Thyroid autoimmunity has been associated with differentiated thyroid cancer although multiple potential biases might have influenced the results of previous studies.
We conducted a case-control study ...nested within the cohort of US active-duty personnel 1996-2014 to assess the association between thyroid autoimmunity, defined by serology, and thyroid cancer diagnosis. The primary exposure was thyroid peroxidase (TPO) antibody status 7-10 years before the thyroid cancer index date. We also assessed whether diagnosis of thyroid autoimmunity mediated any associations identified and if thyroid cancer features differed by autoimmunity status.
Among 451 incident cases of papillary thyroid cancer and matched controls (median age 36 years, 61.4% men), TPO antibody positivity (
negative) 7-10 years prediagnosis was associated with thyroid cancer (odds ratio OR 1.90 95% CI, 1.33 to 2.70). Exploratory analyses suggested an increasing risk of thyroid cancer with higher TPO antibody titer (TPO antibody 550-1,399 IU/mL: OR 2.95 95% CI, 1.37 to 6.36; and ≥ 1,400 IU/mL: OR 3.91 95% CI, 1.66 to 9.24). Positive TPO antibody status remained associated with thyroid cancer after those with diagnosed autoimmunity were excluded, and the association was not mediated by diagnosis of thyroid autoimmunity. Among the cases with diagnosed autoimmunity, 58% thyroid cancers were ≤ 10 mm diameter.
Longstanding prior thyroid autoimmunity up to 10 years before thyroid cancer diagnosis was associated with papillary thyroid cancer risk. The results could not be fully explained by diagnosis of thyroid autoimmunity although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage.
Serum thyrotropin (TSH) concentration and thyroid autoimmunity may be of prognostic importance in differentiated thyroid cancer (DTC). Preoperative serum TSH level has been associated with higher DTC ...stage in cross-sectional studies; data are contradictory on the significance of thyroid autoimmunity at the time of diagnosis.
We sought to assess whether preoperative serum TSH and perioperative antithyroglobulin antibodies (TgAb) were associated with thyroid cancer stage and outcome in DTC patients followed by the National Thyroid Cancer Treatment Cooperative Study, a large multicenter thyroid cancer registry.
Patients registered after 1996 with available preoperative serum TSH (n=617; the TSH cohort) or perioperative TgAb status (n=1770; the TgAb cohort) were analyzed for tumor stage, persistent disease, recurrence, and overall survival (OS; median follow-up, 5.5 years). Parametric tests assessed log-transformed TSH, and categorical variables were tested with chi square. Disease-free survival (DFS) and OS was assessed with Cox models.
Geometric mean serum TSH levels were higher in patients with higher-stage disease (Stage III/IV=1.48 vs. 1.02 mU/L for Stages I/II; p=0.006). The relationship persisted in those aged ≥45 years after adjusting for sex (p=0.01). Gross extrathyroidal extension (p=0.03) and presence of cervical lymph node metastases (p=0.003) were also significantly associated with higher serum TSH. Disease recurrence and all-cause mortality occurred in 37 and 38 TSH cohort patients respectively, which limited the power for survival analysis. Positive TgAb was associated with lower stage on univariate analysis (positive TgAb in 23.4% vs. 17.8% of Stage I/II vs. III/IV patients, respectively; p=0.01), although the relationship lost significance when adjusting for age and sex (p=0.34). Perioperative TgAb was not an independent predictor of DFS (hazard ratio=1.12 95% confidence interval=0.74-1.69) or OS (hazard ratio=0.98 95% confidence interval=0.56-1.72).
Preoperative serum TSH level is associated with higher DTC stage, gross extrathyroidal extension, and neck node metastases. Perioperative TgAb is not an independent predictor of DTC prognosis. A larger cohort is required to assess whether preoperative serum TSH level predicts recurrence or mortality.
Preeclampsia is a common but life-threatening condition of pregnancy. It is caused by poor placentation resulting in release of trophoblast material (including soluble endoglin (sEng)) into the ...maternal circulation leading to maternal vascular dysfunction and to the life-threatening condition of eclampsia. The only cure is early delivery, which can have lifelong consequences for the premature child. The thyroid hormone binding protein transthyretin is dysregulated in preeclampsia, however it is not known if this plays a role in disease pathology. We hypothesised that transthyretin may bind sEng and abrogate its negative effects by removing it from the maternal serum.
The effect of transthyretin on hepatocyte uptake of Alexa-labelled sEng was measured using live cell imaging. Interactions between transthyretin, and sEng were investigated using molecular modelling, direct binding on CnBr Sepharose columns, confocal imaging, and measurement of fluorescence resonance energy transfer.
Transthyretin directly bound to sEng and increased its uptake by hepatocytes. This uptake was altered in the presence of transforming growth factor-β1 (TGF-β1). Molecular modelling predicted that transthyretin and TGF-β1 bind at the same site in sEng and may compete for binding. Endocytosed transthyretin and endoglin entered cells together and co-localised inside hepatocyte cells.
