Increased ferroptosis in leukocytes from preeclamptic women involving the long non-coding taurine upregulated gene 1 (TUG1).

BACKGROUND: Ferroptosis plays a key role in placental development and physiology, and abnormal ferroptosis has been implicated in trophoblast injury leading to preeclampsia (PE). We hypothesize that leukocytes isolated from PE exhibit increased ferroptosis and that extracellular vesicles contain long non-coding (lnc) RNA/mRNAs that modulate oxidative stress and iron toxicity in vascular endothelial cells. METHODS: We measured the expression of key regulators of ferroptosis in leukocytes and extracellular vesicles as well as circulating biomarkers of iron homeostasis and oxidative stress in plasma from women with/without PE at different timepoints during pregnancy. For markers that were dysregulated, we assessed their temporal correlation with established markers of disease activity and marker of endothelial activation. For markers dysregulated in early pregnancy, we assessed their ability to predict the development of PE. RESULTS: We found decreased lncRNA/mRNAs in leukocytes, but not extracellular vesicles, in PE that may modulate oxidative stress and iron toxicity. This decrease in anti-ferroptotic markers does not appear to be related to maternal disease activity or plasma oxidative stress status but rather to attenuated anti-inflammatory expression in these cells. Circulating ferritin was elevated in PE, supporting the hypothesis that PE represents a disbalance in iron homeostasis. Low lncRNA taurine upregulated gene 1 RNA levels in leukocytes at 22-24 weeks were strongly associated with the development of PE. CONCLUSIONS: Our findings suggest that maternal leukocytes in PE show decreased anti-ferroptotic activity that correlates with anti-inflammatory expression. Moreover, some of these changes in ferroptotic activity appear to precede the development of PE.

Acromegaly management in the Nordic countries: A Delphi consensus survey.

OBJECTIVE: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. METHODS: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. RESULTS: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. CONCLUSION: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

Unravelling pituitary tumours in medically treated patients with acromegaly: the impact of systematic MRI reassessment.

BACKGROUND: In acromegaly, the primary tumor is usually found during magnetic resonance imaging (MRI) of the pituitary gland. A remnant tumor after surgery is, however, harder to depict. When a tumor is missed, the remaining option is usually lifelong pharmacological treatment. PURPOSE: To identify tumors by reassessment of all available MRI scans in pharmacologically treated patients, operated or not, and to compare our results with the routine MRI reports. MATERIAL AND METHODS: Adult patients diagnosed with acromegaly and managed at a tertiary care center between 2005 and 2021 and currently on pharmacological treatment were included. MRI scans were evaluated in a standardized manner and classified independently by a radiologist and an endocrinologist into "certain," "suspected," or "no tumor." In case of disagreement, consensus was achieved with a senior neuroradiologist. The results were compared using the clinical radiologists' routine MRI reports. RESULTS: We identified certain and suspected tumors in 29/74 and 36/74 patients, respectively. No tumor was identified in nine patients. In five of these, no MRI contrast agent was given. Discrepancy between our results and the routine MRI reports was found in 31/74 patients (P = 0.01). In 22 patients, the routine reports described no tumor while we identified certain tumors in 2/22 patients and suspected tumors in 13/22 patients. CONCLUSION: In most patients with pharmacologically treated acromegaly, we identified a certain or suspected pituitary tumor. These findings were more frequent compared to the routine MRI reports. Based on our results, patients will be considered for a change in long-term treatment modality.

Adipose tissue distribution is associated with cardio-metabolic alterations in adult patients with juvenile-onset dermatomyositis.

