Calcium-phosphate homeostasis and insulin resistance in men.

BACKGROUND AND AIMS: Data on P homeostasis in insulin resistance (IR) are still conflicting. We investigated calcium-phosphate homeostasis parameters in men with/without IR. METHODS AND RESULTS: 177 volunteers (aged 61.62 ± 12.11), whose body mass index (BMI) was 29.97 ± 6.35, were studied. On fasting blood and spot urine samples, we measured serum creatinine, sodium (sNa), potassium (sK), chloride (sCl), calcium (sCa), phosphate (sP), alkaline phosphatase total activity (ALP), glucose, insulin, parathyroid hormone (PTH), 25-hydroxy-vitamin D [25(OH)D], and urinary electrolytes corrected for creatinine (uNa/Cr, uK/Cr, uCl/Cr, uCa/Cr, and uP/Cr). Through the QUICKI index, we separated subjects with (IR+, n = 68) or without (IR-, n = 109) IR, and their parameters were compared. Associations were assessed by age-adjusted partial correlation, whose coefficients were compared by Fisher's transform. IR + had higher sP (3.54 ± 0.65 vs. 3.35 ± 0.47, p = 0.044) and lower uCa/Cr levels (0.073 ± 0.056 vs. 0.095 ± 0.072, p = 0.047) than IR-. BMI correlated with sP (r = 0.21, p < 0.05) and PTH (r = 0.29, p < 0.01). QUICKI negatively correlated with sCa (r = -0.22, p < 0.05) and positively with uCa/Cr (r = 0.21, p < 0.05), in turn correlating with uNa/Cr (r = 0.45, p < 0.001). In both groups, uCa/Cr correlated with eGFR and uNa/Cr (p < 0.05 to p < 0.001). In IR + only, sP correlated with BMI, PTH with insulin, and uP/Cr (p < 0.05 for all). IR+ and IR-coefficients differed (p < 0.05 to p < 0.001) for the correlation of sP with BMI and of PTH with insulin and uP/Cr. CONCLUSION: The higher sP and lower uCa/Cr levels found in men with IR + suggest that IR could modulate calcium-phosphate homeostasis, likely by affecting their renal handling.

Examining the role of value congruence, professional identity, and managerial job engagement in the budgetary participation-performance link.

BACKGROUND: In health care, important phenomena of perceived incompatibility between professional and managerial values have emerged as consequences of New Public Management reforms. Although there is a growing evidence on the variation in the enactment of hybrid roles by medical managers, existing research in health care management is mostly descriptive with little emphasis on the conditions under which hybrid roles are enacted and, importantly, on the effects of this variation on performance. PURPOSE: In this article, we seek to fill this research gap by empirically examining (a) whether budgetary participation aligns professional and organizational values, (b) the impact of this alignment on employees' work-related feelings and managerial performance, and (c) the effect of professional identity on value congruence. METHODOLOGY: Data were collected by a survey conducted in an Italian hospital, and partial least square was used to test the relationships among variables. RESULTS: Overall, results show that (a) high involvement in budgeting is instrumental in facilitating medical managers' value congruence, and this, in turn, positively effects managerial job engagement; (b) the effect of budgetary participation on value congruence depends on the extent of professional identity; and (c) as a result of enhanced value congruence and managerial job engagement, employees tend to deliver superior role performance. PRACTICE IMPLICATION: Findings of this study provide some guidance for managers on how organizations can take steps to guarantee effective support to hybrid professionals.

Investigating subtle kidney injury in primary hyperparathyroidism by means of sensitive and specific biomarkers.

