Relevance of vitamin D deficiency in patients with chronic autoimmune atrophic gastritis: a prospective study.

BACKGROUND: Chronic autoimmune atrophic gastritis (CAAG) is an autoimmune disease characterized by hypo/achlorhydria. A role of CAAG in the pathogenesis of nutritional deficiencies has been reported, therefore we hypothesized a possible association between CAAG and 25-OH-Vitamin D [25(OH)D] deficiency. Aim of the present study is to evaluate the prevalence of 25(OH)D deficiency in CAAG patients. METHODS: 87 CAAG patients (71 females; mean age 63.5 ± 12.8 years) followed at our Centre from January 2012 to July 2015 were consecutively evaluated. 25(OH)D, vitamin B12, parathormone, and calcium were measured in all the CAAG patients. The results were compared with a control group of 1232 healthy subjects. RESULTS: In the CAAG group the mean 25(OH)D levels were significantly lower than in the control group (18.8 vs. 27.0 ng/ml, p < 0.0001). 25(OH)D levels < 20 ng/ml was observed in 57 patients, while levels < 12.5 ng/ml in 27 patients. A significant correlation between vitamin B12 values at diagnosis and 25(OH)D levels was observed (rs = 0.25, p = 0.01). Interestingly, the CAAG patients with moderate/severe gastric atrophy had lower 25(OH)D values as compared to those with mild atrophy (11.8 vs. 20 ng/ml; p = 0.0047). Moreover, the 25(OH)D levels were significantly lower in CAAG patients with gastric carcinoid as compared to those without gastric carcinoid (11.8 vs. 19.8 ng/ml; p = 0,0041). CONCLUSION: Data from the present study showed a significant reduction of 25(OH)D levels in CAAG patients and a possible impairment of vitamin D absorption in CAAG may be postulated. Any implication to the genesis of gastric carcinoids remains to be elucidated.

25(OH)D Levels in Relation to Gender, Overweight, Insulin Resistance, and Inflammation in a Cross-Sectional Cohort of Northern Italian Workers: Evidence in Support of Preventive Health Care Programs.

OBJECTIVE: In recent years, the welfare of workers and the prevention of chronic disabling diseases has become a topic of great interest. This study investigates serum levels of total 25-hydroxyvitamin D (25(OH)D) in a cohort of overweight-obese and insulin-resistant northern Italian indoor workers in apparent good health followed a nutritional education program. METHODS: An observational cross-sectional study on 385 patients (females = 291, males = 94), age range 18-69 years and body mass index (BMI) > 25 kg/m2, was performed at the Department of Occupational Medicine Milan, Italy, latitude 45.465454 N. We evaluated nutritional intakes, occupational and leisure physical activity, anthropometric measurements, impedance evaluation, blood pressure, the presence of metabolic syndrome (MetS) and nonalcoholic fatty liver diseases (NAFLD) by fatty liver index (FLI). Hematologic and biochemical parameters and (25(OH)D) levels were evaluated from fasting blood samples. RESULTS: Only 10.91% of subjects had optimal values of 25(OH)D; 17.40% of the remaining 89.09% subjects were severely deficient, with no gender difference and insufficient intake of vitamin D. Only 28% declared leisure physical activity; 39.48% had metabolic syndrome and 62.60% had an FLI > 30. An inverse relationship between 25(OH)D levels and BMI was found, with a significant reduction of total 25(OH)D serum concentrations in winter. The homeostasis model assessment-insulin resistance (HOMA-IR) is positively related to BMI and inversely related to 25(OH)D concentrations. A positive correlation between vitamin D and leisure physical activity was found. At univariate analysis adjusted for age, gender and BMI, an inverse relationship between vitamin D and FLI was observed in both genders. The correlation between 25(OH)D levels, inflammation markers, BMI, and FLI showed an increased risk of cardiovascular disease in this cohort of workers. CONCLUSION: Our results suggest the rationale for a large-scale screening program for vitamin D by means of easily implementable low-cost preventive supplementation.

Three-year analysis of repeated laboratory tests for the markers total cholesterol, ferritin, vitamin D, vitamin B12 , and folate, in a large research and teaching hospital in Italy.

