Longitudinal Study Research Articles

Body Mass Index as Effect Modifier of Heatwave and Cold Spell Mortalities: Longitudinal Study in China

Body Mass Index as Effect Modifier of Heatwave and Cold Spell Mortalities: Longitudinal Study in China

Associations between greenspace patterns and mortality in six million Swiss adults: a longitudinal study

Associations between greenspace patterns and mortality in six million Swiss adults: a longitudinal study

DIFFERENCES IN PARENTS' ATTITUDES TOWARDS THE CAUSES OF NEURODEVELOPMENTAL DISORDERS

Neurodevelopmental disorders are a heterogeneous group of clinical conditions characterized by deficits in one or more aspects of development, with the most prevalent subgroups being autism spectrum disorders and intellectual developmental disorders. Longitudinal studies have shown a significant increase in the number of children with autism spectrum disorders over the past few decades compared to the stable prevalence of intellectual developmental disorders. The aim of this study was to examine and compare the attitudes of parents of children with autism spectrum disorders and parents of children with intellectual developmental disorders regarding genetics, vaccination, and stress as causes of these disorders. The sample consisted of 80 parents, with 40 parents of children with intellectual developmental disorders and 40 parents of children with autism spectrum disorders. The study used a survey as the instrument, employing content analysis, interviewing, and scaling techniques. Data were statistically analyzed using quantitative methods in the JASP program. The results showed that parents' attitudes towards genetics as a cause did not statistically differ, with the most of parents not considering genetics as a cause of neurodevelopmental disorders (40%). There was a notable difference between these two subgroups of neurodevelopmental disorders in the number of children who had undergone genetic testing. A third of the participants expressed a negative attitude towards genetic testing in the future. A statistically significant difference was confirmed in attitudes towards vaccination as a cause of disorders. While most parents did not believe that stress caused their child's disorder, a higher number of parents with children who have intellectual developmental disorders cited stress as a contributing factor. Well-informed parents about the origins of neurodevelopmental disorders influence the lives of entire families, reducing the risk of unnecessary exposure of children to various interventions and treatments.

Longitudinal study on prenatal arsenic exposure and its persistence up to 10 years: identification of associated factors

Longitudinal study on prenatal arsenic exposure and its persistence up to 10 years: identification of associated factors

Cognitive and functional brain changes among Italian adolescents and young adults with COVID-19 infection: a longitudinal case control study

Cognitive and functional brain changes among Italian adolescents and young adults with COVID-19 infection: a longitudinal case control study

Association between electrocardiographic abnormalities and flood exposure among middle-aged and elderly people: A national longitudinal study in China

Association between electrocardiographic abnormalities and flood exposure among middle-aged and elderly people: A national longitudinal study in China

Occupational Pesticide Exposure Is Associated with Symptomatic Gallstone Disease in Baseline Data from the Chile Biliary Longitudinal Study (Chile BiLS)

Occupational Pesticide Exposure Is Associated with Symptomatic Gallstone Disease in Baseline Data from the Chile Biliary Longitudinal Study (Chile BiLS)

Residential exposure to green and non-photosynthesising vegetation: comparative effects on academic performance in a longitudinal study of Australian children

Residential exposure to green and non-photosynthesising vegetation: comparative effects on academic performance in a longitudinal study of Australian children

COVID-19 Incidence, Risk Factors, Impact, and Related Stigma Among a Cohort of Persons With HIV in Washington, DC.

Studies on the incidence of COVID-19 among persons with HIV (PWHs) present varied results. Few studies have investigated the impact of COVID-19 infection on health and socioeconomic factors or COVID-19 stigma. We sought to measure the incidence and severity of COVID-19 infection among a cohort of PWHs, characterize associated risk factors and impact, and document perceptions of COVID-19-related stigma. Data for this cross-sectional study come from the COVID-19 survey of participants in the DC Cohort longitudinal study from October 30, 2020, through December 31, 2022. Survey results were linked to electronic health records, including HIV laboratory test results and COVID test results. We conducted analyses comparing demographic, socioeconomic, HIV measures, and stigma among those with and without self-reported COVID-19. Of 1972 survey respondents, 17% self-reported COVID-19 infection, with the greatest incidence in the Omicron wave of the pandemic. We found statistically significant differences by age, employment status, essential worker status, education, and household income. Longer duration of HIV diagnosis was associated with greater incidence of COVID-19. PWHs who were overweight or obese had a greater incidence of COVID-19 compared with those who were not. Over 40% of PWHs with COVID-19 reported experiencing at least 1 form of COVID-19-related stigma. We observed a high incidence of COVID-19 infection among PWHs in DC. Furthermore, a substantial proportion of PWHs with COVID-19 reported experiencing COVID-19-related stigma. These findings add to the existing literature on COVID-19 coinfection among PWHs and highlight the need for awareness and support for those experiencing COVID-19 stigma.

