Julie Lyng Forman

Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women

BACKGROUNDnAdaptive alterations in maternal physiology cause changes in thyroid hormone levels throughout pregnancy, and precise biochemical evaluation is thus highly dependent on gestation-specific reference intervals and expected intra-individual variation.nnnOBJECTIVEnThe aim of the study was the assessment of the intra-individual variation as well as the longitudinal course of thyroid hormones during normal pregnancy and factors that influence the normal reference range for thyroid function. For this purpose, a longitudinal statistical model was applied.nnnDESIGNnIn a cohort of 132 pregnant women, serial blood samples were obtained and ultrasound scans were performed throughout pregnancy.nnnMETHODSnSerum levels of TSH, free and total thyroxine (T(4)), free and total triiodothyronine (T(3)) as well as autoantibodies against thyroid peroxidase and thyroglobulin were measured in 979 serum samples.nnnRESULTSnIntra-individual variations of thyroid hormone concentrations were smaller than inter-individual variations (individuality index range: 0.38-0.71). Maternal height was positively associated with free T(4) (FT(4)) (b=0.003; P=0.031) and pre-pregnancy body mass index with T(3) and free T(3) (b=0.017; <0.001 and b=0.007; P<0.001). Smoking was positively associated with T(4) and FT(4), but it was modulated by gestational age. Gestation-specific reference intervals for thyroid function variables from autoantibody-negative participants are presented.nnnCONCLUSIONSnIn accordance with the data from nonpregnant adults, intra-individual variations of thyroid hormones were smaller than inter-individual variations also during pregnancy. In the evaluation of thyroid function in pregnancy, the individual longitudinal course of thyroid hormones rather than absolute values should be considered. We present a longitudinal model for the prediction of maternal thyroid function tests in pregnant women.

Association between spousal suicide and mental, physical, and social health outcomes a longitudinal and nationwide register-based study

Importance Bereavement after spousal suicide has been linked to mental disorders; however, a comprehensive assessment of the effect of spousal suicide is needed. Objective To determine whether bereavement after spousal suicide was linked to an excessive risk of mental, physical, and social health outcomes when compared with the general population and spouses bereaved by other manners. Design, Setting, and Participants This nationwide, register-based cohort study conducted in Denmark of 6.7 million individuals aged 18 years and older from 1980 to 2014 covered more than 136 million person-years and compared people bereaved by spousal suicide with the general population and people bereaved by other manners of death. Incidence rate ratios were calculated using Poisson regressions while adjusting for sociodemographic characteristics and the presence of mental and physical disorders. Main Outcomes and Measures Mental disorders (any disorder, mood, posttraumatic stress disorder, anxiety, alcohol use disorders, drug use disorders, and self-harm); physical disorders (cancers, diabetes, sleep disorder, cardiovascular diseases, chronic lower respiratory tract diseases, liver cirrhosis, and spinal disc herniation); causes of mortality (all-cause, natural, unintentional, suicide, and homicide); social health outcomes; and health care use. Results The total study population included 3u2009491u2009939 men, 4814 of whom were bereaved by spousal suicide, and 3u2009514u2009959 women, 10u2009793 of whom were bereaved by spousal suicide. Spouses bereaved by a partner’s suicide had higher risks of developing mental disorders within 5 years of the loss (men: incidence rate ratio, 1.8; 95% CI, 1.6-2.0; women: incidence rate ratio, 1.7; 95% CI, 1.6-1.8) than the general population. Elevated risks for developing physical disorders, such as cirrhosis and sleep disorders, were also noted as well as the use of more municipal support, sick leave benefits, and disability pension funds than the general population. Compared with spouses bereaved by other manners of death, those bereaved by suicide had higher risks for developing mental disorders (men: incidence rate ratio, 1.7; 95% CI, 1.5-1.9; women: incidence rate ratio, 2.0; 95% CI, 1.9-2.2), suicidal behaviors, mortality, and municipal support. Additionally, a higher level of mental health care use was noted. Conclusions and Relevance Exposure to suicide is stressful and affects the bereaved spouse on a broad range of outcomes. The excess risks of mental, physical, and social health outcomes highlight a need for more support directed toward spouses bereaved by suicide.

Suction blister lesions and epithelialization monitored by optical coherence tomography

Our objective was to assess epithelialization of suction blister lesions by optical coherence tomography (OCT) and benchmark it to histology using epidermal thickness (ET) as the primary outcome.