OBJECTIVES: Primary aims were to compare adipose tissue distribution in adult patients with juvenile-onset DM (JDM), with matched controls. Secondary aims were to explore how adipose tissue distribution is associated with cardio-metabolic status (cardiac dysfunction and metabolic syndrome) in patients. METHODS: Thirty-nine JDM patients (all aged ≥18 y, mean age 31.7 y and 51% female) were examined mean 22.7 y (s.d. 8.9 y) after disease onset and compared with 39 age/sex-matched controls. In patients, disease activity and lipodystrophy were assessed by validated tools and use of prednisolone noted. In all participants, dual-energy X-ray absorptiometry (DXA) and echocardiography were used to measure visceral adipose tissue (VAT)(g) and cardiac function, respectively. Risk factors for metabolic syndrome were measured and associations with adipose tissue distribution explored. For primary and secondary aims, respectively, P-values ≤0.05 and ≤0.01 were considered significant. RESULTS: Patients exhibited a 2.4-fold increase in VAT, and reduced HDL-cholesterol values compared with controls (P-values ≤ 0.05). Metabolic syndrome was found in 25.7% of the patients and none of the controls. Cardiac dysfunction (systolic and/or diastolic) was found in 23.7% of patients and 8.1% of controls (P = 0.07). In patients, VAT levels were correlated with age, disease duration and occurrence of metabolic syndrome and cardiac dysfunction. Occurrence of lipodystrophy (P = 0.02) and male sex (P = 0.04) tended to be independently associated with cardiac dysfunction. CONCLUSION: Adults with JDM showed more central adiposity and cardio-metabolic alterations than controls. Further, VAT was found increased with disease duration, which was associated with development of cardio-metabolic syndrome.

Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.

TGFBR3L is associated with gonadotropin production in non-functioning gonadotroph pituitary neuroendocrine tumours.

PURPOSE: Transforming growth factor-beta receptor 3-like (TGFBR3L) is a pituitary enriched membrane protein selectively detected in gonadotroph cells. TGFBR3L is named after transforming growth factor-beta receptor 3 (TGFBR3), an inhibin A co-receptor in mice, due to sequence identity to the C-terminal region. We aimed to characterize TGFBR3L detection in a well-characterized, prospectively collected cohort of non-functioning pituitary neuroendocrine tumours (NF-PitNETs) and correlate it to clinical data. METHODS: 144 patients operated for clinically NF-PitNETs were included. Clinical, radiological and biochemical data were recorded. Immunohistochemical (IHC) staining for FSHß and LHß was scored using the immunoreactive score (IRS), TGFBR3L and TGFBR3 were scored by the percentage of positive stained cells. RESULTS: TGFBR3L staining was selectively present in 52% of gonadotroph tumours. TGFBR3L was associated to IRS of LHß (median 2 [IQR 0-3] in TGFBR3L negative and median 6 [IQR 3-9] in TGFBR3L positive tumours, p < 0.001), but not to the IRS of FSHß (p = 0.32). The presence of TGFBR3L was negatively associated with plasma gonadotropin concentrations in males (P-FSH median 5.5 IU/L [IQR 2.9-9.6] and median 3.0 [IQR 1.8-5.6] in TGFBR3L negative and positive tumours respectively, p = 0.008) and P-LH (median 2.8 IU/L [IQR 1.9-3.7] and median 1.8 [IQR 1.1-3.0] in TGFBR3L negative and positive tumours respectively, p = 0.03). TGFBR3 stained positive in 22% (n = 25) of gonadotroph tumours with no correlation to TGFBR3L. CONCLUSION: TGFBR3L was selectively detected in half (52%) of gonadotroph NF-PitNETs. The association to LHß staining and plasma gonadotropins suggests that TGFBR3L may be involved in hormone production in gonadotroph NF-PitNETs.

Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. OBJECTIVE: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). DESIGN: Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028). SETTING: Eight Scandinavian referral centers. PATIENTS: From 1998 to 2005, 191 patients with mild PHPT were included. INTERVENTION: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). MEASUREMENTS: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. RESULTS: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). LIMITATION: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. CONCLUSION: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. PRIMARY FUNDING SOURCE: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.

Long-term control of acromegaly after pituitary surgery in South-Eastern Norway.