Association of CSF α-Synuclein Seeding Amplification Assay Results With Clinical Features of Possible and Probable Dementia With Lewy Bodies.

The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF. In this study, we examine how different clinical features associate with CSF αSyn-SAA positivity in a large group of clinically diagnosed participants with DLB. Cross-sectional and longitudinal CSF samples from the multicentered observational cohort study of the DLB Consortium and similar studies within the Parkinson's Disease Biomarker Program, contributed by academic medical centers in the United States, underwent αSyn-SAA testing. Participants included those clinically diagnosed with DLB and 2 control cohorts. Associations between core DLB features and olfaction with αSyn-SAA positivity were evaluated using logistic regression. CSF samples from 191 participants diagnosed with DLB (mean age 69.9 ± 6.8, 15% female), 50 age-matched and sex-matched clinical control participants, and 49 younger analytical control participants were analyzed. Seventy-two percent (137/191) of participants with DLB had positive αSyn-SAAs vs 4% of the control groups. Among participants with DLB, those who were αSyn-SAA-positive had lower Montreal Cognitive Assessment scores (18.8 ± 5.7 vs 21.2 ± 5.2, p = 0.01), had worse parkinsonism on the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (33.8 ± 15.1 vs 25.6 ± 16.4, p = 0.001), were more likely to report RBD (114/133 [86%] vs 33/53 [62%], p < 0.0001), and had worse hyposmia on the University of Pennsylvania Smell Identification Test (UPSIT) (94/105 [90%] below 15th percentile vs 14/44 [32%], p < 0.0001). UPSIT percentile had the highest area under the curve (0.87, 95% CI 0.81-0.94) in predicting αSyn-SAA positivity and participants scoring at or below the 15th percentile of age and sex normative values had 18.3 times higher odds (95% CI 7.52-44.6) of having a positive αSyn-SAA test. Among 82 participants with longitudinal CSF samples, 81 (99%) had the same αSyn-SAA result for initial and follow-up specimens. A substantial proportion of clinically diagnosed participants with DLB had negative αSyn-SAA results. Hyposmia was the strongest clinical predictor of αSyn-SAA positivity. Hyposmia and αSyn-SAA may have utility in improving the diagnostic assessment of individuals with potential DLB. This study provided Class III evidence that CSF αSyn-SAA distinguishes patients with clinically diagnosed DLB from normal controls.

Associations of Cerebral Blood Flow Patterns With Gray and White Matter Structure in Patients With Temporal Lobe Epilepsy.

