Objective A major cause of readmission after transsphenoidal surgery (TSS) is delayed hyponatraemia. The purpose of this study was to identify predictors of hyponatraemia one week post surgery and ...predictors of 30-day readmissions for hyponatraemia. Design A retrospective cohort study including patients who had TSS performed for pituitary lesions. Method The risk of readmission for hyponatraemia was assessed in consecutive patients between January 2008 and March 2016. The risk of hyponatraemia one week post surgery was assessed in patients admitted for TSS between July 2011 and March 2016. Results Of all included patients, 56/522 (10.7%) were readmitted within 30 days. Hyponatraemia was found in 14/56 (25%) of 30-day readmissions. We did not identify any predictive variable for hyponatraemia on readmission. The number of patients with hyponatraemia on the seventh post-operative day was 26/314 (8.3%). The risk of hyponatraemia one week post surgery was increased by an odds ratio of 2.40 (95% CI: 1.06–5.40) in patients with a tumour abutting the optic chiasm and by an odds ratio of 1.16 (1.04–1.31) per mmol/L decrease in sodium levels on the first post-operative day. Conclusions Hyponatraemia occurred in 25% of readmissions; however, we did not identify any predictive variable for readmission with hyponatraemia. One week post surgery, 8.9% had hyponatraemia. Tumours pressing on the optic chiasm as well as a fall in sodium levels on the first post-operative day were associated with an increased risk of hyponatraemia one week post surgery. We suggest that a day 7 serum sodium <130 nmol/L should lead to concern and the provision of patient advice.
Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels ...and symptoms suggestive of hypogonadism in current and former AAS abusers.
This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18-50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically.
Former AAS abusers exhibited significantly lower median (25th -75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9-17.7) nmol/l vs. 18.8 (16.6-22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05).
Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation. Current AAS abusers exhibited severely decreased AMH and inhibin B indicative of impaired spermatogenesis.
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CONTEXT B-type natriuretic peptides have been shown to predict cardiovascular
disease in apparently healthy individuals but their predictive ability for
mortality and future cardiovascular events ...compared with C-reactive protein
(CRP) and urinary albumin/creatinine ratio is unknown. OBJECTIVE To assess the prognostic value of the N-amino terminal fragment of the
prohormone brain natriuretic peptide (NT-proBNP) vs CRP and urinary albumin/creatinine
ratio in an older adult population. DESIGN, SETTING, AND PARTICIPANTS A population-based prospective study of 764 participants aged 50 to
89 years from a community in Copenhagen, Denmark, in which 658 participants
provided blood and urinary samples and were examined between September 1,
1998, and January 24, 2000. Of these participants, 626 without heart or renal
failure were enrolled. A subgroup of 537 had no history of cardiovascular
disease at baseline. During 5 years of follow-up (to December 31, 2003), 94
participants died and 65 developed a first major cardiovascular event. MAIN OUTCOME MEASURES Risk of mortality and first major cardiovascular event by baseline levels
of NT-proBNP, CRP, and urinary albumin/creatinine ratio levels. RESULTS After adjustment for the cardiovascular risk factors of age, sex, smoking,
diabetes mellitus, hypertension or ischemic heart disease, total cholesterol,
and serum creatinine, the hazard ratio (HR) of mortality for values above
the 80th percentile of NT-proBNP was 1.96 (95% confidence interval CI, 1.21-3.19);
for CRP, 1.46 (95% CI, 0.89-2.24); and for urinary albumin/creatinine ratio,
1.88 (95% CI, 1.18-2.98). Additional adjustment for left ventricular systolic
dysfunction did not markedly attenuate the predictive value of NT-proBNP (HR,
1.82; 95% CI, 1.11-2.98). The absolute unadjusted increase in mortality risk
for participants with values above the 80th percentile vs equal to or below
the 80th percentile was 24.5% for NT-proBNP, 7.8% for CRP, and 19.5% for urinary
albumin/creatinine ratio. The NT-proBNP levels were associated with first
major cardiovascular events (nonfatal myocardial infarction, fatal coronary
heart disease, unstable angina, heart failure, stroke, and transient ischemic
attack) with an adjusted HR of 3.24 (95% CI, 1.80-5.79) vs 1.02 (95% CI, 0.56-1.85)
for CRP and 2.32 (95% CI, 1.33-4.05) for urinary albumin/creatinine ratio
when comparing participants with values above the 80th percentile with those
with values equal to or below the 80th percentile. CONCLUSIONS Measurements of NT-proBNP provide prognostic information of mortality
and first major cardiovascular events beyond traditional risk factors. NT-proBNP
was a stronger risk biomarker for cardiovascular disease and death than CRP
was in nonhospitalized individuals aged 50 to 89 years.