PURPOSE: Sustained cure of acromegaly can only be achieved by surgery. Most growth hormone (GH) secreting pituitary adenomas are macroadenomas (≥ 10 mm) at diagnosis, with reported surgical cure rates of approximately 50%. Long-term data on disease control rates after surgery are limited. Our aim was to estimate short- and long-term rates of biochemical control after pituitary surgery in acromegaly and identify predictive factors. METHODS: Patients operated for GH-secreting pituitary adenomas between 2005-2020 were included from the local pituitary registry (n = 178). Disease activity and treatment data were recorded at one-year (short-term) and five-year (long-term) postoperative follow-up. Biochemical control was defined as insulin-like growth factor 1 (IGF-1) ≤ 1.2 × upper limit of normal value. Multivariate regression models were used to identify factors potentially predicting biochemical control. RESULTS: A total of 178 patients with acromegaly (median age at diagnosis 49 (IQR: 38-59) years, 46% women) were operated for a pituitary adenoma. Biochemical control was achieved by surgery in 53% at short-term and 41% at long-term follow-up, without additional treatment for acromegaly. Biochemical control rates by surgery were of same magnitude in paired samples (45% vs. 41%, p = 0.213) for short- and long-term follow-up, respectively. At short-term, 62% of patients with microadenomas and 51% with macroadenomas, achieved biochemical control. At long-term, the biochemical control rate was 58% for microadenomas and 37% for macroadenomas (p = 0.058). With adjunctive treatment, 82% achieved biochemical control at long-term. Baseline IGF-1 levels significantly predicted biochemical control by surgery at short-term (OR: 0.98 (95% CI: 0.96-0.99), p = 0.011), but not at long-term (OR: 0.76 (95% CI: 0.57-1.00), p = 0.053). CONCLUSION: In unselected patients with acromegaly, the long-term biochemical control rate remains modest. Our findings indicate a need to identify patients at an earlier stage and improve therapeutic methods and surgical outcomes.

Body composition in long-standing juvenile dermatomyositis: associations with disease activity, muscle strength and cardiometabolic measures.

OBJECTIVE: To compare body composition parameters in patients with long-standing JDM and controls and to explore associations between body composition and disease activity/inflammation, muscle strength, health-related quality of life (HRQoL) and cardiometabolic measures. METHODS: We included 59 patients (median disease duration 16.7 y; median age 21.5 y) and 59 age- and sex-matched controls in a cross-sectional study. Active and inactive disease were defined by the PRINTO criteria. Body composition was assessed by total body DXA, inflammation by high-sensitivity CRP (hs-CRP) and cytokines, muscle strength by the eight-muscle manual muscle test, HRQoL by the 36-item Short Form Health Survey physical component score and cardiometabolic function by echocardiography (systolic and diastolic function) and serum lipids. RESULTS: DXA analyses revealed lower appendicular lean mass index (ALMI; reflecting limb skeletal muscle mass), higher body fat percentage (BF%) and a higher android fat:gynoid fat (A:G) ratio (reflecting central fat distribution) in patients than controls, despite similar BMI. Patients with active disease had lower ALMI and higher BF% than those with inactive disease; lower ALMI and higher BF% were associated with inflammation (elevated monocyte attractant protein-1 and hs-CRP). Lower ALMI was associated with reduced muscle strength, while higher BF% was associated with impaired HRQoL. Central fat distribution (higher A:G ratio) was associated with impaired cardiac function and unfavourable serum lipids. CONCLUSION: Despite normal BMI, patients with JDM, especially those with active disease, had unfavourable body composition, which was associated with impaired HRQoL, muscle strength and cardiometabolic function. The association between central fat distribution and cardiometabolic alterations is a novel finding in JDM.

The Influence of DXA Hardware, Software, Reference Population and Software Analysis Settings on the Bone Mineral Density and T-Score Relationship.