Transthyretin can bind sEng and increase its uptake from the extracellular medium. This suggests that increasing transthyretin levels or developing drugs that normalise or mimic transthyretin, may provide treatment options to reduce sEng induced vascular dysfunction.
•Transthyretin binds to soluble endoglin.•Transthyretin increases cell uptake of soluble endoglin.•Transthyretin and soluble endoglin co-localise intracellularly in hepatocytes.
The majority of small papillary thyroid cancers (sPTCs) are treated surgically, rather than by active surveillance. Patient and clinician preference for surgery may be partially driven by the use of ...cancer terminology. Some experts propose that changing terminology would better communicate the indolent nature of sPTCs and improve uptake of active surveillance. Others argue that terminology that includes "cancer" correctly reflects the biological nature of these tumors. The views of informed lay publics can provide value-based perspectives on complex issues and guide policy discussions.
We recruited 40 people for three community juries, held in Sydney, Wodonga, and Cairns, Australia. Participants were of diverse backgrounds and ages, recruited through random digit dialing and a topic-blinded social media strategy. Juries were informed about thyroid cancer, overdiagnosis, and overtreatment, and heard arguments for and against terminology change before deliberation. The deliberative process in Jury 1 led to a refinement of jury charge, the updated version that was then used in Juries 2 and 3.
Jury 1 favored no terminology change, and Juries 2 and 3 were divided on the topic. Key reasons for opposing terminology change included a strong desire to retain terminology that aligns with the pathological definition of cancer, and to avoid even a minimal risk of harm that could arise if patients became complacent in follow-up. Key reasons to support terminology change included a desire to reduce psychological distress, stigma, and discrimination associated with a cancer diagnosis, and an argument that terminology change may be a more effective trigger for health system reform compared with other options. The juries unanimously recommended community education and health system reforms to reduce harms of overtreatment, and expressed an expectation that clinicians and researchers reach agreement on clinical guidelines to promote better uptake of active surveillance.
The conceptual tension between a pathological and an outcome-based understanding of cancer was apparent in deliberation. This highlights an ongoing challenge for those advocating changing disease terminology. Regardless of action on terminology, jurors shared a strong expectation that practical changes would be made to respond to the harms of overtreatment.
Excitons play a dominant role in the optoelectronic properties of atomically thin van der Waals (vdW) semiconductors. These excitons are amenable to on-demand engineering with diverse control knobs, ...including dielectric screening, interlayer hybridization, and moiré potentials. However, external stimuli frequently yield heterogeneous excitonic responses at the nano- and meso-scales, making their spatial characterization with conventional diffraction-limited optics a formidable task. Here, we use a scattering-type scanning near-field optical microscope (s-SNOM) to acquire exciton spectra in atomically thin transition metal dichalcogenide microcrystals with previously unattainable 20 nm resolution. Our nano-optical data revealed material- and stacking-dependent exciton spectra of MoSe
, WSe
, and their heterostructures. Furthermore, we extracted the complex dielectric function of these prototypical vdW semiconductors. s-SNOM hyperspectral images uncovered how the dielectric screening modifies excitons at length scales as short as few nanometers. This work paves the way towards understanding and manipulation of excitons in atomically thin layers at the nanoscale.
The ground-state properties of correlated electron systems can be extraordinarily sensitive to external stimuli, offering abundant platforms for functional materials. Using the multi-messenger ...combination of atomic force microscopy, cryogenic scanning near-field optical microscopy, magnetic force microscopy and ultrafast laser excitation, we demonstrate both 'writing' and 'erasing' of a metastable ferromagnetic metal phase in strained films of La
Ca
MnO
(LCMO) with nanometre-resolved finesse. By tracking both optical conductivity and magnetism at the nanoscale, we reveal how strain-coupling underlies the dynamic growth, spontaneous nanotexture and first-order melting transition of this hidden photoinduced metal. Our first-principles calculations reveal that epitaxially engineered Jahn-Teller distortion can stabilize nearly degenerate antiferromagnetic insulator and ferromagnetic metal phases. We propose a Ginzburg-Landau description to rationalize the co-active interplay of strain, lattice distortions and magnetism nano-resolved here in strained LCMO, thus guiding future functional engineering of epitaxial oxides into the regime of phase-programmable materials.
A supply of maternal thyroid hormone (thyroxine, T4) is essential for normal human fetal development. Human placental trophoblasts synthesize, secrete and take up the T4 binding protein ...transthyretin, providing a route for maternal T4 to enter the placenta. Transthyretin is also involved in T4 transport in other tissues such as the brain choroid plexus. Nicotine alters transthyretin synthesis and function in rat choroid plexus. If nicotine influences trophoblast turnover of transthyretin, then it may directly affect placental transfer of T4 to the developing fetus and contribute to the negative impacts of smoking on fetal growth, development and placental function.
The effect of nicotine on trophoblast uptake of Alexa-labelled transthyretin was measured using live cell imaging. The effect of nicotine on protein expression was measured by western blotting. Interactions between transthyretin, T4 and nicotine were investigated using chemical cross-linking techniques and molecular dynamic simulations.