Neuroimaging studies in patients with temporal lobe epilepsy (TLE) show widespread brain network alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. Here, we studied whole-brain perfusion and vascular network alterations in TLE and assessed its associations with gray and white matter compromises and various clinical variables. We included individuals with and without pharmaco-resistant TLE who underwent multimodal 3T MRI, including arterial spin labelling, structural, and diffusion-weighted imaging. Using surface-based MRI mapping, we generated individualized cortico-subcortical profiles of perfusion, morphology, and microstructure. Linear models compared regional CBF in patients with controls and related alterations to morphological and microstructural metrics. We further probed interregional vascular networks in TLE, using graph theoretical CBF covariance analysis. The effects of disease duration were explored to better understand the progressive changes in perfusion. We assessed the utility of perfusion in separating patients with TLE from controls using supervised machine learning. Compared with control participants (n = 38; mean ± SD age 34.8 ± 9.3 years; 20 females), patients with TLE (n = 24; mean ± SD age 35.8 ± 10.6 years; 12 females) showed widespread CBF reductions predominantly in fronto-temporal regions (Cohen d -0.69, 95% CI -1.21 to -0.16), consistent in a subgroup of patients who remained seizure-free after surgical resection of the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partially constrained by gray and white matter changes (8.11% reduction in Cohen d) and topologically segregated from whole-brain perfusion networks (area under the curve -0.17, p < 0.05). Negative effects of progressive disease duration further targeted regional CBF profiles in patients (r = -0.54, 95% CI -0.77 to -0.16). Perfusion-derived classifiers discriminated patients from controls with high accuracy (71% [70%-82%]). Findings were robust when controlling for several methodological confounds. Our multimodal findings provide insights into vascular contributions to TLE pathophysiology affecting and extending beyond mesiotemporal structures and highlight their clinical potential in epilepsy diagnosis. As our work was cross-sectional and based on a single site, it motivates future longitudinal studies to confirm progressive effects, ideally in a multicentric setting.

Prediction of Future Parkinson Disease Using Plasma Proteins Combined With Clinical-Demographic Measures.

Identification of individuals at high risk of developing Parkinson disease (PD) several years before diagnosis is crucial for developing treatments to prevent or delay neurodegeneration. This study aimed to develop predictive models for PD risk that combine plasma proteins and easily accessible clinical-demographic variables. Using data from the UK Biobank (UKB), which recruited participants across the United Kingdom, we conducted a longitudinal study to identify predictors for incident PD. Participants with baseline plasma proteins and no PD were included. Through machine learning, we narrowed down predictors from a pool of 1,463 plasma proteins and 93 clinical-demographic. These predictors were then externally validated using the Parkinson's Progression Marker Initiative (PPMI) cohort. To further investigate the temporal trends of predictors, a nested case-control study was conducted within the UKB. A total of 52,503 participants without PD (median age 58, 54% female) were included. Over a median follow-up duration of 14.0 years, 751 individuals were diagnosed with PD (median age 65, 37% female). Using a forward selection approach, we selected a panel of 22 plasma proteins for optimal prediction. Using an ensemble tree-based Light Gradient Boosting Machine (LightGBM) algorithm, the model achieved an area under the receiver operating characteristic curve (AUC) of 0.800 (95% CI 0.785-0.815). The LightGBM prediction model integrating both plasma proteins and clinical-demographic variables demonstrated enhanced predictive accuracy, with an AUC of 0.832 (95% CI 0.815-0.849). Key predictors identified included age, years of education, history of traumatic brain injury, and serum creatinine. The incorporation of 11 plasma proteins (neurofilament light, integrin subunit alpha V, hematopoietic PGD synthase, histamine N-methyltransferase, tubulin polymerization promoting protein family member 3, ectodysplasin A2 receptor, Latexin, interleukin-13 receptor subunit alpha-1, BAG family molecular chaperone regulator 3, tryptophanyl-TRNA synthetase, and secretogranin-2) augmented the model's predictive accuracy. External validation in the PPMI cohort confirmed the model's reliability, producing an AUC of 0.810 (95% CI 0.740-0.873). Notably, alterations in these predictors were detectable several years before the diagnosis of PD. Our findings support the potential utility of a machine learning-based model integrating clinical-demographic variables with plasma proteins to identify individuals at high risk for PD within the general population. Although these predictors have been validated by PPMI, additional validation in a more diverse population reflective of the general community is essential.

Early childhood risk factors for later onset of pediatric chronic pain: a multi-method longitudinal study