OBJECTIVE: Kidney involvement is a common complication in primary hyperparathyroidism (PHPT). No study so far has assessed the prevalence of kidney injury developing before the reduction in glomerular filtration rate (GFR) in PHPT. The study was aimed at establishing the potential role of biomarkers of kidney injury in detecting subtle renal damage in patients with PHPT. DESIGN: Cross-sectional study. PATIENTS: A total of 69 postmenopausal patients with PHPT and 41 healthy age- and sex-matched subjects were studied. Exclusion criteria were as follows: GFR < 30 mL/min, chronic inflammatory disease, nephrotic syndrome, infection, malignancy, heart failure, recent exposure to iodinated contrast media or nonsteroidal anti-inflammatory drugs. MEASUREMENTS: We measured a panel of sensitive biomarkers of kidney injury in PHPT vs controls. RESULTS: Mean FGF23 and Klotho were higher in PHPT (72 ± 48 and 811 ± 366 pg/mL, respectively) than controls (53 ± 23.5 and 668.6 ± 17; P < .02 and P < .05). Urine KIM-1/uCr was significantly higher in PHPT (1.4-6  ± 1.3-6 ) than controls (9.2-7  ± 7-7 ; P < .05); this was particularly evident in the CrCl 60-89 mL/min category (1.36  ± 97 vs 8.2-7  ± 3.6-7 ; P < .02). Mean values of urine NGAL/uCr were higher in PHPT with (n = 28) compared to those without kidney stones (n = 35; 1.8-5  ± 1.4-5 and 1-5  ± 8-6 ; P < .0001). We found significant positive associations between urine NGAL/uCr and Ca (R = .292, P < .02) and urine KIM1/uCr and PTH (R = .329, P < .01). CONCLUSIONS: We propose the utilization of these molecules, particularly urine KIM-1/uCr and urine NGAL/uCr ratios for the assessment of subtle kidney injury in patients with PHPT. These molecules are elevated in tubular necrosis and have potential role in the development of kidney damage in PHPT, according to the severity of the disease.

Does DRG funding encourage hospital specialization? Evidence from the Italian National Health Service.

The impact of diagnosis-related group (DRG)-based funding has been analyzed along a wide range of dimensions. Its effects on hospital specialization, however, have been investigated only sparsely. This paper examines such effects in the context of the Italian National Health Service, where decentralization has produced a significant degree of variation in funding arrangements. To this end, a 9-year panel data set covering 762 Italian public and private hospitals was analyzed using a finite mixture model approach. Hospital specialization was measured by the internal Herfindahl-Hirschman Index. Three variables were introduced as proxies for the choices made by Italian Regions with respect to the development and use of their DRG systems. The best finite mixture model identified three groups of hospitals, two of which sizeable. Of these, one included nearly all public hospitals, while the other was composed almost exclusively of small and medium-sized investor-owned hospitals. Averagely, private and smaller hospitals showed a stronger tendency to specialize over time. The positive impact of DRG funding on the hospitals' propensity to specialize found only limited empirical support. Moreover, it emerged as comparatively much smaller for public hospitals vis à vis private ones.

The Epidemiology of Hypoparathyroidism in Italy: An 8-Year Register-Based Study.

Hypoparathyroidism is a rare endocrine disorder, but few studies have focused on the epidemiology and hospital management of the disease and none has been performed in Italy. We investigated the prevalence of different forms of hypoparathyroidism among hospitalized patients in Italy during an 8-year period. This study is designed as a retrospective register-based study. We retrieved data from the "Record of Hospital Discharge" (SDO) of the Italian Health Ministry, from the year 2006 to 2013 and analyzed the codes corresponding to hypoparathyroidism-related diagnoses. The inpatient prevalence of the disease was also calculated after excluding repeated hospitalizations. Overall, 27,692 hospitalization episodes for hypoparathyroidism were identified during the entire period (72.2% in women and 27.8% in men; mean age 49.5 ± 22.9 years). The mean length of stay was 7.4 ± 9.8 days (25.9% of the episodes requiring less than 3 days of stay). The mean hospitalization rate for hypoparathyroidism was 5.9/100,000 inhabitants per year and there was a significant decrease during the period of 2006-2013 (p < 0.0001). The mean hospitalization rate for postsurgical hypoparathyroidism was 1.4/100,000 inhabitants per year and the trend showed a significant reduction during the years (p < 0.0001). The mean prevalence of hypoparathyroidism among inpatients was 5.3/100,000 inhabitants per year, and there was a significant decrease over the years (p < 0.0001). Hypoparathyroidism, particularly the postsurgical form of the disease, is not an uncommon condition among hospitalized patients in Italy. We observed a tendency to a decrease in the frequency of hospitalization during the period 2006-2013.

Effect of a single intravenous zoledronic acid administration on biomarkers of acute kidney injury (AKI) in patients with osteoporosis: a pilot study.

