A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis

Background: We aimed to describe the longitudinal changes in bone mineral content and influencing factors, in children with cystic fibrosis (CF). Methods: One hundred children (50 females) had dual X-ray absorptiometry (DXA) performed. Of these, 48 and 24 children had two to three scans, respectively over 10 years of follow-up. DXA data were expressed as lumbar spine bone mineral content standard deviation score (LSBMCSDS) adjusted for age, gender, ethnicity and bone area. Markers of disease, anthropometry and bone biochemistry were collected retrospectively. Results: Baseline LSBMCSDS was >0.5 SDS in 13% children, between −0.5; 0.5 SDS, in 50% and ≤−0.5 in the remainder. Seventy-eight percent of the children who had baseline LSBMCSDS >−0.5, and 35% of the children with poor baseline (LSBMCSDS<−0.5), showed decreasing values in subsequent assessments. However, mean LS BMC SDS did not show a significant decline in subsequent assessments (−0.51; −0.64; −0.56; p=0.178). Lower forced expiratory volume in 1 s percent (FEV1%) low body mass index standard deviation scores (BMI SDS) and vitamin D were associated with reduction in BMC. Conclusions: Bone mineral content as assessed by DXA is sub-optimal and decreases with time in most children with CF and this study has highlighted parameters that can be addressed to improve bone health

Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction

Diabetes, obesity and Alzheimer’s disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), APP and β-amyloid (Aβ) are linked with vascular disease development and raised BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, raised Aβ and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice raised plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction and raised blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation and raised blood pressure. In humans, raised plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP and protein kinase G (PKG) activity independently of diet whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS-cGMP-PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes

Uric acid levels and outcome from coronary artery bypass grafting

ObjectiveElevated uric acid levels have been associated with an adverse cardiovascular outcome in several settings. Their utility in patients undergoing surgical revascularization has not, however, been assessed. We hypothesized that serum uric acid levels would predict the outcome of patients undergoing coronary artery bypass grafting.MethodsThe study cohort consisted of 1140 consecutive patients undergoing nonemergency coronary artery bypass grafting. Clinical details were obtained prospectively, and serum uric acid was measured a median of 1 day before surgery. The primary end point was all-cause mortality.ResultsDuring a median of 4.5 years, 126 patients (11%) died. Mean (± standard deviation) uric acid levels were 390 ± 131 μmol/L in patients who died versus 353 ± 86 μmol/L among survivors (hazard ratio 1.48 per 100 μmol/L; 95% confidence interval, 1.25–1.74; P < .001). The excess risk associated with an elevated uric acid was particularly evident among patients in the upper quartile (≥410 μmol/L; hazard ratio vs all other quartiles combined 2.18; 95% confidence interval, 1.53–3.11; P < .001). After adjusting for other potential prognostic variables, including the European System for Cardiac Operative Risk Evaluation, uric acid remained predictive of outcome.ConclusionIncreasing levels of uric acid are associated with poorer survival after coronary artery bypass grafting. Their prognostic utility is independent of other recognized risk factors, including the European System for Cardiac Operative Risk Evaluation

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Urinary gonadotrophins: a useful non-invasive marker of activation of the hypothalamic pituitary-gonadal axis

