Lessons learned with Bone Health TeleECHO: making treatment decisions when guidelines conflict.

Clinical practice guidelines provide helpful information for managing patients with metabolic bone disease. Good guidelines are based on the best available medical evidence; however, guidelines from different societies can conflict. Additionally, it is not possible for a guideline to anticipate the vast variability of circumstances, comorbidities, previous medical experiences, cultural differences, and preferences in real-world patients. Bone Health TeleECHO is a strategy for sharing knowledge on the care of patients with skeletal diseases through ongoing interactive videoconferences. We report three cases based on those presented at Bone Health TeleECHO, where, through discussion, treatment outside of commonly used guidelines was ultimately recommended. Guidelines developed by different organizations may provide "evidence-based" or "informed" recommendations which do not account for the variability of clinical circumstances encountered in the care of individual patients. This highlights the importance of Bone Health TeleECHO, where healthcare professionals can share knowledge, individualize treatment decisions, and improve patient care.Learning objectives At the end of this activity participants should be able to:• Distinguish between the onset and off of bisphosphonates versus other medications used in the prevention and treatment of osteoporosis and how this affects choice of a "drug holiday."• Understand the limitations of clinical practices guidelines in the care of an individual patient and how interactive video conferencing can assist with decision making.• Recognize that patients treated with glucocorticoids at high risk for fracture can benefit from more aggressive interventions for osteoporosis.

Images from the surface of asteroid Ryugu show rocks similar to carbonaceous chondrite meteorites.

The near-Earth asteroid (162173) Ryugu is a 900-m-diameter dark object expected to contain primordial material from the solar nebula. The Mobile Asteroid Surface Scout (MASCOT) landed on Ryugu's surface on 3 October 2018. We present images from the MASCOT camera (MASCam) taken during the descent and while on the surface. The surface is covered by decimeter- to meter-sized rocks, with no deposits of fine-grained material. Rocks appear either bright, with smooth faces and sharp edges, or dark, with a cauliflower-like, crumbly surface. Close-up images of a rock of the latter type reveal a dark matrix with small, bright, spectrally different inclusions, implying that it did not experience extensive aqueous alteration. The inclusions appear similar to those in carbonaceous chondrite meteorites.

Examining the treatment gap and risk of subsequent fractures among females with a fragility fracture in the US Medicare population.

Our aim was to evaluate the gap in osteoporosis treatment and the impact of osteoporosis treatment on subsequent fragility fractures. We found osteoporosis medication use lowered risk of subsequent fractures by 21% and that black race, higher CCI scores, dementia, and kidney diseases reduced the likelihood of osteoporosis medication use. INTRODUCTION: The goal of this study was to evaluate the predictors of osteoporosis medication use and compare the risk of fragility fractures within 1 year of a fragility fracture between osteoporosis treated and untreated women. METHODS: We conducted a retrospective, observational cohort study using the national Medicare database. Elderly women (≥65 years) who were hospitalized or had an outpatient/ER service for fragility fracture between January 1, 2011 and December 31, 2011 were included. The outcomes of interest were the correlates of and time-to-osteoporosis medication use and risk of a subsequent fracture within 12 months for treated and untreated women. Cox regression was used to evaluate the predictors of treatment use and the risk of fracture based on treatment status. RESULTS: Women (28,722) (27.7%) were treated with osteoporosis medication within 12 months of index fracture, and 74,979 (72.2%) were untreated. A number of patient characteristics were associated with a reduced likelihood of osteoporosis medication use, including black race, higher Charlson comorbidity index scores, presence of dementia, and kidney diseases in the baseline. The predictor most strongly and positively associated with osteoporosis medication use after fracture was osteoporosis medication use before fragility fracture (HR = 7.87; 95% CI 7.67-8.07). After adjusting for baseline characteristics, osteoporosis medication use lowered the risk of subsequent fractures by 21% (HR = 0.79, 95% CI 0.75-0.83) over 12 months compared to women without treatment. CONCLUSIONS: Demographics and clinical characteristics were strong predictors of osteoporosis medication use. In the US Medicare population, osteoporosis treatment significantly reduced the risk of fragility fractures.