BackgroundPediatric chronic pain (i.e., pain lasting ≥ 3 months) is prevalent, disabling, and costly. It spikes in adolescence, interrupts psychosocial development and functioning, and often co-occurs with mental health problems. Chronic pain often begins spontaneously without prior injuries and/or other disorders. Prospective longitudinal cohort studies following children from early childhood, prior to chronic pain onset, are needed to examine contributing factors, such as early pain experiences and mental health. Using data from a longitudinal community pregnancy cohort (All Our Families; AOF), the present study examined the associations between early developmental risk factors, including early childhood pain experiences and mental health symptoms, and the onset of pediatric chronic pain at ages 8 and 11 years.MethodsAvailable longitudinal AOF data from child age 4 months, as well as 1, 2, 3, 5, 8, and 11 years, were used. Mothers reported their child’s pain experiences (e.g., hospitalizations, vaccinations, gut problems) at each timepoint from 4 months to 8 years, child chronic pain at age 8, and child mental health symptoms at ages 5 and 8 years. Children reported their chronic pain frequency and interference at age 11. Adaptive least absolute shrinkage and selection operator (LASSO) regressions were used to select predictor variables. Complete case analyses were complemented by multiple imputation using chained equation (MICE) models.ResultsGut problems, emergency room visits, frequent pain complaints, and headaches at age 5 or earlier, as well as female sex, were associated with increased risk of maternal reported child chronic pain at age 8. Maternal reported chronic pain at age 8 was associated with higher levels of child-reported pain frequency and pain interferences at age 11. Boys self-reported lower levels of pain interference at age 11.ConclusionsSome, but not all, painful experiences (e.g., gut problems, ER visits, pain complaints) in early life contribute to pediatric chronic pain onset and should be considered for screening and early intervention.

Association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease: an updated meta-analysis

ObjectiveEpidemiological studies have reported an association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the magnitude of the risk and whether this risk changes with the severity...

Outcomes and Survival for Early-Stage Non-Small Cell Lung Cancer Following Wedge Resection or Lobectomy: A Propensity Score-Matched Analysis Using a Novel Peruvian Registry.

Using a previously unreported Peruvian registry of patients treated for early-stage non-small cell lung cancer (NSCLC), this study explored whether wedge resection and lobectomy were equivalent regarding survival and impact on radiologic-pathologic variables. This observational, analytical, longitudinal study used propensity score-matched (PSM) analysis of a single-center retrospective registry of 2,570 patients with pathologic stage I-II NSCLC who were treated with wedge resection (n=1,845) or lobectomy (n=725) during 2000-2020. After PSM, 650 cases were analyzed (resection, n=325; lobectomy, n=325) through preoperative and clinical variables, including patients with ≥1 lymph node removed. Kaplan-Meier curves and multivariable Cox proportional hazard models were created for 5-year overall survival (OS), disease-free survival (DFS), and locoregional-recurrence-free survival (LRFS). The principal complication was operative pain persisting >7 days for lobectomy versus wedge resection (58% vs. 23%, p=0.034) and shorter hospital stays for resection than for lobectomy (5.3 days vs. 12.8 days, p=0.009). The 5-year OS (84.3% vs. 81.2%, p=0.09) and DFS (79.1% vs. 74.1%, p=0.07) were similar and statistically insignificant between resections and lobectomies, respectively. LRFS was worse overall following wedge resection than lobectomy (79.8% vs. 91.1%, p<0.02). Nevertheless, in the PSM analysis, both groups experienced similar LRFS when the resection margin was >10 mm (90.9% vs. 87.3%, p<0.048) and ≥4 lymph nodes were removed (82.8% vs. 79.1%, p<0.011). Both techniques led to similar OS and DFS at 5 years; however, successful LRFS required a wedge resection with a surgical margin and adequate lymph node removal to obtain outcomes similar to lobectomy.

Cardiometabolic criteria as predictors and treatment targets of liver-related events and cardiovascular events in metabolic dysfunction-associated steatotic liver disease.

The diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) requires at least one of five cardiometabolic criteria. It is unclear whether these criteria can be used as predictors and treatment targets for complications including liver-related events and major adverse cardiovascular events (MACE). To investigate the relationship between cardiometabolic criteria and complications. We conducted a nationwide, population-based study of 979,352 patients with MASLD. We investigated relationships between a number of criteria at baseline and liver-related events or MACE risks. In a separate longitudinal analysis, we included patients with five criteria at baseline and investigated the relationship between improving the criteria and the incidence of complications after 1 year. The cumulative incidence of MACE, but not liver-related events, increased with increasing baseline cardiometabolic criteria. In the longitudinal study, multivariable analysis using patients with five criteria (no improvement) as the reference, adjusted hazard ratios (95% confidence interval) of MACE in patients with 4, 3, 2, and 0-1 criteria (1 to 4-5 criteria improvement) were 0.55 (0.52-0.58, p < 0.001), 0.20 (0.17-0.22, p < 0.001), 0.13 (0.11-0.16, p < 0.001), and 0.06 (0.02-0.3, p < 0.001), respectively. The risk of MACE decreased as the cardiometabolic criteria improved. There was no significant association between improvement of the criteria and liver-related events. Cardiometabolic criteria can be used as predictors and treatment targets for cardiovascular event risk in MASLD. Developing predictors and therapeutic targets for liver-related events is a future challenge.