Women with polycystic ovary syndrome (PCOS) were treated with the GLP‐1 receptor agonist liraglutide to investigate the effect on liver fat content, visceral adipose tissue (VAT) and the prevalence ...of nonalcoholic fatty liver disease (NAFLD). In a double‐blind, placebo‐controlled, randomized clinical trial 72 women with PCOS, with a BMI > 25 kg/m2 and/or insulin resistance, were treated with liraglutide or received placebo 1.8 mg/d (2:1) for 26 weeks. Liver fat content was assessed by 1
HMR spectroscopy, VAT by MRI, body composition by DXA, and glucose metabolism by oral glucose tolerance test. Compared with placebo, liraglutide treatment reduced body weight by 5.2 kg (5.6%), liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two‐thirds (all P < .01). Sex‐hormone‐binding‐globulin (SHBG) levels increased by 19% (P = .03), and free testosterone decreased by 19% (P = .054). HbA1c, fasting glucose and leptin were reduced (all: P < .05), whereas measures of insulin resistance, adiponectin and glucagon did not change. In conclusion, 26 weeks of liraglutide treatment in PCOS resulted in significant reductions in liver fat content, VAT and the prevalence of NAFLD.
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The prevalence of cardiac cachexia has previously been estimated to 8–42 %. However, novel treatment strategies for chronic heart failure (CHF) have improved and decreased morbidity and mortality. ...Therefore, we aimed to reassess the prevalence of cachexia in an outpatient CHF clinic and to characterize a CHF population with and without cachexia with respect to body composition and related biomarkers. From 2008 to 2011, we screened 238 optimally treated, non-diabetic CHF patients for cardiac cachexia, defined as unintentional non-oedematous weight loss of >5 % over ≥6 months. CHF patients (LVEF <45 %) with cachexia (
n
= 19) and without (
n
= 19) were compared to controls with prior myocardial infarction and left ventricular ejection fraction (LVEF) >45 % (
n
= 19). The groups were matched for age, sex, and kidney function. Body composition was assessed by dual energy X-ray absorptiometry. The prevalence of cachexia was 10.5 %. Abdominal fat ± SD (%) was reduced in cachectic CHF: 27.4 ± 10.0 versus 37.5 ± 10.6 % (CHF, no cachexia) and 40.6 ± 8.0 % (controls), (
P
< 0.001). NT-proBNP levels were inversely correlated to abdominal fat in a multivariate linear regression analysis adjusted for known predictors of NT-proBNP (LVEF and NYHA); (
β
= −0.28;
P
= 0.018). Myostatin levels were reduced in cachectic CHF compared to controls (
P
= 0.013). The prevalence of cachexia in stable CHF, treated according to recent guidelines, is lower than previously anticipated. Body alterations in cachexia consist mainly of reduced abdominal fat mass, and its inverse correlation to NT-proBNP suggests involvement of abdominal lipolysis. Our data do not support a role of circulating myostatin as a biomarker for muscle wasting.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Context
Thyroid hormone metabolites might affect the heart. The endogenous aminergic metabolite 3-iodothyronamine (T1am) reduces left ventricular ejection fraction (LVEF) in rodents.
...Objective
To investigate concentration of T1am and its association with LVEF and biomarkers of heart function in patients with chronic heart failure (CHF) without thyroid disease, including patients with cardiac cachexia (nonedematous weight loss >5% over 6 months).
Methods
Cross-sectional study. CHF was characterized by LVEF <45% and symptoms. Three groups were included (n = 19 in each group, matched on age, sex, and kidney function): patients with cachexia (CAC), patients without (non-CAC), and control (C) patients with prior myocardial infarction and LVEF >45%. T1am was measured by a monoclonal antibody-based chemiluminescence immunoassay. N-amino terminal pro-BNP (NT-proBNP) concentrations were also analyzed.
Results
Mean (SD) LVEF: CAC, 32 ± 9%; non-CAC, 38 ± 8%; and C, 60 ± 8% (P < 0.0001). TSH, T4, and T3 levels did not differ between groups and did not correlate to T1am. Serum T1am (nmol/L) concentrations were higher in CHF: CAC (mean ± SD), 12.4 ± 6.6; non-CAC, 9.1 ± 5; and C, 7.3 ± 2.9. A negative association between T1am and LVEF was present after adjusting for sex, age, T3, and estimated glomerular filtration rate (P = 0.03). Further, serum T1am levels tended to be associated with NT-proBNP (P = 0.053).
Conclusion
Serum T1am levels were increased in patients with CHF and numerically highest (although nonsignificant) in patients with cardiac cachexia. Increasing T1am concentrations were independently associated with reduced LVEF, suggesting a direct effect on the human heart.