Spine fracture prevalence in a nationally representative sample of US women and men aged ≥40 years: results from the National Health and Nutrition Examination Survey (NHANES) 2013-2014.

Spine fracture prevalence is similar in men and women, increasing from <5 % in those <60 to 11 % in those 70-79 and 18 % in those ≥80 years. Prevalence was higher with age, lower bone mineral density (BMD), and in those meeting criteria for spine imaging. Most subjects with spine fractures were unaware of them. INTRODUCTION: Spine fractures have substantial medical significance but are seldom recognized. This study collected contemporary nationally representative spine fracture prevalence data. METHODS: Cross-sectional analysis of 3330 US adults aged ≥40 years participating in NHANES 2013-2014 with evaluable Vertebral Fracture Assessment (VFA). VFA was graded by semiquantitative measurement. BMD and an osteoporosis questionnaire were collected. RESULTS: Overall spine fracture prevalence was 5.4 % and similar in men and women. Prevalence increased with age from <5 % in those <60 to 11 % in those 70-79 and 18 % in those ≥80 years. Fractures were more common in non-Hispanic whites and in people with lower body mass index and BMD. Among subjects with spine fracture, 26 % met BMD criteria for osteoporosis. Prevalence was higher in subjects who met National Osteoporosis Foundation (NOF) criteria for spine imaging (14 vs 4.7 %, P < 0.001). Only 8 % of people with a spine fracture diagnosed by VFA had a self-reported fracture, and among those who self-reported a spine fracture, only 21 % were diagnosed with fracture by VFA. CONCLUSION: Spine fracture prevalence is similar in women and men and increases with age and lower BMD, although most subjects with spine fracture do not meet BMD criteria for osteoporosis. Since most (>90 %) individuals were unaware of their spine fractures, lateral spine imaging is needed to identify these women and men. Spine fracture prevalence was threefold higher in individuals meeting NOF criteria for spine imaging (∼1 in 7 undergoing VFA). Identifying spine fractures as part of comprehensive risk assessment may improve clinical decision making.

Different in vivo and in vitro transformation of intestinal stem cells in mismatch repair deficiency.

Mutations in mismatch repair (MMR) genes result in microsatellite instability (MSI) and early onset of colorectal cancer. To get mechanistic insights into the time scale, sequence and frequency of intestinal stem cell (ISC) transformation, we quantified MSI and growth characteristics of organoids of Msh2-deficient and control mice from birth until tumor formation and related them to tissue gene expression. Although in Msh2-deficient organoids MSI continuously increased from birth, growth characteristics remained stable at first. Months before tumor onset, normal Msh2-deficient tissue contained tumor precursor cells forming organoids with higher MSI, cystic growth and growth rates resembling temporarily those of tumor organoids. Consistently, Msh2-deficient tissue exhibited a tumor-like gene signature. Normal Msh2-deficient organoids showed increased inheritable transient cyst-like growth, which became independent of R-spondin. ISC transformation proceeded faster in vitro than in vivo independent of the underlying genotype but more under MMR deficiency. Transient cyst-like growth but not MSI was suppressed by aspirin. In summary, as highlighted by organoids, molecular alterations continuously proceeded long before tumor onset in MMR-deficient intestine, thus increasing its susceptibility for ISC transformation.

Novel genes on rat chromosome 10 are linked to body fat mass, preadipocyte number and adipocyte size.

