Several reports have shown good performance of fluorine-18 fluorocholine (F-FCH) PET-computed tomography (CT) for parathyroid localization, although overall evidence remains scarce. We collected data ...from three institutions in the Netherlands and investigated the performance of F-FCH PET-CT as a second-line imaging modality.
We performed a retrospective review of all patients at least 18 years who underwent F-FCH PET-CT for biochemically proven hyperparathyroidism (HPT) and inconclusive ultrasound and sestamibi scintigraphy. Acquisition of PET images was performed 30 min after the administration of 2 MBq/kg F-FCH, together with a low-dose CT.
PET-CT scans were performed in 33 (75%) women and 11 (25%) men with a mean age of 58.9 (range 31-80 years). Three patients had multiple endocrine neoplasia type 1, one patient had tertiary HPT because of Alport syndrome and the remaining patients had sporadic primary HPT. F-FCH PET-CT was positive in 34/44 (77.3%) cases. Of the 35 abnormal glands resected in 33 patients, F-FCH PET-CT could successfully localize 33/35 (94.3%), with only one false-positive result positive predictive value (PPV)=97.1%. Comparison of the 10 patients with negative PET-CT with the 34 patients with positive PET-CT showed no significant differences in age, sex, ratio of preoperative calcium, use of cinacalcet, history of neck surgery, and concomitant multinodular goiter.
Our study shows excellent performance of F-FCH PET-CT in patients with HPT and inconclusive conventional imaging. Because of its favorable characteristics with high performance, prospective studies should be initiated to determine whether this new technique may replace conventional sestamibi scintigraphy as a first-line imaging modality.
Neurogenic bladder is caused by disruption of neuronal pathways regulating bladder relaxation and contraction. In severe cases, neurogenic bladder can lead to vesicoureteral reflux, hydroureter, and ...chronic kidney disease. These complications overlap with manifestations of congenital anomalies of the kidney and urinary tract (CAKUT). To identify novel monogenic causes of neurogenic bladder, we applied exome sequencing (ES) to our cohort of families with CAKUT. By ES, we have identified a homozygous missense variant (p.Gln184Arg) in CHRM5 (cholinergic receptor, muscarinic, 5) in a patient with neurogenic bladder and secondary complications of CAKUT. CHRM5 codes for a seven transmembrane‐spanning G‐protein‐coupled muscarinic acetylcholine receptor. CHRM5 is shown to be expressed in murine and human bladder walls and is reported to cause bladder overactivity in Chrm5 knockout mice. We investigated CHRM5 as a potential novel candidate gene for neurogenic bladder with secondary complications of CAKUT. CHRM5 is similar to the cholinergic bladder neuron receptor CHRNA3, which Mann et al. published as the first monogenic cause of neurogenic bladder. However, functional in vitro studies did not reveal evidence to strengthen the status as a candidate gene. Discovering additional families with CHRM5 variants could help to further assess the genes' candidate status.
In a first step toward standardization, the Primary Aldosteronism Surgical Outcomes investigators introduced consensus criteria defining the clinical outcomes after adrenalectomy for primary ...aldosteronism. Within this retrospective cohort study, we evaluated the use of these consensus criteria in daily clinical practice in 16 centers in Europe, Canada, Australia, and the United States.
Patients who underwent unilateral adrenalectomy for primary aldosteronism between 2010 and 2016 were included. Patients with missing data regarding preoperative or postoperative blood pressure or their defined daily dose were excluded. According to the Primary Aldosteronism Surgical Outcomes criteria, patients were classified as complete, partial, or absent clinical success.
A total of 380 patients were eligible for analysis. Complete, partial, and absent clinical success was achieved in 30%, 48%, and 22%, respectively. Evaluation of the Primary Aldosteronism Surgical Outcomes criteria showed that in 11% and 47% of patients with partial and absent clinical success, this classification was incorrect or debatable (16% of the total cohort). This concept of a “debatable classification of success” was due mainly to the cutoff of ≥20 mmHg used to indicate a clinically relevant change in systolic blood pressure and the use of percentages instead of absolute values to indicate a change in defined daily dose.