Vector and Doppler Ultrasound Velocities Evaluated in a Flow Phantom and the Femoropopliteal Vein

Ultrasound is used for evaluating the veins of the lower extremities. Operator and angle dependency limit spectral Doppler ultrasound (SDUS). The aim of the study was to compare peak velocity measurements in a flow phantom and the femoropopliteal vein of 20 volunteers with the angle-independent vector velocity technique vector flow imaging (VFI) and SDUS. In the flow phantom, VFI underestimated velocity (pxa0=xa00.01), with a lower accuracy of 5.5% (pxa0=xa00.01) and with no difference in precision, that is, error factor, compared with SDUS (VFI: 1.02 vs. SDUS: 1.02, pxa0=xa00.58). Inxa0vivo, VFI estimated lower velocities (femoral: pxa0=xa00.001; popliteal: pxa0=xa00.001) with no difference in precision compared with SDUS (femoral: VFI 1.09 vs. SDUS 1.14, pxa0= 0.37; popliteal: VFI 1.13 vs. SDUS 1.06, pxa0=xa00.09). In conclusion, the precise VFI technique can be used to characterize venous hemodynamics of the lower extremities despite its underestimation of velocities.

Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): tumor expression patterns and prognostic value in oral cancer

BackgroundTumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhibit enhanced expression in many types of cancers, and have been investigated as potential biomarkers for targeted strategies and prognostication. The aim of the study was to investigate the expression patterns of uPAR, TF and EGFR and their potential prognostic value in OSCC.MethodsImmunohistochemical expression of uPAR, TF and EGFR in tumor resection specimens from 191 patients with primary OSCC was analyzed. Overall (OS) and disease-free survival (DFS) was calculated. Associations between biomarker expression, clinicopathological factors and patient survival was analyzed using the Cox proportional hazards model for univariate and multivariate analysis, log rank and Kaplan-Meier statistics.ResultsuPAR and TF exhibited a highly tumor-specific expression pattern while EGFR also showed expression in normal tissues outside the tumor compartment. The overall positive expression rate of uPAR, TF and EGFR was 95%, 58% and 98%, respectively. High uPAR expression across the entire cohort was negatively associated with OS (pxa0=xa00.031, HRxa0=xa01.595 (95%CI 1.044–2.439)) in univariate analysis. The 5-year OS for high and low uPAR expression was 39% and 56%, respectively. The expression of TF and EGFR was not associated with survival outcome.ConclusionsThis study may suggest that uPAR and TF could potentially be attractive targets for molecular imaging and therapy in OSCC due to high positive expression rates and tumor-specific expression patterns. High uPAR expression was significantly associated with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer.

Effect Modifications of Lipid-Lowering Therapy on Progression of Aortic Stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] Study)

Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (pu2009=u20090.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06u2009m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, pu2009=u20090.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all pu2009≥0.14). In conclusion, in a non-prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677).

Respiratory variability of peak velocities in the common femoral vein estimated with vector flow imaging and Doppler ultrasound

Respiratory variability of peak velocities (RVPV) in the common femoral vein measured with ultrasound can reveal venous outflow obstruction. Pulse wave (PW) Doppler is the gold standard for venous velocity estimation of the lower extremities. PW Doppler measurements are angle dependent, whereas vector flow imaging (VFI) can yield angle-independent measures. The hypothesis of the present study was that VFI can provide RVPV estimations without the angle dependency of PW Doppler for an improved venous disease assessment. Sixty-seven patients with symptomatic chronic venous disease were included in the study. On average, VFI measured a lower RVPV than PW Doppler (VFI: 14.11 cm/s; PW: 17.32 cm/s, pu202f=u202f0.002) with a non-significant improved precision compared with PW Doppler (VFI: 21.09%; PW: 26.49%, pu202f=u202f0.08). In a flow phantom, VFI had improved accuracy (p < 0.01) and equal precision compared with PW Doppler. The study indicated that VFI can characterize the hemodynamic fluctuations in the common femoral vein.