RATIONALE, AIMS AND OBJECTIVES: The increasing number of diagnostic tests requests all over the world is a problem that can partially be explained by inappropriate testing. Impact on the total costs of health systems becomes relevant when tests are performed in a large amount. In this paper, retesting of total cholesterol, ferritin, vitamin B12 , vitamin D, and folate is assessed. METHODS: The Quality Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano (Fondazione) decided to perform a first assessment of the appropriate use of the laboratory tests cholesterol, ferritin, vitamin B12 , vitamin D, and folate focusing on the retesting interval for the same patient in the time period January 1, 2012, to December 31, 2014, in every care setting. The minimum retesting intervals were chosen following the ACB recommendations. The Fondazione is a research and teaching hospital with 3 emergency units (adult, pediatric, and obstetric), kidney, liver, lung, cornea, and bone marrow transplant centers and a medical school. Record linkage of laboratory records selected for the time interval January 1, 2012, to December 31, 2014, was applied using tax code. For each marker, the distribution of retesting intervals was evaluated for every year and the total period. With the same record linkage variable, requests on inpatients were identified from hospital discharge records. A cost analysis of inappropriate retesting was performed for every test. RESULTS: We examined 466 035 requests for 113 019 patients. Proportions of tests judged potentially inappropriate varied between 8.1% for 1,25-dihydroxy vitamin D and 37.1% for total cholesterol. The rates of inappropriate tests from year to year never showed significant decrease, and the maximum increase corresponded to an odds ratio of 1.85 (95% CI, 1.36-2.51) for 1,25-dihydroxy vitamin D from 2012 to 2013. Calculated loss of money was approximately €500 000 in the 3 years. CONCLUSIONS: Inappropriate requests represent a waste of time and money resources. Our analysis highlighted economically unacceptable rates of inappropriate retesting, with no evidence of decreasing trend. Actions to raise awareness in clinicians or automated electronic solutions are necessary to limit unnecessary test repetitions.

Impact of Vitamin D on the Clinical Outcome of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: Report on a Series from a Single Institute.

BACKGROUND/AIMS: Vitamin D deficiency is hypothesized to represent a risk factor in several neoplasms. The aim of this study was to determine whether serum 25-hydroxyvitamin D (25-OHvitD) deficiency represents a risk factor for neuroendocrine neoplasms (NENs) and can be associated with overall survival (OS) and progression-free survival (PFS). METHODS: From 2010 to 2015, 138 patients with gastro- entero-pancreatic NENs (61 females; median age, 63 years) were included in the study. Serum 25-OHvitD levels, which were measured at baseline, were defined as deficient if ≤20 ng/mL. In such cases, 25-OHvitD supplementation was administered to the patients. The possible associations between 25-OHvitD levels and disease grading, staging, overall OS, and PFS were considered. Furthermore, the possible association between 25-OHvitD supplementation and PFS or OS was evaluated by Cox proportional hazards regression. RESULTS: Median 25-OHvitD levels were 12.9 ng/mL (range 2-32); in detail, 94 patients (68%) had ≤20 ng/mL, with 46 cases (33%) having ≤10 ng/mL. An inverse correlation was observed between 25-OHvitD levels and OS (p = 0.03, rs = -0.18) and PFS (p = 0.01, rs = -0.22). At Cox proportional hazards regression, mortality was not related to 25-OHvitD levels; however, there was an association between 25-OHvitD supplementation and OS (p < 0.002). CONCLUSIONS: Vitamin D deficiency is highly prevalent among NEN patients. 25-OHvitD supplementation potentially plays an important role in the correction of 25-OHvitD values, and has an influence on the clinical outcome. However, further studies are needed to confirm this observation.

Thyroid Status and Mortality Risk in Older Adults With Normal Thyrotropin: Sex Differences in the Milan Geriatrics 75+ Cohort Study.

BACKGROUND: Thresholds of optimal thyroid status in old age are controversial. We investigated the longitudinal association between thyroid parameters and 10-year all-cause mortality risk in older outpatients with normal thyrotropin (TSH) and modification by sex and age. METHODS: Baseline TSH, free thyroxine (fT4), and free triiodothyronine (fT3) were assessed in the Milan Geriatrics 75+ Cohort Study. 324 men and 609 women older than 75 years had normal TSH. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for the associations between thyroid parameters and mortality risk using Cox regression. Sex-stratified analyses were adjusted for sociodemographic factors and comorbidities. RESULTS: 233 men and 367 women died during follow-up. After adjustment, each 1-mU/L higher TSH was associated with decreased mortality risk in men (HR 0.83, 95% CI 0.69-0.98), but not in women (HR 1.09, 95% CI 0.95-1.24) (p for sex interaction = .006). Each 1-ng/L higher fT4 was associated with increased mortality risk in men (HR 1.11, 95% CI 1.02-1.22), but not in women (HR 0.98, 95% CI 0.93-1.04) (p for sex interaction = .013). Each 1-pg/mL higher fT3 was associated with decreased mortality risk in women (HR 0.77, 95% CI 0.60-0.98), but not in men (HR 0.80, 95% CI 0.57-1.13). The inverse association between TSH and mortality was most pronounced in men older than 85 years. CONCLUSIONS: Among older outpatients with normal TSH, higher TSH and lower fT4 were associated with decreased mortality risk in men but not in women. When assessing thyroid status, sex and age should be taken into account.