BACKGROUND: The genetic architecture of obesity is multifactorial. We have previously identified a quantitative trait locus (QTL) on rat chromosome 10 in a F2 cross of Wistar Ottawa Karlsburg (WOKW) and Dark Agouti (DA) rats responsible for obesity-related traits. The QTL was confirmed in congenic DA.WOKW10 rats. To pinpoint the region carrying causal genes, we established two new subcongenic lines, L1 and L2, with smaller refined segments of chromosome 10 to identify novel candidate genes. METHODS: All lines were extensively characterized under different diet conditions. We employed transcriptome analysis in visceral adipose tissue (VAT) by RNA-Seq technology to identify potential underlying genes in the segregating regions. Three candidate genes were measured in human paired samples of VAT and subcutaneous (SC) AT (SAT) (N=304) individuals with a wide range of body weight and glucose homeostasis parameters. RESULTS: DA.WOKW and L1 subcongenic lines were protected against body fat gain under high-fat diet (HFD), whereas L2 and DA had significantly more body fat after high-fat feeding. Interestingly, adipocyte size distribution in SAT and epigonadal AT of L1 subcongenic rats did not undergo typical ballooning under HFD and the number of preadipocytes in AT was significantly elevated in L2 compared with L1 and parental rats. Transcriptome analysis identified three candidate genes in VAT on rat chromosome 10. In humans, these candidate genes were differentially expressed between SAT and VAT. Moreover, HID1 mRNA significantly correlates with parameters of obesity and glucose metabolism. CONCLUSIONS: Our data suggest novel candidate genes for obesity that map on rat chromosome 10 in an interval 102.2-104.7 Mb and are strongly associated with body fat mass regulation, preadipocyte number and adipocyte size in rats. Among those genes, AT head involution defective (HID1) mRNA expression may be relevant for human fat distribution and glucose homeostasis.

Patients with prior vertebral or hip fractures treated with teriparatide in the Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) observational study.

SUMMARY: In patients in the Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) observational study with and without a prior vertebral or hip fracture, the incidence of nonvertebral fractures was lower with >6 months of teriparatide treatment than during the first 6 months. INTRODUCTION: Clinical evidence on the effect of teriparatide in patients with prior fracture is limited. In the DANCE observational study, the incidence of nonvertebral fragility fractures (NVFX) decreased significantly in patients receiving teriparatide for >6 months (6-24 months) versus >0 to ≤6 months (reference period). METHODS: We performed a post hoc analysis to assess the effect of teriparatide 20 µg/day in patients who entered DANCE with prior vertebral or hip fractures. The incidence of patients experiencing a NVFX for four 6-month intervals during and after treatment was compared with the reference period. RESULTS: Overall, 4085 patients received ≥1 dose of teriparatide. Of 3720 with sufficient data for efficacy analysis, 692 had prior vertebral fracture, including 179 with previous kyphoplasty/vertebroplasty; 290 had prior hip fracture. These patients were older, and those with prior vertebral fractures had more comorbid conditions at baseline than those without prior vertebral fractures. The incidence of patients experiencing NVFX declined over time in all patient groups. The fracture incidence rate declined 49 and 46%, respectively, in patients with and without prior vertebral fracture and was 63 and 46% lower in patients with previous kyphoplasty/vertebroplasty and without prior vertebral fracture. NVFX declined 43 and 48% in patients with and without prior hip fracture. The reduced incidence over time was consistent in the subgroups (all interaction p values >0.05). Patients with prior fracture were more likely to experience serious adverse events. CONCLUSION: The incidence of NVFX decreased over time in patients receiving teriparatide in DANCE regardless of prior fracture status.

Applications of PET imaging with the proliferation marker [18F]-FLT.

[18F]-3'-fluoro-3'-deoxythymidine (FLT) is a nucleoside-analog imaging agent for quantifying cellular proliferation that was first reported in 1998. It accumulates during the S-phase of the cell cycle through the action of cytosolic thymidine kinase, TK1. Since TK1 is primarily expressed in dividing cells, FLT uptake is essentially limited to dividing cells. Thus FLT is an effective measure of cell proliferation. FLT uptake has been shown to correlate with the more classic proliferation marker, the monoclonal antibody to Ki-67. Increased cellular proliferation is known to correlate with worse outcome in many cancers. However, the Ki-67 binding assay is performed on a sampled preparation, ex vivo, whereas FLT can be quantitatively measured in vivo using positron emission tomography (PET). FLT is an effective and quantitative marker of cell proliferation, and therefore a useful prognostic predictor in the setting of neoplastic disease. This review summarizes clinical studies from 2011 forward that used FLT-PET to assess tumor response to therapy. The paper focuses on our recommendations for a standardized clinical trial protocol and components of a report so multi center studies can be effectively conducted, and different studies can be compared. For example, since FLT is glucuronidated by the liver, and the metabolite is not transported into the cell, the plasma fraction of FLT can be significantly changed by treatment with particular drugs that deplete this enzyme, including some chemotherapy agents and pain medications. Therefore, the plasma level of metabolites should be measured to assure FLT uptake kinetics can be accurately calculated. This is important because the flux constant (KFLT) is a more accurate measure of proliferation and, by inference, a better discriminator of tumor recurrence than standardized uptake value (SUVFLT). This will allow FLT imaging to be a specific and clinically relevant prognostic predictor in the treatment of neoplastic disease.