Mepolizumab depletes inflammatory but preserves homeostatic eosinophils in severe asthma.

Eosinophils are key therapeutic targets in severe asthma that are suppressed by IL5 (mepolizumab) and IL5 receptor (benralizumab) blockade. The effect of IL5 pathway biologics on recently described homeostatic (hEOs) and inflammatory (iEOs) eosinophil subsets is unknown. We aimed to determine the relative impact of mepolizumab and benralizumab treatment on eosinophil subset and phenotype, and explore clinical associations of eosinophil subsets with severe asthma characteristics and treatment response. We performed a cross-sectional observational study of severe asthma (eosinophilic n = 32, non-eosinophilic n = 23, mepolizumab-treated n = 25), with longitudinal follow-up of 30 eosinophilic participants at two timepoints (4-24 weeks, >24 weeks) post-commencement of mepolizumab (n = 20) or benralizumab (n = 10). Blood hEOs and iEOs were measured by flow cytometry assessment of surface CD62L protein. iEO proportion was significantly lower in mepolizumab-treated participants in both the cross-sectional and longitudinal study. Mepolizumab and benralizumab depleted iEOs to a similar extent, however a significantly greater number of hEOs remained in mepolizumab participants at follow-up. Greater iEO proportion correlated with poorer asthma control in eosinophilic but not non-eosinophilic asthma. Higher residual iEO proportion correlated with poorer asthma control in mepolizumab-treated individuals. Reduced blood eosinophil viability was observed in around half of mepolizumab-treated participants, which was associated with significantly better asthma control and spirometry. Mepolizumab depletes iEOs and reduces circulating eosinophil viability in severe asthma but preserves a residual population of circulatory hEOs. In contrast benralizumab depleted both iEOs and hEOs. Higher iEO abundance and eosinophil viability are associated with poorer clinical outcomes following mepolizumab-treatment. Monitoring circulating eosinophil phenotype and viability may be useful to predict biologic treatment response in severe asthma.

Informing the management of the post-COVID condition: insights from the Western Australian experience comparing those who tested positive and negative to early COVID-19 strains.

ObjectiveThis study aimed to compare the relative physical recovery and symptoms after SARS-CoV-2 infection between groups confirmed positive or negative to early strains of COVID-19.MethodsA prospective, longitudinal cohort study compared outcomes of metropolitan adults polymerase chain reaction-tested for COVID-19 between March and November 2020 in Western Australia. Control matching was attempted: inpatients (gender, age) and ambulatory clinic (gender, age, asthma, chronic pulmonary disease). One-year follow-up involved three repeated measures: physical function (grip strength and 1-min sit-to-stand) and patient-reported outcomes (Fatigue Severity Scale, modified Medical Research Council dyspnoea scale and Euroqol-5D-5L).ResultsThree hundred and forty-four participants were recruited (154 COVID+, age 54±18years, 75 females [49%]); 190 COVID-, age 52±16years, 67 females [35%]) prior to national vaccination roll-out. No between-group differences in physical function measures were evident at any time point. Fatigue (OR 6.62, 95% CI 2.74-15.97) and dyspnoea (OR 2.21, 95% CI 1.14-4.30) were higher in the COVID+ group at second assessment (T2). On Euroqol-5D-5L, no between-group differences were evident in the physical function domains of self-care, mobility or usual activities at any time point. However, COVID+ participants were less likely to report an absence of anxiety or depression symptoms at T2 (OR 0.41, 95% CI 0.19-0.89).ConclusionsNeither statistical nor clinically meaningful differences in physical function were evident between COVID+ and COVID- participants to 12-months after acute illness. Symptoms of fatigue, dyspnoea, anxiety or depression were more prevalent in the COVID+ group til ~8months after illness with between-group differences no longer evident at 1 year.

