients, aged 28 to 62 years, with a mean body mass index (BMI) of 54.71 +/- 2.52 kg/m(2), before and after successful BPD (mean post-BPD BMI, 44.68 +/- 1.51 kg/m(2)). A control group composed of 10 slightly overweight women, with a mean BMI of 28.5 +/- 0.72 kg/m(2), was also studied. Coenzyme Q(10) (CoQ(10)) levels (also normalized for cholesterol levels) and total antioxidant capacity in blood plasma were assessed in these populations. The most striking datum was the extremely low level of CoQ(10) in postoperative period (0.34 +/- 0.16 vs 0.66 +/- 0.09 mug/mL, P = .04); also, the data corrected for cholesterol levels presented the same pattern, with a more marked significance (152.46 +/- 11.13 vs 186.4 +/- 17.98 nmol/mmol, P = .001). This could be due to lipid malabsorption after surgery. In fact, the pre-BPD data present all the metabolic and hormonal characteristics of severe obesity; and after BPD, there was a net improvement in the metabolic parameters. The first pathophysiologic phenomenon seems to be lipid malabsorption that has been argued to be the cause of insulin resistance reversion. This metabolic interpretation is also confirmed by the absence of significant variations of total antioxidant capacity (57.5 +/- 5.3 vs 66 +/- 5.3). The mechanisms of these phenomena remain to be established. These data suggest the importance of correcting postsurgical metabolic complications, in these clinical populations, with CoQ(10) supplementation.

Effects of testosterone on antioxidant systems in male secondary hypogonadism.

Oxidative stress is involved both in metabolic syndrome and male infertility. Hypogonadism is also associated with increased risk for cardiovascular disease. To investigate the role of gonadal steroids in systemic antioxidant regulation, we determined plasma CoenzymeQ(10) (CoQ(10)) and total antioxidant capacity (TAC) in postsurgical hypopituitaric patients. Twenty-six patients aged 28-55 years were studied 6-12 months after surgery. CoQ(10) levels were measured by high-performance liquid chromatography and TAC by spectroscopy with the use of the mioglobin-H(2)O(2) system, which, in interacting with chromogen 2,2(I)-azinobis-(3-ethylbenzothiazoline-6-sulfonate), generates a radical after a latency time (LAG) that is proportional to antioxidant content. Sixteen patients presented low testosterone values; in 10 patients hypogonadism was isolated, and in 6 patients hypothyroidism also was present. CoQ(10) levels were significantly lower in isolated hypogonadism than in normogonadism. Testosterone treatment, performed in those patients with isolated hypogonadism, induced a significant enhancement both in CoQ(10) level and LAG. CoQ(10) and LAG values correlated significantly, suggesting an interrelationship between different antioxidants. Our data suggest that hypogonadism could represent a condition of oxidative stress, in turn related with augmented cardiovascular risk.

[Survival analysis of malignant mesothelioma treated in Brescia, northern Italy, 1982-2000]. / Analisi della sopravvivenza dei mesoteliomi maligni trattati a Brescia dal 1982 al 2000.

OBJECTIVE: To study the survival for malignant mesothelioma on general population cases over the 1982-2000 period and to evaluate the effectiveness of the new therapeutic protocols (intrapleural immunotherapy and mulitmodality therapy) to improve the prognosis on the group of selected hospital patients treated from 1996 to 2000. DESIGN: Survival analysis of malignant mesothelioma on the general population cases and survival analysis for the 1996-2000 period on the selected group of hospital patients. SETTING: The Malignant Mesothelioma Register of the Brescia Province (northern Italy) and Pulmonology Dept. of the General hospital of Brescia. PARTICIPANTS: 353 mesothelioma cases observed in the province of Brescia from 1982 to 2000, 215 of which are residents in the province and 138 from other provinces, 324 are pleural and 29 peritoneal mesothelioma, 141 of all diagnosed between 1982 and 1995 and 212 between 1996 and 2000. MAIN OUTCOME MEASURES: Observed survival (%) at one, three, five-year and median survival by gender, site and residence on the general population cases treated with conventional therapy and on selected hospital patients group treated with intrapleural immunotherapy and mulimodality therapy. RESULTS: Median survival for pleural mesothelioma is of 233 days for the men and 291 days for the women in the group of incident cases; median survival is higher for cases from other provinces (388 and 496 days respectively). From 1996 the number of cases treated with new therapic protocols is steadily increasing, patients without therapy (or only talcaggio) passed from 87% in the period between 1982-1995 to 43% in the period 1996-2000. Nevertheless, multivariate analysis by the Cox model based on incident cases proved that histological subtype and age are the only most important prognostic factors (cases with fibrous morphology and older age are associated with lower survival). CONCLUSION: In the incident case group the increase of survival for pleural mesothelioma of cases treated with recent therapeutic protocols doesn't reach statistical significance. These results are similar to those of previous studies conducted to identify prognostic factors for mesothelioma survival; they don't permit confirmation of the efficacy of the recent therapy on the population base cases and only allow one to suppose them in the cases of the non resident population. The efficacy of the recent therapy has to be further investigated with regard to the stage of the disease.

[Nasal sinus cancer registry of the province of Brescia]. / Il registro neoplasie naso-sinusali della provincia di Brescia.

Sinonasal cancers (SNC) are neoplasm uncommon; although strictly related to occupational risk factors, in the Brescia province the professional SNC was unknown to the Occupational Health Service until short time ago. During the first nineties, a retrospective study has carried out to detect SNC and it has showed several occupational SNC cases. A local SNC population based Register was subsequently set up in 1994, covering 1,044,544 inhabitants. Between 1981 and 2000 104 SNC, occurred to 74 men and 30 women, have been collected; 98% of them was histologically diagnosed and 87.4% was of epithelial type. 36% of cases is located on maxillary sinus and the 31.7% on the ethmoidal sinus; 43% is the squamous cell carcinoma and 13.7% is the intestinal adenocarcinoma. The annual standardised incidence rates (on the Italian population, census 1981, x 100,000) on 1990-1995 and 1996-2000 are respectively 1 and 1 in men, 0.3 and 0.4 in women, in accordance with those esteemed in others industrialised provinces. In 1990-1995 the survival observed after 1, 3 and 5 years are respectively 83.8%, 67.7% and 48.3%. Anamneses were collected on 83 SNC cases among the epithelial type cancer. In men the 33% was exposed to occupational risk factors: wood (13 cases), leather (6 cases) and chromium (1 case) dusts. Among works probably related to SNC, agriculture, construction and textile reached respectively the 20.5% for both sex, 16.4% for men and 18% for women. As for non occupational risk factors suggested by literature, smoke appear to be the most relevant, related to the 52% of all cases and reaching the 64% in men. Among the women, polyps and inverted papillomas (31%), and also chronic rhinitis and sinusitis (13.6%) are more frequently observed. Some problems still limiting the work and its usefulness are discussed.