Blood pressure and 10-year mortality risk in the Milan Geriatrics 75+ Cohort Study: role of functional and cognitive status.

BACKGROUND: Optimal blood pressure targets in older adults are controversial. OBJECTIVE: to investigate whether the relation of blood pressure with mortality in older adults varies by age, functional and cognitive status. DESIGN: longitudinal geriatric outpatient cohort. SETTING: Milan Geriatrics 75+ Cohort Study. SUBJECTS: One thousand five hundred and eighty-seven outpatients aged 75 years and over. METHODS: The relations of systolic (SBP) and diastolic blood pressure (DBP) with mortality risk were analysed using Cox proportional hazards models. Blood pressure, Mini-Mental State Examination (MMSE) and Basic Activities of Daily Living (ADL) were assessed at baseline. All analyses were adjusted for socio-demographic factors, co-morbidities and medications. RESULTS: One thousand and forty-six patients died during 10-year follow-up. The relationships of SBP and DBP with mortality risk were U-shaped; SBP of 165 mmHg and DBP of 85 mmHg were associated with the lowest mortality. Patients with SBP < 120 mmHg and patients with SBP 120-139 mmHg had 1.64-fold (95% confidence intervals, CI 1.21-2.23) and 1.32-fold (95% CI 1.10-1.60) higher mortality risk than patients with SBP 160-179 mmHg (P values 0.001 and 0.004, respectively). In patients with SBP below 180 mmHg, higher SBP was associated with lower mortality in patients with impaired ADL and MMSE but not in those with preserved ADL and/or MMSE (P for interaction 0.033). Age did not modify the correlation of SBP with mortality. CONCLUSIONS: The correlations of SBP and DBP with mortality were U-shaped. Higher SBP is related to lower mortality in subjects with impaired ADL and MMSE. ADL and MMSE may identify older subjects who benefit from higher blood pressure.

Association between red cell distribution width and risk of venous thromboembolism.

BACKGROUND: An association between high red cell distribution width (RDW) and venous thromboembolism (VTE) has been observed. However, it is not known whether this association differs within various manifestations of VTE, nor if there is an interaction between RDW and thrombophilia abnormalities on the risk of VTE. AIMS: To investigate whether RDW is a marker of the risk of VTE; to identify subgroups of patients in which the association between RDW and VTE is stronger; to investigate a possible interaction between RDW and thrombophilia abnormalities. METHODS: Case-control study on 730 patients with a first objectively-confirmed VTE episode (300 unprovoked and 430 provoked) consecutively referred to our Center between 2007 and 2013, and 352 healthy controls. Blood was taken for a thrombophilia work-up and a complete blood count, including RDW, at least three months after VTE. RESULTS: Individuals with RDW above the 90(th) percentile (>14.6%) had a 2.5-fold increased risk of VTE compared to those with RDW ≤90(th) percentile, independently of age, sex, body mass index, other hematological variables and renal function (adjusted odds ratio: 2.52 [95%CI:1.42-4.47]). The risk was similar for unprovoked and provoked VTE, and slightly higher in patients with pulmonary embolism (adjusted odds ratio 3.19 [95%CI:1.68-6.09]) than in those with deep vein thrombosis alone (2.29 [95%CI:1.22-4.30]). No interaction between high RDW and thrombophilia abnormalities on the risk of VTE was observed. CONCLUSION: Our findings confirm RDW as an independent and easily available marker for stratification of the risk of VTE.

Carbohydrate 19-9 antigen is not a marker of liver disease in patients with cystic fibrosis.