Although introduction of the Primary Aldosteronism Surgical Outcomes consensus criteria induced substantial advancement in the standardization of postoperative outcomes, our study suggests that there is room for improvement in the concept for success given the observed limitations when the criteria were tested within our international cohort. In line, determining clinical success remains challenging, especially in patients with opposing change in blood pressure and defined daily dose.
To evaluate 6 months' eszopiclone treatment upon patient-reported sleep, fatigue and sleepiness, insomnia severity, quality of life, and work limitations.
Randomized, double blind, controlled ...clinical trial.
54 research sites in the U.S.
830 primary insomnia patients who reported mean nightly total sleep time (TST) < or = 6.5 hours/night and/or mean nightly sleep latency (SL) >30 min.
Eszopiclone 3 mg or matching placebo.
Patient-reported sleep measures, Insomnia Severity Index, Medical Outcomes Study Short-Form Health Survey (SF-36), Work Limitations Questionnaire, and other assessments measured during baseline, treatment Months 1-6, and 2 weeks following discontinuation of treatment.
Patient-reported sleep and daytime function were improved more with eszopiclone than with placebo at all months (P <0.001). Eszopiclone reduced Insomnia Severity Index scores to below clinically meaningful levels for 50% of patients (vs 19% with placebo; P <0.05) at Month 6. SF-36 domains of Physical Functioning, Vitality, and Social Functioning were improved with eszopiclone vs placebo for the Month 1-6 average (P < 0.05). Similarly, improvements were observed for all domains of the Work Limitations Questionnaire with eszopiclone vs placebo for the Month 1-6 average (P <0.05).
This is the first placebo-controlled investigation to demonstrate that long-term nightly pharmacologic treatment of primary insomnia with any hypnotic enhanced quality of life, reduced work limitations, and reduced global insomnia severity, in addition to improving patient-reported sleep variables.
The aim of our study was to modify the basis compound ß-TaON, which crystallizes in the monoclinic baddeleyite-type, by incorporation of appropriate dopant ions, in order to obtain anion-deficient ...cubic fluorite-type phases, which are of interest as solids with mobile nitrogen ions. For this purpose, scandium-doped tantalum oxide nitrides were prepared by ammonolysis of amorphous oxide precursors. An unexpected variety of phases with different structural features was observed: bixbyite-type phases of general composition Sc
x
Ta
1−
x
(O,N)
y
with 0.33≤
x≤1 and 1.7≤
y≤1.9, yellow colored metastable anatase-type phases such as Sc
0.1Ta
0.9O
1.2N
0.8 or Sc
0.15Ta
0.85O
1.3N
0.7 and, additionally, anosovite-type phases Sc
x
Ta
3−
x
O
2
x
N
5−2
x
with 0≤
x≤1.05. Selected phases were investigated by UV/vis spectroscopy. Anatase- and anosovite-type compounds show brilliant colors. In the anatase-type phase, a possible anion ordering was examined by theoretical methods. Additionally, energy calculations on phase stability were performed for Sc
x
Ta
1−
x
O
1+2
x
N
1−2
x
in the baddeleyite, rutile, and anatase structure types with varying amounts of dopants.
New anatase- and bixbyite-type phases obtained as single-phase samples in the system Sc–Ta–O–N.
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Metamizol (dipyrone,
1), a widely used drug with effective analgesic and antispasmodic properties, shows severe side effects like agranulocytosis and anaphylactic shock reactions, the reasons of ...which are not known until today. After oral administration
1 is completely metabolized. All hitherto known metabolites have an intact pyrazolinone ring structure like the parent compound and are completely extractable from urine with polar organic solvents. However, only a fractional amount of the applied dosage can be recovered by this procedure.