<p>Abstract</p> <p>Background</p> <p>Non-invasive screening investigations are rarely used for assessing the activation and progression of the hypothalamic-pituitary gonadal axis through puberty. This study aimed to establish a normal range for urinary gonadotrophins in children progressing through puberty.</p> <p>Methods</p> <p>Urine samples were collected from 161 healthy school children (76 boys, 85 girls) aged 4–19 yrs. Height and weight were converted to standard deviation score. Pubertal status, classified by Tanner staging, was determined by self-assessment. Urinary gonadotrophins were measured by chemiluminescent microparticle immunoassay. Results were grouped according to pubertal status (pre-pubertal or pubertal).</p> <p>Results</p> <p>Of the 161 children, 50 were pre-pubertal (28 boys; 22 girls) and 111 were pubertal (48 boys; 63 girls). Overall, urinary gonadotrophins concentrations increased with pubertal maturation. All pre-pubertal children had a low urinary LH:Creatinine ratio. LH:Creatinine ratios were significantly higher in pubertal compared to pre-pubertal boys (<it>p</it><0.001). In girls, FSH:Creatinine ratios were significantly higher in the pubertal group (<it>p</it> = 0.006). However, LH:FSH ratios were a more consistent discriminant between pre-pubertal and pubertal states in both sexes (Boys 0.45 pubertal vs 0.1 pre-pubertal; girls 0.23 pubertal vs 0.06 pre-pubertal).</p> <p>Conclusion</p> <p>Urinary gonadotrophins analyses could be used as non-invasive integrated measurement of pubertal status which reflects clinical/physical status.</p

Urinary gonadotrophins: role in assessment and management of disorders of puberty

Introduction: With improvements in assays and the increasing need for non-invasive, out-patient based investigations, there is a renewed interest in the use of urinary gonadotrophins (UG) for assessing pubertal progress. This study aims to establish the correlation between serum and urinary LH and FSH in patients undergoing investigation or management of pubertal disorders. Methods/design: Retrospective evaluation of eight patients undergoing investigation for pubertal delay (five males and three females) and 21 patients (six males and 15 females) for early puberty or suppression of puberty by GnRH agonist (GnRH-a) therapy. Median ages (range) for the boys and girls were 14.4 years (8.9–17.2) and 9.2 years (4.2–17.3), respectively. Non-timed spot urine samples were collected for all cases and 11 (five males and six females) of these were on GnRH-a. Of the 29 cases, matched serum gonadotrophins were available in 15 cases (seven males and eight females). UG were measured by chemiluminescent microparticle immunoassay and corrected for urinary creatinine. Results: In both pubertal males and females, UG were significantly higher than during-GnRH-a treatment: For the 15 cases with matched serum and urine samples, median serum LH and ULH:creat were 1.5 U/l (0.1–21.9) and 0.16 (0–1.37), respectively. There was a strong correlation between these values (r2, 0.92), independent of sex. Conclusion: These preliminary data suggest that UG reflect serum gonadotrophin concentrations and the finding of low UG in patients on GnRH-a therapy suggest that this test may represent a useful non-invasive method of assessing and monitoring effectiveness of GnRH-a therapy

On the condition number of the influence matrix belonging to some first kind integral equations with logarithmic kernel

SIGLETIB: RN 2394 (910) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Serum anti-Müllerian hormone in the prediction of response to hCG stimulation in children with DSD

The relationship between serum anti-Müllerian hormone (AMH) and the testosterone response to hCG stimulation test is unclear. Children who had hCG stimulation tests in one tertiary centre between 2001-2018 were included (n,138). Serum testosterone (T) was measured before (D1) and after 3 days (D4) of hCG stimulation. Sixty-one of these children also had prolonged hCG stimulation for 2 more weeks and serum T measured after 21 days (D22). All children had a serum AMH measured on D1. Of the 138 children, D4 T was normal in 104 (75%). AMH was low in 24/138 (17%) children and 16 (67%) of these had a low D4 testosterone. Median AMH in those who had a normal vs low D4 T was 850 pmol/l (24, 2280) and 54 pmol/l (0.4, 1664), respectively (p&lt;0.0001). An AMH &gt;5th centile was associated with a low D4 testosterone in 18/118 (13%, p&lt;0.0001). Of the 61 children who had prolonged hCG stimulation, D22 T was normal in 39 (64%). AMH was low in 10/61(16%) children and 9 (90%) of these had a low D22 testosterone. Median AMH in children who responded and did not respond by D22 was 639 pmol/l (107, 2280) and 261 pmol/l (15, 1034) (p&lt;0.0001). A normal AMH may provide valuable information on overall testicular function. However, a low AMH does not necessarily predict a sub-optimal testosterone response to hCG stimulation. [Abstract copyright: © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: [email protected].