Ca(2+)-binding protein expression in primary human thyrocytes.

We recently identified several Ca(2+)-binding proteins (CaBP) from the S100 and annexin family to be regulated by TSH in FRTL-5 cells. Here, we study the regulation of S100A4, S100A6 and ANXA2 in primary human thyrocytes (PHT) derived from surrounding tissues (ST), cold benign thyroid nodules (CTN) and autonomously functioning thyroid nodules (AFTN). We investigated the expression and regulation of CaBP and the effect of their expression on Ca(2+) and TSHR signaling. We used an approach that accounts for the potential of an individual PHT culture to proliferate or to express thyroid differentiation features by assessing the expression of FOS and TPO. We found a strong correlation between the regulation of CaBP and the proliferation-associated transcription factor gene FOS. PKA and MEK1/2 were regulators of ANXA2 expression, while PI3-K and triiodothyronine were additionally involved in S100 regulation. The modulated expression of CaBP was reflected by changes in ATP-elicited Ca(2+) signaling in PHT. S100A4 increased the ratio of subsequent Ca(2+) responses and showed a Ca(2+) buffering effect, while ANXA2 affected the first Ca(2+) response to ATP. Overexpression of S100A4 led to a reduced activation of NFAT by TSH. Using S100A4 E33Q, D63N, F72Q and Y75K mutants we found that the effects of S100A4 expression on Ca(2+) signaling are mediated by protein interaction. We present evidence that TSH has the ability to fine-tune Ca(2+) signals through the regulation of CaBP expression. This represents a novel putative cross-regulating mechanism in thyrocytes that could affect thyrocyte signaling and physiology.

Association between teriparatide adherence and healthcare utilization and costs in real-world US kyphoplasty/vertebroplasty patients.

UNLABELLED: The objective of this study was to examine the association between teriparatide adherence and healthcare utilization and costs in real-world US kyphoplasty/vertebroplasty (KV) patients. Among KV patients newly initiating teriparatide, significantly increased pharmacy costs associated with high teriparatide adherence were offset by significantly lower inpatient utilization and medical costs. INTRODUCTION: This study seeks to examine the association between teriparatide adherence and healthcare utilization/costs in real-world US KV patients. METHODS: Identified patients from a large US administrative claims database were aged 50+ with KV from 1/1/2002-12/31/2010 (first observed KV = index). Included individuals had 6+ months of pre-index continuous enrollment and no pre-index teriparatide, cancer, or Paget's disease. Follow-up period for patients initiating teriparatide was ≤36 months post-index. Three teriparatide adherence cohorts were constructed using the proportion of days covered (PDC) during the follow-up period: low (PDC ≤ 0.5), medium (PDC >0.5-≤ 0.8), and high (PDC >0.8). Repeated KV admissions, any inpatient admission, number of inpatient admissions, and per-patient-per-month (PPPM) inpatient, outpatient, pharmacy, and total costs were compared between cohorts. The associations between teriparatide adherence and healthcare utilization/costs were examined using multivariable regression models, adjusting for patient demographics and clinical characteristics. RESULTS: Included were 1,568 patients (mean age, 75 years; 82% female): 403 (26%) had low adherence, 382 (24%) medium, and 783 (50%) high. After multivariable adjustment, high adherence was significantly associated with the lowest PPPM inpatient (low = $1,287; medium = $1,005; high = $678) and outpatient (low = $1,464; medium = $1,244; high = $1,077) medical costs, but with increased pharmacy costs (low = $752; medium = $1,159; high = $1,616; all P < 0.05), leading to similar total costs (low = $3,344; medium = $3,376; high = $3,351) between cohorts; high adherence was also significantly associated with the lowest odds of repeated KV admission, any inpatient admission, and number of inpatient admissions (all P < 0.05). CONCLUSIONS: Among KV patients initiating teriparatide, significantly increased pharmacy costs associated with high teriparatide adherence were offset by significantly lower inpatient utilization and medical costs.