AIMS: The pilot study was designed to evaluate the early effect of intravenous (i.v.) zoledronic acid (ZA) on renal function. METHODS: Five mg i.v. ZA was administered to 23 patients with osteoporosis (17 women and 6 men, mean age 73 ± 7 SD years). Urinary NGAL, KIM-1, and MCP-1, plasma (p) MCP-1 and serum (s) IL-18, serum calcium (sCa), Creatinine clearance (CrCl), parathyroid hormone (PTH), plasma C-terminal FGF23 (pFGF23), serum (s) Klotho, calcium excretion (CaEx) and renal threshold phosphate concentration/GFR (TmPO4 /GFR) were assessed at baseline, 24 h and Day 30 after administration. RESULTS: There was a significant decrease in sCa and CaEx at 24 h (-4.1 ± 2.8%, P < 0.01 and -28 ± 59%, P < 0.05, respectively) and Day 30 (-3.9 ± 4%, P < 0.001 and -26 ± 43%, P < 0.01) and a significant increase in PTH (79.8 ± 95.8%) at Day 30 (P < 0.001) compared to baseline. TmPO4 /GFR decreased significantly at 24 h and Day 30 (-8.6 ± 15.9%, P < 0.05 and -11.3 ± 13.5%, P < 0.001) compared to baseline. We observed no difference in the concentration of pFGF23, sKlotho and urinary AKI biomarkers at any time points. Mean levels of sIL-18 and pMCP-1 increased significantly at 24 h (44 ± 88%; P < 0.01 and 198 ± 237%; P < 0.001) and returned to baseline at Day 30. CONCLUSIONS: Our pilot study suggests that there is no direct acute effect of ZA on kidney function. The increase in plasma MCP-1 and serum IL-18 concentration could be associated with the stimulation of immunity mechanisms occurring soon after the administration of the drug. Secondary hyperparathyroidism develops shortly after the infusion of ZA and is maintained even after 1 month.

Measures of type 2 diabetes burden in Italy assessed using the AMD dataset over a twelve year span across the Great Recession.

Patients with Type 2 Diabetes Mellitus (T2DM) are rapidly increasing in Italy due to aging, preventable risk factors, and worsening socioeconomic context. T2DM and its sequelae take a heavy toll on healthcare systems and the economy, given costly management, difficulties in coping with everyday life, and decreasing patient/worker productivity. Considering long life expectancy in Italy and a decreasing mortality rate due to T2DM, this study aims to calculate the years lived with disability (YLDs) of T2DM and its sequelae grouped into three categories: Neuropathy, Chronic Kidney Disease and No Complications, taking into consideration sex, year, and geographical location. This is the first attempt to measure YLDs from data that do not rely on self-reported diabetes diagnoses. Data come from the Italian Diabetologists Association dataset, the most comprehensive longitudinal source of national outpatient data. YLDs are obtained by multiplying the number of individuals living with a specific health condition and a disability weight which represents the magnitude of health loss associated with that particular condition. Findings show increasing YLD age-standardized rates for T2DM and its sequelae, especially Neuropathy, with the trend being stronger in the central macro-region and among men, and that 2009 marks a structural change in YLD growth rate. Systematic data collection for measuring the burden of diseases is key, among other things, to policy-making and implementation.

Carotid intima-media thickness in surgically or conservatively managed patients with primary hyperparathyroidism.

CONTEXT: Current evidence of cardiovascular (CV) risk in primary hyperparathyroidism (PHPT) is still inconsistent. OBJECTIVE: To prospectively investigate changes of early atherosclerosis in patients with PHPT undergoing parathyroidectomy (PTx) or conservative management, according to Consensus criteria. METHODS: Biochemical parameters of PHPT, CV risk factors (systolic and diastolic blood pressure-BP-, total-, HDL- and LDL-cholesterol, triglyceride, glycosilated hemoglobin, and HOMA-IR), and carotid intima-media thickness (IMT) and plaque were assessed in 52 consecutive postmenopausal PHPT patients both at baseline and ≥24 months after surgery (PTx: n = 22) or conservative management (no-PTx: n = 30). RESULTS: At baseline, PTx and no-PTx showed comparable age, BMI, renal function, 25(OH)D levels, and did not differ for CV risk factors, IMT and plaques, nor for the prevalence of smoking, diabetes mellitus, antihypertensive or statin therapy, while differing for all parameters characterizing PHPT. Follow-up length in PTx was longer (p = 0.004) than in no-PTx. Parameters characterizing PHPT significantly improved ≥24 months after surgery, whereas in no-PTx serum phosphate slightly decreased and PTH increased. Systolic and diastolic BP increased at follow-up in both groups, while other CV risk factors did not significantly vary. In PTx IMT did not significantly vary after surgery (0.85 ± 0.14 to 0.89 ± 0.22 mm, p = 0.366), whereas it significantly increased in no-PHPT (0.80 ± 0.18 to 0.93 ± 0.23 mm, p = 0.008), even adjusting for BP values. Plaque prevalence and incidence did not significantly differ in the two groups. CONCLUSION: Our results suggest that in postmenopausal PHPT patients subclinical atherosclerosis could be halted by PTx, whereas it worsens over time in not operated patients with milder disease.