Serum concentration of carbohydrate 19-9 antigen (CA 19-9), a sensitive marker of pancreatic cancer and cholangiocarcinoma, increases in a variety of liver diseases due to higher production and release by bile duct cells. Biliary epithelial cells are primarily affected in liver disease associated with cystic fibrosis (CF), which develops in up to 30% of CF patients. Our aim was to evaluate the usefulness of serum CA 19-9 concentration as a test of liver involvement in CF. Serum concentration of CA 19-9, liver enzymes, bile acids, and total amylase was determined in 107 CF patients (49 with and 58 without liver disease) and 56 healthy subjects. Serum CA 19-9 concentration was significantly higher in CF patients (67 U/ml, 95% CI 53.5-80.5 U/ml) than in controls (11.8 U/ml, 95% CI 2.5-44 U/ml; p < 0.001) and in CF patients with liver disease (92.3 U/ml, 95% CI 75-109.5 U/ml) compared to CF patients without liver disease (46.6 U/ml, 95% CI 27.8-65.4 U/ml; p < 0.001). In CF patients, stepwise logistic regression analysis identified alanine aminotransferase, gamma-glutamyltranspeptidase, amylase, and CA 19-9 as the most useful predictors of liver disease (p < 0.0001). Receiver-operating characteristic (ROC) curve analysis revealed gamma-glutamyltranspeptidase and CA 19-9 as the best tests for identification of liver disease in CF patients; at a CA 19-9 cut-off arbitrarily fixed at 73 U/ml, positive and negative predictive value was 70% and 78%, respectively (sensitivity 57%, specificity 81%). To increase sensitivity to 94%, the cut-off had to be fixed at 31 U/ml, which corresponds to a specificity of only 36.2% (predictive value 33%). Our study indicates that measurement of the serum CA 19-9 concentration alone cannot be proposed as a reliable test of early hepatic involvement in CF.

Use of serum-soluble intercellular adhesion molecule-1 as a new marker of endometriosis.

OBJECTIVE: To investigate the hypothesis that soluble intercellular adhesions molecule-1 (sICAM-1) may be used as a new serum marker of endometriosis. DESIGN: Prospective cohort study. SETTING: An academic department specializing in gynecologic laparoscopy. PATIENT(S): Consecutive series of 120 women of reproductive age who underwent laparoscopy for benign gynecologic conditions. INTERVENTION(S): Data were collected on baseline clinical characteristics, and surgical and histologic diagnosis. MAIN OUTCOME MEASURE(S): Serum concentration of both CA125 and sICAM-1. RESULT(S): Endometriosis was documented in 71 women (stage I to II in 24 cases and stage III to IV in 47 cases). Serum levels of sICAM-1 were only slightly but not significantly increased in women with endometriosis compared with women without the disease. However, serum concentration of sICAM-1 in the 21 women who were found to have deep peritoneal endometriosis was significantly enhanced when compared with both women without the disease and those with other forms of endometriosis. The sensitivity and specificity of sICAM-1 in detecting deep peritoneal endometriosis were 0.19 and 0.97, respectively; whereas those of CA125 were 0.14 and 0.92, respectively. When both parameters were used concomitantly, the sensitivity and specificity were 0.28 and 0.92, respectively. CONCLUSION(S): Although the present study tends to support a role of sICAM-1 in the development of endometriosis, serum concentrations of this molecule do not seem to be an effective indicator for the diagnosis of either the early or advanced stage of endometriosis. However, an integrated clinical and laboratory approach using both CA125 and sICAM-1 may be helpful in specifically identifying women with deep peritoneal endometriosis.

Human chorionic gonadotropin patterns after a single dose of methotrexate for ectopic pregnancy.

OBJECTIVE: The great variability in human chorionic gonadotropin (HCG) levels after a single dose of methotrexate (MTX) for ectopic pregnancy makes it difficult to predict treatment failure. We describe different patterns of HCG levels. STUDY DESIGN: Fifty patients were injected i.m. with 50mg/m(2) of MTX for an ectopic pregnancy. Venous blood samples for HCG detection were obtained on the day of treatment (day 0), day 3 and day 7 and weekly until values were undetectable. Patients were classified as: group 1, persistent pathology (n=11); group 2, complete resolution with a decrease of HCG levels at day 3 (n=30); group 3, complete resolution after a rise of HCG values at day 3 (n=9). Statistical analysis was performed using the Mann-Whitney non-parametric test with 95% confidence intervals. RESULTS: Values of day 0 were similar for all the groups. HCG levels of group 3 decreased rapidly after day 3 and at day 7 they were significantly different from levels of group 1. Differences in HCG levels between groups 2 and 3 became indistinguishable from day 21. CONCLUSION: The observation of patients undergoing resolution after an initial increase of HCG levels justify an expectant management for 1 week in clinically stable patients. The strategy to separate HCG curves in patients undergoing resolution may shed light on the different clinical responses to therapy for ectopic pregnancies. However, the phenomenon of the immediate rise of HCG should be better investigated.