The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) study: 2-year nonvertebral fragility fracture results.

UNLABELLED: This observational study evaluated the occurrence of nonvertebral fragility fractures (NVFX) in over 4,000 men and women with osteoporosis treated with teriparatide (TPTD). The incidence of new NVFX decreased for patients receiving TPTD treatment for greater than 6 months. No new significant safety findings were observed in this large trial. INTRODUCTION: The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) study evaluated the occurrence of NVFX in patients receiving TPTD for osteoporosis in a real-world setting. METHODS: DANCE is a multicenter, prospective, observational trial that examined the long-term effectiveness of TPTD in men and women with osteoporosis whom study physicians judged to be suitable for TPTD therapy. Patients received 20 µg TPTD per day by subcutaneous injection for up to 24 months and were followed for 24 months after treatment cessation. The incidence of patients experiencing a new NVFX, defined as a fracture associated with low trauma, was evaluated during four 6-month periods in both the treatment and cessation phases with >0 to ≤6 months serving as the reference. We also observed the spectrum and occurrence of serious adverse events. RESULTS: Of the 4,167 patients enrolled, 4,085 took one or more doses of TPTD (safety population); 3,720 were included in the efficacy analysis. The incidence of patients experiencing a NVFX was 1.42, 0.91, 0.70, and 0.81 % for the four treatment periods, respectively, and 0.80, 0.68, 0.33, and 0.33 % for the four periods after treatment cessation. Differences for each period were statistically significant compared with the reference period (first 6-month interval, each p < 0.05). No new significant safety findings were observed. CONCLUSIONS: In this study, the incidence of NVFX decreased for patients receiving TPTD for all three treatment periods >6 months compared to 0 to ≤6 months, and this trend persisted throughout the cessation phase. TPTD was generally well tolerated.

Nonanolides of natural origin: structure, synthesis, and biological activity.

Naturally occurring nonanolides (synonym decanolides) are a large family of secondary metabolites with an interesting 10- membered macrolide subunit. Metabolites of the nonanolide family have been found to have various biological activities, including cytotoxic, phytotoxic, antimalarial, antifungal, antibacterial, and antimicrofilament activities. An early review of the chemistry and bioactivity of nonanolides was presented in 1996, covering the literature published between 1975 and 1995. During the past decades, the broad spectrum of bioactivity and the intriguing structure of the medium-sized ring in nonanolide analogues have continuously drawn the attention of biologists and natural product and synthetic chemists, resulting in a great number of publications. This review summarizes in whole the recent progress in the field of the nonanolides of natural origin, aiming to give the readers a brief view of the compounds, concerning their natural occurrence, structural elucidation, biological activities, total synthesis, and structure-activity relationships. The article covers the literature published in the period from the beginning of 1996 to July 2011.

Vesta's shape and morphology.

Vesta's surface is characterized by abundant impact craters, some with preserved ejecta blankets, large troughs extending around the equatorial region, enigmatic dark material, and widespread mass wasting, but as yet an absence of volcanic features. Abundant steep slopes indicate that impact-generated surface regolith is underlain by bedrock. Dawn observations confirm the large impact basin (Rheasilvia) at Vesta's south pole and reveal evidence for an earlier, underlying large basin (Veneneia). Vesta's geology displays morphological features characteristic of the Moon and terrestrial planets as well as those of other asteroids, underscoring Vesta's unique role as a transitional solar system body.

Gender differences for initiating teriparatide therapy: baseline data from the Direct Assessment of Nonvertebral Fracture in the Community Experience (DANCE) study.