Effect of 2 Years of Monthly Calcifediol Administration in Postmenopausal Women with Vitamin D Insufficiency.

BACKGROUND: We assessed the long-term (24 months) efficacy and safety of monthly calcifediol (0.266 mg) in the correction and maintenance of total 25(OH)D levels in postmenopausal women with basal values <30 ng/mL. METHODS: We initially enrolled 45 consecutive patients during the period September 2019-September 2020. After an initial visit, patients were instructed to return at 3, 6, 9, 12 and 24 months for measuring serum total 25(OH)D, ionised calcium, creatinine and isoenzyme of alkaline phosphatase (bALP). Here, we report only the per-protocol analysis, because the COVID-19 pandemic precluded adherence to the scheduled visits for some patients. RESULTS: The patients' mean age was 62.4 ± 9.0 years. Mean basal 25(OH)D levels were 20.5 ± 5.3 ng/mL. There was a continuous increase of mean 25(OH)D values (p for trend < 0.001). However, mean values at month 24 (36.7 ± 15.9) were not significantly different in respect to values at month 12 (41.2 ± 11.18). At 24 months, only 1 out 19 patients had a value <20 ng/mL. There was a significant decrease with time of mean values of bALP (p < 0.0216), with no significant changes between 12 and 24 months. No significant changes were observed as far as ionised calcium or creatinine were concerned. CONCLUSIONS: The long-term administration of calcifediol maintains stable and sustained 25(OH)D concentrations, with no safety concerns.

Bone Marrow Adipose Tissue Is Increased in Postmenopausal Women With Postsurgical Hypoparathyroidism.

CONTEXT: Suppression of bone turnover, greater trabecular volume, and normal-high normal all-site bone mineral density (BMD) are hallmarks of postsurgical hypoparathyroidism (HypoPT). Impairment in the trabecular microarchitecture with possible higher risk of vertebral fractures (VF) in women with postmenopausal HypoPT has also been described. Currently, no data on bone marrow adipose tissue (BMAT) are available in HypoPT. OBJECTIVE: To assess BMAT by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) in postmenopausal women with chronic postsurgical HypoPT. METHODS: This cross-sectional pilot study, conducted at an ambulatory referral center, included 29 postmenopausal women (mean age 66 ± 8.4 years) with postsurgical HypoPT and 31 healthy postmenopausal women (mean age 63 ± 8.5). Lumbar spine MRI was performed and BMAT was measured by applying PRESS sequences on the L3 body. Lumbar spine, femoral neck, and total hip BMD were measured by dual x-ray absorptiometry (DXA); site-matched spine trabecular bone score (TBS) was calculated by TBS iNsight (Medimaps, Switzerland); VF assessment was performed with lateral thoracic and lumbar spine DXA. RESULTS: Fat content (FC) and saturation level (SL%) were higher (P <.0001 and P <.001), while water content (W) was lower in HypoPT compared to controls (P <.0001). FC significantly correlated with years since menopause and body weight (P <.05) in HypoPT, while TBS negatively correlated with FC and SL% (P <.05) and positively with residual lipids (RL) and W (P <.05). CONCLUSION: We demonstrate for the first time that BMAT is increased in postmenopausal women with postsurgical hypoparathyroidism and negatively associated with trabecular microarchitecture.

Impairment in muscle strength and its determinants in primary hyperparathyroidism: A study in postmenopausal women.