Adrenal Suppression in Infants Treated with Topical Ocular Glucocorticoids

PURPOSEnTo analyze the incidence of adrenal suppression and the glucocorticoid (GC) dose per kilogram body weight given in infants treated with standard protocol for topical ophthalmic GCs after congenital cataract surgery.nnnDESIGNnRetrospective, consecutive case series.nnnPARTICIPANTSnAll children younger than 2 years of age who underwent operation for congenital cataract between January 2011 and May 2015 in 1 center.nnnMETHODSnPatient charts were reviewed to collect data on results and timing of a standard corticotropin (adrenocorticotropic hormone [ACTH]) stimulation test and GC dose per kilogram body weight.nnnMAIN OUTCOME MEASURESnIncidence of adrenal suppression in children tested on GC treatment. Glucocorticoid dose per kilogram body weight.nnnRESULTSnAmong 26 consecutive infants, 15 (58%) were tested while they were still on GC treatment. Ten of these 15 infants (67%) had adrenal suppression, 2 of whom had obvious clinical signs of Cushings syndrome and 1 of whom had signs of Addisonian crises during general anesthesia. Eleven of the 26 infants (42%) were tested at a median time of 21 days (range, 6-89) after treatment cessation, and they all had normal test results. Children with suppressed adrenal function had received cumulative GC doses per body weight that were significantly higher the last 5 days before testing compared with children with normal test results. Infants with adrenal suppression were treated with hydrocortisone replacement therapy. Adrenal function recovered after a median of 3.1 months (range, 2.3 months to 2.3 years).nnnCONCLUSIONSnTwo thirds of the infants tested during treatment with a standard GC protocol after congenital cataract surgery showed adrenal suppression. There was a significant association between the cumulative daily dose of GCs and the test result. Because adrenal suppression is a serious but treatable condition, we recommend a systematic assessment of adrenal function in infants treated with doses of topical ocular GCs comparable to our regimen and careful evaluations of other treatment regimens.

Rectal Insulin Instillation Inhibits Inflammation and Tumor Development in Chemically Induced Colitis

Background and AimsnEpithelial expression of the insulin receptor in the colon has previously been reported to correlate with extent of colonic inflammation. However, the impact of insulin signalling in the intestinal mucosa is still unknown. Here, we investigated the effects of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer.nnnMethodsnThe mice were generated by utilizing the intestinal- and epithelial-specific villin promoter and the Cre-Lox technology. All mice included in the cohorts were generated by crossing [vil-Cre-INSR+/-] × [INSRfl/fl] to obtain [vil-Cre-INSR-/-], and their floxed littermates [INSRfl/fl] served as the control group. For the intervention study, phosphate-buffered saline with or without insulin was instilled rectally in anaesthetized wild-type mice with chemically induced colitis.nnnResultsnWe found higher endoscopic colitis scores together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we showed that topically administered insulin in inflamed colons of wild-type mice reduced inflammation-induced weight loss and improved remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores and reduced cyclooxygenase 2 mRNA expression, and developed significantly fewer and smaller tumours compared with the control group receiving phosphate-buffered saline only.nnnConclusionsnRectal insulin therapy could potentially be a novel treatment, targeting the epithelial layer to enhance mucosal healing in ulcerated areas. Our findings open up new possibilities for combination treatments to synergize with the existing anti-inflammatory therapies.

Interindividual and regional relationship between cerebral blood flow and glucose metabolism in the resting brain

Studies of the resting brain measurements of cerebral blood flow (CBF) show large interindividual and regional variability, but the metabolic basis of this variability is not fully established. The aim of the present study was to reassess regional and interindividual relationships between cerebral perfusion and glucose metabolism in the resting brain. Regional quantitative measurements of CBF and cerebral metabolic rate of glucose (CMRglc) were obtained in 24 healthy young men using dynamic [15O]H2O and [18F]fluorodeoxyglucose positron emission tomography (PET). Magnetic resonance imaging measurements of global oxygen extraction fraction (gOEF) and metabolic rate of oxygen ([Formula: see text]) were obtained by combined susceptometry-based sagittal sinus oximetry and phase contrast mapping. No significant interindividual associations between global CBF, global CMRglc, and [Formula: see text] were observed. Linear mixed-model analysis showed a highly significant association of CBF with CMRglc regionally. Compared with neocortex significantly higher CBF values than explained by CMRglc were demonstrated in infratentorial structures, thalami, and mesial temporal cortex, and lower values were found in the striatum and cerebral white matter. The present study shows that absolute quantitative global CBF measurements appear not to be a valid surrogate measure of global cerebral glucose or oxygen consumption, and further demonstrates regionally variable relationship between perfusion and glucose metabolism in the resting brain that could suggest regional differences in energy substrate metabolism. NEW & NOTEWORTHY Using method-independent techniques the study cannot confirm direct interindividual correlations of absolute global values of perfusion with oxygen or glucose metabolism in the resting brain, and absolute global perfusion measurements appear not to be valid surrogate measures of cerebral metabolism. The ratio of both perfusion and oxygen delivery to glucose metabolism varies regionally, also when accounting for known methodological regional bias in quantification of glucose metabolism.