UNLABELLED: The prospective, observational Direct Assessment of Nonvertebral Fracture in the Community Experience (DANCE) study shows that, among patients with risk factors for osteoporosis, women are more likely to be screened and to receive appropriate treatment than men. There needs to be greater awareness that osteoporosis affects both men and women. INTRODUCTION: The prospective, observational DANCE study evaluated teriparatide use in the mainland USA and Puerto Rico in patients with osteoporosis in a community setting. This analysis compares baseline characteristics of women and men that may contribute to differences in initiation of teriparatide therapy. METHODS: Investigators prescribed teriparatide 20 µg/day subcutaneous injection for ≤24 months to 3,698 patients (3,342 women, 356 men) whom they considered appropriate candidates for therapy. Study entry was guided by product labeling. Specific timing and frequency of office visits were not mandated. Treatment decisions were based on the clinical judgment of study investigators and local standards of care. RESULTS: At baseline, similar proportions of women and men had prior fragility fractures (57% and 59%, respectively) and comorbid conditions that increase fracture risk (83% and 84%, respectively). Women were older than men (mean age 68 vs. 65 year; P < 0.0001) and more likely to have received prior osteoporosis therapy (88% vs. 62%; P < 0.0001). Investigators prescribed teriparatide more often for women than men based on general frailty (21% vs. 16%; P = 0.0151), low body mass index (17% vs. 10%; P = 0.0005), and an inadequate response (58% vs. 36%; P < 0.0001) or intolerance to previous therapy (23% vs. 12%; P < 0.0001). Chronic glucocorticoid therapy was the reason investigators cited most frequently for initiating therapy more often in men than in women (17% vs. 10%; P < 0.0001) CONCLUSIONS: These results suggest that patients' gender may influence the reasons physicians initiate teriparatide therapy in a community setting.

Potential role of a navigator gene NAV3 in colorectal cancer.

BACKGROUND: The recently described navigator proteins have a multifaceted role in cytoskeletal dynamics. We report here on the relevance of one of them, navigator 3 (NAV3), in colorectal cancer (CRC). METHODS: We analysed changes in chromosome 12 and NAV3 copy number in CRC/adenoma samples of 59 patients and in 6 CRC cell lines, using fluorescence in situ hybridisation, loss of heterozygosity, and array-CGH. NAV3 target genes were identified by siRNA depletion, expression arrays, and immunohistochemistry. RESULTS: NAV3 deletion and chromosome 12 polysomy were detected in 30 and 70% of microsatellite stability (MSS) carcinomas, in 23 and 30% of adenomas and in four of six CRC cell lines. NAV3 amplification was found in 25% of MSS samples. NAV3 alterations correlated with lymph node metastasis. In normal colon cells, NAV3 silencing induced upregulation of interleukin 23 receptor (IL23R) and gonadotropin releasing hormone receptor. In MSS and microsatellite instability tumours, IL23R immunoreactivity correlated with Dukes' staging and lymph node metastases, whereas nuclear beta-catenin correlated with lymph node metastases only. CONCLUSION: NAV3 copy number changes are frequent in CRC and in adenomas, and upregulation of IL23R, following NAV3 silencing, strongly correlates with Dukes' staging and lymph node metastases. This suggests that NAV3 has a role in linking tissue inflammation to cancer development in the colon.

Kinetic quantitation of cerebral PET-FDG studies without concurrent blood sampling: statistical recovery of the arterial input function.