Neuromuscular impairment is described among the non-classical complications of primary hyperparathyroidism (PHPT). However, the extent of this complications and related mechanisms have not been fully addressed. The study aimed at assessing muscle strength and its main determinants in postmenopausal women with PHPT. We studied 48 postmenopausal women with PHPT (mean age 60.8 ± 5.6 SD years; BMI 25.6 ± 5.5 kg/m2) and 38 healthy postmenopausal women (mean age 58.6 ± 5.9; BMI 25.2 ± 3.5). In all subjects, the maximum voluntary contraction (MVC, Newton, N) was measured by Hand held Dynamometer (Kayser Italia srl, Livorno, Italy) and the lumbar spine, total hip, femoral neck, and non dominant distal one-third radius areal BMD (aBMD) by dual X-ray absorptiometry (DXA) (Hologic, Waltham, MA). Serum ionized calcium (Ca++), parathyroid hormone (PTH), phosphorus (P), and 25-hydroxyvitaminD [25(OH)D] levels were measured in both groups. A subgroup of 30 PHPT women agreed to participate to the follow-up sub-study and were re-assessed 24 months after parathyroidectomy (n = 15) or after baseline evaluation (n = 15). Patients with PHPT had significant lower MVC values compared to healthy women (p < 0.001). As expected, serum Ca++ and PTH levels were higher and P lower in PHPT compared to controls. We observed a significant association between MVC and total hip and one-third radius aBMD (R = 0.320 and 0.370, p < 0.05) and negative association with Ca++ (R = -0.340, p < 0.05) in the PHPT group; MVC was positively associated with one-third radius aBMD (R = 0.360, p < 0.05) and negatively with age, BMI and myostatin (R = -0.390, -0.340 and -0.450, p < 0.05) in the group of healthy women. The linear model using BMI, Ca++, P, 25(OH)D, PTH, myostatin, and aBMD as covariates showed that one-third radius aBMD was positively associated with MVC in PHPT patients (p < 0.02) and in healthy subjects (p < 0.001). Additionally, serum PTH and myostatin were negatively associated with MVC in healthy subjects (p < 0.03 and p < 0.01). The linear model showed that surgery was associated with an increase in MVC (p < 0.05) in PHPT patients after 24 months, all other variables being equal and by controlling for baseline values of MVC. Handgrip strength is significantly impaired in postmenopausal women with PHPT. Some common mechanisms influencing muscle function exist in PHPT and in healthy subjects; they are associated with the reduced aBMD at cortical sites. Hypercalcemia seems to be one of the main determinants of impairment in muscle strength in PHPT, while no role is played by myostatin.

The Mutual Interplay between Bone, Glucose and Lipid Metabolism: The Role of Vitamin D and PTH.

BACKGROUND: We sought to investigate the mutual interplay between bone, glucose and lipid metabolism in a wide cohort of community-based subjects. METHODS: We studied 1240 blood donors (F/M ratio 1/3.2, mean age 41.9 ± 11.7 SD). Serum ionized (Ca++), magnesium (Mg++), 25-hydroxy-vitamin D [25(OH)D], PTH-1-84, 1,25-dihydroxyvitamin D [1,25(OH)2D], total cholesterol (C), HDL-C, triglycerides and glucose were measured and LDL-C levels were calculated in all subjects. RESULTS: 25(OH)D negatively correlated with BMI (R = -0.11), PTH (R = -0.16) (p < 0.0001), total C (R = -0.06, p < 0.05) and triglycerides (R = -0.13, p < 0.0001) and positively with 1,25(OH)2D (R = 0.12) and creatinine (R = 0.17) (p < 0.0001). Serum PTH positively correlated with total C (R = 0.08, p < 0.01), LDL-C (R = 0.1, p < 0.001), triglycerides (R = 0.09, p < 0.01) and glucose (R = 0.15, p < 0.0001) and negatively with HDL-C (R = -0.09, p < 0.01). The odds of showing abnormal serum triglycerides and HDL-C increased as 25(OH)D decreased (p < 0.0001 and p < 0.03) and PTH increased (p < 0.03 and p = 0.05), while the odds of showing abnormal LDL-C levels increased in association with elevated PTH (p < 0.01). CONCLUSION: Vitamin D, PTH, glucose and lipid metabolism are mutually influenced. Hypovitaminosis D predisposes toward worsening lipid profiles through the actions of PTH, while serum PTH levels per se associate with higher glucose and LDL-C levels.

Quality of life and sexual functioning among endometrial cancer patients treated with one week adjuvant high-dose-rate vaginal brachytherapy schedule.