Different dual-energy x-ray absorptiometry (DXA) hardware can affect bone mineral density (BMD) measurements and different reference populations can affect t-scores. Long-term analyses describing differences in the relationship between BMD and t-scores are lacking. BMD-values were plotted against t-scores for 241 Lunar DXA scans on females obtained over 18 years from several centers in Sweden and Norway. The result of the plot was compared to hardware/software versions, reference populations and different software analysis settings (Basic vs Enhanced analysis for total body and Single Photon Absorptiometry (SPA) vs Lunar calibration for forearm). For the forearm compartments, we found different BMD-t-score relationships depending on the use of SPA or Lunar calibration (p<0.001). With Lunar calibration, BMD-values were 24% higher, but there was no effect on t-scores. Total body measurements with iDXA scanners and Enhanced analysis for Prodigy scanners (software version 14.10) resulted in a different BMD-t-score relationship compared to the other hardware/software versions (p<0.001), with the largest discrepancy for lower BMD-values. Switching from Basic to Enhanced analysis generally decreased BMD-values and often changed t-scores (both increased and decreased). For the femoral neck, there were two different BMD-t-score relationships caused by different reference populations (p<0.001). In contrast to total body, the difference for femoral neck was more pronounced for higher values, with little impact in the clinical decision-making area. Hardware, software, reference populations and software analysis settings can affect the BMD-t-score relationship, but do so differently for different compartments. The BMD-t-score-plot is a simple and effective tool to discover systematic differences. Longitudinal analyses of DXA scans should be performed based on raw data analyzed in "one run" with the same software version and settings, in order to avoid systematic differences.

Effect of high-intensity training on bone health and body composition in lung transplant recipients: A secondary analysis of a randomized controlled trial.

BACKGROUND: Loss of bone mineral and skeletal muscle mass is common after lung transplantation (LTx), and physical activity (PA) may prevent further deterioration. We aimed to assess the effects of 20-week high-intensity training (HIT) on body composition, bone health, and PA in LTx recipients, 6-60 months after surgery. METHODS: In a randomized controlled trial, 51 LTx recipients underwent Dual-energy X-ray absorptiometry (DXA), and PA level and sedentary time were objectively recorded by accelerometers for seven consecutive days. Of these, 39 participants completed the study, including 19 participants in the HIT group and 20 participants in the standard care group. RESULTS: Following the intervention, ANCOVA models revealed a nonsignificant between-group difference for change in lean body mass (LBM) and bone mineral density (BMD) of the lumbar spine of 0.4% (95% CI = -3.2, 1.5) (p = .464) and 1.0% (95% CI=-1.3, 3.4) (p = .373), respectively. Trabecular bone score (TBS) of the lumbar spine (L1-L4), however, increased by 2.2 ± 5.0% in the exercise group and decreased by -1.6 ± 5.9% in the control group, giving a between-group difference of 3.8% (95% CI=0.1, 7.5) (p = .043). There were no between-group differences in PA or sedentary time. CONCLUSION: High-intensity training after LTx improved TBS significantly, but not PA, LBM or BMD.

Assessing Periprosthetic Bone in Total Wrist Arthroplasty: The Validity of DXA.