Serum concentrations of the thyroid hormone T1am was elevated in patients with CHF, negatively associated with LVEF, but not associated with TSH, T4, or T3.
Data from recent cardiovascular outcome trials in patients with type 2 diabetes (T2D) suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors can prevent development of heart failure (HF) and ...prolong life in patients without HF. Ongoing event-driven trials are investigating whether the same effect is present in patients with well-defined HF. The mechanism behind the effect of SGLT2 inhibitors in patients with T2D and the potential effect in patients with overt HF is presently unknown.
This is a randomized, double-blinded, placebo-controlled, parallel group, clinical trial including HF patients with reduced left ventricular ejection fraction (HFrEF) with an ejection fraction ≤ 40% on optimal therapy recruited from specialized HF clinics in Denmark. The primary aim is to investigate the effect of the SGLT2 inhibitor empagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP). Secondary endpoints include cardiac biomarkers, function and hemodynamics, metabolic and renal parameters, daily activity level, and quality of life. Patients are assigned 1:1 to 90 days treatment with empagliflozin 10 mg daily or placebo. Patients with T2D are required to be on recommended doses of anti-glycemic therapy with a hemoglobin A1c (HbA1c) of 6.5-10.0% (48-86 mmol/mol). To show a between-group difference in the change of NT-proBNP of 30%, a total of 189 patients will be included.
The Empire HF trial will elucidate the effects and modes of action of empagliflozin in HFrEF patients with and without T2D and provide important mechanistic data which will complement ongoing event-driven trials.
Clinicaltrialsregister.eu, EudraCT Number 2017-001341-27 . Registered on 29 May 2017. ClinicalTrials.gov, NCT03198585 . Registered on 26 June 2017.
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The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of ...the Danish Fabry cohort and report 20 years' (2001-2020) experience in cascade genetic screening at the Danish National Fabry Disease Center. The Danish Fabry cohort consisted of 26 families, 18 index patients (9 males and 9 females, no available data for 8 index-patients) and 97 family members with a pathogenic GLA variant identified by cascade genetic testing (30 males and 67 females). Fourteen patients (5 males and 9 females; mean age of death 47.0 and 64.8 years respectively) died during follow-up. The completeness of the Fabry patient identification in the country has resulted in a cohort of balanced genotypes according to gender (twice number of females compared to males), indicating that the cohort was not biased by referral, and further resulted in earlier diagnosis of the disease by a lower age at diagnosis in family members compared to index-patients (mean age at diagnosis: index-patients 42.2 vs. family members 26.0 years). Six previously unreported disease-causing variants in the GLA gene were discovered. The nationwide screening and registration of Fabry disease families provide a unique possibility to establish a complete cohort of Fabry patients and to advance current knowledge of this inherited rare lysosomal storage disorder.
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Plasma growth differentiation factor-15 (GDF-15) biomarker levels increase in response to inflammation and tissue injury, and increased levels of GDF-15 are associated with increased risk of ...mortality in patients with heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve outcome in HFrEF, have been shown to increase plasma GDF-15 in diabetic patients. We aimed to investigate the effect of empagliflozin on GDF-15 in HFrEF patients.
This Empire HF Biomarker substudy was from the multicentre, randomized, double-blind, placebo-controlled Empire HF trial that included 190 patients from June 29, 2017, to September 10, 2019. Stable ambulatory HFrEF patients with ejection fraction of ≤ 40% were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo for 12 weeks. Changes from baseline to 12 weeks in plasma levels of GDF-15, high-sensitive C-reactive protein (hsCRP), and high-sensitive troponin T (hsTNT) were assessed.
A total of 187 patients who were included in this study, mean age was 64 ± 11 years; 85% male, 12% with type 2 diabetes, mean ejection fraction 29 ± 8, with no differences between the groups. Baseline median plasma GDF-15 was 1189 (918-1720) pg/mL with empagliflozin, and 1299 (952-1823) pg/mL for placebo. Empagliflozin increased plasma GDF-15 compared to placebo (adjusted between-groups treatment effect; ratio of change (1·09 95% confidence interval (CI), 1.03-1.15: p = 0.0040). The increase in plasma GDF15 was inversely associated with a decrease in left ventricular end-systolic (R = - 0.23, p = 0.031), and end-diastolic volume (R = - 0.29, p = 0.0066). There was no change in plasma hsCRP (1.09 95%CI, 0.86-1.38: p = 0.48) or plasma hsTNT (1.07 95%CI, 0.97-1.19: p = 0.18) compared to placebo. Patients with diabetes and treated with metformin demonstrated no increase in plasma GDF-15 with empagliflozin, p for interaction = 0·01.
Empagliflozin increased plasma levels of GDF-15 in patients with HFrEF, with no concomitant increase in hsTNT nor hsCRP.
The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585.
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