Purpose: To examine quality of life (QOL) and sexual functioning in a series of patients with intermediate- and high-intermediate risk endometrial cancer, treated with exclusive adjuvant one week high-dose-rate (HDR) vaginal brachytherapy (VBT) schedule. Material and methods: Between July 2008 and October 2013, 55 patients with diagnosis of endometrial cancer were treated with adjuvant exclusive VBT. All patients had undergone surgical treatment with a laparotomy approach before VBT. Post-operative VBT was administered 6-8 weeks after surgery. Treatment was delivered to vaginal vault using Nucletron HDR unit with iridium-192 source at a dose of 21 Gy/3 fractions of 7 Gy each, three times a week, every other day, prescribed at 0.5 cm depth of vaginal wall, and 3 cm in length from the apex. QOL was assessed using European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire Core-30 (QLQ-C30), and EORTC cancer-specific quality of life questionnaire (QLQ-CX24). Results: Median follow-up time was 92 months (range, 42-162 months). Questionnaires were carried out respectively at 1, 3, 6, 12, 24, 36, 48, and 60 months after the end of BT. Response rate to questionnaires was 100% (n = 55). Nineteen patients (35%) answered all the questions of surveys, while 36 patients (65%) completed the surveys, except for questions on sex activity, vaginal function, and sex enjoyment. Longitudinal analysis during 5-year follow-up period showed a statistically significant trend towards worsening of fatigue, constipation, and diarrhea. Overall physical functioning and role functioning was not impaired after VBT. Over the time, sex enjoyment improved, except for elderly patients. For emotional functioning, sex worry and social functioning presented no significant time-related effect. Conclusions: One week brachytherapy schedule to vaginal cuff is generally well-tolerated. QOL does not worsen after applying vaginal brachytherapy.

An ANN experiment on the Indian economy: can the change in pollution generate an increase or decrease in GDP acceleration?

In recent years, the concept of sustainable development has enriched numerous scientific researches. Therefore, the combination of economic growth and the environment has been the subject of numerous econometric and statistical models. They demonstrated that there is a two-way relationship between economic growth and pollution. So, we use data from the World Bank database (1971-2014) to assess the possibility that a change (positive or negative) in pollution in India generates a gross domestic product acceleration. Through a Machine Learning approach via artificial neural network analysis, empirical findings show that a deep neural network can predict the outcome under study. The novelty of this paper is to have determined the results through a model based on a comparison with a highly developed country (Japan). The results obtained show that in a country like India, 76% of the time, a change in pollution evolves into a change in the acceleration of the economic growth.

Vertebral Fracture Assessment in Postmenopausal Women With Postsurgical Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is a rare endocrine disorder whose skeletal features include suppression of bone turnover and greater volume and width of the trabecular compartment. Few and inconsistent data are available on the prevalence of vertebral fractures (VF). OBJECTIVE: To evaluate the prevalence of VF assessed by vertebral fracture assessment (VFA) in postmenopausal women with chronic postsurgical hypoparathyroidism. DESIGN: Cross-sectional study. SETTING: Ambulatory referral center. PATIENTS OR OTHER PARTICIPANTS: Fifty postmenopausal women (mean age 65.4 ± 9 years) with chronic postsurgical hypoparathyroidism and 40 age-matched healthy postmenopausal women (mean age 64.2 ± 8.6). MAIN OUTCOME MEASURES: Lumbar spine, femoral neck, and total hip bone mineral density were measured by dual X-ray absorptiometry (Hologic Inc., USA) in all subjects. Site-matched spine trabecular bone score was calculated by TBS iNsight (Medimaps, Switzerland). Assessment of VF was made by VFA (iDXA, Lunar GE, USA) using the semiquantitative method and the algorithm-based qualitative assessment. RESULTS: All-site BMD values were higher in the hypoparathyroid vs the control group. By VFA, we observed a 16% prevalence of VF in hypoparathyroid women vs 7.5% in control subjects. Among those with hypoparathyroidism who fractured, 5 (62.5%) had grade 1 wedge, 2 (25%) had grade 2 wedge, and 1 (12.5%) had grade 2 wedge and grade 2 biconcave VF. In the hypoparathyroid group, 57% with VFs and 32% without VFs had symptoms of hypoparathyroidism. CONCLUSION: We demonstrate for the first time that in postmenopausal women with chronic postsurgical hypoparathyroidism, VFs are demonstrable by VFA despite normal BMD.