INTRODUCTION: Dual-energy X-ray absorptiometry (DXA) can measure bone mineral density (BMD) around joint arthroplasties. DXA has never been used in total wrist arthroplasties (TWA). We investigated (1) whether BMD differs between 2 TWAs implanted in the same cadaver forearm, (2) the effect of forearm rotation and wrist extension on measured BMD around TWA in a cadaver, and (3) the precision of DXA in a cadaver and patients. METHODOLOGY: One ROI around the distal and 1 and 3 ROIs (ROI1-3) around the proximal component were used. Ten DXA scans were performed on forearm and femur mode convertible to orthopedic knee mode without arthroplasty, with ReMotion, and with Motec TWA in one cadaver forearm. Ten scans with 5° increments from 90°-70° pronation and 0°-20° extension, were performed with Motec. Precision was calculated as coefficient of variation (CV%) and least significant change (LSC%) from cadaver scans and double examinations with femur mode converted to orthopedic knee mode in 40 patients (20 ReMotion, 20 Motec). RESULTS: BMD was higher in all Motec than corresponding ReMotion ROIs (p < 0.05). BMD changed with 10° supination in the distal ROI and ROI1, and with 5° extension in the distal ROI (p < 0.05). In the cadaver the orthopedic knee mode was more precise than the forearm mode in 3 Motec ROIs (p < 0.05). In patients CV was 2.21%-3.08% in the distal ROI, 1.66%-2.01% in the proximal ROI, and 1.98%-2.87% with 3 ROIs. CONCLUSIONS: DXA is feasible for BMD measurement around the proximal component using the orthopedic knee mode, but not the distal component of TWA.

Burden of illness in not adequately controlled chronic hypoparathyroidism: Findings from a 13-country patient and caregiver survey.

OBJECTIVE: To address knowledge gaps regarding burdens associated with not adequately controlled chronic hypoparathyroidism. DESIGN: Global patient and caregiver survey. STUDY POPULATIONS: Patients with chronic hypoparathyroidism not adequately controlled on conventional therapy and their caregivers. MEASUREMENTS: Health-related quality of life (HRQoL) and health status were evaluated using the 36-item Short Form version 2 (SF-36 v2.0) and Five-Level EuroQoL 5 Dimensions (EQ-5D-5L) instruments, respectively. Hypoparathyroidism-associated symptoms were assessed by a disease-specific Hypoparathyroidism Symptom Diary and caregiver burden via the Modified Caregiver Strain Index (MCSI). RESULTS: Data were obtained from 398 patients and 207 caregivers. Patients' self-rated hypoparathyroidism-related symptom severity was none (3%), mild (32%), moderate (53%) or severe (12%). Per the Hypoparathyroidism Symptom Diary, patients reported moderate, severe or very severe symptoms of physical fatigue (73%), muscle cramps (55%), heaviness in limbs (55%) and tingling (51%) over a 7-day recall period. Impacts (rated 'somewhat' or 'very much') were reported by 84% of patients for ability to exercise, 78% for sleep, 75% for ability to work and 63% for family relationships. Inverse relationships were observed between patient self-rated overall symptom severity and HRQoL and health status assessment scores-the greater the symptom severity, the lower the SF-36 and EQ-5D-5L scores. Caregiver burden increased with patient self-rated symptom severity: none, 1.7 MCSI; mild, 5.4 MCSI; moderate, 9.5 MCSI; and severe, 12.5 MCSI. CONCLUSION: Patients with not adequately controlled hypoparathyroidism reported substantial symptoms and impacts. Greater patient symptom severity was associated with decreased patient HRQoL and health status assessments and increased caregiver burden.

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.

Cut-off values for sufficient cortisol response to low dose Short Synacthen Test after surgery for non-functioning pituitary adenoma.