Development and psychometric properties of the Japanese version of Child and Youth Resilience Measure-Revised (CYRM-R) among Japanese youth

Objectives Resilience is the ability to navigate adversity and recover from challenging situations. Developing resilience at a young age promotes mental health and provides benefits throughout one's lifespan. Validated measures for assessing resilience at a young age are required in both clinical practice and epidemiological studies. The Child and Youth Resilience Measure-Revised (CYRM-R) is a tool used worldwide to assess resilience in children and young people. The objective of this study was to develop a Japanese version of the CYRM-R and investigate its psychometric properties.Methods Children in grades 5-9 were recruited via a two-stage cluster random sampling taken from the Japan Adolescent and Youth (JAY) Longitudinal Cohort Study. The participants completed the Japanese version of the CYRM-R . The CYRM-R consists of two subscales, personal resilience and caregiver resilience, with a total of 17 items. The linguistic validity of the Japanese version of the CYRM-R was ensured through translation and back-translation.Cronbach's alpha coefficients were examined for the total score and the two subscales to assess the internal consistency of the Japanese version of the CYRM-R scale. In addition, correlation coefficients of the subscales were calculated. For factorial validity, a confirmatory factor analysis was conducted on the same two-factor structure as in the original version to assess the model's goodness of fit. Results A total of 2,266 children (50.0% male) were included in the study. The overall Cronbach's alpha of the Japanese version of the CYRM-R obtained from this sample was 0.956; For the personal resilience subscale, Cronbach's alpha was 0.932; for the caregiver resilience subscale, it was 0.919. Significant positive correlations were also found between subscales (r = 0.827, p < 0.001). A confirmatory factor analysis was conducted using a two-factor structure for validity. The model fit was good (RMSEA = 0.085, SRMR = 0.041, CFI = 0.934).Conclusion The Japanese version of the CYRM-R maintained the same two-factor structure as the original version. The study findings showed that the Japanese version of the CYRM-R had adequate internal consistency and factorial validity for assessing resilience in children and youth. Therefore, this scale is a valuable tool for identifying individuals or groups at risk in terms of children's resilience and for evaluating the effectiveness of support and interventions.

Association of Free Thyroxine with Progression-Free Survival in Intermediate and High Risk Differentiated Thyroid Cancer.

Supraphysiologic thyroxine (T4) doses are used in intermediate and high-risk patients with differentiated thyroid cancer (IR/HR-DTC) to suppress tumor progression by thyrotropin (TSH). However, preclinical data suggest that T4 can also act as a growth stimulus for cancer, but there is no clinical evidence supporting this claim. We analyzed the association between free T4 (FT4) and progression-free survival (PFS) in patients with IR/HR-DTC. This longitudinal cohort study, approved by multi-institutional review board, included patients with IR/HR-DTC treated uniformly with total thyroidectomy, radioiodine (RAI), and TSH suppression therapy, with at least three TSH and FT4 values available. Association between FT4 and PFS at landmarks 6, 12, and 18 months was assessed by Kaplan-Meier survival curves, while competing risks were assessed through Cox proportional hazards model. From 739 screened patients 382 met the inclusion criteria and were characterized by a median age of 46 (34-59) years, 64.1% women, treated with a median RAI dosage of 159 (110-410) mCi. During follow up of 7.1 (3.4-12.7) years 34.6% experienced disease progression.Elevated FT4, observed in 29.3% of patients, was not associated with worse PFS (HR 0.9, CI 0.54-1.5, p=0.69), while age (HR 1.02, CI 1.004-1.04, p=0.01), tumor size (HR 1.15, CI 1.04-1.28, p=0.01), and metastases to the lateral neck lymph nodes (HR 2.9, CI 1.7-4.74, p<0.001), bones (HR 4.87, CI 1.79-13.3, p=0.002), and brain (HR 5.56, CI 2.54-12.2, p<0.001) were associated with shorter PFS. Contrary to preclinical evidence, elevated FT4 levels do not affect PFS in patients with IR/HR-DTC.