Inhibition of the RANKL with denosumab has no effect on circulating markers of atherosclerosis in women with postmenopausal osteoporosis: a pilot study.

PURPOSE: We evaluated the early effect of denosumab on circulating markers of atherosclerosis in women with postmenopausal osteoporosis. METHODS: Denosumab (60 mg) was administered subcutaneously every 6 months (m) in 27 women (mean age 75 ± 5 years) with postmenopausal osteoporosis and high cardiovascular risk for a total of 24 m. Zoledronic acid was administered in 6 age-matched women as a single intravenous dose. Serum levels of vascular cell adhesion protein 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E and P selectin, CD-40 ligand (CD40L), interleukin-6 (IL-6), matrix metalloproteinase (MMP) 1 and 9, monocyte chemoattractant protein-1 (MCP-1), fibrinogen (FBG), and high sensitivity C-reactive protein (hs-CRP) were measured at baseline, 15 days (d), 2, 6 and 12 m after dosing. In the denosumab group, observation was extended to 24 m as secondary endpoint. RESULTS: Serum ICAM-1 levels showed significant increase in the zoledronic acid group (+18 ± 0.1%; p < 0.01) at 12 m. In the denosumab group, we observed a significant increase in serum CD40L (+2 ± 0.8%; p < 0.001), MMP-1 (+11 ± 0.4%, p < 0.02), and MMP-9 (+39.4 ± 0.8%, p < 0.01) at 24 m. There was a significant increase in serum FBG and hs-CRP in both groups at 12 m (denosumab:+2.2 ± 0.2% and +50.3 ± 1.6%; zoledronic acid: +9.4 ± 0.1 and +81.8 ± 0.8%; p < 0.01). No significant between-group differences were found. CONCLUSIONS: 24-m treatment with denosumab has no effect on the circulating markers of atherosclerosis in women with postmenopausal osteoporosis. Fluctuation of serum ICAM-1, CD40L, MMPs, FBG and hs-CRP can be ascribed to perturbation of immunological mechanisms stimulated by denosumab and zoledronic acid.

Finite mixture models for mapping spatially dependent disease counts.

A vast literature has recently been concerned with the analysis of variation in disease counts recorded across geographical areas with the aim of detecting clusters of regions with homogeneous behavior. Most of the proposed modeling approaches have been discussed for the univariate case and only very recently spatial models have been extended to predict more than one outcome simultaneously. In this paper we extend the standard finite mixture models to the analysis of multiple, spatially correlated, counts. Dependence among outcomes is modeled using a set of correlated random effects and estimation is carried out by numerical integration through an EM algorithm without assuming any specific parametric distribution for the random effects. The spatial structure is captured by the use of a Gibbs representation for the prior probabilities of component membership through a Strauss-like model. The proposed model is illustrated using real data.

Factors affecting vitamin D deficiency in active inflammatory bowel diseases.

BACKGROUND: Hypovitaminosis D is prevalent in inflammatory bowel disease (IBD) and may be associated with disease activity. AIM: This study evaluated vitamin D (VitD) status in an Italian cohort of IBD patients, not taking VitD supplementation. We investigated risk factors for VitD deficiency and its correlation with disease activity. METHODS: VitD levels were measured in 300 consecutive outpatients (42% with Crohn's Disease (CD) and 58% with ulcerative colitis (UC), 56% male) from a tertiary referral center. Data from the IBD cohort were compared with those of 234 healthy controls, matched by sex, age, and the month in which VitD levels were measured. RESULTS: The mean VitD level in IBD patients was significantly lower than in controls (18.9 ng/ml vs. 25 ng/ml, p < 0.001) when accounting for gender, age, and season. VitD deficiency was present in 62% of IBD patients. Risk factors for deficiency were: age <40 and ≥60 years, winter, previous surgery, C-reactive protein (CRP) ≥0.5 mg/dl, and erythrocyte sedimentation rate ≥20 mm/h. In multivariate analysis, VitD levels were negatively influenced by disease location and CRP in UC. CONCLUSIONS: Although VitD deficiency was more prevalent than expected in healthy controls living in a Mediterranean country not at high risk of hypovitaminosis D, it was more common and severe in IBD patients. This study also found an association between VitD status and disease activity.