To clarify the reason of this deficit of unknown metabolites we followed the hypothesis of oxidative rupture of the heterocyclic ring during metabolism of
1. On the basis of former in vitro results we now were able to identify in quality three oxalic acid derivatives and one acetic acid phenylhydrazide as new metabolites of metamizol in the allantoic fluid (AF) of incubated hen's eggs as well as in human urine by means of GC–MS analysis and comparison with unequivocally synthesized authentic reference compounds. Whereas the oxamazide
7, the phenylhydrazide
8 and
N-methyloxamic acid
9 are only present in trace concentrations and therefore cannot account for the deficit in the balance of metabolites, the oxalic acid monohydrazide
11 seems to be excreted in higher amount. But quantitative determination of this new metabolite would be required to answer the open questions concerning the biotransformation of metamizol and thereby to detect new facts about mode of action and side effects of this drug.
Background
Various diagnostic tests are available to establish the primary aldosteronism (PA) diagnosis and to determine the disease laterality. Combined with the controversies in the literature, ...unawareness of guidelines and technical demands and high costs of some of these diagnostics, this could lead to significant differences in work-up strategies worldwide. Therefore, we investigated the work-up before surgery for PA in daily clinical practice within a multicenter study.
Methods
Patients who underwent unilateral adrenalectomy for PA within 16 centers in Europe, Canada, Australia and the USA between 2010 and 2016 were included. We did not exclude patients based on the performed diagnostic tests during work-up to make our data representative for current clinical practice. Adherence to the Endocrine Society Guideline and variables associated with not performing adrenal venous sampling (AVS) were analyzed.
Results
In total, 435 patients were eligible. An aldosterone-to-renin ratio, confirmatory test, computed tomography (CT), magnetic resonance imaging and AVS were performed in 82.9%, 32.9%, 86.9%, 17.0% and 65.3% of patients, respectively. A complete work-up, as recommended by the guideline, was performed in 13.1% of patients. Bilateral disease or normal adrenal anatomy on CT (OR 16.19; CI 3.50–74.99), smaller tumor size on CT (OR 0.06; CI 0.04–0.08) and presence of hypokalemia (OR 2.00; CI 1.19–3.32) were independently associated with performing AVS.
Conclusions
This study is the first to examine the daily clinical practice work-up of PA within a worldwide cohort of surgical patients. The results demonstrate significant variability in work-up strategies and low adherence to The Endocrine Society guideline.
Introduction
Complete resolution of hypertension after adrenalectomy for primary aldosteronism is far from a certainty. This stresses the importance of adequate preoperative patient counseling. The ...aldosteronoma resolution score (ARS) is a simple and easy to use prediction model only including four variables: ≤ 2 antihypertensive medications, body mass index ≤ 25 kg/m
2
, duration of hypertension ≤ 6 years and female sex. However, because the model was developed and validated within the USA over a decade ago, the applicability in modern practice and outside of the USA is questionable. Therefore, we aimed to validate the ARS in current clinical practice within an international cohort.
Materials and method
Patients who underwent unilateral adrenalectomy, between 2010 and 2016, in 16 medical centers from the USA, Europe (EU), Canada (CA) and Australia (AU) were included. Resolution of hypertension was defined as normotension without antihypertensive medications.
Results
In total, 514 patients underwent adrenalectomy and 435 (85%) patients were eligible. Resolution of hypertension was achieved in 27% patients within the total cohort and in 22%, 30%, 40% and 38% of patients within USA, EU, CA and AU, respectively (
p
= 0.015). The area under the curve (AUC) for the complete cohort was 0.751. Geographic validation displayed a AUC within the USA, EU, CA and AU of 0.782, 0.681, 0.811 and 0.667, respectively.
Discussion
The ARS is an easy to use prediction model with a moderate to good predictive performance within current clinical practice. The model showed the highest predictive performance within North America but potentially has less predictive performance in EU and AU.
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