Kinetic quantitation of dynamic positron emission tomography (PET) studies via compartmental modeling usually requires the time-course of the radio-tracer concentration in the arterial blood as an arterial input function (AIF). For human and animal imaging applications, significant practical difficulties are associated with direct arterial sampling and as a result there is substantial interest in alternative methods that require no blood sampling at the time of the study. A fixed population template input function derived from prior experience with directly sampled arterial curves is one possibility. Image-based extraction, including requisite adjustment for spillover and recovery, is another approach. The present work considers a hybrid statistical approach based on a penalty formulation in which the information derived from a priori studies is combined in a Bayesian manner with information contained in the sampled image data in order to obtain an input function estimate. The absolute scaling of the input is achieved by an empirical calibration equation involving the injected dose together with the subject's weight, height and gender. The technique is illustrated in the context of (18)F -Fluorodeoxyglucose (FDG) PET studies in humans. A collection of 79 arterially sampled FDG blood curves are used as a basis for a priori characterization of input function variability, including scaling characteristics. Data from a series of 12 dynamic cerebral FDG PET studies in normal subjects are used to evaluate the performance of the penalty-based AIF estimation technique. The focus of evaluations is on quantitation of FDG kinetics over a set of 10 regional brain structures. As well as the new method, a fixed population template AIF and a direct AIF estimate based on segmentation are also considered. Kinetics analyses resulting from these three AIFs are compared with those resulting from radially sampled AIFs. The proposed penalty-based AIF extraction method is found to achieve significant improvements over the fixed template and the segmentation methods. As well as achieving acceptable kinetic parameter accuracy, the quality of fit of the region of interest (ROI) time-course data based on the extracted AIF, matches results based on arterially sampled AIFs. In comparison, significant deviation in the estimation of FDG flux and degradation in ROI data fit are found with the template and segmentation methods. The proposed AIF extraction method is recommended for practical use.

Teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: an analysis by gender and menopausal status.

SUMMARY: The effects of teriparatide versus alendronate were compared by gender and menopausal status in patients with glucocorticoid-induced osteoporosis. At 18 months, increases in lumbar spine BMD were significantly greater in the teriparatide versus alendronate group in postmenopausal women (7.8% versus 3.7%, p < 0.001), premenopausal women (7.0% versus 0.7%, p < 0.001), and men (7.3% versus 3.7%, p = 0.03). INTRODUCTION: In patients with glucocorticoid-induced osteoporosis (GIO), teriparatide significantly increased bone mineral density (BMD) and decreased vertebral fractures compared with alendronate. We examined effects of teriparatide versus alendronate by gender and menopausal status. METHODS: This was a multicenter, randomized, double-blind study of teriparatide 20 microg/day versus alendronate 10 mg/day in patients with GIO (277 postmenopausal women, 67 premenopausal women, 83 men). Primary outcome was change in lumbar spine BMD. Secondary outcomes included change in hip BMD, change in bone biomarkers, fracture incidence, and safety. RESULTS: At 18 months, mean percent increases from baseline in lumbar spine BMD were significantly greater in the teriparatide versus alendronate group in postmenopausal women (7.8% versus 3.7%, p < 0.001), premenopausal women (7.0% versus 0.7%, p < 0.001), and men (7.3% versus 3.7%, p = 0.03). Radiographic vertebral fractures occurred in one teriparatide (one postmenopausal) and ten alendronate patients (six postmenopausal, four men), and nonvertebral fractures occurred in 12 teriparatide (nine postmenopausal, two premenopausal, one man) and eight alendronate patients (six postmenopausal, two men). The proportion of patients reporting adverse events in teriparatide versus alendronate groups was consistent across subgroups. CONCLUSION: Among men and pre- and postmenopausal women with GIO, lumbar spine BMD increased more in patients receiving teriparatide compared with alendronate.

Neonatology/Paediatrics - Guidelines on Parenteral Nutrition, Chapter 13.

There are special challenges in implementing parenteral nutrition (PN) in paediatric patients, which arises from the wide range of patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg, and their varying substrate requirements. Age and maturity-related changes of the metabolism and fluid and nutrient requirements must be taken into consideration along with the clinical situation during which PN is applied. The indication, the procedure as well as the intake of fluid and substrates are very different to that known in PN-practice in adult patients, e.g. the fluid, nutrient and energy needs of premature infants and newborns per kg body weight are markedly higher than of older paediatric and adult patients. Premature infants <35 weeks of pregnancy and most sick term infants usually require full or partial PN. In neonates the actual amount of PN administered must be calculated (not estimated). Enteral nutrition should be gradually introduced and should replace PN as quickly as possible in order to minimise any side-effects from exposure to PN. Inadequate substrate intake in early infancy can cause long-term detrimental effects in terms of metabolic programming of the risk of illness in later life. If energy and nutrient demands in children and adolescents cannot be met through enteral nutrition, partial or total PN should be considered within 7 days or less depending on the nutritional state and clinical conditions.