Nicotine blocks uptake of transthyretin-T4 by human placental trophoblast cells. Nicotine reduces the expression of the trophoblast scavenger receptor class B type 1 (SR-B1) that plays a role in transthyretin-T4 uptake. Molecular dynamic modelling suggests that when T4 is bound to transthyretin, nicotine binding increases tetramer stability, reducing the ability of the transthyretin-T4 complex to enter trophoblast cells.
Our data suggest that nicotine exposure during pregnancy reduces transplacental transport of transthyretin and T4 to the placenta and developing fetus. This may contribute to the negative effects of smoking on fetal growth, development and pregnancy viability.
•Nicotine blocks uptake of transthyretin-T4 by human placental trophoblast cells.•Nicotine treatment decreases levels of scavenger receptor class B type 1 in trophoblasts.•Molecular dynamic modelling suggests that when T4 is bound to transthyretin, nicotine binding increases tetramer stability.
The epidemiology of amyloidosis in Queensland, Australia Wisniowski, Brendan; McLeod, Donald S. A.; Adams, Rebecca ...
British journal of haematology,
September 2019, 2019-09-00, 20190901, Letnik:
186, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Summary
Published studies on the epidemiology of amyloidosis have relied on death certificate data for case ascertainment. We estimated the incidence and mortality burden of amyloidosis among ...residents of the Australian state, Queensland, aged ≥20 years for the years 1999–2013 based on case ascertainment from histopathology reports. Information systems for participating laboratories were scrutinised to identify histopathology reports that documented a diagnosis of amyloidosis. Case mortality status was determined via linkage to the National Death Index. A total of 447 cases of amyloidosis were identified, with a median age at diagnosis of 66 years. A plasma cell dyscrasia was identified in 72% of patients who had paraprotein studies performed. The estimated incidence for Queenslanders aged ≥20 years was 12·1 cases per million person years. The median survival was 2·45 years. Age at diagnosis, presence of a paraprotein, earlier year of diagnosis, and inner regional location of residence (compared with residence in a major city) were independently associated with reduced survival. Our data confirms previously reported incidence data for amyloidosis of approximately 10 cases per million patient years and indicates that survival for Queensland patients with amyloidosis is improving, though it remains poor for the elderly and patients with AL amyloidosis.
Background
Falls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to ...determine whether monthly high‐dose vitamin D supplementation reduces risk and incidence of falls.
Methods
We used data from the randomized, double‐blind, placebo‐controlled D‐Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60–84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking >500 IU/day supplementary vitamin D were ineligible. Each year, we collected blood samples from ~450 randomly sampled participants from each trial arm and measured 25‐hydroxyvitamin D 25(OH)D. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3‐month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random samples of participants (surveys, n = 16 000; diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention‐to‐treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763); registered 4 July 2013.
Results
Mean treatment duration was 4.3 years (standard deviation SD = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively; approximately half were randomized to vitamin D (surveys: 50.1%; diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio OR 1.02, 95% confidence interval CI 0.95–1.10). There was an interaction with body mass index (BMI) (P‐interaction = 0.001); vitamin D increased risk in participants with BMI < 25 kg/m2 (OR 1.25, 95% CI 1.09–1.43), but there was no effect in those with BMI ≥ 25 kg/m2 (OR 0.95, 95% CI 0.87–1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups.
Conclusions
Monthly high‐dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation.
Risk of thyroid cancer following hysterectomy Rahman, Sabbir T.; Pandeya, Nirmala; Neale, Rachel E. ...
Cancer epidemiology,
June 2021, 2021-Jun, 2021-06-00, 20210601, Letnik:
72
Journal Article
Recenzirano
•Having undergone a hysterectomy was associated with increased thyroid cancer risk.•The association appeared stronger for those having hysterectomy to treat menstrual bleeding disorders.•The overall ...association did not seem to be mediated by greater healthcare access.
Hysterectomy has been associated with increased thyroid cancer risk but whether this reflects a biological link or increased diagnosis of indolent cancers due to greater medical contact remains unclear.
We recruited 730 women diagnosed with thyroid cancer and 785 age-matched population controls. Multivariable logistic regression was used to assess the association overall, and by tumour BRAF mutational status as a marker of potentially higher-risk cancers. We used causal mediation analysis to investigate potential mediation of the association by healthcare service use.
Having had a hysterectomy was associated with an increased risk of thyroid cancer (odds ratio OR = 1.45, 95 % confidence interval CI 1.07–1.96). When stratified by indication for hysterectomy, the risk appeared stronger for those who had a hysterectomy for menstrual disorders (OR = 1.67, 95 % CI 1.17–2.37) but did not differ by tumour BRAF status. Approximately 20 % of the association between hysterectomy and thyroid cancer may be mediated by more frequent use of healthcare services.
The observed increased risk of thyroid cancer among those with hysterectomy may be driven, at least partly, by an altered sex steroid hormone milieu. More frequent healthcare service use by women with hysterectomy accounts for only a small proportion of the association.
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