OBJECTIVE: The aim was to study the prevalence of secondary adrenal insufficiency before and after surgery for non-functioning pituitary adenomas, as well as determine risk factors for developing secondary adrenal insufficiency. A secondary aim was to determine adequate p-cortisol response to a 1-µg Short Synacthen Test after surgery. DESIGN: Longitudinal cohort study. METHODS: One hundred seventeen patients (52/65 females/males, age 59 years) undergoing primary surgery for clinically non-functioning pituitary adenomas were included. P-cortisol was measured in morning blood samples. Three months after surgery, a Short Synacthen Test was performed. RESULTS: All tumours were macroadenomas (mean size 26.9 mm, range 13-61 mm). The surgical indications were visual impairment (93), tumour growth (16), pituitary apoplexy (6) and headache (2). Before surgery, 17% of the patients had secondary adrenal insufficiency (SAI), decreasing to 15% 3 months postoperatively. Risk of SAI was increased in patients operated for pituitary apoplexy (p < 0.001), while age, sex, tumour size and complication rate were not different from the remaining cohort. Three months after surgery, all patients with baseline p-cortisol ≥ 172 nmol/l (6.2 µg/dl) and peak p-cortisol during Short Synacthen Test ≥ 320 nmol/l (11.6 µg/dl) tapered cortisone unproblematically. In patients with intact hypothalamic-pituitary-adrenal axis, p-cortisol peaked < 500 nmol/l (18.1 µg/dl) during Short Synacthen Test in 48% of patient. CONCLUSION: Pituitary surgery is safe and transsphenoidal surgery rarely causes new SAI. Relying solely on morning p-cortisol for diagnosing secondary adrenal insufficiency gives false positives and the Short Synacthen Test remains useful. A peak p-cortisol ≥ 320 during (11.6 µg/dl) Short Synacthen Test indicates a sufficient response, while < 309 nmol/l (11.2 µg/dl) indicates secondary adrenal insufficiency.

Content and system development of a digital patient-provider communication tool to support shared decision making in chronic health care: InvolveMe.

BACKGROUND: Chronic conditions present major health problems, affecting an increasing number of individuals who experience a variety of symptoms that impact their health related quality of life. Digital tools can be of support in chronic conditions, potentially improving patient-provider communication, promoting shared decision making for treatment and care, and possibly even improving patient outcomes. This study aimed to develop a digital tool for patient-provider communication in chronic health care settings and describes the data collection and subsequent content and software development of the InvolveMe tool. InvolveMe will provide patients with the opportunity to report symptoms and preferences to their health care providers (HCP), and to use secure messaging to interact with the HCPs. METHOD: The study employed a combination of interviews with patients with chronic conditions and focus groups with HCPs, examining experiences with chronic conditions and the potential use of a digital tool for support. Participants were recruited from two outpatient clinics at a university hospital. Data collected from interviews and focus groups were analysed using thematic analysis. Content and software development was informed by the data collection and by tool development workshops. RESULTS: Analyses from interviews with patients (n = 14) and focus groups with HCPs (n = 11) generated three main themes: 1) Making symptoms and challenges visible, 2) Mastering a new life, and 3) Digital opportunities for follow-up. Each main theme generated separate subthemes. Theme 1 and 2 gave input for content development of the symptom and needs assessment part of the tool, while theme 3 provided ideas for the software development of the InvolveMe tool. Tool development workshops with patients (n = 6) and HCPs (n = 6) supplemented the development. CONCLUSIONS: A digital tool such as InvolveMe has the potential to support shared decision making for patients with chronic health conditions. Through integration with an existing patient portal such a tool can provide opportunities for meaningful interactions and communication between patients and HCP's, particularly with regards to symptoms, needs and preferences for care.

Adipokines and macrophage markers during pregnancy-Possible role for sCD163 in prediction and progression of gestational diabetes mellitus.

AIMS: The risk of gestational diabetes mellitus (GDM) is increased in overweight and obese women potentially involving secreted mediators from adipose tissue. Our main aim was to evaluate if circulating adipokines and monocyte/macrophage markers were dysregulated in GDM and the influence body mass and indices of glucose metabolism had on this association. We further explored if early detection of these markers improved prediction of GDM and if they remained modified during long-term follow-up. MATERIALS AND METHODS: Population-based prospective cohort study in 273 pregnant women with markers measured four times during pregnancy and at 5-year follow-up. RESULTS: sCD163 was higher (25% at 14-16 weeks, P < 0.001) and adiponectin lower (-17% at 14-16 weeks, P < 0.01) early in pregnancy and at 5-year follow-up in GDM women, independent of BMI, and other GDM risk factors. Leptin, adiponectin, and chemerin were robustly associated with glucose metabolism throughout pregnancy while sCD163 was inversely associated with ß-cell function early in pregnancy in women with increased BMI. Finally, the markers at 14 to 16 weeks displayed modest discriminatory properties with regard to prediction of GDM (AUC < 0.7). Using a combination of fasting glucose and sCD163, 53% of GDM could be identified when 25% of the population scored positive suggesting some merit in a multimarker approach. CONCLUSIONS: sCD163 and adiponectin were dysregulated in GDM, independent of body mass. None of the adipokines or monocyte/macrophage activation markers displayed clinically useful properties alone for early detection of GDM. Activation of monocytes/macrophages may be an important event in the early development of GDM.