The relative influence of serum ionized calcium and 25-hydroxyvitamin D in regulating PTH secretion in healthy subjects.

BACKGROUND: While the inverse relationship between serum ionized calcium (Ca2+) and PTH is well-established, the relationship between 25(OH)D and PTH showed conflicting results. The study aimed to evaluate the relative contributions of age, sex, serum Ca2+, ionized magnesium (Mg2+), 25(OH)D and 1,25(OH)2D in regulating PTH secretion in healthy subjects. METHODS: This is a secondary analysis of an observational study performed from March 2014 to July 2015 carried out in 2259 blood donors (1652 men and 607 women, age range 18-68 years). Subjects with parathyroid disorders and taking drugs that affect mineral metabolism were excluded. RESULTS: Significant correlations [between Ca2+ and PTH (r = -0.223, p < 0.001), 25(OH)D and PTH (r = -0.178, p < 0.001) and between PTH and age (r = 0.322, p < 0.001)] were found. As a preliminary step to multivariate analysis, a regression tree analysis was performed using PTH as response variable and age, Ca2+, Mg2+, 25(OH)D, 1,25(OH)2D and sex as explanatory variables to determine the effect of each covariate on the response variable. For subjects <38 years, 25(OH)D was the most important parameter in regulating PTH. For subjects ≥38 both 25(OH)D and Ca2+ levels regulated PTH secretion. Subjects with 25(OH)D < 13 ng/mL had average higher PTH; in this group only, subjects with Ca2+ ≥ 1.30 mmol/L had average lower PTH compared to subjects with Ca2+ < 1.30. The multivariate analysis showed that all variables had a significant effect (p < 0.001) on PTH. Anova Type III errors c indicated that 25(OH)D accounted for 32.1% of the total variance in PTH, Ca2+ accounted for 18% of the total variance, BMI for 14.3%, and 1,25(OH)2D for 11.1%. The remaining percentage was attributable to age and sex. This was confirmed by the regression tree approach, where 25(OH)D and Ca2+ accounted for the largest variation in the average levels of PTH. DISCUSSION: Under stable conditions 25(OH)D plays a significant role in regulating PTH secretion. Under conditions of relative vitamin D sufficiency, Ca2+ also plays an important role.

Assessment of Skeletal Muscle Mass in Older People: Comparison Between 2 Anthropometry-Based Methods and Dual-Energy X-ray Absorptiometry.

OBJECTIVES: Sarcopenia is a common geriatric syndrome, whose diagnosis implies the assessment of muscle mass. Dual-energy x-ray absorptiometry (DXA) is the reference method for clinical practice, but it is not universally available. We compared DXA with 2 anthropometry-based methods to assess muscle mass in older adults. DESIGN: Cross-sectional. SETTING: Ambulatory patients. PARTICIPANTS: 148 (87 female and 61 male) white older adults. MEASUREMENTS: Mid-arm muscle circumference (MAMC), whole skeletal muscle mass estimated by the Lee's formula (eTSMM), and relative skeletal muscle index (RSMI). RESULTS: Men and women did not differ for MAMC and RSMI, whereas eTSMM was higher (P < .001) in men. MAMC and eTSMM correlated with RSMI, in the whole sample as in men and women separately (P < .001). According to the McNemar test, the frequencies of older men and women with low muscle mass identified by eTSMM did not differ from those detected by RSMI (P = .066) at variance with MAMC. Using EWGSOP (European Working Group on Sarcopenia in Older People) criteria for RSMI as standard reference, the receiver operating characteristic (ROC) curves provided redefined cut-offs of reduced muscle mass: 18.6 cm in women and 22.3 cm in men for MAMC, and 17.7 kg in women and 28.3 kg in men for eTSMM. The areas under the ROC curves (AUCs) for MAMC were 0.882 in women (sensitivity 89%, specificity 84%) and 0.826 in men (sensitivity 94%, specificity 67%). The AUCs for eTSMM were 0.8913 in women (sensitivity 95%, specificity 81%) and 0.878 in men (sensitivity 97%, specificity 67%). No significant difference was found between the ROC curves of MAMC and eTSMM in both sexes. CONCLUSION: Two simple anthropometric methods, possibly used in every clinical setting, could be valuable screening tools for low muscle mass in older subjects.