Bone Matrix Levels of Dickkopf and Sclerostin are Positively Correlated with Bone Mass and Strength in Postmenopausal Osteoporosis.

Wnt signaling plays a pivotal role in maintaining bone mass. Secreted pathway modulators such as sclerostin (SOST) and Dickkopfs (DKKs) may influence bone mass inhibiting the canonical Wnt pathway. We evaluated whether bone protein content of secreted Wnt antagonists is related to age, bone mass, and strength in postmenopausal osteoporosis. We measured cortical and trabecular bone contents of SOST and Dickkopf-1 (DKK1) in combined extracts obtained after ethylenediaminetetraacetic acid and guanidine hydrochloride extraction in 56 postmenopausal women aged 47-74 (mean, 63) yr with a previous distal forearm fracture and a hip or spine Z-score less than 0. Our findings were (i) SOST and DKK1 protein levels were higher in trabecular bone, (ii) cortical and trabecular DKK1 and trabecular SOST correlated positively with bone matrix levels of osteocalcin (r between 0.28 and 0.45, p < 0.05), (iii) cortical DKK1 correlated with lumbar spine bone mineral density (BMD) (r = 0.32, p < 0.05) and femoral neck BMD (r = 0.41, p < 0.01), and (iv) cortical DKK1 and SOST correlated with apparent bone volumetric density and compressive strength (r between 0.34 and 0.51, p < 0.01). In conclusion, cortical bone matrix levels of DKK1 and SOST were positively correlated with bone mass and bone strength in postmenopausal osteoporotic women.

Vitamin D assays and the definition of hypovitaminosis D: results from the First International Conference on Controversies in Vitamin D.

The First International Conference on Controversies in Vitamin D was held in Pisa, Italy, 14-16 June 2017. The meeting's purpose was to address controversies in vitamin D research, review the data available, to help resolve them, and suggest a research agenda to clarify areas of uncertainty. The serum 25-hydroxyvitamin D [25(OH)D] concentration [i.e. the sum of 25(OH)D3 and 25(OH)D2 ] remains the critical measurement for defining vitamin D status. Assay variation for 25(OH)D has contributed to the current chaos surrounding efforts to define hypovitaminosis D. An essential requirement to develop a consensus on vitamin D status is that measurement of 25(OH)D and, in the future, other potential vitamin D biomarkers [e.g. 1α,25(OH)2 D3 , 3-epi-25(OH)D, 24,25(OH)2 D3, vitamin D-binding protein, free/bioavailable 25(OH)D and parathyroid hormone] be standardized/harmonized, to allow pooling of research data. Vitamin D Standardization Program tools are described and recommended for standardizing 25(OH)D measurement in research. In the future, similar methodology, based on National Institute for Standards and Technology standard reference materials, must be developed for other candidate markers of vitamin D status. Failure to standardize/harmonize vitamin D metabolite measurements is destined to promulgate continued chaos. At this time, 25(OH)D values below 12 ng ml-1 (30 nmol l-1 ) should be considered to be associated with an increased risk of rickets/osteomalacia, whereas 25(OH)D concentrations between 20 ng ml-1 and 50 ng ml-1 (50-125 nmol l-1 ) appear to be safe and sufficient in the general population for skeletal health. In an effort to bridge knowledge gaps in defining hypovitaminosis D, an international study on rickets as a multifactorial disease is proposed.